lijjij;; lill" ( 4? J THERAPEUTICS: ITS PRINCIPLES AND PRACTICE. BY HORATIO C. WOOD, M.D., LL.D. (Lafayette, Yale, Pennsylvania), PROFESSOR OF MATERIA MEDICA AND THERAPEUTICS IN THE UNIVERSITY OF PENN- SYLVANIA ; MEMBER OF THE NATIONAL ACADEMY OF SCIENCE. AND HORATIO C.JVyOOD, JR., M.D., DEMONSTRATOR OF PHARMACODYNAMICS IN THE UNIVERSITY OF PENNSYLVANIA. THIRTEENTH EDITION. THOROUGHLY REVISED AND ADAPTED TO THE EIGHTH (1905) EDITION OF THE UNITED STATES PHARMACOPOEIA. PHILADELPHIA AND LONDON: J. B. LIPPINCOTT COMPANY. 1907. Entered, according to act of Congress, in the year 1875, by J. B. LIPPINCOTT & CO., 7n ike office of the Librarian of Congress, at Washington, Copyright, 1879, 1882, and 1883, by J. B. LIPPINCOTT & Co. Copyright, 1885, by J. B. LIPPINCOTT COMPANY. Copyright, 1888, by J. B. LIPPINCOTT COMPANY. Copvrieht, 1891, by J. B. LIPPINCOTT COMPANY. Copyiight, 1894, by J. B. LIPPINCOTT COMPANY Copyright, 1897, by J. B. LIPPINCOTT COMPANY. Copyright, 1900, by J. B. LIPPINCOTT COMPANY. Copyright, 1905, by J. B. LIPPINCOTT COMPANY. Copyright, 1906, by J. B. LIPPINCOTT COMPANY. CLECTROTYFED AND MINTED BY J. B. LIPPINCOTT COMPANY, PHILADELPHIA, U. 8. A. TO DR. GEORGE B. WOOD, LL.D -, THIS BOOK IS DEDICATED BY THE AUTHOR, HIS NEPHEW, AS A TOKEN OF RESPECT AND AFFECTION. PREFACE TO THE THIRTEENTH EDITION. THE extraordinary favor with which the Twelfth Edition of this work was received by the medical profession, exhausting in four months the entire edition, has offered an opportunity as well as an inspiration for the revision of the work. Among the more important alterations which have been made is the reconsideration of the effects of alcohol especially upon the circulation, which has been necessitated by very recently appearing researches ; a more elaborate discussion of the value of the scopolamine- morphine anaesthesia ; a consideration of the use of copper for the purifi- cation of water ; the addition of an article written by Dr. George B. Wood on Dunbar's hay-fever antitoxin ; and many minor alterations of the text to conform with pharmacological researches which have appeared within the last year. Besides these changes an important innovation has been made in the amplification of the Disease Index. The plan which has been adopted has been to give under each disease a list of the drugs which have been recommended, with a short summary of the action or use of the various remedies, so that the physician can tell in a few minutes which medicine is most likely to prove useful for an individual case under consideration. It is hoped by this means that the Index of Diseases will prove in fact as well as in name, a guide to therapeutics. With a full appreciation of the kind reception with which this work has been received both in America and in Europe, the Authors have used every effort in their power to make the work deserving of the confidence which has been reposed in it. UNIVERSITY OF PENNSYLVANIA, June, 1906. PREFACE TO THE FIRST EDITION. AT the present time, when the shelves of private and public libraries are groaning beneath their ever-increasing loads, when a thousand presses in every city send forth day and night their printed messages until the earth is filled with them, it seems almost presumptuous for any one to offer new volumes to the world. Indeed, art is so long, life is so short, that every student has the right to demand of an author by what authority he doeth these things, and to challenge every memoir for its raison d'etre. This being so, it assuredly will not appear ego- tistical for the author to state that his voluntary task was first suggested by his own wants, and that to its performance he has brought the train- ing, labor, and experience of years spent in the laboratory, the study, the class-room, and the hospital ward. There are a number of excellent treatises upon materia medica and therapeutics ; yet in various attempts at original research, as well as in the ward and the lecture-room of the hospital, I have keenly felt the want of something more. There are many points of view from which a subject can be looked at ; there are many paths by which it may be approached ; and to me, other points of view, other modes of approach, have been far more enticing than those adopted in our standard treatises. The old and tried method in therapeutics is that of empiricism, or, if the term sounds harsh, of clinical experience. As stated by one of its most ardent supporters, the best possible development of this plan of investigation is to be found in a close and careful analysis of cases before and after the administration of a remedy, and, if the results be favorable, the continued use of the drug in similar cases. It is evident that this is not a new path, but a highway already worn with the eager but weary feet of the profession for two thousand years. That very much has been thus accomplished it were folly to deny. Leaving out of sight the growth of the last two decades, almost all of the current therapeutic knowledge has been gained in this way. Therapeutics developed in this manner cannot, however, rest upon a secure foundation. What to-day is believed is to-morrow to be cast aside, certainly has been the law of advancement, and seemingly must continue to be so. What has clinical therapeutics established perma- nently and indisputably ? Scarcely anything beyond the primary facts vii viii PREFACE TO THE FIRST EDITION. that quinia will arrest an intermittent, that salts will purge, and that opium will quiet pain and lull to sleep. To established therapeutic facts the profession clings as with the heart and hand of one man, clings with a desperation and unanimity whose intensity is the measure of the unsatisfied desire for something fixed. Yet with what a Babel of discordant voices does it celebrate its two thousand years of experience ! This is so well known that it seems superfluous to cite examples of the therapeutic discord ; and one only shall be mentioned, namely, rheumatism. In this disease, bleeding, nitrate of potassium, quinine, mercurials, flying blisters, purgation, opium, the bromides, veratria, and a host of other remedies, all have their advocates clamorous for a hearing ; and above all the tumult are to be heard the trumpet- tones of a Chambers, ' ' Wrap your patients in blankets and let them alone. ' ' Experience is said to be the mother of wisdom. Verily she has been in medicine rather a blind leader of the blind ; and the history of medical progress is a history of men groping in the darkness, finding seeming gems of truth one after another, only in a few minutes to cast each back to the vast heap of forgotten baubles that in their day had also been mistaken for verities. In the past, there is scarcely a con- ceivable absurdity that men have not tested by experience and for a time found to be the thing desired ; in the present, homoeopathy and other similar delusions are eagerly embraced and honestly believed in by men who rest their faith upon experience. Narrowing our gaze to the regular profession and to a few decades, what do we see ? Experience teaching that not to bleed a man suffering from pneumonia is to consign him to an unopened grave, and experience teaching that to bleed a man suffering from pneumonia is to consign him to a grave never opened by nature. Looking at the revolutions and contradictions of the past, listening to the therapeutic Babel of the present, is it a wonder that men should take refuge in nihilism, and, like the lotos-eaters, dream that all alike is folly, that rest and quiet and calm are the only human fruition ? Since the profession has toiled so long and found so little, if further progress is to be made we must question the old methods and search out new ones, which haply may lead to more fruitful fields. In the ordinary affairs and business of life, when anything is to be accom- plished, the effort always is to discover what is to be done, and then what are the means at command. A primary knowledge of the end to be accomplished, and a secondary acquaintance with the instruments, are a necessity for successful human effort ; and until the sway of this law is acknowledged by physicians, medicine can never rise from the position of an empirical art to the dignity of applied science. Until within a comparatively recent period, it has been impossible to comply with this law. But, through the advances made by the pathologists and PREFACE TO THE FIRST EDITION. ix by the students of the natural history of disease, we are fast learning the; methods in which nature brings the body back to health. When this is done, when disease is thoroughly understood, we shall have wrought out the first element of the problem, shall have complied with the first requirement of the law. It is scarcely within the province of a therapeutist, and certainly is not possible within the scope and limits of this work, to discuss at length the natural history of disease ; but it is allowable to point out evident in- dications for relief ; and this I have done to a greater or less extent throughout the book. The work of the therapeutist is chiefly with the second portion of the law. Evidently, it is his especial province to find out what are the means at command, what the individual drugs in use do when put into a human system. It is seemingly self-evident that the physiological action of a remedy can never be made out by a study of its use in dis- ease. Under all circumstances, the problem is one of the most com- plex with which the human mind has to grapple ; and to introduce into this problem the new and ever-varying factors of the effect of disease and its natural vibrations on the system is to put the matter beyond human prescience. In spite, then, of Dr. Niemeyer's assertion that experiments made with medicaments upon the lower animals or upon healthy human beings have, as yet, been of no direct service to our means of treating disease, and that a continuation of such experiments gives no prospect of such ser- vice, it is certain that in these experiments is the only rational scientific groundwork for the treatment of disease. We must discover what in- fluence a drug exerts when put into the body of a patient before we can use it rationally ; and we can gain this coveted knowledge only in the method indicated. It has been strenuously objected, especially to experiments upon ani- mals, that drugs do not act upon the lower creatures in the same manner as they do upon man. When I first commenced the studies whose out- come is the present volume, I was profoundly impressed with the truth of this oft-repeated assertion and with the difficulties which it put in the way. To-day I do not believe that, stated in its broad sense, it is true. Indeed, more strongly, I assert that it is not true ; that, in the vast majority of cases, the actions of drugs upon man and upon the lower animals are, though seemingly different, in reality similar ; that the more knowledge we acquire the fewer exceptions remain unexplained ; and that the whole matter is in all probability subject to laws whose devel- opment will greatly aid in our explanation of various obscure clinical phenomena. The general proofs of these assertions are sufficiently obvious, I think, in the following pages to render it unnecessary for me to dwell upon them at length here : moreover, if they be not so obvious to others as to myself, space is here wanting for a full discussion of the subject. x PREFACE TO THE FIRST EDITION. I can only make a few general remarks, and point out some of what I believe to be the governing laws. In the first place, degree and quality are distinct things, and should not be confounded. Yet they frequently are ; and because it requires as much morphia to kill a pigeon of a pound weight as to destroy a man, we are told that medicines act differently upon man and the lower ani- mals. Evidently the conclusion is a non sequitur, and difference of sus- ceptibility is no proof of difference in the mode of impression. A tea- spoonful of Epsom salt may purge one man, while it may require ounces to affect another. Evidently there is a difference of susceptibility ; but when the impression is once made it is of the same character in each case. As with man and man, so with man and the pigeon, suscepti- bility is no measure or gauge of the character of the impression. A large number of drugs indeed, it may be said, the larger number of important drugs exert in the system antagonistic actions. Thus, atropia stimulates the spinal cord, but destroys the conducting power of the nerve-trunks. It is evident that as one or other of these in- fluences predominates, will there be convulsions or paralysis. Now, if for any reason one animal be exceedingly sensitive to the spinal action of atropia, that animal will in belladonna-poisoning suffer from convul- sions, while its fellow, which is affected chiefly by the nerve-action of the drug, will, under like circumstances, have paralysis. Here the mere clinician, with his superficial knowledge, seeing the paralyzed and the convulsed lying side by side, says, What a hopeless muddle ! Poor fools, these vivisectors ! they will never come to any good ! In truth, the dif- ferences in symptoms in these and in many other cases simply depend upon differences in susceptibility ; and the only lesson that the circum- stance teaches is the importance of discovering the laws which govern these susceptibilities. A law which governs the susceptibility to the action of drugs is, that the more highly specialized any system is the more readily affected is it by a medicine. Thus, the cerebrum of a man is far more highly organ- ized than that of any other animal, and consequently he is far more sen- sitive to the action of drugs which affect the cerebrum than are the lower forms. Again, in the frog the spinal system is especially developed, probably, in proportion to the cerebrum, more so than in any other of the animals commonly experimented with : consequently the batrachian is excessively sensitive to remedies which, like strychnia, affect the spinal cord. In obedience to this law, we have resulting the action of opium, an action which has been considered the strongest proof of the hope- lessness of any attempt to explain the effects of drugs upon a man by experiments upon the lower animals. In man, opium causes deep stupor and general relaxation ; in the frog, it causes tetanic convulsions. The explanation of these seeming inconsistencies is, however, very evident when the whole subject is looked at. Opium in all animals has a double action, one upon the cerebrum and one upon the spinal centres. In the PREFACE TO THE FIRST EDITION. xi frog, the latter being the more highly organized, the spinal action over- comes the cerebral ; in man, the cerebrum being the more sensitive, stupor replaces the convulsions : yet in man convulsions sometimes occur in opium-poisoning, and in the frog the dose can be so managed as to cause stupor. A second law which seems to hold sway over the action of drugs upon different animals is that great differences of function in a system affect its relation to drugs : thus, in an herbivorous animal the aliment- ary canal is very different from what it is in the carnivora, whose diges- tive organs in turn differ from those of man, the omnivore. Medi- cines which act upon the alimentary canal are apt to vary in their effects upon different orders of animals. Converse to the above law is that which renders systems which are little specialized similarly acted upon by drugs in different classes of animals. Thus, the general structure and the functions of the circulatory system are very uniform among vertebrates, as is also the action of those drugs which affect chiefly the circulation : thus, aconite, or digi- talis, or potash, influences in the one way the heart of the frog, of the rabbit, and of man. There are a very few apparent exceptions to the uniformity of the action of drugs upon all animals which seemingly contravene the laws that have been mentioned. These exceptions are so few, however, that without doubt advancing knowledge will by and by explain them all and show what are the laws which for the time being hold in abeyance or overcome those already stated. An asserted fact which has recently been brought forward as re- vealing the worthlessness of animal experimentation is that some monkeys are not susceptible to the action of strychnia, while others are. Granting the truth of the asserted fact, it certainly is explainable. It is at least conceivable that a given species of animal may, by the gradually acquired habit of feeding upon a substance containing a nar- cotic poison, acquire an insusceptibility to the influence of that poison which shall as it were belong to its specific type, or, in other words, be an acquired specific character. The nervous system of the opium-eater becomes accustomed to the stimulant, and it is not impossible that a measure of the habit should be transmitted. If the Darwinian law of the gradual evolution by the survival of the fittest have any force, these curious apparent freaks of medicines in regard to their physiological action may be the result of this law, especially since it is species which are affected. It is not all monkeys that are proof against strychnia, but, as we are distinctly told, only one species of monkey ; and, so far as I know, it is not all deer that are said to thrive when fed upon tobacco, but only the Virginia deer. Whether this conception be or be not a mere fancy, this much is to my mind very clear, that the few scattered'ex- ceptions ought not to outweigh the immense mass of evidence upon the xii PREFACE TO T.HE FIRST EDITION. other side, and that it is inconceivable that drugs, in their relations to animal organisms, differ from all other created things in not being subject to law. In the early portion of this preface I stated that the work had grown out of a need felt by myself : that need was for a book into which should be gathered the many scattered facts in regard to the physiological action of medicine, a book in which an attempt should be made to sift the true from the false, to reconcile seeming differences, to point out what we know and what we do not know, and to give a platform from which investigators might start forward without the ne- cessity of being, as is so often the case, ignorant of what was already achieved, or of spending a great deal of time in a wild hunt through the almost boundless, but often scattered and inaccessible, ranges of Continental literature. The plan of the present work has been to make the physiological action of remedies the principal point in discussion. A thoroughly scientific treatise would in each article simply show what the drug does when put into a healthy man, and afterwards point out to what diseases or morbid processes such action is able to afford relief. Unfortunately, in the great majority of cases our knowledge is not complete enough for this, and the clinical method has to be used to supplement the scientific plan. I have added to the book a consideration of toxicology, so far as it is of interest to the physician. This has been done for several reasons. First, it was necessary to study the action of poisonous drugs upon man, in order to make out their physiological action ; secondly, physicians are constantly required to diagnosticate and to treat cases of poisoning ; thirdly, it is often of the greatest importance for a medical man in a court of law to be able to state what are the symptoms and post-mortem appearances produced by a given poison, what diseases they simulate, and how far and in what they differ from the phenomena of these diseases. That part of the science of toxicology which treats of the recognition of poisons in the cadaver, or in food and drink, belongs to the domain of the chemist, and I have avoided it altogether. For a similar reason, in the sections on materia medica, the chemical relations of mineral substances have not been discussed at all. ABBREVIATIONS. A. A. Archiv fur Augenheilkunde. A. A. P. Archiv fur Anatomic und Physiologic. A. C. J. American Chemical Journal. A. D. S. Archiv fur Dermatologie und Syphilis. A. de P. Archives de Physiologic nor- male et pathologique. A. E. P. P. Archiv fur experimentelle Pathologic und Pharma- kologie. A. G. M. Archives ge'ne'rales de Me"de- cine. A. G. P. Archiv fur die gesammte Physiologic des Menschen und der Thiere. A. Hk. Archiv der Heilkunde. A. I. B. Archives italiennes de Bio- logic. A. I. M. N. Archivio italiano per le malattie nervose. A. I. Past. Annales de PInstitut Pas- teur. A. I. P. Archives internationales de Pharmacodynamie. A. J. M. S. American Journal of the Medical Sciences. A. J. P. American Journal of Physi- ology'. A. K. C. Archiv fur klinische Chi- rurgie. Al. Z. Ps. Allgemeine Zeitschrift fur Psychiatric. A. M. Ex. Archives de Me'decine ex- pe'rimentelle et d' Ana- tomic pathologique. Amer. Med. American Medicine. Am. Lan. American Lancet. A. N. Alienist and Neurologist. An. d'H. Annales d' Hygiene. An. O. Annals of Ophthalmology. Ann. O. Annales d'Oculistique. A. Op. Archiv fur Ophthalmologie. A. of Op. Archives of Ophthalmology. A. Ph. Archiv fur Anatomic und Physiologic, physiologisches Abteilung. A. Pharm. Archives de Pharmacody- namie. A. R. Aerztliche Rundschau. A. S. Z. Aerztliche Sachverstandigen- Zeitung. Aus. M. Gaz. Australian Medical Ga- zette. Aus. M. J. Australian Medical Journal. A. V. K. Archiv fur Verdauungs- Krankheiten. A. Z. Apotheker-Zeitung. B. A. M. Bulletin de P Academic de Me'decine de Paris. B. A. R. B. Bulletin de 1' Academic Royale de Me'decine de Beige. B. G. T. Bulletin ge"ne"ral de The"rapeu- tique me"dicale et chirurgi- cale. B. K. Ch. Beitrage zur klinischen Chirurgie. B. K. W. Berliner klinische Wochen- schrift. B. M. Le Bulletin Me"dicale. B. M. J. British Medical Journal. B. M. S. C. P. Bulletin et Me"moires de la Socie'te' Clin- ique de Paris. B. M. S. H. Bulletin Socie'te' Me"dicale des Hopitaux des Paris. B. M.S. J. Boston Medical and Surgi- cal Journal. B. P. A. Beitrage zur Pathologischen Anatomic und zur Allge- meinen Pathologic. Cb. B. Centralblatt fur Bacteriologie. Cb. C. Centralblatt fur Chirurgie. Cb. I. M. Centralblatt fur Innere Medi- cin. Cb. N. Centralblatt fur Nervenheil- kunde. Cb. P. Centralblatt fur Physiologic. C. B. S. A. Correspondenzblatt der Schweizerische Aerzte. Chi. M. J. Chicago Medical Journal. C. K. M. Centralblatt fiir klinische Medicin. Cl. M. Clinica Moderna. Cl. M. I. La Clinica Medicale Italienne. C. M. J. E. Chicago Medical Journal and Examiner. XIII XIV ABBREVIATIONS. C. M. R. V. Contributions to Medical Research. Vaughn. Ann Arbor. 1903. C. M. W. Centralblatt fur medicin- ischen Wissenschaften. C. R. A. S. Comptes-rendus de 1'Acade'mie de Sci- ence, Paris. C. R. S. B. Comptes-rendus de la Socie"te de Biologic, Paris. D. A. K. M. Deutsches Archiv fiir klinische Medicin. D. C. Dermatologisches Centralblatt. D. J. M. S. Dublin Journal of the Medical Sciences. D. Kl. Deutsche Klinik. D. M. W. Deutsche medicinische Wo- chenschrift. D. Z. Ch Deutsche Zeitschrift fiir Chirurgie. D. Z. N Deutsche Zeitung fiir Nerven- heilkunde. Ed. M. J. Edinburgh Medical Journal. E. M. N. L'Echo Medical du Nord. Fort. M. Fortschritte der Medicin. G. A. M. T. Giornale della Reale Academia di Medi- cina di Torino. G. H. M. C. Gazette Hebdomadaire de Mdecine et de Chi- rurgie. G. I. M. P. Gazzeta Internazionale de Medecina Practica. G. K. H. Monatsberichte iiber die gesammtleistungen auf dem Gebeite der Krank- heiten des Ham und Sex- ual-Apparates. G. M. P. Gazette Mddicale de Paris. Gl. M. J. Glasgow Medical Journal. Guy H. R. Guy's Hospital Re- ports. Hk. Die Heilkunde. H. S. Jb. Hoffmann and Schwalbe's Jahresberichte iiber die Fortschritte der Anatomic und Physiologic. I. B. I. M. Internationale Beitrage zur Inneren Medicin. In. Dis. Inaugural Dissertation. J. A. M. A. Journal of the American Medical Association. J. A. P. Journal of Anatomy and Phys- iology. J. Chem. S. Journal of the Chemical Society of London. J. de 1'A. P. Journal de 1'Anatomie et Physiologic. J. de P. P. Journal de Physiologic et de Pathologie Generale. J. de Th. Journal de The"rapeutique. J. Ex. M. Journal of Experimental Medicine. J. M. R. Journal of Medical Research. J. N. M. D. Journal of Nervous and Mental Diseases. J. P. Journal of Physiology. J. Pr. Journal des Praticiens. J. P. and B. Journal of Pathology and Bacteriology. K. T. W. Klinisch-Therapeutische Wochenschrift. L. L. London Lancet. Lyon M. Lyon Me"dicale. L. M. R. London Medical Recorder. L. S. Lo Sperimentale. M. A. Merck's Archives. M. C. C. Medicinische-Chirurgisches Centralblatt. M. C. Tr. Medico-Chirurgical Transac- tions. Med. R. Medical Register. M. H. H. B. Marine Hospital Hygienic Laboratory Bulletin. M. M. W. Miinchener medicinische Wochenschrift. M. News. Medical News. M. N. A. S. Memoirs of the National Academy of Science. M. P. D. Monatshefte fiir praktische Dermatologie. M. P. N. Monatsschrift Psychiatric und Neurologic. M. R. Merck's Report. M. S. Rep. Medical and Surgical Re- porter. M. T. G. Medicarl Times and Gazette. M. W. Medicinische Wochenschrift. N. Cb. Neurologisches Centralblatt. N. O. M. J. New Orleans Med. Journal. N. Y. M. J. New York Medical Journal. N. Y. M. R. New York Med. Record. N. Y. M. T. New York Medical Times. O. M. R. Ohio Medical Recorder. O. R. Ophthalmic Record. Pa. M. S. J. Pacific Medical and Sur- gical Journal. Path. Intern. Pathologie Interne. Ph. Post. Pharmaceutical Post. ABBREVIATIONS. xv P. J. and Tr. Pharmaceutical Journal and Transactions. P. M. C. P. Pester medizinisch Chirur- gische Presse. P. M. J. Philadelphia Medical Journal. P. M. T Philadelphia Medical Times. P. P. S. L. Proceedings of the Physio- logical Society of Lon- don. Pract. Practitioner. Press. M. B. La Presse Me"dicale Bel- gique. Pr. M. W. Prager medicinische Wo- chenschrift. Prog. M. Le Progres Medicale. P. Tr. R. S. L. Philosophical Transac- tions of the Royal Society of London. Q. J. P. M. Quarterly Journal of Psy- chological Medicine and Medical Jurisprudence. R. C. Revue de Chirurgie. R. M. S. R. Revue Medicale de la Suisse Romande. R. Med. Revue de Medecine. Rif. M. La Riforma Medica. R. T. Revue de Therapeutique. Sb. G. W. Sitzungsberichte der konig- liche Gesellschaft der Wissenschaften. S. Jb. Schmidt's Jahrbiicher der in- und auslandischen gesammten Medicin. S. M La Semaine Medicale. St. L. C. R. St. Louis Clinical Record. St. L. M. S. J. St. Louis Medical and Surgical Journal. S. L. P. C. Y. Studies from the Labora- tory of Physiological Chemistry of Yale University'. St. P. M. W. St. Petersburger medi- cinische Wochen- schrift. T. G. Therapeutic Gazette. Ther. Geg. Die Therapie der Gegen- wart. Th. M. Therapeutische Monatshefte. T. M. Therapeutic Monthly. Tr. A. O. S. Transactions of the Amer- ican Ophthalmological Society. Tr. I. C. C. Transactions of the Inter- national Congress of Charity, Corrections, and Philanthropy. Tr. P. C. M. S. Transactions of the Philadelphia County Medical Society. Tr. R. S. Ed. Transactions of the Royal Society of Edinburgh. T. W. Therapeutische Wochenschrift. U. M. M. University Medical Maga- zine. U. N. M. T. Untersuchungen zur Na- turlehre des Menschen und der Thiere. Mole- schott. U. P. L. W. Untersuchungen aus den Physiologisches Labo- ratorium zu Wiirzburg. U. P. M. B. University of Pennsylva- nia Medical Bulletin. V. A. P. A. Virchow's Archiv fiir path- ologische Anatomic und Physiologic. V. A. S. Verein der Aerzte in Steier- mark. V. C. M. Verhandl. des Congresses fiir Innere Medizin. V. V. N. K. I. M. Verhandlungen des Vierten Nord- ischen Kongresses fiir Innere Medi- zin. W. A. W. Sitzungsberichte der kaiser- lichen Akademie der Wis- senschaften zu Wien. Math. Naturwiss. Kl. W. G. H. Wochenschrift fiir die ge- sammte Heilkunde. Wb. G. A. W. Wochenblatt der k. k. Gesellschaft der Aerzte in Wien. W. K. R. Wiener klinische Rundschau. W. K. W. Wiener klinische Wochen- schrift. W*. M. Bl. Wiener medicinische Blat- ter. W. M. P. Wiener medicinische Presse. Z. B. Zeitschrift fiir Biologic. Z. C. P. P. Zeitschrift (Beitrage) zur Chemischen Physiologic und Pathologic. Z. F. H. I Zeitschrift fiir Hygiene und Infectionskrankheiten. Z. K. M. Zeitschrift fiir klinische Medi- cin. Z. Mb. Zeitschrift fiir Medicinal- beamte. Z. P. C. Zeitschrift fiir physiologische Chemie. TABLE OF CONTENTS. PART I. REMEDIES, REMEDIAL MEASURES, AND REMEDIAL METHODS WHICH ARE NOT DRUGS. PAGE CHAPTER I. General Considerations ; Massage ; Feeding of the Sick, includ- ing General Considerations, Liquid Meat Foods, Milk Foods, Artificially Digested Foods i CHAPTER II. The Treatment of Systemic States, including Exhaustion and Neurasthenic Conditions, Corpulence, and Lithiasis 16 CHAPTER III. CALORIC : Local Use of Heat ; General Use of Heat ; Local Employment of Cold ; Cold as a Tonic and Stimulant ; Cold in Pyrexia 28 CHAPTER IV. ELECTRICITY : General Considerations, including Electrical Physics and Physiology as applied to Human Medicine ; Employment of Electricity for the Diagnosis, Prognosis, and Therapeusis of Motor and Sensory Affections ; Application of Electricity to the Nerve-Centres, and Use as a Tonic ; Magnetism 41 PART II. DRUGS. Preliminary Considerations ; Pharmacy ; Therapeutics ; Pharmacology ; Prep- arations ; Indications for the Use of Medicine ; General Methods of Thera- peutics, including Homoeopathy ; Modes of Administration ; Doses, and the Circumstances that modify them ; the Art of Prescribing and Com- bining Medicines ; Incompatibilities ; Classification 60 DIVISION I. SYSTEMIC REMEDIES. CLASS I. GENERAL REMEDIES. ORDER I. NERVINES. FAMILY I. ANTISPASMODICS : Musk ; Valerian ; Ammonium Valerianate ; Valyl ; Validol ; Validolum Camphoratum ; Asafcetida ; Hoffmann's Anodyne ; Hops ; Lactucarium ; Cimicifuga ; Cypripedium ; Acetic Ether ; Sumbul 73 FAMILY II. ANESTHETICS : Nitrous Oxide ; Somnoform ; Ether ; Chloro- form ; Ethyl Chloride ; Ethyl Bromide ; Methyl Bromide ; Pental ; Methy- lene Bichloride ; Practical Anaesthesia ; Local Anaesthesia : Eucaine ; Tropacocaine ; Anaesthesin ; Orthoform ; Stovaine ; Alypin ; Nirvanin ; Practical Local Anaesthesia 82 FAMILY III. SOMNIFACIENTS : Opium ; Morphine ; Codeine ; Peronine ; Dio- nin ; Heroin ; Chloretone ; Amylene Hydrate ; Ethyl Carbamas ; Amylene Chloral ; Methylal ; Hedonal ; Isopral ; Veronal ; Hypnone ; Chloralformamid ; Chloralose ; Butyl-chloral Hydrate ; Chloral ; Sul- phonal ; Tetronal ; Trional ; Paraldehyde ; Amylene Hydrate ; Urethan . 125 FAMILY IV. DELIRIFACIENTS : Belladonna Leaf and Belladonna Root ; Atropine ; Hyoscyamus ; Hyoscyaminae Sulphas ; Scopola ; Hyoscinae Hydrobromidum ; Homotropinae Hydrobromidum ; Cannabis Indica ; Coca 167 xviii TABLE OF CONTENTS. PAGE FAMILY V. EXCITO-MOTORS : Nux Vomica ; Strychnine; Brucine .... 211 FAMILY VI. DEPRESSO-MOTORS : Calabar Bean ; Potassium Bromide ; Am- monium Bromide ; Sodium Bromide ; Strontium Bromide ; Calcium Bro- mide ; Lithium Bromide ; Hydrobromic Acid ; Bromal Hydrate ; Bromo- form ; Gold Bromide ; Bromolene ; Bromipin ; Bromocoll ; Bromalin ; Amyl Nitrite ; Ethyl Nitrite ; Potassium Nitrite ; Sodium Nitrite ; Nitro- glycerin ; Erythral Tetranitrate ; Lobelia ; Gelsemium ; Tobacco ; Conium 230 FAMILY VII. RESPIRATORY STIMULANTS AND DEPRESSANTS : Aspido- sperma ; Aspidospermatine ; Aspidosamine ; Quebrachine ; Hypoque- brachine ; Quebrachamine 276 ORDER II. CARDIANTS. FAMILY I. CARDIAC STIMULANTS : Ammonium and its Salts ; Camphor ; Oil of Camphor ; Camphoric Acid ; Alcohol ; Methyl Alcohol ; Digitalis ; Apocynum ; Strophanthus ; Caffeine ; Convallaria Majalis ; Sparteine ; Adonidin 279 FAMILY II. CARDIAC DEPRESSANTS : Antimony and its Salts ; Veratrum Viride ; Veratroidine and Jervine ; Veratrum Album ; Veratrine ; Arnica ; Aconite ; Aconitine ; Hydrocyanic Acid ; Silver Cyanide ; Cyanogen ; Bitter Almonds ; Benzaldehyde ; Tartaric Acid ; Citric Acid ; Lemon- Juice ; Acetic Acid ; Vinegar ; Oxalic Acid 359 ORDER III. NUTRIANTS. FAMILY I. ASTRINGENTS : Tannic Acid ; Tannalbin ; Ichthyol ; Ichthalbin ; Isarol ; Gallic Acid ; Galls ; Gambir ; Kino ; Haematoxylon ; Rhatany ; Hamamelis ; Oak Bark ; Red and Pale Rose ; Geranium ; Rhus Glabra ; Agaric ; Cotarnine ; Alum ; Aluminii Sulphas ; Aluminii Hydroxidum ; Lead, its Salts and Preparations ; Bismuth, its Salts and Preparations ; Cerii Oxalas ; Zinc, its Salts and Preparations ; Copper, its Salts and Preparations ; Silver, its Salts and Preparations 402 FAMILY II. TONICS : Iron, its Salts and Preparations ; Manganese, its Salts and Preparations ; Sulphuric Acid ; Hydrochloric Acid ; Nitric Acid ; Nitro- Hydrochloric Acid ; Lactic Acid 443 FAMILY III. ALTERATIVES : Phosphorus ; Zinc Phosphide ; Arsenic and its Preparations ; Mercury, its Salts and Preparations ; Gold Salts ; Iodine, its Salts and Preparations ; lodoform ; lodol ; lodipin ; Aristol ; Noso- phen ; Europhen ; Soziodol ; lodoformogen ; Cod-Liver Oil ; Phosphoric Acid ; Calcium Phosphate ; Hypophosphites ; Colchicum Seed and Col- chicum Root ; Tannacol ; Tannopine ; Tannoform ; Sarsaparilla ; Guaiac Wood and Guaiac Resin ; Mezereum ; Jambul ; Thiosinamine ; Taraxa- cum ; Stillingia ; Xanthoxylum ; Animal Drugs : Nuclein ; Gelatin ; Thyroid Body ; Suprarenal Capsules ; Pituitary Body ; Spleen ; Thymus Gland ; Toxins and Antitoxins . .... 459 FAMILY IV. ANTIPERIODICS : Cinchona and its Alkaloids ; Warburg's Tinc- ture ; Methylene-Blue ; Eucalyptus 557 FAMILY V. ANTIPYRETICS : Salicylic Acid ; Oil of Gaultheria ; Aspirin ; Mesotan ; Glycosal ; Salicylic Amylester ; Salicin ; Salophen ; Antipyrin ; Acetopyrine ; Eupyrine ; Acetanilid ; Phenacetin ; Phenocoll Hydrochlo- ride ; Exalgine ; Salipyrin ; Pyramidon ; Thermol ; Pyrosal 586 TABLE OF CONTENTS. xbc CLASS II. LOCAL REMEDIES. PAGE FAMILY I. STOMACHICS : Quassia ; Gentian ; Columbo ; Chirata ; Berberis ; Wild Cherry Bark ; Cinnamon ; Aromatic Fluidextract ; Cloves ; Nut- meg ; Mints ; Allspice ; Cardamoms ; Ginger ; Black Pepper ; Capsicum ; Oil of Cajuput ; Oil of Sassafras ; Orange Peel and Orange Flowers ; Umbelliferous Aromatics ; Chamomile ; Serpentaria ; Cascarilla .... 621 FAMILY II. EMETICS : Ipecacuanha ; Apomorphine ; Mustard ; Zinc Sulphate 632 FAMILY III. CATHARTICS : Manna ; Frangula ; Fel Bovis ; Cascara Sagrada ; Euonymus ; Leptandra ; Tamarind ; Cassia Fistula ; Magnesia ; Sul- phur ; Sulphurated Potassa ; Sulphurated Lime ; Castor Oil ; Mercurials ; Rhubarb ; Aloes ; Senna ; Magnesium Sulphate ; Solution of Magnesium Citrate ; Granulated Magnesium Citrate ; Sodium Sulphate ; Sodium Phosphate ; Rochelle Salt ; Seidlitz Powder ; Jalap ; Colocynth ; Scam- mony ; Compound Cathartic Pills ; Podophyllum ; Elaterium ; Gamboge ; Croton Oil 644 FAMILY IV. DIURETICS : Squill ; Scoparius ; Calomel ; Theobromine and other Xanthin Compounds ; Agurin ; Theophyllin ; Sweet Spirit of Nitre ; Digitalis ; Sugar ; Potassium and its Salts ; Lithium and its Salts ; Piper- azine ; Lycetol ; Urotropin ; Quinic Acid ; Piperazine Quinate ; Urotropin Quinate ; Lithium Quinate ; Helmitol ; Hetralin ; Urasol ; Strontium and its Salts ; Buchu ; Pareira ; Uva Ursi ; Chimaphila ; Triticum ; Juniper ; Oil of Erigeron ; Oil of Sandal- Wood ; Canada Turpentine ; White Tur- pentine ; Oil of Turpentine ; Chian Turpentine ; Copaiba ; Cubebs ; Matico ; Cantharides ; Kava ; Yohimbine 678 FAMILY V. DIAPHORETICS : Turkish Baths and Russian Baths ; Jaborandi ; Dover's Powder ; Sweet Spirit of Nitre ; Spirit of Mindererus 717 FAMILY VI. EXPECTORANTS : Atomization ; Lobelia ; Ipecacuanha ; Tartar Emetic ; Ammonium Chloride ; Grindelia ; Balsam of Peru ; Balsam of Tolu ; Garlic ; Squill ; Tar ; Terebene ; Oil of Sandal- Wood ; Saponine ; Senega ; Quillaja ; Ammonise ; Marrubium ; Sanguinaria ; Sulphuretted Hydrogen 730 FAMILY VII. EMMENAGOGUES : Griffith's Mixture ; Potassium Permanga- nate ; Cantharides ; Guaiac ; Savine ; Rue ; Tanacetum ; Pennyroyal ; Apiol ; Viburnum Opulus ; Viburnum Prunifolium 741 FAMILY VIII. OXYTOCICS : Ergot ; Hydrastis ; Hydrastine ; Hydrastinine ; Cotton-Root 745 FAMILY IX. IRRITANTS AND COUNTER-IRRITANTS : Soft Soap ; Chrysaro- bin ; Cantharides ; Mustard ; Capsicum ; Oil of Turpentine ; Ammonia ; Burgundy Pitch ; Carbon Disulphide 765 FAMILY X. ESCHAROTICS : Caustic Potash ; Vienna Paste ; Arsenous Acid ; Zinc Chloride ; Corrosive Sublimate ; Solution of Mercuric Nitrate ; Sulphuric Acid ; Nitric Acid ; Chromic Acid ; Bromine ; Zinc Sulphate ; Copper Sulphate ; Burnt Alum ; Pyrogallic Acid 776 FAMILY XI. DEMULCENTS : Gum Arabic ; Tragacanth ; Slippery Elm ; Irish Moss ; Licorice Root ; Starch ; Flaxseed ; Sassafras ; Althaea ; Ice- land Moss ; Barley 782 FAMILY XII. EMOLLIENTS : Lard ; Oil of Sweet Almonds ; Cacao Butter ; Linseed Oil ; Olive Oil ; Oleic Acid ; Lanolin ; Glycerin ; Saccharin ; Petrolatum ; Poultices 786 FAMILY XIII. PROTECTIVES : Adhesive Plaster ; Lead Plaster ; Soap Plaster ; Collodion ; Solution of Gutta-Percha 796 xx TABLE OF CONTENTS. DIVISION II. EXTRANEOUS REMEDIES. PAGE FAMILY I. ANTACIDS : Sodium and its Salts ; Lime, its Salts and Prepara- tions ; Chalk, or Calcium Carbonate ; Calcium Haloid Salts 797 FAMILY II. ANTHELM'NTICS : Pinkroot ; Azedarach ; Wormseed ; Cusso ; Santonica ; Santonin ; Male Fern ; Pumpkin Seed ; Turpentine ; Pome- granate Root and its Alkaloids ; Thymol ; Kamala ; Picric Acid .... 805 FAMILY III. DIGESTANTS : Pepsin; Pancreatin ; Extract of Malt; Papain . 815 FAMILY IV. SLBSORBENTS : Charcoal, Wood and Animal 819 FAMILY V. DISINFECTANTS : Cold and Heat ; Mercuric Bichloride ; Binio- dide of Mercury ; Silver Nitrate ; Chlorine ; Potassium Permanganate ; Hydrogen Dioxide ; Acetozone ; Phenol ; Creosote ; Guaiacol ; Salol ; Cresol ; Naphtalin ; Naphtol ; Betol ; Menthol ; Thymol ; Thymacetin ; Resorcin ; Formaldehyde ; Volatile Oils ; Benzoin ; Benzoic Acid ; Cin- namic Acid ; Sulphurous Acid ; Fluorides ; Boric Acid ; Practical Dis- infection 820 APPENDIX. Apothecaries' Measure ; Metrical Weights and Measures ; Relations of Apothe- caries' and Metrical Weights and Measures first, to each other ; second, to Cubic Measure ; Table of the Alcoholic Strength of Distilled Liquors, of Wines, and of Malt Liquors ; Diagrams of Motor Points 879 THERAPEUTICS: ITS PRINCIPLES AND PRACTICE, PART I. REMEDIES, REMEDIAL MEASURES, AND REMEDIAL METHODS WHICH ARE NOT DRUGS. CHAPTER I. GENERAL CONSIDERATIONS MASSAGE FEEDING OF THE SICK. GENERAL CONSIDERATIONS. IN the treatment of chronic disease it is of the utmost importance that the physician inquire minutely into the personal habits of the patient and insist upon their regulation in accordance with the needs of the case. The importance of the alcoholic habit as a cause of local and constitu- tional disease is recognized by many who fail to perceive as clearly the effects of the excessive use of other stimulants. Insomnia, general ner- vousness, and various cardiac derangements are frequently the result of the tobacco-habit, and will not yield to any treatment until the abuse is corrected. Headache, general unrest, nervousness, and many other symp- toms may be the outcome of excessive tea- or coffee-drinking, and espe- cially is this the case when these nerve-stimulants are employed to enable the victim to continue excessive labor. Among the lower classes, and pre-eminently among sewing-women, the nervines just mentioned fre- quently replace substantial food, and the resulting headaches and nerve- failure are to be relieved only by a total alteration of the food-habits. The physician should also carefully study the clothing of his clientele : especially is this necessary in regard to young children. Some mothers so overload the child as to keep the skin in a condition of habitual relaxa- 2 MASSAGE. tion, impeding the natural, free movements, and causing general over- heating. More frequently, however, young children are clothed too little than too much. Bare legs and bare arms in cold climates are fertile sources of illness. There cannot be two opinions in regard to the superi- ority of wool over cotton as a material for underclothing. The well-known effect of wet clothing in causing colds is due to the rapidity with which it conducts heat away from the body. Wet cotton is almost as good a con- ductor of heat as water itself, whereas woollen garments when wet still resist the passage of heat. During exercise cotton underwear becomes damp with perspiration, and in the subsequent cooling of the body fails almost entirely as a protective, whereas a woollen shirt under similar cir- cumstances maintains the temperature of the vital organs. Modern merino underclothing is essentially cotton, and is entirely unfit for wear by deli- cate persons in cold or changeable climates. Persons who suffer from frequent catarrhs or are of a rheumatic or gouty diathesis, or whose nutri- tion is habitually feeble, should always wear next to the skin either wool or silk. When the question of expense is not vital, heavy silk under- garments are as serviceable as those made of wool, and, indeed, in rheu- matic cases, in our experience, are superior to woollen underwear. In very many persons, and especially in those who suffer from frequent diar- rhoeas and indigestions, or derangements of the abdominal viscera, the abdominal bandage should be habitually worn, in addition to the ordinary underclothing. It should be sufficiently wide to cover the whole abdomen, should be either of silk or of wool, and should be so made as to be readily put on and to fit closely to the body. A simple piece of flannel of suffi- cient size, secured in its place by means of ordinary safety-pins, makes, perhaps, as serviceable an abdominal bandage as can be obtained. Both abdominal bandage and underclothing should be worn at night, although, for purposes of cleanliness, it is preferable to change them upon going to bed. The physician should always inquire into the bathing-habits of the patient. Cleanliness and the maintenance of the proper condition of the skin require the use of the bath at least twice a week. In some very deli- cate persons the general bath produces marked depression, but this can almost always be avoided by the use of very hot water. If the hot or warm bath be employed habitually, it should be preferably taken at night, and, unless under very exceptional circumstances, the hot bath should always be immediately followed by cold sponging or the cold shower- bath, or by a plunge into cold water. MASSAGE. The term massage is used as the generic name for external manipula- tions which are employed for the purpose of affecting the nervous and muscular systems and the general circulation. From time immemorial such procedures have been used upon both man and domestic animals. In the sick-room, in the arena, upon the race-course, and in the luxurious MASSAGE. 3 pursuit of health their usefulness has been abundantly proved by the ancient Greeks and Romans, by modern civilized nations, and by barbar- ous or semi-barbarous people. As remedial measures they were spoken of in the writings of the Chinese three thousand years before the Christian era, and were fully recognized by Hippocrates and Celsus. Massage is not rubbing of the skin, although it has in all probability grown out of the practice of such rubbing. General massage is practised to affect the general condition of the body. Local massage is for the relief of local affections. The methods of massage are so complicated that their discussion requires more space than can be here spared for them. Moreover, they can scarcely be learned even from the largest volume treating solely upon the subject, but must be acquired by practice under the guidance of a person having the necessary technical knowledge. A masseur must have sufficient knowledge of anatomy to understand the general drift of the circulation and the positions and shapes of the muscles and of the muscle- masses, must be cleanly and agreeable in person, and must be possessed of the proper technical skill. Especially is this true when the attempt is to treat local disease. Under such circumstances a really accurate knowl- edge of the shapes and positions of muscles, tendons, joint surfaces, and other portions of the affected limb is essential. Unless under very peculiar circumstances, the sex of the operator should be that of the patient. Massage is usually practised upon the bared skin, and we think that this is preferable, although we have known skilful and successful manipulators who preferred that the patient should have thin, tight-fitting underclothes. The question as to whether the skin should be anointed before massage is one concerning which practice differs. The object of massage is to affect, not the skin, but the underlying tissue, and when there is special sensitive- ness or irritability of the skin there can be little doubt as to the imperative necessity of some ointment. Vaseline may be employed. A very excel- lent material is pure and fresh cocoa-nut oil. Only so much of the grease should be used as is necessary to render the skin soft and pliable and to enable the fingers to glide easily over it. Without entering into any detailed discussion of the physiological action of massage, it is sufficient to point out that general massage acts very much like general exercise, without the attendant expenditure of nerve and muscular force on the part of the patient. During prolonged muscular inaction, whether from indolence, disease, feebleness, or other cause, the muscular structure itself suffers some degra- dation and the peripheral circulation becomes very feeble. Much of the albuminous liquid which escapes from the blood-vessels and diffuses itself through the tissues, after serving the purposes of nutrition, is taken up by the lymphatic system and returned to the great blood-vessels. If there be any vis a tergo driving this liquid from the periphery to the centre, it is so feeble that the return of the juices depends chiefly upon the squeezing of the various juice-channels during muscular contractions. During ha- 4 MASSAGE. bitual inactivity the movement of fluids in the lymph-channels outside of the blood-vessels is excessively sluggish, and it is one great object of the stroking movements in massage to force these juices onward ; it is for this reason that these movements are directed from the periphery towards the centre. It is not probable that the whole effect of the stroking is me- chanical. The influence of peripheral nervous irritations upon internal organs and upon the general circulation is recognized by almost every one, and every invalid knows the power of soothing strokes and touches in relieving nervousness and even pain. General stroking movements, if properly administered, are to most persons very quieting, and not rarely, when opportunity is afforded, general massage is followed by quiet sleep. The kneading and percussion movements of massage act chiefly upon the local circulation, increasing its activity in the same way that spank- ing causes a blush upon the young. Kneading performs, however, still another function. Under certain circumstances the fibres of muscles within their sheaths or the neighboring individual muscles through their sheaths become agglutinated, and even the skin itself may get to be abnormally tense and attached to the subdermal tissue, a condition which, when it occurs in the lower animals, is known as " hide- bound." Moreover, gouty or inflammatory exudations may form in almost any portion of the body. Kneading especially has power to mechanically loosen aggluti- nated fibres, to break up masses of exudation, and to so stimulate the local circulation in deeply seated tissues as to cause exudations to disap- pear or even glandular and lymphatic enlargements to be reduced. General massage is employed advantageously in various neurasthenic conditions, and forms an important part of the system of treatment known as the Rest-Cure (see page 17). When there is marked feebleness or nervousness, massage should at first be practised very gently, but, except in rare cases, it will soon be found grateful to the patient. During the processes of the rest-cure, both massage and the faradic current will fre- quently reveal the existence of unsuspected spots of tenderness in various parts of the body. Such tenderness marks local congestion, or very often gouty exudation, and the best results follow from the gradual but persistent application, day after day, of increasingly powerful massage, often aided by very rapidly interrupted faradic currents, to the centres of tenderness, which almost invariably disappear sooner or later. Closely allied to these sore spots is the tenderness of the so-called spinal irritation, or spinal anaemia. When this spinal tenderness is pronounced, great care is necessary in the gradual application of massage and the faradic current to the affected region. If the operator be sufficiently careful at first to work only upon the borders of the tenderness, and gradually to approach the centre, excellent results can usually be obtained. Under these cir- cumstances massage is useful not only as part of the general plan of treating the constitutional condition, but also by its local power in dis- persing congestions and allaying nervous irritations. The first seance in general massage should not last longer than half an MASSAGE. 5 hour, but in a little time a full hour will be required. When there is lack of digestive power, constipation, or any similar symptom, the outcome of sluggishness of the abdominal circulation and nerve-supply, local massage of the abdominal and pelvic regions should be freely employed. Abdominal massage for the purpose of affecting circulation in the intestines should be performed as follows. For one or two moments the abdominal muscles themselves should be kneaded, the individual move- ments being transversely directed across the muscle-fibres ; next, in order to influence the small intestines, a series of circular sweeping strokes should be made around the umbilicus, one hand following the other rap- idly so as to complete the circles, firm pressure being instituted with the outer portion of the palms ; then kneading movement should be per- formed, beginning at the region of the ileo-caecal valve, each movement being transverse to the course of the large intestine, the series of move- ments following the large intestine upward to the hypochondriac region, then transversely, and finally downward along the whole course of the colon. In some cases, especially when there is enlargement of the liver with torpor, good is to be achieved by kneading movements directly over and upon the diseased organ. When along with the enlargement of an abdominal viscus there is a condition of softness, great care should be ex- ercised not to injure the organ by too firm pressure. This applies espe- cially to the pulpy condition of the spleen sometimes seen in malarial disease. Local massage is of great value in the treatment of sprains, chronic inflammations of the joints, and various other surgical affections, but should rarely be practised when the symptoms of the inflammation are at all acute. In subacute or chronic rheumatism affecting muscular or fibrous tissue it is of great value, especially when combined with judicious passive movements. Under its practice adhesions are broken up, exudations are dispersed and finally absorbed, and the natural condition of the parts re- stored. In various forms of paralysis local massage is very useful in main- taining muscular nutrition. When the nerve-lesion is in the cerebrum, the muscles do not suffer in their nutrition, except secondarily from in- activity, and massage is usually not required in the early weeks of the affection. After a stroke of hemiplegia it is rarely proper to begin massage for two or three weeks ; but whenever the temperature of the arm de- cidedly and permanently falls, or serous exudation into the cellular tissue marks a loss of vascular tone, or when evidences of returning control over the muscles are manifest, local massage is often of service. At first the stance should not last more than five minutes, but after a time it may continue for ten or even fifteen minutes. In those forms of palsy, such as infantile paralysis, in which the trophic centres in the spinal cord are especially implicated, massage is of great importance. In acute cases it should be commenced as soon as the subsidence of fever and other symp- toms of constitutional irritation marks the passage of the first stage of 6 FEEDING OF THE SICK. activity in the spinal lesion. When the infantile paralysis develops grad- ually, massage may be employed as soon as the paralysis is recognized. It does not directly influence, to any extent, the fundamental spinal lesion, but, by maintaining a healthy condition of the peripheral apparatus, is of the greatest service in those cases in which there is a tendency to more or less complete repair of the structure of the spinal cord. In various local paralyses, as from pressure, from rheumatic affections of the nerves, or from other temporary or removable conditions of nervous or muscular tissue, massage may do much good. When the loss of power in a muscle is due to direct violence, as occurs with especial frequency in the deltoid muscle from falls on the shoulder, massage should be assiduously em- ployed as soon as the primary inflammation produced by the injury has subsided. In such cases the treatment is of especial advantage in dis- persing exudations and restoring the muscles and the muscle-fibre bundles to their normal relations and their normal looseness. FEEDING OF THE SICK. The present article is not a treatise upon diet or dietetics ; the books upon this subject are sufficiently numerous, but their scope is often too wide for the needs of the medical practitioner. In elaborate discussions upon the contained percentage of nitrogen and general food- qualities of various articles of diet, upon the cost and commercial history of foods, upon the amount of food necessary to sustain life, and upon the most economical forms of military, prison, and hospital rations, etc. , the con- sideration of the feeding of the sick in private practice is often so over- whelmed as to be lost entirely. We propose to give here a brief practical summary of the methods of feeding in sickness when pecuniary consider- ations are of secondary importance. The proper feeding in acute diseases accompanied by high fever varies to some extent according to the individual affection, but is subject to general principles which are sufficient practical guides for most cases. All such acute diseases are for present purposes readily divided into those in which the acute febrile stage is very short and those in which it is pro- longed. When the acute febrile stage is very severe and temporary, it is usually associated with a complete anorexia, which the practitioner may obey with safety. In the first day or two of the onset of an acute pneu- monia, violent scarlet fever, or similar affections, there is no cause for alarm even if the patient take no food. The digestive power at this time may be in complete abeyance. After, however, the first day or two of such an attack, and whenever the febrile reaction is prolonged, a loss of appetite amounting even to a disgust with food is no excuse for abstinence. All such states, with their accompanying diseases, tend to fatal result through exhaustion, and much can be done by proper feeding to prevent complete failure of vital power. The older writers upon dietetics taught that a fever patient was not to be fed, and some modern authors reiterate the old dictum. Fever is not, however, any centra-indication to food. FEEDING OF THE SICK. 7 It is, indeed, usually associated with loss of digestive power, and if under such circumstances the stomach be overloaded with coarse food the symp- toms will be aggravated by the resulting acute indigestion. The amount of nourishment received by a body is measured, not by the amount of food put into the stomach, but by the amount which is assimilated ; and in febrile complaints the effort of the physician must be directed, not to the filling of the stomach, but to the obtaining of as large an assimilation of food as is possible without disturbing the alimentary canal. Any symp- toms of gastric or intestinal disturbance should be the signal for the imme- diate lessening of the food. Such gross manifestations as vomiting, sour or nauseous eructations, and gastric distress are perceived at once by the most careless ; but in typhoid fever we have seen skilful practitioners over- look the real cause of an excessive tympany or an increased diarrhoea, and continue the overfeeding while attempting to relieve these symptoms by medicine. Such practice is exceedingly reprehensible. In febrile adynamic diseases the feeding should be at short intervals, with small amounts of liquid food of a nutritious, easily digested character, and our own experience leads us more and more to the habitual use of foods which have been partially digested artificially. The question of night-feeding in severe cases is an important one. Our belief is that death occurs much more frequently in adynamic diseases between one and five o'clock in the morning than at any other time, a circumstance largely attributable to the habitual withholding of food and stimulants during the night. Sleep is essential to the recuperation of vital force, but an exhausted patient usually goes to sleep readily after the par- tial awakening which is sufficient for the administration of a milk punch, or else sleeps in so broken a manner that the careful nurse can give the food at short intervals without awakening him. In no typhoid case of severe type should an interval of more than three hours be allowed to elapse at night without food and stimulants, and the amount given at a single time should be so increased that almost as much will be taken during the night as during the day. In typhoid cases alcohol in some form should be given with the food, in not too large proportion. Alcoholic liquors in moderate amount stim- ulate the stomach and aid digestion and absorption, but in large amount interfere with these processes. It may be set down as a general rule with few exceptions that all foods given in protracted febrile states should be in liquid form. Liquid foods may be divided into Liquid Meat Foods, Milk Foods, and Artificially Digested Foods. LIQUID MEAT FOODS. It must be remembered that all articles of the present class are stimulants rather than nutrients. Most of them do not contain more than one per cent, of albuminous substances. Under this heading we include all liquid preparations of meat made without arti- ficial digestion. At one time these liquid preparations of meat were supposed to repre- 8 FEEDING OF THE SICK. sent the whole nutritive value of the meat, but recently all nutritive power has been denied to them. They contain kreatin, kreatinin, sarkosin, sar- kin, xanthin, kreanin, inosite, fat, and inorganic salts, with a very small amount of albuminous principles. It is not probable that any of these substances, except the albumin and the fat, are capable of being assim- ilated and used as food. The experiments of Kemmerich also indicate very strongly that they are not nutrients, for he found that animals fed exclusively upon these preparations died even more quickly than those left to starve. There can be no doubt that death under these circum- stances was largely due to the depressing effect of the inorganic salts con- tained in the extracts. Clinical experience, in a measure, conforms with this scientific reasoning. At a time when beef essence and beef tea were very largely relied upon as nutrients in Philadelphia, it was found that they acted better when milk was also given. In his earlier trips into the wilderness, involving much physical labor, H. C. Wood took with him the best artificial meat extracts to serve as condensed food, but, after a few trials, found that they were unable to sustain prolonged effort, as the guides put it, " they do not stick to a man's ribs," and, although at that time the theory was that they were concentrated nourishment, practi- cal experience soon led to their abandonment. Although of little use as food, these substances are valuable stimulants, and may by reviving temporarily an exhausted patient prepare the way for the digestion of food. In a series of experiments made upon the frog's heart by Thomas J. Mays (Therap. Gaz., vol. ii. p. 152), it was found that ( the artificial beef extracts and concentrated beef preparations had a very de- cided influence in maintaining the activity of the systoles. Notwith- standing Mays' s arguments to the contrary, however, we believe that the effect of beef extracts upon the frog's heart is entirely similar to that of the phosphate of calcium (see CALCII PHOSPHAS). In typhoid and other similar low fevers it is an excellent plan to give beef essence or beef tea alternate hours with milk punch. During convalescence a hot bowl of beef tea or beef essence after exertion such as carriage-riding, walking, etc. , may act very well as a stimulant. By the addition of various sub- stances these liquid preparations of meat can be made nutritive : thus, an egg rapidly stirred into a bowl of beef essence forms a very useful stimu- lating food. There are in the market various extracts of beef claiming to represent, in a solid form, beef essence. The better forms of these articles undoubtedly do represent in great part beef essence, but they are dis- tinctly inferior to the freshly made preparation in taste, and in containing no albumin : so that it is always better to employ the fresh beef essence if it can be procured. Liquid meat foods are divisible into those that are raw and those that are cooked. Of the raw foods of the class, the best is meat juice. This is made, according to the directions of Pettenkofer and Voit, by selecting lean meat from the round of beef, cutting it into small pieces, and ex- pressing the juice in a press of sufficient power, such as now can be pur- FEEDING OF THE SICK. 9 chased at any of the larger drug-stores. This juice contains, in addition to the salts and extractives, the albumin that remains fluid after the rigor mortis, chiefly serum-albumin and coloring matters. The proportion of albumin is about six per cent. : by heating the albumin is precipitated, but it is not affected by salt or by mere warming. Meat juice is a valuable preparation when a powerful stimulation is desired and the digestive forces are exceedingly weak, as in the feebleness or collapse that follows cholera infantum and other infantile diarrhoeas. Its taste is that of raw meat, and is so disagreeable to many persons as to prevent its use. Liebig's beef tea is made by adding seven ounces of water and three or four drops of hydrochloric acid to one and a half pounds of lean beef, allowing to stand one hour, passing through a hair sieve, and washing out the meat with three ounces, of water. This infusion contains, on the average, not more than one per cent, of albumin. The hydrochloric acid added to the water is not sufficient to dissolve the myosin of the muscle : so that this preparation can be looked upon as nothing more than a dilution of meat juice, and is very inferior. To have any effect it must be given in enormous quantities. The cooked concentrated liquid forms of meat extracts are beef tea and beef essence. Neither of these can be considered to have distinct nutritive value. It is very rare for them to contain more than one per cent, of albuminous substances; but they are powerful stimulants, and for such purposes are as useful as the expressed meat juice. To make beef tea, cut one pound of round of beef into small cubes not larger than half an inch in diameter; soak for two hours on the back of the range, in an earthenware pipkin, with one pint of cold water, and allow to simmer for about fifteen minutes, and finally to boil for three minutes; add half a teaspoonful of salt and pepper, pro re nata. To make beef essence, prepare the meat as for beef tea ; put it into an earthen- ware bottle without water and loosely cork ; set this in a pot of cold water and bring very gradually to the boiling point ; boil for twenty minutes or half an hour. Soups are liquid preparations which resemble beef tea and beef essence in containing the extractives of meat, but which differ from these prepara- tions in having in them various nutritive substances. Soup is therefore both a stimulant and a nutrient, the amount of nutrient material varying greatly according to the preparation of the soup. The lighter forms of soups are commonly spoken of as broths. They may be used when the stomach rejects less readily digested forms of food. To make chicken broth, take three pounds of chicken well cleaned, cover with cold water, boil from three to five hours (until the meat falls to pieces), strain, cool, and skim off the fat. To a pint of this add salt and pepper and two table- spoonfuls of soft rice which has been previously thoroughly boiled in salt water ; bring the broth to a boil. In preparing the rice, half a cupful should be boiled for thirty minutes with a teaspoonful of salt in a pint of water. To make mutton broth, take one pound of lean, juicy mutton, chopped fine, and proceed as with chicken broth. io FEEDING OF THE SICK. In the preparation of soups the first thing is the making of the so- called stock, or basis for the soup. There are two distinct stocks : one which may be known as the brown stock, the other as clear stock or con- somme. To make brown stock, take four pounds of shin of beef, four quarts of cold water, ten whole cloves, four peppercorns, a bouquet of herbs (sweet marjoram, summer savory, thyme, and sage), one tablespoonful of salt, three small onions, one turnip, one carrot, two stalks of celery, two sprigs of parsley. Cut the meat from the bones, after which place the bones and one-half of the meat in a soup- kettle and allow to stand for half an hour in the cold water. Heat gradually, and allow to simmer for six or seven hours. Brown the remainder of the meat in two tablespoonfuls of beef-drippings, and add with the other meat and with the vegetables chopped fine, when the kettle is put on the fire to simmer. After it has simmered the required time, strain the stock and set aside to cool, the fat being removed from the top. The stock is then ready for use. To make consomme or clear stock, proceed in exactly the same way as for brown stock, except that three pounds of the knuckle of veal are to be added to the meat, and all the meat is to be put in at once without browning. After the stock has been formed, in order to clear it add the white and the shell of one egg and the juice and rind of one lemon, beating them all up together ; then put on the fire, bring to the boiling point, strain through a sieve, and again through a napkin, without pressure or squeezing, and serve. In making the soups the stocks must never be allowed to boil, or at most must be brought only for a moment to the boiling point. To make Julienne soup, put one pint of the brown stock on the fire to heat, after which a pint of finely chopped vegetables (turnip, carrot, etc. ) , with half a tea- spoonful of salt, should be put on with a little water to parboil. This being done, add the vegetables to the stock, and season with half a saltspoonful of pepper. Vermicelli soup is made by adding half a cup of vermicelli to a pint of the brown stock. Cook the vermicelli for ten minutes in salted boiling water, season with a half-teaspoonful of salt and a half-saltspoonful of pepper, and add to the warm stock. A very elegant stimulating and nutritious soup can be made out of consomme by boiling ordinary pearl sago in salt water for from two to three hours, until the grains become swollen almost to bursting, and then stirring the sago into the consomme while still boiling. MILK FOODS. Of all liquid foods milk is the best and the most gen- erally applicable to the treatment of disease. Cow's milk contains, in round numbers, 87.5 parts of water, 3 parts of casein, 0.75 part of albu- min, 3.6 parts of fat, 5 parts of sugar, and 0.07 part of inorganic salts. One pint of milk contains, in round numbers, 0.6 ounce of solid albumi- nous substance, o. 6 ounce of fat, and o. 8 ounce of sugar. When two quarts of milk are taken in the course of twenty-four hours, about two and a half ounces of fat are ingested, an amount too great for an inefficient ali- mentary canal to digest, so that it is often necessary to skim the milk. As milk contains practically no indigestible residue, it leaves behind it in the alimentary canal no fecal matter, and its use therefore frequently pro- FEEDING OF THE SICK. n duces constipation. In cases of diarrhoea this tendency to a binding action can be increased by boiling the milk, a process which coagulates the albu- min of the milk and slightly lessens, if the scum be removed, its nutritive value. When milk is used very freely and the digestion is feeble, there is always danger of the formation in the stomach of a coagulum so dense that the gastric juice will not be able freely to penetrate it. This difficulty can usually be overcome by a little care. The addition of from half an ounce to an ounce of lime-water to every five or six ounces of milk has a distinct tendency to prevent too rapid and firm coagulation. Sipping milk instead of drinking it in other words, putting the milk in the stomach in small quantities at a time has a still greater power in repressing the formation of hard coagulum. When the digestive powers are feeble, milk should be taken slowly in small quantities at a time. In some cases it is very important that it be drunk hot, but without previous boiling. There are various useful nutrient and stimulant foods prepared with alcohol in milk, as follows : To make wine whey, bring half a pint of milk to the boiling point ; add half a pint of sherry wine, and allow to stand in a warm place for five minutes ; strain, and sweeten to taste. The whey which is left consists almost exclusively of wine and water, with milk sugar and milk salts. It contains very little nutriment, but is sometimes tolerated by the stomach which refuses other food. To make milk punch, take half a pint of milk ; pour into it from a dessertspoon- ful to a tablespoonful of brandy, rum, or whiskey, according to the needs of the patient ; sweeten and spice with nutmeg to taste. This preparation represents all the nutritive value of milk and the stimulating effects of the liquor. If the stomach be at all delicate, a tablespoonful of lime-water should always be added to it before putting in the brandy. To make eggnog. Eggnog is a heavy, rich, highly nutritive liquid, which must be employed in limited quantities, and very carefully when there is any delicacy of stomach. The yolk of one egg may be added to half a pint of milk, afterwards from half an ounce to an ounce of brandy, and the white then beaten in. Sometimes when the stomach rejects almost all forms of food, the addition of carbonic acid water to the milk meets with success. Equal quantities should be employed, and the casein of milk should be coagu- lated in fine flakes. A light, powerfully stimulant beverage, somewhat similar to the one just mentioned, but to some palates more elegant, is made by the addition of champagne to milk. There are certain forms of fermented milk which are valuable as being easily digested by the stomach and very acceptable to the palate. They also render possible some variety of food to persons largely restricted to milk diet. Koumiss, or kumys, is a fermented liquid prepared by the Tartars from mares' milk. In this country it is made from cows' milk : it is to most persons a very agreeable beverage, which in nutritive qualities represents the same quantity of milk, and is by most stomachs much more easily digested. It is very well suited for the treatment of convalescence and of chronic diseases, though it may be used, often with great advantage, in acute febrile illnesses. Take an ordinary beer-bottle 12 FEEDING OF THE SICK. with a patent shifting cork, put in it one tablespoonful of white sugar, one pint of milk, one-sixth of a cake of Fleischmann's yeast or one drachm of strong liquid yeast, shake well, allow to stand from eight to ten hours in a temperature of from 85 to 95 F., shake well, and put upon the ice to cool. This ought to be used within twenty-four hours after being made. The longer the fermentation is allowed to continue the more sour is the koumiss ; and its condition should be regulated to suit the individual palate and stomach of the patient. If it be desired, it may be flavored by the addition of a small piece of vanilla bean to the milk before fermen- tation. Matzoon differs from koumiss in that it contains no carbonic acid, is thicker, and more cheesy in its flavor. It occurs in the market in various brands, but we know of no practical method of making it at home. It is the product of a peculiar fungus known as the kefir ferment. Milk may be used as the basis of a number of farinaceous or starchy liquids. It must be remembered that these starchy compounds are more or less difficult of digestion, and during the progress of an acute, severe febrile illness they must be employed with the greatest caution. In con- valescence and in chronic invalidism, however, they are often very ser- viceable. In making these preparations it is essential that they be closely watched and stirred, to prevent burning, unless they be cooked over hot water. To make oatmeal porridge, stir two ounces (half a cupful) of crushed oatmeal into a pint of milk, previously warmed, and afterwards cook from twenty to thirty minutes ; add salt to the taste. To make baked floiir porridge, a very excellent porridge, of easy digestion, and especially valuable when there is a tendency to looseness of the bowels, take one pint of flour, pack tightly in a small muslin bag, throw it into boiling water and boil for five or six hours, cut off the outer sodden portion, grate the hard core fine. and stir into boiling milk to the desired thickness. To make arrow-root porridge, stir two teaspoonfuls of arrow-root in half a teacupful of cold milk until a perfectly smooth mixture is made ; have on the fire a pint of milk, and, while this is boiling, add the arrow-root little by little, stirring constantly until cooked, i.e., from one to two minutes after the last is poured in ; add sugar, nutmeg, and wine, according to taste or the exigencies of the case. When milk is not to be had, or a very low diet is required, water may be substituted. The secret of properly preparing arrow-root is in having the first mixture with milk absolutely smooth and free from lumps. To make chocolate porridge, a very palatable gruel to many persons, mix to- gether one-quarter pound of best chocolate, grated, one-half pound of rice flour, two ounces of arrow-root, and one-quarter pound of loaf-sugar, grated ; add a table- spoonful of this mixture to a pint of hot milk, and let it boil five minutes ; then remove the preparation from the stove and serve hot. It should have the consist- ency of gruel. To make tomato porridge, a very excellent porridge or puree, highly nutritious and useful during convalescence, take one quart of canned tomatoes, bring to a boil, strain while hot through a hair sieve ; bring a quart of milk to a boil, add suf- ficient flour to make a thick paste, stir in, and continue to boil until the flour is cooked (about twenty minutes) ; stir the strained tomatoes gradually, a little at a time, into the boiling milk ; cook five or ten minutes, seasoning to taste. To make sago porridge or sago jelly, wash the sago well in cold water, put a small teacupful of it in half a pint of water to soak overnight, and in the morning put this mixture into one pint of hot water ; squeeze into it the juice of a thinly FEEDING OF THE SICK. 13 pared lemon, and allow to simmer slowly for twenty minutes ; then sweeten, add wine according to taste or the exigencies of the case, and pour into moulds to cool. To make tapioca porridge, soak two tablespoonfuls of clean tapioca in two teacupfuls of cold water overnight ; in the morning add a little salt and one pint of milk, or water if milk is not allowed ; simmer until quite soft ; stir well while cooling ; when done, pour into a bowl, and add sugar, wine, and nutmeg, accord- ing to taste or the exigencies of the case. ARTIFICIALLY DIGESTED FOODS. In low fevers the powers of the alimentary canal are certainly much impaired, and foods which have undergone more or less complete artificial digestion outside of the body are very useful. In all cases in which the typhoid symptoms are severe, milk should constitute the chief reliance, and should be partially digested before ad- ministration. When the disease is prolonged, and especially when the mental condition is clear, the patient frequently tires of milk. Under these circumstances various liquid foods prepared by the partial digestion of solids are of great importance. Artificially digested foods are also of value during convalescence, and their employment constitutes a very important part of the treatment of gastric and intestinal catarrhs. Most peptones have a distinctly bitter taste, which may be very objectionable in indi- vidual cases. This taste can be partially overcome by the addition of flavoring substances or extracts, and often may be altogether avoided by arresting the process of artificial digestion before completion. At first thought pepsin would appear to be the most available ferment for the preparation of peptones ; but practical experience has led to re- liance upon pancreatin. Pancreatin, pancreatic extracts, and pancreatic liquors are now found abundantly in commerce. The superiority of the secretion of the pancreatic gland as a practical ferment is connected with the fact that it contains two distinct classes of digestive principles, namely, pancreatic diastase, which dissolves starch, and trypsin, which acts upon albuminous principles. It is of great importance to be able to determine readily the value of any preparation of pancreatin. The test devised by William Roberts {Digestive Ferments, London, 1881) appears to be very practical. If pancreatin be added to fresh milk without an alkali, in the course of a few minutes the liquid acquires the property of curdling abundantly upon boiling ; and Roberts estimates the value of a pancreatin by the number of cubic centimetres of milk which are trans- formed by one cubic centimetre of the sample at a temperature of 40 C. to the curdling point in five minutes. The liquor pancreaticus used by Roberts had a power oscillating between fifty and seventy. A test which may be substituted for that of Roberts, and which is especially applicable to the ordinary pancreatic extracts or so-called pancreatin, is based upon the peptonizing power of the powder. Five grains of it added to twenty grains of sodium bicarbonate should so alter the casein contained in one pint of milk at a temperature of 115 F. in an hour, that no coagu- lation will occur upon the addition of nitric acid. 14 FEEDING OF THE SICK. To make peptonised milk, dilute a pint of milk with a quarter of a pint of water, heat to about 140 F., add two teaspoonfuls of liquor pancreaticus (Roberts's) with twenty grains of sodium bicarbonate, digest in a warm place for an hour or an hour and a half, raising momentarily to the boiling point ; at the temperature of the sick-room, 65 F., the digestion will usually require about three hours. Or milk may be peptonized by dissolving five grains of pancreatin with twenty grains of sodium bicarbonate in an ounce of warm water, adding to a pint of milk, and keep- ing at a temperature of 1 10 F. for one hour. Thoroughly peptonized milk has a disagreeable bitter taste, so that in practice the peptonizing process is usually not allowed to come to completion. It must, however, be remembered that the taste is a test of the peptonizing, and that the so-called peptonized milk which has no bitter taste is simply milk mixed with pancreatin, nothing more. Probably the greater part of the peptonized milk given to the sick is practically simple milk. To m^fx. peptonized milk gruel, prepare a thick gruel with arrow-root, oatmeal, sago, or other similar farinaceous articles, add, while still hot, an equal quantity of milk, and subsequently, when cooled to 100 F., for each pint twenty grains of sodium bicarbonate and two teaspoonfuls of liquor pancreaticus or five grains of pancreatic extract, digest in a warm place for two hours, boil the mixture momen- tarily, and strain. To make peptonized beef tea, simmer half a pound of minced beef for two hours in a pint of water containing twenty grains of sodium bicarbonate, allow to cool to about 100 F., digest at this temperature with a tablespoonful of liquor pancreaticus or ten grains of pancreatic extract for three hours, decant and momen- tarily boil. This beef tea is said to be about equivalent to milk in nutritive value, containing 4.5 per cent, of organic solids, three-fourths of which is peptone. To make peptonized oysters, a palatable and nutritious dish, mince six large or twelve small oysters, and add to them, in their own liquor, five grains of pancre- atic extract with twenty grains of sodium bicarbonate ; bring the mixture to 100 F., and maintain, with occasional stirring, at that temperature for thirty minutes, then add one pint of milk and keep the temperature steadily up for ten or twenty min- utes ; finally the mass is to be brought to the boiling point, strained, and served. Gelatin may be added, and the mixture served cold as a jelly. Cooked tomato, onion, celery, or other flavoring suited to the individual taste and condition of the patient may be added at the beginning of the artificial digestion. To make pancreatized milk toast, digest soft milk toast for from thirty to fifty minutes with pancreatin and sodium bicarbonate until it becomes an almost homo- geneous pulpy mass, which, when the crusts have been removed, is usually readily retained by the irritable stomach. In extreme cases, however, it may advanta- geously be strained and the fluid portion alone used, in which the partially pep- tonized solution of casein of the milk is reinforced by the actually digested gluten and starch of the bread, together with a very little dextrin. Plain, light sponge- cake may be similarly digested, and occasionally forms a desirable change. RECTAL ALIMENTATION. In severe gastritis and in gastric ulcer it is sometimes necessary to enforce a temporary or even a somewhat pro- longed abstinence from food. In diphtheritic paralysis of the throat, as well as in strictures of the oesophagus, it may be almost impossible to get food into the stomach, and in various cases the food is vomited whenever it is ingested. Under any of these circumstances feeding by the rectum becomes a matter of the utmost importance. There is no reason for be- lieving that the rectal or even the colonic secretions have digestive power. Absorption goes on slowly from the rectum, but, according to Landois, very rapidly from the colon itself. For these reasons injections which are FEEDING OF THE SICK. 15 used for the purpose of nourishing the patient should be bland, concen- trated, and thoroughly digested ; peptonization should always be com- plete. Moreover, the material should be thrown high up into the colon. It should be given not oftener than three times in twenty-four hours, and the colon should be thoroughly washed out by a high injection of simple water at least twice in the twenty-four hours. If there be irritability of the colon, it may be necessary to add opium to the nutritive material injected. Again, in many cases whiskey or brandy may be very useful. In most cases it is best to give the injection not oftener than twice in the twenty- four hours, and to wash out the colon an hour before administration. The presence of a putrid odor in the discharges is evidence that more food is given than the colon can work up, and the colon is as much irritated by overfeeding as is the stomach. In colonic as well as in gastric feeding it is the amount absorbed and not the amount ingested that does good. In 1872, from the pancreas of swine or cattle, W. O. Leube made a food preparation which he experimentally proved to yield nutritive material to the blood of dogs when injected into the colon, and by whose colonic exhibition he maintained life for four weeks in a patient whose stomach rejected all food. Leube' s formula may be found in detail in the tenth edition of this book, but is here omitted because it has no superiority over preparations made with commercial pancreatic extracts. As milk and eggs contain all the food necessary for the sustenance of life, and are more rapidly and readily digested than is meat, all that is necessary is to digest them thoroughly before injection. From half a pint to a pint of milk with two or three eggs may be employed at each injection. It is however impossible to maintain nutrition with rectal feeding for any length of time. CHAPTER II. THE TREATMENT OF SYSTEMIC STATES. EXHAUSTION AND NEURASTHENIC CONDITIONS. DEPRESSION is a condition of temporarily lowered vital activity pro- duced by the presence of some poison in the system. Exhaustion is a condition of absolute lack of power in which the functional activity is repressed, not by a depressing substance, but by the inability of the affected part. In practice it is essential to distinguish between these two states. The one requires treatment by stimulants, while the other is often, al- though temporarily relieved, permanently aggravated by the use of stimu- lants. Exhaustion, especially of the nervous system, is frequently spoken of as a disease, under the name of neurasthenia. It is not a disease, how- ever, but a condition, which may be the result of overstrain or overwork or of some chronic disease. It is essential that in every case of alleged neurasthenia very careful examination should be made to detect the pres- ence of organic kidney disease, chronic diarrhoea, or other possible cause of the exhaustion. The amount of work necessary to produce neuras- thenic exhaustion is dependent upon the original amount of power in the organism. In persons born of neurotic feeble parentage or of parents exhausted by overstrain, the working power may be very slight. Ex- haustion may be local or it may be general. This applies to the nervous system as well as to the other apparatus of the body. A local nervous exhaustion tends towards developing into a general condition. Thus, a writer's palsy may be the first symptom of a general break-down. Sper- matorrhoea, at first due purely to local exhaustion of the implicated nerve- centres, if unchecked very generally develops into general neurasthenia. The same is true of cerebral exhaustion following excessive mental work. The exhaustion is to be relieved only by recuperation, and recuperation is to be obtained only by rest and the assimilation of food. The nature of the rest depends upon the character of the exhaustion. In cases of pure cerebral exhaustion with the bodily powers untouched and the physical powers not much implicated, freedom from care and from all mental work, conjoined with life in the open air, is the essential of cure. It must be remembered that sight-seeing is as exhausting to the brain as is the hardest study, and that in extreme cases even the seeing of friends may overtax the brain, so that isolation may be essential. Such isolation may be obtained, if the bodily powers remain good, by travel in the wil- 16 EXHAUSTION AND NEURASTHENIC CONDITIONS. 17 derness, or on the ocean, or in other positions where intercourse with the world is impossible. In cases of extreme neurasthenia or nervous exhaus- tion the so-called rest-cure is a method of treatment of great value. It is essential for its successful employment that it be modified to suit the needs of the individual case : if employed as a set mould into which every case is to be forced, it will frequently do harm. The principles of the rest-cure are absolute rest, forced feeding, and passive exercise. Absolute rest is often prescribed by the physician with- out being sufficiently definite and insisted upon. When it is desired to apply it most strictly, it should be clearly explained that the patient is not to be allowed to get out of bed even to pass urine or faeces, nor to feed himself or herself, nor perform any act of the toilet whatsoever. The rest also must be for the mind as well as for the body, and it is essential that the patient be isolated. In obstinate, severe cases of neurasthenia complete and absolute isolation is a sine quti non, and especially when there is a decidedly hysterical element is it necessary to separate the patient entirely from her friends. Under these circumstances there must be a well-trained nurse who is personally agreeable to the patient. The confinement would be very irksome to any except the most exhausted patient were it not for the daily visit of those engaged in the treatment. To provide further against ennui, the nurse should be a good reader, so that under the definite instructions of the physician she can occupy a certain portion of the time in reading to the patient. In order to maintain the functions of the skin, the patient should be well sponged with hot water in bed every morning after breakfast. A strong solution of salt, or, better, sea-brine, is to be preferred to simple water, and frequently it may be followed by the use of alcohol. In very feeble cases the alcohol may be employed alone. We have seen very good effects from momentarily rubbing each portion of the skin with ice just after bathing. When rubbing with ice is practised, the water used in the bathing should be as hot as can be borne. In giving the bath the patient should be stripped, and lie between blankets, so that exposure of the whole body is avoided while each part is thoroughly washed. No exertion on the part of the patient should be allowed. Women should not be permitted to arrange their own hair. The question of feeding is one of great importance, and requires the utmost care and attention from the physician. The end to be attained is to feed the patient as much as can be digested, but not to overfeed and derange the digestion. Food should be given at intervals of two or three hours, and must be both light and nutritious. It should, at least at first, consist largely of milk, except in those rare cases in which that fluid does really disagree with the stomach and is not merely thought to do so. The milk should be skimmed or given in the form of koumiss. Beef juice and other concentrated meat essences are valuable as stimulants, and may be used especially as the basis of soups. Various farinaceous articles of food may be added to them : if an egg be stirred into the concentrated bouillon i8 THE TREATMENT OF SYSTEMIC STATES. or beef essence just as it ceases boiling, a nutritious and to many persons palatable dish is obtained. When constipation exists, oatmeal porridge, Graham bread, and fresh or dried fruits may be allowed if readily digested by the patient. In order to give an idea of a general plan of the dietary, the following schedule of the daily life is given. It must be altered from day to day, so as not to weary the patient by its monotony. Such a schedule should always be put in the hands of the nurse, who should be required to follow it strictly. Success will in a great measure depend upon the practical skill and tact of the physician in his adaptation of the diet to the individual requirements of the case : 8 A.M. Rolls or toast ; cocoa or weak coffee, or roasted wheat coffee ; beef- steak, tenderloin, or mutton-chop. 9 A.M. Bathing. 11 A.M. Oatmeal porridge, with milk, or else a pint of koumiss. 12 M. Massage. 2 P.M. Dinner : bouillon with or without egg ; beefsteak, rice, roast white potatoes ; dessert of bread-pudding, blanc-mange, or similar farinaceous articles of diet. 4 P.M. Electricity. 5 P.M. Milk toast. 9 P.M. Half a pint of skimmed milk or koumiss. In many cases the patient at first can take very little food, and it is frequently best to begin the treatment with an entirely liquid diet, giving milk every two hours, or some nutritious soup, with milk or plain farina- ceous food, and only after a time gradually accustoming the patient to solid food. Not rarely a prolonged treatment by the so-called milk diet is of avail. The rest-cure is, indeed, largely based upon a careful regu- lation of the food. Passive exercise is to be obtained by the use of electricity and massage, the object being to get the effects of exercise upon the nutrition and cir- culation without the expenditure of the patient's nerve-force. By the use of electricity muscular contractions are secured that simulate those which are voluntary, and more or less thoroughly replace them. The faradic current is alone used. It is applied in two ways : first, to the individual muscles ; second, to the whole body. The s6ances should be daily, the operator beginning at the hand or the foot, and systematically faradizing each muscle of the extremities and the trunk. The slowly interrupted current is generally preferable, but advantage is sometimes gained by varying the rapidity of the interruptions. The general rule is to select that current which produces most muscular con- traction with the least pain. The poles should be applied successively to the motor points of the muscles, so as to contract each firmly and thoroughly. This process should occupy from thirty to forty minutes. The electrodes are then to be replaced by large sponges well dampened with salt water : one of these should be put at the nape of the neck and the others against the soles of the feet, and a rapidly interrupted current, EXHAUSTION AND NEURASTHENIC CONDITIONS. 19 as strong as the patient can bear, should be sent through the body for twenty minutes or half an hour. It is unnecessary for the physician to remain during this time. In some cases the electrical programme may be varied so as to get a local stimulant action from the general current. Thus, when digestion is enfeebled and the bowels are costive, for a portion of the time one of the sponges may be placed upon the epigastric region. In women, when there is great abdominal and pelvic relaxation, one pole may be placed high up in the vagina. We have seen old-standing pro- lapsus cured in this way. The principle of rest-cure for the relief of exhaustion has a very wide application. Thus, in the treatment of acute diseases, such as typhoid fever, in which death results from exhaustion, it is of the utmost impor- tance that absolute rest be prescribed very early. Before the diagnosis can be certainly established, and when there is merely a suspicion of typhoid fever developing, the patient should be put to bed, and should not be allowed to get out for any purpose. One great object of nursing is the saving of the strength of the patient and the prevention of exhaus- tion by disturbance. Mere uncleanliness, a low voice to a deaf patient, a loud, high-pitched voice to one whose hearing is acute, failure to under- stand quickly the whims and caprices of a sick man or woman, are tor- menting things, which may take away the rest and even destroy the life of a patient. It is almost equally essential that all fussiness be avoided. The nurse who is continually asking the patient whether he will have this or that, or wants this or that, or is shifting the blinds, or fixing the fur- niture, or moving about unnecessarily, may not only be disagreeable, but may do great harm. In applying the rest-cure to the treatment of the individual case, it must be remembered that the system is based upon certain principles, and that these principles are frequently, in the individual case, best carried out by a modification of the details of the plan which has been given. Not rarely advantage is obtained by daily sending the patient out carriage- riding, or even from taking walking exercise once a day. In other cases the rest-cure may be very advantageously combined with more protracted out-door life and exercise, the patient being required simply to pass twelve, fourteen, or sixteen hours out of the twenty-four in bed and the remaining time in the open air. It is impossible, within moderate scope, to describe all the modifications of the method which will occur to the skilful physician. The time of continuance of the rest-cure varies greatly : even in extreme cases the patient should be allowed to sit up at the end of six or at most eight weeks, and in many instances three weeks of seclusion is all that is absolutely essential. The period of convalescence requires care. An attempt to return rapidly to the performance of household duties or to the ordinary labors of life will usually dissipate the acquired strength, and for the gain to be permanent it is in most cases necessary that the patient be sent to some quiet sea-shore, mountain, or country resort, in 20 THE TREATMENT OF SYSTEMIC STATES. order by out-door life and gradually increasing exercise to harden into permanent form the flesh and strength which have been laboriously gathered. TREATMENT OF CORPULENCE. In the treatment of corpulence it must be remembered in the first place that the same line of treatment is not suitable for every case. Speaking broadly, we may divide cases of corpulence into two classes (excepting those associated with some apparent organic cause) : those due to defective oxidation and those due to excessive food-supply. The patients of the first class are mostly anaemic and of little muscular power, while those of the second are plethoric and robust, and their excretion of urea is, as a rule, much above normal. For the purposes of prognosis this division of obesity is very impor- tant. In the overfed, reducing the food-supply may be all that is needed ; in the so-called " fat anaemics" it may be very difficult or perchance im- possible to increase oxidation ; hence in those who are at once fat and feeble the prognosis is grave in proportion to the feebleness. For the purposes of therapeusis the division is not so important as it may seem at first sight, excepting in so far that it points out that in a fat anaemic the effect of regulating the diet is less than it is in those who are obese and plethoric. In each class it is essential to increase oxidation as much as possible, since few persons will tolerate prolonged semi-starvation. The fat anaemic often, however, bear rigid dieting badly, and with them, there- fore, great care must be exercised in the reduction of the food. Certain drugs have some influence in increasing oxidation ; in the anaemic, iron seems to increase the activity of the destructive processes of the body and to aid in reducing flesh. On the other hand, in such subjects the alkalies, especially the potash salts, though they increase tissue-waste, may be harmful and augment the weakness. Contrariwise, however, when there is an abundance of strength in an obese subject, the continuous use of alkalies, and especially of alkaline laxatives, may be of great service. It must be remembered that very often in these cases there is lack of activity in the intestinal glands and much retention of half-assimilated materials. The value of Kissingen, Carlsbad, and other alkaline purgative waters, and the results sometimes obtained in obesity by treatment at the various alkaline spas, are very familiar ; but the alkaline laxative ought to be, as it is in fact at the various springs, used only as an adjuvant to the more serious treatment. The keeping of the patient in a state of chronic purgation is, after all, but a crude method of affecting metabolism, and if too prolonged may have a local injurious effect on the intestinal tract. The use of the thyroid gland in obesity will be considered at greater length in another portion of this book. It is enough here to point out that the extract of the gland does increase oxidation of the carbohydrates of the body, and that therefore it is often useful in the treatment of TREATMENT OF CORPULENCE. 21 obesity as an addition to the regulation of the food and the use of exercise. Given in excess it produces deleterious results, and when used for too long a time appears to largely lose its power. The natural and most important means at command for the increasing of oxidation is exercise, and the practice of regulated exercise is at the basis of all proper systems of weight-reduction. The amount and form of exercise to be prescribed in any individual case depend upon the peculiarities of the patient and his surroundings. Certain general principles, however, apply to every case, and if these are observed the details may vary indefinitely. First, the exercise must be regular and persistent ; second, it must involve not only certain muscles, but all the muscles of the body ; third, it must be sufficient in amount to produce an effect, it should always, indeed, be carried as far as is pos- sible without the production of exhaustion ; fourth, it must be sufficiently active to produce sweating, which, in many cases, may be encouraged by the use of warm clothing during exercise. Professional trainers, indeed, attach much importance to sweating as a means of reducing weight. It probably acts not only by dehydrating the body, but also by hastening the elimination of partially used-up materials, and is particularly indicated when there is any gouty tendency. In selecting the form of exercise care should be taken that it be as little irksome as possible to the patient, and if it can be made a pleasure much will be gained. Bicycling offers an inexpensive and convenient means of muscular exertion, but has the disadvantage of not calling into play the muscles of the shoulders and arms. Golf seems to have an attraction for its devotees strong enough to make them forget that they are under "the doctor's orders." A travelling or hunting trip through the wilderness of the Rocky Mountains or the forests of Maine or Canada affords, as we can vouch for from personal experience, a most efficient, and to those who are willing to forego some of the luxuries of civilization a pleasant, method of reducing flesh. A foot-exercise with whose fat-destroying tendency every trainer is familiar is running. The influence which it has upon heart and lungs does not differ from that of mountain-climbing, and, if there be any truth in the teachings of Oertel as to the value of pulmonic and cardiac gym- nastics, running ought to be of especial value when the heart and lungs are giving evidences of being specially affected by the fat-accumulation. Boat-rowing, or even canoeing, may serve the purpose of the fat man. Wood-sawing is largely employed in some European anti-fat sanitariums, and is undoubtedly efficient. It can be very readily graduated by re- quiring one or two sticks more to be sawn each successive day. Gym- nastic exercise, lifting of weights with pulleys, etc. , may be employed, and even horseback-riding may be made efficient. Oertel further be- lieves that mountain-climbing affords a method of gymnastically training the heart and lungs which may be of the greatest service in the treatment of a weak heart. 22 THE TREATMENT OF SYSTEMIC STATES. It must, however, be remembered that the heart is in an essentially different position from the voluntary muscle. The muscle loses its power through want of exercise, and is brought back from its soft, flaccid condition by exercise. Weak- ness of the heart-muscle, on the other hand, is practically never the result of lack of exercise of the heart, but is due to the accumulation of fat about the muscular fibres or to degeneration of the muscle, to exhaustion from overwork, or to the presence of some poison in the blood. If the cardiac weakness be connected with a fatty change in the muscle which is the result of general fatty infiltration of the body, the removal of such fat-infiltration will be accompanied by improvement of the muscle of the heart, which improvement may probably be aided by cardiac ex- ertion. If, on the other hand, the cardiac weakness is the result of overstrain or of a true fatty degeneration, the probabilities are that it will be increased rather than diminished by cardiac exertion. In all cases the exercise should at first be gentle and should be in- creased very carefully. Thus, mountain-climbers or runners should at first stop every few feet, to allow heart and lungs to recover themselves. Due regard must be had for the patient's general condition ; especially must it be remembered that the stout, flabby body is often associated with a weak heart-muscle which sudden severe exertion may easily overtax. Dis- regard of this fact has indeed occasionally led to a fatal result. The fat of the body is chiefly if not exclusively derived from the hydrocarbons of the food. The notorious diet-list of Mr. Banting, which gave rise to the term " bantingism," was in no respect novel, but only conformed to the universally recognized principle that in corpulency with- drawal of carbohydrates from the food is necessary. The extent to which the diet can be reduced depends, at least in the plethoric group of cases, almost entirely on the patient's strength of will. To accomplish any good the intake must self-evidently be less than the output, that is, the demands of the system must never be satisfied, and the body must obtain the necessary force from the energy stored up in the fatty tissues. In short, the patient must undergo a mild form of star- vation. The craving for food can be to some extent assuaged by the fat- free proteids ; but as these are insufficient for the needs of a healthy organism, no amount of them will entirely satisfy the appetite. It is, therefore, plainly impossible to overcome the repugnance of patients to the diet by indefinitely increasing meat and other nitro- genous foods. Further, the excessive use of nitrogenous foods throws a strain upon the kidneys in requiring them to cast off an excessive amount of waste material ; and if in such cases there be a gouty diathesis there is danger of the production of arthritic symptoms. No single dietary is suitable for all cases ; the practitioner should make a list in accordance with the circumstances of the individual case. In such list the actual weight of food to be taken should be given, as, without such check, the hungry man will always eat more than he be- lieves he does. As samples we give, however, two dietary lists the first is that of Banting ; the second, which was devised by Ebstein, has been much used in Germany, and seems to us the better of the two. TREATMENT OF CORPULENCE. 23 BANTING. 6 A.M. One pint of black coffee and one ounce of coarse brown bread or biscuit. 9 A.M. Four ounces of lean meat, three ounces of brown bread or biscuit, and half a pint of coffee. 2 P.M. Six ounces of lean meat, three ounces of brown bread or biscuit, six ounces of green vegetables, and half a pint of water, followed by half a pint of coffee. 6 P.M. Half a pint of coffee. At supper two ounces of brown bread or biscuit, and a couple of glasses of sherry or claret. Fruit ad libitum, liquorice powder pro re nata. EBSTEIN. BREAKFAST. Two hundred and fifty grammes of tea without sugar or milk ; fifty grammes of white bread, with plenty of butter. LUNCH. Fatty soup, made from a marrow-bone ; from one hundred and twenty to one hundred and eighty grammes of flesh, containing much fat ; some vegetables ; stewed fruit without sugar ; two or three glasses of wine. Later in the afternoon, one cup of tea without milk or sugar. EVENING. One cup of tea without milk or sugar, thirty grammes each of bread and butter, one egg, or a piece of fat ham or fat roast meat, or cheese, and fresh fruit ; no alcohol. The following table, based upon the analysis of Carl Zahn, shows the comparative amounts of the different forms of food furnished by the rations of Banting and of Ebstein contrasted with the average normal : Albuminous Materials. Fat. Carbohydrates. Normal .... 30. drachms. 25. drachms. 92. drachms. Banting .... 25.5 drachms. 2. drachms. 5.25 drachms. Ebstein .... 25.5 drachms. 21.25 drachms. 11.75 drachms. As a foundation upon which the physician may arrange his bill of fare, the following table, originally compiled by Zahn, is appended. It gives the approximate amount of food-material in various common articles of diet in parts by weight. Food. Water. Albu- min. Fat. Hydro- carbons. Mean of ten different kinds of simple soups . . Mean of ten rich soups 91- 8l 2 I.I 2 6 r-5 7. 2 5-7 Q 7 Boiled beef, lean, from young heifer 66.=. 28 4. 1.7, Boiled beef, fat, from young heifer AQ 18 12. 1 Beef from steers and oxen, boiled ;68 7A 2 7.5 O 4, Beef from steers and oxen, roasted Roast meats, including beefsteak, game, birds, etc., reckoned as an average 59- s8 38.2 l8 2 1-7 2.7 Veal, roasted 78 1C 7 52 Fricasseed veal with fat and milk 7 22 3. IO 4. IO. Fat roasted pork or goose 4O Z tA 6 24. 2 Smoked ham CQ 77 25 08 8 II Boiled fish 74 2O 22 IO o 60 o.7o Shell-fish 80 Q7 17 OQ O TA. Mean of seven different kinds of meat-foods . . 44.20 8.70 15. 28.9 THE TREATMENT OF SYSTEMIC STATES. Food. Water. Albu- min. Fat. Hydro - carbons. 72 4O I QO i 3.0 21 2O 7-1 2 IO 320 21 80 Potatoes boiled . . 7O I 80 3IO 24 Salad green ... Q/i 2 I 4O 2 2 2 Vegetables in general average 62 2 6 40 I 4O White bread ... AO 4S 6 is O /I /I SI 12 Black bread 5J ii S7 i 18 T 1 "it 5 !8 81 08 Milk 8? 42 3A1 -5 6s 4 81 Cream . 6s si T. 61 26 7 S i C2 QO 27 4 06 O Q7. 3 77 Butter I A AQ O 71 8-t 27 o s8 ic CQ 17 AA 40 80 S 21 Lard O 7O o 26 OO O/l Sugar , ... 2 l6 O 3S 06 12 Vinegar .... . . QA O 4 One egg, estimated not by percentage, but by amount in average egg 8 2S 3 I A "T I 7C T O OS "Z Tea .... Q7 Q O 1 o 6 Coffee Q4 7 o 18 O S2 I 4 Q-3 7. i 60 2 2O i 6 80 3 7 9 6 T. 8 It is the general custom to reduce the amount of water in the treat- ment of corpulent persons. This practice is apparently opposed to all our present knowledge of physiology ; it is impossible to see how water can increase the formation of fat, and theoretically it would seem that it should hasten the catabolic processes of the body. It may be. however, that empiricism has passed science, and that the common belief is correct, although we confess that we follow its beckoning with reluctance. Es- pecially in those cases where there is a lithsemic tendency, as there usually is in the plethoric type of corpulence, the stoppage of water may do much harm by encouraging the retention of gouty poisons in the system. LITHIASIS. Although the gouty diathesis is one of the most frequent of bodily complaints in middle-aged persons of the upper class, and an enormous amount of study and research has been devoted to the determination of its dietetic treatment, yet no positive scientific knowlege exists for our theoretic guidance. This is the fault of the pathologist rather than of the therapeutist. The ultimate nature of the gouty diathesis remains as much unknown as the ultimate nature of syphilis. We are therefore forced to rely upon an unsatisfactory empiricism. It would be very easy to quote contradictory statements from various clinicians of authority. In the brief space here possible it seems wisest to avoid both theoretic discussion and quotations from authorities, and we shall give simply our own views as based upon wide reading and very large experience in the treatment of gouty patients. In the hygienic treatment of gouty patients it is essential that exercise LITHIASIS. 25 be taken systematically and with regularity. If circumstances permit, prolonged moderate exercise in the open air (such as may be obtained by horseback-riding, rowing, hunting, etc. , or even by walking) is to be pre- ferred. Gymnastic or house exercises may very well be substituted for this out-door work under special circumstances. The form is not a matter of much importance, provided the exercise involves the whole muscular system. The amount of exercise must be graduated to the needs of the individual case, different persons having no more the same measure of physical strength or the same needs for physical work than have different measures the same capacity. The endeavor must be always to push the exercise until it produces distinct physical weariness, and a better effect will usually be obtained if the exertion be sufficiently violent to cause free sweating. For the robust, hard muscular labor prolonged through many hours may be necessary ; while in the feeblest subjects it may be essential to begin with passive exercise associated with the least possible active exercise ; but day by day the physical exertion can be increased, and the results of systematic training in anaemic, feeble, gouty persons are some- times astonishing. Gouty patients may, for the purpose of dietetic discussion, be arranged in three classes : first, those who are robust and vigorous ; second, those who, with a distinct feebleness of constitution and sluggishness of habit, have a marked tendency to the accumulation of fat ; third, those whose nutrition and general vital forces are habitually on a low level. In robust gouty persons it is essential that the quantity of food be lessened : such patients should be taught to rise habitually from the table with the appetite not thoroughly satisfied. In the second class of patients some control over the appetite is not rarely imperative, while in the third class of patients it is often equally essential to administer food beyond the cravings of the stomach. As individual cases occur grading all the forms of the gouty diathesis insensibly one into the other, the regulation of the quantity as well as of the quality of the food becomes a matter to be adjusted to the individual case. There are certain articles of food which should be denied to all gouty subjects. First of these in the list we would place cane sugar. The manifest effect of overindulgence in cane sugar in the lithaemic diathesis is probably not dependent upon any influence which it exerts on the general system, but upon the ease with which it undergoes fermentation in the alimentary canal and gives rise to acid products. Acid fruits, including the tomato and American strawberries, are also to be avoided by all gouty subjects, while non-acid fruits, if ripe, are often of great service and may be taken freely. In gouty patients of the first class the albuminous principles of the food should be much decreased, but clinical experience proves that the form in which the albumin is taken is not unimportant. Red meats are especially to be denied ; white meats, except pork, fish, eggs, and milk are to form the main staples of animal food. Chicken is much preferable to turkey. Game is denied by most authorities, but we have 26 THE TREATMENT OF SYSTEMIC STATES. never seen any harm from its use. The waste muscle-products, such as kreatinin, xanthin, etc. , have probably some connection with the in- jurious effects produced by red meats. If this be so, strong stock soups, which contain an abundance of these principles, ought to be injurious ; and we have certainly known of violent attacks of gout apparently precip- itated by the free use of beef tea, beef essence, and other similar stimulant liquids. If soups, therefore, are employed, they should be vegetable rather than stock soups. Ordinarily carbohydrates may be taken in mod- eration. Green vegetables, including roots, are especially serviceable. The proper dietetic treatment of anaemic gouty subjects distinctly in- clined to corpulence is a matter of difficult determination. The first thought would lead the physician to order a reduction in the habitual ingestion of albumin ; but we have certainly known very good results produced in patients of this class by lessening very decidedly the carbo- hydrates in the food. When this is done, the albuminous ingestion must be increased rather than decreased, in order to support the system. In many of these cases, however, it will be found that the patient habitually takes an overplus of food, and much good may be achieved by lessening the quantity : in such patients the carbohydrates can be largely withdrawn and the habitual ingestion of albumin not increased. It is especially in patients of this class that the sagacity of the physician in modifying the diet to suit the needs of the individual will meet with reward. Our own plan has been in doubtful cases to make tentative alterations of the diet, to regulate the quantity of food, withdraw carbohydrates, and order the albuminous nourishment to be taken chiefly in the form of fish, white meats, eggs, and milk. If the patient improve, the diet is evidently suit- able for the individual case ; if there be no improvement, or if there be aggravation, the diet should be at once altered. In anaemic, impoverished, gouty subjects the best results are not rarely to be achieved by the employment of generous diet combined with the moderate use of alcoholic liquors. In selecting the drink, malt liquors and acid wines are to be avoided. Our own experience is that diluted spirits offer the best form for the administration of alcohol. In any obstinate gouty case which fails to yield to the ordinary regu- lation of diet the so-called milk diet should be tried. It is not at present possible to give any sufficient scientific reason for the alterations which are occasionally produced in diseased human systems by the exclusive milk diet. The whole story of changes wrought by the milk diet in nutrition we do not know. It evidently, however, has a pronounced influence upon primary digestion in the intestinal tracts. It offers organic principles in so simple a form as to reduce to the minimum the labor of digestion, and probably to relieve greatly the hepatic and other similar glandular organs from excess of labor. By virtue of the large quantity of water it contains it enormously increases the flow of the urine and probably of the secretion of the skin, and in some cases is no doubt of great service in washing out excrementitious material from the body. Whatever may be the proper LITHIASIS. 27 scientific explanation of the fact, it is certain that in many cases of gouty diathesis and in various other abnormal conditions of nutrition an exclu- sive milk diet is extremely beneficial. Thus, in fatty anaemic subjects a course of two or three weeks of milk diet sometimes alters the nutrition so that afterwards feeding and tonics produce effects which were previously not attainable. We have always suspected that in these patients there is an underlying gouty diathesis. We have seen many cases of gouty disease of a chronic and subacute type in which remedial measures had entirely failed, but which yielded easily, though slowly, to an exclusive milk diet. Very frequently when it is simply intended to fatten the patient, or in the combating of the gouty diathesis, milk is given largely with other food ; but to get the peculiar full effects of a milk diet it is essential that the patient abstain, at least for a time, from all other food. After two or three weeks oatmeal or cracked wheat or stale bread may be allowed, then green vegetables, and slowly the patient may thus be restored to ordinary diet. In severe cases, however, milk diet may be persisted in for weeks, and it is possible for the human adult to work laboriously and live ex- clusively upon milk. In order to afford sufficient nitrogenous nutriment, from five to seven pints of milk a day must be taken. This amount of milk contains too much fat for the needs of the system : it should there- fore be skimmed. The so-called skimmed milk sold from creameries is, however, not suitable, because the fat has been too absolutely withdrawn from it, and because it is usually not so fresh as is desirable. The skim- ming of the milk should not be too close. It is essential that the milk be taken at intervals of not longer than two hours, and that it be drunk by sipping rather than by gulping, so as to avoid any danger from the formation of hard clots in the stomach. When the digestion is good the milk may be taken cold. When the digestion is very feeble it should be taken hot. But boiled milk should not be employed, as it is of more difficult digestion than is unboiled milk. During the progress of the milk course constipation is almost invariably present : this must be over- come by the administration of drugs. In gouty subjects saline laxa- tives are preferable. CHAPTER III. CALORIC. THERE are two conditions of the force caloric, spoken of as distinct entities, but which are merely relative terms, expressive of the presence of an excess or of the absence of the normal amount, or, more strictly speaking, normal intensity of the force. Cold and heat, in connection with the human body, respectively mean an intensity of caloric below and above 98.5 F. USE OF HEAT. LOCAL USE OF HEAT. The continuous application of moist heat acts as a relaxant to the sur- face of the body, producing probably a local congestion and exerting the influence of a slow counter-irritation. It is often practised with advan- tage in cases of sprains and internal inflammation. The local use of an intense dry heat has recently been shown to be very advantageous in various local disorders of the limbs, and even of the trunkal muscles. For the purpose there are upon the market various forms of apparatus which agree in the general principle that the heat is chiefly applied by means of superheated air in a small chamber, with pro- vision by means of ventilators and other devices for the removal of the moisture that comes from the skin. When proper care is exercised with an efficient apparatus the degree of heat that is borne without suffering is very remarkable. We have frequently carried the temperature up to 340 F. If, however, under these circumstances any moisture collects upon the surface of the part, blistering results. With most, if not all, forms of apparatus the parts should be lightly wrapped in patent lint. A temperature below 240 F. is rarely of service. In most cases, however, it is better to use in the beginning a lower temperature at one or two stances, partly for moral reasons and partly because the skin is often at first very sensitive, although it rapidly becomes accustomed to the higher temperatures. The duration of the application of the heat varies from ten to forty minutes. We know of no experimental evidences as to the exact effect of this high temperature upon the affected joint. The fact, however, that the general bodily temperature may be raised three or even four degrees is evidence that there is a great absorption of heat, and that there probably is a local heating far above the highest fever point. Moreover, a distinct enlargement often occurs in the heated part, so that there must be an 28 GENERAL EMPLOYMENT OF HEAT. 29 excess of blood drawn to it. Probably both the circulation and the chemical movements in the joint are greatly accelerated. Certainly a re- markable absorption of exudates often occurs. We have frequently seen an acute attack of gout precipitated by the application to a long-diseased joint about which there was much exudation. This acute attack has often been accompanied by a very perceptible lessening of the exudate : we believe such attacks to be due to the absorption into the blood of gouty acids or salts which had been liberated from the tissues of the joint. Although this method of treatment was first brought forward for the cure of rheumatism, there is a priori no reason for supposing that it can especially affect the general rheumatic condition, much less the rheumatic diathesis, unless the patient be well wrapped up in blankets and the local heat be used as a general sudorific measure, when whatever relief a free sweating can produce may be obtained. On the other hand, the method is of very great value in the treatment of local inflammatory conditions with exudation, whether these be or be not of rheumatic origin. In sub- acute and chronic t' m tne dog ^ was about 111 F. In man a similar series of phenomena are developed by exposure to excessive heat, although, owing to his extraordinary power of cooling his body and of protecting it against cold, he is able to bear extremes of temperature far beyond the points which would prove fatal to any given species of animals. Yet when his body is heated the results are the same, as is proved by the terrible mortality of sunstroke. "To prove the second proposition, I" [H. C. Wood] "caused hot water to flow through pigs' bladders fitted as a sort of bonnet to the heads of cats and rabbits. It is evident that with small animals we can in this way heat the brain without heating materially the remainder of the body. It was found that coma, with or without convulsions, was produced. Some- times the stupor came on gradually, hebetude slowly deepening into coma, but in other instances unconsciousness was developed very suddenly. It was also found that severe nervous symptoms and death were produced when the brain reached the temperature which was fatal to the animal in the hot box. Without occupying more space, the conjoint labors of Lauder Brunton and Liebermeister have proved that the accelerated pulse in fever is largely due to the action of the heat upon the heart and its nerves : so that the second proposition may be considered demonstrated. " In regard to the third proposition, I have frequently taken animals out of the hot box perfectly unconscious and plunged them into a bucket of cold water, have watched the temperature of the water rise while that of the animal fell, and as the bodily heat came towards normal have seen the coma disappear, so that within ten minutes the at first absolutely comatose and dying rabbit would be skipping about on the grass. I have placed a man whose temperature was nearly 110 F. , who was unconscious, with a feeble running pulse of 160 or 170, irregular, jerking, slow respirations, and every indication of immediate death, in a bath of 60 F. , and within a minute and a half have seen consciousness partially restored, and in another minute and a half the man trying to get out of the bath. What 3 34 CALORIC. could the bath do to affect the man so profoundly and so quickly but with- draw the heat ? That the heat was present, and that it was withdrawn, the thermometer proved. If the drowsiness had been due to simple con- gestion of the brain, very certainly would the bath, by driving the blood from the surface, have increased the trouble. It must be borne in mind that this case is by no means unparalleled : similar instances of the good effects of the sudden withdrawal of heat in rheumatic hyperpyrexia have been recorded by both English and German observers, and recent Con- tinental literature is full of reports of the relief of nervous symptoms in various pyrexias by the abstraction of heat. ' ' Finally, as excessive heat is present in fever, as excessive heat, when present, is not only able, but is forced, so to speak, by its own attributes, to produce disturbance of the functions of innervation and circulation, and as the withdrawal of the excessive heat in fever is followed by instan- taneous relief of the symptoms of disturbed innervation and circulation, surely the conclusion is logically inevitable that excessive temperature is the chief cause of the other symptoms of fever, and that in acute pyrexia threatening life the heat should be withdrawn as rapidly as possible by means of the cold bath." CHRONIC PYREXIA. The effects of a long-continued pyrexia, not suffi- ciently intense to induce immediate serious symptoms, upon the structure of the various tissues have been elaborately investigated by Liebermeister, 1 who found that the liver, spleen, kidneys, voluntary and involuntary muscles, blood-vessels, and even the nerve-centres undergo a granular degeneration during the continued pyrexia. The lesion was constantly present in the bodies of those who had suffered in this way during life, entirely independently of the nature of the primary disease. In cases of infectious fever in which the temperature had never been high, this gran- ular degeneration did not exist. Previous to the investigation of Lieber- meister, Zenker had demonstrated that the muscles undergo a peculiar granular degeneration in typhoid and other fevers ; and the fact has been abundantly attested by later observers. We do not know that the observa- tions of Liebermeister as to the occurrence of this lesion in non-infectious pyrexia have been confirmed, but we have no doubt of their correctness. It is evident that in all fevers a primary therapeutic indication is to reduce the temperature. Of course, if possible, this should be done by checking the excessive production of heat ; but, unfortunately, this often lies out of our power, and we are forced to abstract the heat by mechanical means. It is a priori impossible to determine what effect upon the production of heat the rapid abstraction of it would have, but, from the well-known powers of the organism to resist external cold, it seems probable that the heat-production would be increased rather than diminished by the abstrac- tion of caloric. An experimental study of this problem has been made by several observers, but with, unfortunately, different results. Weis- flog* has found that the local abstraction of heat by a cold sitz-bath causes a rise in the temperature of the axilla, and that in fever-patients, COLD IN PYREXIA. 35 unless the sitz-bath is prolonged over twenty-minutes, no fall of the bodily temperature results. In 1860 Kernig 4 found that a healthy man in a bath of the temperature of from 28 to 30 C. produces about twice as much heat as normal ; in a bath of 24 C. , about three times as much ; and in a bath of 20 C., about four times as much. Liebermeister 5 found that in a healthy man exposure to cold for a brief period of time causes a rise in the bodily temperature, and on extending his researches into fever proved that where the external cooling was not too powerful or too long continued the same was true of fever-patients. From this it follows that the use of external cold stimulates heat-production. This, to our minds, has been confirmed by the chemical researches of J. Gilde- meister, 6 of Lehmann, T and of Liebermeister 8 himself upon men, and by those of A. Roehrig and N. Zuntz 9 upon animals, all of which show that both in health and in fever very much more carbonic acid than nor- mal is eliminated under exposure to cold. This would appear to prove that cold baths increase the production of animal heat. It seems most probable that this is the case ; but A. Murri believes that he has proved that the cold baths have no such influence.* At any rate, the investiga- tions of Liebermeister and others have shown that the first rise of tem- perature produced alike in healthy and in fever subjects by exposure to a moderate and not too long continued cold is followed after removal of the cold by a fall of bodily temperature of greater or less degree. While, therefore, external cold probably first stimulates, it afterwards depresses the production of animal heat. The further experiments of Liebermeister 8 upon the elimination of carbonic acid are also in accord with his tem- perature-study, for he found that after the bath the elimination sank below normal, and so continued for a considerable period. If the cold bath really affects the fever-process, it ought distinctly to reduce the excretion of urea. That it has this action would seem to be proved by the research of Sassetzky , 10 who found that the continuous use of the cold bath invariably lessened the urinary elimination of nitrogenous material and of the phosphates, although it increased the total flow of urine. The subject is, however, a very difficult one, chiefly because it is almost impossible to know in any individual case what the elimination of urea would have been if no baths had been used. Bauer and Kiinstle " gave to the patients cold baths upon alternate days, and found that the excretion of urea was in each case greater on the days when baths were used than on those on which they were not employed. These experi- ments have been quoted as showing that the cold bath increases the ex- cretion of urea, but in Schleich's 12 investigations on the effects of hot baths the increase of the excretion of urea frequently did not show itself until the day after the bath. It is probable, therefore, as believed by Schleich, that the destruction of albuminous substance in the tissues is * We have never seen the brochure of A. Murri {Del Potere regulatore della Tem- Peratura animate, Firenze, 1873). It is abstracted in the London Medical Record, vol. i. 36 CALORIC. not manifested in urea-elimination until after twenty-four hours, or, in other words, that twenty-four hours are necessary for the completion of the formation and the excretion of urea: so that if the baths are used, for example, on Monday the urinary solids will indicate their effects not on the same day but on Tuesday. If this be correct, the experiments of Bauer and Kunstle are in accord with those of Sassetzky in showing that the cold bath lessens the formation of urea in fever. During the bath the pulse of the fever-patient usually becomes much smaller and harder, and the sphygmographic tracings made by Winter- nitz before and after the use of the cold bath (if tracings of this kind can be trusted) indicate that there is after the cold bath greatly increased arterial tonus. (See Verhandl. des Congr. fur Innere Med. , 1886.) It may be that the good obtained by the cold bath is really due to a reflex action upon the nerve-centres, and is not entirely the result of the with- drawal of the heat.* The results of the physiological study of the effects of cold in fever may be summed up as follows. During a sufficiently prolonged applica- tion of cold the bodily temperature falls, although an increased production of heat i.e., consumption of tissue at first occurs. After the applica- tion, the bodily temperature continues to fall, or but slowly regains its former position : the present evidence at our disposal indicates, but is not sufficient to prove, that this slow regaining of bodily temperature is due to a diminished production of animal heat, that is, to a decrease in the waste of tisszie and in the formation of urea and carbonic acid. When the use of cold in fever was first recommended in this work the method was looked upon with disfavor by so many medical practi- tioners, especially in the United States, that it seemed necessary to discuss, carefully and in detail, the statistics of the subject to show that these were sufficiently large to be decisive, and were sufficiently plain in their teaching * Naunyn (Archiv f. Exper. Path, und Pharm., 1884, Bd. xviii., Heft i and 2), indeed, denies that the good achieved is due to withdrawal of heat at all. In his experiments he found that if he maintained proper ventilation, carefully giving fopd and water, he could gradually heat rabbits up to the temperature of 107 and 108 F., and keep them at this temperature for weeks without their evidencing any inconvenience and without the production of any internal lesions. Krishaber was also able to maintain in a dry room 117 F., his own temperature reaching 107, pulse 85, respiration 35. Naunyn, as the result of his experience, is a very strong advocate of the employment of frequent baths in the treatment of fever, but believes that they act by indirectly reducing bodily waste and increasing renal secretion, strengthening the pulse, and stimulating the nerve-centres. L. Schweinburg and C. Pollak ( Centralbl. f. Gesam. Therap., March, 1887) have found in a series of apparently very careful experiments that cold hip-baths notably increase blood-pressure and lessen pulse-rate, while hot hip-baths have the oppo- site effect. Naunyn believes that better results are obtained from the use of constant lukewarm baths than from the employment of excessively cold baths. In very severe cases, marked by dicrotic pulse and disturbance of the sensorium, the bath treatment, according to Naunyn, should be commenced before the axillary temperature reaches 103 F., and frequently a warm bath may in such case be given between two cold baths. Such a treatment is especially indicated when there is marked delirium, tremor, subsul- tus tendinum, or great restlessness ; a warm bath in the evening then seldom fails to produce some favorable result. COLD IN PYREXIA. 37 to demonstrate the value of the practice. As, however, at present almost all medical authorities are in accord in recommending the early use of cold in pyrexia, we have omitted from the present edition these statistics, and would refer any doubtful student to the ninth edition of this work, page 63. The cold-water treatment has been employed upon a large scale, espe- cially in typhus and typhoid fevers, but there can be no doubt of its value in scarlet fever, in diphtheria, septic&mia, and other germ diseases accom- panied by high bodily temperature. In diphtheria or anginose scarlatina the general use of cold may often with great advantage be combined with a local application of the ice-bag or the ice-poultice to the throat. During the summer months serous diarrhoea {cholera infantuni], in some of its forms, annually destroys large numbers of children in this country. In most of these cases the bodily temperature is, first or last, much elevated, and the diarrhoea is produced and maintained by the heat, as originally pointed out by Comegys. 13 All the ordinary methods of drug-adminis- tration frequently fail, or, at most, succeed only in keeping the child alive until the heat of the weather subsides. Under these circumstances, antipyretic treatment acts in a magical manner. Usually simple bathing in water of about 75 F. , at intervals of from three to six hours, will be found sufficient, but in some cases the plan recommended by Comegys may be required, namely, cold affusions while the child is sitting in a cold bath. The effect is usually immediate, quiet and sleep at once replacing the wakeful restlessness so distressing to mother and child. There may be a few instances of sudden collapse with low temperature from exhaustion by the serous discharges, but usually cases in which the disease is said to "go to the head' ' are those in which the temperature rises so high as to produce brain-symptoms ; under these circumstances the vigorous use of external cold is imperatively demanded. The high temperature that prevails in sthenic pneumonia would appear urgently to demand the abstraction of heat, and, although the prejudices of the profession and the laity were in the beginning strongly opposed to the use of the cold bath in pulmonary inflammation, gradually the method has come into practice. Liebermeister, in one of his early publications, stated that whilst in six hundred and ninety-two cases of pneumonia treated in the hospital of Basel in various ways the mortality was 25.3 per cent., in two hundred and thirty cases treated in the same hospital by the thorough antipyretic method the mortality was only 16.5 per cent., and there can be no doubt that in properly selected cases bathing does great good. It must, however, be remembered that a moder ite pyrexia does not do great harm to the system unless it continues for a length of time, and hence in those diseases which, like pneumonia, last but a few days the reduction of temperature is not so important as in affections in which the fever is of long continuance. Thus, a temperature of 103 F. may be disregarded in a short pyrexia, whereas in a typhoid fever it would call imperatively for the use of external cold. Further, in acute internal in- flammations the temperature can very frequently be reduced with ad- 38 CALORIC. vantage by the local application of cold ; thus, in pneumonia cold com- presses to the chest may be employed ; in dysentery the free use of ice suppositories and of large injections of ice-cold water is often of the greatest service, both by the local and general influence. It being acknowledged that in cases with long- continued pyrexia the external use of cold is a much safer and more efficient means of reducing the temperature than are antipyretic drugs, the practical question presents itself as to what are the centra-indications to the use of cold in typhoid and other allied fevers. According to ideas formerly held, bronchitis and pneumonia would especially seem to be in the way. The serious lung affections of. low fevers are, however, chiefly dependent upon the general adynamia, which is in turn largely the result of the excessive temperature ; and we have no doubt of the correctness of the assertion made by Liebermeister, that in the exanthematous fevers " pneumonia, hypostatic congestion, and the like offer no reason for suspending the baths ; the hypostatic troubles sometimes disappear under their use." If in the beginning of a typhoid fever a severe bronchitis or pneumonia arise without great elevation of temperature, some hesitation may properly be felt in producing active antipyresis with cold. If, however, the symptoms occur late in the fever they do not centra-indicate the use of the bath ; and even early in the fever, if the pyrexia be severe, balneal measures should be practised. Liebermeister affirms that perforation of or hemorrhage from, the bowels is a contra- indication to the use of cold in typhoid fever, because cold has a tendency to produce determination of blood to the internal organs. The experience of Wunderlich 14 is, however, very much op- posed to this idea of Liebermeister' s. He treated sixteen typhoid cases of severe intestinal hemorrhage with cold baths, with but two deaths, neither of which resulted directly from the hemorrhage, one being from intestinal perforation and one from severe pneumonia. This mortality is certainly a very small one, for when cold water was not employed, out of thirty-two cases Griesinger had ten deaths ; out of twenty-one, Jenner lost seven ; out of fourteen, Gietl lost six ; and Jaccoud 15 had six deaths in six cases. Bauer, 16 however, is in agreement with Liebermeister in believing that the baths should be discontinued during intestinal hemorrhage. Yet their views seem to be based upon preconceived theory rather than upon actual trial. The proportion of cases in which intestinal hemorrhage occurs does not seem to be increased by the cold-water treatment ; at least Gols- dammer 17 states that under the older methods thirteen thousand five hun- dred and sixty-three cases gave five hundred and thirty of intestinal hem- orrhage, while five thousand six hundred and thirty -six cases of cold-water treatment yielded two hundred and forty of intestinal hemorrhage, the percentage being in the two cases respectively 3.9 and 4. 2. Menstruation is not a centra-indication. Brandt appears to consider any contra-indica- tion to the use of the cold bath in typhus fever a myth, and the drift of the testimony is such that no local internal disease except feeble heart COLD IN PYREXIA. 39 ought to be considered as absolutely contra-indicating the use of cold baths when the temperature is high in typhus or typhoid fever. It is otherwise when there is a general tendency to collapse, when the heart is so weak that local stases of blood occur in almost all the internal organs. Under these circumstances the circulation has not sufficient power thoroughly to equalize animal heat, so that it is possible to cool the exterior of the body several degrees without materially affecting the tem- perature of the interior. Moreover, the first effect of cold water upon the surface of the body is to drive blood into the interior, and if the heart be excessively feeble there is grave danger of severe internal congestion, and even of paralysis of a feeble right heart. The great contra- indication to the use of external cold is, therefore, profound adynamia or excessive heart weakness. Whenever there is any doubt in the practitioner's mind upon this score in an indi- vidual case, the attempt should be made to reduce the temperature within bounds by immersion in tepid water. In carrying out the antipyretic treatment of fever certain general con- siderations should never be forgotten. So long as the temperature of the body remains distinctly above the normal there is no danger of any patient taking cold. The fall of the bodily temperature may continue after the removal of the patient from the bath ; hence it is important that the pa- tient be taken out of the bath so soon as the temperature reaches 100.5 F. The temperature at which the bathing should be commenced varies with the probable length of the pyrexia ; in typhoid fever we would put the limit at 102.5 F- * n tne mouth. As it is possible to cool the axilla with- out cooling the interior of the body, all temperatures should be taken in the mouth or the rectum. The object of the bath is a reduction of the temperature, and unless this is effected no good results. On the other hand, it is always of importance to avoid, as far as may be, shock, dis- comfort, or the possibility of overdoing the heat-reduction ; hence the rule in the choice of the methods of cooling the body to employ that which will accomplish the desired effect with the least disturbance. Rarely in the adult, more frequently in the child, free sponging of the exposed body with cold water and alcohol will suffice. Next in power comes the cold pack, in which the naked patient is wrapped in a sheet dripping with ice- water, left uncovered save by the sheet, and sponged with cold water from time to time. Next is the tepid bath, 90 F. ; then the tepid bath cooled, whilst the patient is in it, by the addition of cold water or of pieces of ice. Some prefer to put the patient directly into water of 75 F., but the gradual cooling of the bath seems to us preferable. When a portable bath-tub can be brought to the bedside of the patient and readily filled and emptied, its use is accompanied by less fatigue and disturbance than are any other efficient means of employing cold. The patient, wrapped in a sheet, is to be lifted into the bath by two attendants, and then made comfortable with pillows, etc. Unless the pyrexia be very severe, the bath should be at a temperature of 90 F. and 40 CALORIC cooled down pro re nata. When no portable bath-tub is at hand, efficient antipyresis may be had by lifting the patient, wrapped in a sheet, upon a cot covered with a rubber blanket, and sousing rather than sponging him with cold water from a large carriage-sponge. If the sacking-bottom or the canvas of the cot be so loose as to sag down several inches, and the rubber blanket be turned up at the bottom and top over a wide board nailed across the top and bottom, the patient during the sponging lies in a big pool of water, and all the effect of the cold bath is obtained by removing with a carriage-sponge this water as fast as heated, and sousing fresh cold water (ice-water, if necessary) freely over the upper part of the patient. Sometimes the bed in which the patient lies can be arranged with a rubber sheet drawn up over the pillow and down over the foot, folded into a trough, and the cold water applied without wetting the bed. During the bath the hands should be kept out of the water, and the surface of the body should be briskly rubbed so as to divert the attention of the patient, and also to prevent as far as may be the driving of the blood from the surface of the body by the local effects of the cold. When the circulation is weak, advantage is often gained by putting the feet or even both feet and hands upon a hot-water bag. The temperature of a fever patient should during the treatment be taken every three or four hours. Theoretically the bath should be re- peated whenever the temperature gets above the limit, 102.5 F. , but practically it is best not to use the bath oftener than once every three or four hours. It should be administered if required during the night as well as during the day, and its use should not be allowed to interfere with any other treatment which may be indicated. In explaining the use of the method to the patient or friends, it must not be forgotten that the cold bath in typhoid fever and other acute dis- eases associated with high pyrexia does not arrest the disease-processes ; and, whilst it may greatly lessen the mortality, it shortens the duration of the disease only in so far as it prevents complications. On the other hand, the disease-processes do not exhaust the patient so much as when the fever is allowed to continue unchecked, so that convalescence is usually much more rapid than under the older plan of treatment. By the anti- pyretic treatment the intense prostration, delirium, stupor, carphologia, involuntary passages, and other manifestations of the typhoid state are greatly lessened. REFERENCES. 1. MOSLER .... V. A. P. A., Ivii. 9. ROEHRIG and ZUNTZ . A. G. P., iv. 66. 2. LlEBERMEISTEK . D. A. K. M., 1. IO. SASSETZKY . . . V. A. P. A., XC1V. 517. 3. WEISFLOG . . . . D. A. K. M., ii. 570. n. BAUER and KUNSTLE . D. A. K. M., xxiv. 4. KERNIG . . . A. A. and P., 1860. 12. SCHLEICH . . . A. E. P. P., 1875. 5. LIEBERMEISTER . Beobacht. und Versuche 13. COMEGVS . . . . P. M. T., v. 665; A. J. M. iiber die Anwendung des S., Oct. 1876. kalten Wassers, etc., 14. WUNDERLICH . S. Jb., clvi. 101. Leipzig, 1868. 15. JACCOUD . . . . Path. Intern., ii. 758. 6. GILDEMEISTER . V. A. P. A., Hi. 131. 16. BAUER ... . S. Jb., clvi. 101. 7. LEHMANN . . . . V. A. P. A., 1873. Iviii. 17. GOLSDAMMER . B. K. W., 1877, 98. 8. LIEBERMEISTER . D. A. K. M., x. 89, 425. CHAPTER IV. FIG. i. 7\ c 1 \ I ^ \ z ELECTRICITY. GENERAL CONSIDERATIONS. Electricity is a force which is developed in various ways, but which is essentially the same entity under all circum- stances. When it is obtained by rubbing two surfaces together, it is known as frictional electricity ; when it is obtained by the union of two dissimilar metals, it is called galvanism. Frictional electricity is almost never used in medical practice, and we shall say nothing more about it in this book. There are a large number of different patterns or arrangements of the elements which generate gal- vanism, but the ideal or typical cell may be said to be formed of two dissimilar metals immersed in some cor- rosive liquid and connected with each other by a piece of wire externally. Under these circumstances the current starts from the metal most easily corroded, passing through the liquid to that less easily acted upon, and from this over the external wire to the starting-point. The external end of the least easily corroded plate is therefore always giving off electricity, and is known as the -f or positive pole, while the corresponding end of the other plate is constantly re- ceiving electricity, and is spoken of as the or negative pole. When wires are attached to these plates they become, as it were, prolongations of the plates, and their ends constitute the poles. Thus, in the diagram, C= copper, Z= zinc, P and N=- poles, and the arrows show the direc- tion of the current. The positive pole is called the anode (<*vcE, upward, and represents is more than (the point of the < being towards the lesser quantity). Then the formulas are : An Cl C < Ca Cl C A r\ r- \ r- ^ r* i muscle normal. An O C > Ca O C ) An Cl C = Ca Cl C ) . . .. fi nrl musc ' e m the nrst stage of degeneration. x\n v_/ v- v_^cl v_y V^ ) An Cl C > Ca Cl C | muscle in a more advanced stage of degenera- An O C < Ca O C j tion. After the latter reactions of degeneration (De R of some authors) have been established, if the muscle continues to undergo change, the 54 ELECTRICITY. galvanic irritability slowly diminishes, stronger and stronger currents being required to produce an effect. When a certain stage is reached, all reac- tions cease, save a feeble An Cl C, and at last this is lost and the muscle does not respond at all. When recovery occurs, the electrical reactions of the muscle pass upward along the pathway they have descended. The practical importance of the reaction of degeneration is greatly lessened by the circumstance that its demonstration usually requires much skill and patience,* and that it probably is never present when a muscle still retains its integrity as regards the faradic current. For the purposes of the practitioner, the failure of response to the latter current is the best test as to the condition of a muscle. When a muscle loses its power of responding to the rapidly interrupted faradic current in a week or ten days after the occurrence of paralysis, whether the reaction of degeneration can or cannot be satisfactorily demonstrated, the inference is very positive that the lesion either is one of the nerve-trunk or, if of a nerve-centre, is of such a character as seriously to involve the trophic cells of the spinal cord. If a few days later such muscle is unable to respond to any faradic current, this inference becomes a certainty. Under these circumstances, the possible lesion is narrowed down to poliomyelitis, a conceivable de- structive myelitis, and an affection of a nerve-trunk. The persistence of muscular contractility intact for some weeks after the occurrence of a palsy depending upon an organic lesion proves that the disease is of cerebral origin, or, being spinal, is of such nature as not to compromise seriously the trophic nerves of the cord. In applying these rules, it must not be forgotten that whenever a muscle is not used it loses its contractile power, so that even in paralysis from cerebral hemorrhages the muscles finally degenerate, although this degeneration is rarely so complete as in peripheral palsies. It is not the fact of degeneration, but its degree, and especially the period of time which elapses between its occurrence and the commencement of the paralysis, that is the important factor in the diagnosis. In cerebral palsies no distinct loss of functional activity in the muscles is usually perceived sooner than six weeks after the onset of the attack ; and even after years have elapsed some response may often be elicited by strong slowly inter- rupted or reversed currents. There are certain palsies in which the electro-muscular contractility is really or apparently above normal. Very frequently the excessive contrac- tions produced are not so marked in the muscles to which the currents are applied as in other muscles, whose movements are in reality reflex in their nature. In all these cases the probabilities are that there is a condition of acute hyperaemia or of excessive functional irritability of the spinal cord. In hysterical paralysis any aid to diagnosis is often of very great * In attempting to bring out the reaction, the clock-work current-breaker as usually furnished by instrument-makers is useless ; the hand current-breaker may be employed, but almost requires an assistant. Hence some electricians use a pedal rheotome, which enables the operator to cut off the current without moving his hands. ELECTRICITY. 55 value, and it has been asserted that in this class of palsies the preser- vation of electro-contractility with loss of electro-sensibility is always present, and is of diagnostic import. Our experience, nevertheless, is very positive that in hysterical palsy both electro-contractility and electro- sensibility are frequently normal. When, however, the paralyzed muscle responds to galvanic currents, and the patient is to a great extent, or altogether, insensible to their passage, a very positive diagnosis of hysteria may be given. The electro-contractility is never seriously compromised in hysterical palsy. In using galvanism as an aid in prognosis, the condition of the mus- cular contractility is always to be considered in conjunction with the nature of the lesion and the length of time it has existed. Taking first ordinary hemiplegia as the type of cerebral palsies, it must be borne in mind that the actual existent amount of paralysis is really the product of two essentially different factors. The nerve-centre is primarily damaged, and after a time the muscle also suffers loss of structural in- tegrity from want of use. The restoration of the nerve-centre does not necessarily involve the restoration of the muscle, so that in a case of hemi- plegia of some standing the cerebrum may have recovered itself partially or entirely, and yet the muscle be in such a state of degeneration as to be unable to respond to the impulse transmitted to it from the nerve-centre. Under these circumstances, galvanic treatment, although unable to affect the nerve-centres to any extent, does great good by restoring the muscular tone. It is manifestly impossible in such a case to determine before treatment how far the nerve-centre has recovered itself, or, in other words, to what extent the existing paralysis is of centric and to what extent of muscular origin. When, in a case of apoplectic hemiplegia, there is no recovery of the power of voluntary movement after the lapse of six weeks, the prospect of decided improvement from electrical treatment is very gloomy, because the probabilities are altogether in favor of the existence of a serious, persistent centric lesion. If, however, there is some motion, the probabilities of improvement are inversely propor- tionate to the structural health of the muscles, i.e., the worse the state of the muscle the better the expectation of relief. If the tone and the electro-contractility of the muscles are normal, the centric factor is the chief one in the production of the paralysis, and little good is to be achieved by the use of the galvanic current. On the other hand, if the muscles have undergone a very decided degeneration, much good is to be expected. No hopes of absolute cure should, however, be held out, be- cause, in the great majority of cases, after the muscles have been fully restored the nerve-centre is found to be more or less damaged. The im- provement under the use of electricity is usually at first rapid, but after a time ceases altogether, because, the muscles having recovered their tone, it is not possible to affect to any great extent the sole remaining cause of the paralysis, i.e. , the centric lesion. Under these circumstances it is useless to continue treatment. 56 ELECTRICITY. In poliomyelitis, early in the attack the galvanic current is of little value in determining the prognosis, except that the general law is, that the more rapidly electro- contractility is lost the more serious is the case. In advanced cases the duration of the attack and the condition of the electro-contractility in the muscles are both to be considered. If no response to an electric current can be obtained, the prognosis is always very grave ; although even under such circumstances a decided improve- ment has occurred in a small percentage of the cases we have treated. If the case be an old one, the preservation of some degree of electro-contrac- tility indicates that the structural lesion in the cord is not a fatal one ; and as, under these circumstances, the muscles can always be more or less per- fectly restored, the prospect of improvement is very good. The preserva- tion of electro-contractility late in the disorder, when the centric lesion is no longer progressing, is of much more import than it is in the first few weeks or months of the case, when the central trouble may be increasing. In peripheral palsies the prognosis depends upon the nature of the nwve-lesion rather than upon the condition of the muscle ; but it must be remembered that when a muscle has absolutely lost its power of respond- ing to any electrical current its restoration is always a matter of difficulty and of some doubt. In regard to therapeusis, the first point to be determined in acute cases is, very often, when to commence electrical treatment. When the lesion is of such nature as not to provoke any irritation of the nerve-centre, no time should be lost. Thus, if a man is unable to use his arm because he has slept with it under his head and thereby paralyzed the nerve by pressure, galvanism should be at once employed. When, however, the lesion is of such character as of necessity to irri- tate the nerve-centres, the case is different. The local stimulation of the peripheral nerve-fibres by the electrical current does, in some way not yet definitely understood, affect the nutrition of the nerve-centres ; and when these nerve-centres are in a state of active excitement or inflammation, a peripheral galvanic irritation may do serious injury. Hence the rule that when an acute palsy is connected with active irritation of the nerve-cen- tres, galvanism should not be used upon the muscles until the centric dis- turbance has subsided. Thus, in hemiplegia from cerebral hemorrhage the muscles must be allowed to rest not only until all symptoms of centric irritation have passed away, but also until the brain has become so accus- tomed to the clot that the latter no longer acts as a foreign body. It is usually from three to six weeks before electricity can be used with advan- tage in these cases. Again, in acute cerebritis, cerebral or spinal menin- gitis, and myelitis, the employment of galvanic currents should be strictly forbidden until a stage is reached when the effects of the inflammation, and not the inflammation itself, are to be dealt with. When it has been decided to commence the use of electricity, it is next to be determined what current shall be employed. It has already been shown that there are no inherent mysterious differences in the various ELECTRICITY. 57 currents ; yet there is a practical difference, and the clinical rule of choice is, Always select that current which produces the greatest amount of muscu- lar contraction with the least amount of pain ; trying the rapidly inter- rupted faradic or the rapidly interrupted chemical current and the slowly interrupted faradic or the slowly interrupted chemical current, and always, when these fail to elicit response, the slowly reversed chemical current, which, if necessary, may be increased in strength until the patient can no longer bear the pain. The current having been selected, the individual muscles must be gal- vanized at each seance. After what has been said, it is not necessary to speak at this point as to the best methods of applying the currents to the muscles, but only to insist upon the fact that it is not so much the electricity as the con- tractions induced by it that benefit the palsied parts, and that conse- quently the electro-motor points of the muscles should always be sepa- rately reached. The diagrams given in the Appendix will point out more clearly than would any description the approximate positions of the motor points, which vary somewhat in their location in various individuals. Some deep-seated muscles we are not able to reach directly, but we can reach them indirectly by galvanizing the nerves which supply them. There are certain precautionary rules which must never be lost sight of in the electrical treatment of palsies. Pain is an evil, and its infliction is always to be avoided as far as possible. Hence the rule never to use stronger currents than is necessary. It is very possible to fatigue a healthy muscle, much more a diseased one. A weak muscle may be greatly in- jured by being over-fatigued. Hence the rule that currents are not to be applied to muscles sufficiently long at a time to induce fatigue. In gen- eral, an electrical stance should last from ten to twenty minutes, no one muscle being subjected to the currents for more than five minutes, and it may be repeated daily, or three times a week. Sensory System. Affections of the sensory nerves are of three kinds, pain, hypersesthesia, and anaesthesia. The use of electricity for the relief of these disorders is almost entirely empirical, indeed, is often purely experimental in an individual case, as no clinical laws regulating the use or enabling us to decide as to the applicability of the agency have as yet been worked out. It may be laid down, however, as an axiom, that the galvanic current is powerless to relieve the pain of phlegmonous inflammations, and that its use should be restricted chiefly to nervous pain or neuralgia. It is also true that the currents are possessed of no therapeutic power over neural- gia dependent upon central organic lesions ; this is also probably true of such neuralgias as migraine, malarial hemicrania, and some toxic neu- ralgias, in which, although there is no perceptible organic lesion, there is some deep-seated, inherent deficiency either in the central nervous system or in the constitution or condition of the patient. When, as in sciatica, the so-called neuralgia is due to a neuritis, 5 8 ELECTRICITY. galvanism may be of great service. It should not be applied, however, until the stage of very acute inflammation is past. In regard to the selection of the current, our experience is that it must be purely em- pirical. The most usually successful is a very mild (four to eight cells) chemical current, which should be passed steadily for ten minutes down the nerves. It should not be so strong as to give actual pain, and must not be interrupted. As in the great majority of cases this method of application yields the best results, it should always be tried first. When it does good, it nearly always affords relief during the passage of the current, at once or after, at the most, two or three sittings. Further, the period of relief soon begins to extend beyond the seance and gradually grows longer and longer. Some cases receive most benefit from a rapidly interrupted faradic current, which should therefore be tried if the continu- ous current fails. To the employment of electricity should, of course, always be added the proper local and constitutional treatment of the case. In hysteria, in some cases whose nature is very obscure, and rarely as a sequela or result of a serious cerebral or spinal lesion which may have been more or less completely recovered from, there exist local anesthesias of the skin. When these are not dependent upon a too serious organic lesion, they are often very much benefited, or even cured, by the use of the electric brush. This should be large and composed of fine wires, while the other electrode should consist of a large, well-wetted sponge, placed upon a distant part of the body. Either the faradic or the chemical current may be employed ; in either case it should be a very strong one. Toxaemic anaesthesias, such as those sometimes produced by arsenic, we have seen benefited by electrical treatment with the dry brush. APPLICATION TO THE NERVE-CENTRES, AND USE AS A TONIC. Galvanism in various forms has been applied locally to the nerve-centres in various diseases. In regard to the brain, we have never yet met with any clear clinical evidence of good having been accomplished ; and, with our present physiological knowledge, it is difficult to imagine in what way or under what circumstances cerebral galvanization can produce good results. On the other hand, harm certainly has been wrought by the application of strong currents to the head. Galvanic currents passed through the brain can act only as irritants, and we agree entirely with the dictum of Cyon {Principes or ih of an average adult dose," 68 PRELIMINARY CONSIDERATIONS. the prescription, all the ingredients should first be put down, then the number of doses should be decided upon, and the individual amounts of each substance marked seriatim. It is a very good custom always to place first upon the list the strongest of the drugs employed. The art of combining remedies is not a difficult one ; but in practice certain principles should not be lost sight of. Chief of these are, to pre- scribe as few remedies as possible, and to use no powerful drug without a very distinct idea of what it is intended to do. Whenever it is desired to give a powerful remedy in increasing doses until its physiological effect is produced, it should always be given by itself. Thus, it may be necessary to give arsenic so as to impress the system, at the same time that iron is indicated ; but the two remedies should be given separately, so that the dose of either can be increased or diminished independently of the other. The principles of combination, formulated below, were long ago enun- ciated by Paris, but are to-day as imperative as ever. Medicines are combined, First. To augment, correct, or modify the action of a medicine. Thus, purgatives act much more kindly when a number of them are united together. The chief reason of this probably is, that as different remedies affect different portions of the gut, the whole intestine is best reached by a union of the diverse substances. It may take an intense irritation of the mucous membrane to purge as actively as does a mild irritation of both the mucous membrane and the muscular coat. There are powerful medicines which act similarly upon some parts of the organism, but dissimilarly upon other parts. By combining such remedies powerful effects can be obtained at the points where the two lines of action cross each other, without influencing to a great extent other portions of the system. Thus, chloral produces sleep by its action upon the brain, and also has a distinct influence upon the heart, but none upon the intestinal tract. Morphine acts upon the brain, and does not influence the heart, but has a powerful effect upon the intestinal tract. By combining chloral and morphine we get an overwhelming conjoined influence upon the brain in producing sleep with the least possible dis- turbance of the heart and of the intestinal tract. Secondly. To obtain the joint action of two or more diverse remedies. Thus, in a cough mixture, morphine may be included to quiet the cough, while ipecacuanha and squill (in accordance with the first principle) are added to affect the mucous membrane. The application of this principle requires caution, or the practitioner will be led into that chief abomina- tion, polypharmacy. It is worse than futile to attempt to prescribe for every symptom. It is the underlying cause of the disorder or the under- stratum of bodily condition which must be sought out and prescribed for simply. Thirdly. To obtain a special combination which is really a new remedy, or which experience has shown acts almost as a new remedy. Thus, when to potassium iodide in solution corrosive sublimate is added, PRELIMINARY CONSIDERATIONS. 69 a new chemical compound is formed, which experience has shown to be of great value in syphilitic diseases. Griffith's antihectic mixture is another instance of the use of chemical changes, the protocarbonate of iron being formed out of the sulphate of the metal and the carbonate of potassium. In the famous Dover's powder no chemical change occurs, but the ordinary action of opium upon the skin is so enhanced that the combination may be looked upon almost as a new remedy. Fourthly. To afford a suitable form. Thus, acacia is added to make an emulsion, or confection of rose to make a pill. In the choice of excipients, care should be exercised to select a substance free from medi- cal properties, having no chemical incompatibility with the medicinal agent, and of suitable physical character. Bread-crumbs often make a good basis for pills ; but with silver nitrate they are chemically incom- patible, on account of the chlorides in them. When writing a prescrip- tion, the utmost care should be taken to use such excipients that the combination shall not only be attractive to the eye, but also as little repul- sive to the palate as may be. Whenever possible, the pill form should be employed with bitter or disagreeable medicines. The pill may be readily coated with silver-foil ; tonic pills may be coated with iron by shaking or rolling them in ferri pulvis while soft and sticky. Sugar-coated pills and " compressed pills" are liable to get so hard and insoluble that their use requires caution. In regard to mixtures, flavoring oils should be freely used, and the power of glycerin to conceal the disagreeable taste of many substances should be remembered. Whenever practicable, nauseous medicines should be given in capsules. These occur in two forms. Hard capsules are prepared to be filled extemporaneously. They can be made large enough to hold ten minims, although this size cannot be easily swal- lowed by every person without a little training. The soft, flexible cap- sules are filled by the manufacturing chemists. They can be readily swallowed by most persons up to the size of one drachm. Not only may solid preparations be given in capsules, but also essential oils, volatile liquids, fixed oils, and fluid extracts ; indeed, almost any liquid the dose of which is not too large. Incompatibilities. In combining remedies, the subject of incompati- bilities must never be lost sight of. The kinds of incompatibilities are two in number, physiological and chemical. The first of these it would require large space to discuss fully, and any one familiar with the text of the book, if possessed of the slightest reasoning powers, can readily make all necessary deductions. In many works on materia medica long lists of chemical incompati- bilities are given in the accounts of individual drugs. These lists have seemed to us useless, as we have never met with a student who could com- mit and retain them. Moreover, they contain so much matter of no practical use that the valuable portion is hidden from sight. A certain amount of chemical knowledge is essential to the student, and is not to be taught in a book like the present. He who would ignorantly combine 70 PRELIMINARY CONSIDERATIONS. sulphuric acid and a carbonate needs to restudy his chemical text-book. All that we shall do here is to point out certain principles and a few especial reactions. The following rules may serve for a guide : Soluble salts which can by mutual decomposition form an insoluble compound will undergo such decomposition when they meet in solution, and will precipitate, unless in some very rare instances, in which a double salt is formed. Soluble salts which are not capable of forming an insoluble salt never precipitate, and rarely undergo decomposition, when they meet in solu- tion. Mineral acids decompose salts of the weaker (carbonic, acetic, etc.) acids, and form ethers with alcohol and alcoholic preparations. Alkalies precipitate the alkaloids and the soluble non-alkaline metallic salts. Glucosides, such as santonin and colocynthin, should not be prescribed with free acids or emulsin. Tannic acid and all substances containing it are incompatible with alkaloids and glucosides and drugs containing them, with albumin and gelatin, with most soluble metallic salts used in medicines. Iodine and iodides are incompatible with the alkaloids and the sub- stances containing them, as well as with most soluble metallic salts. The potassium iodide * should always be prescribed alone, or only in com- bination with corrosive sublimate (with which it forms a double salt), or with iodine itself. Tinctures and other alcoholic preparations containing resin precipitate the latter when water is added. Silver nitrate should always be prescribed alone, or in combination with opium or extract of hyoscyamus only. Most vegetable extracts de- compose it, and with creosote it is said to make an explosive compound. Corrosive sublimate is incompatible with almost everything, and should be given in simple syrup : even the compound syrup of sarsaparilla is said to decompose it. Syrup of squill, containing acetic acid, is incompatible with ammonium carbonate, but not with the chloride. Lead acetate and subacetate are incompatible with almost everything, but are nevertheless frequently used in lotion with opium, the insoluble compound formed being therapeutically active. Vegetable infusions are generally incompatible with metallic salts. CLASSIFICATION. This book has been arranged in accordance with the scheme directly hereafter set forth. Some of the families as here defined are not thoroughly natural, but most of the groups have much of unity in themselves and of propriety in their relations. Thus, antispas- * Death has resulted from a prescription containing strychnine and potassium iodide, all the alkaloid being taken at the last dose. PRELIMINARY CONSIDERATIONS. 71 modics are little better than a heap of incongruities, but delirifacients are singularly united together and opposed to somnifacients, while anti- periodics, perhaps, ought to be merged in the alteratives, with which through arsenic they are closely related. DIVISION I. SYSTEMIC REMEDIES, substances which act on the solid or fluid tissues of the body. DIVISION II. EXTRANEOUS REMEDIES, substances which are em- ployed to act on secretions, excretions, or other liquid or solid bodies which are not human tissues. SYSTEMIC REMEDIES. CLASS I. GENERAL REMEDIES, drugs which affect the tissues of the body generally or such organized systems as reach all portions of the body. ORDER I. Nervines, drugs which affect the nervous system. ORDER II. Cardiants, drugs which affect the circulation. ORDER III. Nutriants, drugs which affect the nutritive movements of the body. NERVINES. A. Medicines which act on the cerebrum. B. Medicines which act on the lower or neuro-muscular apparatus. A. FAMILY I. Antispasmodics, feeble cerebral stimulants which are em- ployed for the relief of minor spasms and other nervous symptoms, the result of insufficient nerve-power. FAMILY II. Anesthetics, drugs which are used for the production of anaesthesia. FAMILY III. Somnifacients, drugs which when in sufficient doses produce deep sleep without delirium. FAMILY IV. Delirifacients, drugs which when in sufficient doses produce delirium, followed by stupor. B. FAMILY V. Excito-motors, drugs which produce violent tetanic spasms. FAMILY VI. Depresso-motors, drugs which cause paralysis. CARDIANTS. FAMILY I. Cardiac Stimulants, drugs which increase the arterial pressure. FAMILY II. Cardiac Depressants, drugs which lower the arterial pressure. NUTRIANTS. FAMILY I. Astringents, drugs which call into exercise the vital func- tion of contractility. 72 PRELIMINARY CONSIDERATIONS. FAMILY II. Tonics, drugs which so influence nutrition as to increase the reconstruction or upbuilding of the tissue or tissues concerned. FAMILY III. Alteratives, drugs which so modify nutrition as to over- come certain chronic pathological processes. FAMILY IV. Antiperiodics, drugs which so modify nutrition as to overcome the effects of malarial poisoning. FAMILY V. Antipyretics, drugs which so modify nutrition as to over- come febrile movements. CLASS II. LOCAL REMEDIES, drugs which affect one organ or appa- ratus more or less isolated from the remainder of the body. FAMILY I. Stomachics* FAMILY VIII. Oxytocics. II. Emetics. " IX. Irritants. III. Cathartics. " X.Escharotics. _ ' ' IV. Diuretics. X I . Demulcents. V. Diaphoretics. " XII. Emollients. " Ml. Expectorants. " XIII. Protective*. " VII. Emmenagogucs. EXTRANEOUS REMEDIES. FAMILY I. Antacids. FAMILY IV. Absorbents. " II. Anthelmintics. " V. Disinfectants. lll.Digestants. * The definitions are not given in these families, as they are old and well known and their names show the reader to what organs each applies. It should be stated, however, that the family stomachics contains drugs which are used simply as stimulants to the gastro-intestinal tract, including, therefore, Simple Bitters, so called, and Arematics. DIVISION I. SYSTEMIC REMEDIES. CLASS I. GENERAL REMEDIES. ORDER I. NERVINES. FAMILY I. ANTISPASMODICS. UNDER the name of Antispasmodics are grouped in this treatise a number of medicines generally of very feeble powers, but of frequent use. In certain conditions of the nervous system conditions associated with weakness rather than with simple depression the nerve-centres appear to be more susceptible than is normal to external impressions, as well as to those impulses which originate in the cerebral centres themselves and are connected with the emotions. As a result of this state, various symptoms arise, of trifling import, but often apparently severe, and always annoying. Such symptoms, in their mildest form, constitute the state of unrest known as nervousness ; in their severer type they may rise in intensity up to the wildest convulsion of hysteria. It is in this class of affections that the so- called antispasmodics are useful. As the condition which they relieve is always associated with weakness, they are often spoken of as " nerve- stimulants." In regard to most of them there is but little evidence of their increasing power or functional activity when administered to healthy individuals. Some of them act slightly upon the circulation when given in very large doses, and a few when administered as freely as possible in- duce slight cerebral symptoms, such as vertigo ; but, except camphor and Hoffmann's anodyne, none are capable of producing serious poisoning. As any theory of the method in which the hysterical convulsion originates of its immediate causes and the mechanism of its production would, with our present knowledge, be at best but an ingenious speculation, the safest plan in regard to the action of drugs belonging to the class now under consideration is to accept the teachings of clinical experience as to facts, and to avoid theorizing as to the way in which the results are brought about. MOSCHUS MUSK. U. S. A highly odorous, unctuous substance, obtained from the glands situ- ated just in front of the preputial orifice of the Moschus moschiferus, or musk-deer of Thibet. The genuine musk-sac is to be distinguished from 73 74 GENERAL REMEDIES. imitations of it by the hairs being arranged concentrically around a minute orifice. As it occurs in commerce, musk is very greatly adulterated. PHYSIOLOGICAL ACTION. Musk appears to act upon the nervous system simply as a mild stimulant and antispasmodic. Jorg and Sundelin have experimented with it upon healthy men with somewhat contradictory results. According to the first-named observer, twenty grains of it induce exhilaration without lassitude, but, according to the latter authority, may cause giddiness, drowsiness, and lassitude. Both observers noted a slight increase in the frequency of the pulse. THERAPEUTICS. Musk is at present very little used, but it is strongly recommended by some of the older writers in various spasmodic affec- tions, especially in hysterical convulsions. In hiccough it has been con- sidered a specific. In our experience, in the crisis of low fevers when the symptoms of nervous exhaustion are extreme and threaten death, musk is a very valuable remedy. Thus, in advanced typhoid fever a condition sometimes develops in which the pulse is exceedingly feeble, and the tem- perature has a tendency to rise to a great height, but yields almost imme- diately to the use of cold, only, however, to remount as soon as the cold is withdrawn. We have seen musk at such time control the temperature, steady the pulse, and apparently save life. In other cases of advanced fevers the powers of the system entirely give out, and the patient passes into a condition of collapse, with subnormal temperature, and mayhap coma- vigil : this state we have also seen relieved by musk. Originally recommended by Trousseau in the ataxic pneumonia of drunkards, musk may be a useful remedy in any forms of adynamic pneumonia when there is wild or muttering delirium. From ten to fifteen grains of musk (the best attainable) must be given at a dose, preferably by rectal injection, suspended in mucilage. The effect of the single dose lasts about six hours. The dose of the Tincture of Musk (TINCTURA MOSCHI five per cent., U. S.) is from one to two fluidrachms (4-8 C.c. ). VALERIANA VALERIAN. U. S. The root of the Valeriana officinalis, an herbaceous perennial of Europe. It consists of a short, yellowish- white rhizome, with numerous fibrous roots, of a bitter taste and peculiar odor. Valerian depends for its activity upon a volatile oil and the valerianic acid which it contains. PHYSIOLOGICAL PROPERTIES. The physiological action of valerian is very feeble. The extraordinary excitement which it produces in cats is probably due to a suggestive odor rather than to any direct influence. Large doses of valerianic acid cause in rabbits some acceleration of the pulse and respiration, followed by lessened frequency of these functions and general lassitude. Enormous doses may produce a fatal gastro-en- teritis. According to Butte, 1 the extract of valerian has a pronounced effect in checking the destruction of glucose in the blood. Upon man, very large doses (gii to giv) are said to produce a feeling ANTISPASMODICS. 75 of warmth in the stomach and quickening of the pulse, followed by nausea, vomiting, and colicky pains. THERAPEUTICS. Valerian is useful in the state of unrest familiarly known as nervousness, is much used in the minor disturbances of hysteria, and has been employed, though with little advantage, in mania a potu and adynamic delirium as an adjuvant to more powerful drugs. The dose of the fluid extract (FLUIDEXTRACTUM VALERIANS, U. S. ) is one fluidrachm (4 C.c.) ; of the ammoniated tincture (TiNCTURA VALE- RIANS AMMONIATA twenty per cent., U. S. ), one to three fluidrachms ; of the simple tincture (TINCTURA VALERIANS twenty per cent, U. S.), one to three fluidrachms (4-10 C.c.). AMMONII VALERAS. U. S. Ammonium valerate or Ammonium valerianate, a white salt in quadrangular plates, effloresces in a dry and deli- quesces in a moist atmosphere, has the odor of valerianic acid and a sharp, sweetish taste, and is very soluble in water and in alcohol. According to W. E. Parke, 1 it produces in the frog convulsions followed by general paralysis, both the convulsions and the palsy being of spinal origin, and also is capable by local contact of killing any of the higher nerve-tissues. These effects are probably due to the ammonia, and throw no light upon the therapeutic action of the drug, which is about equivalent to valerian, but sometimes has especial usefulness in nervous headache. Dose, ten grains (o. 65 Gm. ) , generally administered in the form of an elixir. VALYL. Valerianic acid Dimethylamid. This is a colorless liquid with a pun- gent, acrid taste, which has been physiologically investigated by Kionka, s who states that it produces cerebral excitement, attended with convulsions, followed in the cold-blooded animals by general paralysis ; the convulsions probably being of cerebral origin since there is no increased reflex activity. It is said primarily to increase the blood-pressure slightly, probably by contracting the blood-vessels, but to have little action upon the heart or respiration. Locally it is somewhat irritant, but may be given in a four per cent, aqueous solution, and has been used with success, in hysterical vomiting, neurasthenia, hysteria, and similar neuroses. Dose, four to fifteen grains three times a day, preferably administered with an equal amount of tallow in gelatin capsules. VALIDOL. This is a colorless liquid, of a mild pleasant smell and a slightly bitter taste ; said to contain thirty per cent, of menthol combined chemically with seventy per cent, of valerianic acid. It was originally proposed by Schwersenski * in the treatment of pruritis, gastralgia, coryza, and various mucous inflamma- tions, and as an antispasmodic, in migraine, neurasthenia, hysteria, and other neuroses. Other clinicians have commented favorably upon the drug as an anti- emetic and stomachic. It is stated to be chiefly eliminated in the urine, to which it imparts a peculiar odor. Dose, five to twenty drops ; locally, a ten to fifteen per cent, ointment is recommended. Validolum camphoratum is a ten per cent, solution of camphor in validol. ASAFCETIDA ASAFETIDA. U. S. An exudation obtained by incising the living root of the Ferula foe- tida, an umbelliferous plant of Afghanistan. It occurs mostly in ir- regular opaque masses of a dull yellowish or pinkish brown, white when 76 GENERAL REMEDIES. freshly broken, of a bitter acrid taste and a strong garlicky odor. Asa- fetida is composed chiefly of gum and resin, but its properties are in great part due to the volatile oil, of which it contains from 3.5 to 4.5 per cent. PHYSIOLOGICAL ACTION. When taken into the stomach, asafetida acts as a local stimulant and carminative, and on this account is in some parts of the East used as a condiment. The oil is without doubt absorbed. The evidence as to its action upon healthy men is both scanty and con- tradictory. Thus, while M. Pidoux took half an ounce in a single dose without perceptible effects other than to render his secretions horribly offensive for two days, Jorg and his disciples found that in twenty-grain doses it produced gastric uneasiness and pain with alvine dejections, in- creased the pulse-frequency and animal warmth, quickened the respira- tion, and caused headache, giddiness, and erotic excitement. THERAPEUTICS. Asafetida is the most efficient of the antispasmodics, and may often advantageously be substituted for valerian in functional s^asm, in hysteria, and in nervousness. It differs from valerian in having a much more decided action upon the mucous membranes. It is an excellent carminative, and in the form of injection is constantly used for the relief of tympanites. It is valuable in dyspepsia, with flatulent colic and costiveness, of the aged or hysterical. As a stimulating expecto- rant and anti spasmodic, it is useful in whooping-cough and in chronic bronchial catarrh, especially in old people with an asthmatic tendency. In infantile convulsions, in infantile colic, and in flatulent constipation, asafetida enemata (f^ii to f^ss of milk) are useful and harmless. DOSE. Dose of the Pills of Asafetida (PILUL^E ASAFCETID^, U. S. , three grains each), two to four ; of the mixture or milk of asafetida (EMULSUM ASAFCETID^ four per cent, U. S. ), half to one fluidounce (15-30 C. c. ), or for injections, one to eight fluidounces (30-2400.0. : of the tincture (TixcTURA ASAFCETID^E twenty per cent. , U. S. ), half to one fluidrachm (2-4 C.c. ). SPIRITUS .dETHERIS COMPOSITUS COMPOUND SPIRIT OF ETHER. U. S. Hoffmanri s Anodyne consists of 325 parts (by volume) of ether, 650 parts of alcohol, and 25 parts of ethereal oil. It is a colorless, inflam- mable liquid, of an aromatic, ethereal odor, and a burning, slightly sweetish taste. Its specific gravity is 0.815. SPIRITUS ^ETHERIS, U.S. , which contains no ethereal oil, is often improperly sold under the name of Hoffmann's anodyne. It can be distinguished at once by the fact that forty drops of the genuine preparation will render a pint of water distinctly milky, whilst the simple spirits of ether has no such effect. Ethereal Oil (OLEUM ^THEREUM, U. S. ) is a transparent, nearly colorless, volatile liquid, of a peculiar aromatic odor, and a sharp, bitter taste. Its specific gravity is 0.91. It is heavy oil of wine, prepared by the action of an excess of sulphuric acid on alcohol, and diluted with an equal part of strong ether. ANTISPASMODICS. 77 PHYSIOLOGICAL AND THERAPEUTIC ACTION. H. A. Hare found that the heavy oil of wine caused a rise, followed, if the dose were large enough, by a very marked fall both of the pulse-rate and of the arterial pressure. As the primary rise in the arterial pressure did not occur after section of the spinal cord, it must be, at least in large part, due to stimula- tion of the vaso-motor centre. The fall of pressure is probably in part the outcome of a direct depressant action of the drug upon the heart, since that viscus finally suffers diastolic arrest ; but, as in the earlier period of lowered pressure the individual heart-beats were extremely full and strong, it is probable that vaso-motor paralysis precedes cardiac depression and causes the lowered pressure by widening out the blood-paths. This vaso- motor palsy Hare believes to be chiefly of peripheral origin. In his studies upon frogs, Hare failed to detect any indication of an action of the oil upon the spinal cord, nerves, or muscles. He found the toxic properties of the heavy oil of wine to be very feeble ; thirty cubic centimetres given by the mouth to a small dog (weight twelve pounds) failed to produce marked symptoms. It is therefore evident that the small quantity of the heavy oil of wine contained in Hoffmann' s anodyne can exert no very pro- nounced influence upon the human system, and that the effect of Hoff- mann's anodyne is chiefly that of ether and alcohol combined. Clini- cal experience indicates, however, that Hoffmann's anodyne is more calmative than the simple combination of ether and alcohol. It is a very efficient carminative, and is also a useful antispasmodic in all the disorders for which such remedies are employed, especially when there is a ten- dency to failure of the circulation ; in valvular cardiac disease it is often very effective in relieving mild heart-pains. The dose is one to two fluidrachms (4-8 C.c. ), repeated in half an hour or an hour, if required, and given in cold water. HUMULUS HOPS. U. S. The strobiles of Humulus Lupulus, or the hop-vine, cultivated in North- ern and Middle Europe and in the United States. Hops are soft, green- ish cones, one or two inches in length, composed of thin, leaf-like, imbri- cated scales, having a bitter taste and a heavy narcotic odor. At the bases of the scales is a yellowish powder, official under the name of /,//- pulinum. Lupiilin is in minute grains, and contains, according to Payen, two per cent, of volatile oil, 10.30 per cent, of bitter principle, and fifty to fifty-five per cent, of resin. Volatile oil of hops is yellowish, and has a strong odor of the drug and an acrid taste. The bitter principle has been obtained by Lermer in brilliant rhombic columns, of an acid reac- tion. Hops is a bitter tonic and a very feeble narcotic, which has been given to quiet nervous irritability, and to strengthen digestion in neuras- thenia, and even in delirium tremens. In abnormal sexual excitement it has been much used, but is of no value. Dose of the tincture (TiNCTURA HUMULI, U. S. , 1890), half a fluidounce to three fluidounces (15-9 C.c. ) ; the oleoresin of Lupulin (OLEORESINA LUPULIN.E, U. S.), ten minims 78 GENERAL REMEDIES. to a fluidrachm (o. 6-4 C. c. ) , in capsules if desired ; the fluid extract (FLUIDEXTRACTUM LUPULIN^:, U. S.), half a fluidrachm to one flui- drachm (2-4 C. c. ). A hop poultice is made by moistening with hot water the hops contained, alone or mixed with an equal part of Indian meal, in a gauze bag of the required size and shape. CIMICIFUGA BLACK SNAKE-ROOT. U.S. The root of Cimicifuga racemosa, an indigenous herbaceous plant, growing abundantly in shady woods, attaining a height of six or seven feet, and readily distinguished by its very large multi-compound leaves and its long-branched spikes of whitish polyandrous flowers, naked when open. The root consists of a knotted head, with numerous fine, brittle rootlets ; the odor is faint, and the taste bitterish, somewhat astringent and acrid. The nature of its active principle has not been determined. Commercial Cimicifugin or Macrotin is an amorphous resinous sub- stance. The tendency of the drug to deteriorate on keeping indicates the presence of a volatile principle. PHYSIOLOGICAL ACTION. There have been no cases of poisoning by cimicifuga, but large doses produce giddiness, intense headache, general prostration (evidences that it has influence upon the cerebrum), with re- duction of the pulse-force and rate, and occasionally vomiting, but the emetic action is never violent. That the overdose of cimicifuga has physi- ological activity is shown by the experiments of Hutchinson, 1 who found that in frogs it acts as a depressant of the sensory side of the spinal cord, producing complete anaesthesia with loss of reflex activity at a time when voluntary movement is still preserved, the development of the anaesthesia not being prevented by shutting off access of the poison from the periph- eral nerves by tying the arteries of the leg, and both motor nerves and muscles being found after death functionally active. Upon the circulation cimicifuga acts as a depressant, producing in the mammal fall of the arterial pressure and slowing of the pulse, and causing finally diastolic arrest of the heart. As the slowing of the pulse is not prevented by previous sec- tion of the vagi, and as the isolated frog's heart becomes slow and in a little while paralyzed after direct contact with the cimicifuga, it is evident that the drug acts as a direct depressant to the heart-muscle ; but, since Hutchinson found that asphyxia is incapable of causing rise or pressure while the heart is still beating strongly, it is probable that it not only de- presses the heart but also the arterial system. Under the influence of the drug the respiration becomes slow and suffers final arrest. THERAPEUTICS. Cimicifuga was originally proposed by Young* in 1831 as a remedy in chorea, and in the simple chorea of childhood its value is unquestionable. It must be given until it produces physiological effects, and in most cases the consentaneous exhibition of iron and laxa- tives materially aids it. We have seen it promptly cure urticaria of ner- vous origin after complete failure of the usual treatment. In acute in- flammatory rheumatism, cimicifuga has been highly recommended, but is ANTISPASMODICS. 79 at present very rarely, if ever, used. In chronic bronchitis it is sometimes employed with asserted benefit when there is free expectoration. ADMINISTRATION. The best preparation is the fluid extract (FLUID- EXTRACTUM CiMiCiFUG^E, U. S. ) ; dose, from twenty minims to a fluidrachm (1.2-4 C.c. ). Tincture (TiNCTURA CIMICIFUG^E twenty per cent., U. S.) ; dose, one to two fluidrachms (4-8 C.c.). EXTRACTUM U. S. ; dose, five to twenty grains (0.3-1.3 Gm. ). CAMPHORA MONOBROMATA. U. S. Monobromated Camphor or Bro- mated Camphor. Bromated camphor occurs in large acicular crystals several inches long. Our present knowledge of the physiological properties of bromated camphor rests upon the work of Bourneville, 1 of Lawson, 2 of Pathault,* of Richard Peters,* and of Pellicani. 5 In frogs there is progressive loss of reflex excitability and of voluntary movement (Peters), which, according to Pellicani, is due to paralysis of the motor nerves. Death is caused by arrest of respiration (Peters). In mammals the drug produces violent convulsions, muscular weakness passing almost into paralysis, reduction of temperature (after small doses preceded by a rise Peters), great decrease in the rate of the respiration and of the pulse, with occasional periods of hurried respiration (Peters), profound sleep or stupor, and finally death. Bourneville states that the blood-vessels of the eyes and ears are diminished in calibre. Upon man the drug probably acts as upon other warm-blooded animals ; in a case reported by M. Rosenthal, 8 forty- five grains of it caused tremblings, marked slowing of the pulse, and coma of six hours' duration. Bromated camphor was first introduced by Deneffe 7 as a nervous sed- ative, and as an antispasmodic, especially in delirium tremens, but is of little value ; it is still used in hysteria, and has an especial reputation in sexual excitement and spermatorrhoea. It is taken with difficulty, and is apt to irritate the stomach. It is too irritant for hypodermic use. Dose, five to ten grains (0.3-0.6 Gm. ), in capsule or coated pill, and repeated as necessary. CYPRiPEbiUM, U. S., is the rhizome and roots of Cypripedium pubescens and Cypripedium parviflorum, to which are attributed tonic, diaphoretic, and antispasmodic properties. They are said to contain a volatile oil but no alkaloids. Cypripedin of the drug stores is an impure oleoresinous substance, the dose of which is given as from one-half to three grains. Cypripedium is especially recommended for the allaying of functional nervous excitability and in hypochondriasis. The fluid extract, FLUIDEXTRACTUM CYPRI- PEDII, U. S., may be given in doses of fifteen to thirty minims (1-2 C.c. ). AETHER ACETICUS. U. S. Official Acetic ether is a transparent, colorless, somewhat fragrant liquid, containing ten per cent, of alcohol. 8o GENERAL REMEDIES. It has been used to a slight extent in medicine as a stimulant and anti- spasmodic. It resembles ordinary ether somewhat in its action, but is less volatile and less rapidly absorbed and eliminated. It is capable of producing anaesthesia, but is in every respect much slower and less certain in its action than ordinary ether, and is practically of no value. Dose, internally, fifteen minims (i C.c. ). SUMBUL. U. S. A root supposed to be that of Ferula sumbul has long been used under the name of -musk-root as an antispasmodic. It contains two resins and a volatile oil, and is a feeble nerve stimulant, thought by some to be useful in amenorrhcea, hysteria^ and allied condi- tions. The dose of FLUIDEXTRACTUM SUMBUL, U. S., is thirty minims. Of the EXTRACTUM SUMBUL, U. S., four grains (0.25 Gm. ) ; but much larger amounts may be given without the induction of distinct symptoms. LACTUCARIUM. U. S. The concrete juice of the Lactuca virosa,* or garden lettuce, occurs as a dark reddish-brown to a light yellowish, hard extract, having a faintly narcotic odor and bitter taste. A peculiar soothing, hypnotic influence has been attributed to it, but its activities are so feeble that in a number of trials with very large doses we have been unable to perceive any effect whatever. According to Fronmiiller, 1 lactucin is even less active than the crude drug. In France lactu- carium is used locally as a narcotic demulcent in the treatment of diseases of the throat. The usually assigned dose of lactucarium is thirty grains (2 Gm. ), that of the fluid extract (FLUIDEXTRACTUM LACTUCARII) half a fluidrachm (2 C.c.). TINCTURA LACTUCARII fifty per cent, U. S. ; dose, one to two fluidrachms (4-8 C.c. ). SYRUPUS LACTUCARII ten per cent., U. S. ; dose, half to one fluid- ounce (15-30 C.c.). Much larger quantities may be given without effect. REFERENCES. VALERIAN. 2. LAWSON Practitioner, 1874, 1875. i. BUTTE C. R. S. B., 1891, iii. 3- PATHAULT . . . Bromure de Camphor, a. PARKE Th. G., 1887, 167. Paris, 1875. 3. KIONKA D. M.W., Dec., 1901. 4- PKTBRS S. Jb., ci. 126. 4. SCHWERSENSKI . . Th. M., 1897. 5- PELLICAN1 . . . . S. Jb., ci. 6. ROSENTHAL . . . S. Jb., ci. 127- 7. DENEFFB .... Presse M. B., 1871. 1. HUTCHINSON . . . Th. G., 1887, 731. LACTUCARIUM 2. YOUNG A. M.J.S., 1831, ix. LACTUCARIUM. CAMPHORA MONOBROMATA. '' FRO ^ LER . . Deutsche Klinik, 1865. I. BOURNEVILLE . . PrOg. M., 1874. * For a case of reputed poisoning by Lactuca virosa, see Schmidt's Jahrb., clxxi. 137. FAMILY II. ANESTHETICS. THE term Anesthetics is here employed as the name of a group of volatile substances, whose vapor has the power of producing loss of con- sciousness, preceded by or accompanied with loss of sensibility and di- minished muscular action. The medical properties of these substances are largely due to their volatility, by virtue of which they are very rapidly absorbed and almost as rapidly eliminated by the mucous membrane of the lungs. As a consequence of this, their action is easily controlled. A very large number of theories have been brought forward to account for the peculiar effects of anaesthetics ; of the more important of these theories an elaborate discussion may be found in the tenth edition of this work. There is, however, nothing more mysterious in the action of ether and chloroform upon the nerve-centres than there is in the influence of opium or strychnine upon these centres, the influence of the anaes- thetic being as certainly direct and vital as is that of any other drug which acts upon human organs or tissues. The action of anaesthetics may be modified by the injection of nar- cotics. Morphine given hypodermically about half an hour before the exhibition of the anaesthetic is said to have a decided effect in prolonging the anaesthesia. Chloral administered shortly before etherization certainly causes the first stages of the latter to be much quieter than usual, and also prolongs the narcosis. Some years since Neudorfan 1 introduced into Berlin the use of oxygen gas with chloroform in the production of anaes- thesia ; more recently the method has been revived in America.* It has even been asserted that the oxygen increased the anaesthetic effect of the chloroform. There is not at present writing sufficient evidence, however, of the value of the method. The chief purposes for which anaesthetics are used are to relieve pain and to relax spasm. To meet the first indication they are employed by surgeons especially ; but they are also exceedingly valuable in cases of suffering from disease. It must be borne in mind that their action is transitory and is accompanied by more or less disturbance of the general system, and that consequently they are to be employed only when the pain is exceedingly severe and transient. To relieve pain, anaesthetics are used with great propriety during childbirth.^ In natural labor it is not * See Boston Med. and Surg. Journ., 1896, and New York Med. Record, 1896. t We see no reason for believing that anaesthesia of the mother seriously influences the child, and do not think that much weight can be attached to the assertions of Hofmeier (Berlin. Klin. Wochensch., 1883, xx. 230) that there is produced an increased elimination of nitrogen in the new-born babe. 6 81 82 GENERAL REMEDIES. commonly necessary to produce complete anaesthesia. When the full effect of either ether or chloroform is induced, there is almost always a weakening, and very often an abolition, of the uterine contractions. The anaesthetic should be administered in such quantities as to relieve the pain without decidedly interfering with the muscular spasm. In certain cases this can be done, in others it is impracticable. We have obtained advan- tageous results in some cases by suspending the pains for about half an hour by means of ether, and then entirely withdrawing the anaesthetic. By this treatment the weak, painful, ineffectual efforts of a worn-out, ner- vous patient may often be converted into regular, successful efforts. The risk of post-partum hemorrhage is materially increased by anaesthetics, so that it is well to administer after their use two drachms of the fluid extract of ergot as soon as the perineum is well distended by the child's head.* Anaesthetics are frequently used in surgery for the purpose of relaxing spasm, as in cases of dislocation, hernia, etc. In medicine they have been employed in various forms of convulsions, and are especially valuable in severe hysterical convulsions, in puerperal eclampsia, and in spinal convulsions ; in epilepsy they are very rarely called for ; in infantile convulsions they may be sparingly used when the convulsion itself threatens life. In various spasms of the excretory ducts or canals, and especially during the passage of calculi, they act very favorably, both by relieving pain and by producing relaxation. In asthma, and in spasmodic stricture of the oesophagus, as in all other cases of oft-repeated spasm, they should be administered only to meet temporary indications, as their habitual use is deleterious. NITROGEN MONOXIDE NITROUS OXIDE. Nitrous oxide is a colorless, almost inodorous, gas, of a sweetish taste. It is a very active supporter of combustion. Water absorbs nearly its own bulk of it. It is made by the distillation of ammonium nitrate, which resolves itself into the gas and water. Nitrous oxide gas is now sup- plied in condensed form. In making nitrous oxide the temperature should never be allowed to rise above 482 F. , for fear of generating nitric oxide. PHYSIOLOGICAL ACTION. The inhalation of pure nitrous oxide gas is followed in from a half to three minutes by unconsciousness, which usually comes on quietly, but is sometimes preceded by hilarious, erotic, or pugnacious excitement. During the anaesthesia the face presents a bloated, swollen, intensely livid appearance. The question whether nitrous oxide produces anaesthesia through in- herent properties of its own, or whether it acts simply by shutting oxygen off, has been much discussed and variously answered. * Deaths from anaesthetics are very rare during parturition, but have occurred. (See C. B. Vanzant, Cincinnati Lancet, 1893, xxx.) ANESTHETICS. 83 It is well established that nitrous oxide will not support life. A taper will bum in it, it is true, but the liberation of oxygen is due to the high heat, and at the temperature of the body nitrous oxide is a stable compound. In 1864 Ludimar Hermann, 1 as the result of his experiments, came to the con- clusion that the addition of oxygen to nitrous oxide puts an end to its anaesthetic properties, and that it acts simply as an asphyxiant. In 1873 MM. Jolyet and T. Blanche 2 arrived at the opinion that nitrous oxide has no direct effect upon the sys- tem, and that the narcosis is due to the lack of oxygen in the body ; basing their conclusions upon the following facts experimentally determined by them : i. Seeds will not germinate in nitrous oxide ; 2. An animal lives no longer in nitrous oxide than in nitrogen ; 3. Anaesthesia occurs at the time that the blood of an animal becomes black ; 4. Animals breathing an air containing sixty to eighty per cent, of nitrous oxide and twenty to forty per cent, of oxygen are unaffected ; 5. Analyses of the blood of two dogs yielded the following results : No. i. Conscious. No. 2. Unconscious. Carbonic acid 46 per cent. Nitrous oxide 29 per cent. Oxygen 19.7 per cent. Carbonic acid 36.6 per cent Nitrous oxide 34.6 per cent. Oxygen 3.3 per cent. And other analyses showed that the coma was not developed until the oxygen in the blood was reduced to three or four per cent. The statements of the French observers just quoted have been abundantly corroborated by the observations of various subsequent investigators. Colton,* Elihu Thomson, 4 and H. C. Wood have separately and repeatedly demonstrated that animals will live no longer in nitrous oxide than they will in an atmosphere of hydrogen or nitrogen, or even in a vacuum. In a long series of experi- ments, H. C. Wood 5 found that two minutes and thirteen seconds were required to produce complete anaesthesia with pure nitrous oxide gas, while in mechanical as- phyxia the same result was reached in two minutes and nine seconds. Thomson also asserts that in man the inhalation of pure nitrogen causes the symptoms of nitrous oxide narcosis. H. C. Wood further determined that the introduction of minute quantities of oxygen into nitrous oxide prolonged the time necessary for the pro- duction of anaesthesia in direct proportion to the percentage present, ten or even eight per cent, of oxygen suspending entirely the anaesthetic action of nitrous oxide gas upon the dog. The average time required for the production of anaesthesia was nearly doubled by the addition of three per cent, of oxygen, and increased more than twelvefold by the use of five per cent of oxygen. An examination of the analyses of blood given above shows that the final loss of consciousness is not due to the presence of carbonic acid in the liquor sanguinis, since nearly ten per cent, more of that gas was present in the blood of the conscious (No. i) than in that of the unconscious dog (No. 2), and also that it is more rational to believe that the decrease in the oxygen rather than the slight increase in the amount of the nitrous oxide made the difference between consciousness and unconsciousness. In conformity with this are the researches of C. A. MacMunn 6 and Amory ; the former observer finding that when an animal is killed by nitrous oxide the arte- rial blood gives only spectrum lines of reduced haemoglobin, while after death from chloroform the lines of oxyhaemoglobin are very apparent. Amory 7 demonstrated that during nitrous oxide narcosis the amount of carbonic acid exhaled from the lungs is only two-thirds of that eliminated before the inhalation, and that immedi- ately after the recovery of consciousness less than one-third the normal amount of carbonic acid is given off. If the anaesthesia were due to the presence of carbonic acid in the blood, there should be during and immediately following the return of consciousness great increase in the elimination of this gas. It is evident, however, that during the whole narcosis little or no carbonic acid can be produced because 84 GENERAL REMEDIES. there is little or no oxygen in the blood ; and that consequently when the animal recovers consciousness there can be no pronounced elimination of carbonic acid until by the process of oxidation carbonic acid is formed. As inert gases produce symptoms like those of nitrous oxide anaesthesia, as all these gases have in common with nitrous oxide the function when inhaled of shutting off the supply of oxygen, and as oxygen is necessary for the perform- ance of life functions, it is natural to conclude that the shutting off of the oxygen by the nitrous oxide is the cause of the anaesthesia. It has been urged as an objection to this theory that the circulatory phenomena produced by the inhalation of nitrous oxide are essentially different from those of mechanical asphyxia. It must, however, be borne in mind that the phenomena of mechanical asphyxia are largely due to the presence of an excess of carbonic acid in the blood, whilst in the asphyxia produced by nitrous oxide there is no excess of carbonic acid, so that the phenomena present are simply the outcome of a lack of oxygen. It is, therefore, a priori, to be expected that the symptoms of mechanical and of nitrous oxide asphyxia should differ to a certain extent. In an elaborate series of experi- ments H. C. Wood IT found that the inhalation of nitrous oxide is usually followed by a rise of the arterial pressure, accompanied by a great disturbance of the pulse ; the pulse at first becoming irregular and tumultuous, but by and by settling, so that when anaesthesia is complete the pulse-wave is remarkably large and full and the rate very slow. The rise and fall of the arterial pressure in nitrous oxide anaesthesia was found to vary remarkably, not only in different inhalations, but at different periods of the same inhalation. Sometimes the rise was sudden, sometimes it was gradual ; sometimes it was maintained until near death, sometimes it was inter- rupted very early ; sometimes it was not very well marked, sometimes it was enormous. Dr. Amory 7 has found, in experiments with the cerebrometer upon the dog, that there is, during the anaesthesia, increased blood-pressure in the cerebrum, with stasis in the capillaries. These results show that the circulatory phenomena produced by nitrous oxide resemble those of mechanical asphyxia as closely as could, a priori, be expected. Notwithstanding all the evidence which has just been given, there is much reason for believing that nitrous oxide has anaesthetic properties ; and that although the unconsciousness which is produced when pure nitrous oxide is inhaled is largely the outcome of the deprivation of oxygen, yet the drug is capable of producing narcosis by its own inherent properties. Martin Goldstein 8 found that when he put frogs in an atmosphere of pure nitrous oxide they became motionless, with a complete loss of the reflexes, in fifteen min- utes ; whilst when they were put in an atmosphere of nitrogen or some other in- different gas they preserved their irritability for some hours. It is known that whilst the nervous system of the mammal requires for its activity the presence of oxygen, the nervous system of the frog remains functionally active for some hours after all circulation that is, after all carrying of oxygen to it has ceased. Believing that if he could increase the amount of nitrous oxide in the blood he could get an anaesthetic action from it, Paul Bert experimented by exposing the animal in a chamber having air so compressed that the pressure was at least that of two atmospheres, and found that under these circumstances he could obtain anaes- thesia with a mixture of eighty-five per cent, of nitrous oxide and fifteen per cent, of oxygen, but that when nitrogen was substituted for nitrous oxide no anaesthesia was produced. Bert's method was for a time employed for the purposes of sur- gical anaesthesia in Paris and in some other capitals of Europe, the clinical records showing that it is possible to produce anaesthesia with the gas in the pro- ANAESTHETICS. 85 portion named above. Practically, however, the necessary apparatus was found to be too cumbersome and expensive for use. In 1881 Klikovitch, of St. Peters- burg, used with alleged success in parturition Paul Bert's mixture of gases without pressure. In 1891 Van Arsdale 9 found that it was possible in rare cases to produce anes- thesia in the human being with mixtures of oxygen and nitrous oxide in the propor- tion of fifteen to eighty-five per cent. , and that in many cases a mixture in the pro~ portion of ten to ninety per cent, would produce a moderately complete anaesthesia without cyanosis. In a research extending over three years, F. W. Hewitt 10 corroborated the assertions of Van Arsdale, finding that it is possible, in some cases at least, to produce deep and satisfactory anaesthesia, without obvious asphyxial manifestations, by mixtures of nitrous oxide and oxygen containing even as much of the oxygen as is present in our atmosphere. George T. Kemp " made a series of experiments, some of which seem to be very decisive. Thus, an animal having been anaesthetized with nitrous oxide, a slit in the canula was adjusted so that it let in just sufficient air to keep the animal alive and anaesthetized. When nitrogen was substituted for nitrous oxide, the amount of air remaining the same, the dog gradually came out of his anaesthesia. Experiments with the blood showed that, though at times perfect anaesthesia existed with as high a percentage of oxygen in the blood as 16.8, it usually was 8.5, and sometimes not until the percentage was reduced to 7.9. For reasons given in his paper, which we cannot go over here, Kemp believes that with this amount of oxygen metabolism remains about normal, a conclusion, however, which the evidence he brings forward hardly proves. If nitrous oxide, as the evidence at present indicates, is capable of producing unconsciousness by virtue of its inherent properties, it must act upon the cerebrum, but it is remarkably inert in regard to other por- tions of the organism. The chief evidence as to its influence upon the spinal cord is that of Goldstein, that it diminishes the reflexes in frogs. That its action on the spinal cord is very feeble seems to be shown by the fact, which has been repeatedly asserted, that in human beings the con- junctival reflexes often persist after deep anaesthesia has been produced. The experiments of Waller and of Amory show that nitrous oxide does not affect the motor nerve trunks. Ulbrich believes that it produces alterations in the blood, but Hermann, Jolyet and Blanche, Goldstein, MacMunn, 12 Buxton, 13 and Halliburton are in accord with Kemp in assert- ing that it does not make any compound with haemoglobin. Further, Kemp is in accord with H. C. Wood's experiments in showing that it has no definite influence upon the heart or the arteries. THERAPEUTICS. Of all the anaesthetics, nitrous oxide is the safest. It is probably administered to more than seven hundred and fifty thousand persons yearly, and yet only four recorded deaths are certainly attributable to it. * The opinion of Cartwright u and of W. Ottley , 15 that in cases of heart disease permanent increase of the cardiac weakness is caused by nitrous gas inhalation, is not established. The final fall of blood-pressure produced by * Not including the case reported in the Dental Cosmos, June, 1872. (See Brit. Journ. Dent. Sci., Feb. 1873 ; Brit. Med. Journ., 1877, i. 460; Ibid., 1883, ii. 729; Dent, and Surg. Microcosm, Oct. 1895.) In one of these cases the result is said to have been due to syncope. 86 GENERAL REMEDIES. the gas was found in the experiments of H. C. Wood to be due to paral- ysis of the vaso-motor apparatus, probably of asphyxial origin, and death always occurred from respiratory paralysis, the heart continuing to beat powerfully after respiration had ceased and the arterial pressure had fallen very low. Even when alarming symptoms occur during nitrous oxide anaesthesia, the results are very rarely disastrous, because the loss of func- tion has been due, not to the presence of a poison, but to the absence of oxygen, and although the paralysis may be complete, the life-power sleeps before it dies, and is ready to react to oxygen. Immediate artificial res- piration is the one remedy for the treatment of alarming symptoms during nitrous oxide asphyxia. In diseases of the kidney nitrous oxide is probably far safer than any of the liquid anaesthetics, since in the experiments of Thomson and Kemp 18 it was found to have no other effect upon the kidneys than that which it exerted upon the general circulation. Experience has not confirmed the assertion of Lafont, that nitrous oxide anaesthesia is prone to be fol- lowed by miscarriage, chlorosis, and epilepsy. His especial warning against the production of diabetes mellitus, and his statement that glyco- suria may be produced by the drug in the dog, remain unconfirmed by clinical or experimental evidence, although a well-known Philadelphia surgeon persistently attributed his own fatal diabetes to the use of nitrous oxide. In experiments made by George S. Woodward and Alfred Hand in the laboratory of the University of Pennsylvania it was found impos- sible to produce glycosuria in the dog. On account of the high blood- pressure with venous stasis which occurs during nitrous oxide anaesthesia, atheroma or other diseases of the arterial walls should be considered a centra-indication to the use of the gas, and fatal apoplexy * has occurred during or immediately after its administration. ADMINISTRATION. The difficulty with the practical use of nitrous oxide for other than the brief anaesthesia required in teeth extraction and other forms of minor surgery has been the extreme fugaciousness of the anaesthesia, as well as the asphyxial symptoms always present. It is affirmed that these difficulties are overcome by the consentaneous use of oxygen with the gas. Undoubtedly the asphyxial symptoms are greatly lessened, but the allegation that the period of recovery after the with- drawal of the gas is distinctly prolonged has not, in our experience, been sustained. In various cases we have noticed the return to conscious- ness as complete in from twenty-eight to forty seconds. With great care in the administration of the mixed gases, the anaesthesia can be, it is true, almost indefinitely prolonged, but the danger of recovery at any moment is great. It is common for operators to vary the percentage of oxygen according to the appearance of the patient, often giving first pure nitrous oxide and adding oxygen without any definite measure- ment when the asphyxial symptoms set in ; watching the effect of the * See Dental Cosmos, 1890 ; also Therap. Gaz., 1896, xii. ANAESTHETICS. 87 oxygen and increasing or lessening it according to the facial expression of the patient. Matthew H. Cryer, of the University Dental Faculty, states that the apparatus prepared in London according to Hewitt's plan is impracticable owing to the fact that an easy reflux is afforded for the two gases into each other, and has worked out an apparatus which seems to be satisfactory and is not over-cumbersome. The method is certainly a distinct advance, in that it enables the operator at any mo- ment to have the subject breathe pure oxygen if disagreeable symptoms occur. Nitrous oxide is sometimes used in conjunction with ether, the primary anaesthesia of nitrous oxide allowing the patient to pass under the ether without the unpleasant excitement. Le Breton 18 is probably correct in his belief that this method is safer than ether alone, because of the smaller amount of ether required. ETHER. U. S. Ethyl oxide is a colorless, very volatile liquid, obtained by the dehy- dration of alcohol by sulphuric acid. It is very inflammable, as is also its vapor, which is two and a half times heavier than air. It is freely soluble in alcohol, and is itself a powerful solvent. Its odor is strong and peculiar ; its taste is hot. Its specific gravity, when pure, is 0.713, and its boiling point 95 F. Ether of the U. S. Pharmacopoeia contains ninety-six per cent, of ethyl oxide, and should boil "when a test-tube, containing some broken glass and half filled with it, is held for some time in the hand. ' ' Locally, ether is a violent irritant ; it is absorbed with rapidity through the mucous membranes both of the lungs and of the gastro- intestinal tract. When taken freely it is eliminated largely unchanged by the lungs. PHYSIOLOGICAL ACTION. The first effects of ether when inhaled are burning in the fauces and a feeling of strangulation, each due to the local impression of the irritant vapor. The primary indications of its systemic action are a sense of exhilaration and a lightness in the head, associated with a roaring or buzzing in the ears. These are soon succeeded by a feeling of the immediate surroundings being afar off, which soon fades into semi-unconsciousness, with visions and illusions. These are of vari- ous characters, and are often accompanied by a species of delirium. Some patients weep, others laugh ; some shout, some pray, some rave, and some become exceedingly pugnacious. In rare instances the dreams are erotic ; and cases are on record in which there were distinct evi- dences of the occurrence of a complete venereal orgasm. In this stage the patient in most cases may be more or less perfectly aroused. There is rarely sufficient anaesthesia for practical purposes before the period of complete unconsciousness. The second stage of ether-narcosis may be considered to begin with the complete loss of consciousness. Muscular rigidity may persist for a length of time, but usually it soon passes off, and the patient lies relaxed 88 GENERAL REMEDIES. and quiet, with slow, regular, automatic respiration. * The occurrence of stertorous respiration, due to a paresis of the muscles of the palate, shows that the stage of muscular paralysis is being reached. It should, except in rare cases, be the signal for the immediate withdrawal of the anaesthetic. The face during etherization is reddish ; marked pallor and lividity are respectively important indications of failure of the heart's action and failure of respiration. The stage of excitement generally lasts only a few minutes, but in some cases is prolonged, and in nervous women may pass into a violent fit of hysterics, which soon yields, however, to a persistent use of the anaesthetic. The pulse is quickened and increased in force by ether, and it will often maintain itself during a prolonged narcosis. If the vapor of ether be taken in a concentrated form, there is often in the beginning a momentary arrest of respiration, accompanied by a decided sense of suffocation, evidently the result of the irritant action of the vapor upon the upper air-passages. So soon as this has passed off, the respira- tions are usually accelerated as well as deepened ; but as the stage of anaesthesia is reached they become slower, and, if the inhalation of the ether be persisted in, they grow not only more and more distant, but also more and more shallow, until they are gradually extinguished. The respiratory phenomena seem to be the same in the lower mammalia as in man. The primary arrest of respiration during the first stages of etherization is undoubtedly due to a local irritation of the mucous membranes of the air-passages. According to Kratschmer, 1 in the rabbit it is prevented by previous section of the trigeminal nerves, but not by division of the vagi ; nor does it occur when the ether is administered through a tracheal fistula. This would indicate that the respiratory disturbance is due to irritation of the peripheral trigeminal nerves, but H. A. Hare * has found that in the dog tracheal irritation with ether produces respiratory arrest, which is, however, prevented by previous section of the vagus. As stated by P. Knoll, 3 the arrest of respiration is sometimes replaced by very irregular breath- ing. The importance of the matter is increased by the fact that Kratschmer has noticed that the disturbances of respiration are accompanied by spasm of the glottis. It is evident that these disturbances are reflexes due to irritation of the trigeminal nerves in the upper, and of the pneumogastric filaments in the lower respiratory tract. They are especially interesting in connection with the asserted direct or indirect effect of ether upon the recurrent laryngeal nerve, f It is possible, but not probable, that some of the accidents which have happened early in human anaesthesia have been due to these respiratory reflexes ; the important practical fact is that aberrations of respiration occur- * For a full discussion of motor phenomena during profound anaesthesia, see Rudolf Jaksch ( Wien. Med. Wochensch., 1889, xxxix. 359). t F. H. Hooper was, we believe, the first to note that stimulation of the recurrent laryngeal nerve causes a dilatation of the glottis in the thoroughly etherized dog, although in the normal animal it always produces a constriction. This remarkable observation has given rise to several investigations, the most extended of which is that of H. P. Bow- ditch (Amer.Journ. Med. Set., 1887, xciii.), to which the reader is referred fora full sum- mary and discussion of the matter. Dr. Bowditch corroborates the observation of Hooper, and also finds that during partial etherization weak irritation of the recurrent nerves causes dilatation and strong irritation constriction of the glottis. As yet no satisfactory explanation of these curious phenomena has been offered. ANESTHETICS. 89 ring in the beginning of an etherization are to be overcome by persistence in the inhalation, after which the respirations will become slower, deeper, and more regular ; indeed, as pointed out by Kronecker, 4 the late and dan- gerous arrest of respiration during anaesthesia occurs only after the reflex function has been abolished. When the administration is continued to the end, the respirations become very slow and more and more shallow until extinguished. Irregularities of respiration occurring in the later stages of an etherization are of the most serious import, and demand immediate withdrawal of the drug. Clinical experience confirms the experimental proof obtained by Knoll, that these late disturbances of respiration are the result of the direct influence of the drug upon the respiratory centres. According to Eulenberg, 5 in the beginning of anaesthesia produced either by ether or by chloroform, the knee-jerk in man is increased ; when chloroform is employed, this increase soon disappears, but with ether it endures even into the narcosis. Upon the lower animals ether acts as upon man, and it has been shown by Claude Bernard 6 that the most primitive infusoria are suscepti- ble to its influence. Both in man and the lower animals the cerebral functions are the first to be affected by ether. According to the experiments of H. C. Wood, Jr., 7 when the ether is given in such a manner to the dog as to avoid all violence of administration, and in minute dose, the first positive indication of the loss of intellection is failure of the perception and interpretation of sound, the sense of sight lasting somewhat longer. Loss of coordination and loss of motor power, though with a continuation of movement, are the next phenomena. It was further demonstrated in these experiments that there is a stage of ether narcosis in which the sensibility is distinctly lessened, although no motor changes are demonstrable. This affords confirmation of the early experiments of Flourens, 8 who found that the order in which during etherization the power of responding to pricking is lost was, first, in the posterior or sensory portion of the spinal centres ; second, in the anterior or motor portions of the spinal cord ; and, third, in the medulla oblongata. Longet 9 has confirmed this order, except that by using powerful galvanic currents he was able, even in the deepest narcosis, to get a response from the anterior portion of the cord. The order of the involvement of the nerve-centres in man and animals is first the cerebrum, next the sensory centres of the cord, next the motor centres of the cord, next the sensory centres of the medulla ob- longata, and finally the motor centres of the medulla oblongata. Waller 10 found that if he brought dilute ether or chloroform vapor in direct contact with a motor nerve, that nerve lost its power of transmit- ting electrical impulses. If the vapor had not been too concentrated, the nerve recovered its function after removal of the anaesthetic. The recovery after chloroform was less rapid than after ether. If the observations of Longet (loc. cit., 382) and Serres 17 be correct, the sensory nerve-fibres 90 GENERAL REMEDIES. are more susceptible to the influence of ether than are the motor. They found it possible, however, by the direct application of ether to a nerve, to produce a condition in which pinching the nerve below the point of application caused no pain, although voluntary movement was preserved, and galvanization of the nerve-trunk above the point of application in- duced spasms in the tributary muscles, i.e., the power of conducting an impulse downward was preserved, that of conducting it upward was lost. By a longer application of the anaesthetic the function of the efferent as well as of the afferent fibres was abolished, temporarily at first, but, if the application were persisted in, permanently. Owing to the great sensitiveness of the nerve-centres in man, most if not all of the phenomena of etherization are of centric origin. Indeed, Conly " found that in animals killed by ether, chloroform, or chloral, the motor nerves and muscles preserve their function longer than in animals killed by sudden violence. Nevertheless, F. S. Locke 12 found that in the frog, at least, the muscles are directly affected by etherization ; there being not only a lessening of the height of the contraction under stimula- tion, but also an alteration in its form. Upon the motor system of organic life ether certainly acts, but much less energetically than upon the voluntary system. Thus, after death from ether the vermicular movements of the intestine, although less active than normal, are very rarely, if ever, entirely absent. Wright 18 has demonstrated histological changes in the pyramidal cells of the nervous centres due to the administration of ether or chloroform. The more prolonged the exposure to the anaesthetic, the slower is the return to the normal. Circulation. The first effect of ether is usually to cause a pronounced rise in the arterial pressure, which is commonly maintained even through a prolonged ether narcosis, and may continue until manifest failure of res- piration ; usually, however, it is after a time succeeded by a fall of pressure. Blauel found, in tonometrical studies upon man, that during ether anaes- thesia the pressure is raised in seventy-nine per cent, of the cases, not affected in nine per cent. , lowered in twelve per cent. What evidence we have upon the subject indicates that the primary action of ether upon the heart is that of a stimulant, though later if in sufficient amount it un- doubtedly acts as a cardiac depressant ; that this depressing action is feeble, is shown by the experiments of Tunnicliffe and Rosenheim, who found that in the excised mammalian heart two per cent, of ether in the blood did not stop the heart. The rise of blood-pressure appears, however, not to be entirely cardiac, since Sansom 13 found that the vessels of the frog's web are thrown into a persistent spasm by the inhalation of ether ; and Bowditch and Minot M conclude as the result of their experiments that in the mammal the drug first stimulates, afterwards depresses, the vaso-motor centres. Blood. It is frequently asserted that ether when added to blood coagulates it. A. Schmidt, however, states that the coagulation is due ANAESTHETICS. 9I to ozone which has been generated in the ether, since freshly distilled ether does not coagulate albuminous substances. The researches of Wittich 15 and of A. Schmidt 16 have shown that when ether is added to the blood of horses,* cats, or rats, the red corpuscles disappear in a very short time, and, as their stroma cannot be demon- strated by the aid of reagents, this disappearance is due to its solution. The oxyhaemoglobin thus set free is dissolved in the serum, but the pres- ence of the ether soon causes it to crystallize. There is no proof that these changes occur to any extent when ether is inhaled ; and the usual rapid recovery from the effects of the anaesthetic indicates that there is no profound alteration of the blood, f An imperfect study by Harley of the effect of ether on the gases contained in drawn blood indicates that ether does not exert much in- fluence upon their proportional amounts. It is, however, quite possible that a more thorough investigation would give a different result. J SUMMARY. Locally ether is a violent irritant. In excess it prob- ably depresses all higher tissues, but it especially acts upon, first, the cerebrum, next upon the sensory, and then upon the motor side of the spinal cord. It usually produces death by asphyxia, due to depression of the respiratory centres. Its first action upon the circulation is that of a stimulant to the heart, and perhaps also to the vaso-motor cen- tres. The large dose finally depresses both heart and blood-vessels. THERAPEUTICS. For a discussion of the use of ether as an anaesthetic, see page 104. Administered by the mouth, ether has been used with advantage in various forms of colic, but is generally inferior to chloroform. When, however, as in cases of retrocedent or internal gout, there is with the painful gastric and intestinal spasm a condition bordering on collapse, the stimulant properties of ether make it very valuable. In sudden sinking -spells, either from poison or from natural causes, ether, as a powerful and very quickly acting stimulant, is often indicated. In some cases of this description it may even be administered by inhala- tion. Of course, under these circumstances, its influence should not be carried nearly to the point of producing anaesthesia. As an anthelmintic, ether has been used with asserted success against the tape-worm. For this purpose, an ounce and a half have been ad- ministered at once, followed in two hours by a full dose of castor oil. In hysteria, neuralgia, nervous headache, and spasmodic neuroses, such as hiccough and asthma, ether is occasionally employed with benefit. * Schmidt (loc. cil., 23) says that sometimes crystallization fails in the blood of the horse. t On the continent of Europe, ether is used hypodermically as a cardiac stimulant. In a number of cases, however, it has produced local paralysis of neuritic origin. J For literature, cases, and discussion, see Schulz, Deutsch. Militar. Zeitsch., 1903, 92 GENERAL REMEDIES. When ether is swallowed, it produces a sense of strangulation and choking which seriously interferes with its use. For this reason, it i= often given in capsules, or in ice-cold water. Probably large doses are best administered by putting them, mixed with an equal amount of brandy, on finely cracked ice before drinking. The dose is from one fluidrachm to half a fluidounce (4-15 C.c. ). Etherization by the rectum has been tried, but has been discarded on account of the severe irritation of the rectum and lower bowel which it causes, as well as because of the slowness of the production of insensi- bility. CHLOROFORMUM CHLOROFORM. METHENYL CHLORIDE. This substance, which was discovered in 1831 by Samuel Guthrie, of Sackett's Harbor, New York, is produced by the action of chlorine upon alcohol. It is a colorless, limpid, and neutral fluid, which is for practical purposes non-inflammable, although it can be made to burn with a greenish flame. Its taste is hot and sweetish, its odor fragrant and peculiar. It is soluble in alcohol and in ether, but when dropped into water it sinks, if pure, as transparent globules without milkiness. The alcoholic solution, when moderately diluted with water, forms an aromatic, sweetish liquid. It is antiseptic, and does not coagulate albumin. The U. S. Pharmacopoeia recognizes Chloroform, and requires that it should contain by weight 99 to 99.4 per cent, of absolute chloroform and o. 6 to i per cent, of alcohol. PHYSIOLOGICAL ACTION. Local Effects. Although somewhat of an anaesthetic, chloroform applied locally is a powerful irritant. On the skin it produces redness and burning ; if the evaporation be restrained, vesication will be induced by it. Taken into the mouth, it causes a burning sensation, and, when swallowed, a sense of warmth in the stomach. Absorption and Elimination. Chloroform is rapidly absorbed through the mucous membrane of the respiratory and digestive apparatus. Its exact fate in the body is at present unknown. It is certainly eliminated, at least in part, unchanged in the expired air after administration by the mouth (Benedicenti 1 ); and after its inhalation has been detected by Fubini and by Siolfatti * in the urine. It is probably, however, in part decomposed in the system, since A. Zeller s has found that the chlorides of the urine are nearly doubled by its inhalation. The vapor of chloroform, when inhaled, produces symptoms seemingly similar to those induced by ether, except that the choking sensations are absent, and that the stage of excitement is generally, but not always, shorter and less violent than is that of etherization. General Action. The division of chloroform-narcosis into three stages was first proposed by Sabarth, 4 and, though somewhat arbitrary, is prac- tically useful. In the first of these the symptoms are similar to those of ANAESTHETICS. 93 alcoholic intoxication. This stage is generally very short, but in athletic persons, and especially in those who have been intemperate, it may be very long and very violent, and may persist after loss of consciousness. In drunkards, this excitement at times cannot be overcome without grave danger to life. During this first stage, although consciousness is not lost, the sensibility is generally blunted, but very rarely is it altogether annulled. Coleman (Sansom, Chloroform, 55, Philadelphia, 1866) states, however, that he has extracted his own teeth without pain ; and Snow re- lates the anecdote of a child who played with his toys during the operation of lithotomy. During the second stage, which is that of anaesthesia, the conscious- ness and sensibility are abolished, the muscles are relaxed, and the patient lies perfectly quiet. This is the surgical stage, during which ordinary operations are performed. As already intimated, in some cases the first and second stages are united, so that violent excitement, muscular spasm, and rigidity may coexist with loss of consciousness and of sensibility. The third stage is one of profound narcosis, with stertorous breathing, intense muscular relaxation, abolition of the ordinary reflexes, and fall of bodily temperature.* This is always a condition of danger, and its in- duction by chloroform, except under very peculiar circumstances, is un- justifiable. The pulse in the first stage of chloroform -narcosis may be quickened, even apparently strengthened ; in the second stage it is generally about normal in frequency, but is more or less weakened ; in the third stage it is rapid and weak. Noel 5 calls attention to a cervical venous pulse, most marked in the external jugulars, which he asserts frequently occurs during the waking up from chloroformization. He believes it to be a symptom of serious cardiac embarrassment. E. Simonin 6 found that the temperature usually rises during the first stage (o. i-o.9 C. ), falls slightly during the second or remains above normal, and falls decidedly during the third stage, f * Baudin (Le Progres Med., Sept. 1874) called attention to the pupil as a guide in chloroformization, stating that, although at first it is uniformly dilated, afterwards it is uniformly immovably contracted, and that this is the period for operating. Schlager is in accord with Baudin ; in one hundred and twenty out of one hundred and twenty-two cases observed, the pupil was dilated during the stage of excitement, and during com- plete anaesthesia narrowly contracted. He also states that if during anaesthesia the pupil return to normal, more chloroform is required, but if it suddenly dilate, danger is immi- nent. At present, however, the condition of the pupil cannot be considered a safe guide in anaesthetization. Dogiel (Reicherfs Archiv fur Anal., 1866) affirms that in rabbits, during the stage of excitement, the pupil is contracted, during anaesthesia dilated. Schiff has strenuously combated the conclusions of Baudin ; and in a very careful series of ex- periments on animals W. H. Winslow found that the state of the pupil varies greatly in the same stage of anaesthesia. Thus, in complete anaesthesia, sometimes the pupil was widely dilated, sometimes contracted ; and death sometimes occurred with a dilated, sometimes with a contracted pupil, in the former case probably being syncopal, in the latter asphyxial (Phila Med. Times, vi. 275). fAs the result of chemical studies, Julius Pohl (Arch. f. E.rfi. Pathol. n. Pharm., 1891, xxviii.) believes that more chloroform exists during the narcotic period in the brain- tissue than in the blood coming to it. 94 GENERAL REMEDIES. The experiments of Holmgren, Kratschmer, H. C. Wood; Jr., 7 and others have demonstrated that the action of chloroform upon the nervous system is entirely parallel to that of ether (see page 88), the difference being simply one of intensity of power. In practical anaesthesia the stage of excitement is usually much less severe with chloroform than with ether, but, according to H. C. Wood, Jr., this hyperexcitation depends largely upon the ether vapor being too concentrated ; when the anaesthesia was induced in animals slowly with a very small percentage of ether in the air, the stage of excitement was greater with chloroform than with ether. The motor disturbances seen early in chloroformization, as in etherization, have been supposed to indicate a condition of spinal stimulation, but have been shown by Bert 8 to be of purely psychical origin. Bernstein 9 found that there was no perceptible difference in the con- ducting power of the two ischiatic nerves of a frog chloroformed after one of its iliac arteries had been tied. Circulation. In some animals the first effect of the inhalation of chlo- roform upon the circulation is a decrease in the frequency, of the heart's action. Dogiel believes that this is due to a stimulation of the inhibitory centres, because he has found that it does not occur after section of the vagi. The after-increase in the rapidity of the pulse appears to be due, at least in part, to paralysis of the inhibitory centres, upon which chloroform seems to act as upon the oculo-motor centres, producing in them at first excessive functional activity, but afterwards functional paralysis. Both Kratschmer and Knoll (see page 88) have noticed in rabbits, when either ether or chloroform is inhaled through the nose, a momentary rise of arterial pressure corresponding to an arrest of respiration, and, like it, evidently produced by irritation of the peripheral trigeminal branches. As was first proved by the English Chloroform Committee, 10 after the first half-minute of the inhalation of chloroform there is a progressive lowering of the arterial pressure. This has been confirmed by all ob- servers on the lower animals, and Blauel 88 has shown by tonometrical experiments that the same phenomenon occurs in man. The matter of dispute has been as to the cause of this fall, whether it is of cardiac or vascular origin. Injected into the jugular vein,* chloroform instantly arrests the heart's action and destroys its muscular irri lability. f Even the vapor of chloroform, when locally applied to the exposed heart, paralyzes it." When artificial respiration is main- tained, the effect of chloroform is very apparent." By a very ingenious series of experiments, MacWilliam 1& has proved that very early in chloroform anaesthesia there is a marked diminution of the force of the auricular and the ventricular beats, accompanied by dilatation of the cardiac chambers, due to the direct influence of the chloroform. Again, as stated by Gaskell and Shore, even the tracings of the Hyderabad Commission demonstrate that from the very beginning of chloroformi- * See also MacWilliam's experiments. t Glover (Edinb. Med. Journ., 1842), Gosselin (Arch. Gen., 1848), Anstie, and H. C. Wood. ANAESTHETICS. 95 zation the excursions of the heart-beat, as shown on the Pick manometer in the most typical manner, get smaller and smaller as the pressure falls. Indeed, as Gaskell and Shore say, " every one would agree with the Commission that they [the pulse-waves] are of the typical kind which would be produced if direct weaken- ing of the heart were the cause of the fall of blood-pressure in chloroform adminis- tration." Tunnicliffe and Rosenheim, 39 using the method of Locke, found that i to 25,000 in the blood of chloroform notably affected the heart, and Schafer and Schar- lieb, ibid., have reached similar results. In the experiments of E. H. Embley, 40 made in the method of Hering upon the mammalian heart isolated from nervous and respiratory influences, it was determined that the heart is so sensitive to the vapor of chloroform that 0.8 per cent, in the blood will produce paralysis in sixteen minutes, and with two per cent., arrest occurs in one minute twenty-five seconds. In an elaborate series of experiments, Sherrington and Sowton (B. M. J. Supp., 1903, ii.) found that the heart muscle rapidly takes up chloroform from the blood- vessel, the tension or amount of the chloroform in the muscle depending not upon the length of time of exposure but upon the percentage of chloroform in the fluid circulating in the coronary arteries ; it was further determined that the presence of the chloroform in the muscle is accompanied by depression of function, and that when the percentage is great muscular paralysis occurs. The important obser- vation was also made that the susceptibility of the hearts of different cats to chloro- form varies. The thought naturally arises from this research that sudden death may occur during chloroform anaesthesia from the momentary sudden increase of the percentage of chloroform in the blood. The concurrent testimony of numerous investigators is so strong that the conclusion cannot be escaped from that chloroform is a direct cardiac de- pressant. This, however, does not disprove the theory of vaso-motor dila- tation as one of the sources of arterial depression in chloroform anaesthesia. The only experiments with which we are acquainted, to which any weight should be attached, as indicating that chloroform primarily paralyzes the vaso- motor centres, are those published as long ago as 1874 by H. P. Bowditch and C. S. Minot. 12 In these experiments, which were made upon curarized animals, "irritation of the saphena nerve caused a much less marked rise of blood-tension than when the anaesthetic was not used. Sometimes there was absolutely no rise of tension to be observed, while at other times the rise was from one-third to one- half that produced by the same irritation on an animal not subjected to the action of chloroform." Further compression of the carotid in the chloroformed animal did'not cause the customary spasm and rise of arterial pressure. It must be remembered that these experiments of Bowditch and Minot were made at a time when the importance of the subject had not been fully realized ; that on the carotid but a single experiment was made ; and that there was fre- quently in the experiments of Bowditch and Minot a great rise of pressure follow- ing irritation of the sensitive nerve, though the rise was not as great as in the normal dog. It must also be remembered that chloroformization interferes with the functional activity of the sensory side of the nervous system, so that an impulse produced by irritation of the sensitive nerve fails to reach the vaso-motor centres in full force. In many of the experiments of Bowditch and Minot, irritation of the saphenous nerve produced distinct rise of pressure, showing that the vaso-motor centre was not paralyzed, though the arterial pressure had fallen very distinctly : moreover, late in chloroform-poisoning there is a vaso-motor paralysis, and it may very well be that in the single carotid experiment of Bowditch and Minot the chloroformiza- tion had been carried on to the fullest extent. 96 GENERAL REMEDIES. Whilst undoubtedly in advanced chloroformization there is vascular paralysis, there seems to be at present no proof that this vascular paraly- sis occurs as one of the primary or early symptoms produced by the drug. On the other hand, there is much evidence to show that the first action of chloroform is to produce vascular contraction. Sansom and Harley state that there is a spasm of the small vessels, which can be readily seen to occur in the web of the frog during chloroformization. Not until the third stage is reached, according to these authors, do the vessels relax into dilatation. If these observations be correct, chloroform first stimulates and afterwards depresses the vaso-motor centres. In accordance with this are the im- portant experiments of Gaskell and Shore, 11 who find that the local application of chloroform to the medulla or its injection into the cerebral artery produces an im- mediate rise of blood-pressure, usually accompanied by a slowing of the heart, which is followed by a fall of pressure so soon as the chloroform is able to diffuse itself throughout the circulation. Gaskell and Shore further so connected the carotid arteries and jugular vein of an animal (A) with the similar vessels of a second animal (B) that the brain of A was fed exclusively with blood from B. It is plain that chloroform given to B would reach the brain of A but would not reach the heart of A. Under these circumstances it was found that chloroform adminis- tered to B produces rise of blood-pressure in A. In a second series of experiments the blood-vessels of A were so connected with those of B that when chloroform was administered to B it reached the heart of A and all other portions of the body except the brain. When this was the case, chloroform given to B produced an immediate fall of pressure in A without there having been any rise. In other words, when chloroform reached the vaso-motor centres and not the heart, it caused rise of arterial pressure ; when it reached the heart and not the vaso-motor centres, it caused fall of pressure. In accord with the results of Gaskell and Shore, it has been found by Embley that the local application of chloroform to the vaso-motor centres produces rise of the arterial pressure, which is presumably due to stimu- lation of the vaso-motor centres. In common with other observers, Embley found that later in the chloroformization there is a vascular paralysis which he believes to be due to a direct action of the chloroform on the muscles of the heart vessels. Putting all the evidence together, it seems to us to have been demon- strated by physiologists, first, that chloroform is a direct depressant and paralyzant to the heart-muscle or its contained ganglia /* second, that the fall of blood-pressure which occurs in chloroformization is at first due to this direct depression of the heart, but subsequently to coincident vascular and cardiac faihire. Respiration. So soon as psychical excitement has passed off, or, at first, if there be no such excitement, the respirations may be rendered slower by chloroform, but after a time they are generally quickened, and as the inhalation is persisted in they become more and more shallow, * The work of the Hyderabad Commission has become so celebrated that it hardly seems necessary to explain that they reached with extreme positiveness the conclusion that chloroform kills purely through the respiration, and that it is a perfectly safe anaes- thetic. Rather strangely, they based their belief that the fall of Wood-pressure under chloroform is not due to weakening of the heart chiefly upon certain atypical tracings which they obtained. The publication of these tracings shows, in the language of Gas- kell and Shore, " that these cases afford no proof whatever that the heart's action is not impaired by the action of chloroform." ANAESTHETICS. 97 irregular, and distant, and finally cease. In 1870 Paul Bert 16 asserted that during chloroformization there is more than the normal percentage of oxygen in the blood, but in 1885 he affirmed that there was less than the normal percentage. " There does not seem to be much doubt that the results of L. G. de Saint-Martin 18 are correct, namely, that whilst (probably on account of excessive respiration from excitement) in the beginning of chloroformization there is sometimes hyperoxygenation of the blood, the rule during full anaesthesia is decrease of the oxygen of the blood with increase of the carbonic acid. According to the work of E. H. Embley, chloroform is a very active vagus stimulant, raising the excitability of the vagus centrically, and it has been urged that sudden death occurs during chloroformization from inhibitory cardiac arrest. Before, however, this conclusion can be con- sidered established further experiments seem necessary. Death has frequently occurred from chloroform after the inhalation of a few whiffs of vapor. The theory was suggested many years ago that the cause of car- diac arrest is irritation of the respiratory mucous membranes, producing a fatal cardiac inhibition ; a conclusion which reached confirmation in the observations of Vulpian, that the heart under the influence of chloral, a substance closely allied to chloroform, is equally sensitive to slight inhibitory impulses. Out of this has grown the practical suggestion that the surgeon should wait until complete chloroform- ization, lest the irritation produced by the first cut should produce a momentary excessive inhibition. In a number of experiments, however, made by H. C. Wood, it was found that the application of chloroform to the upper respiratory passages of the dog would distinctly inhibit but never arrest cardiac movement. Embley believes that these chloroform deaths are due to an excessive excitation of the inhibitory centric apparatus, and are therefore the outcome of an intense inhibition exercised upon the heart, whose spontaneous excitability is diminished by the chloroform vapor. He bases this conclusion upon his experimental observations, that when inhalations of chloroform of the strength of two per cent, and upward have been given and the blood-pressure has fallen, stimulation of the vagi with the faradic current fatally inhibits the heart. It should be noted, however, that if this observation be correct it proves not centric but peripheral stimulation ; or what is equally probable, diminished power of the heart-muscle to resist inhibitory impulses. The curious observation was also made by Embley that when the breathed air contained not more than five per cent, of chloroform, the vagus excitability was slightly depressed. It seems to us evident that at present the question as to exactly what rdle inhibition plays in chloroform deaths has not been finally answered. Blood. As was first demonstrated by Harley, 19 five per cent, of chloro- form in the blood destroys the red corpuscle with a final deposition of crystals of oxyhaemoglobin. Boettcher 20 was, we believe, the first to study these changes closely. The first alteration noticeable in the red blood-disks is a diminution of their size, which A. Schmidt and F. Schweiger-Seidel 21 assert to be due to contraction, because when blood is treated with water until the red globules disappear, and carbonic acid gas is passed through the liquid until they reappear, on the addition of chloroform the sharply contoured bodies will be seen to undergo marked contraction. As was first shown by Boettcher and confirmed by Schmidt and Schweiger-Seidel, chloro- 7 98 GENERAL REMEDIES. form alone produces no other alteration than contraction in the red blood-disks. If, however, air be admitted to blood containing chloroform, the corpuscles rapidly disappear, dissolving the serum, out of which, after a time, oxyhaemoglobin crys- tallizes. Both of the authorities quoted believe that the latter changes are due to oxidation. Boettcher states that chloroform-vapor mixed with air converts enough of the oxygen of the latter into ozone to react with iodized starch-paper ; and Schmidt and Schweiger-Seidel have found that an excess of carbonic acid in the blood interferes with the changes caused by chloroform. The facts just noted indi- cate that the blood changes are the result of simple oxidation, but the studies of F. Kriiger 41 show that chloroform, at least outside of the body, produces a series of chemical changes in the haemoglobin. How far, during ordinary narcosis, chloroform causes changes in the blood is uncertain. A very sensitive test of the destruction of the red disks in the body is found in the production of icterus ; icterus following chloroformization is very rare, but the assertion of Frerichs that it does occur is correct. Bernstein 23 and Leyden 24 have found traces of bile- pigment in the human urine after chloroform-narcosis ; whilst Nothnagel 18 detected bile coloring-matter' in the urine of rabbits after subcutaneous injection of chloroform or ether. Husemann 26 intimates, on what author- ity we do not know, that after anaesthesia bile-acids (the precursors of icterus) appear in the urine ; but Kappeler," in twenty-five cases of chlo- roform-narcosis, was not able to obtain a trace of biliary coloring-matter. Sokolovski M asserts that the first few hours after chloroformization there is a decrease of the immature white blood-corpuscles, with an increase of the mature white blood-corpuscles, followed by gradual return to normal. After death during chloroform anaesthesia the presence of gas has been fre- quently noticed in the blood-vessels and in the heart. Contrary to the conclusions reached by various authors, Kappeler " has shown that usually, if not always, the gas has been liberated by putrefactive changes occurring after death. The state- ment of Pirogoff, that he has witnessed the throwing out of gas from the blood during life, has never been confirmed, but it is possible that the chloroform may have some influence upon the capacity of the blood for holding gases. General Nutrition. That chloroform affects the general nutrition of the body is demonstrated by the wide-spread fatty degeneration which sometimes follows long-continued narcosis produced by it (see page 116), as well as by the observations of Strassmann, 29 who found that a pronounced increase of the nitrogenous elimination follows chloroform- narcosis, an increase which would seem to be directly due to the anaes- thetic, since Salkowski demonstrated that chloroform-water given to dogs distinctly increases the destruction of nitrogenous substances in the body without producing narcosis.* According to the researches of Strassmann 80 and of Salkowski, 81 chloroform is an active antiseptic and germicide. Both Salkowski and * J. Petruechky (Deutsche Med. Wochensch., 1891, xvii.) has noticed that after death from chloroform the intercellular juices become rapidly acid, and he has found that this is not peculiar to chloroform, but takes place also after death from ether, arsenic, and other poisons. ANESTHETICS. 99 A. Bertels S2 find that the drug also checks the action of pepsin and other unformed ferments. THERAPEUTICS. For a discussion of the use of chloroform as an anaesthetic, see page 103. When administered by the mouth in sufficient quantity, chloroform produces symptoms similar to, but much more permanent than, those which it causes when inhaled. It is, however, very rarely, if ever, used in this way for its constitutional effect, but is sometimes of advantage in severe neuralgia. When for any reason quinine cannot be administered in an ague, a sufficient dose of chloroform (fgss to fgi) to produce a mild narcosis, just before the expected time for the recurrence of the chill, will often abort it. Chloroform by the mouth has been also highly recommended as a vermifuge in cases of tape-worm, but is of doubtful value. When chloroform is taken into the stomach, a considerable portion of it is, without doubt, evaporated, so that the intestinal canal becomes filled with the vapor. Chloroform, therefore, when so placed exerts both a local anodyne and a stimulant carminative action. For this reason it is valuable in ordinary colic and in colica pictonum. Externally, as a rubefacient and anodyne, chloroform is very largely combined with other substances into liniments, which are especially useful in cases of chronic neuralgic or rheumatic pains. Poisoning has been produced by the swallowing of chloroform. The symptoms induced have been stupor, with contracted, or, in later stages, dilated, pupils, and a stertorous respiration, which finally becomes very irregular, shallow, and often distant. The amount necessary to destroy life probably varies greatly, but, according to L. Lewin, a single drachm has produced death. In some cases M the fatal result has occurred from secondary gastritis many days after taking the medicine ; and not rarely violent gastritis with jaundice apparently from inflammation of the gall- ducts has been produced. Recovery has occurred after the ingestion of three ounces without vomiting ; M also five ounces. The treatment consists in the use of the stomach-pump and of the various ordinary methods of arousing a narcotized patient, especially the alternate cold and hot douche, artificial respiration, and the very cautious use of diffusible stimuli if re- quired. Death may occur during the narcosis, or the patient may sur- vive this and perish from inflammation of the trachea, oesophagus, and stomach, caused by the local action of the chloroform. The recognition of chloroform as the probable cause of any given death cannot be based upon the post-mortem appearances. Indeed, the latter are of no value in deciding such a question. The anaesthetic may, however, be recovered by distillation of the lungs and blood within a cer- tain period of time after death. As to the length of this time, so far as we are aware, no investigations have been made. Criminal Relations. Experiments made at the Philadelphia Hospital and confirmed by Dolbeau M and by Paugh " have proved that persons ioo GENERAL REMEDIES. sound asleep may be chloroformed without being awakened. Anaesthesia cannot, however, be produced in any one partially awake, or even sleeping lightly, without his or her knowledge. .Quite a number of professional men have been accused, and some convicted on the charge, of committing rape on females in whom they had induced anaesthesia. No doubt the women believed that they had been violated ; but it is certain that in many of the cases they mistook for the real act the subjective erotic sensations induced by the chloroform or ether. The valuelessness of the testimony of persons as to occurrences during the time of their intoxication with anaesthetics should be recognized in law as a governing principle of evidence. ADMINISTRATION. The internal dose of chloroform is from fifteen drops to a fluidrachm (0.9-3.7 C.c. ). The deep injection of half a drachm of chloroform has been recommended very strenuously by Bartholow in obstinate neuralgia, and has found some favor in France. ss In the only case in which we have tried it, one of trigeminal neuralgia, the local symptoms caused by it were so severe as to imperil the life of the patient. The U. S. Pharmacopoeia recognizes a spirit (SriRiTUS CHLO- ROFORMI six per cent., U. S. ), dose, one to two fluidrachms (3.7-7.5 C.c.) ; an emulsion (EMULSUM CHLOROFORMI four per cent., U. S. ) ; a liniment (LINIMENTUM CHLOROFORMI thirty per cent., U. S. ) ; and a water (AQUA CHLOROFORMI, U. S.), dose, four fluidrachms (16 C.c.). CHLORIDUM. U. S. Ethyl chloride is a colorless, ex- tremely volatile liquid of specific gravity (at o C. ) of 0.918, boiling at 12.5 C. On account of its volatility, it has been much used under various names to produce local anaesthesia by freezing. Recently ethyl chloride has been employed as a general anaesthetic. It acts very rapidly and recovery occurs abruptly on removal of the drug. Ware has col- lected 1 1 , 207 cases of its use, with one death. Other deaths have been reported by Hacker, by Allen 5 and by Gifford 6 . It was partially studied physiologically in 1892 by Wood and Cerna, 1 who found that it produced an amount of circulatory depression disproportionate to its anaesthetic properties, and was so fugacious in its action as to be scarcely fit for use as a general anaesthetic. In Lebet's 2 experiments upon rabbits, the intra- venous injection was found to produce great circulatory depression ; on the isolated frog's heart the twenty-five per cent, solution of ethyl chloride appeared to act as an irritant rather than a depressant. Moreover, Malherbe and Roubinovitch 3 have proven with Retain' s sphygmomano- meter that in man the arterial tension is almost always clearly lessened. Ware 4 found the drug best administered by means of modified nitrous oxide inhaler. ETHYL BROMIDE is a colorless, very volatile, very fluid liquid, having the specific gravity 1.49, of a sweet, chloroform-like smell ; not readily inflammable ; insoluble in water, but mixing with ether, chloroform, fat, ANAESTHETICS. 101 and ethereal oils in all proportions. It does not solidify at 32 F. Any preparation of it which has color, or seems irritating, or has a disagreeable smell, is unfit for medicinal use. It must clearly be separated by the practitioner from ethylene bromide, which has a specific gravity 2.16, and solidifies at 32 F. into a crystalline mass. Scherbatscheff has collected four deaths produced by the substitution of ethylene bromide for ethyl bromide. 1 Ethyl bromide degenerates under the influence of light and air, and should, therefore, always be kept in small bottles of dark glass, closely corked. Proposed as an anaesthetic in 1849, exploited by Rabuteau in France and by L. Turnbull in the United States in 1876-77, ethyl bromide has been used to a considerable extent as an anaesthetic. Its influence usually manifests itself in a few seconds and lasts not longer than three minutes after the removal of the inhaler. Various observers state that sensibility is not rarely lost before consciousness, and Montgomery has especially noted that during parturition ethyl bromide will do away with most of the suffering without arresting the pains or producing complete relaxation of the muscles ; indeed, it appears to be common for the general muscular tonus to be greatly increased by it. According to John H. Brinton, muscular excitement, as shown by rigidity, local spasms, and even general tetanus with opisthotonos, occurs so frequently as seriously to interfere with the anaesthetic use of the drug, especially as this condition during a surgical operation is attended by great increase of hemorrhage. 2 During narcosis the corneal and pupillary reflexes are usually preserved, and the eyes are sometimes wide open and crossed from contractions of their muscles (Gilles 8 ). The physiological action of ethyl bromide has been partially studied by Schneider, Thornton and Maxwell, 4 Abonyi, 5 H. C. Wood, 14 Ginsburg," and S. W. Cole 16 with results apparently not altogether concordant. * All observers agree that in the narcosis the arterial pressure finally falls, but Ginsburg and Schneider note that this fall is preceded by a rise in the arterial pressure, which appears not to have been present in the experiments of Thornton and Maxwell or of H. C. Wood. Ginsburg believes that the fall of arterial pressure is due to a paralysis of the vaso- motor centres, and Abonyi was not able to detect any alterations in the beat of the excised heart of the frog when narcosis was produced. The recent work of Tcherbacheff, who found that ethyl bromide causes death from cardiac paralysis with or without pulmonary oedema, accords, how- ever, with the early conclusions of H. C. Wood that ethyl bromide acts upon the heart in a manner similar to chloroform. The respiratory action of ethyl bromide has not been carefully studied. It probably is a centric depressant. Ch. Livon finds, from analysis of the gases of the blood, that during the anaesthesia produced by the ethyl * We are not aware that the purity of the ethyl bromide used has been proved by any of the experimenters. Linguistic difficulties in regard to the Slavonic papers have com. pelled us to rely upon abstracts. 102 GENERAL REMEDIES. bromide there is lessening of the carbonic acid with augmentation of the oxygen. In the absence of conclusive statistics, ethyl bromide appears to be at least as immediately dangerous as chloroform, and distinctly more so in its secondary results. It is true that Gilles claims that with a commer- cially pure bromide twenty thousand successive administrations of ethyl bromide in Germany had been without death, and that the fatal results have been due to impurity in the drug. This certainly does not apply to the deaths recorded by A. Gleich 7 and Suarez de Mendoza. 8 When a very brief anaesthetic effect is desired, ethyl bromide may be used as probably no more dangerous than chloroform ; but the fugacious- ness of its action and the muscular excitement which it causes forbid its general employment in major surgery, whilst the recent developments of local anaesthesia greatly lessen the field of its utility in minor operations. The ease with which ethyl bromide undergoes change offers a serious dif- ficulty to its use. Certainly the surgeon should see that the individual specimen employed has every appearance of being pure. Hennicke has proved that ethyl bromide undergoes decomposition in the system with the liberation of bromine compounds, and as bromine is much more poisonous than chlorine, it is to be, a priori, expected that ethyl bromide will be more apt to produce wide-spread organic changes in the general tissues than is the older anaesthetic. In accordance with this, cases have been reported by Reich 9 and by Flatten, 10 in which the inhalation of the bromide has been followed by persistent vomiting, gen- eral weakness, and death (in from one to seven days), and in which the liver, the kidneys, and the heart-muscles were found to have undergone acute fatty degeneration. Methyl bromide. Certain other bromide compounds have been suggested as anaesthetics. Methyl bromide seems to be very poisonous, especially on account of its prolonged action, probably due to slow elimination. For nineteen cases of poisoning by it, see A. Jaquet (Deutsches Archivf. klin. Med., vol. Ixxi. ). PENTAL TRIMETHYLETHYLENE. This is a colorless, highly inflammable liquid, boiling at 100 F., originally proposed by W. Lombardino as a practical anaesthetic. It acts with great promptness without marked disagreeable symptoms, producing a short narcosis, which is, however, longer than that caused by ethyl bromide. In three hundred narcoses by it, P. Philipp 1 failed to find any depression of the heart or severe asphyxia. Pental is also commended by Kleindienst, who, however, noted that very frequently three or four days after the narcosis there was abundant albuminuria, and not rarely haematuria or haemoglobinuria occurs. In a study of the drug by David Cerna, 2 anaesthesia caused by it in the dog was found to be accompanied always by marked fall of the arterial pressure, and the conclusion was reached that the remedy depresses the heart. The alleged action of pental upon the kidneys, if it be true, negatives its use as a practical anaesthetic. From the statistics of Gurlt,* it is the most dangerous of all the anaesthetics, there having been three deaths in the six hundred reported narcoses. METHYLENE BICHLORIDE was introduced to the notice of the profession by B. W. Richardson, 1 as an anaesthetic similar to, but more pleasant and possibly safer ANESTHETICS. 103 than, chloroform, and has been rather extensively used in London. It has never been largely employed in this country. There is no way of knowing how many times it has been administered, but nine cases of death from its use are recorded. 2 The detailed phenomena in these cases indicate that, like chloroform, methylene bichloride kills by paralyzing the heart. It is not probable that it will ever come into general use as an anaesthetic. PRACTICAL ANAESTHESIA.* Although various substances have from time to time been used as anaesthetics, the surgical profession has prac- tically settled down to the employment of either ether or chloroform, and experience seems to show that there are no other known agents which act as well as do these two liquids. The question as to which of them should be preferred is a vital one, as are also the questions how to recognize and how to treat the accidents which occur during anaesthesia. It must be in the beginning granted that the production of anaesthesia is always at- tended by a danger which, though small, is positive, and that fatal acci- dents will always occur from time to time. There are few things in medical literature more tiresome than the arrogant assertions of various surgeons that they have never had a fatal accident from chloroform or ether because of the special methods by which they have used them. May their conceit die with them. All that a surgeon can hope for is to reduce the number of these accidents to a minimum. In selecting the agent, convenience of administration both to the sur- geon and to the patient is, of course, of importance ; but we hold that such advantage ought not to be pitted against danger of fatal results. For reasons which were given in H. C. Wood's address before the Berlin International Congress, it is doubtful whether half the deaths produced by anaesthetics are reported, but thousands have been recorded. The ratio of deaths to inhalations for chloroform is given by Lyman as i in 5860 ; by Richardson as i in 2500 to 3000 (see also Coats, 1 ) ; whilst Andrews records it for ether as i in 23,204, and Lyman as i in 16,542. In nearly one million of inhalations (George M. Gould 2 ), the mortality was, with chloroform, i in 3749 ; ether, i in 16,675. Garree 3 gives the deaths in three hundred and fifty thousand cases of recent inhalation of ether as i in 14,000. Gurlt* in over three hundred and thirty thousand cases gets the mortality for chloroform as i in 2075 ; ether, i in 5112 ; chloroform and ether mixed, i in 7613 ; A. C. E. , i in 3370; ethyl bromide, i in 5396^ These statistics are, taken together, so enormous * From time to time various surgeons have essayed to assist in the production and prolongation of anaesthesia by the use of narcotic alkaloids. Hypodermic injections of morphine given half an hour before the inhalation of the drug have been much employed, but it is doubtful whether they are of real advantage. In 1900, Schneiderlin proposed the substitution of scopolamine-morphine narcosis for ordinary surgical anaesthesia and his method has found some following (see p. 189). f Although not able to give definite statistics upon the fact, we are strongly inclined to believe that deaths from anaesthesia, and especially from ether, are proportionately more frequent in Europe than in America. If this be so, one reason, it seems to us, is to be looked for in the use of the Clover and other forms of closed inhalers, with which the anaesthesia produced is to a greater or less extent due to mechanical asphyxiation. io 4 GENERAL REMEDIES. in extent and so concordant that it must be considered established that the ratio of deaths from chloroform is about four times greater than that from ether. The assertion that the inhalation of chloroform is less dangerous in tropical than in temperate climates has been made so frequently and so earnestly by various surgeons practising in hot countries, and is seemingly so sustained by statistics, that it is probably correct. It has received a curious confirmation from a study of reported deaths from chloroform by Thomas R. Evans, 5 which appears to show that most of these deaths have occurred during the cold seasons of the year. It is entirely possible that the increased volatility of chloroform at high temperature facilitates its elimination from the body and thereby lessens the dangers of its use. The advantages of chloroform over ether are that it is less disagree- able to the patient, produces less excitement, more speedily reduces the subject to insensibility, and is less apt to cause excessive after-nausea and vomiting. These advantages do not at all counterbalance the great danger to life, and we believe that the surgeon is not justified in using chloroform unless under certain circumstances and for certain definite reasons. Moreover, we believe that many of the so-called disadvantages of ether can be overcome by a little care. If the stomach be empty, the after- nausea will rarely be severe, and when the ether is properly given with an Allis inhaler, the average time required for the production of complete insensibility is eight minutes, and the sense of suffocation and the symp- toms of excitement are rarely pronounced. A study of the reasons of the great fatality of chloroformization leads to a study of the methods by which chloroform and ether produce death. The earlier teaching of H. C. Wood was, in accordance with the general professional belief, " First, that although ether in moderate doses acts as a stimulant to the circulation, yet, in overwhelming amount, it is capable of depressing the heart, but that such depression of the heart is always less than the depression of the respiration ; secondly, that chloroform may produce death by paralysis of the respiratory centre, or by a simul- taneous arrest of respiration and circulation, but that primary paralysis of the heart may occur, and is especially prone to do so when the chloro- form vapor has been given in concentrated form. ' ' These teachings have been very strongly combated by the so-called Hyderabad Commission, led by Lauder Brunton, of London, who, as the result of four hundred and fifty experiments made upon the pariah Some years since a method of rapid etherization, in which the ether was put into a gallon jar and the patient forced to breathe in and out of the jar, was tried by Agnew in the University Hospital. Anaesthesia was produced almost at once with very little excite- ment, but in a very brief period the Clinic nearly lost two patients from anaesthesia, and the method fell at once into desuetude. It was really a plan of asphyxiation rather than of etherization. The Rolh-Drager inhaler is an apparatus invented for the purpose of giving a mixture of chloroform with oxygen. It is claimed by Roth that under these cir- cumstances the chloroform remains unchanged, although Ernst Falk believed that his chemical studies have demonstrated that after twenty minutes of narcosis there is a dis- tinct decomposition of the chloroform (D. M. W., 1902, xxviii., and 1903, xxix.). ANESTHETICS. 105 dogs of India, came to the absolute conclusion that chloroform never kills by causing sudden stoppage of the heart. There is no space in the present volume to go over in detail the evidences which were brought for- ward by H. C. Wood in his Berlin address. It was, however, we think, definitely proved that the clinical and experimental facts are accordant, and ' ' that chloroform acts much more promptly and much more power- fully than does ether, both upon the respiratory centres and the heart ; that the action of chloroform is much more persistent and permanent than is that of ether ; that chloroform is capable of causing death either by primarily arresting the respiration or by primarily stopping the heart, but that commonly both respiratory and cardiac functions are abolished at or about the same time ; that ether usually acts very much more power- fully upon the respiration than upon the circulation, but that occasionally, and especially when the heart is feeble, ether is capable of acting as a cardiac paralyzant and may produce death by cardiac arrest at a time when the respirations are fully maintained." These conclusions, which were based upon a thorough examination of clinical records and a very large number of experiments performed in the laboratory, have since been confirmed by John A. MacWilliam, 6 who has recorded cases of death in the lower animals from chloroform, in which there was primary collapse of the heart ; and by the studies of the Lancet Commission, 7 which found that out of three hundred and fifty-seven deaths caused by chloroform, whose records it had examined, the fatal result was caused by cardiac failure two hundred and twenty-seven times, by respiratory failure eighty times, and by simultaneous failure of the two functions seventy-seven times.* MacWilliam also found that in the dog cardiac weakness and dilata- tion are always caused by chloroform, and in rare instances are produced by ether. Both chloroform and ether are capable of causing arrest of the heart by a direct action upon the viscus, but chloroform is more apt to cause fatal accidents than is ether, partly because its influence upon the heart is very much more decided, and partly because it persists much more tenaciously than does ether in its action upon the whole organization after its administration has been interrupted. It lets go its hold much less easily and much less rapidly than does ether.f Alexander Wilson believes that the ' ' cardiac failure 1 ' of chloro- formization is chiefly a vaso-motor paralysis. Undoubtedly vaso-motor paralysis plays a part in the production of the untoward results, but we see no sufficient reason for supposing that it is the chief factor. Another fact worthy of notice is the question whether the lowered blood-pressure itself has any effect upon the respiration. In a research * Further, see cases reported by Alexander Wilson (London Lancet ', September n, 1897) ; also by Jamieson (Australia Med. Gaz., 1903, xxii.). t A possible explanation of this peculiar tenacity is that chloroform is stored in the nerve-centres, outside of the blood-vessels. Julius Pohl (Arch f. Exp. Pathol. u. Pharm., 1891, xxviii.) affirms that his analyses have proved that more chloroform exists during the narcosis in the brain-tissues than in the blood coming to it. 106 GENERAL REMEDIES. published by H. C. Wood and W. S. Carter, 8 it was proved that lowered arterial pressure has only a comparatively feeble effect upon the respira- tion, although a great fall of pressure does depress the respiratory func- tion. Evidently prolonged failure of respiration tends to depress the circulation, and prolonged failure of circulation tends to depress the respi- ration. The two functions are thus far interrelated.* On account of its being less dangerous, ether should always be selected as the anaesthetic agent in general surgery unless definite reasons exist for the preference of chloroform. These reasons may be epitomized as fol- lows. First, when, as in the case of war, circumstances make it practically impossible to obtain the bulkier anaesthetic. Second, when the symptoms themselves are of such character as immediately to threaten life, especially if at the same time there be, as in a tetanic convulsion, some existing con- dition which greatly interferes with the entrance of the anaesthetic into the lungs. Third, the existence of certain contra-indicating bodily conditions hardly to be spoken of as disease. How cogent the reasons under the present heading are to be considered we are uncertain, but F. W. Hewitt affirms that in old people with very rigid chests etherization is often attended by great difficulty and chloroform is well borne, and also cites extreme obesity as a bodily state in which ether is not well borne, and in which chloroform or a mixture of ether and chloroform is preferable. Fourth, existence of certain diseases which, to a greater or less extent, not only contra-indicate the use of an anaesthetic, but also, when the anaes- thetic must be used, modify the choice of the agent by the surgeon. The existence of a contra-indicating disease does not forbid the use of an anaesthetic. If a major surgical operation be imperatively demanded, and if it be impossible by the use of local anaesthetics to prevent the pain and emotional excitement which would attend the operation in a perfectly conscious sensitive patient, the surgeon must decide whether the needs of the case overbalance the added risk to the operative procedure. The * Mixed Anesthetics.^ number of combinations of one or more anaesthetics have been to a greater or less extent used by surgeons with the hope of overcoming or avoid- ing the deleterious effects of the one ingredient by the action of another. The most used of these is the so-called A. C. E. mixture, composed of one part of alcohol, by weight, two parts of chloroform, and three parts of ether. The latest is Schleich's mixture, in which the attempt is made to have an anaesthetic the boiling point of which shall ap- proximate to the bodily temperature, and for this purpose benzine is used as a diluent. The proportions of Schleich's mixture are three parts chloroform, ten parts ether, one part benzine. The difficulty with all these combinations is that their ingredients are not chemically combined but simply mixed together, and therefore obey each the law of its own volatility; so that the surgeon can 'never be certain of knowing exactly what the patient is inhaling at any time ; the only certainty being that the original mixture is not being taken into the lungs. In regard to Schleich's mixture, H. C. Wood, Jr. (Phila. Med. Journ., April, 1899), has demonstrated that the benzine is not, as affirmed by Schleich, a " nearly inert" diluent ; on the contrary, it is, although almost devoid of anaes- thetic properties, a powerful depressant of the respiratory centres and also of the heart and probably of the vaso-motor system. It is evident that Schleich's mixture is distinctly inferior either to ether or chloroform used alone. If the surgeon is intent on having what may be termed a " mixed anaesthesia," it would seem better to put ether upon the inhaler or sponge, and then a few drops of chloroform. ANESTHETICS. 107 contra-indicating diseases are of such importance as to demand here extended consideration. They are : Organic Brain Diseases, including Tumors ; Atheromatous Conditions of the Blood-Vessels ; Organic Affections of the Heart, of the Lungs, and of the Kidneys. Brain. Brain-tumors and other organic forms of cerebral disease are very serious centra-indications to the use of anaesthetics ; even where there is no demonstrable brain-lesion, if there be reason strongly to suspect atheroma of the vessels, anaesthesia should be induced with the greatest reluctance. In a number of cases apoplexy has resulted during or imme- diately after the anaesthesia. Moreover, death has frequently abruptly occurred immediately after the sudden removal of a large cerebral tumor the introduction of the finger between the lobes of the brain or other procedure which affects the intracranial pressure. These deaths have resulted both from respiratory failure and from sudden cardiac arrest, and are probably the result of the loss of the resisting power of the respiratory and vaso-motor centres, making them unable to withstand variations of brain-pressure which in their normal condition would not seriously influ- ence them. It is evident that the surgeon should be as careful as possible in his operative procedures to avoid sudden disturbances of the brain. In regard to the choice of the anaesthetic in a cerebral case there would seem to be more danger of apoplectic hemorrhage from the use of ether than from chloroform, on account of the increase of arterial pressure pro- duced by ether, but the persistency of chloroform and the depressing influence which it has upon the heart are much more serious disadvantages than any possible increase of blood-pressure by ether ; and in a discussion which took place in the College of Physicians of Philadelphia, November, 1902, a number of cerebral surgeons of large experience were unanimous in asserting that in cerebral surgery ether is the least dangerous anaesthetic. Disease of the Heart. When valvular disease of the heart does not produce any distinct functional disarrangement of the heart, and when the heart-muscle is in a fair condition of health, anaesthesia may be induced, provided the circumstances of the case are such as to justify the surgeon taking a slightly increased risk. The key to the situation is not the valvular lesion, but the condition of the muscle. A loud murmur usually depends for its loudness not only upon the character of the valvular lesion but also upon the force which drives the blood through the diseased orifice. A loud murmur is, therefore, on the whole, not more strongly contra- indicative of anaesthesia than is a feeble one ; indeed, as the feeble murmur is more commonly associated with feeble heart-walls, greater care must be exercised when such murmur exists than when a loud bruit everywhere forces itself upon the physician's attention. In all cases of heart disease, whenever it is possible to avoid the use of an anaesthetic by the employ- ment of cocaine or by other local device, this should be done. No condi- tion of the heart is, however, an absolute centra-indication to the use of the anaesthetic ; under certain circumstances anaesthesia may be produced when the heart is in advanced fatty degeneration. It must be remem- io8 GENERAL REMEDIES. bered that the shock and nerve-strain which attend a major surgical oper- ation without anaesthesia would endanger the arrest of a fatty heart even to a greater degree than would the anaesthesia, so that the question is, after all, as to the imperativeness of the proposed operation. In diseases of the heart the action of chloroform upon the heart makes it very dangerous. In cases with wide-spread pulmonic engorgement, and a tendency to exudation into the lung-vessels and smaller bronchial tubes. The local irritant action of ether upon the mucous membranes is so deleterious that the surgeon is placed, as it were, between Scylla and Charybdis, and may in an individual case have great difficulty in deciding what is best. Some surgeons prefer under these circumstances the so-called A. C. E. Mixture, which is, however, of very doubtful advantage (see page 1 06 note). A better mixture consists of six parts of ether and one of chloroform, added together at the time of use. Chloroform is especially dangerous when orthopnoea exists ; it is doubtful whether in such a case its use is ever justifiable. Disease of the Respiratory Apparatus. The existence of severe or- ganic disease of the lungs seems to be a less serious bar to the use of anaesthetics than would be naturally expected. Of all the chronic pul- monic affections, probably emphysema, associated as it so frequently is with weakness of the right heart, causes the most solicitude to the anaes- thetizer. The irritant local action of ether is an important element when the lining membrane of the tubes or air-vessels is seriously implicated ; indeed, our own opinion is very positive that in some of the deaths which have occurred in persons with diseased kidneys from oedema of the lungs directly after etherization the cause of death has been the local irritant action of the ether.* It would appear also that wide-spread organic changes in the lungs sometimes so interfere with the absorption of ether that it becomes exceedingly difficult to produce complete anaesthesia. The dictum of Hewitt, that in extreme emphysema, in chronic bronchitis attended by expectoration and dyspncea, and in advanced pulmonary phthisis, chloroform or some other mixture containing chloroform should be employed, is, we believe, correct. * Ether Pneumonia. Severe and even fatal pneumonia has so frequently followed the use of anaesthetics that the possibility of its occurrence must be considered one of the serious dangers of anaesthesia. Allowing that particles of food may enter the lungs during the narcosis and produce inflammatory changes, there has been a tendency to believe that ether pneumonia more frequently follows the use of ether than of chloro- form, and is due to the local irritant action of the ether. The research of Richard Holscher 9 has led him to the conclusion that the pneumonia is really due to the in- halation of bacteria from the mouth into the lung, that during etherization there is prac- tically no irritation of the bronchial mucous membranes by ether, and that the rales which are heard during the narcosis are due to the inhalation of saliva, which may largely be avoided by lowering the head, turning it to one side, and keeping the mouth as free as possible from the secretion. Any mechanical obstacle to breathing, according to Hol- scher, greatly increases the likelihood of the inspiration of saliva, and the consequent danger of pneumonia. According to our belief, this research, although extremely im- portant and suggestive as pointing out one cause of ether pneumonia, does not disprove the deleterious effect of the irritant action of ether. ANESTHETICS. 109 In all cases of lung disease it is important to remember that the more chronic the disorder the less important is it as a contra-indication to the use of an anaesthetic, and that anaesthetics are especially badly borne when there is acute or subacute pulmonary disease. Only under the most urgent circumstances should anaesthesia be attempted when in an acute pulmonary disease the symptoms are of sufficient intensity to produce even slight dyspnoea. In recent pleurisy or pleuro-pneumonia, with any embarrassment of the respiration or duskiness of the countenance, anaes- thetization is attended by very grave risk. In obstructive laryngeal disease, or when contraction of the lumen of the trachea, either from within or without, produces dyspnoea, extreme caution must be exercised in the use of the anaesthetic. Under these cir- cumstances the chances of ether increasing the mechanical asphyxia by irritating the larynx or trachea are very great, so that chloroform is pref- erable ; or chloroform may be employed at first, and ether given when the reflexes have been abolished by the obtunding of the nerve-centres. When the laryngeal obstruction is of the nature of a spasm. and not of an organic change, the use of the anaesthetic is free from extraordinary dan- ger ; but it must be remembered that frequently in such cases there is more or less laryngeal irritation, so that chloroform is preferable to ether, a conclusion which is strengthened by the necessity which often exists for the prompt action of the anaesthetic. In certain cases the mechanical obstruction may be a tumor in the mouth or other lesion above the respiratory tract proper, but if the respi- ration be interfered with, the general principles just enunciated hold good. Hepatic Conditions. L. G. Guthrie 35 has called attention to the exces- sive fatality attending the use of chloroform in children suffering from fatty degeneration of the liver. The time of death in nine recorded cases was from ten hours to nine days after the operation, so that the cases really belong among those considered in the After-effects of Anaesthesia (see page 116). There is sufficient ground for the generalization that anaes- thesia should be produced with the greatest reluctance in all persons suf- fering from chronic fatty degeneration of the liver, and that when anaes- thesia must be produced in such cases, ether and not chloroform should always be selected. Diseases of the Kidney. So far as our reading goes, Thomas A. Emmet was the first to report cases of fatal urinary suppression produced by the inhalation of ether in persons suffering from chronic Bright' s dis- ease. His statements have been followed by reports of numerous similar cases, and led to the wide-spread opinion that ether should not be used when there was chronic disease of the kidneys. It is now, however, established that chloroform is capable of causing severe renal irritation, and the whole drift of the evidence is to show that in this respect it is much more active than is ether, so that, although renal disease is a contra- indication to the use of any anaesthetic, if anaesthesia must be produced under the circumstances, ether is safer than is chloroform. no GENERAL REMEDIES. Albuminuria may be considered a sufficiently accurate evidence of renal irri- tation to enable the practitioner to use it as a working test. A large number of studies as to the effect of anaesthetics upon the urine have been made by different clinicians. Eisendrath 81 states that albuminuria was produced in his cases, 25 per cent, by ether, 32 per cent, by chloroform ; and casts were found in 28.3 per cent, after ether, 21.4 per cent, after chloroform. In Wunderlich's studies the results were 24.6 per cent, after ether, 34.8 per cent, after chloroform.* Ogden found tube-casts in 70 per cent, of etherizations. Statements of other investigators, whom we shall not quote in detail, indicate that the occurrence of distinct albuminuria after anaes- thesia in persons with sound kidneys is less frequent than these statistics would indicate ; but all the statistics strongly point towards the opinion that, whilst both ether and chloroform seriously affect the kidneys, ether is less dangerous than is chloroform. These clinical conclusions are certainly borne out by the results obtained in animals by various investigators. According to Kemp and Thompson, during etherization in the animal there is always accompanying the first rise of blood- pressure an expansion of the kidney followed by a shrinkage of the organ, if the anaesthesia be prolonged ; but this has been found by Buxton and Levy ( B. M. J. , 1900, ii., September 22) not to be a constant phenomenon. Buxton and Levy failed to produce complete suppression with ether, but did get lessening of the secretion, and as the result of their research think that there is very little evidence to show that ether has an active direct influence upon the secreting structure of the kidney. All observers seem to find that in chloroformization the volume and activity of the kidney steadily decrease. The choice of the surgeon between the two great anaesthetics should, in most cases of renal disease, be influenced by the existence of secondary effects of the disease. If, for instance, in any case there were pronounced degeneration of the heart-muscles, the selection should fall upon ether. If there were any reason, on the other hand, to believe that there was in the case a tendency to serous exudation, the danger of the production of cedema of the lungs by ether through its local irritant action would be sufficient reason for the selection of chloroform. In doubtful cases of car- diac complication it might be good practice to commence the anaesthesia with ether, and, when once its stimulating action was established, to con- tinue the narcosis by the use of chloroform. After-effects of Anesthesia. Many yeirs ago Liman affirmed that at least some of the deaths following operations which have been attributed to the operative procedure have been due to the chloroform. The cor- rectness of this view we have demonstrated by having such deaths occur in the lower animals after both chloroform and ether when there had been no surgical operation, the animal regaining consciousness, but by and by passing into a condition of profound asthenia, with loss of all functional * For elaborate articles on the action of chloroform on the urine and kidneys, see F. Nachod (Archiv f. Klin. Chirurgie, 1890, li.), also Offergeld 36 . Babacci and Bebi (II Polyclinico, 1896, iii.), reach the conclusion that, although ether produces slight changes in the kidneys more frequently than does chloroform, it never causes such profound alteration. As bearing upon the question of the effect of ether anaesthesia upon the kidney, it is interesting to state that F. S. Watson and W. T. Bailey have found that in the normal kidney, so far as the so-called Phloridzin Test is concerned, ether increases functional activity of the kidney, but when the kidney is already diseased seems from the beginning to depress the renal function (Med. and Surg. Rep., Boston City Hospital, 1902). ANESTHETICS. m power, ending in death. These deaths are due to anatomical changes in important organs. About a decade since it was shown by Unger and by Path, 21 that when, in the dog, narcosis is maintained for a length of time by the inhalation of chloroform, there is produced a fatty degeneration which is usually most marked in the liver and kidneys and in the heart-muscles, but may be pronounced in the spleen, in the gen- eral epithelial tissues, and in the voluntary muscles. These researches have been confirmed in their general results in numerous experiments upon animals by Strassmann, 22 by Ostertag, 23 and by Kast and Mester. 24 Tedeschi, 25 in an elaborate study upon guinea-pigs, has found that the first anatomical alteration produced by chloroform consists of cloudy swelling which may go on to degeneration, or may subside ; and that even when a considerable degree of apparent fatty degeneration has occurred recovery is possible. He also found that these alterations were most severe in the nervous system, which is somewhat contrary to the general opinion. Botscharoff 26 and S. Schmidt 37 assert that they have demonstrated alteration of the heart-ganglia, especially vacuolation of the cells, after prolonged chloroformization. Eugene Fraenkel '" found in four human subjects, dying after pro- longed chloroformization, wide-spread necrotic degeneration, especially affecting the heart-muscles and the epithelium of the kidney, and Car- michael and Beattie 37 and Stiles and Macdonald M have reported wide- spread fatty changes in man following chloroform anaesthesia. As these observations have been abundantly confirmed ( Handler, ^ Ambrosius, 29 and our own laboratory), it must be considered proved that chloroform has the power of producing tissue-degeneration, ending in death. The possibility of after-effects from the anaesthetic should certainly influence the choice of surgeons. According to Desgrez and Nicloux, 32 chloroformization of the lower animals causes a great increase in the amount of carbon monoxide in the blood. As this substance is produced by the decomposition of chloro- form by an alkali, and as Desgrez and Nicloux have failed to find that it is increased in the blood by etherization, it probably is produced in the blood by the destruction of the chloroform, which destruction must be accompanied by the formation of various chlorine compounds. On the other hand, the destruction of ether in the system can scarcely yield other than harmless educts, so that, a priori, after-effects are much more probable from the use of chloroform than from ether. This proba- bility is strongly confirmed both by experimental and clinical evidence. As the result of many years' experience in the physiological laboratory, we are very sure that after-deaths are much more frequent in animals which have been chloroformed than after ether. In experiments performed by William Carter and H. C. Wood in the University laboratory, tissue-changes similar to those caused by chloro- form were found in the dog after etherization. These studies have been corroborated by the researches of Ferdinand Schenck * and of Tedeschi. Again, in a woman whose death occurred twenty-four hours after a pro- longed etherization in the University Hospital, without obvious cause, H2 GENERAL REMEDIES. wide-spread tissue-changes were found. Miiller 59 found that chloroform, ether, ethyl chloride, ethyl bromide, and chloral hydrate were all capable of producing these changes, but that they were less marked after ether than after chloroform. In his experiments it was found that if a second narcosis was produced before the repair processes were completed the baneful effects were much intensified even if different anaesthetics were used. He warns therefore that after a prolonged anaesthesia no second narcosis should be undertaken for at least three days later. In this connection may be mentioned the observations of E. Becker 10 * who, in two hundred and fifty experiments made with ether, ethyl bro- mide, and chloroform, found that the anaesthesia was followed by pro- nounced acetonuria, which he believed to be due to increased destruction of albumin. In three diabetics he noticed great increase in the amount of acetone in the urine, an indication that under certain circumstances diabetes should be considered a centra-indication to the use of an anaes- thetic. Brachett Stone and Low * report seven cases of fatal acetonuria following ether anaesthesia in children suffering with muscular atrophies. ADMINISTRATION. The methods of the administration of chloroform and ether naturally differ. With ether the nearer the saturation of the air is reached the quicker will be the induction of anaesthesia, and the effort has generally been to give the anaesthetic in as concentrated a form as possible. It is certain, however, that the disagreeable symptoms of the first stage of ether may be largely avoided by the primary use of a very much diluted vapor. According to Snow, air at 80 F. , when saturated with ether, contains seventy-one per cent, of the vapor. Ether was formerly habitually given by making out of stiff paper or card-board a cone that would fit, when a saturated napkin had been placed into it, over the nose and mouth of the patient. Although by this method anaesthesia is rapidly insured, the discomfort of the patient is brought to a maximum. Much better results are reached by laying five or six thicknesses of surgical gauze lightly over the mouth and nose 01 the patient, and then dropping from a properly prepared bottle the ether, drop by drop, upon the gauze just below the nostrils. Ether is also given by means of various inhalers ; the so-called ' ' closed' ' inhalers, in which there is only a small supply afforded of atmos- pheric air, are, in our opinion, exceedingly dangerous ; whilst the Allis inhaler offers the perfection of method for the production of ether anaes- thesia, f In Europe various inhalers are employed for the administration * Confirmed by Luzzati (Comment. Clin., 1895). t The inhaler invented by O. H. Allis is based upon the theory that the patient to be etherized should be supplied with an abundance of air impregnated with the vapor of ether. It consists essentially of a series of foldings of muslin on a wire framework, arranged almost like the gills of a fish, so as to allow the air to pass freely through, but everywhere to come in contact with the ether. It should be placed upon the face of the patient dry, and the ether gradually poured on from a so-called " Polyclinic" bottle, which has two fine tubes through the cork, one short, to admit air, and one reaching to near the bottom, so that the ether can be poured through it in a fine stream. ANESTHETICS. 113 of chloroform, but in this country they are rarely, if ever, used. A napkin or a few folds of surgical gauze may be laid over the nostrils and mouth, and the chloroform dropped upon this. Whatever plan be em- ployed, it is of vital moment that the vapor be well diluted ; not more than three and one- half per cent, of it should be contained in the inspired air. The use of ether at night requires care. We have seen a flame, by lighting the vapor, pass over eight feet and set on fire the ether sponge and the patient. Since the vapor of ether is heavier than air, when the anaes- thetic is used at night the light should always be elevated. The adminis- tration of chloroform at night is also not free from danger. Attention has been called by various practitioners to violent catarrhal inflammations of the respiratory passages, and even to fatal pneumonias, which have been produced by the use of chloroform in confined rooms with artificial light. It has been shown by the analyses of Bosshard and others that, under the circumstances mentioned, by the decomposition of chloroform there is liberated free chlorine and also phosgene gas, to which probably are due the local inflammations.* ACCIDENTS. In 1848 Dume"ril and Demarquay 11 showed that during anaesthesia there is a reduction of temperature. This has been confirmed by Bouisson 12 and by Sulzynski. 1S This fall of temperature may, when narcosis is prolonged, amount to 2 F. Whether this fall of temperature be, as asserted by Scheinson, 14 due to a lessened production of the bodily heat, or whether, as seems to us more probable, it be the outcome of an increased dissipation of bodily heat, is of no practical importance to the surgeon. The immediate lesson is, that prolonged severe operation should be done in very hot rooms, and that when the bodily heat falls it should be maintained by the external use of heat, in some cases even by the employment of a hot-water mattress. In practical anaesthesia it is a matter of the gravest importance to recognize the coming on of accidents. Cessation of respiration may be sudden ; more usually it is gradual. Irregularities of respiration, and increasing shallowness of respiration appearing during the advanced stages of anaesthesia, are most urgent signals for the withdrawal of the anaes- thetic and the use of prompt measures for relief. Failure of the pulse is, of course, of still more serious import, but it is often so sudden as not to be noticed immediately. It is always accompanied or immediately pre- ceded by a peculiar change in the facial color or expression, and the anaesthetizer should therefore not merely watch the pulse, but especially the face.f In discussing the treatment of the accidents of anaesthesia it seems essential first to point out certain procedures which have been very largely * Consult Zweifel (Berl. Klin. Wochensch., 1889), D. R. Patterson (London Prac- titioner, xlii.), and Brandenberg (Corr. Bl. f. Schweizer Aerzte, 1897, xxvii. ; Arch.f. Hygiene, 1891, xiii.). t For methods of determining the percentage of chloroform in a mixture of its vapor with air, see Brit. Med. Journ., 1903, vol. i. p. 1420. 8 practised in the past and are still not rarely employed, but which are either of no value or harmful. The first of these is as to the use of ether ; second, as to the administration of alcohol. Hypodermic injections of ether, although frequently employed, are so absolutely absurd that one wonders at the fatuity of surgeons. Ether in the blood acts as ether, whether it finds entrance through the lungs, through the rectum, or through the cellular tissue ; and the man who would inject ether hypodermically into a patient who is dying from ether, should, to be logical, also saturate a sponge with the ether and crowd it upon his unfortunate victim. Owing to the closeness of the relations of alcohol to ether and chloroform, H. C. Wood many years ago taught that the administration of alcohol during anaesthesia was a doubtful procedure ; subsequently, R. Dubois 15 determined that in the alco- holized animal much less chloroform is required to kill than in the normal animal. Then H. C. Wood 36 experimentally proved that alcohol injected into the vein of a dog whose heart is depressed by chloroform, if in sufficient dose to exert any per- ceptible influence, always increases the cardiac weakness, or, if in considerable dose, immediately paralyzes the viscus. Without doubt patients have been killed by alcohol given to relieve cardiac failure during anaesthesia. Experiments similar to those with alcohol just spoken of were made by H. C. Wood : with ammonia, which was found usually to have a distinct, although very fugacious, influence upon the chloroformed heart ; with digitalis, which was found to have a very powerful stimulant influence upon the heart and blood-pressure ; with amyl nitrite, which failed to produce any pronounced influence for good ; with caffeine, which seemed to have little or no power ; and with strychnine, which had some slight influence upon the blood-pressure, but an enormous one upon the respiration of the chloroformed animal. Thus, a respiration which had practically ceased for ten seconds, sud- denly, under the influence of an injection of strychnine, became very quick and full. Cocaine was not tried, but studies made with it since upon chloralized dogs indicate that it has distinct value, especially when given with the strychnine. At the time of the experiments just spoken of adrenalin had not been discovered, but as the most powerful known stimulant to the circulation it must be of great possible value in the treatment of the cardiac accidents of anaesthesia. Before epitomizing the treatment of the accidents of ansesthesia it seems proper to discuss in detail certain mechanical measures which may be practised with advantage, namely, Inversion of the Body, Cardiac Massage, and Artificial Respiration. Inversion of the Body. In the first edition of the present treatise it was written : "Whenever there is any failure of the heart's action, as is nearly always the case, the body should be laid at an angle of forty degrees, with the head downward, so as to favor the passage of arterialized blood to the brain" (E. L. Holmes 16 ). Some years after this the method was asserted in France to have just then originated with Nelaton. It undoubtedly has value. The body of the animal whose circulation has been paralyzed by chloroform acts in a measure like a tube filled with liquid. When the feet are raised above the head there is a marked increase in the blood- pressure in the carotid, with decrease in the blood-pressure in the femorals ; and when, on the other hand, the feet are dropped below the head, the blood-pressure fails in the carotid, but rises in the femorals. The respiration is not affected by the procedure, but a heart which has entirely ceased will often suddenly resume its work when the feet are elevated. Inversion causes the blood which has collected in the extremely relaxed abdominal vessels to flow into and distend the right side ANAESTHETICS. 115 of the heart, and this distention may have sufficient influence to stimulate into action a failing organ. Cardiac Massage. In 1889 Prus 33 succeeded in restoring animals to life, after cardiac arrest during anaesthesia, by rhythmically contracting the bared heart with his fingers, and this so-called "cardiac massage" has been employed to a consider- able extent by surgeons. W. W. Keen s * collected twenty-eight recorded cases with four successes ; since this paper one complete recovery has been reported by Sen- cert 41 . Three methods have been used : (i) By compression between the hands, one being applied outside the chest and the other directly upon the heart after an abdominal section, but without opening the diaphragm. (2) By abdominal section, and after opening the diaphragm seizing the heart within the pericardial sac. (3) By resection of the chest wall, incision of the pericardium, and grasping the heart with one or both hands. The third of these methods involves a major operation in surgery, adding distinctly to the surgical dangers of the patient. Especially when the abdomen has already been opened by the surgeon, the first, and even the second method is easily practised without very serious surgical results. It is at present doubtful whether cardiac massage will ever restore cardiac action when the intravenous injection of adrenalin and the practice of forced artificial respiration would not succeed, but to the use of these methods that of the simpler form of cardiac massage (No. i), especially in abdominal operations, may well be added. Artificial Respiration. The one measure which H. C. Wood found in his ex- periments upon fatally anaesthetized animals to surpass, in practical efficiency, all others combined was artificial respiration, by means of which animals were fre- quently resuscitated after all cardiac and respiratory movements had apparently ceased. It is evident that the ordinary methods of practising artificial respiration in man are exceedingly imperfect and feeble, and that in the accidents of anaesthesia so- called forced artificial respiration should be at once employed (see address on Anesthesia). The principle of forced artificial respiration consists simply of pumping air into the lungs by means of a bellows. Fell's apparatus is efficient, but unnecessarily complicated ; a simpler one is described in the foot-note.* When no apparatus is at hand, forced insufflation by breathing into the patient's mouth may be tried. A. E. Prince n reports a case saved in this way. In using this apparatus, the mask should be first tried, care being exercised to see that the tongue is well drawn forward and held in place by a thread through it, and that the epiglottis is kept open. If the lungs do not fully expand, the intubation- tube may be used. Whether the mask or the intubation-tube be employed, the lungs should be thoroughly but slowly expanded by each stroke of the bellows, and a respiratory rate of about sixteen to twenty a minute be steadily maintained. It is essential to free the lungs and blood of chloroform as rapidly as possible, by quickly changing the residual air of the lungs ; but of course due care must be ex- ercised that no force sufficient to rupture air-vesicles be employed. When the * Apparatus for Artificial Respiration. Fell's apparatus consists of a pair of foot bellows by which air is forced into a receiving chamber, which is connected with an apparatus for warming the air, and a valve which can be opened and shut by a movement of the finger. This valve, in turn, leads to the tracheal tube. When the valve is opened the air rushes through the chamber into the lungs and expands them ; the finger is lifted, the valve shuts, the lungs contract, and so the respiration goes on. A much simpler, cheaper, and probably equally efficient apparatus may consist simply of a pair of bellows of proper size, a few feet of india-rubber tubing, a face-mask, and two sizes of intubation-tubes ; there should also be set in the tubing a double tube, with an opening similar to that commonly found in the tracheal canula of the physiological laboratory, so that the operator can allow the escape of any excess of air thrown by the bellows. Fell (Journ. Amer. Assoc., 1892, xix.) insists on the superiority of his appa- ratus, and possibly in a large surgical clinic it might be well to provide his rather compli- cated mechanism. u6 GENERAL REMEDIES. symptoms are protracted, and the bodily temperature falls, the bodily heat must be maintained by external warmth, and the temperature of the room, unless the air entering the lungs be artificially heated, should not be less than 80 F. In the light of all our present clinical and experimental knowledge, the following rules may be formulated as embodying the treatment of the accidents of anaesthesia : First. Unless the pulse be beating actively, partially or wholly invert the body of the patient. Second. Place the index fingers of each hand upon the corresponding cornua of the hyoid bone, whilst the middle fingers rest upon the angle of the jaw, and then press forward and upward, the same force serving to extend the head upon the neck ; if this fail to open the glottis, by means of a tenaculum, thrust far back into the base of the tongue,* draw it forward. Third. Make a momentary effort to stimulate respiration by slapping the chest, by douching with cold water, or by the method, suggested by Hare, of pouring a little ether on the bared abdomen, so as to get the effect of cold. Do not waste time, if respiration has failed, in any of these attempts. Fourth. Use certain drugs as follows : Ammonia may sometimes be given by the mouth, but ordinarily is of no value. Strychnine and cocaine, administered hypodermically or intravenously, are often of the greatest service. Digitalis given hypodermically acts too slowly to be available ; probably injected intravenously it would be a very valuable remedy, but we know of no clinical records of such use. Adrenalin, especially in cases of cardiac failure, administered intravenously in hot (105 F. ) normal saline solution, f may be of the utmost service ; from twenty to thirty minims of the i : 1000 adrenalin solution in half a pint of the saline solution may be slowly injected in cases of persistent circulatory failure ; as much as two drachms of the adrenalin solution in two pints of the normal saline may be given in the course of one and a half hours. When the symptoms are not very alarming, smaller amounts than those spoken of above are preferable. Fifth. Practise artificial respiration immediately and very actively throughout (forced respiration if the apparatus be at hand), even when the heart is primarily affected. It must be remembered that the residual air of the lung may retain the vapor of the anaesthetic and continue to yield it to the system for a considerable time after the cessation of its administration. * Benjamin Howard asserts that the common practice of drawing out the tongue has no influence in raising the paralyzed epiglottis, which he affirms can be accomplished only by extending the head and neck ; but in the elaborate experiments made in the University laboratories by Hobart A. Hare and Edward Martin it was demonstrated that the method of Howard is inferior to that given in the text (Medical News, 1889). t The restorative cardiac action of hot normal salt solution intravenously adminis- tered has been demonstrated in a series of experiments upon animals by S. Gomberg, 20 and is said to have been long recognized practically in Russia. ANAESTHETICS. 117 LOCAL ANESTHESIA. Of the drugs which are employed for the production of local anaesthe- sia, cocaine still stands pre-eminent, but its common use for other purposes has led us to discuss its physiological action and therapeutic use fully in the chapter on Delirifacients. EUCAINE. Under the name of eucaine two allied chemical substances have been put upon the market, each depending, according to Vinci, 1 for its anaesthetic properties upon the presence of a benzoyl molecule in its constitution. These substances have been distinguished in commerce by the names of Alpha-Eucaine and Beta-Eucaine. Alpha-Eucainr; is chemically n-methyl-benzoyltetramethyl-y-oxypiperidincarboxy- licmethylester ; Beta-Eucaine is benzoylvinyldiacetonalkamine. At one time alpha-eucaine was the eucaine of the market, but it has been super- seded by beta-eucaine as less irritating and less toxic. Eucaine of the drug stores is at present beta-eucaine. Beta-eucaine is soluble in water to the extent of about three and one-half per cent. The acetate has been proposed as more soluble. According to Vinci, 2 alpha-eucaine is a depressant to the spinal cord, and Ver Eecke has found it to be a direct muscle paralyzant which acts more powerfully upon the heart-muscle than upon the voluntary muscle, so that death from cardiac diastolic arrest occurs before complete general paralysis. Ver Eecke states that in mammals the arterial pressure is markedly affected and the respiration is first stimulated and finally paralyzed centrically. The statement of Ver Eecke, 3 that the drug causes increased destruction of nitrogenous tissues, is scarcely borne out by the tabulated reports of his experi- ments. Ver Eecke failed to find the poison in the urine after its administration, and believes that it undergoes destruction in the body. According to Ver Eecke, in chronic poisoning with alpha-eucaine there is a wide-spread fatty degeneration which is especially marked in the heart-muscle. Vinci found that beta-eucaine paralyzes the peripheral motor nerves as well as the sensory, does not dilate the pupil, paralyzes the vaso-motor centres, and slows the heart even after the vagus has been paralyzed with atropine. THERAPEUTICS. As a local anaesthetic eucaine is somewhat less powerful than cocaine, and does not produce primary vaso-motor constriction nor vaso-paralytic after-effects. The three to five per cent, solution will rapidly and completely anaes- thetize the cornea without dilating the pupil or paralyzing the pupillary reflexes. The concentrations and dosage of the solutions generally recommended are as follows -. The strength of solution may vary from 2 per cent, in ophthalmology to 10 per cent, in the nose and throat. For infiltration anaesthesia according to either Schleich's or Braun's method i to 1000 up to 0.3 Gm. (5 grains) ; for regional analgesia 2 to 5 per cent, solution. The influence of eucaine upon the general system is so slight that fifteen grains of it have been injected hypodermically (G. W. Spencer*) without the production of any marked symptoms. It may prove of value in gastric pain or vomiting. The maximum dose is said to be three grains. TROPACOCAINE BENZOYL-TROPEIN. This alkaloid was isolated by Giesel from the narrow-leaved coca-plant of Java. It is obtained as an oily liquid, which solidifies in radiating crystals, and is soluble in chloroform, ether, or benzin. It has been physiologically studied by Arthur P. Chadboume, who finds that locally it acts in a manner similar to cocaine, without, however, causing ischaemia or congestion of the mucous membrane with which it is brought in contact. It was found by Chadbourne to be only half as toxic as cocaine. In lower mammals it produces in sufficient dose loss of coordi- u8 GENERAL REMEDIES. nation, followed by violent convulsions, disturbances of the respiration, coma, and death by centric asphyxia. The convulsions are of cerebral origin. Upon the cir- culation the drug seems to have only a comparatively feeble influence, causing, however, when in sufficient amount, a steady fall in the arterial pressure. The tem- perature usually begins to rise before the convulsion, and has been noted as high as 4 C. above the normal. When tropacocaine is put in the eye, anaesthesia is said to come on and disappear more quickly than with cocaine, sensation being sus- pended in less than half a minute after the application of a three per cent, solution : mydriasis is usually absent, never very pronounced. It is claimed for tropacocaine that it is especially superior to cocaine for the pro- duction of spinal anaesthesia, being very much less apt to produce fever and other disagreeable symptoms (K. Schwarz 5 and F. Neugebauer 6 ). According to Neu- gebauer, 0.05 to 0.06 gramme of the alkaloid may be injected. AN^ESTHESIN, the ethyl-ester of P-amido-benzoicacid, a white, inodorous pow- der, sparingly soluble in cold water, whose hydrochloride makes a one per cent, solution, which is, however, so irritant that when used hypodermically it produces a burning sensation, and should therefore be diluted before injection. In the experi- ments of Binz, colossal doses of aneesthesin given to rabbits were found to produce only a transient methaemoglobinaemia ; no renal irritation or methaemoglobinuria were noted, and it is asserted that practically ansesthesin is not poisonous, but that it is a very active local anaesthetic. Anaesthesin has been found very useful in painful hemorrhoids, three to seven grains in suppositories ; in vesical tenesmus, especially of women, in soluble bougies of five grains ; in pruritus vulvcz, in various eczemas with great irritation, especially about the genitals, a ten per cent, ointment may be used. In irritation of the throat and palate, lozenges containing from three-tenths to six-tenths of a grain are stated to be effective. Internally, anaesthesin has been used in gastrodynia and in vomiting, in dose of from five to seven grains (0.3-0.5 Gm.). Subcutin is white crystalline powder, soluble in one per cent, of cold water, a compound of anaesthesin and paraphenol-sulphuric acid, introduced by Ritsert. 7 It is asserted that it is germicidal, non-toxic, and, in one per cent, solution, especially useful for the production of infiltration-anaesthesia. ORTHOFORM is a white bulky powder very slightly soluble in water. It will not produce loss of sensation through the skin nor mucous membrane but is an effi- cient anaesthetic when applied to raw surfaces. As it also possesses some antisep- tic power it is used chiefly as a dusting powder to burns or other painful wounds. In gastric ulcer it will at times greatly relieve the pain, for which purpose five to ten grains (0.3-0.6 Gm.) may be given at a dose. It is of great service in alleviat- ing pain in tuberculous laryngitis. STOVAINE. This benzoyl derivative was brought forward by Tourneau as being less toxic than cocaine. It has been used in spinal analgesia by Tuffier 18 who asserts that it is not followed by unpleasant after symptoms. He injected one-half c.c. (7 minims) of a 10 per cent, solution. It should not be used in connection with adrenalin. ALYPIN. The benzoyl-tetramethyl-diamino-ethyl-dimethyl carbinol, suggested by Impens, 19 is a crystalline soluble powder not decomposed by boiling nor precipi- tated by moderate quantities of sodium bicarbonate. It seems to be much less toxic than cocaine and equally active as an anaesthetic, and differs from that alka- loid in not dilating the pupil nor affecting accommodation. It produces vascular dilatation instead of contraction. About the eye a 2 to 4 per cent, solution may be employed but in the nose and throat Seifert * recommends a 10 per cent, strength. ANESTHETICS. 119 NIRVANIN. Di - ethyl -glycocyl-para-amido ortho-oxy - benzole acid- methyl- ester-hydrochloride. Introduced into practical medicine by A. Einhorn and R. Heinz. 15 This substance is readily soluble in water and is a pronounced local anaes- thetic, but, according to reports, not equal in activity to cocaine. A. Luxenburger, 16 as the result of experimental research, concludes that it is so much less poisonous than cocaine that a two per cent, solution is very effective and may be freely used for the production of infiltration-anaesthesia. According to the same authority, the maximum amount of nirvanin to use is eight grains (0.55 Gm.). PRACTICAL LOCAL ANAESTHESIA. If it were possible to prevent the absorption of one of the active local anaesthetics after its injection into a tissue for a sufficient length of time, the method of local anaesthesia would be applicable to a very large proportion of surgical operations. When, as in the case of a felon, the part to be operated on can be tightly sur- rounded by a constricting bandage, so as to almost entirely shut off circu- lation, it is very easy to inject a local anaesthetic and afterwards to operate without the production of pain. Rarely, however, is the surgical task so easy, and the several processes discussed below have been invented for the purpose of overcoming the practical difficulties. Infiltration- Anessthesia. In this process, as devised by Schleich, the original attempt was to increase the activity of cocaine by adding to its benumbing power the influence of the interference with the circulation of the part, and of pressure upon the nerve-trunks of the part, produced by the injection of large quantities of water directly into the tissue to be operated on. In this process, as originally devised, the skin having been frozen by means of an ethyl spray, the point of a large hypodermic syringe is thrust into its papillary layer and a small mass of the fluid is injected, not under, but into, the skin. The needle of the syringe is then pressed in a little deeper and a new injection made, the process being con- tinued until a sufficient depth is reached. This method has been applied not only in minor but also in major surgery. During a large operation it may be necessary to repeat from time to time as the knife of the sur- geon cuts more and more deeply into the tissues. Three solutions were used by Schleich. No. i, of medium strength, may be made by dissolving at the time of using a powder composed of one and a half grains of cocaine hydrochlorate, one-third of a grain of morphine hydrochlorate, and three grains of common salt in twenty-seven drachms of sterilized water. No. 2, the weakest solution, contains only one-tenth the percentage of cocaine in No. i ; whilst No. 3, the strongest solution, contains double the percentage. No. 3 is used only when there is an active inflammatory lesion of moderate extent, as in case of a furuncle. In many cases it is essential that not only the part to be opened but the tissues beneath it be infiltrated. Thus, a furuncle or abscess may be completely encompassed with a zone of artificial oedema. A most important modification of the method of Schleich' s infiltration- anaesthesia has been brought to the notice of the profession by its inventor, H. Braun, 8 who found that if, by local cooling, the vitality and circulation of a tissue be interfered with, absorption of the injected cocaine will be so 120 GENERAL REMEDIES. long delayed that the symptoms of poisoning will be put off almost indefi- nitely or may fail to develop at all. Acting upon this knowledge, Braun obtained from the conjoint use of adrenalin and cocaine such satisfactory results as to apparently open a new field for the use of local anaesthesia : by employing a one to five per cent, solution of cocaine to which had been added from i : 10,000 to i : 100,000 of adrenalin, and beginning the operation from one to one and a half hours after the injection, he was enabled to do trunkal operations without causing suffering. FIG. 6. Showing mode of injecting the fluid under an abscess in successive whorls. (Schleich.) FIG. 7. Showing the syringe-point in the papillary layer of the skin. Braun' s method for the production of local anaesthesia has been fol- lowed by so much of success by various surgeons * that it would seem to be demonstrated that adrenalin, by its powerful constringing influence upon the blood-vessels, not only very sensibly increases the benumbing action of the local anaesthetic, but also, by lessening the rate of the absorp- tion of the drug, greatly increases the duration of its local activity. The further suggestion of A. E. J. Barker, 9 that the conjoint use of beta-eucaine and adrenalin affords a most excellent method of producing infiltration- anaesthesia, has been followed out in Philadelphia by various surgeons with great satisfaction. The plan may be readily carried out by the fol- lowing method : Powders containing three grains (o. 2 Gm. ) of beta-eucaine and twelve grains (o. 8 Gm. ) of pure sodium chloride are to be kept on hand by the surgeon. At the time of operation, one such powder is added to 100 c.c. of boiling distilled water, which is allowed to cool, and i c.c. of adre- nalin chloride solution (i : 1000) is added, so that 100 c.c. of the resulting * See Braun, Cb. C., 1903; Honigman, Ibid.; Gangitans, B. M. /., 1903, ii. ; Lef- mann, M. M. W., 1902; Braun, A. K. C., Bd. Ixix. ANESTHETICS. 121 liquid contain twelve grains of beta-eucaine and 0.015 grain of adrenalin chloride. The whole 100 c.c. may be used at one infiltration-anaesthesia, but, according to Barker, from 50 to 60 c.c. usually suffice, even in such considerable operations as for the cure of hernia, castration, etc. It is of course essential that an aseptic syringe be employed, and the needle should be of platinum with iridium point, so that it can be dis- infected in the flame of an alcohol lamp immediately before use. In his original discussion of infiltration-anaesthesia, Schleich recog- nized that it was possible to produce a transitory anaesthesia by infiltra- tion with pure water, and it has been shown by S. G. Gant 17 that in cases of superficial abscesses and other surgical diseases, and in situations in which injected water will for the time being, as it were, be dammed up in the tissues, it is possible to do painless minor operations by simply throwing sterile water into the parts in such amounts as to produce great distention. The technique of the method is as follows : A fold of the skin on one end of the line of the incision is compressed between the thumb and forefinger, and then has slowly injected into it a few drops of water so as to produce a small, localized, blister-like distention. This is repeated until the whole line of incision has been gradually injected with water into, not under, the skin. The needle is then plunged through this distended line, and subcutaneous injections are rapidly made until a firm, whitish, ridge-like swelling is produced, through which the incision can usually be made without pain. The method seems to be especially applicable to rectal diseases. In external thrombotic hemorrhoids the water should be injected between the layers of the skin overlying the clot ; in cutaneous hemorrhoids both the skin and the tumor should be distended tightly ; in external hemor- rhoids each tumor must be distended so tightly as to cause it to turn white. In rectal operations the skin and subcutaneous structure up to the anal margin, then the mucosa and submucosa, the external and, if necessary, the internal sphincter muscle, must be distended with water slowly injected. In deep rectal operations, involving extensive cutting or curetting, water anaesthesia seems not to suffice. Centric Local Anesthesia. Corning, A. Bier, 10 Seldowitsch, 11 and Tuffier 12 introduced into the practice of surgery the injection of cocaine into the spinal canal for the production of wide-spread anaesthesia below the point of injection, and the method has been successfully employed, so far as the absence of pain is concerned, by various surgeons in a large number of major operations in the lower portions of the body. Experi- ence has, however, shown that this method is attended by so much diffi- culty and danger that it has almost passed out of vogue. In performing the operation the hollow needle is introduced into the vertebral canal, as in the operation of lumbar puncture, and from one-sixth to one-third of a grain of cocaine is injected, the most absolute antiseptic precautions being taken throughout. Loss of sensation in the lower extremities is usually complete in ten minutes and begins to go off in about an hour. Serious nervous disturbances have 122 GENERAL REMEDIES. been present in a large proportion of the cases and fatal results have been frequent One surgeon reported five deaths in one hundred intraspinal injections ; and, ac- cording to H. Mohr-Bielefeld, 13 all available statistics taken together show that one death is to be expected in every two hundred spinal anaesthesias. Much more available for the purposes of practical surgery than is cen- tric anaesthesia is the process which may be known as Neural Anesthesia, As long ago as 1884 the injection of cocaine into a nerve-trunk for the purpose of producing anaesthesia in the region supplied by the nerve was suggested, not very clearly, by Hall and Halstead. 11 In the production of neural anaesthesia cocaine has been almost universally employed by surgeons, but whether it has or has not superiority over eucaine has not as yet been determined. The selected local anaesthetic is to be injected immediately in contact with the nerve, if it be a small one, or into the nerve-trunk itself if the nerve be large. So injected, cocaine produces a complete break in the conducting power of the nerve, affecting, it is affirmed, not only the fibres which are connected with the pain sense, but all afferent fibres, so that, when the incision is made into the region of the peripheral distribution of the nerve, not only is there no pain, but no sur- - gical shock, all nervous impulses going upward from the lower part operated upon being shut off from the nerve-centres. When the nerve is small and easily reached, the injection of a two per cent, solution of cocaine may be made into its sheath without previous incision ; but when an amputation or other large operation is to be performed, it is essential to expose under infiltration-anaesthesia the one or more nerves involved, and inject a solution of cocaine, which should not be stronger than one per cent. , directly into the centre of the nerve. When neural anaesthesia is practised, it is essential that the most absolute antiseptic precautions be taken. A priori, it might be expected that the process would involve the danger of the production of neuritis, but so far the clinical reports do not indicate that such danger exists. REFERENCES. ANAESTHETICS. 14 CARTWRIGHT . . Lancet, 1876, 689. i. NEUDORFAN . . . B. M. J., 1896, i. J5 QTTLEY Lancet, 1883, i. 95. NITROUS OXIDE. j6. THOMSON and KEMP . N. Y. M. R., 1898, ii. i. HERMANN . . . . A. A. and P., 1864. 17. WOOD T. G., Aug. 1890. a. JOLYET and BLANCHE . A. de P., July, 1873. 18. LE BRETON . . . P. M. J., 1902, ix. 586. 3. COLTON The Physiological Action of Nitrous Oxide Gas, ETHER. Philadelphia, 1871. i. KRATSCHMER . . W. A. W., 1870, Abt. ii. 4. THOMSON .... P. M. T., Nov. 15, 1873. 2. HARE U. M. M., i. 419. 5. WOOD Dental Cosmos, May, 1893. 3. KNOLL W. A. W., Oct. 1876. 6. MACMUNN. . . . The Spectroscope in Medi- 4- KRONECKER . . . C. B. S. A., 1890. cine, London, 1880. 5. EULENBERG . . . H. S. Jb., 1883, 117. 7. AMORY N. Y. M. J., Aug. 1870. 6. BERNARD .... Prog. M., 1876, 77. 8. GOLDSTEIN . . . A. G. P., xvii. 7- WOOD U. M. M., July, 1898. 9. VAN ARSDALE . . A. J. M. S., cii. 8. FLOURENS . . . . C. R. S. B., 1847, xxiv. 161 10. HEWITT M. C. Tr., Ixxxii. et at. 11. KEMP B. M. J., 1897, ii. 9- LONGET A. G. M., 4 s., xiii. 374. 12. MACMUNN. . . . D. J. M. S., 1879, 210. 10. WALLER B. M. J., Nov. 20, 1897. 13. BUXTON Trans. Odontol. Soc. of ii. CONLY C. R. S. B., Feb. 13, 1876. Great Britain, 1887, xix. 12. LOCKE J. Ex. M., 1896, i. ANESTHETICS. 123 REFERENCES. Continued. 13. SANSOM Chloroform, Phila., 1866. 14. BOWDITCH and MINOT . B. M. S. J., May, 1874. 15. WITTICH . . . . S. Jb., cxlii. 212. 16. SCHMIDT . . . . V. A. P. A., 1864, xxix. 19. 17. SERRES A. G. M., 4 s., xiii. 433. 18. WRIGHT J. P., 1901, xxvi. 30. CHLOROFORM. 1. BENEDICENTI . . G. A. M. T., 1895, 378. 2. SIOLFATTI .... Rif. M., 1895, i. 591. 3. ZKLLER Z. P. C., viii. 74. 4. SABARTH .... Das Chloroform, Wiirz- burg, 1866. 5. NOEL L. M. R., 1877, 457. 6. SIMONIN Cb. C., 1877, 234. 7. WOOD U. M. M., July, 1898. 8. BERT . . . . . . C. R. S. B., 1867, Ixiv. 9. BERNSTEIN . . . S. Jb., cxlii. 227. 10. ENGLISH CHLOROFORM COMMITTEE . Proc. Royal Med. Chir. Soc., London, xlviii. 326. 11. GASKELL and SHORE . B. M. J., 1893, i. 12. BOWDITCH and MINOT . B. M. S. J., 1874. 13. Ed. M. J., 1842. 14. J. A. and P., xiii. 226. 15. MACWILLIAM . . B. M. J., 1890, ii. 16. BERT J. del'A. and P., May, 1870. 17. BERT C. R. S. B., July, 1885. 18. ST .-MARTIN ... La Respiration, Paris, 1893. 19. HARLEY P. P. S. L., 1865. 20. BOETTCHER . . . V. A. P. A., xxxii. 126. 21. SCHMIDT and SCHWEIGER-SEIDEL . Bericht. d. konigl. sachs. Gesell. d. Wissensch., math.- phys. Kl., 1867, 190. 22. KAPPELER . . . . A. K. C., 1887, xxxi. 23. BERNSTEIN . . . U. N. M. T., 1870. 24. LEYDEN Beitr. z. Path. d. Icterus, Berlin, 1866. 25. NOTHNAGEL . . . B. K. W., i866. 26. HUSEMANN . . . S. Jb., cli. 84. 27. KAPPBLER .... Die Anaesthetica, Stutt- gart, 1880. Z. P. C., viii. V. A. P. A., cxv. C. M. W., 1888. Fort. M., 1891, ix. V. A. P. A., 1892, cxxx. B. M. J., 1882, i. 776. An. d'H., Jan. 1874. E.G. T., xciii. 433. N. Y. M. R., July 11,1885. . J. A. M. A., 1901, xxxvi. 1409. 38. BLAUEL B. K. C., 1901, xxxi. 271. 39. TUNNICLIFFE and ROSBNHEIM . P. P. S. L., 1903. 40. EMBLEY . . . . B. M. J., 1902. 41. KRUGER Z. C. P. P., 1902, iii. 42. SHERRINCTON and SOWTON . B. M. J. Supp., 1903, ii. ETHYL CHLORIDE. 1. WOOD and CERNA . Tr. P. C. M. S., 1892. 2. LEBET In. Diss., Berne, 1901. 3. MALHERBE and ROUBINOVITCH . B. M., June, 1902. 4- WARE N. Y. M. R., 1901, lix. 5. ALLEN A. J. M. S., Dec. 1903. 6. GlFFORD . B. M. J. July 8, 1905. 28. SOKOLOVSKI . . . Z. 29. STRASSMANN . . V. 30. STRASSMANN . .C. 31. SALKOWSKI . . .F< 32. BERTELS. . . . . V. 33- B. 34. DOLBEAU . . . . Ai 35- B. 36. N. 37. PAUGH J. ETHYL BROMIDE. 1. Th. M., 1889, iii. 2. T. G., viii. 3. GILLES B. K. W., 1892, xxix. 4. THORNTON and MAXWELL . T. G., 1892. 5. ABONYI Wiener Klinik., 1891, No. i. 6. GLEICH W. K. W., 1892, v. 7. SUAREZ DE MENDOZA . B. A. M., 1894. 8. REICH Th. M., 1893. 9. FLATTEN . . . . Z. Mb., 1897, No. 7. 10. WOOD P. M. T., 1879-80, x. 11. GINSBURG .... In. Dis., St. Petersburg. 12. COLE B. M., 1903, i. PENTAL. 1. PHILIPP A. K. C., 1892, xlv. 2. CERNA Trans. Texas State Med. Ass., 1893. 3. GURLT A.-K. C., 1893, xlvi. METHYLENE BICHLORIDE. 1. RICHARDSON . . M. T. G., 1867, 478. 2. B. M. J., 1883, ii. 104. PRACTICAL ANAESTHESIA. 1. COATS Gl. M. J., xxxiv. 323. 2. GOULD M. News, Oct. 1892. 3. GARREE B. K. Ch., 1894, xi. 4. GURLT . .'. . . A. K. C., Iv. 473. 5. EVANS N. Y. M. R., 1897, i. 6. MACWILLIAM . . B. M. J., 1890, ii. 7. LANCET COMMISSION . Lancet, 1893, i. 8. WOOD and CARTER . J. Ex. M., 1892, ii. 9. HOLSCHER . . . A. K. C., 1898, Ivii. 10. BECKER V. A. P. A., 1895, cxl. 11. DUMERIL and DEMARQUAY . A. G. M., 1848, 2 s. xvi. 12. BOUISSON .... Trait6 th6orique et pra- tique de la Methode anesthdsique, Paris, 1850. 13. SULZYNSKI . . .In. Dis., Dorpat, 1865. 14. SCHEINSON ... A. Hk., 1869. 15. DUBOIS Prog. M., 1883, xi. 951. 16. HOLMES Chi. M. J., Sept. 1868. 17. PRINCE N. Y. M. R., 1892. 18. GOMBERG . . . . D. Z. Ch., xxxix. 19. PATH P. M. C. P., 1887. 20. STRASSMANN . . V. A. P. A., cxv. 21. OSTERTAG . . . . V. A. P. A., cxviii. 22. KAST and MESTER . Z. K. M., 1891, xviii. 23. TEDESCHI . . . . Cl. M., 1897, iii. 24. BOTSCHAROFF . . In. Diss., Kiew, 1893. 25. FRAENKEL . . . V. A. P. A., cxxvii.,cxxix. 26. BANDLER . . . . S. Jb., cclii. 27. AMBROSIUS . . . V. A. P. A., Suppl. 1895. 28. SCHENCK ... Z. Hk., 1898. 29. EISENDRATH Chicago Med. Rep., 1896, x. 30. DESGREZ and NICLOUX . C. R. S. B., 1898, 274. 31. PRUS W. K. W., 1900. 32. KEEN T. G., 1904. 33. GUTHRIE . . . . L. L., 1903, ii. 34. WOOD Trans. International Med. Congress, Berlin, 1881. 35. SCHMIDT . . . . A. A. P., 1897. 36. OFFERGELD . . . A. K. C. 1904, Ixxv, 758. 37. CARMICHAKL and BEATTIE . Lancet, Aug. 12, 1905- 124 GENERAL REMEDIES. REFERENCES. Continued. 38. SriLESand MACDONALD . Scot. Med.Surg.J. 8. Aug. 1904, p. 97. 9. 39. MULI-EK A. K. C. 1905, Ixxv, 896. 10. 40. BRACHETT STONE and Low . B. M. S. J. cli, n. p. 2 12. 41. SENCERT . . . . C. R. S. B. 1905, Iviii, 1080. 13. 14. LOCAL ANAESTHESIA. 1. VINCI Th. M., June, 1896. 15. 2. VINCI A. I. B., 1899, xxxi. 32. 16. 3. VER EECKE . . . B. A. R. B., 1897, x. i. 4. SPENCER . . . . U. M. M., 1896. 17- 5. SCHWARZ . . . . M. M. W., 1902, xlix. 18. 6. NEUGEBAUER . . W. K. W., 1901, xiv. 19. 7. RITSERT S. J., Bd. cclxxix. 20. BRAUN A. K. C., 1903, Ixix. BARKER L. L., July, 1903. BIER D. Z. Ch., li. 3. SELDOWITSCH . . Ch. C., 1899, xxvi. mo. TUFFIER .... P. M. J., Dec. 1899. MOHR-BlELEFELD . M. W., 1902. HALL and HALSTEAD . N. Y. M. J., Dec. 1884. EINHORN and HEINZ . . M. M. W., xlviii. LUXENBURGER . M. M. W., 1899; P. M. J., July, 1899. GANT N. Y. M. J., Jan. 1904. TUFFIER . . . . W. K. W. 1905, 377 IMPENS D. M. W. 1905, xxxi, 1154. SEIFERT . . . . D. M. W. xxxi, 1352. FAMILY III. SOMNIFACIENTS. IN the family somnifacients are placed in this treatise those drugs whose chief use in practical medicine is for the production of sleep. Hyoscine is a valuable hypnotic, but as it is found in plants associated with the delirifacient alkaloids, and is physiologically more closely allied to them than to the opium alkaloids, it will be considered under the head of Delirifacients. OPIUM. U.S. The inspissated juice of the unripe capsules of the Papaver somni- ferum, or poppy. It is obtained by incising the capsules with a small, sharp knife, and twenty-four hours afterwards scraping off the exuded juice with a blunt blade. Opium is produced in various parts of the world, chiefly in Turkey, Asia Minor, Persia, and India, but also to a very slight extent in England, Germany, and the United States. Our market is almost exclusively supplied from Asia Minor, with the variety known as Smyrna or Turkey Opium. This occurs in masses from the size of the fist to that of a child's head, irregularly globular, more or less flattened, covered externally with the capsules of a species of Rumex or dock, hard externally, softer and of a reddish-brown color within, and of a strong narcotic odor and taste. On exposure to the air, opium becomes hard and brittle, and is readily reduced to a powder of a yellowish-brown color. It yields its principles to water, alcohol, and diluted acids, forming dark brown solu- tions. It is a very complex body, containing the alkaloids morphine, codeine, narceine, narcotine, thebaine, papaverine, porphyroxine, crypto- pine, meconine, opianine, and paramorphine, besides meconic, thebolactic, and sulphuric acids, extractive matter, gum, glucose, fixed oils, a volatile odorous principle, and other substances of no importance. Local Action. The local action of opium and its chief alkaloid ap- pears to be purely sedative. Elimination. After its absorption morphine probably passes into all the secretions ; after its hypodermic administration it has been detected in the gastric juice by Orlt, 1 and in the saliva by Rosenthal,* but it largely escapes with the urine, in which it has been found by Hilger ( quoted by Gscheidlen), Bouchardat, 3 Lefort,* Kausmann, 5 Eliasson, 6 and Wormley. 7 According to Faust, 11 the most important channel of elimina- 125 126 GENERAL REMEDIES. tion is the alimentary tract ; it is to some extent excreted by the salivary glands as well as the mucous membrane of the stomach and bowels, to be probably reabsorbed. This has been proved not only by experiments upon animals in which the morphine was injected subcutaneously, but also in the human individual (Rosenthal, 8 P. Binet, 9 Hamburger 10 ). Elimination probably goes on slowly, as Wormley detected the alkaloid in urine passed three days after its ingestion, and in habitual opium-eaters morphine may be present in the urine seven days after the cessation of the habit. 11 A. Antheaume and A. Mouneyrat 12 detected morphine in the body of an opium-eater who had died fourteen days after the last dose. It was found most abundantly in the liver, next in the brain, next in the kidneys. Without doubt a considerable portion of morphine escapes from the body un- changed, but, according to Cloetta, 59 from fifty to seventy per cent, is destroyed in the body. The theory advanced by E. S. Faust, 13 that the immunity produced by the habitual use is due to increased power of the body to destroy morphine, has been shown by Cloetta, however, to be untrue. PHYSIOLOGICAL ACTION. When opium is taken in such dose as to produce its mildest physiological effects, it exerts a quieting influence, inducing a peculiar dreamy condition of bodily comfort and happy con- tent, during which images and ideas float before the mind, and by their endless and effortless repetition shorten the time, which seems to lose itself in rest. It is commonly asserted that there is a stage of the action of opium in which the activity of the mental faculties is exalted. This may be so in some persons, and especially in those who have accustomed themselves to the use of the drug as a stimulant ; but our experience is that in those who do not habitually take opium true mental power is, during all the stages of the action of the drug, diminished rather than in- creased. The state induced is the fabled calm of the lotus-eater rather than the energetic activity of production. Even in those who are accus- tomed to the use of opium as an aid to work, it is probable that the imagi- nation rather than the reasoning faculty is excited by it. After a length of time, varying according to the idiosyncrasies of the patient and the dose of the drug, the condition which has been noted gradually passes into sleep, either light and dreaming, or natural, or heavy and deepening into stupor, according to the amount of the drug ingested. On awaken- ing, the patient may return at once to his normal condition, but very often he experiences a state of depression, as shown by languor, a little headache, nausea, or even vomiting, which may last for some hours. After very large doses, the first stage of the action of opium is very short, or it may be entirely wanting, sleep coming on almost at once. Thus, we have seen deep coma produced in three minutes by a hypo- dermic injection of morphine. The symptoms of the second stage of opium -poisoning closely resemble those of congestion of the brain : the pupils are strongly contracted ; the face is more or less suffused, often SOMNIFACIENTS. 127 deeply cyanosed ; the pulse full, slow and strong ; the skin generally dry and warm ; the respiration slow and deep, and, it may be, sterto- rous ; unconsciousness is apparently complete, though generally the sub- ject can be aroused by violent shaking or by shouting in his ear, but relapses at once when left to himself. When the patient is aroused, the respirations become more rapid, and the skin often regains almost at once its normal color. Death very rarely occurs during this second stage of opium-poisoning. When the symptoms do not gradually amel' iorate, the third stage, that of prostration, is developed. The coma is now profound, and to arouse the patient may be impossible ; the pupils are absolutely contracted or, as death approaches, are widely dilated ; the respirations are distant, slow, feeble, and imperfect, and often inter- rupted by intervals of death-like quiet ; the countenance is at once pallid and cyanosed ; the pulse continually grows more rapid and more feeble ; the cold and moist skin finally becomes covered with a clammy sweat. Even yet the patient may recover j the return to life being very gradual ; when death occurs, it is by failure of the respiration, but amid an almost complete extinguishment of the vital functions. Although the symptoms which have been narrated are those usually produced by opium, yet in certain individuals the drug provokes quite different phenomena. Thus, not infrequently there is an excessive de- pression following the opiate sleep. This state is seen most frequently in neuralgic or neuropathic females. The symptoms are a feeling of weakness and prostration, often accompanied by chilliness, dull headache, and giddiness, but especially marked by intense nausea and repeated vomit- ing. Very frequently vomiting does not take place so long as absolute rest in the horizontal position is maintained : indeed, an almost diagnostic sign of this affection may be found in the fact that the stomach is quiet so long as the patient keeps the head upon the pillow, but the distress occurs at once upon rising up. In some cases this condition of depression even replaces the normal second stage, so that opium, instead of inducing quiet sleep, will provoke alarming depression and vomiting, either with or without drowsiness. Thus, cases have been reported in which one- fourth of a grain, or a somewhat greater quantity, of morphine, hypo- dermically injected, has been followed at once by syncope, with strug- gling for breath, and apparently imminent or even present death.* A rarer idiosyncrasy exists in those persons who are rendered by opium very delirious, it may be even wildly so. In certain cases of opium- poisoning, partial or complete convulsions have occurred amidst the more usual phenomena, f Severe itching of the skin is a common phenomenon when the action of opium is going off, and there are persons in whom such violent erythema is produced even by therapeutic doses as to forbid * See Report of the Committee on the Hypodermic Method of Injection, Medico-Chi- rurgical Transactions, i. ; see also Medical Times and Gazette, 1868, cases reported by Braine and by Roberts. t Cases, Brit. Med. Journ., 1876, ii. 496 ; Pacific Med. and Surg. Journ., July, 1876. 128 GENERAL REMEDIES. the use of the drug (case, Wien. Med. Presse, xxiv. 568) ; R. V. Jaksch 14 reports temporary blindness as produced by opium. Glycosuria has been noticed both in animals and man ( Adler ; l5 also Luzzatto l7 ). Opium appears to act so differently upon the lower animals than upon man that it seems necessary to discuss the former action by itself. As long ago as 1826 Charvet 16 stated that opium in the invertebrata causes pro- gressive loss of power in the contractile tissue, ending in death ; in fishes, paralysis and convulsions ; in birds and mammals, paralysis, convulsions, and stupor. In the frog, opium and morphine act similarly, producing primarily a condition of violent tetanus, with great increase of the reflex activity, ending, if the dose have been large enough, in a progressive paralysis with disturbed respiration, and finally cessation of the same. W. Baxt 18 states that when a very minute dose is used (15.25 milligrammes) after a period of heightened excitability there is stupor with in- creased reflex excitability as it passes off. As was first shown by Kolliker, and abundantly demonstrated since, the tetanus is not prevented by section of the spinal cord, and, with the heightened reflex activity, is therefore due to spinal excitement. It is probable, however, as affirmed by Kolliker, 19 by Albers, 2 " and by Meihuizen, 21 that some of the convulsions are epileptiform. Albers states also that convulsive movements occur in limbs after section of their nerves, a fact which seems to us very doubtful. S. Weir Mitchell 72 has shown that birds, as represented by pigeons, chickens, and ducks, are very insusceptible to the toxic action of opium and its chief deriva- tive, morphine. It appears to be impossible to kill a pigeon by opium given by the mouth, and of morphine from eight to fifteen grains are required to produce a fatal result ; but when given hypodermically from two to three grains of the alkaloid suffice. The symptoms induced have been very uniform : they are unsteadiness, labored breathing, increasing signs of dyspnoea, unaltered pupils, and, finally, gen- eral convulsions and death. No true hypnotic effect has been observed, but a curi- ous and very great rise of temperature just before death was noted in one case. As Flourens affirms that a single grain of the aqueous extract of opium will throw a sparrow into a profound stupor, it can scarcely be considered as proved that the drug acts upon all birds as upon those experimented with by Mitchell. According to M. L. Gurnard, 2 " in the cat morphine produces violent hyper- excitability', great restlessness, agitation, hallucinations, dilated pupils, accelerated heart and respiration, from which the animal returns to its normal condition unless the dose have been very large, when tetanic convulsions develop. Upon dogs* morphine acts very much as upon man.t In very many cases, if not in the majority, eight to ten grains of the alkaloid injected into a dog of mod- erate size will cause deep sleep, amounting to coma, so that the animal will remain in any position in which he may be placed. The length and depth of this sleep are, of course, proportionate to the dose : when at all profound, it is accompanied by marked insensibility to pinching and other forms of external irritation. A repe- tition of irritation, and especially a sudden loud noise or shaking, will, however, arouse the animal, precisely as in man. Indeed, sometimes the dog, even when comatose, seems more than normally sensitive to sudden noise, trembling and starting in an almost convulsive manner. After awaking, the dog shows unmis- * According to JofTroy and Serveaux (Archiv d. Med. Exfter. Anal. Path., 1898, x.), the fatal dose of morphine is : for dogs, intravenously 0.029 gramme per kilo, hypodermi- cally 0.035 per kilo ; for rabbits, intravenously 0.15 per kilo, hypodermically 0.25 per kilo. t Harley, The Old Vegetable Neurotics, 107, London, 1869 ; Claude Bernard, Ar- chives Generates, ii. 437, 6th series, 1864 ; J. I. Reese. American Journal of the Medical Sciences, Jan. 1871. SOMNIFACIENTS. 129 takable signs of nervous and psychical depression. In walking, the hind legs are dragged, as though semi-paralyzed ; the eyes are haggard ; the naturally brave animal cowers in a corner or seeks to hide himself, no longer recognizing his mas- ter, and does not return to his natural condition for many hours. After smaller doses the effects are proportionately less intense. It has been shown by Harley that in some dogs, precisely as in some people, morphine fails to exert its usual hypnotic action, but produces great depression, as evinced by faintness, prolonged nausea, and retching, interrupted only by intervals of dreamy delirious somnolency. In the horse (Harley) two or even three grains of morphine hypodermically injected produce sometimes a slight drowsiness, sometimes no perceptible effect. Doses of from four to six grains cause great restlessness and accelerated pulse. The mouth is moist, the temperature of the skin and its secretion increased ; the animal paws continually, and treads about in his stall with an almost rhythmical movement. After twelve grains, Harley noticed in some cases very great excite- ment, as shown by marked increase in the rapidity of the heart's action, by mus- cular rigidity and tremors, and by the animal's walking rapidly to and fro, slobber- ing and sweating profusely. In another horse, after an immediate strong erection of the penis and copious emission of semen, heavy sleep came on, interrupted after the third hour by the usual symptoms of excitement. Thirty-six grains of mor- phine acetate caused in a powerful hunter deep comatose sleep, commencing in fifteen minutes and lasting for three hours, when it was replaced by intense restless- ness and severe delirium, continuing for seven hours. During this time the animal was perfectly blind. Previously to these studies, Barbier had found that four drachms of the aqueous extract of opium produced violent tremblings, apparent insensibility to external irritants, convulsions without coma, and death. One hun- dred grains of morphine acetate killed a horse by convulsions in three hours. Ernst . Hess M has shown that in the ruminants morphine produces first excitement and then narcosis. In the mouse, according to the experiments of Harley, the first effect of an injection of from one-twentieth to one-twelfth of a grain of morphine is a tonic cramp-like contraction of the muscles, especially of the trunk, of such character that periods of forced rest alternate with a slow, laborious creep, which seems to originate not in the limbs but in the trunk itself. There is in this state no tendency to somnolency, but, on the contrary, an abnormal sensitiveness to loud sounds, which cause the mouse to resume for a moment active running movements. The breathing is irregular, the pulse accelerated, and finally stupor develops itself, and coma deepens into death by dyspnoea ; or, otherwise, recovery, preceded by con- vulsive movements of the hinder part of the body, is gradually brought about. In reviewing the action of morphine upon the lower animals, it becomes very evident that two classes of phenomena are everywhere dis- cernible, i.e. , the spinal and the cerebral, and that the higher in the scale of life any given animal may be the more marked are the brain- symptoms. These cerebral phenomena are mostly sleep and stupor ; but, as is well known, in some human individuals morphine acts as a delirifacient ; and it seems very probable that the peculiar restlessness of the horse under the influence of the alkaloid is due to delirium, and not to spinal excitement. When looked at in this manner, it seems to us that morphine does not act so differently as has been generally asserted upon the lower ani- mals and upon man. The immensely higher cerebral organization of the latter, with the immensely greater sensitiveness which it involves, makes the man correspondingly more susceptible to the cerebral action of the 130 GENERAL REMEDIES. drug : hence not only is he affected by much smaller doses of the alka- loid than are the lower animals, but as the spinal symptoms are trium- phant in the frog because its spinal system is vastly more developed than its cerebral, so in man the cerebral symptoms mask the spinal because in him the brain is more developed than the cord. The two creatures man and the frog occupy the two extremes of the series ; between them is probably to be found every gradation.* The action of opium upon dogs and rabbits is sufficiently close to that upon man to enable us to reason from experiments upon the former as to the influence of the alkaloid upon the circulation and respiration in the latter. Indeed, so far as these functions are concerned, morphine appears to act identically in both instances. Action on the Nervous System. The cerebral symptoms produced by opium are without doubt due to a direct influence of the drug upon those cells which preside over intellectual action and consciousness. Opium is frequently spoken of as a cerebral stimulant, and some of the world' s most famous writings have undoubtedly been produced under its influence. It appears, however, to be especially related with those tissues that are connected with imagination, so that it is the imagination rather than the reasoning functions which is affected by it. In this respect it is not so true an intellectual stimulant as is caffeine. It is undoubtedly a stimu- lant to the spinal cord ; but, as has already been shown, the cerebrum in man is so infinitely more susceptible to its influence than is the spinal cord that this spinal effect is rarely perceptible in man, even in toxic dose. Nerves. According to Gscheidlen, 28 morphine primarily increases and secondarily depresses the excitability of the motor nerves of the frog, the period of heightened functional activity not being demonstrable after enor- mous doses. Albers 20 affirms that depression may develop into com- plete paralysis of function, though Gscheidlen has never been able to verify this. Gscheidlen further asserts that the local application of morphine intensifies and protracts the excitability of an afferent nerve in strychnine- poisoning. No phenomenon of human poisoning by opium can be attrib- uted to its action on nerve-trunks, but the relief of pain sometimes obtained by the local use of opium would indicate that in concentrated form it depresses the sensory fibres even of human nerves. Action on the Circulation. In man the circulatory phenomena are a slight primary evanescent acceleration of the pulse-rate (see Nothnagel - 5 ), succeeded by the characteristic slowing and increased fulness and force of the pulse, which is followed by a return to the normal pulse, or a great increase of rapidity and loss of strength, during the third stage. Gscheidlen has found in rabbits and dogs after the injection of morphine, first an increase in the pulse-rate, then a decrease, and finally return to * A curious corroboration of the views expressed in this paragraph is found in the fol- lowing sentence taken from Althaus (Diseases of the Nervous System, New York, 1878, 135) : " In infants, however, and also in the lower races of mankind, as in negroes and Malays, convulsions are observed after its [opium] ingestion." SOMNIFACIENTS. 131 the normal pulse, or else increased rapidity. Sphygmographic studies of the effects of small doses of morphine have been made with various results by several observers : undoubtedly in some individuals therapeutic amounts of the alkaloid depress sensibly the circulation, but, in agreement with Riegel and Preisendorffer, 26 it can scarcely be doubted that therapeu- tic doses have no sensible effect upon the circulation in the ordinary man. It has been found by M. L. Guinard 27 that in the dog morphine produces primarily a slight rise of the arterial pressure, followed by a fall during the period of narcosis. The slow, full pulse of the second stage of opium -poisoning is due to an action of the drug upon the inhibitory cardiac nerves, as may also possibly be in some manner the increased arterial pressure ; for Gscheid- len has experimentally demonstrated that after section of the vagi mor- phine is powerless to lower the pulse, and also that division of the nerves during the second stage of morphine-poisoning is followed by an extra- ordinary rise in the pulse-rate. That the peripheral ends of the vagi are stimulated was proved by the fact that cardiac arrest took place when the distal ends of the cut nerve were more feebly irritated than would suffice to affect the unpoisoned animal ; and that the inhibitory cerebral centres are stimulated was demonstrated by the instantaneous very great fall of the pulse-rate, amounting in some cases to one- half in less than half a minute, which ensued upon the injection of a large dose of the alkaloid into the carotid, i.e. , into the brain and the inhibitory centres. The rapid feeble pulse of the third stage of opium-poisoning Gscheidlen found to be due, at least in a measure, to paralysis of the peripheral vagi ; for at such time stimulation of the peripheral end of the cut nerve was powerless to affect the heart. The experiments of Gscheidlen also indicate that morphine exerts first a slight stimulating, then a depressing influence upon the heart-muscle or ganglia, since, after isolation of the viscus by section of the cord, sym- pathetic, and pneumogastric, life being sustained by artificial respiration, a large dose of morphine induced a momentary increase in the number of the cardiac contractions, followed by a marked decrease and finally extinguishment of the same. This conclusion is confirmed by Ringer and Sainsbury, 25 * who found that opium first increased the power of the cut- out heart of the frog, then depressed it, and finally caused diastolic arrest. The question of the action of morphine upon the vaso-motor system is of great interest, but cannot at present be fully answered. Gscheidlen believes that it first stimulates and then depresses it, and asserts that after the injection of a large dose the arterioles in the mesentery can be seen to contract, and later (third stage) to dilate. The objections to this sort of evidence are sufficiently stated elsewhere in this book ; and the rise of the arterial pressure, which he also adduces as an argument, may be accounted for without calling upon the aid of the vaso-motor nerves. While, therefore, it is probable that morphine does exert the influence he asserts for it, the question must still be considered as sub I 3 2 GENERAL REMEDIES. judicc : that the vaso-motor system is not paralyzed even in extremis is shown by Gscheidlen's experiment, in which electrical stimulation of the cord at such time induced immediate rise of the arterial pressure. The action of morphine upon the brain is certainly independent of any action on the vessels.* Action on the Respiration. Death occurs from opium, in the great majority of cases, by failure of the respiration ; and that such failure is due to a direct action of the poison upon the respiratory centres in the medulla is proved by the fact that morphine affects the breathing of dogs and rabbits whose pneumogastrics have been cut as much as it does those whose nerves are entire (Gscheidlen). The action of opium or morphine upon the elimination of carbonic acid has been studied by Boeck and Bauer * and by Chittenden and Cum- mins.* 1 Their results are concordant in showing that the effect of the alkaloid upon carbonic acid production is in direct relation to its influence upon the muscular system. The elimination is increased when convul- sions occur, but decreased when narcotic quietude is produced. Accord- ing to Reichert, 12 the fall of temperature produced by the toxic dose of morphine is caused by a lessening of heat production, which is due to depression of thermogenic centres in the caudate nucleus. Luzzatto 60 found that under the influence of morphine there is a very marked increase in the destruction of nitrogenous tissue. Action on the Pupil. Since morphine locally applied does not affect the pupil, it follows that its contracting action upon the latter is through the nerve-centres. It is probable, but has not, that we are aware of, been experimentally proved, that the contraction of the pupil is, at least, largely due to stimulation of the oculo-motor nerve-centres, and that the-dilatation of the pupil as death approaches is due to a paralysis of the same. Indeed, it cannot well be otherwise ; for if the primary contraction were due to paralysis of the sympathetic, the secondary wide dilatation would be im- possible ; the dilating force i.e. , the sympathetic having been with- drawn, the pupil would not widely expand even if the contracting force i.e. , the oculo-motor were paralyzed. In birds (S. Weir Mitchell) the pupil is not affected, probably for anatomical reasons (see Atropine}. In horses it is widely dilated (Harley) ; and in dogs it dilates before contracting (Reese, apparently confirmed by Experiment No. 8, Har- ley), or sometimes remains unchanged (Harley). At present these anomalies can- not be explained. Secretions. Opium ordinarily checks all the secretions of the body, although this influence is capable of being modified by certain drugs so as to produce a sudorific action. By it the urinary secretion is habitually diminished, owing, as has been shown by Thompson, 33 to a direct action upon the kidneys. Retention, which after a full dose of opium is not rare, depends upon the blunting of the sensibility of the bladder. * Consult Binz, Arch. f. Exper. Pathol. und Pharm., vi. 310; Vulpian, Lcqons sur VAppar. vaso-moteur, ii. 156. SOMNIFACIENTS. 133 Intestines. Opium, and to a less extent morphine,* has a very pro- nounced influence upon the digestive tract, in many persons producing nausea, in all lessening the appetite and the activity of digestion and causing constipation. The disorder of digestion and the constipation are in part, at least, due to an arrest of secretion, probably both in the stom- ach and in the intestines ; but they are also probably to some extent due to the checking of peristalsis, an effect which can often be shown in men, and which Nothnagel 34 and Ott 35 have demonstrated upon animals, f Both Nothnagel and Ott affirm that the toxic dose of morphine in the lower animals increases peristaltic movement, which affords a pos- sible explanation of the diarrhoea sometimes seen in chronic opium-eaters. The checking of peristalsis appears to be due to stimulation of the inhibitory nerve apparatus ; the increase to paralysis of the same. SUMMARY. Opium is a cerebral stimulant, whose action soon passes into sedation and the production of sleep, and has the power of relieving pain in some -way as yet not thoroughly known ; probably, however, by benumbing the perceptive centres in the brain. It acts upon the spinal cord of many of the lower animals as a stimulant, but in man its influence is not perceptible. It both slows the pulse and in- creases to some extent the force of the circulation by an action upon the inhibitory nerve-centres, probably both centric and peripheral, and by a slight stimulant influence upon the heart-muscle or its intrinsic ganglia. It is a centric respiratory depressant ; it contracts the pupil by a centric action which is probably that of stimulation of the oculo- motor nerve-centres. THERAPEUTICS. The chief indications for the use of opium are con- sidered below, seriatim. Nearly all of them flow evidently from the known physiological action of the drug ; others, however, although established by clinical experience, and undeniable, are not so plain in their philosophy. 1. To relieve pain. As an analgesic, opium is without a rival in the materia medica, except it be the anaesthetics. It is used to allay pain arising from any cause whatever, except acute inflammation of the brain, and is preferred to the anaesthetics whenever the pain has any permanency. In painful spasm it is especially useful, as it seems very frequently to quiet the motor as well as the sensory disturbance. 2. To produce sleep. Sleeplessness occurring in acute disease, and not dependent upon cerebral inflammation, may very frequently be re- lieved by opium. While it is often necessary to use the drug freely in such affections as delirium tremens, care should be exercised not to over- whelm the nerve-centres by enormous doses. In habitual sleeplessness * Vamossy (Deutsche Med. Wochensch., 1897, xxiii.) has endeavored to determine experimentally why opium causes constipation more than does morphine. He finds, however, that neither narcotine, thebaine, codeine, kryptopine, nor laudanine is equal in power of checking peristalsis to morphine ; and that it is not probable that any of them are responsible for the constipating effects of the crude drug. t The theory of Hirsch, that morphine causes contraction of the pylorus, is very im- probable, since, granting the correctness of his experimental results, a more probable explanation is that gastric peristalsis is checked by the alkaloid. 134 GENERAL REMEDIES. great caution must be used in the employment of opium, not so much on account of the disturbance of digestion which it is liable to cause, as for fear of producing the ' ' opium habit. ' ' Chloral is perhaps a more generally applicable hypnotic than opium. Be this, however, as it may, we have found the combination of morphine and chloral singularly effi- cient. In low fevers, adynamic delirium often coexists with sleeplessness, and is then best met by opium. 3. To allay irritation. In various forms of nervous erethism, opium is most valuable ; but when the affection is at all chronic, the dangers of the opium habit should not be lost sight of. On the other hand, in acute cases, as in the excitement which so frequently attends hemoptysis, the drug should be used freely. In many cases of disease, opium is serviceable by sustaining the system against an irritation for the time being irremediable, by blunting the sensibilities. In this way it is useful in the advanced stages of small-pox, and in various surgical affections, in which it also does good by allaying pain. In various local irritations opium is continually employed, as in colic caused by undigested food, and in bronchitis to quiet cough. By allaying irritation and pain, opium affords relief in most cases of inflammation ; but in certain varieties of the affection it seems to do much more than this, exerting, in some way at present difficult to explain, a life-saving influence. In peritonitis, after due depletion, or in cases not requiring depletion, it should always be exhibited in large doses at regu- lar intervals, in such a way as to keep the patient in a state of decided narcotism. In severe acute vomiting, opium is one of the most reliable remedies. It is best used in the form of suppositories. Although, by checking secretion and peristalsis, opium usually causes constipation, yet when obstruction of the bowels is produced by spasm due to an irritation or inflammation, by relieving the latter the drug will sometimes act as a most efficient laxative. 4. To check excessive secretion. For this purpose opium is very largely employed in diarrhoeas, and is very efficient either alone or in combi- nation with various remedies. In enteritis and in dysentery, although no less frequently used than in diarrhoea, it is of service as an antiphlogistic and analgesic rather than by checking secretion. In diabetes insipidus, the combination of it and gallic acid has been much used, and is often effective. In true saccharine diabetes, opium is of very great value in many cases, often ameliorating the symptoms, and, in conjunction with re- stricted diet, sometimes even effecting a cure. Of course, however, like all other known remedies in this disease, it most frequently acts simply as a palliative. It must be given in large ascending doses, the patient for the time being indeed made an opium-eater, a procedure justified only by the fatal nature of the malady. 5. To support the system. Opium appears in low fevers, and in vari- SOMNIFACIENTS. 135 ous protracted adynamic illnesses, to afford actual support to the system in some way not as yet made out. This is especially the case when, from any reason, sufficient food to keep up life cannot be taken or retained. Opium is a valuable remedy for the purpose of protracting and rendering more comfortable life in the aged. When the bodily powers are failing, and various functional disorders are from time to time occurring, it is often possible to check, by the use of opium, attacks which, if allowed to obtain headway, would extinguish the flickering life. Further, in many cases of feeble very old and suffering people the habitual use of opium under careful restriction of the physician is not only justifiable, but necessary if life is to be maintained as long as possible. In such persons the danger of forming an opium habit which shall do injury is reduced to a minimum. 6. As a sudorific. In 1873 A. Loomis 36 stated that in acute urtzmia large hypodermic injections of morphine would control the convulsions, at the same time producing a profuse diuresis, which has been confirmed by Fiset." The method of treatment has been largely followed, in some instances with very happy effect, but in other cases has apparently pro- duced death. Whenever the kidneys are seriously diseased the free administration of opiates is attended by much danger, because the chief channel through which the opium alkaloids escape from the system is choked up. As a general sudorific opium is used almost exclusively in the form of Dover's powder. (See Dover's powder in Diaphoretics.) TOXICOLOGY. The positive medico-legal diagnosis of opium-poison- ing from the symptoms alone is not possible, even in the most character- istic cases, because the phenomena produced by cerebral congestion, apoplexy, and uraemia may be identical with those of opium-poisoning. Inequality of the pupils, which has been considered proof that a case is not narcotism, has been reported by Taylor 88 as present in poisoning. In atypical cases without a history, even the working diagnosis may be very difficult. The spinal symptoms may entirely overshadow the cerebral phenomena ; trismus, tetanic convulsions, tonic rigidity of the muscles, spastic gait, marked heightened reflexes, and ankle clonus have been reported as produced by the drug in the adult.* In children it is com- mon for the nerve-centres to be at once overpowered by the poison, so that the second stage may be very much shortened or entirely aborted, and collapse with unconsciousness develop almost at once.f Treatment of Opium- Poison. Tannic acid is feebly antidotal to mor- phine, but it has been entirely displaced by potassium permanganate, which rapidly destroys the alkaloid by oxidation. The allegation that potassium permanganate is capable of following morphine into the blood and there destroying it is, a priori, improbable, and it has been experi- mentally shown that the hypodermic injection of potassium permanganate * For cases, see Philadelphia Med. Journ., 1903, xiii. 497, 539, 613. t For discussion of effect on nursling and foetus when morphine is given to the mother, see Amer. Journ. Obstet., 1877. 136 GENERAL REMEDIES. in morphine-poisoning is futile. * Nevertheless, during the whole nar- cosis, there should be repeated administrations of potassium permanganate by the mouth for the purpose of destroying morphine excreted into the stomach. Besides the administration of the antidote, the indications in opium-poisoning are to evacuate the stomach, to maintain respiration, and to keep up the circulation when failing. The first of these indications may be met in two different ways : by an emetic, and by the stomach- pump or tube used as a siphon. There is often in narcotic poisoning great difficulty in getting an emetic to act, owing to the obtunding of the sensibility of the nervous system by the poison. For this and other reasons, so palpable as not to need mentioning, only a prompt stimulant emetic should be used. Antimony, on account of its depressing influence, should always be avoided. Mustard flour is almost always to be had at once, and is very efficient. A heaped tablespoonful stirred up in a tumblerful of warm water should be exhibited as soon as possible, and, if it fail to act in fifteen minutes, should be repeated ; if this fail, a powder of thirty grains each of zinc sulphate and ipecacuanha may be given, to be repeated at intervals of twenty minutes. Large draughts of warm water should be administered in the intervals, and also between the acts of vomiting, so as thoroughly to wash out the stomach. The stomach-pump f is of no value when the solid drug has been ingested, but, if at hand, is preferable to emetics when a fluid preparation has been taken, because of the prompt- ness and thoroughness of its results. To maintain respiration is the ultimate object of all the measures which are commonly undertaken for the purpose of arousing the system in opium- poisoning. Unconsciousness in itself is of no moment, but as it deepens the sensibility of the respiratory centres grows less, and con- sequently the involuntary breathing is less rapidly or less perfectly per- formed. More than this, when at all awake, a patient suffering from opium-poisoning can be made to supplement the almost suspended auto- matic breathing by voluntary respiration, and every effort to induce him to do this should be used. It is often surprising how an apparently un- conscious man can be made to breathe by a command shouted in his ear. * See Leedom Sharp ( Therap. Gaz., 1895) ; also E. Q. Thornton and Charles A. Holder (Therap. Gaz., 1897). f The siphon stomach-pump may be readily extemporized. It consists simply of an india-rubber tube three and a half to four and a half feet in length, of proper calibre, which is passed into the stomach. The external end being elevated, water is poured into it until the stomach is full ; then, without the tube being allowed to empty itself, the external end is dropped, when, of course, the flow of water is reversed. The value of strychnine as a respiratory stimulant in various forms of narcosis was first demonstrated in the laboratory by H. C. Wood, and subsequently cases were reported by Clara Dercum ( U. M. M., 1870) and others. In regard to the value of atropine, E. F. Bashford (A. I. P., 1901, viii.) confirms its usefulness in opium-poisoning ; whilst in a very elaborate paper E. T. Reichert (T. M., 1901) reaches the conclusion that very frequently the overdosing of cases of morphine- poisoning with atropine has contributed to the fatal result, and that it is only of use as a respiratory and stimulating agent before the third stage of the poisoning is reached ; and further, that, on account of its in many ways synergizing with morphine, it is dangerous when given in overdose. In these conclusions Reichert seems to us correct. SOMNIFACIENTS. 137 To keep a patient awake, walking, flagellations with small, fine twigs, shaking, shouting, and various other methods which may suggest them- selves, should be practised. Care should always be exercised not to carry these useful measures unnecessarily far, and perhaps add physical exhaustion to the natural prostration of the third stage. The strong faradic current offers a means of causing pain, and therefore of rousing the patient, without leaving bruises or other after-effects. The cold douche is also an excellent method of rousing the patient and at the same time of especially stimulating respiration. The simplest method of application is to support the head and shoulders of a patient stripped to the waist over a common wash-tub, and to dash the water over the chest and head. The effect is much greater if ice-cold water and water a little hotter than the hand will bear (115 F. ) be used in quick succession. Very strong coffee has been used from time immemorial, and may be substituted by the alkaloid caffeine. The alkaloids which are to be relied upon, however, are strychnine, cocaine, and atropine, and of these the most valuable is probably strychnine, next cocaine. The alka- loids should be given hypodermically, in moderate doses at short intervals, until some effect is manifested upon the respiration. The pupil is not a safe guide as to the administration of atropine, which alkaloid should, indeed, never be given in very large doses. In all cases it is better to use two or more of these alkaloids than larger doses of a single one. When in advanced stages the circulation fails, digitalis and strychnine are the chief remedies, but alcohol may be used carefully, the danger being that any excess of it may aid in depressing the heart. In severe cases it is wise to give digitalis hypodermically before the end of the second long stage, so as to get its stimulating influence upon the heart in the coming de- pression. As the result of numerous experiments, E. T. Reichert 89 reaches the conclusion that cocaine is almost completely antagonistic to morphine, combating the influence of the morphine not only upon respiration and circulation, but also upon the general metabolism, and synergizing with the morphine only in its action upon the spinal cord. He finds that, on the whole, it acts more powerfully upon morphinized than upon normal dogs. For cases in which cocaine was used in opium-poisoning, see Amer. Med. Journ. , 1901. In bad cases of opium-poisoning the use of artificial respiration should not be postponed. In some cases the Sylvester method may suffice, but, as was first shown by Fell, 40 forced respiration (see page 115) should be resorted to whenever respiration fails. Fell" has reported recovery obtained in this way after the ingestion of thirty-three grains of morphine. So long as any movement of the heart continues, the forced respiration should be steadily maintained. Inhalations of oxygen apparently saved life in a case reported by Playfair. 42 In some cases the lungs become filled with bronchial mucus ; under such circumstances good may be achieved by placing the patient in an inverted position. It is often i 3 8 GENERAL REMEDIES. essential to keep up the temperature of the body by artificial means. Lauder Brunton and Cash have found that the fall of temperature in the poisoned mammal is not prevented by placing the animal in a temperature a little below that of the body, and the ordinary methods used in the sick- room to heat the cooling human body are of very little service. The hot bath or a water bed, two-thirds filled with water of the temperature of 150 F., may be employed. The subcutaneous or intravenous injec- tion of normal saline solution has proven of value in desperate cases ; the solution probably aids in the elimination of the poison and the main- tenance of the circulation. Opium-poisoning usually has no sequelae, but amaurosis 43 and glyco- suria 44 have been reported. In regard to the amount of opium which will cause death, the smallest fatal dose in the adult on record is one-sixth of a grain of morphine.* According to A. Calkins, 45 four grains f of crude opium placed in the ear have caused death ; also four grains by the mouth in more than one case. According to the authority just quoted, out of twenty-nine reported cases in which a fluidounce of laudanum was taken, nine died. The maximum doses from which recovery has occurred without emesis are fifty-five grains of the solid opium and six ounces of laudanum. The death of an adult female has been attributed, with doubtful accuracy, to thirty grains of Dover's powder, given in divided doses. 46 Recovery is asserted after eighteen grains of morphine without vomiting (William C. Chaffee) , thirty grains with vomiting (Playfair 42 ), and even thirty-three grains (Fell 41 ). For full details as to the results of the habitual use of opium or its alkaloid, the reader is referred to the treatise of Albrecht Erlen- meyer (Die Morphiumsuchi} . No confidence can be placed in the state- ments of the opium-eater, and it is essential for cure that such person be in a hospital or be confined to an apartment under the care of an absolutely reliable nurse, so that the orders of the physician can be strictly enforced. The basis of the treatment must consist in the with- drawal of the narcotic, and there are three distinct ways in which this can be effected. First, the opium may be suddenly taken away ; secondly, it may be taken away rapidly, but not suddenly ; thirdly, it may be with- drawn very gradually. The first of these methods is undoubtedly in most cases efficient, but is often attended by grave danger of collapse, and has no distinct advantages over the plan of rapid withdrawal. The time required for the very gradual withdrawal of the remedy is too great for practical purposes, and the sufferings of the patient are too long drawn out. Unless the daily dose has been extraordinary or the patient is in a very feeble condition, it is safe to withdraw the narcotic entirely * A number of cases are now on record in which death has been produced in the adult by the hypodermic use of from one-sixth to one-half grain of morphine. Consult Oiicago Med. Examiner, May, 1878; Quart. Journ. Psychology . Med., 1868, ii. 739; also Bost. Med. and Surg. Journ., 1885, i. f Taken from the Journal de Chimie, 1831. Assuredly there is a mistake in this case- SOMNIFACIENTS. 139 in from seven to twelve days. A convenient plan is to direct that a solu- tion of morphine or opium be prepared, and whenever a dose is taken out an equivalent amount of water be added. The chief symptoms that follow the rapid withdrawal are excessive malaise, insomnia, complete loss of appetite, vomiting, diarrhoea, and great feebleness. We have never yet seen a case in which these symptoms were so uncontrollable as really to cause alarm for the safety of the patient. Much may be done by proper feeding. The food should consist of highly nutritious, stimu- lating, and easily digested articles, and in severe cases should be liquid, such as milk, rich soups, etc. When the circulation fails, alcohol may be used, and much relief may be afforded by massage, and often by simple rubbing of the patient. General electrical stimulation and faradization of the muscles is often useful, not only by its effect upon the circulation, but also by distracting the attention of the patient from his sufferings. The use of the alkaloid cocaine as a stimulant has been recommended. Good results may be obtained from the free internal administration of the fluid extract of coca, but the use of hypodermic injections of cocaine seems hardly justifiable, as the danger of setting up the cocaine habit is too great. If gastro- intestinal irritation exists, bismuth may be administered freely. The diarrhoea is usually controllable by mild vegetable astringents, especially if combined with sulphuric acid. If the bodily temperature falls at all, it must be maintained by external warmth. Potassium bromide, ammonium valerianate, Hoffmann's anodyne, and other similar feeble nerve-sedatives may be employed and give some comfort. Moral sup- port and stimulation are essential, and massage or other device which aids in passing the time of suffering is most beneficial. Opium- Smoking. The various nations of the Orient use opium as an intoxicant by smoking in one of two ways. In Turkey and neighboring countries it is placed upon tobacco, in a small pipe. In the East it is usually made into a thick, almost plastic, liquid, a large drop or ball of which is held over the flame of a small oil lamp, and the resulting fumes inhaled through pipes of various forms. For an elaborate study of the chemistry of the opiums used in various countries, see Apotheker Zeitung, 1903. Moissan has found in the smoke of opium morphine, pyrrol, pyridine and various homologues, acetone, and various hydropyridine bases, all of which are physiologically active. This analysis has been confirmed by Hartwich and Simon, who believe that the activity of the opium smoke depends not so much upon the morphine as upon the other products of the destructive distillation. ADMINISTRATION. When it is desired to produce very decided nar- cotism by the use of repeated doses of opium, the drug should always be given in liquid preparation, since opium pills sometimes become very hard and undergo solution so slowly that their accumulation in the ali- mentary canal is possible. On the other hand, in diarrhoeas, or in sick- ness of the stomach, old opium pills are thought by some to act better than do more soluble forms of the drug. Many persons cannot take opium on account of the very great sec- 140 GENERAL REMEDIES. ondary nausea and depression which it produces. It has been supposed that these disagreeable after-effects are due to the narcotine in opium ; but this can hardly be, seeing that they often follow the use of the pure alkaloid, morphine. The deodorized tincture of opium agrees with some individuals better than any other preparation of the drug ; and, as first pointed out by Da Costa, by giving a drachm of potassium bromide with twenty-five drops of it, the after-effects of the narcotic are often en- tirely avoided. In many neuralgic women the knowledge of this fact is an inestimable boon ; in others the unpleasant symptoms are not averted by the bromide. Children always bear opium very badly, * and to them only the weaker liquid preparations should be given. Dover's powder should especially be avoided. It is probable that in its manufacture on the large scale the ingredients are sometimes not thoroughly mixed : at least we have seen cases in which the symptoms caused by it were seemingly so out of pro- portion to the dose as to suggest that more than the official amount of opium was present. In acute vomiting from any cause, in dysentery, in strangury and other irritations of the urino-genital organs, great advantage is often to be gained from the use of opium by the rectum. Suppositories made out of the extract (gr. ss to i), or enemata of laudanum (gtt. xxx to xl), may be used in these cases. The latter should be made by adding the narcotic to a tablespoonful of starch-water. The dose of opium for an adult is from one to two grains ; for a child a year old, one-twenty-fourth of a grain. The U. S. Pharmacopoeia directs that opium in its normal moist condition should contain not less than nine per cent, of morphine, and that dried powdered opium (Orii PULVIS, U. S. ), out of which the preparations are made, should contain from twelve to twelve and a half per cent, of the alkaloid. The solid preparations are the deodorized opium ( OPIUM DEODO- RATUM, U. S. ), containing from twelve to twelve and a half per cent, of morphine made by depriving powdered opium of all substances soluble in benzin, dose, one to two grains (0.06-0.12 Gm. ) ; pills of opium (PiL- UL^E OPII, U. S.), containing one grain each of powdered opium (0.065 Gm. ) ; extract (EXTRACTUM OPII, U. S.), containing twenty per cent. of morphine, three-quarters of a grain (0.05 Gm. ) are about equal to one grain (0.065 Gm.) of powdered or deodorized opium, and on ac- count of its being the most fixed in its strength of any of the solid preparations of opium, as well as of its being free from the noxious con- stituents of opium, and of its solubility favoring prompt absorption, it is the most useful and reliable of all the solid preparations of the drug ; Dover's powder ( PULVIS IPECACUANHA ET OPII, U.S.), one part of opium, one part of ipecacuanha, eight parts of sugar of milk. * In a babe a day old, one minim of laudanum (E. Smith, Lancet, 1854), and in one aged nine months, a few drops of paregoric (Wood, Host. Med. and Surg. Journ., 1858), are said to have proved fatal. SOMNIFACIENTS. 141 Paregoric (TiNCTURA OPII CAMPHORATA, U. S. ) has in a fluid- ounce i. 85 grains of opium, besides benzoic acid, oil of anise, and camphor ; in consequence of the last ingredient, it is more constipating than are the other preparations of opium, and hence is preferred in diarrhoea-mixtures. It is also much used in cough-mixtures. Dose, fei to f^i (3.75-30 C.c. ). The other liquid preparations all now represent ten per cent, of powdered opium by weight, and may be given in doses of ten to fifteen minims (0.6-0.9 C.c.). The deodorized tincture (TINCTURA OPII DE- ODORATI, U. S. ) contains no narcotine, and none of the odorous principle of opium. It therefore is less apt to cause nausea than are the other preparations. Its drop almost equals the minim in size. The other preparations are TINCTURA OPII, U. S., or Laudanum (one hundred and twenty drops to the fluidrachm) ; TINCTURA IPECACUANHA ET OPII, U. S., VINUM OPII, U. S. , or Sydenham's Laudanum (formerly ^i to 51) ; ACETUM OPII, U. S. , or Black Drop. MORPHINA. U. S. This alkaloid occurs in minute, colorless, shining crystals, according to Guy melting at 330 F. and subliming at 340 F. ; insoluble in cold and nearly so in boiling water ; only slightly soluble in cold alcohol and ether ; freely soluble in boiling alcohol and in the fixed and volatile oils. The Morphine Acetate (MORPHINE ACETAS), Sulphate (MORPHINE SULPHAS), and Hydrochlorate (MURIATE OF MORPHINE, MORPHINE HYDROCHLORAS) are all official. The first is a white powder ; the last two occur snow-white in feathery crystals. They are soluble in water, of a bitter taste, and physiologically and therapeutically equivalent. THERAPEUTICS. The salts of morphine differ in their therapeutic value from opium chiefly in that they act with less power as sudorifics and in checking secretion in the bowels, and consequently are less con- stipating. The smallness of their dose and their perfect solubility fit them for hypodermic use. Almost the only purpose for which they are used in this way is to relieve pain. The advantages of the method are the quickness of the results and the increased power of relieving suffering which the remedy seems to acquire. In cases of severe pain hypoder- mics are invaluable ; but it must be borne in mind that sometimes they cause most unpleasant symptoms. We have seen very alarming results from the injection of one-sixth of a grain, which dose is said to have caused death. In females, unless very robust, the maximum dose should be one-eighth of a grain (0.008 Gm. ) ; in men, one-sixth to one-quarter (0.01-0.016 Gm.). The dose of a salt of morphine corresponding to a grain of opium is one-quarter of a grain. CODEINA. U. S. Codeine Sulphate ( Codeina Sulphas, U. S. ) and Phosphate ( Codeince Phosphas, U. S. ) have the advantage over the alkaloid of greater solu- bility, the latter dissolving in two and a quarter parts of water. According to the statements of various observers, codeine produces in the lower animals symptoms very similar to those caused by morphine, I 4 2 GENERAL REMEDIES. namely, in the frog, heightened reflexes, tetanic cramp with convul- sions, also coma ; in the pigeon, restlessness, disturbances of respiration, violent convulsions ; in the dog, disturbances of respiration, languor, con- vulsive twitchings, also sleep. For detailed discussion of the observations of various investigators, see tenth edition of this work. In man codeine is a very uncertain and feeble hypnotic, whose action, especially after large doses, is sometimes attended by marked restless- ness. The statements of various clinicians as to its effects and practi- cal value vary very greatly, the variance probably depending largely upon the quality of the codeine used, in many cases the drug exhibited having in all probability been contaminated with morphine. In S. Weir Mitchell's "experiments upon himself five grains produced no symptoms except slight increase in the pulse-rate, nausea, some giddiness, and a sense of heaviness about the head ; results which are in accord with the earlier experiments of Harley. Contrariwise, A. S. Myrtle 18 records a case of severe poisoning caused by four grains of codeine. There was first vascular excitement and exhilaration, then depression with great anxiety, nausea and vomiting, pale, cool, clammy skin, slight contraction of pupil, and sleeplessness, with slight delirium. Two cases of serious poisoning by eight grains have been reported.* In our experience codeine has proved to be a practically useless rem- edy except in doses of half a grain for the purpose of controlling bron- chial irritation in phthisis and other diseases. The dose of the alkaloid may be set down as from half a grain to two grains (0.03-0.13 Gm. ), but in the administration of the larger amount the practitioner should be sure he has a preparation that does not contain morphine. In former editions of this treatise the non-official opium alkaloids narceine, narcotine, thebaine, papaverine, laudanine, porphyroxine, anarcotine, and crypto- pine were discussed at length, but, as they have failed entirely to come into use as therapeutic agents, their consideration is here omitted : a full summary of our knowledge of their physiological action may be found in the tenth edition of this work. MORPHINE DERIVATIVES. Various derivatives of the alkaloid morphine are physiologically active, but only two of them are at present used, PERONINE (morphine benzyl- ester hydrochloride), an account of which may be found in previous editions of this book, having fallen into complete desuetude. DIONINE (mono-ethyl-ester of morphine hydrochloride} is a white crys- talline powder, soluble in seven parts of water. Although no careful physiological research has been made upon it, it appears to share to a slight extent the analgesic and hypnotic powers of morphine, and not ordinarily to produce nausea, constipation, or other disagreeable after- effects. It is affirmed to be more active than morphine in the sup- * See Brit. Med. Journ., 1888, ii., and New York Med. Record, 1893, xliv. SOMNIFACIENTS. 143 pression of cough, and to be also actively antihydrotic, so that it is of especial value in advanced pulmonary tuberculosis. It has also been com- mended in asthma and as an anaphrodisiac ; also in dysmenorrhcea. The dose is from one-quarter to one-half a grain in powder, pill, or solution. The general professional verdict seems to be that, on the whole, it resem- bles heroine in its therapeutic value, but is less powerful. Local Effect. As first noted by Wolffberg, one drop of a two per cent, solution of dionine placed upon the conjunctiva immediately produces smarting and burning pain, free lachrymation, marked injection of the con- junctival blood-vessels, chemosis of the conjunctiva, and occasionally swell- ing of the lid. This ' ' dionine reaction ' ' varies very much ; sometimes it almost fails to appear. Under these circumstances a stronger solution, for example, five to ten per cent., will usually avail, or, according to Darier, an even more active effect may be produced if a morsel of powdered dionin is used, or if the solution is injected beneath the conjunctiva. The irritative effects of the drug are at times exceedingly violent, and Darier believes that the edema of the conjunctiva, and, moreover, one that spreads to the lids and tissues of the face, is more pronounced in the subjects of vascular disease, nephritis and scrofula. The dionine reaction takes place in the normal as well as in the diseased eye. Usually it subsides materi- ally within an hour. It may continue for a number of hours, although the pain and smarting almost always disappear in a very short space of time, to be followed by a period of analgesia lasting for several hours. The phenomena of dionine reaction have been aptly described by Wolffberg by the term "lymphatic inundation," and Darier, who is particularly enthusiastic in his recommendation of the value of this medi- cament, thinks that lymphatic inundation washes out not only the sur- face of the eyeball but also the subconjunctival and intracorneal lymph- spaces, and perhaps even the intraocular spaces. There is, according to this author, not only an afflux of liquid but also of lymphocytes, whose duty he believes is concerned with the defence of the parts, so that there is a more active production of antitoxins and phagocytes. Whether the drug really has an action upon the diseased processes of the eye them- selves and aids its resolvent power by a subtraction of pathologic fluid, or whether its influence should be regarded as that of a counter-irritant, or whether it depends upon its power of increasing lymphatosis, has not been decided, and at present it is probably not possible to say that it does more than stimulate the lymphatic and vascular circulation of the eye. So far as I am aware, the only untoward recorded result from its action is one case of macular hemorrhage in practice. Violence of reaction without ultimate bad results is not an uncommon phenomenon. Its indications in ophthalmic therapeutics are numerous, and in general terms it may be stated that it has a favorable influence in alleviating pain- ful inflammations of the anterior portion of the eye, and in relieving the dis- tress incident to increased intraocular tension, that is, glaucoma. There is much evidence to show that it facilitates the absorption of atropine, eserine, I 4 4 GENERAL REMEDIES. pilocarpine, etc. It is useful in iritis, irido-cyclitis, simple and infected corneal ulcers, herpes of the cornea, superficial and parenchymatous kera- titis, and in the various types of glaucoma. There is some evidence that it is of value in deeper inflammatory processes, for example, in uveitis, and it certainly relieves post-operative inflammation and infection. It would seem, according to an observation of Dr. Callan, which I think I can confirm from personal experience, that it facilitates the regeneration of corneal tissue. It may be suitably combined with cocaine, atropine, ese- rin or pilocarpine where these drugs are also indicated ; but I believe that a better result is reached if the dionine is used separately, and the atropin, cocaine, etc., is instilled immediately afterwards. In a very brief time, usually after the third or fourth day of its use, the eye establishes a species of immunity, and the dionine reaction almost fails to appear. Therefore it should be used for two or three days, and then omitted for three days, when again the reaction is likely to appear, or, if it does not appear, the strength of the solution may be increased. It is the practice of some surgeons, following Darier's recommenda- tion, to use a five per cent, solution. If, however, this occasions too much reaction, in my own experience a one per cent, solution acts favor- ably, and I have almost abandoned the employment of the stronger prep- arations, except when a very decided reaction is desirable, or when im- munity has been secured. Instead of employing dionine in solution, it may be used in powder, for example, a twelfth of a grain, or the powder may be dusted directly upon an ulcerated surface. With this method of em- ployment, recommended by Darier, I have had little experience. I have also not prescribed it as a salve, although this method of employment has been advised and commended by others. Darier has used it subconjunc- tivally, combining it with a physiological salt solution under these circum- stances, by injection. The reaction is very violent ; but, for example, in detachment of the retina, is said to be of service. The asserted power of dionin of clearing up corneal scars I believe to be doubtful, but it certainly is effective and very useful in certain inter- stitial deposits, such as those of interstitial keratitis, both in the early and in the late stages of the disease. The solutions should be freshly pre- pared to be of service.* HEROINE (diacetic ester of morphine}, which occurs as a colorless, odorless, bitterish crystalline powder, is nearly insoluble in water, but forms a hydrochlorate which is freely soluble both in water and in alcohol. According to Dreser, 49 confirmed by Strube, 50 it produces in the lower animals stupor with convulsions, but has very little influence upon the circulation. Ott 51 has found that in the frog it lessens reflex activity, and in sufficient doses causes complete paralysis which is independent of any effect upon the motor nerve or muscle. * This account of the local effect and of the ophthalmic use of dionin was written by Professor George E. de Schweinitz. SOMNIFACIENTS. 145 All observers are in accord that it has very little action on the circu- lation. According to Ott, in doses of from one-twentieth to one-tenth of a grain it produces in the rabbit slight elevation of the pressure without much change in the pulse-rate. The dominant action of heroine is upon the respiratory centre. Both Impens 52 and Marshall 5S state that in small doses it slows the rate but slightly increases the depth of the respiration, while in large amounts it lessens both the frequency and the depth. Accord- ing to Impens, heroine does not diminish the irritability of the respira- tory centre towards carbonic acid, as do both morphine and codeine ; this statement is, however, in direct conflict with Dreser. From the experiments of Impens and Mayor there can be little room for doubt that, at least as regards the lower animals, it requires less heroine to kill than it does morphine. It is probable that this statement holds true also for the human being. As has been pointed out, however, by Impens and by Morel-Lavallee, 54 heroine is a less dangerous drug than morphine, because the efficient dose is disproportionately smaller than the fatal dose in comparison to morphine. In other words, although it re- quires about half the quantity of heroine that it does of morphine to kill, it requires only about one-fourth of the quantity to exercise its maximum sedative effect upon the respiratory centre. Toxic symptoms following the use of heroine are uncommon. Two and a half grains are said to have produced in an asthmatic adult syncope, myosis, blindness, and subnormal temperature, lasting for many hours, 55 and Dover reports great prostration, dilated pupils, with mental aberration, produced by three grains. Thompson M reports death in a case of severe mitral disease, which he attributed to heroine. In a few instances nausea and vomiting have followed the use of heroine, perhaps due, as claimed by Robinson, to some chemical change in the drug. In a number of cases heroine has caused constipation. As an hypnotic or analgesic heroine is certainly very much inferior to morphine, but it has the advantage that in chronic cases it does not pro- duce the agreeable sensations which render the latter drug so dangerous. In arresting cough it has seemed, in our experience at least, equal to mor- phine in activity, and has the great advantage of not checking secretion either in the lungs themselves or in the alimentary canal. According to Strauss, 57 it has distinct anaphrodisiac properties, making it useful in vari- ous forms of sexual excitement, such as nymphomania and masturbation. It has been recently asserted, especially by E. Elischer, 58 that it is so active as a local analgesic that one-quarter of a grain introduced into the vagina will relieve the suffering even of uterine cancer. Rosenberg commends a two and a half grains to the fluidounce solution as a local anaesthetic in diseases of the throat, and especially in laryngeal tuberculosis. When there is excessive cough, as in asthma, bronchitis, whooping-cough, heroine is a very valuable drug ; \\\ phthisis it has the further virtue of reduc- ing the tendency to sweating. Dose, from one tenth to one-third of a grain (0.007-0.023 Gm.). The hydrochlorate may be used hypodermically. 146 GENERAL REMEDIES. CHLORALUM HYDRATUM. U. S. CHLORAL HYDRATE. U. S. Chloral, which is itself not used in medicine, is an oily liquid giving off, at the ordinary temperature, pungent fumes ; it is made by the action of chlorine on alcohol ; by union with water it is converted into a hydrate. Chloral Hydrate is a volatile, crystalline solid, of a hot, burning taste, insoluble in cold chloroform, but very soluble in water, ether, and alcohol. It usually occurs as transparent, colorless tablets, but sometimes in acic- ular or even in rhomboidal crystals. If an alkali be added to a solution of chloral hydrate, it breaks up into formic acid and chloroform, which latter, when water has been the solvent, at once separates in the form of oily drops. Local Action. Chloral is distinctly germicidal and antiseptic, and was at one time used to some extent for preserving cadavers, keeping urinals pure, and allied purposes. As shown by Keen, 1 a solution of twenty to forty grains to the ounce will preserve animal tissues almost in- definitely without interfering with their microscopic structure. It is also somewhat irritant in its action, and after a time sedative to the sensory nerves, and, it may be, to all tissues. Absorption and Elimination. Chloral is absorbed with great rapidity, its action being often manifested within five minutes after its ingestion. It circulates through the body as chloral ; its exact fate in the system has not been determined, but it probably escapes from the body in part unchanged and in part in the form of compounds. It was recognized in the urine by A. Tomascewicz 2 by means of the delicate isocyan- phenol reaction * of Hoffmann. Feltz and Ritter 3 believed that they had found sugar in the urine of chloralized animals, but Von Mering and Mus- culus and F. Echard * have shown that the substance which reduces the copper solution will not undergo fermentation, and Von Mering and Mus- culus have separated it, as urochloralic acid, in colorless, shining needles, often arranged in star-like groups, soluble in water and in alcohol, insol- uble in ether. The existence of this acid has been confirmed and its chemical properties studied by A. Borntraeger 5 and by E. Kiilz, 6 who found it to be physiologically inert. PHYSIOLOGICAL ACTION. General Action. When chloral is given to man or other mammals in moderate doses, the most prominent result in the great majority of instances is a quiet sleep, as closely allied as pos- sible to natural sleep. The subject can readily be aroused from the lighter degrees of this, waking to full consciousness, but soon dropping off again when left quiet. The pulse is in this degree of action not affected, or is rendered a little slower ; the pupil is contracted, but becomes nor- mal so soon as the subject is awakened ; the respiration is deep, full, and regular. When larger amounts are given, the sleep is much deeper, and may pass into profound coma ; the respirations fall in number ; the pulse * Many chemists have failed to find chloral for want of a delicate test. F. Ogston (Edinb. Med. and Surg. Journ., xxiv. 292) affirms that ammonium sulphide affords a means of recognizing minute amounts of the drug. SOMNIFACIENTS. 147 is weakened and rendered slower, but may become rapid and irregular if the dose has been toxic ; the temperature is reduced ; the muscular sys- tem is relaxed, and both sensibility and reflex action are diminished. If a fatal dose has been taken, all these symptoms are intensified : with coma, intense muscular relaxation, weak, thready pulse, and a pupil contracted at first, but afterwards dilated, the victim gradually sinks into death, paralyzed and anaesthetic. The immediate cause of death is usu- ally a centric paralytic arrest of respiration ; but in many cases there appears to be a simultaneous arrest of the cardiac action, and it is prob- able that fatal syncope may at times occur. At the post-mortem exami- nation, congestion of the meninges and substance of the brain and cord, and of the lungs, is commonly found. The blood is thought by Richard- son ' to coagulate less firmly than when normal. The most constant and prominent of all the symptoms produced by moderate doses of chloral is sleep : this is without doubt due to a direct action of the drug upon the cerebrum. In most cases, as already stated, it is quiet, but sometimes it is restless, and in man has occasionally even been wildly delirious, although it is somewhat uncertain whether the latter condition may not have been due to impurities in the drug. It seems to be well established that in the milder degrees of this sleep there is no anaesthesia. We have seen the hyperaesthesia * spoken of by De- marquay 8 after small doses of chloral, and there can be no doubt that it is an occasional, if not a constant, phenomenon. Rajewsky 9 states that there is in frogs a corresponding period of over-excitability of the reflex centres, and that in rabbits he has noticed a glowing heat borne without much complaint, when pinching would produce violent outcries. In very large doses chloral produces anaesthesia ; but, unless the amount em- ployed be so great as to be toxic, this anaesthesia is in most cases very trifling. Motor System. The paralysis and loss of reflex excitability induced by chloral are not muscular in their origin, for Labbee has found that after death the muscles respond perfectly to galvanism. Both Labbe and Rajewsky have found that the motor nerves are in no wise affected by large or even fatal doses of chloral, which must therefore act upon the spinal cord to produce the paralytic phenomena. The experiments of Rajewsky have afforded positive confirmation of the conclusion arrived at by this process of exclusion ; for he found that in the latter stages of chloral-poisoning direct irritation of the spinal cord gave rise to much less severe spasms than in the unpoisoned animal. Before this paralytic stage is reached, as already stated, Rajewsky affirms that in the frog there is a period of increased reflex activity, and that at this time stimulation of the spinal ganglia shows that they are more susceptible than normal. The * Bouchut (New York Med. Gazette, Dec. 1870), Dieulafoy and Krishaber (Amer. Journ. Med. Sci., Jan. 1870), Giovanni and Ranzoli (Schmidt's Jahrbucher, cli.), and Rajewsky (Ibid.) confirm this, while Liebreich and Labbe deny it ; Hammarsten, who has noticed such hyperaesthesia, is inclined to think it apparent rather than real. I 4 8 GENERAL REMEDIES. observer last named states that these phenomena occur just as freely after destruction of Setschenow's centre in the frog as before, and are there- fore independent of it. Circulation. According to Demarquay, when chloral has been ad- ministered to animals there is evident enlargement and engorgement of all their blood-vessels ; and Rajewsky states that he has found sinking of the blood-pressure in rabbits caused by small as well as large doses of the drug. On the other side, Labbe"e 10 asserts that the rabbit's ear grows pale after the injection of a very feeble dose. In man, Bouchut has ob- tained sphygmographic traces which he thinks indicate a primary increased arterial tension. Nancias, of Venice, has found the tension normal, but Anstie and Andrews u confirm the results of Bouchut when small doses are employed. Preisendorfer, 12 in a series of sphygmographic studies, thought that there might be a brief primary rise of arterial press- ure in man, as in animals, but under the full action of chloral the arterial pressure steadily sinks. We do not think that much confidence is to be attached to the clinical observations of Bouchut and of Anstie and Andrews, since the sphygmograph seems to be an entirely unreliable instrument when used for the comparative study of arterial pressure ; and in confirmation of the statements of Rajewsky, David Cerna has found in our own laboratory that it is not possible in curarized animals to elevate arterial pressure with any dose of chloral, so that if any rise of pressure (as seems improbable) is ever produced in the normal man or animal by chloral, such rise must be indirect and, probably, due to respiratory dis- turbance. Very large doses, according to both Andrews and Da Costa," decidedly lessen arterial pressure. The characteristic influence of thera- peutic, and still more of toxic, doses is to produce a fall in the blood- pressure, usually accompanied by a lessening in the frequency of the heart's action, which Cerna believes to be largely due to an influence upon the cardio-inhibitory centres ; although Rajewsky affirms that the slowing of the pulse in the frog and in the rabbit is produced after section of the inhibitory nerves, and is therefore independent of them. The fall of blood -pressure is probably owing in part to the vaso-motor paralysis, but perhaps in largest part to depression of the heart. The vaso-motor palsy is probably chiefly caused by an action upon the dominant centre, but Robert u has shown that there is also, after a very large dose of the chloral, palsy of the coats of the vessels. When toxic doses have been employed, the heart, after numerous pauses, is finally arrested in diastole. Analogy indicates very strongly that this arrest is due to a direct influence upon the heart-muscle or ganglia, and the researches of Sidney Ringer and H. Sainsbury 15 and of David Cerna 1S seem to demonstrate (the con- trary results obtained by Labb6e notwithstanding) that when chloral is brought in direct contact with the isolated heart of the frog there is an immediate and persistent loss of power, ending finally in diastolic arrest. In poisoning in man, the pulse has towards the last been very feeble, generally rapid and irregular, and even in some cases in which recovery SOMNIFACIENTS. 149 has occurred it has been altogether absent for a time. The experiments of Ringer and Sainsbury are so concordant with this that it appears to be established that chloral is a direct depressant to the heart, which is capable of suddenly and unexpectedly destroying life, precisely as does chloroform. Respiration. In full doses, chloral lessens the number of respirations per minute, causing them to become slow and full ; when toxic doses are taken this action becomes more and more marked, the rhythm is much affected, and the respiration grows markedly irregular, and sometimes very rapid and shallow, until it ceases. As these phenomena occur equally after section of the vagi (Rajewsky), the influence of chloral must be exerted upon the respiratory centre at the base of the brain. Tissue Change. Charles Richet" has found that toxic doses of chloral reduce very greatly the elimination of carbonic acid, at the same time that they lower the bodily temperature. So far as large doses are concerned, A. Gritzka 18 is in accord with this, although he asserts that small doses increase carbonic acid elimination. It is plain that the pro- found muscular quiet produced by chloral must lead to lessened oxida- tion. Julius Peiser 19 affirms that chloral increases the degeneration of albuminous tissues. Abdominal Action. Clinically chloral has no perceptible action upon the gastro-intestinal mucous membrane, save as a local irritant ; but, ac- cording to the experiments, of Wertheimer " and Lepage 21 and of Charles Dubois, it increases in the animals both pancreatic and biliary secretion, chiefly, but not altogether, as the result of its local influence in the duo- denum and jejunum. Temperature. A most remarkable action of chloral is upon the tem- perature : in this point all observers are in accord with Richardson, of London, who has seen the temperature fall 6 F. in a rabbit which recovered. Bouchut has noticed a fall of 2 (C. ?) in an infant, and Da Costa and other observers have noticed slighter reductions of tem- perature in man after therapeutic doses. In a case reported by Levin- stein, 22 after six drachms of chloral the temperature rose to 39.5 C. (102.1* F. ), and subsequently fell to 32.9 C. (91.22 F. ). Ham- marsten has found that the fall of temperature is very rapid, 6 C. in an hour, and that it occurs in animals well wrapped up and laid in a warm place. SUMMARY. Upon the cerebrum chloral acts as a powerful hyp- notic ; in full doses it acts as a depressant upon the centres at the base of the brain and upon the spinal cord : it causes slowing and weak- ness of the heart's action, and probably vaso-motor paralysis, also centric slowing of the respiration, -with loss of reflex activity, muscular weakness, and some anaesthesia, all of spinal origin ; in fatal doses it usually produces a gradual death by paralyzing the respiratory centres in the medulla, although in rare cases it kills suddenly by directly par- alyzing the heart, which always stops in diastole. Its action in very small doses is uncertain, but there is some evidence to indicate that it irritates or stimulates the spinal and the cardiac centres. On the 150 GENERAL REMEDIES. vagi and on the motor nerve-trunks it has no marked influence. It does not undergo the chloroformic decomposition by the alkali of the blood or in the system, and is eliminated as uro-chloralic acid. Action as Chloral. Liebreich 23 was led to the discovery of the value of chloral as a practical medicine by the knowledge of the fact that it is converted when in solution by alkalies into chloroform and formic acid, and the expectation that chloroform would be generated by the alkalinity of the blood. This theory, which at one time held, has been so com- pletely disproved as almost to have been lost sight of. A discussion of it may be found in full in the tenth edition of this treatise. Suffice it for the present to say that it is proved that chloral circulates in the blood as chloral, that no conversion of it takes place in the body into chloroform, and that the symptoms which it produces are distinct from those caused by chloroform ; chloral producing a much longer and more intense sleep than does the proportionate dose of chloroform, but having a very much feebler anaesthetic influence ; and further, that in the ' ' salt frog, ' ' with a circulating fluid completely neutral, chloral acts precisely as in the normal frog (Rajewsky). THERAPEUTICS. The results of the clinical use of chloral are in strict accord with its known physiological action. The indication which it most usefully meets is to induce sleep. The more purely nervous the wakefulness the more successful the remedy. When from functional over- excitement of the brain due to excessive mental strain, or from anxiety or other kindred cause, the patient cannot sleep, chloral is, probably, the most certain of the hypnotics. On the other hand, when severe pain causes wakefulness, chloral is of very little value, at least in doses which we think safe. Sometimes even in these cases sleep will come, but it will very often be a restless, troubled sleep, with moaning or other indications of suffering ; and it may be that the patient on awaking will complain that he has suffered more while sleeping than when awake. In the sleeplessness occurring at times during convalescence from acute disease, chloral is very efficacious. In the early stages of fevers it is sometimes of advantage ; Russell M recommends it especially in the -wild delirium of typhus in its earlier stages. In advanced fever-cases, when the symptoms are gravely adynamic, we believe that the use of chloral would be very perilous. In delirium tremens it often induces sleep readily, but not rarely it fails, even in large dose. In the sleepless- ness of acute puerperal or non-puerperal -mania there is abundant testi- mony to the value of chloral. It must not be forgotten that chloral is a dangerous remedy when there is cardiac weakness ; and when in any of the diseases just spoken of there is reason to suspect a fatty or even a feeble heart, great care must be exercised in the administration of chloral. Under such circumstances the dose of fifteen grains should not be ex- ceeded, and should not be repeated more than once unless after an in- terval of several hours. The second indication to meet which chloral may be employed is to SOMNIFACIENTS. 151 relax spasm. For this purpose it has been used with advantage in puer- peral and ur&mic convulsions. It must be remembered that in many of these cases, although next to chloroform the best palliative, it is only a palliative, and must be used merely to quiet the nervous disturbance until other remedies can have time to act. In tetanus it has been affirmed that chloral is the remedy. Joseph R. Beck* 5 has collected, of the traumatic form of the disease, thirty-six cases, with twenty-one recoveries, in which chloral constituted the whole or the major part of the treatment. References * are given below to fifty-six cases in addition ; so that the figures stand forty-eight recoveries and forty-four deaths. These results do not seem to warrant the high estimate which has been set upon the value of chloral in tetanus. Very extraordinary results have been ob- tained by Macnamara 26 in tetanus by using chloral simply at bedtime (forty grains), with an occasional dose (thirty grains) in the morning when there is high temperature ; and administering brandy, milk, and eggs very freely during the day. Chloral is undoubtedly a valuable remedy in tetanus and in strychnine-poisoning ; there is, however, no reason for relying upon its exclusive use.f In trismus nascentium, as originally recommended by Widenhofer," it is undoubtedly very valuable. Widenhofer gave it to the young babe in one- and two-grain doses by the mouth, or, when the spasms prevented, in double the quantity by the rectum. In chorea it is not directly curative, but is of great importance when it is essential to temporarily check the violence of the movements. As a nocturnal quietant and hypnotic, it is of the highest value in cases of acute chorea in which speedy death is threatened from the incessant and violent movements ; also in cases com- plicated with fractures, where a temporary lull is of importance. In puerperal convulsions its use in large doses has met with a great deal of favor. A half-drachm may be exhibited at once, and half the quantity every hour or two pro re nata. * RECOVERY. Fergusson (Edin. Med. Journ., July, 1871) ; Watson {Lancet, 1870) ; Bartlett ; May ; Ballantyne ; Gushing (Pacific Med. and Surg. Journ.) ; Lovegrove (Brit. Med. Journ., 1872, 493) ; Herndon (Atlanta Med. and Surg. Journ., 1873, 69) ; Mac- namara (Indian Med. Gaz., April, 1871) ; Richelot (Bulletin Therap., Ixxxvi.) ; Lucian Papillaud (Gaz. Medicale, 1875, 176) ; Bourdy (Bull. Therap., Ixxxvi.) ; Cane (Lancet, 1876. i. 564) ; Cauvy (Bull. Therap., xciii. 186) ; Durand (Centralbl.f. Chirurgie, 1876, 778) ; Laurens (Le Progres Med., 1876, 180) ; Pugliese (Journ. de Therap., 1875, 244) : each one case ; Cargile (Lancet, 1877, ii. 158), three cases ; Boon (London Pract., xx. 161), two cases ; Roberts (Amer. Journ. Med. Sci., Ixxiv. 420), three cases ; Garnett (Cincinnati Lancet and Clinic, 1880, 316), two cases. FATAL. Porta (Schmidt's Jahrbucher, cli. no), two cases ; Macnamara (Indian Med. Gaz., April, 1871), six cases; Baudon (Bulletin Therap., Ixxxvi.), three cases; Blin (Ibid.), three cases ; Petit (Centralbl.f. Chir., 1876,792), three cases; Roberts (Amer. Journ. Med. Sci., Ixxiv. 420), three cases ; Cruveilhier (intravenous) (Bulletin Therap., Ixxxvi.) ; Labbee (Ibid.) ; Itard (Schmidt's Jahrb., cli.) ; Lannelongue (Bulletin Therap., 1874, Ixxxvii.) ; Verneuil (Ibid., 1874, Ixxxvii. ) ; Boon (London Practitioner, xx. 161) ; Boucquier (Centralbl.f. Chir., 1876, 717) ; Bresson (Le Progres Med., 1876, 180) ; Pug- liese (Journ de Therap., 1875, 244) : each one case. t For a paper discussing the relations of chloral to various mostly unimportant alka- loids, see Arch.f. Exber. Path, und Therap., ix. 440. 152 GENERAL REMEDIES. In the convulsions of children it has been employed with apparent good ; in cramps, in singultus, in the spasmodic nocturnal enuresis of children, in laryngismus stridulus and other spasmodic affections of the glottis, in nocturnal 'emissions ; in whooping-cough, and in all forms of severe spasmodic disorder when it is desired temporarily to suppress the motor disturbance, chloral remains the standard remedy. In asthma it has sometimes been of use, but more often it has failed. Its hypodermic use in the algid stage of cholera, as recommended by Dr. Hall, 28 appears to us of very doubtful value. The third indication for which chloral has been used is to relieve pain. That it will do so when given in very large doses there can be no doubt ; but, unless the dose be so large as to be dangerous, chloral is of little value as an analgesic. Its powers in this direction are incomparably less than those of opium, and its habitual use is attended by grave dangers. As originally suggested by Lyon Playfair, 29 chloral may be given in the early stages of labor to lessen the severity of the pain ; it is stated also to be of service as a relaxant when there is rigidity of the os. Fifteen grains may be administered and repeated in half an hour if necessary. Locally a solution of chloral (ten per cent, to saturation) has been used with asserted very good effects as a stimulant and antiseptic in foul ulcers, buboes, bedsores, etc., especially when the discharge is free, as a haemostatic when there is oozing of blood, and as an antiseptic and local anaesthetic in uterine and other cancers. Applied to the skin, it is a powerful irritant, and has been proposed as a vesicant,* but is said to cause excessive pain. 30 The intravenous injection of chloral, as suggested by Or6, si for the purposes of anaesthesia, and for the combating of tetanic spasms, is en- tirely unjustifiable and is at present rarely practised, death having in various cases resulted from the unexpected violence of its action or from the coagulation of the blood which it produced. TOXICOLOGY. The minimum fatal dose of chloral is hardly estab- lished, but thirty grains have produced death. (See Administration.} In very many cases, however, recovery has occurred after the taking of sev- eral drachms ; indeed, Eshleman has reported recovery after the inges- tion of four hundred and sixty grains. There are no pathognomonic lesions found after death from chloral, but a dark, bloated countenance and other evidences of death from asphyxia have been noted. The treatment of chloral-poisoning is identical with that of opium- poisoning, consisting in the free use of internal and external stimulants, such as sinapisms, dry heat, frictions, flagellations, etc., to maintain the circulation, and of shaking, walking, application of the dry electric brush, cold douches, etc., to keep up the respiration. In practising these According to Bonnet (Union Pharm., xlii. 490), one gramme of chloral hydrate, rubbed up with oil of sweet almonds or vaseline and spread on a diachylon plaster twelve by fifteen centimetres and placed on the skin, will in fifteen minutes cause burning pain, after which time it should be removed and the part covered with cotton wool. During the sleep which usually follows the absorption of the chloral a blister will form. SOMNIFACIENTS. 153 measures it must be remembered, however, that the patient in chloral- poisoning is much more apt to die of exhaustion, and especially of cardiac failure, than in opium-poisoning, and that therefore those methods of arousing the nerve-centres which do not, like walking, require the expendi- ture of effort on the part of the patient are to be preferred. Artificial respi- ration should always be resorted to before natural respiration altogether fails, and Clemens 32 has found that animals asphyxiated by chloral may often be at once aroused by the inhalation of oxygen. Atropine and strychnine are important remedies. B. W. Stone 33 reports recovery from four hundred and twenty-five grains of chloral after the hypodermic use of one-fifth of a grain of strychnine in divided doses. Digitalis may be given to sustain the heart. I. M. Booth M reports a case of recovery after about one hundred and ten grains of chloral under the use of tincture of belladonna. Lauder Brunton K has shown that if the bodily temperature be maintained artificially animals survive doses of chloral usually fatal, and in human chloral-poisoning the bodily warmth should be maintained by the use of dry external heat, hot blankets, hot baths, and other devices. While some affections have been erroneously attributed to chronic chloral-poisoning, there seems to be no doubt that its long-continued use often does produce serious symptoms. The cases are divisible into two or three groups, which are, however, really artificial, as is shown by the occurrence of cases belonging to two or even three of the groups. In the first group the respiration is chiefly affected. The dyspnoea may be slight, and may only be felt at times, as after exertion or after meals ; but it may be constant and alarming. Cases of this character are re- ported by Jastrowitz, by Schule, and by Ludwig Kirn. 36 In one instance (N. R. Smith 37 ), death from bronchial effusion is belreved to have been caused by chloral. Kirn 88 affirms that in some cases mental disturbance with hallucinations occurs. In the second group of cases, eruptions of the skin are the chief manifestations of the toxaemia. In the mildest of these there is no distinct rash, only the occasional appearance of transient red blotches on the face or neck. But a very extraordinary tendency exists towards the production of a rash or discoloration at the slightest cause, so that drink- ing a glass of wine will produce an intense, even livid, erythematous red- ness of the face. In other instances there is marked erythema (Schule 89 ), occurring first in spots upon the face, but extending downward to the trunk, becoming more and more general, and showing a marked ten- dency to follow the nerve-trunks. This erythema is seemingly due to vaso-motor weakness, and consequently is allied to other more urgent symptoms seen in chloral toxaemia. Sometimes it invades the mucous membranes, which become red, swollen, and cedematous ; and if the glands are involved, as in a case reported by Chapman, 10 the result may be serious. A deeper implication of the vaso-motor and cardiac nervous system was probably the cause of the general oedema, profound weak- ness, and failure of heart-action in the case recorded by N. R. Smith 154 GENERAL REMEDIES. {he. "/.), and possibly also of the desquamation of the cuticle and ulcer- ations about the nails noted in some of his cases by the same physician. In the third group of cases, petechiae, ecchymoses, ulcerations, and even high fever and other pyaemic symptoms, are asserted to have been produced by the continuous use of chloral. It seems to us, however, very doubtful whether the drug really was the cause of the sypmtoms which have been recorded by Crichton Brown, by Monkton, and by Kirn. The habitual use of chloral as a narcotic has been indulged in, it is asserted, to a considerable extent, and George F. Elliott 41 reports symp- toms like those of delirium tremens as following the withdrawal of the accustomed draughts. ADMINISTRATION. Although the continuous use of chloral may lead to a very serious chronic poisoning, we have no knowledge that the chloral itself accumulates largely in the system ; and it certainly has no cumu- lative action like that of digitalis, in which a sudden outbreak of symp- toms occurs without warning. On the other hand, the single large dose of chloral in rare cases acts with unexpected violence. It has fre- quently been given in doses of thirty grains. That this is not entirely safe, however, is shown by the case of Reynolds," in which forty-five grains caused most alarming symptoms ; by that of Watson, 43 in which eighty grains, given in ten-grain doses spread over thirty-six hours, nearly proved fatal ; and especially by a number of cases recorded by H. W. Fuller, 44 in some of which very alarming symptoms followed the ex- hibition of thirty grains, and in one death in a healthy young woman of thirty. Schwaighofer, 45 of Vienna, records coma and death in a drunkard following the ingestion of half a drachm. W. H. Lathrop 46 details the case of a man previously healthy, but suffering from delirium tremens, who took sixty grains between 12 and i P.M., at 2.30 P.M. twenty grains more, and at 3 P.M., no effect being manifest, twenty grains more. His physi- cians then left him sleepless and complaining only of a slight paralysis of- the lower extremities ; and almost in a moment he was dead. Other cases might be quoted, 47 but the above are sufficient to show that chloral may kill suddenly and unexpectedly. An observation of Vulpian 48 throws much light upon these sudden deaths. He found that galvanization of a divided vagus would cause in a chloralized animal not momentary, but permanent, arrest of respiration, if the centric end was selected, or permanent diastole of the heart if the distal part of the nerve was attacked. It is very probable that in a man under the influence of chloroform or of chloral, death may be precipitated by a slight peripheral inhibitory irritation. We think the practical deduc- tion from the known facts is that twenty grains (1.3 Gm.) is the highest safe dose of chloral ; that this amount should not be repeated oftener than once an hour, and, when sixty grains have been taken, not again for some hours, unless in very urgent cases, as acute tetanus or violent chorea threatening speedy dissolution. SOMNIFACIENTS. 155 SULPHONMETHANUM. U.S. Sulphonal (di(sthylsulfondimethylmethane) y discovered by E. Bau- mann in 1866, belongs to the group of rather numerous physiologically active compounds known as the disulphones, of which three ethyl com- pounds namely, sulphonal, which contains two ethyl radicals ; trional, which contains three ethyl radicals ; tetronal, which contains four ethyl radicals have been used as hypnotics in practical medicine. The original statement of Baumann and of Kast, that the hypnotic powers of these drugs is in direct relation to the number of ethyl radicals in their chemical make-up, has been confirmed by Diehl. Sulphonal, which was first physiologically investigated by A. Kast, 1 occurs in thick, colorless prisms, soluble in from eighteen to twenty parts of boiling water, not soluble in one hundred parts of cold water, slightly soluble in ether, benzol, and chloroform ; tasteless, odorless, and of very persistent constitution. PHYSIOLOGICAL ACTION. Local Action. Elimination. Sulphonal is not at all irritant, and, indeed, locally it appears to be inert. Owing to its great insolubility it is absorbed very slowly from the stomach, the method of its absorption being at present unknown. When taken in large amount it escapes to some extent from the kidney unchanged, but the greater portion of it is converted into an organic sulphur compound, which, according to the researches of W. J. Smith (confirmed by Bau- mann and Salkowski 2 ), is probably athyl-sulphonic acid. General Action. The symptoms which are produced in man by even large therapeutic doses of sulphonal are simply quiet sleep, out of which the patient wakes after some hours in his normal condition, or not rarely with a certain amount of giddiness and lack of mental tone. Probably on account of the difficulty of its absorption, with the conse- quent escape of it from the alimentary canal, sulphonal has very rarely produced death when taken in a single dose. In one case recovery occurred after one hundred and twenty grains, although there were complete abolition of the reflexes and loss of the radial pulse. 3 E. Neisser * has recorded a case in which one hundred grammes caused a profound sleep lasting ninety hours, a fall of bodily temperature to 96 F. , and a symmetrical minutely papulous eruption upon the hands, but no great disturbance of the heart or breathing or of the reflexes ; after recovery there was a marked ataxia of speech and movement which disappeared in a week. That the single dose of sulphonal may prove fatal is, however, es- tablished by the following cases : Petitt 5 states that he has seen coma ending in death produced in a woman by two grammes. In a case recorded by G. Hoppe-Seyler and Ritter 6 fifty grammes produced death in seventy hours, the symptoms having been coma, cyanosis, and high fever. The expired air had the odor of mercaptan, and the urine contained unaltered sulphonal. Pronounced fatty necrosis of the intestinal and renal epithe- lium, fatty degeneration of the heart, and broncho-pneumonia were found in the 156 GENERAL REMEDIES. body. The broncho-pneumonia was believed by Hoppe-Seyler to be the result of the aspiration of the contents of the mouth and gullet, due to the insensibility of the epiglottis. In the frog, the dog, and the rabbit sulphonal produces sleep, which, if the dose be sufficiently large, deepens into coma, and is accompanied by paresis, tremors, and convulsions. Knoblauch affirms that not infre- quently the loss of power in the hind legs precedes sleep, and that weak- ness and ataxia are prominent symptoms after large doses. The convul- sions, which are said to be epileptic, are produced by very large toxic doses only. Our knowledge of the physiological action of sulphonal is very imper- fect. Its dominant influence is upon the cerebral cortex. According to Kast, the blood-pressure is not altered by doses which produce sleep, and the rise of arterial pressure noticed by Shick in non-curarized animals may have been produced by failure of respiration. It probably depresses the motor spinal cord, although this has not been proved, and Shick states that in some of his experiments the reflex activity was increased, and that the decline of the reflexes is in fact due to stimulation of Setschenow's centre. According to Shick, it has no influence upon the motor or sensory nerves, nor upon the muscles. Kast found that there is neither microscopic nor spectroscopic blood changes in animals acutely poisoned by the drug. The drift of the pres- ent evidence indicates that sulphonal has no distinct effect upon tissue change, but the matter is sub judice. * THERAPEUTIC USE. Sulphonal is a valuable hypnotic, having, how- ever, little or no analgesic effects, and being extremely slow in its action and scarcely as certain and satisfactory as is trional. Sleep usually develops in from a half to one hour after the dose, in most cases gradually, but sometimes with abruptness. It is usually quiet, and not followed by any disagreeable after-effects, although sometimes mental confusion and lassitude remain during the following day ; these after-results being, in our experience, especially apt to occur in cases in which there is a distinct depression of the brain-nutrition. Where the sleeplessness is due to pain, sulphonal is usually not serviceable ; but in the insomnia of insanity it often acts well. Later experience, however, does not seem to carry out the original assertion of Kast, that sulphonal is especially useful in cases of insomnia from cardiac diseases. In such affections it appears to be not only an uncertain, but even a dangerous drug, inferior to chloral, f At present this disagreeable action of the drug does not seem *The most important papers are those of Gritzka (Inaug. Dis., Berlin, 1891), W. J. Smith (London Pract., 1889 an d 1892), and Martin Hahn (Virchow's Archiv, cxxv.). John Gordon ( British Med. Journ., 1893, i. ) has found that in weak solution sulphonal and urethan retard slightly the action of pancreatin solution upon starch, strong solutions of the drug having no effect ; that chloralamid, antifebrin, and antipyrin are without such power ; but that paraldehyde, whether in weak or strong solution, has a very profound effect, f See Joachiam ( Therap. Monalsh., iii.) ; also Schmey (Ibid., 1888, ii.). SOMNIFACIENTS. 157 to be explainable by any influence exerted upon the heart. It is possible that it is due to irritation of already congested kidneys. The action of sulphonal upon the reflexes would indicate its employ- ment in spasmodic diseases, and it has been used with asserted good results in epilepsy, hiccough, chorea, and nocturnal cramps ; according to E. Andrews, 7 it is very effective against the spasm of fractures. It has also been commended as a sexual sedative in chordee and spermator- rhoea. In our own practice, sulphonal given an hour after meals has seemed to have value as an intestinal antiseptic. It is asserted that it is a very useful remedy in colliquative night-sweats. TOXICOLOGY. Occasionally even the single dose of sulphonal pro- duces nausea (even severe gastric pain : Dauthville 8 ), languor, headache, depression, or pronounced mental disturbance. In rare cases sulphonal causes excitement. Although prodromic symptoms probably always usher in chronic sul- phonal-poisoning , they are so slight and so lacking in anything charac- teristic that in a large majority of cases the condition appears to develop abruptly, and usually, notwithstanding the suspension of the remedy, con- tinues to the fatal issue, death occurring in about seventy-five per cent. of the cases. The first manifestations are increasing lassitude and weak- ness, nausea, and gastro-intestinal disturbance as shown by diarrhoea or constipation. Ordinarily the first symptom noted is the pink coloration of the urine, which deepens until the fluid becomes of a dark red color, stain- ing the linen upon which it falls. Usually this coloration of the urine is soon followed by obstinate constipation, violent vomiting, spasm of the abdominal muscles, and tenderness upon pressure in the region of the liver and stomach. At the same time there develop irregularity of gait, ataxia, suppression of perspiration, paresis of the upper extremities or per- chance paresis of irregular groups of muscles, pronounced weakness of the legs, loss of the patellar and other reflexes, parsesthesia, muscular spasms, and finally a condition of profound collapse, with albuminous, hemor- rhagic, or suppressed urine, ending in death. After death, wide-spread fatty degeneration, involving in some cases the heart, but especially affect- ing the liver and kidney, has been found. In some cases the renal changes have been confined to a glomerular or cortical nephritis,* with or without hemorrhage ; in other instances the destruction of the kidney has been more complete. Probably the most characteristic symptom is the appearance of haematoporphyrin in the urine ; its recognition is best made with the spectroscope. It has been shown by Salkowski (confirmed by Kast 9 ), that ethyl-sulphonic acid is not poisonous, and haematoporphyrin appears also to be free from toxic properties ; so that the symptoms of chronic poisoning are probably due to an * A. E. Taylor and Joseph Sailer ( Contributions William Pepper Lab., Philadelphia, 1900, cxx.) found that the degenerated cells of the liver, spleen, lymphatics, and kidney were loaded with green pigment, whilst the blood-serum contained haematoporphyrin. 158 GENERAL REMEDIES. accumulation of sulphonal in the system, and are of largely primary and not of sec- ondary character, though some of them may be in fact uraemic. The explanation of the occurrence of haematoporphyrinuria is at present very difficult ; * frequently it does not come on until several days after the ingestion of the last dose. In a fatal case of acute poisoning reported by Hoppe-Seyler and Ritter it was not present. As has been demonstrated by Garrod and Hopkins, 10 the urine of patients taking sulphonal does not ordinarily contain more haematoporphyrin than is often seen in health. It is generally thought that the haematoporphyrin is a decomposition product of haematin, and Stokvis u believes that the haematoporphyrinuria is due to the absorp- tion of altered blood from hemorrhages which have been produced in the mucous membrane of the stomach and intestines by sulphonal, an explanation which is rejected by Kast and Weiss, 12 and also by Garrod and Hopkins, for apparently sufficient reasons. The observation of Garrod and Hopkins, that the increase of urinary haematoporphyrin is not accompanied by a corresponding increase in the excretion of iron, and the fact that in the cases recorded by Percy Smith there was no lessening in the number of the red blood-corpuscles nor of the haemoglobin, lend probability to the assertion of Quincke (confirmed by Herting 13 ), that the coloring- matter of the urine is not in reality haematoporphyrin, differing from it in its spectro- scopic lines. Franz Miiller, however, found in a case of sulphonal-poisoning which recovered that the haemoglobin fell during the period of red urine to forty-five per cent. , returning afterwards to eighty-five per cent. ; whilst Hoppe-Seyler believes that the anatomical changes in sulphonal-poisoning are really secondary to the destruction of the red blood-disks. The exanthem of sulphonal-poisoning may be bullatous, but is usually a minutely papulous eruption, which has been described by some as resembling that of measles, by others as like that of scarlet fever. It is not rarely symmetrical, and often shows a disposition to follow the nerve- trunks, so that it is probably neurotic, a conclusion which is strongly con- firmed by the fact that unmistakable multiple neuritis has been reported as caused by the continued use of sulphonal (W. Erbsloh 15 ). In the treatment of sulphonal-poisoning the first attention should be given to seeing that the bowels are well opened, which usually requires very energetic measures. The use of the alkaline carbonates, as sug- gested by Miiller, 14 probably offers the best hope of any therapeutic measures, f Large amounts of water, which may carry the alkali, should be introduced both by the mouth and by hypodermoclysis, to wash the poison out of the system. ADMINISTRATION. The dose of sulphonal is from ten to forty -five grains (0.7-3 Gm. ). It is absorbed with difficulty, and should always be administered in fine powder diffused in water or milk, or enclosed in capsules. We have seen compressed pills of sulphonal pass through the body unchanged, and have no doubt that the reported great slowness or even failure of action has often depended on improper methods of admin- istration. It should be an invariable rule when sulphonal is given * In an elaborate research upon rabbits, Neubauer (A. E. P. P., 1900, Bd. xliii.) attempted unsuccessfully to determine how the haematoporphyrin is produced by sul- phonal. In agreement with Kast and Weiss, he was unable to produce haematoporphyrin. by digesting the normal organs of the rabbit with sulphonal. f Alkaline waters, however, in Pollitz's case ( Vierteljahr.f. Gerichtl. Med., 1898, v.} apparently failed to do any good. SOMNIFACIENTS. 159 continuously every two weeks to suspend its employment for some days, so as to allow the system to clear itself ; and the urine should also always be carefully watched and the first appearance of the red tint be the signal for immediate withdrawal. SULPHONETHYLMETHANUM. U. S. Trional {diethylsulphonmethylethylmethane) occurs in commerce as a colorless, shining, bitter crystalline powder, soluble in three hundred and twenty parts of cold, easily soluble in hot water ; also in alcohol and ether. Tetronal (diethylsulphondiethylmethane), although affirmed by Baumann and Kast to be more powerful as an hypnotic than trional, has failed to come into practical use as an hypnotic. Locally trional seems to be inert. It is absorbed much more rapidly than is sulphonal and acts much more promptly. Concerning its elimi- nation we have no information. Given to man in doses of from fifteen to twenty grains, it usually causes in from fifteen minutes to an hour a quiet, apparently normal, sleep. There appears to be no recorded case of fatal acute poisoning by trional. Sixty grains are said to have produced haematoporphyrinuria (Berger 1 ), but one hundred and twenty grains have been recovered from without very serious symptoms (Collatz 2 ). One hundred and twenty grains (Wightwick and Rolleston s ) caused dilated pupils, profound muscular relaxation, loss of reflexes, and pronounced cardiac depression, without haematoporphyrinuria. Although trional is less apt than is sulphonal to cause chronic poisoning, a number of cases have occurred. The symptoms have been great lassitude, giddiness, headache, tinnitus aurium, gastro-intestinal pain, vomiting, ob- stinate constipation, pronounced tremors, ataxia, especially shown by an uncertain gait, and in one or two cases even a pronounced general paresis, with loss of control over the sphincter ; also lessened secretion of the urine, and haematoporphyrinuria. Strangury has been noted, whilst even the therapeutic dose may cause excessive acidity of the urine. These symptoms differ from those produced by sulphonal chiefly in that the haematoporphyrinuria is less pronounced, and in that the premonitory symptoms are more marked. As Hart has reported double wrist- and foot-drop, with diminished reflexes and loss of motor power, it is probable that trional may produce a peripheral neuritis. In acute trional-poisoning the stomach should be evacuated ; very dilute solution of sodium carbonate should be given freely by the mouth and by hypodermoclysis ; strychnine and cardiac stimulants used hypo- dermically pro re nata. In chronic poisoning the most important part of the treatment is the free administration in every possible way of a one per cent, solution of sodium carbonate.* Beyond the fact that the dominant influence of trional is upon the cere- * For cases of poisoning, see Vogel (Berl. Klin. Woch, 1899, 875) ; also Munch. Med. Woch., xiii. 928; Coleman, Med. News, 1900, Ixxvii. 129; jChurch, American Med., 1901, ii. 729 ; Hart, American Journ. Med. Set, 1901, cxxi. 160 GENERAL REMEDIES. brum, we have little definite knowledge as to the way in which it acts. According to Haenel, 4 the rate of the mental function is distinctly les- sened by it, and continues slow for some time after the sleep period. If it be true, as asserted by Egasse, 5 that in animals trional sleep is at- tended by increase in the activity of the reflexes, it probably stimulates the spinal cord. Kronfeld, 6 as the result of sphygmomanometrical studies, affirms that the blood-pressure is always lowered during sleep caused by trional, the fall being due, in his belief, to depression of the vaso-motor centres. Trional may be given in hot water or hot milk or in capsules. Dose, ten to thirty grains (0.66 to 2 Gm. ). PARALDEHYDUM. PARALDEHYDE, U. S., which was first brought to the notice of the profession by Cervello, is a colorless liquid, having a boiling point of 123.5 C. , and an extremely disagreeable odor and taste. Local Action. Paraldehyde is locally irritant, and is likely, when taken in large doses, to disturb the stomach, or at least to give rise to disagreeable eructations. Absorption and Elimination. Absorption of paraldehyde commences at once, and its action is usually manifested in a few minutes. Its elimi- nation begins promptly, but is carried on slowly, so that the breath fre- quently reeks of it for hours after the patient has awakened. Its chief channel of escape is probably through the respiratory organs, but it has been found in the urine by Gordon and Raimann, and Raimann also believes that it escapes to some extent with the perspiration. It appears not to be destroyed in the system. PHYSIOLOGICAL ACTION. According to the physiological studies of Cervello, PreVost, and Gordon, the injection of from one-half to one drachm of paraldehyde produces in the rabbit and dog loss of sensibility, and in a very short time deep sleep with general muscular relaxation, some slow- ing of the breathing and of the rapidity of the heart, without, however, distinct lowering of the blood-pressure. After very large doses reflex excitability is abolished, and death takes place through respiratory paral- ysis, the cardiac action and blood-pressure long resisting the action of the drug. In man paraldehyde produces a deep sleep, with, if the dose have been large enough, loss of reflex activity, some slowing of the respi- ration and pulse-rate, and slight fall in the temperature. The symptoms usually pass off without disagreeable after-effects, but after very large doses there are sometimes malaise, headache, giddiness, nausea, or even vomiting. Usually there is some diuretic action. Nervous System. Paraldehyde* probably produces sleep by a direct action upon the cerebral cells. Bokai and Barcsi * have found that there is marked relaxation of the cerebral blood-vessels, but this is probably the * Cappelli and Brugia * have also noted lessening in the size of the brain, under the in- fluence of paraldehyde, in a man suffering from defect of the skull. SOMNIFACIENTS. 161 result, not the cause, of the arrest of brain function. The characteristic effect of the drug upon muscular action is depression, which is probably of spinal origin, though this has not been absolutely proved. Bokai and Barcsi affirm that after small doses there is a period of heightened re- flexes. Circulation. Upon the circulation paraldehyde has very little influ- ence, nor is the blood itself affected except by the very largest doses. According to Henoque, intravenous injections of paraldehyde in the animal are followed by disappearance of the absorption-band in the yellow- green of the spectrum oxyhaemoglobin. Nutrition. According to Dockendorff, the elimination of nitrogen and phosphorus is somewhat lessened by paraldehyde, and in cases of chronic poisoning in man the elimination of phosphates has been found to be very low. Heemoglobinuria has been noticed in the horse, but not in other animals poisoned with paraldehyde. TOXICOLOGY. Very large doses of paraldehyde have been taken with- out fatal results, although death is alleged to have been produced by four ounces (Drage 5 ). In one case reported by Raimann,* nearly eight hun- dred grains produced simply deep sleep lasting nineteen hours, without evil result. Probst 5 reports one case in which nine hundred grains gave sleep lasting twenty-two hours, without serious symptoms ; and another in which nearly five ounces of paraldehyde, taken within thirty-six hours, produced profound coma, marked lividity, excessive muscular relaxation and vomiting, slight fall of temperature, without pronounced depression either of the heart's action or of the blood-pressure, and without complete loss of the reflexes. The urine at first was in no way abnormal ; later it contained acetone. On the second day mental aberration appeared and continued, and on the fifth day distinct tremors appeared : by the seventh day the case was convalescent. Although chronic poisoning has frequently been produced by paraldehyde, we know of no recorded fatal case. Disturbances of the digestion are common. More characteristic is a psychic disturbance somewhat resembling delirium tremens and in many cases associated with tremors and muscular weakness. These symptoms usually subside with the cessation of the taking of the drug. In one case 6 thirty-five grammes were taken daily for a year. In a second case 7 five grammes were taken daily for thirteen years, without the pro- duction of any symptoms. In the experiments of Bokai and Barcsi it was found possible to produce in the animal, by the continued use of paral- dehyde, fatty degeneration of the liver and of the heart-muscle, but no such result has been noted in man. In some cases nasal ulcers, skin eruptions, and various vaso-motor disturbances are said to have been produced by the long administration of the drug. Paraldehyde is a very useful hypnotic in the numerous cases of mild insomnia, such as is seen in neurasthenia, and is also used as an adjuvant to other remedies in delirium tremens, insanity, and the more serious forms of morbid wakefulness not dependent upon pain. ii 162 GENERAL REMEDIES. ADMINISTRATION. The dose of paraldehyde is from one-half to two drachms. Its unpleasant taste may be partially hidden by the use of the aromatic oils. MINOR HYPNOTICS. Chloretone, Acetonchloroform, or Trichlor Tertiary Butyl Alcohol, is a white crystalline compound with a camphoraceous odor ; very soluble in strong alcohol and ether, soluble to the extent of about one per cent, in cold, more soluble in boiling, water.* PHYSIOLOGICAL ACTION. In proper dose chloretone causes in the lower ani- mals a profound sleep, with complete and prolonged anaesthesia, without marked effect upon the respiration or blood-pressure. This condition may be continued as long as four days, and the animal wake unharmed ; but if the dose has been suffi- cient, after several days of sleep death occurs from asphyxia. According to E. M. Houghton and T. B. Aldrich, 1 applied locally to the frog's heart, it slows the rate and produces a more complete systole, and has no action upon the blood itself. Locally applied it is a sensory nerve paralyzant. Houghton and Aldrich having failed to detect it, acetone, or chloroform in any of the excretions of the poisoned animal, believe that it undergoes decomposition in the body. THERAPEUTICS. Chloretone has been used to a considerable extent in practical medicine, but appears not to have fulfilled the expectations of the profession, and is not employed as much as formerly. Its local irritant effect greatly interferes with its use as an anaesthetic, but its one per cent, solution is distinctly antiseptic and sometimes acts well upon foul, irritable ulcers and wounds. It has also been em- ployed in doses of from five to eight grains in vomiting, gastric cancer, and other painful local conditions of the stomach. As an hypnotic it has been used in ordinary insomnia, delirium tremens, and various forms of insanity, but is uncertain in its action. According to Wharton Sinkler, 2 it is useful in epilepsy, and especially in petit mal, in doses of from three to five grains, three times a day. We know of no deaths reported from chloretone ; one hundred and twenty grains taken during twenty-four hours (W. M. Donald 3 ) caused profound sleep lasting for six days, without any untoward symptoms except gastric irritability. The pulse ranged from 85 to 104, and the bodily temperature fell to 96 F. During the latter part of the sleep the patient could be aroused for brief conversation, t The dose of chloretone has been set down from twelve to fifteen grains (0.8-1 Gm.), but we have exhibited thirty grains in the twelve hours without the produc- tion of any symptoms whatever ; and Wade, 4 who has used the drug largely, gave the average dose as from thirty-five to fifty grains. Laboratory Use. Chloretone is highly commended by some physiologists for use in the laboratory, but we have found the difficulty of administration, growing out of its insolubility, to interfere seriously with its practical employment. When recovery from the anaesthetic sleep is desired, 0.2 Gm. per kilo body-weight may be given ; but when, as in class demonstration, it is intended to put the animal to death, much larger doses may be administered in many cases without interfering with the experiment. * Chloretone was discovered by Willgerodt in 1881, and suggested as a substitute for chloral by him in 1884. In 1891 John J. Abel began to experiment with it, and in 1894 demonstrated its usefulness as a practical hypnotic and anaesthetic for the physiologist (see Science, January, 1895). Abel states that Faust has found that urethan and chloretone rubbed together make a fluid. The physiological properties of this substance do not seem to have been investi- gated. t According to Impens (A. I. P. T., 1901, viii. 77), chloretone is a much more danger- ous hypnotic than chloral, the ratio of the somnifacient to the fatal dose being only as 1:1.7. SOMNIFACIENTS. 163 CARBAMAS. U. S. Ethyl Carbamate. Urethane. Carbamic Ether. This ester of carbamic acid occurs in the form of odorless columnar crystals or scales, of a cooling, saline taste, soluble in less than one part of water. It was originally proposed by Schmiedeberg 12 as an hypnotic which acts directly upon the cerebral cortex, depresses the motor side of the spinal cord, but has very little influence upon the circulation, the arterial pressure remaining normal even during deep narcosis. Clinical experience has shown that urethane is somewhat uncertain in its action, but that it may be used, sometimes with satisfactory results, as an hyp- notic and also as an anti-convulsant in puerperal and other serious eclampsia as well as in tetanus. The official dose of it is fifteen grains (i Gm.), but seventy- five grains have been taken without very distinct effects, and twice the official dose may be given without danger. AMYLENE HYDRATE, a clear, colorless liquid, of a penetrating odor, soluble in eight parts of water, was brought forward in 1885 by Von Mering and Thier- felder, 13 and is said by its discoverers to act very much like chloral, but to require double the dose. Five grammes of amylene hydrate inhaled by a man produced profound narcosis, paralysis of the extremities, dilated pupil, abolished reflexes ; slow, deep, irregular respiration ; failing pulse, with depression of the temperature. The drug appears to differ from most other hypnotics in being a poison both to the voluntary and cardiac muscles. The assigned dose is from thirty to forty minims (2-2.5 C.c.). AMYLENE CHLORAL. Dormiol. This drug, formed by the union of chloral and amylene hydrate, is a colorless, oily liquid with a camphor-like odor, insoluble in water. There is much recorded clinical evidence as to its value in insomnia which is not dependent upon the existence of pain. It has been largely employed in insane asylums, and it is asserted that it has no disagreeable after-effects ; that it is not depressant to the heart, and may be used in cardiac insomnia ; and that when continuously exhibited it does not produce chronic poisoning. Its action is prompt, but somewhat fugacious, and patients rapidly become accustomed to its use. Dose, from ten grains to one drachm (1-4 Gm.) in capsules or dropped in cold water. METHYLAL, brought forward by Personali, is said by Motrokhin, when inhaled by man in doses of two ounces, to produce sleep with loss of sensibility, without any effect upon the heart. Popoff, however, affirms that it acts directly upon the cardiac muscle. It is so rapidly absorbed and eliminated that it should probably be considered an anaesthetic rather than an hypnotic, and it is said that it very rapidly loses its power over patients. Dose, from one to two drachms (4-8 Gm.). HEDONAL (Methyl-propyl-carbinol-urethane}. This occurs in colorless crystals, sparingly soluble in cold water, of a disagreeable somewhat menthol-like taste, which are believed to split up in the system into carbon dioxide, ammonia, and urea. It has been brought forward as an hypnotic, which in severe cases of insom- nia or when the patient is kept awake by pain, is of little service, but is valuable in mild cases on account of having no disagreeable after-effects. No cases of poisoning by it have been reported, and so far its prolonged use has not been followed by disagreeable symptoms. It is not known to have any influence upon the circulation, and, resembling trional in its action, has been especially commended as an alterna- tive to that drug. Probably owing to the formation of urea, it sometimes acts as a diuretic, and, according to de Moor, this action is much increased by its adminis- tration in solution. Dose, from fifteen to forty-five grains (1-3 Gm.), preferably administered in capsules half an hour before the desired effect. ISOPRAL ( Trichlorisopropylalkohol). This substance, which has been proposed as an hypnotic, occurs in microscopic prisms, melting at 49 C. , readily soluble in 164 GENERAL REMEDIES. water, alcohol, or ether, readily subliming, and having a camphor-like odor and aromatic taste. According to Impens, 1 * it is readily absorbed through the skin, the subcutaneous tissue, and the digestive tract, its effects when taken internally being manifested in from three to five minutes. It is said also that a stream of air directed over warmed isopral will produce marked narcosis in the lower animals in ten or twelve minutes. It is eliminated through the kidneys chiefly as a glycuronic acid compound, trichlorisopropylglycuronic acid, although it is believed also to escape to some extent through the respiratory tract. According to Impens, in proportion to its narcotic influence it is only half as poisonous to the lower animals as is choral. The dose for man does not seem to have been determined. In the dog the smallest dose certain to produce sleep is said to be 0.093 gramme per kilogramme, 0.6 gramme being the lethal dose. YERONAL (Di-ethyl-malonyl-nrea). This drug occurs in odorless, colorless, slightly bitter crystals, soluble in one hundred and forty-five parts of water at 68 F. Originally brought forward by E. Fischer and J. von Mering 15 as an hypnotic, veronal has been tested by various clinicians in all forms of insomnia, with reports which are very favorable. It has been found by Mendel and Kron and by Weber* to be especially valuable in the treatment of insomnia with motor excitement or active hallucinations, also in depressive insanity ; contrary to the statements of some clinicians, Mendel and Kron deny its value as an antineuralgic. Concerning its general physiological action we have little knowledge, but C. Trautmann 16 affirms as the result of experimental studies that it lessens nitrogenous elimination. Various authorities assert that it leaves no after-effects ; but Jolly, Rosenfeld, and Wiirth have noticed after its taking, malaise, headache and giddiness, and even disturb- ances of speech, chiefly when it has been given in very large doses. Originally recommended in doses of half a gramme, veronal has been given prac- tically up to one and a half grammes, but has been reported by various observers as efficient in much less amount ; so that at present from ten to fifteen grains (0.6-1 Gm. ) may be considered as its dose.f HYPNONE or ACETOPHENONE, originally suggested by Dujardin-Beaumetz, according to various authorities, acts more powerfully as a paralyzant than as an hypnotic, and has been condemned by a large number of clinicians. The maximum dose given by Rey, without, however, the production of sleep, was sixty drops, or twenty-three grains (1.5 Gm. ). CHLORALFORMAMIDUM. U. S. Under the names of chloralamid, chloralform- amid, a compound of chloral and formamid has been used as an hypnotic and has been made official. It is a slightly bitter crystalline substance, soluble in twenty parts of water and one and a half parts of strong alcohol. It is decomposed by hot water, but its solution in cold water is moderately permanent ; it is rapidly decom- posed by alkalies. In the lower animals, chloralamid produces lethargy, narcosis, sleep, and, finally, if it has been taken in sufficient amount, death from failure of respiration. According to Langgaard, 5 in the rabbit the sleep is accompanied by pronounced decrease in the amount of air drawn in and out of the lungs and pro- nounced lessening of the blood-pressure. These results, however, are scarcely in accordance with those of other observers. Otto Halasz 8 found the blood-pressure very slightly affected. Von Mering and Zuntz have shown that the fall in the air movements of respiration obtained by Langgaard was not greater than that which results from sleep, and also obtained deep sleep and even complete anaesthesia in the rabbit without fall of the arterial pressure. * For references, see D. W. M., 1903, pp. 608, 726. f See S. Jb., Bd. cclxxviii., cclxxix, for abstracts of the literature to date ; also Ther. Caz., 1903. SOMNIFACIENTS. 165 In a series of experiments made by David Cerna and H. C. Wood in the lab- oratory of the University, it was found that the influence of chloralamid upon the circulation is very feeble, only the largest toxic dose lowering the arterial pressure at all. In the dog the respirations were always enormously hurried by the drug, although no experiments were made to determine the absolute amount of air moved. The action of the drug upon the spinal cord was also very feeble, and no perceptible influence was shown upon the nerves and muscles ; but the effect upon the cerebral cortex was very pronounced. THERAPEUTICS. Chloralamid is a rather slowly acting and uncertain hypnotic, which usually does not cause any unpleasant after-effects, but sometimes produces confusion, giddiness, and headache. It has been especially recommended by Hage- mann and Hiifler 7 for the relief of cardiac asthma. Our knowledge of its physio- logical action seems to show that the assertions of various clinicians, that it is better borne than chloral in cases where there is cardiac weakness, have a foundation in fact. It should be given in doses of from thirty to fifty grains (1.9-3.2 Gm. ), admin- istered in watery solutions or capsules half an hour before the expected time of sleep. CHLORALOSE occurs in small crystals, having a very bitter and disagreeable but not acrid taste. It is freely soluble in hot water, slightly so in cold water. It was first brought forward as a remedial agent by Hanriot and Richet, 8 who state that five grammes of it will produce in a dog of ten kilogrammes' weight symptoms of intoxication followed by a most profound sleep in which all sensibility is lost, although the reflex activities are greater than normal ; that upon the circulation it has but little power, the arterial pressure, even when there is profound unconsciousness, being scarcely affected ; that during the unconsciousness not only is the motor side of the spinal cord more active than normal, but the cerebral cortex is excessively excitable, the animals experimented upon offering a strong contrast with chloral- ized dogs, in which the cerebral cortex is almost devoid of responding power. The statements of its discoverers, that, taken in doses of five grains, it would produce in man a profound sleep lasting for many hours, and not followed by unpleasant after-effects, have not been sustained. Its action is very variable ; the dose of ten grains will in many cases produce no effect, and yet in other cases has caused com- plete unconsciousness with marked cyanosis and slowing of the pulse. Its thera- peutic influence has frequently been attended by very unpleasant symptoms, such as tremors, partial or general paralysis, great slowing of the pulse and cardiac depres- sion, involuntary discharge of urine during sleep, excessive vomiting, and delirious intoxication. In our experience, although occasionally useful, the drug has not proved generally satisfactory. Dose, from five to ten grains (0.3-0.65 Gm.).* BUTYL-CHLORAL HYDRATE. This substance, formed by the action of chlorine gas upon aldehyde, crystallizes in small, glittering tables, is soluble with difficulty in water, and when in solution breaks up in the presence of an alkali into sodium chloride, sodium formate, and bichlorallylene. Under the name of croton-chloral, it was introduced into practical medicine by Oscar Liebreich, 9 because he found that, whilst acting in general like chloral, it depressed less powerfully the pulse and respiration, and especially affected the trigeminal nerve, lessening its sensibility before the appearance of narcosis, a drachm of it producing complete anaesthesia of the head and eyeballs. According to Liebreich, toxic doses produce deep sleep, trigeminal anaesthesia, and arrest of respiration, the circulation being maintained with great tenacity. These assertions of Liebreich have not, however, been sus- tained. J. von Mering found that the cornea remained sensitive until respiration was reduced to half its normal rate ; that in dogs, cats, and rabbits the drug, in small or in large dose, lessened the blood-pressure, and when brought in concen- trated form in contact with the heart, arrested its movements. These results have * See Brit. Med. Journ., 1893, ii. For cases of unpleasant action, see Schmidt's Jahrb., ccxlv. ; also Revue Neurolog., 1894, ii. i66 GENERAL REMEDIES. been confirmed by E. Lahousse 10 and H. Mindel Schmidt," so that it is very difficult to perceive wherein the action of croton-chloral practically differs from that of chloral. Croton-chloral was asserted by Liebreich to be very powerful in relieving neu- ralgia, tic douloureux, and other painful affections of the trigeminus, and consider- able support has been given by clinicians to his statement. On the whole, however, the drug has failed to sustain itself, and is at present but little used : that it has any greater effect than chloral is very doubtful. It is usually administered in doses of from five to twenty grains (0.32-1.3 Gm. ), in syrup. The safest plan is to give five grains every half-hour until thirty grains have been taken or relief afforded. Liebreich uses it according to the following formula : butyl-chloral hydrate, five to ten parts ; glycerin, twenty parts ; distilled water, one hundred and thirty parts. Dose, half an ounce, followed in five minutes by a second, and ten minutes later by a third unless relief is afforded. REFERENCES. OPIUM. ORLT B. K. W., 1889, xxvi. ROSENTHAL . . . C. K. M., 1893, i. BOUCHARDAT . . S. Jt>., CXX. LEFORT J. Ch., xi. KAUSMANN ELIASSON . In. Dis., Dorpat, 1868. In. Dis., Konigsberg, WORMLEV . . . . U. M. M., 1890. ROSENTHAL . . . C. K. M., 1893, xiv. BINKT R. M. S. R., 1895, xv. HAMBURGER . . S. Jb., ccxlix. L. M. R., 1887. ANTHEAUME and MOUNEYRAT . C. R. A. S., 1897, cxxiv. 1475. FAUST A. E. P. P., 1900, 44. JAKSCH D. M. W., 1888, xiv. ADLER ...... Pr. M. W., 1900, xxv. CHARVBT .... Pereira's Materia Medica, 1035, Philadelphia, 1854. LUZZATTO . . . . A. E. P. P., 1904, Hi. 95. BAXT A. A. and P., 1869, 128. KOLLIKKR . . . . V. A. P. A., x. 248. ALBERS V. A. P. A., xxvi. 229. MEIHUIZEN ... A. Ph., 1873, vii. MITCHELL . . . . A. J. M. S., Jan. 1869, Jan. 1870. GUINARD . . . . C. R. S. B., 1890, cxi. HESS A. W. P. T., 1901, xxvii. NOTHNAGEL . . . Handb. der Arzneimittel- lehre, Berlin, 1870. RIEGBL and PREISENDORFFER . D. A. K. M., xxv. 48. GUINARD . . . . C. R. S. B., 1895. GSCHEIDLEN . . Untersuch. aus dem Physi- olog. Lab. zu Wiirzburg, 1869, 2ter Theil. 29. RINGER and SAINSBURY . B. M. J., Mar. 1883. 30. BOECK and BAUER . Z. Bi., x. 339. 31. CHITTENDEN and CUMMINS . S. L. C. Y., ii. 32. REICHERT .... P. M. J., March 9, 1901 ; also U. P. M. B., 1903. 33. THOMPSON . . . A. A. and P., 1894. 34. NOTHNAGEL . . . V. A. P. A., Ixxxix. 2. 35. OTT N. Y. M. J.. 1883. 36. LOOMIS N. Y. M. R., 1873. 37. FISET N. Y. M. R., 1874. 38. TAYLOR .... Med. Juris., 1873, 205. 39. REICHERT . . . . T. G., Aug., 1902. FELL Medical Examiner, June, 1899. PLAYFAIR . CALKINS . MITCHELL MYRTLE . 40. FELL N. Y. State Med. Ass., L. L., 1898, ii. 545. S. Jb., clvii. 74. La France Med., 1883, ii. Q. J. P. M., 1868, ii. 739. C. M. J. E., July, 1882. A. J. M. S., Jan. 1870, 26. B. M. J., 1874, i. 478. DRESER Th. M., 1898. STRUBE B. K. W., 1903, xl. 1076. OTT Medical Bulletin, 1899, xxi. 410. IMPENS A. G. P., 1899, Ixviii. 527. MARSHALL . . . B. M. J., 1902, Oct. 18. MOREL-LAVALLEE . R. Med., 1900, xx. 872. Ph. Post, 1899, 743. THOMPSON . . . N. Y. M. J., 1900, Ixxi. 171. STRAUSS M. M. W., 1902. xlix. ELISCHER .... Hk., Feb. 1902. CLOETTA .... A. E. P. P., 1903, 1. 451. LUZZATTO . . . . A. E. P. P., 1904, Hi. 95. CHLORAL. KEEN A. M. J. S., July, 1875. TOMASCEWICZ . . A. G. P., ix. 35. FELTZ and RITTER . C. R. S. B., Ixix. 966. ECHARD A. E. P. P., xii. 276. BORNTRAEGER . In. Dis., Marburg, 1879. KULZ A. G. P., 1882, 506. RICHARDSON . . M. T. G., Sept. 4, 1870. DEMARQUAY . . . B. G. T., Ixxvii. 307. RAJEWSKY . . . . S. Jb., cli. LABBEE A. G. M., 1870, xvi. 338. ANSTIE and ANDREWS . Amer. Journ. Insan- ity, July, 1871. PREISENDORFFER . D. A. K. M., xxv. 48. ANDREWS and DA COSTA . A. J. M. S., April, 1870. KOBERT T. G., 1887. RINGER and SAINSBURY . B. M. J., March; 1883. CERNA U. M. M., Nov. 1891. RICHKT A de P., 1890, ii. GRITZKA .... In. Dis., Berlin, 1891. PEISER Thesis, Halle, 1892. WERTHEIMHR . . C. R. S. B., 1903. WERTHEIMER and LEPAGE . E. M. N., 1903. SOMNIFACIENTS. 167 REFERENCES. Continued. 13. LEVINSTEIN . 23. LlEBREICH . 24. RUSSELL . . 25. BECK .... 26. MACNAMARA 27. WIDENHOFER 28. HALL .... 29. PLAYFAIR . . 31- 32. CLEMENS 33. STONE . . 34. BOOTH . . 35. BRUNTON 36. KIRN . . 37. SMITH . . 38. KIRN . . 39. SCHULE . . L. L., 1874., i. . W. M. W., August, 1869. . Gl. M. J., Feb. 1860. .St. L. M. S. J., June, 1872. . Practitioner, Nov. 1874. . B. M. S. J., 1874. . L. L., May 2, 1874. . L. L., 1874, i. N. Y. M. J., xxxvii. 445. . Etudes sur l'Anesth6sie Chirurgicale, etc., Paris, 1875- . S. Jb., cli. 99. . Louisville Med. News, xv. 179-. . L. L., 1884, i. 468. . J. A. P., 1874, viii. . Al. Z. Ps., 1872, xxix. . B. M. S. J., 1871. . B. K. W., xx. 721. . Al. Z. Ps., xxviii. CHAPMAN . . . . L. L., 1871. ELLIOTT L. L., 1873, i. 754. REYNOLDS .... Practitioner, March, 1870. WATSON M. and S. Rep., Jan. 27, 1871. FULLER L. L., March, 1871. SCHWAIGHOFER . Irish Hosp. Gaz., 1873. LATHROP .... Year-Book of Therapeutics and Pharmacy, 1872, 254. B. K. W., 1876. VULPIAN . . . . C. R. S. B., Ixxxvi. 1303. SULPHONAL. KAST B. K. W., 1888. BAUMANN and SALKOWSKI . C. M. W., 1892, XXX. B. M. J., 1898, ii. NEISSER S. Jb., ccxxxi. PETITT M. News, 1899, Iv. HOPPE-SEYLER and RITTER . S. Jb., ccxxvii' 194. ANDREWS . . . . J. A. M. A., 1892. DAUTHVILLE . . Thesis, Paris, 1889. KAST A. E. P. P., 1892, xxxi. 10. GARROD and HOPKINS . J. P. and B., 1895-96. iii. 11. STOKVIS S. Jb., ccxlviii. 12. KAST and WEISS . B. K. W., 1896, xxxiii. 13. HERTING . . . . S. Jb., 1894, ccxliv. 14. MULLER W. K. W., 1894, 252. 15. ERBSLOH . . . . D. Z. N., 1903. TRIONAL. 1. BERGER M. M. W., 1895. 2. COLLATZ . . . . B. K. W., 1893. 3. WIGHTWICK and ROLLESTON . L. L., 1903, i. 1096. 4. HAENKL Psycholog. Arbeit., 1897, ii. 5. EGASSE B. G. T., 1894, ii. 6. KRONFELD . . . W. M. Bl., 1898, xxi. PARALDEHYDE. 1. BOKAI and BARCSI . P. M. C. P., 1885-86. 2. CAPPELLI and BRUGIA . A. I. M. N., 1886, i. 3. DRAGE L. L., Sept. 1900. 4. RAIMANN .... W. K. R., 1899, Nos. 19, 20, 21, 22. 5. PROBST M. P. N., 1903, Bd. xiv. 6. V. A. S., 1887, xiv. 7- Cb. N., 1900, S. 139. MINOR HYPNOTICS. 1. HOUGHTON and ALDRICH . J. A. M. A., Sept. 23, 1899. 2. SINKLE-R T. M., July, 1901. 3. DONALD T. G., Jan. 1900. 4. WADE J. N. M. D., 1900. 5. LANGGAARD . . . Th. M., 1889. 6. HALASZ W. M. W., 1889. 7. HAGEMANN and HUFLER . M. M. W., iSi;. 8. HANRIOT and RICHET . C. R. S. B., 1893. 9. LIEBREICH . . . B. M. J., Dec. 1873; Feb. 1876. 10. LAHOUSSH . . . .A. Pharm., 1895, i. 11. SCHMIDT .... Cb. C., 1877, 210. 12. SCHMIEDEBERG . A. E. P. P., XX. 210. 13. VON MERING and THIERFELDER . Z. P. C., 1885, 1. 9. 14. IMPENS T. M., Sept. 1903. 15. FISCHER and VON MERING . Ther. Geg., v. 97. 16. TRAUTMANN . . Ther. Geg., 1903. FAMILY IV. DELIRIFACIENTS. IN the present group are considered medicines whose preparations, when taken into the system, cause marked dilatation of the pupil and act upon the cerebral nerve-cells so as to produce delirium. BELLADONNA FOLIA BELLADONNA LEAF. U. S. BELLADONNA RADIX BELLADONNA ROOT. U. S. The leaves and root of Atropa Belladonna, an herbaceous perennial, a native of Europe, but cultivated in this country, and attaining a height of some three feet. The dried leaves are oval, entire, on a short foot- stalk ; they have a faint narcotic odor, and a sweetish, sub-acrid, slightly nauseous taste. The dried cylindrical branched root is from one to several inches in diameter, much longer, fibrous, externally reddish brown, internally whitish, almost odorless, with a very feeble sweetish taste. The dominant alkaloids of belladonna are hyoscyamine and atropine, belladonnine and other alkaloids, whose isolation from it has been alleged, being either present in exceedingly minute quantities or derivatives from the more important alkaloids. There is even much reason for believing that atropine itself is a secondary product derived from hyoscyamine, chiefly during the process of manufacture. The toxic effects and the therapeutic uses of belladonna are those of atropine, which alkaloid should always be preferred to the cruder preparations of the drug when a distinct physiological effect is desired. ATROPINA. U. S. Atropine* occurs in silky prismatic and acicular, often aggregated, crystals, of a bitter, burning taste, without odor, practically insoluble in water, and therefore always used in the form of the sulphate. It is most abundant in the root, and, according to M. Lefort, 1 in that of young plants. PHYSIOLOGICAL ACTION. Local Action. Elimination. Atropine is not irritant, but when locally applied in sufficient concentration is probably paralyzant to most of the higher forms of protoplasm, overpowering the capillary walls, the sensory and motor nerves, and even muscular and glandular cell-action. A. Zeller 2 has found that a one per cent, solution of atropine brought in contact with the blood, outside of the body, checks the movements of the corpuscles. Atropine is absorbed with great rapidity from the primse vise and slowly but certainly through the skin. It is eliminated in great part or altogether unchanged, chemists having failed to find in any secretion the * For the relations of atropine to other mydriatic alkaloids, see HYOSCINE, page 187. 168 DELIRIFACIENTS. 169 natural decomposition product, ecgonin, and Wiechowski having re- covered, on an average, thirty-three per cent, of the injected atropine from the urine. It has been found in all the tissues of the poisoned individual, and S. Fubini and O. Bonanni 3 have detected it in the milk, but it chiefly escapes by the kidneys ; hence poisoning may often be diagnosed by dropping the urine of the patient in the eye of a cat or other domestic ani- mal, when mydriasis will be produced.* General Action. Usually the only symptom induced in man by the smallest physiological dose of atropine (one-hundredth to one-sixtieth of a grain) is dryness of the throat and mouth, and possibly some dis- order of vision. When larger amounts are given, this dryness is more intense, and is associated with redness of the fauces, dilated pupils, dis- ordered vision, and possibly diplopia. The pulse is sometimes at first rendered less frequent, but this decrease is very transient, and certainly in many cases cannot be demonstrated at all. After a toxic dose of the alkaloid, often from the first, certainly always in a short time, the heart's beats become excessively rapid, the pulse rising to 120, or even 160 ; and in a little while a peculiar bright red flush appears on the face and neck, and may spread over the whole body. This erythema resembles the rash of scarlet fever, but lacks punctation, and is usually not followed by des- quamation. Early in atropine-poisoning there may be forcible expulsion of urine, and even erections of the penis ; later there is urinary retention. With the symptoms above enumerated, intellection may remain perfect ; but there is generally some lightness of head, giddiness, and confusion of thought, as well as a staggering gait and restlessness. Occasionally, even medicinal doses cause spectral illusions. Drowsiness is not a usual or at all characteristic symptom. When the dose has been suffi- cient there develops a peculiar talkative, wakeful delirium, in which the patient lives in a world of his own, engrossed by spectres and visions which throng him, and completely oblivious to the surrounding realities. Thus, we have seen a lady remain for a long time stooping and holding fast to the bed-post, to which she talked in the most voluble manner, as though it were an intelligent, living entity. Sometimes this delirium is wild, and the patient almost uncontrollably violent. After a time, sleep may come on, and on waking complete consciousness may be regained, or the symptoms may gradually subside. Lividity of the face and evident imperfect aeration of the blood are not seen in atropine-poisoning, except in the stage of imminent peril. When an enormous dose of the alkaloid has been taken a fatal stupor with mus- cular relaxation may develop almost at once ; or severe convulsions may appear and persist, with or without furious maniacal delirium. Probably, however, in all fatal cases stupor and muscular paralysis finally develop ; and although there is marked failure of the circula- tion, the immediate cause of death is asphyxia, produced by depression * For a chemico-physiological study of tropine and other derivatives from atropine, see Archivf. Exper. Pathol. u. Pharm., v. 403. 1 70 GENERAL REMEDIES. both of the respiratory nerve-centres and of the respiratory nerve-trunks. Congestion of the lungs and of the membranes, and even of the sub- stance of the brain and cord, may be found after death, and, according to M. Lemattre,* congestion of the retina is an almost characteristic lesion. Upon the lower animals belladonna to a great extent acts as upon man, although its influence is much less powerful in them, and very much larger doses are required. Seeming differences of action are in most cases simply apparent, not real. In the dog, as in man, the pulse-rate is very greatly increased by atropine, while in the rabbit it is not. As will be shown hereafter, the rise of the pulse-rate caused by atropine is largely due to paralysis of the par vagum. Atropine paralyzes the par vagum in the rabbit as much as in the dog, but in the domestic rabbit pneumogastric paralysis, by section or otherwise, is never followed by a rise of the pulse-rate at all comparable to that seen under similar circumstances in the dog. Evidently the action of the drug is identical in the two cases, although the symptoms are different. In their sensitiveness to atropine animals differ very much, and, as a general rule, herbivora are less susceptible than carnivora. Thus, the rabbit may be fed for days entirely upon belladonna-leaves without injury, and many grains of atropine are necessary to kill him. Pigeons we have found will often re- cover after the hypodermic injection of two grains of atropine, and, according to Fe're', 1.75 grammes taken by the mouth will not kill a hen of 2.9 kilogrammes' weight. A very curious fact, which we have repeatedly verified, is that the pupils in pigeons cannot be dilated by the use of belladonna. According to Richet, the monkey offers an extraordinary resistance to the action of atropine. Circulatory System. Atropine may cause a primary slowing of the pulse (very brief and only to be occasionally demonstrated), followed by an extraordinarily rapid pulse, with a very great rise in the arterial press- ure ; followed after a time, if the dose have been sufficient, by a progres- sive lowering of pressure until death is reached, the rapidity of the pulse being maintained until the end. As in atropinized animals neither section nor galvanization of the vagi affects the pulse-rate, the increase of the pulse-rate must be largely due to paralysis of the trunk or of the peripheral endings of the vagi. The primary fall of the pulse, in accordance with the experiments of Bezold and Bloebaum, 4 is due to stimulation of the inhibitory cardiac centre ; these observers having found that when atropine is injected into the carotid so as to reach the pneumogastric centres before the pneumogastric nerve-endings, there is instantaneously a great fall in the rate of the heart's beat. Of course, in the fully atropinized animal any effect of the drug upon the inhibitory centres is masked by the inability of the paralyzed vagi to carry impulses from the centre, and, in fact, only in especial cases is the primary slowing manifested, f * Quoted by Tardieu (Sur I'Empoisonnement, Paris, 1867, 752). t See Stille's Therapeutics, \. 725. Mitchell, Keen, and Morehouse found it in about one-third of the cases after large hypodermic injections, Da Costa in a large proportion (Amer. Journ. Med. Set., July, 1865), and Miss Mary Putnam in some cases (New York Medical Record, 1873). DELIRIFACIENTS. 171 By large doses of atropine both the batrachian and mammalian heart are depressed and arrested in diastole, out of which they cannot be aroused by stimulation ; and Bezold and Bloebaum have found that after section of the spinal cord and vagi full doses of atropine lessen at once the arterial pressure. It is therefore established that overwhelming doses of atropine act as a direct paralyzant upon the heart-muscle. The question as to the effect of small doses has been much debated, but probably very minute quantities exert a feeble, stimulating influence upon the mammalian heart ;* thus, Ramson discovered that atropine causes in the heart of the octopus excitation of the muscular fibre ; O. Langendorff 5 found that when the cut-off apex of the frog's heart was touched with a minute quantity of atropine it immediately commenced to beat ; f and G. Beyer 7 noticed that the ventricles of the isolated terrapin' s heart are stimulated by minute quantities of the alkaloid, although they are arrested in diastole by larger amounts. This action of the drug upon the heart-muscle is probably the cause of the increased pulse-rate which has been noted as occurring when atropine is given after division of the vagi, although it is possible that this increase is due to stimulation of the accelerators. J The recorded evidence obtained by the direct observation of the capil- laries under the microscope during poisoning of frogs by atropine is, on the whole, in favor of the view that minute doses of atropine cause contractions of the vessels ; but much more decisive proof is to be obtained as to the effect of atropine upon the vaso-motor system by a study of the arterial pressure. It was first proved that the alkaloid is powerless to produce rise of the arterial pressure after separation of the vaso-motor centres, by high-up section of the spinal cord, from the blood- vessels of the body, by Bezold and Bloebaum, whose statements were con- firmed in 1873 by H. C. Wood. 8 Further, Bezold and Bloebaum have found that when a small dose of atropine is injected into the carotid artery, that is, into the vaso-motor centres, there is an instantaneous rise of pressure. There can be no doubt that the chief factor in the great rise * Harnack (Archivf. Exper. Pathol. Pharm., ii. 328) finds that the minutest dose of atropine increases the rapidity of the heart's action after stimulation of its inhibitory centres by muscarine and consequent slowing of its beat. t The reports as to the action upon the rate of the frog's heart are somewhat at variance, Eowditch and Luciani having noted an increase, Gnauck 6 a lessening, in the cardiac pul- sations ( Verhandl. Physiolog. Gesellsch. zu Berlin, 1881). H. Schapiro states that this variance is accounted for by the fact which he has discovered, that whereas at high tem- perature (15 C.) the pulsations are diminished, at low temperature (7 C.) they are increased. J See University Med. Magazine, May, 1891 . $ A fuller discussion of this subject may be found in the tenth edition of this book. It is omitted here because we do not think that evidence of this character is of much im- portance. The contraction of the capillaries by a local application may be the result of mechanical or other irritation. Moreover, the alterations in the calibre of the vessels are so slight, and are so apt to occur from other causes than the drug given, as to leave great play for the imagination of the observer, a source of fallacy whose importance is indicated by the ever-varying results obtained by the different investigators. 172 GENERAL REMEDIES. of arterial pressure produced by atropine is a stimulating influence upon the vaso-motor centres. The final fall of blood-pressure in atropine-poisoning is due to its de- pressing influence upon the heart-muscle and upon the muscles in the walls of the capillaries. The local application of the alkaloid to the web of the frog's foot is soon followed by a complete paralytic dilatation of the vessels ; further, Bezold and Bloebaum have found that in atropine- poisoning the arterial muscular coats finally lose their irritability, but that, so long as they retain it, galvanic stimulation of a sympathetic nerve does not fail to induce contraction in the tributary vessels. Cerebrum. The delirium which is so characteristic of atropine-poison- ing shows that it has especial relations with the cerebral cortex. Alber- toni 9 finds that neither the single large dose nor the repeated continu- ous dose has any power in preventing the epileptic seizure resulting in dogs from the stimulation of the motor zone of the cortex : enor- mous toxic doses seem only to render the response slower and less vivid. The influence of atropine upon the psycho-motor centres would, there- fore, appear to be slight. It should be noted that atropine is not in a proper sense hypnotic, the stupor which it produces being due to an overwhelming of the cerebral cortical centres, and not being preceded by sleep. Motor Nerves. The original discoveries of S. Botkin, 10 that tying the vessels of a frog's leg, so as to shut off access of atropine to the nerve, interferes with the development of paralysis during the poisoning in such leg, and that the nerves after death from atropine-poisoning have in the frog largely lost their power of responding to galvanic currents, have been abundantly confirmed by Lemattre, by Bezold and Bloebaum (Joe. cit., 20), by Meuriot, 11 by Eraser, and others. Although in mammals a notable amount of functional power is retained by the motor nerve up to death from atropine, yet it is demonstrated that atropine is a distinct depressant to the motor nerves, both in the higher and in the lower ani- mals ; and, according to Bezold and Bloebaum, both the nerve-trunks and the peripheral intra-muscular nerve-endings are affected. All experi- menters agree that no stage of super- excitability preceding that of depres- sion can be discovered. Sensory Nerves. The action of atropine upon the sensory nerves is similar to its influence upon the motor nerves, although less powerful.* S. Botkin found that if in the atropinized frog the nerve of one leg had been protected from the poison by tying the artery, irritation of the foot of the non-protected leg at a time when that leg was completely paralyzed would cause spasm in the opposite limb whose motor nerve was pro- tected ; yet later in the poisoning, although irritation of the foot of the protected leg would cause movement in that leg, no irritation of the op- * For objections to Miss Mary Putnam's paper ( N. Y. Med. Rec., 1873), which would indicate that the sensitive nerves are especially affected by atropine, see tenth edition of this treatise. DELIRIFACIENTS. 173 posite poisoned foot was able to induce response, showing that at first the sensory nerve was intact in the paralyzed leg, but that it finally suc- cumbed to the poison. Meuriot found that if a frog be bound tightly around the body so as to interrupt the circulation, and then be poisoned by atropine in the front part of its body, at first irritations in any part will give rise to general spasms, but after a time in order to get any movements of the hind legs it is necessary to apply an irritant to them. Again, the hinder parts of a frog were so bound by ligatures as to cut off on the one side all commu- nication except by the nerves, and on the other to leave free the nerve and the vessels. A large injection of atropine was then given, and when the moment came that irritation of the periphery of the leg whose circu- lation was free would no longer cause reflex spasms, the artery of this leg also was tied, so that both legs, the one atropinized, the other not, were now connected with the body of the frog only by their nerves. Strych- nine was given hypodermically, and it was found that, while irritation of the atropinized leg had no effect, stimulation of the non-atropinized leg gave rise to general convulsions. It is plain, however, that the influence of atropine upon the sensory nerve is feeble ; for, although Botkin con- firmed the experiments of Bezold and Bloebaum, he found that immersion of a sciatic nerve for some little time in a two and a half per cent, solution of the alkaloid did not, in the strychnized frog, prevent the nerve trans- mitting the impulse, since irritation of the foot would produce general convulsions. Spinal Cord. Thomas R. Eraser 12 discovered in 1869 that if a frog receive an injection of about one-thousandth part of its weight of atropine, a condition of perfect paralysis and abolition of reflex action comes on after a time, and lasts from two to four days, to be succeeded by a tet- anoid stage, with violent convulsions of spinal origin and excessive excita- bility of the reflex centres. For reasons given in full in the tenth edition of this treatise, Fraser came to the conclusion that atropine stimulates the spinal cord, and that during the paralytic stage of the poisoning this con- dition of the cord is masked by the paralyzed state of the efferent nerves. This conclusion, however, has been disproved by Ringer and Murrell, who found that tying an artery so as to protect the nerve-trunks from the poison did not hasten the development of the tetanus ; and also showed that in some poisoned frogs voluntary and reflex action return before the supervention of the tetanus. It is evident that both paralysis and tetanus are due to an action upon the spinal centres, the drug so acting upon the spinal cord as first to paralyze and then intensify its reflex activity. The theory approved by Ringer and Murrell, that both the paralysis and the tetanus are due to a depressant action upon this cord, is plausible and probably correct. According to this theory the spinal cord has within it two functions, motion and inhibition, certain cells giving off motor impulses, certain nerve-fibres inhibiting these motor impulses. In the normal cord the I 7 4 GENERAL REMEDIES. motor cells are under continual inhibition ; under the influence of atropine it is believed that both motor and inhibitory functions are paralyzed ; hence the general paralysis. After a time, however, the motor cells recover themselves so as to be able to generate impulses freely, although the in- hibitory function of the cord is still depressed, the effect being an appar- ently true spinal excitement, which is due to lack of inhibition, the motor cells being actually weak. At such a time a peripheral impulse reaching the motor cell, instead of giving rise to a simple reflex action, and then being inhibited, passes on and starts a series of reflex movements in- volving all the muscles and constituting a tetanic convulsion.* The experiments of Lemattre indicate that belladonna exerts a similar paralyzant and convulsant action in mammals ; both Eraser's and Reich- ert's experiments confirm this. It is very certain that in man atropine exerts this double influence, for the records of poisoning cases are at once the records of convulsions and of paralysis. It would seem that early profound paralysis occurs when a very large dose of the poison has been taken in a concentrated alkaloidal condition, and consequently has been rapidly absorbed and suddenly precipitated upon the nervous system. Voluntary Muscles. The voluntary muscles escape unscathed in atro- pine-poisoning. It is true that Lemattre has shown that the contractility of a striated muscle may be destroyed by soaking it in a very concen- trated solution of the alkaloid ; but long before any such action can take place in life the animal is killed ; consequently after death from belladonna the contractility of the voluntary muscles is found unimpaired. On the non-striated muscles the action of atropine is pronounced, but its exact nature is at present writing somewhat uncertain. It may, we believe, be considered proved that the toxic dose of atropine finally depresses all non-striated muscles ; the original assertion of Bezold and Bloebaum, that this paralysis may become so complete that the strongest faradic currents are unable to cause movements either in the intestines, bladder, uterus, or ureters, being probably correct. The uncertainty is as to the effects of small doses. P. Keuchel 1S seems to have proved that by a certain dose of atropine a condition is reached in which, although the peristaltic movements of the intestines are active, galvanism of the splanchnic the inhibitory nerves of the in- testinal coats fails to have effect. If this be true, atropine paralyzes the peripheral inhibitory intestinal apparatus precisely as it does that of * The conjunction of excessive irritability with lack of power in motor cells is a com- mon condition in hysteria and neurasthenia. The fact discovered by H. C. Wood, that choreic movements of the dog are increased by atropine and diminished by quinine, an inhibitory stimulant, fits very well with the theory of the text, and also with the further facts discovered by E. T. Reichert, that if a dog to which a supra-fatal dose of atropine has been given be kept alive by artificial respiration, choreic movements occur which are arrested by intravenous injections of quinine. It would appear that choreic movements are the result of inhibitory weakness ; that atropine, increasing inhibitory weakness, in- creases choreic movements ; and that quinine, stimulating inhibition, decreases these movements ; and that the two alkaloids, so far as inhibition is concerned, are directly antagonistic. DELIRIFACIENTS. 175 the heart. I. Ott u states that very minute doses of atropine prevent the 'production of peristalsis by salt placed upon the intestines, whilst large doses exaggerate the action of the salt. Admitting the correctness of the experiments of Ott and Keuchel, it is evident that atropine first stimu- lates the intestinal inhibitory nervous system and then paralyzes it. This, moreover, is corroborated by the fact that the smallest dose used by Keuchel was 0.075 g ram > by Ott 0.015 g ram > both observers experi- menting on the rabbit. When Ott used 0.45 grain he got the same result as did Keuchel. Respiration. The medicinal dose of atropine ordinarily has no ap- parent effect upon the respiration ; but both in man and in the lower animals the toxic dose usually, though not always, accelerates the respi- ratory movements. Researches upon the effect of atropine upon the respiratory movement* of air have been made by H. C. Wood, 15 Heubach, 16 E. Orlowski," E. Vollmer, 18 and Unverricht. 19 The experiments of Heubach, Orlowski, Vollmer, and Unverricht were made upon animals under the influence of morphine ; H. C. Wood's experi- ments were upon normal, morphinized, and chloralized dogs. The first effect of atropine in the normal animal is greatly to increase the respiratory air-movement. This primary excitement is usually soon followed by a decrease, which is not, how- ever, sufficient to overcome the first rise ; so that the air-movement remains for a long time distinctly above the normal. In the chloralized dog the effect of atro- pine in increasing air-movements is constant and pronounced. In H. C. Wood's experiments (two in number), as also in Orlowski's and Unverricht's, with animals under the influence of opium, no increase, but rather a decrease, in the air-move- ment was the result of injections of atropine. In Heubach' s and in Vollmer' s experiments, which were numerous, atropine distinctly increased the air-movement in the morphinized dog. The action of opium upon the respiration in the dog is at present so little understood that the question of the centra-action of atropine and morphine is entirely apart from that of the action of atropine. There is also reason for believing that the toxic dose of atropine paralyzes the peripheral pneumogastric nerve in the lungs, since in profound atropine-poisoning no marked influence is ex- erted upon the respiratory rhythm by section of the pneumogastric. As section of the vagi (Bezold and Bloebaum) does not prevent the increase of the respiratory air-movement produced by atropine, it must be concluded that atropine is a centric respiratory stimulant, which, as has been determined by Reichert, becomes a depressant or paralyzant when in toxic dose. In Reichert' s experiments it was found that if a dose two or three times the minimum lethal dose was given internally to the dog, the animal could be kept alive for hours by artificial respiration and ultimately recover. During the period of recovery certain remarkable phenomena habitually recurred, for an account of which the reader is referred to Reichert' s article. Glandular System. It is generally believed that the suppression of secretion in the salivary, mucous, and sweat-glands is due to paralysis of the terminal ends of the nerves, since Keuchel has shown that stimu- * See Respiratory Stimulants. 176 GENERAL REMEDIES. lation of the chorda tympani fails to excite the flow of saliva, while irritation of the sympathetic will cause secretion. Mathews,* 5 however, combats this theory, and believes that the action of atropine is upon the gland-structure, asserting that paralysis of the nerve will not prevent secretion. Small doses of atropine sometimes, but not always, increase the flow of urine. After the toxic dose the urine may be at first augmented, but is usually lessened very early, and may finally be entirely suppressed.* The assertion of Meuriot, that the urinary secretion rises and falls in atropine-poisoning with the arterial pressure, is not in accord with the results obtained by Walti, 20 who found atropine to produce in the rabbit, independently of its action upon the circulation, a steady lessening in the urinary secretion. Harley 21 affirms that medicinal doses of atropine de- cidedly increase the solids of the urine, slightly the urea and uric acid, very markedly the phosphates and the sulphates. Our knowledge of the action of atropine upon the secretions of the alimentary canal is very imperfect. It has been a matter of traditional and clinical belief that the secretions are increased, and Harley gives some experiments which he asserts corroborate this ; Meuriot, on the other hand, states that they are lessened. We cannot find, however, any experiments that seem to us decisive ; and clinical evidence cer- tainly indicates that the intestinal secretions, if affected at all, are in- creased. Temperature. In moderate doses atropine causes a pronounced rise in temperature, but in very large decidedly toxic amounts it lessens animal heat. Thus, in the dog, Meuriot has obtained an augmenta- tion of from i to 3 C. , and Dume'ril, Demarquay, and Lecomte of 4 C. In fatal poisoning of the same animal, these observers have noticed a fall respectively of 5. 10 and 3 C. In man, Meuriot, in the use of medicinal doses, has observed the temperature to rise 0.5 to 1.1 C. , and Eulenburg 0.5 to 0.8 C. According to I. Ott and C. Collmar," this increase is independent of the blood-pressure, occurring both when the pressure is elevated and when it is depressed, and is accompanied by a greater increase of heat-production than of heat-dissipation. It is there- fore due to the increased heat-production, which is the result, in all prob- ability, of an influence upon the nerve-centres. Ott and Collmar believe that this influence is a stimulation of the thermo-genetic centres in the spinal cord, and that the rise of temperature is paralleled by that which occurs in tetanus. It seems to us more probable that it is due to paralysis of thermo-genetic inhibition. The final fall of temperature in atropine-poisoning is probably, at least in part, caused by the vaso-motor paralysis. Eye. In all animals except birds, atropine causes mydriasis with paralysis of accommodation and probably lessening intra-ocular pressure. See case of Gross (loc. cit.), also of Morer (Ann. Soc. de Med. de Gand, 1873). DELIRIFACIENTS. 177 The dilatation induced by the local application of atropine is not due to a direct action of the drug upon the muscular fibres of the iris ; for as all of these, both the radiating and the circular, are of the same nature (non-striated \i\ mammals), their antagonism is simply due to position ; and it seems inconceivable that mere position should affect the relations between a muscle and a drug. Moreover, Bernstein and Dogiel (con- firmed by G. Engelhardt) found that while galvanic irritation of the oculo- motor nerve was unable to cause contraction of the pupil in the atropin- ized eye, yet when the electrodes were applied to the eyes in such a way as to affect directly the iris, contraction occurred, phenomena explain- able only by the theory that the nerve-endings were paralyzed, while the muscle was unaffected. The statement first made by Wharton Jones, M that the reason atropine does not dilate the pupils of birds is that their irides have no radiating fibres, has been dis- proved by the beautiful anatomical researches of Alex. Ivanoff and Alex. Rollett M (confirmed by Johannes Diegel 25 ) . Although Bonders w says that the pupillary action of atropine "is slight in birds, in which it was formerly overlooked, " in our own experiments the most thorough application of very strong solutions to the eyes of pigeons has had no distinct effect. According to the experiments of Szpilman and Luchsinger, lack of action of atropine is probably due to the muscular fibres of the irides of birds being non-striated. In the oesophagus of the bird the muscle is non- striated, and atropine paralyzes it ; in the oesophagus of the rabbit the muscle is striated, and atropine has no action ; in the cat a portion of the oesophagus has smooth muscular fibres, a part striated, and the former is paralyzed, the latter un- affected, by atropine." The dilatation of the pupil by the local application of atropine* is certainly independent of any nerve-centres farther back than the ciliary ganglion. This is proved by the following facts. Claude Bernard 28 and Lemattre both have found that atropine-mydriasis occurs in animals after section of the oculo-motor, and we have seen it in cases of complete oculo-motor paralysis in man. It also takes place after section of the trigeminus or of the cervical sympathetic, or of both of these nerves, as is shown by the testimony of numerous observers and by our own experiments. In man we have seen it after paralysis of the sympathetic.* 9 The dilation of the pupil by the local application of atropine is indepen- dent not only of the central nervous system, but also of the ciliary ganglion, and is due to an action exerted directly upon the nerve-endings in the iris. The experiments of Bernstein and Dogiel, confirmed by Engelhardt, already quoted, are in themselves almost enough to establish the truth of this proposition. More direct evidence is not, however, wanting. Thus, Vierordtf has found that atropine locally applied causes mydriasis after the removal of the ciliary ganglion. * Contraction of the pupil before dilatation noticed in dogs ( Reese) and rabbits ( Ross- bach and Frohlich) is probably caused reflexly by the irritant action of the atropine. t Unfortunately, the only notice we have seen of this capital experiment is in Her- mann's Grundriss der Physiologic. No reference is given, and we have been unable to find the original paper. 178 GENERAL REMEDIES. I. Hoppe so has discovered, and Y. Valentin 31 has confirmed the discovery, that in the eye of the frog removed from the body atropine will produce dilatation of the pupil. According to Borelli, 32 mydriasis is produced by the alkaloid when applied to the eye of a man just dead. Lastly, the presence of the alkaloid in the humors of the atropinized eye has been proved by numerous observers, among whom may be mentioned Lemattre and Bonders, who have found that the liquids removed from such an eye are capable of causing dilatation of the pupil of another eye. The dilatation is, at least in part, due to paralysis of the peripheral filaments of the oculo-motor nerve. Both Bonders and Stellwag von Carion M insist that the paralysis of accommodation is proof of paralysis of the oculo-motor nerve, and it seems to us they do so with truth. However this may be, there is abundant direct proof that the oculo- motor fibres are paralyzed, since the experiments of Griinhagen, which prove that galvanization of the exposed oculo-motor nerve d es not affect the atropinized pupil, have been confirmed by Engelhardt M and by Rossbach and Frohlich. 85 It is probable that the sympathetic or dilating nerve-fibres of the iris are stimulated. Clinical experience certainly shows that the dilatation produced by a mydriatic is not merely a passive movement of relaxation, but is active, capable of tearing up inflammatory adhesions even when of some firmness. Again, the dilatation that occurs after the paralysis of the oculo-motor nerve in man and after its destruction in animals is not at all equal to that produced by atropine, and, indeed, can be largely increased by the action of the drug ; further, in the eye separated entirely from the nerve-centres (see above) atropine still causes a wide dilatation ; facts which necessitate the belief either that the alkaloid acts upon the sympathetic fibrillae or that the peripheral fibres of a nerve are in themselves nerve-centres, acting upon the muscle of themselves even when separated from their centres. It has been urged against the view here taken that even the widest artificial mydriasis is increased by galvanization of the sympathetic. De Ruiter states the contrary ; but, since Griinhagen, Hirschmann, and Engelhardt separately affirm as the re- sult of personal experiment the correctness of the asserted fact, it must be ac- cepted. Granting its truth, we do not think it warrants the deduction, since it is conceivable that an agent may excite the peripheral filaments of a nerve greatly, and yet not to such a point that they will be incapable of further excitation. Schultz believes there is in his experiments no stimulation of the dilator fibres, because when the superior cervical ganglia is destroyed and time allowed for the degenera- tion of the peripheral nerve-fibres, atropine, whilst dilating both pupils, does not destroy their inequality. This does not, however, seem to us to prove Schultz's conclusion, for it may well be that it is the intramuscular endings of the sympathetic nerve which is stimulated rather than the sarcolemma of the muscles themselves, a theory rendered more probable by the fact that Schultz found that pieces of the iris of a cat, when exposed to a five per cent, solution of atropine, did not lose their irritability. A priori, it is strongly to be expected that the action of atropine upon the pupil will be the same whether it is carried to the pupil by the blood or is applied locally by the surgeon. The correctness of this conclusion is shown by the following evidence. Lemattre asserts that he has secured mydriasis in normal eyes by placing in them aqueous humors taken from dogs poisoned with atropine ; others, however, have DELIRIFACIENTS. 179 failed to get the dilatation. It has been asserted by authorities, and ex- perimentally corroborated by H. C. Wood, that atropine given hypo- dermically caused dilatation of the pupil in the lower animals after section both of the trigeminus within the skull and of the sympathetic in the neck ; H. C. Wood has shown that this also occurs after such section of the parts behind the eye up to the optic nerve as secures complete isola- tion of the iris from any nerve-centre. What is true of the lower animals is also true of man ; accident having afforded H. C. Wood the opportunity to give atropine hypodermically to a man whose eye had been separated from all connection with the nerve-centres, it was found that the pupil was still dilated by the drug.* Our knowledge of the action of atropine upon the pupil may be summed up as follows. Atropine applied locally causes mydriasis by paralyzing the peripheral ends of the oculo-motor nerve, and probably by stimulating the peripheral ends of the sympathetic. Atropine given internally causes mydriasis, not by influencing the nerve-centres, but by being carried in the blood to the eye itself and there acting precisely as when applied locally. SUMMARY. In full medicinal doses atropine produces a sort of febrile state, -with dryness of the mouth, dilatation of the pupil, in- creased rapidity and force of the circulation, quickened respiration, elevation of temperature, and secretion of febrile urine. The toxic dose intensifies the symptoms just narrated, and adds to them a peculiar wild delirium. The stage of excitement may be many hours long, -with very rapid heart-action and high arterial pressure ; after a time it is followed by one of general functional failure, marked by stupor, fall of blood-pressure, depression of reflexes, and death from asphyxia. The cerebral symptoms are due to direct influence of the alkaloid upon the cerebral cortex. The primary increase of respiration is the outcome of centric stimulation ; the terminal depression and asphyxia are pro- duced by secondary depression of the respiratory centre, and espe- cially by depression of the respiratory nerves. Upon the spinal cord the therapeutic dose probably has no influence, but the toxic dose acts as a depressant, affecting, however, more powerfully the motor nerve- trunks than it does the spinal centre and to a less degree the sensory nerves. There is some reason for suspecting that the drug primarily acts as a feeble stimulant to the various inhibitory centres, but its pronounced characteristic effect is that of a paralyzant of peripheral inhibition, acting in this way upon the spinal cord itself, upon the pneu- mogastric nerve, and upon the splanchnics so as to increase intestinal peristalsis. The rapid pulse is chiefly the outcome of a paralyzed in- hibition, although the heart may be feebly stimulated. The primary rise of blood-pressure produced is chiefly due to stimulation of the vaso-motor centres, although probably the work of the heart itself is increased. The final fall of pressure is due to depression of the heart and of the muscular coats of the vessels, which is part of a general action upon non-striated muscle-fibres, and which results in suspension of intestinal peristalsis and in retention of urine. * For elaboration of details, see tenth edition of this book. i8o GENERAL REMEDIES. THERAPEUTICS. In practical medicine atropine is employed in direct conformity to its physiological action, so that its use is best discussed under the headings of the various indications to meet which it may be administered. To relax Spasm. As the powers of atropine to relax spasm de- pend on its influence upon the peripheral nerve-filaments and the muscle- tissue, it is evident that it is a practical remedy only in those cases in which the spasm is due to some local cause connected with a mus- cle or its supplying nerve ; hence it has been found especially useful in rheumatic torticollis, in the violent contractures and spasms sometimes accompanying neuritis, and especially such as follow nerve-wounds. It is essential to inject the alkaloid directly into the contracted muscle, so as to get its concentrated influence upon the affected nerve and muscle, little or no relief usually being produced by so small an amount of the remedy as would reach the diseased part after absorption through the blood. The non-striated muscles are more affected by the atropine than the striated, and consequently the drug is found to be more efficacious in spasm of the involuntary than of the voluntary muscles. It is serviceable in lead colic, in simple spasmodic colic, in spasmodic dysmenorrhcea, in spasmodic constriction of the bowels with obstinate constipation, in laryn- gismus strididus, in nervous coiigh, in asthma, in hiccough, and in whooping- cough, in which last disease, as originally advised by Bretonneau, it has been largely used ; also, even in the spasms accompanying the passage of renal and biliary calculi, where of course it usually fails. Wherever it is possible, it should be used locally in spasm of the involuntary as well as of the voluntary muscles. Thus, in spasm of the urethra, the ointment should be rubbed in along the canal ; in rigid os uteri, the extract should be applied directly to the os ; in asthma, belladonna should be inhaled, by means either of the cigarette or of the atomization of a decoction of the leaves ; in spasm of the sphincter ant from fissure or other cause, it should be applied directly to the part by poultice or ointment. Under the present indication may be considered the use of the remedy in consti- pation. In doses of one-quarter to one-half grain of the extract, bella- donna is of great service as an addition to laxative pills. In that form of incontinence of urine in children in which the real cause is an irritability of the bladder, so that spasmodic contraction occurs under the stimulus of a small portion of urine, the continuous use of large doses of atropine is often of great service by reducing the irritability of the walls of the bladder, with which, owing to the method of its excretion, the alkaloid is brought in local contact. To relieve Pain. In accordance with its known physiological action, atropine is of very little value for the purpose of relieving pain, unless such pain be connected with spasm, or unless the pain be due to ulcera- tion or other local cause so situated that the atropine can be brought in direct contact in concentrated form with sensory nerve-endings. To impress the Heart and Blood- Vessels. In certain diseases, such as DELIRIFACIENTS. 181 pneumonia, congestion of the lungs, etc. , in which the local affection is closely connected with dilatatien of the blood-vessels, Harley has highly commended atropine as a vaso-motor contractant. In most of these affections, however, the remedy has failed to establish itself. In acute coryza and angina it acts most favorably, its influence upon the circulation being probably supported by its specific action upon the glandular appa- ratus of the mucous membranes involved, and possibly by its relaxing the pharyngeal muscles. As a stimulant to the circulation, belladonna has probably not been employed as much as it ought. Graves, however, commends it especially when the pupil is contracted in typhus fever, and it has been used with asserted advantage in erysipelas, scarlet fever, etc. In cases of sudden collapse occurring in acute disease and marked by falling of the tempera- ture below normal, with great loss of the arterial tension and free sweat- ing, atropine is of the greatest value. Such collapse is not infrequent in young children in the advanced stages of pneumonia, pleurisy, or other pulmonic disease, and is also prone to happen in puerperal mania and similar maniacal states occurring in exhausted patients. It is similar in its character to that which is produced by perforations of the stomach or intestine or as the result of surgical or accidental traumatisms. It is a condition of shock in which the loss of temperature is chiefly the result of vaso-motor paralysis. Proper treatment of this condition consists chiefly in the free use of external heat and the hypodermic injection of atropine, strychnine, and the tincture of digitalis ; in many of these cases alcoholic stimulants are worse than useless. To arrest Secretion. In mercurial salivation atropine arrests almost at once the discharge of saliva, and seemingly facilitates greatly the return to health. In colliquative sweats, as originally recommended by Da Costa, 86 it is probably the most valuable known remedy. One-sixtieth to one- eightieth of a grain of atropine used hypodermically, at bedtime, will very frequently prevent the usual night-sweat. In colliquative diar- rhoea it has been recommended by M. Delpage, and very probably will be found of service. Inunctions of the breast with belladonna ointment are habitually employed for the purpose of arresting the secretion of milk, and in the experiments of Hammerbacher S7 upon a goat, atropine given internally lessened the secretion, especially of the watery portions of milk. Employment in Poisoning. It is stated that as far back as 1570 it was affirmed that opium and belladonna are, in their influence upon the sys- tem, antagonistic. In the early part of the present century their em- ployment as counter-poisons was again brought prominently before the profession ; but, although a few scattered earlier records of their use as such exist in medical literature, it was not until the paper of William F. Norris 38 appeared that general attention was attracted to the subject. After nearly twenty- five years of discussion,* the opinion given in the * For an account of this discussion, see tenth edition of this treatise. 182 GENERAL REMEDIES. first edition of this work, that the two drugs are not, strictly speaking, antagonistic, has become a certainty. Atropine, is, however, a valuable remedy in opium-poisoning as a powerful and prompt respiratory stimu- lant. In protracted opium- narcosis the cardiac and vaso- motor actions of atropine are of service ; but it should never be forgotten that the main influence for good is upon the respiratory centres. The first improve- ment from atropine in these cases is usually increased frequency of respi- ration ; and as the breathing becomes less embarrassed the other symp- toms ameliorate, largely because of the increased aeration of the blood. The double nature of profound opium-narcosis must not be lost sight of : the blood is saturated with carbonic acid almost to the dead-line, and much of the unconsciousness, much of the failing circulation, much even of the embarrassed respiration, is due to the presence of the gas. As soon as the system is in a measure relieved of this load, it begins to re- bound ; emetics act, consciousness returns to some extent, the circulation frees itself, and the road leading towards health is entered upon. Atropine should be administered as soon as there is decided failure of the respira- tion. With it should be given strychnine, which, as was first pointed out by H. C. Wood, is at least equally as efficient as atropine. Both alkaloids should be given hypodermically, the doses being large but not toxic : one- fortieth of a grain of atropine and one-fifteenth of strychnine are, in most instances, fair commencing doses. Repetition should be chiefly guided by the effect upon the respiration, although judgment should be formed in part from a bird's-eye view of the whole case. No more of the alka- loids should be used than is necessary to sustain the respiration ; so long as this function is improving they should be withheld. Whenever there is failure of respiration in other poisonings than that of opium, atropine in conjunction with strychnine is useful. It has been especially commended as an antidote to poisonous fungi* As a Local Sedative. Locally and freely applied, belladonna is a sedative, and, we believe, to glandular as well as to muscular and nervous tissues. In this way it is often very useful in various local inflammations. In the form of a plaster it frequently appears to do good in palpitation of the heart. Its use locally in spasms and in neuralgia has been suffi- ciently dwelt on. In mastitis, its local application to the breast is often very efficacious. Whenever belladonna is used locally, in order to get its good effects it must be employed freely. At the same time, it should be remembered that a number of cases of poisoning by its external ap- plication have been reported. 39 ' * In children it must be used with caution ; in adults, with a reasonable amount of care, its external use is safe, pro- vided directions be given to have it washed off so soon as any affection of the sight or dryness of the throat is induced. Use in Diseases of the Eye. f The instillation of a four grains to the ounce solution of atropine sulphate into the eye is followed in about * Atropine antagonizes the action of muscarine (the alkaloid of many of the poisonous mushrooms) on the cardiac inhibitors as well as on the respiration. t For this section the authors are indebted to Professor George E. de Schweinitz. DELIRIFACIENTS. 183 fifteen minutes by dilatation of the pupil, usually reaching its maximum in from twenty-five to thirty-five minutes, and lasting until the third day. In about twenty-five minutes the power of accommodation begins to be lost, and in from an hour and a half to two hours is usually fully annulled : return begins on the second day, but the function may not be fully regained for over a week. Atropine is used by ophthalmologists : First, to dilate the pupil for purposes of ophthalmoscopy and to expose the lens in cases of incipient cataract so that all portions of it may be carefully examined, but is inferior in this respect to more rapidly and fugacious acting mydriatics, particu- larly a four per cent, solution of cocaine, a one and a half per cent, solution of homatropine, or a ten per cent, solution of euphthalmine. Second, in iritis and irido-cyditis to give rest to the iris and to prevent the de- velopment of synechia and occlusion of the pupil area with exudates ; for this purpose it is the best of the mydriatics. Third, to paralyze accommo- dation when it is desired to determine with accuracy the refraction of the eye for the fitting of spectacles and other purposes, and to overcome spasm of accommodation ; in such cases repeated instillations of the atro- pine solution may be necessary. Fourth, to give rest to the eye, to exert an anodyne alterative influence, and to lessen the liability to iritis in various forms of keratitis and ulcers of the cornea ; in phlyctenular kera- titis it is especially useful, and in perforating ulcers, particularly if they have a central situation, it overcomes the prolapse of the iris ; for this purpose it must be used very freely. The existence of glaucoma, or any tendency to it, is a centra-indica- tion to the use of atropine. It may in chronic glaucoma precipitate an acute attack, and in acute glaucoma causes marked increase of pain, of congestion, and of the already excessive intra-ocular tension. Belladonna was at one time highly commended as a prophylactic against scarlet fever. The original teaching of George B. Wood, that as such, however, it has no value, has been abundantly confirmed in later times. TOXICOLOGY. Sufficient has already been said about the general symptoms of belladonna- poisoning. Those which are characteristic are the dryness of the throat, the increased frequency of breathing, the dilated pupils, the red efflorescence on the skin, the rapid pulse, the active talkative delirium, sometimes convulsions, all ending in abolition of function, as shown by stupor, rapid feeble pulse, cold extremities, and paralysis. Morel 41 calls attention to a sort of laryngitis produced by poisonous doses of belladonna, characterized by pain in the larynx, rough- ness of voice, and the expectoration of minute, pearly, tough pellets. It was present in the advanced stages of two cases of poisoning under his care. Raphael " has noted glycosuria as a symptom of belladonna-poison- ing and has experimentally produced the condition with atropine in rabbits. The minimum fatal doses of the preparations of belladonna are scarcely known. 1 84 GENERAL REMEDIES. An enema representing eighty grains of the root has produced death in five hours ; i2 but, on the other hand, recovery has occurred after the ingestion of three drachms of the extract.* A tenth, or even a twentieth, of a grain of atropine will often produce alarming symptoms ; yet Chambers 43 reports recovery in a child four years old who had taken about two teaspoonfuls of a solution containing a grain of the alkaloid in half an ounce, and Stracham in a child of five years from a tablespoonful of glycerin containing one-half per cent, of alkaloids. After death from belladonna, no characteristic lesions are to be found. In the treatment of belladonna-poisoning, the stomach should be emptied by means of emetics or the stomach-pump, and tannic acid ex- hibited as an imperfect antidote. The various symptoms must then be met as they arise, respiration and circulation being maintained as in other narcotic poisoning ; according to Reichert, recovery may follow after a dose much larger than the maximal fatal quantity if artificial respiration be persisted in. The exact value of opium in belladonna-poisoning has not been determined, and its employment should be tentative, although good is to be expected from its judicious use. Physostigma and jabo- randi appear to be somewhat antagonistic to atropine within certain limits, and jaborandi has been used in atropine-poisoning. (See Calabar Bean and Jaborandi. ) After toxic doses of belladonna, there is generally complete retention of urine ; and as this secretion contains the greater part of the ingested poison, and as reabsorption from the bladder is at least conceivable, the catheter should be used early. ADMINISTRATION. Belladonna is never used internally in substance. All the preparations of the U. S. Pharmacopoeia except two (designated below) are made from the leaves. They are the tincture (TINCTURA BELLADONNA FOLIORUM ten per cent., U. S. ), dose, ten to thirty minims (0.6-1.9 C.c. ); the alcoholic extract (EXTRACTUM BELLADONNA FOLIORUM, U. S. ), dose, one-eighth to one-half grain (0.008-0.032 Gm. ); the fluid extract of the root (FLUIDEXTRACTUM BELLADONNA RADICIS, U. S. ), dose, one to two minims (0.060.12 C.c.); the plaster (EMPLAS- TRUM BELLADONNA, U. S. ) contains three parts of extract of bella- donna leaves to seven of adhesive plaster ; the ointment (UNGUENTUM BELLADONNA, U. S. ) contains ten per cent, of extract. The liniment (LINIMENTUM BELLADONNA, U. S.) is made by adding five per cent, of camphor to the fluid extract. Atropine sulphate (ATROPIN^E SUL- PHAS, U. S. ) is most commonly used, on account of its solubility in water. Dose, one-hundredth to one-sixtieth of a grain (0.00065-0.001 Gm.), increased in cases of poisoning. In dropping an atropine solution in the eye for local effect the head should be so inclined that the fluid will run out of the outer canthus, whilst pressure may be applied upon the optic end of the lachrymal duct to prevent passage of the solution into the mouth. Poisoning through the local use of the remedy by oph- thalmic surgeons has often occurred. * Taylor's Medical Jurisprudence, London, 1873, 432. DELIRIFACIENTS. 185 STRAMONII FOLIA. U. S. Stramonium Leaves. The leaves of the Datura Stramonium., or Jamestown Weed, are recognized by the U. S. Pharmacopoeia, but have passed into almost complete desuetude. In the numerous cases of poisoning which have been produced by the use of the plant the symptoms have been precisely those of belladonna-poisoning, and the treatment is the same in the two poisonings. The alleged active principle, daturine, is, according to Ladenburg, a mixture of atropine and hyoscyamine ; and in the experimental studies of Charles Laurent, 1 the physiological effects of daturine were not to be distinguished from those of atropine. The preparations of stramonium are at least as power- ful as the corresponding preparations of belladonna, but are rarely used. Stramonium leaves have been very widely employed in the form of cigarettes, or a powder, to be smoked in a pipe or otherwise in the treat- ment of spasmodic asthma ; also, less frequently, as a narcotic cataplasm for inflamed hemorrhoids. In either case some care is necessary to avoid poisoning. The dose of the extract (ExTRACTUM STRAMONII, U. S. ) is one- fourth to one-half grain (0.016-0.032 Gm. ); of the tincture (TiNCTURA STRAMONII SEMINIS ten per cent., U. S. ), fifteen to thirty minims (1-2 C.c. ); of the fluid extract (FLUIDEXTRACTUM STRAMONII, U. S. ), one to two minims (0.06-0.12 C.c.). The ointment (UNGUEN- TUM STRAMONII, U. S. ) contains ten per cent, of the extract. HYOSCYAMUS. U. S. Hyoscyamus niger is a coarse herbaceous biennial, indigenous in England, and naturalized in the Northern United States, whose leaves and flowering tops of the second year's growth are official. The leaves are large, oblong-ovate, deeply sinuated, and very hairy. Hyoscyamus contains two alkaloids, hyoscyamine and hyoscine. Amorphous hyoscy- amine of commerce is a mixture of hyoscyamine and hyoscine. Hyoscine is separated from it as a syrupy liquid which yields crystallizable salts. PHYSIOLOGICAL ACTION. The clinical experiments of Schroff, Dul- lenberg, Laurent, 2 and especially of Harley 1 show that the symptoms produced by large doses of hyoscyamus are similar to those caused by belladonna, excepting that there is a greater tendency to sleep and that the delirium is less furious. The assertion of Schroff, 8 that pneumonia is in the rabbits a characteristic lesion of hyoscyamus-poisoning, is nega- tived by the results obtained by Lemattre and by Laurent. The experi- ments of Laurent and of Heilmann 4 are in accord in showing that hyoscy- amus acts upon the circulation, the respiration, the neuro-muscular system, and the intestines very similarly to belladonna. THERAPEUTICS. Hyoscyamus may be used to fulfil any of the indi- cations for which belladonna is employed. Clinical experience appears in a measure to bear out the assertions of various authorities as to the superiority of hyoscyamus as an hypnotic. It has been much employed as a calmative and hypnotic by alienists in various forms of delirious i86 GENERAL REMEDIES. insanity, but is inferior to hyoscine. The diagnosis and treatment oi hyoscyamus-poisoning are identical with those of belladonna-poisoning. The preparations are the extract (EXTRACTUM HYOSCYAMII, U. S.), dose, one to three grains (0.06-0.19 Gm. ) ; the tincture (TINCTURA HYOSCYAMI ten per cent. , U. S. ) , dose, half a fluidrachm to two flui- drachms (2-8 C.c. ) ; and the fluid extract (FLUIDEXTRACTUM HYOS- CYAMI, U. S. ), dose, five minims (0.3 C.c.). HYOSCYAMIN^E SULPHAS. U. S. Hyoscyamine sulphate is a whitish powder, sometimes indistinctly crystalline, very soluble in water, and having a bitter taste. According to J. C. Shaw, 6 crystallized hyoscyamine affects the system of voluntary movement and the circulation, including the heart and the vaso-motor system, exactly as atropine does. In a single experiment the respiration did not seem to be affected as by atro- pine ; but this is contradicted by results arrived at by previous experi- menters, and needs confirmation. Upon man Shaw believes, as do many other alienists, that hyoscyamine acts as a soporific. He states that it is less powerful as a mydriatic than is atropine, and that it diminishes the respiratory rate. It must be remembered that these studies have been made upon lunatics ; before the conclusions can be accepted as estab- lished, much more elaborate experimental researches are necessary, also studies upon normal individuals, and especially contrasting studies made with atropine and hyoscyamine upon maniacs ; by the use of alternate doses upon the same individual any difference of action of the two drugs could readily be detected. It should also be remembered that in his studies of hyoscyamine upon normal men Richter 7 noted no tendency to sleep. In a careful comparative study of hyoscyamine and atropine upon a case of acute mania by Sydney Ringer, 8 the two alkaloids were found to act practically alike. Commercial hyoscyamine was formerly very impure, and a grain has been given with impunity ; but one-fortieth of a grain of the pure alkaloid has produced violent poisoning. 9 SCOPOLA. U. S. Under this name the U. S. Pharmacopoeia recognizes the rhizomes of the Scopola carniolica, a plant which is common in the hilly districts of Central and Southwestern Europe. The Japanese plant, ,51 japonica, is so closely allied to the European plant that many botanists have doubted its specific distinctness, and the rhizome of the Japanese species appears to be identical in its physiological properties with that of S. carniolica. Scopola rhizomes contain hyoscyamine, atropine, and scopolamine, with perhaps minute quantities of other alkaloids. Of these alkaloids, hyoscyamine appears to be the predominating one, but scopolamine exists in considerable quantity. Scopolamine, at first supposed to be a distinct alkaloid, is now officially recognized as identical with hyoscine. According to the researches of Horatio C. Wood, Jr. ,* the crude prepa- rations of scopola act upon cold- and warm-blooded animals precisely as DELIRIFACIENTS. 187 do the corresponding preparations of belladonna, but the chemistry of the subject would seem to indicate that scopola, containing hyoscine, must have more somnifacient influence than has belladonna. Further, in clin- ical studies made by R. W. Wilcox 2 it was found that when scopola is applied externally it does not yield its alkaloid to absorption as does bella- donna. In the manufacture of plasters scopola extract has been largely used as a substitute for belladonna extract, but in the light of the research of Wilcox, the revisers of the U. S. Pharmacopceia of 1900 have refused to countenance such substitution, and the only crude official preparation of scopola is the fluid extract (FLUIDEXTRACTUM SCOPOLA, U. S.). Dose, one or two minims (0.06-0.1 C.c. ). HYOSCINE HYDROBROMIDUM. U. S. Hyoscine Hydrobromide, Scopolamine Hydrobromide. Hyoscine hydrobromate occurs in minute, colorless, rhombic crystals, which are freely soluble in water and in alcohol. The symptoms which are produced in man by decided doses of hy- oscine are dryness of the mouth, flushing of the face, great sleepiness, associated in some cases with semi-delirious mutterings, and a feeling of giddiness like that of intoxication. The respirations are lessened in fre- quency and the pulse-rate is usually somewhat diminished ; * mydriasis is usually, but not always, pronounced. After very large doses the symp- toms mentioned are more intense ; the pulse becomes slow and full, but, according to the sphygmographic tracings of J. B. Andrews, without alteration of tension, the pupils dilated, the mouth and throat excessively dry, and the voice hoarse or even partially suppressed, probably from paralysis of the vocal cords. The respirations are slow and full, and are said by H. M. Wetherill to be sometimes Cheyne- Stokes. The face and the general surface of the body are suffused, muscular relaxation is pro- nounced, and loss of coordination usually very evident. The skin, so far from being abnormally dry, is commonly bathed in perspiration. Several observers assert also that there is a rise of temperature. Some- times the delirium is active, accompanied by visual hallucinations, and clonic convulsions with opisthotonos have been noted. Mairet and Com- bemale 11 found that monkeys when poisoned by it gave evidences of the presence of hallucinations, such as are sometimes produced in man. PHYSIOLOGICAL ACTION, f Circulation. The effect of hyoscine upon the circulation is slight ; according to H. C. Wood, small doses produce some slowing of the pulse but no changes in the pressure, while very large doses produce a slight fall in pressure due to depression of both It has been noted a little accelerated. (Case, Therap. Gaz., 1889, J. S. Gibb.) t The fact that numerous observers had asserted that the impure amorphous hyoscya- mine of commerce was more powerful than the pure crystallized alkaloid led H. C. Wood, in 1884, to a physiological and therapeutic study of hyoscine, which led to the use of the remedy in practical medicine. Other physiological studies of the alkaloid have since been made by Gley, Rondeau, Mairet and Combemale, A. Sohrt (In. Dis. Dorpat, 1886), i88 GENERAL REMEDIES. heart and vasomotor centres. Kochmann, 12 however, finds that small doses produce a slight rise in the pressure through stimulation of the vaso- motor centres, and that the fall from large amounts is purely cardiac. He agrees with Wood that there is no marked change in the pulse-rate after the use of small doses, but he obtained after large doses stimulation of the vagi and consequent lessening of the pulse-rate. On the other hand Robert asserts, that the alkaloid acts upon the peripheral ends of the car- diac inhibition as does atropine, producing a marked increase in the rate of the pulse. Since, however, Claussens, 13 Wood, and Kochmann are all in agreement that no dose of the drug produces this effect, it would seem that there must have been some mistake in the results of Kobert. Nervous System. All the authorities quoted are in agreement that hyoscine is a depressant to the cerebrum. Kochmann found that the electrical irritability of the psychomotor area is lessened by the drug and that there is no analgesia during the sleep it produces. According to H. C. Wood, it is a depressant to the motor side of the spinal cord. Respiration. According to both Wood and Kochmann hyoscine acts as a depressant to the respiration, although it requires comparatively large doses to produce any marked alteration in this function. In fatal poison- ing by the drug death is always due to asphyxia. In this connection it is interesting to note that in the dog, as in man, it is almost impossible to kill with a single dose of hyoscine ; Kochmann has injected as much as o. 5 Gm. (7^ grains) into a small dog intravenously without destroying life. Secretions. Upon the secretions hyoscine acts much like atropine, producing lessening in the saliva, and, according to Kochmann, also in the sweat and mucous secretions. In cases of human poisoning, however, the skin is usually covered with moisture. Pupil. Upon the pupil hyoscine acts like atropine, a half of one per cent, solution rapidly paralyzing accommodation and dilating the pupil. It is said that it does not produce any irritation, and that its maximum effects are reached in one-third the time necessary for those of atropine, and are more permanent and less affected by eserine. * MM. E. Gley and P. Rondeau s have found that the mydriasis is not prevented by previous destruction of the cervical sympathetic in the rabbit, and that irritation of the sympathetic nerve will increase the dilatation. SUMMARY. The dominant physiological action of hyoscine is upon the cerebral cortex, producing sleep often accompanied by a low de- lirium. It is also a centric depressant of respiration, and depresses, though somewhat feebly, the whole motor cord : upon the sexual cen- tres it acts more powerfully. Its influence upon the circulation is very slight, and it appears to exert no distinct influence on the nerves or Claussens, Kobert (apparently a restatement of the work done by his pupil Sohrt), and Kochmann. The results described by Kobert differ so markedly as to render it probable that he had either a different or an impure alkaloid. The experiments of H. C. Wood were made with hyoscine obtained from Merck. * John Tweedy, Lancet, Dec. 1886. DELIRIFACIENTS. 189 muscles. On the mucous membrane and probably on the muscles of the throat it acts powerfully, suppressing secretion and interfering with function. THERAPEUTICS. Hyoscine is a valuable hypnotic in those forms of insomnia in which sleep is banished by a continual flow of thoughts or mental images passing through an excited brain ; hence it is often very effective in the insomnia of delirium, of acute mania, or of other forms of insanity. In some cases of insanity with cerebral excitement most excellent results are produced by the administration every three to five hours of small doses that will calm without causing sleep. As an hypnotic the alkaloid lends itself very well to combinations, intensi- fying greatly the influence of morphine, chloral, trional, and other drugs of the class. In cases of severe kidney disease it would seem to be a safer hypnotic than is morphine, and as it has no sedative influence upon the heart, it may be used when the feeble condition of that viscus forbids chloral. The use of enormous doses (grain one-fiftieth to one- twentieth) of hyoscine as a curative remedy in acute insanity has been advocated by H. R. Costons, and a remarkable case is recorded by Balagopal,* in which one-sixth of a grain was given hypodermically to a patient suffering from violent, acute mania. Immediately after the injection the patient fell, crying that he was dying ; his face became deadly pale, the conjunctiva insensitive, the breathing difficult and stertorous, the limbs spasmodically contracted. After recovery, which occurred without remedies other than hypodermic injections of ether, the patient's mental condition rapidly improved, and in a week he was well. Probably through its influence upon the spinal centres hyoscine is useful in all cases of sexual excitement, such as nymphomania, sperma- torrhoea, and allied affections. It is the most certain remedy that we have in ordinary cases of over-frequent seminal emissions, which can usually be controlled by the administration of the one-hundred-and- twentieth to one-eightieth of a grain on going to bed. As an analgesic hyoscine is of little value, though Winnett 5 states that it is very serviceable in the crises of locomotor ataxia. It has been used to a considerable extent in certain spasmodic disorders. Edlesen, as early as 1881, affirmed its value in asthma and whooping-cough. Erb has used it with advantage in various spasms. In spinal accessory spasm it has in our hands failed. On the other hand, in pronounced paralysis agitans, attended by much aching pain, we have seen it give very great relief from both pain and tremors. Usually in these cases it should be administered only at bedtime, as it is merely a palliative, and if used continually is prone to lose its power. In 1900 Schneiderlin suggested the hypodermic injections of large doses of morphine and scopolamine for the production of surgical anes- thesia. In this method doses ranging from one-sixth to one-half grain of morphine are given in conjunction with from one-hundredth to one-fiftieth i 9 o GENERAL REMEDIES. grain of hyoscine are injected an hour before the operation. The idea was founded on an erroneous conception of the physiological action of hyoscine which is in no proper sense the antagonist of morphine and pos- sesses but feeble analgesic properties. H. C. Wood, Jr. 10 collected the reports of nearly 2000 cases, with 9 deaths, giving the frightful mortality of i : 221. Moreover in 69 per cent, of the cases ether or chloroform was required to produce sufficient anaesthesia for operation. It is possible that in certain classes of cases the method may occasionally prove of value, but as a routine measure it cannot be too strongly condemned. TOXICOLOGY. No fatal case of poisoning by hyoscine is on record. H. A. Hutchinson 6 took a quarter of a grain of very impure hyoscine : quiet coma with entire muscular relaxation was produced, and lasted eleven hours. The fiftieth of a grain has, however, several times caused very alarming symptoms, and much smaller doses are affirmed to have produced serious effects (see Carey 7 ). O' Hara 8 saw one-ninety-sixth of a grain administered hypodermically produce very severe disturbance, lasting for twenty-eight hours, with total lack of remem- brance of occurrences which took place during the seven hours following the in- jection ; while Root 9 asserts that one-three-hundredth of a grain given by the mouth produced violent poisoning, and even one-twelve-hundredth very pro- nounced symptoms. The dispensing of such minute quantities of a drug is so diffi- cult that it is probable that more of the alkaloid was given than is alleged. ADMINISTRATION. Hyoscine very rarely if ever causes other dis- agreeable after-effects than dryness of the throat, although occasionally some headache has been noted. The action of hyoscine given hypoder- mically is manifested inside of ten minutes, and lasts from six to eight hours. In severe excitement, especially that of violent insanity, the dose should be repeated every six or eight hours. The dose for hypodermic use is from the one-hundred-and-fiftieth to one-eightieth of a grain (o. 6 0.8 milligramme). Excessive susceptibility to the action of hyoscine being a not infrequent idiosyncrasy, it is best to give at first amounts below the minimum dose here stated. The tastelessness of hyoscine makes it easy to administer to insane or other patients without their knowledge. Owing to its great influence upon the throat, hyoscine is strongly contra-indicated in cases of acute disease of the throat sufficiently violent to interfere with deglutition or respiration. Thus, we have seen it, when given in violent anginose scarlatina with delirium, cause such rapid increase in the difficulty of respiration as to suggest that it played an important role in the production of the fatal asphyxia. HOMATROPIN^G HvDROBROMiDUM. U. S. Homatropine Hydrobro- mide. Homatropine is an alkaloid artificially produced from atropine, the hydrobromate of which is preferred for practical use on account of its being stable and not hygroscopic. It is said to cause, when taken inter- nally, symptoms similar to those caused by atropine, except in regard to the circulation. The retardation of the pulse has been proved by Tweedy DELIRIFACIENTS. 191 and Ringer, Beyer, and De Schweinitz and Hare l to be, at least in part, the result of a direct action of the drug upon the heart-muscle or its con- tained ganglia, since in the frog and in the terrapin the application of homatropine hydrobromate to the exposed heart in situ reduces very greatly the number of the beats. In the dog injection of the alkaloid into the jugular vein is followed by a fall of as much as thirty or forty beats per minute, which De Schweinitz and Hare believe to be in part due to stimulation of the vagi nerves, because section of the vagi causes a marked increase in the pulse-rate, ' ' although not such a rise as would appear if the inhibitory apparatus was intact." De Schweinitz and Hare found that the fall of the pulse-rate was accompanied by a marked fall of the ar- terial pressure. Since the production of asphyxia was followed at this time by a pronounced rise in the arterial pressure, it would appear that the fall of pressure is not the result of a vaso-motor paralysis, but of the cardiac influence of the drug. It has been shown by the experiments of Tweedy and Ringer, con- firmed by De Schweinitz and Hare, that homatropine produces in the frog a brief period of tetanus, followed by absolute muscular relaxation, with abolition of reflex and voluntary activity, followed in from six to eight hours, if the dose has been properly proportioned, by return of vol- untary movements, associated with tetanic spasms of great intensity. The convulsive movements and the paralysis are, according to De Schweinitz and Hare, of spinal origin, as the nerve-trunks and muscles are not affected. The cause of death is centric respiratory paralysis. The influence of the alkaloid upon the eye is practically identical with that of atropine, except that it is somewhat more feeble and is much more temporary. The pupil begins to dilate in from seven to twenty minutes after the instillation of the drug, and accommodation fails in from forty to ninety minutes ; in from one to seventy-two hours the recovery is com- plete. According to De Schweinitz, a solution of one in eighty is suf- ficiently strong to paralyze accommodation completely, provided it be dropped repeatedly into the eye. When it is desired simply to dilate the pupil for ophthalmoscopic examinations, a single application of a solution of four grains to the ounce suffices. Homatropine as a practical mydriatic has the advantage of fugaciousness of action, of being not at all irritant, and of being little prone to produce systemic disturbance. CANNABIS INDICT INDIAN CANNABIS. U. S. The alcoholic extract of Indian hemp is a blackish, resinous extract, of a decided narcotic odor and a peculiar taste. In the East hemp and its educts are used as narcotic stimulants. Gunjah is the dried plant as sold in the bazaars of Calcutta for smoking. Churrhus, known in Egypt as hashish, is the resinous exudation with the epidermis, etc. , scraped off the leaves. Various substances have been announced as the active principle of cannabis indica, cannabin, cannabinon, tetano-cannabene, oxycannabin, i 9 2 GENERAL REMEDIES. cannabene, etc. Cannabinol of Wood, Spivey, and Easterfield is, ac- cording to Fraenkel, 5 inert, and should be known as psuedocannabinol, the name cannabinol being retained for a distinct substance which he, Fraenkel, has isolated and found to be active. PHYSIOLOGICAL ACTION. When given in full doses, cannabis indica produces a feeling of exhilaration, with a condition of revery, and a train of mental and nervous phenomena which varies very much ac- cording to the temperament or idiosyncrasies of the subject, and very probably also, to some extent, according to the nature of his surround- ings. The sensations are generally spoken of as very pleasurable ; often beautiful visions float before the eyes, and a sense of ecstasy fills the whole being ; sometimes the venereal appetites are greatly excited ; sometimes loud laughter, constant giggling, and other indications of mirth are present. Some years since, in experimenting with an extract made from the American plant, H. C. Wood took a large dose, and de- scribed the result as follows : * "About half-past four P.M., September 23, I took most of the extract. No immediate symptoms were produced. About seven P.M. a professional call was requested, and, forgetting all about the hemp, I went out and saw my patient While writing the prescription, I became perfectly oblivious to surrounding ob- jects, but went on writing, without any check to or deviation from the ordi- nary series of mental acts connected with the process, at least that I am aware of. When the recipe was finished, I suddenly recollected where I was, and, looking up, saw my patient sitting quietly before me. The conviction was irresistible that I had sat thus many minutes, perhaps hours, and directly the idea fastened itself that the hemp had commenced to act, and had thrown me into a trance-like state of considerable duration, during which I had been stupidly sitting before my won- dering patient. I hastily arose and apologized for remaining so long, but was as- sured I had only been a very few minutes. About seven and a half P.M. I returned home. I was by this time quite excited, and the feeling of hilarity now rapidly in- creased. It was not a sensuous feeling, in the ordinary meaning of the term ; it was not merely an intellectual excitation ; it was a sort of bien-ttre, the very opposite to malaise. It did not come from without ; it was not connected with any passion or sense. It was simply a feeling of inner joyousness ; the heart seemed buoyant beyond all trouble ; the whole system felt as though all sense of fatigue were forever banished ; the mind gladly ran riot, free constantly to leap from one idea to another, apparently unbound from its ordinary laws. I was disposed to laugh ; to make comic gestures ; one very frequently recurrent fancy was to imi- tate with the arms the motions of a fiddler, and with the lips the tune he was sup- posed to be playing. There was nothing like wild delirium, nor any hallucinations that I remember. At no time had I any visions, or at least any that I can now call to mind ; but a person who was with me at that time states that once I raised my head and exclaimed, ' Oh, the mountains ! the mountains !' While I was perform- ing the various antics already alluded to, I knew very well I was acting exceedingly foolishly, but could not control myself. I think it was about eight o'clock when I began to have a feeling of numbness in my limbs, also a sense of general uneasi- ness and unrest, and a fear lest I had taken an overdose. I now constantly walked about the house ; my skin to myself was warm, in fact my whole surface felt flushed ; my mouth and throat were very dry ; my legs put on a strange, foreign feeling, as though they were not a part of my body. I counted my pulse and found it one hundred and twenty, quite full and strong. A foreboding, an undefined, horrible fear, as of impending death, now commenced to creep over me ; in haste I sent for DELIRIFACIENTS. 193 medical aid. The curious sensations in my limbs increased. My legs felt as though they were waxen pillars beneath me. I remember feeling them with my hand and finding them, as I thought at least, very firm, the muscles all in a state of tonic con- traction. About eight o'clock I began to have marked ' spells,' periods when all connection seemed to be severed between the external world and myself. I might be said to have been unconscious during these times, in so far that I was oblivious to all external objects, but on coming out of one it was not a blank, dreamless void upon which I looked back, a mere empty space, but rather a period of active but aimless life. I do not think there was any connected thought in them ; they appeared to be simply wild reveries, without any binding cord, each a mere chaos of dis- jointed ideas. The mind seemed freed from all its ordinary laws of association, so that it passed from idea to idea, as it were, perfectly at random. The duration of these spells to me was very great, although they really lasted but from a few seconds to a minute or two. Indeed, I now entirely lost my power of measuring time. Seconds were hours ; minutes were days ; hours were infinite. Still, I was perfectly conscious during the intermissions between the paroxysms. I would look at my watch, and then after an hour or two, as I thought, would look again and find that scarcely five minutes had elapsed. I would gaze at its face in deep disgust, the minute-hand seemingly motionless, as though graven in the face itself ; the laggard second-hand moving slowly, so slowly. It appeared a hopeless task to watch during its whole infinite round of a minute, and always would I give up in despair before the sixty seconds had elapsed. Occasionally, when my mind was most lucid, there was in it a sort of duplex action in regard to the duration of time. I would think to myself, It has been so long since a certain event, an hour, for example, since the doctor came ; and then reason would say, No, it has been only a few minutes ; your thoughts or feelings are caused by the hemp. Nevertheless, I was not able to shake off this sense of the almost indefinite prolongation of time, even for a minute. The paroxysms already alluded to were not accompanied by muscular relaxation. About a quarter before nine o'clock, I was standing at the door, anxiously watching for the doctor, and when the spells would come on I would remain standing, lean- ing slightly, perhaps, against the door-way. After a while I saw a man approach- ing, whom I took to be the doctor. The sounds of his steps told me he was walking very rapidly, and he was under a gas-lamp, not more than one-fourth of a square distant, yet he appeared a vast distance away, and a corresponding time approach- ing. This was the only occasion on which I noticed an exaggeration of distance ; in the room it was not perceptible. My extremities now began to grow cold, and I went into the house. I do not remember further, until I was aroused by the doctor shaking or calling me. Then intellection seemed pretty good. I narrated what I had done and suffered, and told the doctor my opinion was that an emetic was indi- cated, both to remove any of the extract still remaining in my stomach, and also to arouse the nervous system. I further suggested our going into the office, as more suitable than the parlor, where we then were. There was at this time a very marked sense of numbness in my limbs, and what the doctor said was a hard pinch pro- duced no pain. When I attempted to walk up-stairs, my legs seemed as though their lower halves were made of lead. After this there were no new symptoms, only an intensifying of those already mentioned. The periods of unconsciousness became at once longer and more frequent, and during their absence intellection was more imperfect, although when thoroughly roused I thought I reasoned and judged clearly. The oppressive feeling of impending death became more intense. It was horrible. Each paroxysm would seem to have been the longest I had suffered ; as I came out of it, a voice seemed constantly saying, ' You are getting worse ; your paroxysms are growing longer and deeper ; they will overmaster you ; you will die.' A sense of personal antagonism between my will-power and myself, as affected by the drug, grew very strong. I felt as though my only chance was to struggle against these paroxysms, that I must constantly arouse myself by an effort of will ; and that effort was made with infinite toil and pain. I felt as if some evil 13 i 9 4 GENERAL REMEDIES. spirit had control of the whole of me except the will-power, and was in determined conflict with that, the last citadel of my being. I have never experienced anything like the fearful sense of almost hopeless anguish and utter weariness which was upon me. Once or twice during a paroxysm I had what might be called nightmare sensations : I felt myself mounting upward, expanding, dilating, dissolving into the wide confines of space, overwhelmed by a horrible, rending, unutterable despair. Then, with tremendous effort, I seemed to shake this off, and to start up with the shuddering thought, Next time you will not be able to throw this off, and what then ? Under the influence of an emetic I vomited freely, without nausea, and with- out much relief. About midnight, at the suggestion of the doctors, I went up-stairs to bed. My legs and feet seemed so heavy I could scarcely move them, and it was as much as I could do to walk with help. I have no recollection whatever of being undressed, but am told I went immediately to sleep. When I awoke, early in the morning, my mind was at first clear, but in a few minutes the paroxysms, similar to those of the evening, came on again, and recurred at more or less brief intervals until late in the afternoon. All of the day there was marked anaesthesia of the skin. At no time were there any aphrodisiac feelings produced.. There was a pro- nounced increase of the urinary secretion. There were no after-effects, such as nausea, headache, or constipation of the bowels." The sense of prolongation of time present in most cases of hemp intoxication is evidently due to the immense rapidity of the succession of ideas. The mind measures time by the duration of its own processes, and when an infinitude of ideas arise before it in the time usually occu- pied by a few, time becomes infinitely prolonged to the mind. It is a life- time in the minute. A very common mental phenomenon, not easily explained unless as a result of disassociation of the cerebral hemispheres, is a condition of double consciousness, a sense of having two existences, of being at the same time one's self and somebody else. In some cases Indian hemp produces, in addition to or even in the place of the symptom already spoken of, marked disturbances of motility. Convulsions have been noticed by Lawrie, 2 and local spasms, with salaam convulsions, by F. H. Brown. According to O' Shaughnessy, the induc- tion of catalepsy is not rare among the Hindoos. Whatever may be the symptoms of the first stage, sooner or later, if the dose be sufficient, drowsiness comes on. Generally, before it is marked, partial anaesthesia, often with partial loss of strength, is mani- fested, especially in the lower limbs. The pupils are dilated, the pulse is quickened, and finally the subject falls into a heavy sleep, out of which he generally awakes hungry, without any of the wretched gastric sensa- tions or the malaise felt after an opiate. Confusion of thought, however, may persist for some hours. Cannabis exerts no constipating influence upon the bowels, and appears to increase, rather than decrease, the excre- tion of the kidneys. In the dog, hemp extract causes exaltation followed by profound sleep (Hans Zeitler, 3 H. A. Hare 4 ). That the drug has very little influence upon the vital functions is shown by the enormous amounts required to kill. Hare noted both in the dog and in the frog heightened, followed by markedly lessened, reflex activity. The loss of reflex activity was DELIRIFACIENTS. 195 the result of an influence exerted upon the sensory side of the cord or upon the sensory nerve-trunk, the anaesthesia in the frog being complete at a time when voluntary movement was preserved ; further, when the drug was applied directly to the nerve-trunk it produced sensory palsy. Although probably a local anaesthetic, cannabis indica is too irritant to be applied to delicate mucous membranes. THERAPEUTICS. Hemp has been used in this country chiefly for the relief of pain , but also to some extent as an hypnotic. As an analgesic, it is very much inferior to opium, but may be tried when the latter is for any reason contra-indicated. In full doses, in neuralgic pains, it certainly often gives relief. It has been very largely employed to induce euthanasia in the advanced stages of phthisis, and constitutes, it is said, a popular nostrum employed for that purpose. In tetanus, Indian hemp has been used quite largely, and is sometimes apparently an aid to other remedies ; it should be given to intoxication. As first suggested by Seguin, hemp extract, administered for months continuously in such doses as will keep just within the limit of distinct physiological effects, is often effective in migraine. ADMINISTRATION. Extract of hemp is a very unsatisfactory drug from the fact that one-eighth of a grain of one extract will produce de- cided intoxication, and many grains can be taken of another extract that cannot be distinguished physically or chemically from the first specimen. The only way of using it with advantage is for the practitioner to try various samples in ascending doses, and use those which are active in the dose which he has found to be effective. The foreign extracts are, on the whole, more reliable than those made in America. It should always be borne in mind that, though the symptoms may seem alarming, there is much less danger in intoxication from hemp than from alcohol. No cases of fatal poisoning have been recorded. The dose of the official tincture (TINCTURA CANNABIS INDICES ten per cent., U. S. ) is thirty minims (2 C.c. ) ; of the fluid extract (FLUIDEXTRACTUM CANNABIS IN- DICT, U. S. ), one minim (o. 12 C.c.) ; of the extract (EXTRACTUM CAN- NABIS INDIC^E, U. S. ), one-sixth to one-fourth of a grain (0.01-0.016 Gm. ) : all of these doses may be indefinitely increased until symptoms are produced. Notwithstanding the assertions of Fronmiiller and Hiller, the tannate of cannabene of Merck has in our trials of it seemed to be inert. COCA. U. S. The leaves of Erythroxylon Coca, a South American shrub, which is very largely cultivated in Peru and neighboring countries, resemble in size and shape those of tea, but are not dentate, and are distin- guished from most medicinal leaves by a slightly curved line, running from the base to the apex, on each side of the midrib, and produced by the peculiar folding of the leaf in the bud. In 1855 Gardeke dis- covered in coca an alkaloid to which he gave the name Erythroxyline ; but this principle was first thoroughly studied by Albert Niemann, from 196 GENERAL REMEDIES. whom it received the name Cocaine, by which it is now usually known. It occurs in colorless, transparent prisms, soluble in seven hundred and four parts of cold water, and forms with the acids very bitter, soluble, crystallizable salts ; besides cocaine, the leaves contain a peculiar tannin, known as coca-tannic acid. PHYSIOLOGICAL ACTION. Local Action. Locally applied, cocaine acts as a very distinct and certain anaesthetic, as was noted by Moreno y Maiz in 1862, and by Von Anrep in 1880, although it was not until Sep- tember, 1884, that Karl Roller 1 demonstrated the practical value of the drug. According to the observations of Von Anrep, the nerves of special sense are as readily affected as are those of common sensibility : thus, co- caine placed upon the tongue abolishes at the place of contact, for the time being, the sense of taste. At the point of contact there is at first marked pallor, but after a short time very pronounced redness. In sensitive membranes like the conjunctiva, cocaine also causes at first much pain. The primary pallor is alleged to be due to a very powerful constriction of the small blood-vessels, and has led F. H. Bosworth 2 to the conclusion that cocaine produces rigid contraction in unstriped muscular fibres when- ever it comes in contact with them. The anaesthesia is not, however, due to any spasm of the vessels, but to a direct action upon the nerve-trunk. Applied to the bared nerve, cocaine paralyzes first the sensitive and afterwards the motor fibres (Feinberg 5 ). Arloing 4 asserts that the con- centrated solution of cocaine placed on the bared nerve produces a dis- tinct organic change in the nerve. According to the experiments of Peter Albertoni 5 and of B. Dan- ilewsky, 6 cocaine in sufficient concentration acts upon all forms of proto- plasm, first exciting and then paralyzing functional activity. Absorption and Elimination. The soluble salts of cocaine are ab- sorbed with great rapidity. They have the power of passing with almost equal ease through all mucous membranes, so that their absorption is almost immediate when they are employed locally in the nose, urethra, or other part ; hence the large number of serious poisonings which have resulted from their local use. The ultimate fate of cocaine in the body is at present somewhat uncertain. It appears to escape to some extent through the urine unchanged (Thomas Moreno y Maiz 7 and others), but the amount that has been recovered by chemists has been so small (five per cent., Wiechowski 42 ) as to lead to the wide-spread belief that the alkaloid is in great part destroyed in the system ; and Glasenap 4S believes that he has found ecgonin, a decomposition product, in the urine. General Action. From the days of the Incas the leaves of the coca plant have been enormously used by the natives of Western South America as a stimulant, and it is stated that about forty million pounds of them are annually harvested. Mixed with ashes or a little lime, they are chewed, and are said to increase greatly for the time being the muscular strength and endurance. Although coca is thus employed habitually, no scientific observers have given detailed reports of the DELIRIFACIENTS. 197 symptoms which it causes in the South American natives, observers con- tenting themselves with the mere statement that the physical and mental powers of the natives are greatly stimulated by the drug. Moderate doses appear to increase temporarily, to a very extraordinary degree, both physical and mental power. Various travellers concur in praising the peculiar sense of calm and happiness, the insensibility to fatigue, and the increase of bodily and mental activity which the drug produces. Montegazza states that when he took two hundred grains of the leaves he was in a short time plunged into a condition of peculiar delirious beati- tude, in which he seemed to be isolated from the rest of the world and to live in a peculiar atmosphere of active calm. In a little while there came also a sense of plenitude of power which was accompanied by a real increase of physical ability, so that gymnastics which in his ordi- nary condition were impossible to him became easy. This state was suc- ceeded by a natural profound sleep, lasting sometimes for twenty-four hours. Thus, on one occasion Montegazza took thirty-five grammes, and an hour later nine grammes, etc., until he had taken in the course of two hours sixty grammes in all. The heart, which after the earliest dose had been slow in its action, directly after the second dose suddenly became rapid and very violent in its beats ; but at the end of the two hours the palpitations had ceased, although the pulse was still 128 per minute. There was now a condition of intoxication similar to that which is produced by hashish. Montegazza was possessed by a feeling of intense beatitude and inner joyousness, while a succession of visions and phantasma- goria, most brilliant in color and form, trooped rapidly before his eyes. He seemed to himself to look upon a world of shifting and incessant activity, as into a kaleidoscope. He rapidly passed into a delirious condition, in which he ap- peared to himself to be unconscious, although when addressed he would answer rationally. To his own consciousness he was, as it were, buried in a revery, or perhaps a more accurate description would be to say that he felt as though, by a sudden rush of intellectual and emotional life, he was carried out of himself, and knew not whether he was in or out of the body. An hour or two later he was suffi- ciently calm to say to his friends "that God was unjust, in that he had made man to live without eating coca. I prefer a life of ten years of coca to one of a thousand years without it." As this state was passing off, he was seized with an almost irre- sistible desire to reproduce its delirium by taking more coca. Finally, however, he fell into a condition of sleep, which lasted only three hours. After this he was able to resume at once his ordinary occupations, and offered no physical evidence of his coca debauch. The moderate daily use of coca, according to our best information, is not injurious, and increases the working powers ; but, according to Poeppig, the habit of excessive use is readily formed, and produces very serious results. The first symptoms are usually those of disorder of the digestive organs. Little by little the power of digestion is lost ; an incurable insomnia is developed, emaciation becomes extreme, ascites appears, and the patient finally dies in a condition of general marasmus. Other authors especially dwell upon the enfeeblement of the intellectual faculties as very marked in those who use the stimulant to excess. Tschudy states that the inveterate coca-chewer can be recognized by his i 9 8 GENERAL REMEDIES. uncertain step, his general apathy, his sunken eyes surrounded by a deep purple aureole, his trembling lips, his green encrusted teeth, his exces- sively fetid breath, and the peculiar blackness about the corners of the mouth. Pronounced aphrodisiac properties have been attributed to coca, but they seem to rest upon tradition rather than upon demonstrated experi- ence. According to M. Unanne, the ancient inhabitants of Peru repre- sented Venus by a female figure with a coca-leaf in her hand, and the coca still plays an important part in the nuptial ceremonies of the Indians. It has been affirmed by Tschudy and Unanne that coca is able to take the place of food ; but this is clearly not the case. Weddell himself states that although an Indian chewing the coca could go on foot many hours without fatigue and without food, yet at the end he would eat more at one repast than he himself would take in two days. He accords with Bibra 8 in stating that coca has the power of putting aside for some time the sense of hunger. While, however, it may mask the appetite, it certainly does not nourish the body, and it is indeed most probable that the absence of hunger is the outcome of a local benumbing of the gastric nerves. Thomas Moreno y Maiz made several crucial experiments by keeping animals in pairs without food, and giving to one coca freely. These experiments have been repeated by B. von Anrep, 9 and in every case the animal which received the coca died at least as early as its mate. The symptoms which have been present in cocaine-poisoning, or have been produced by the coca-leaf or its preparations, in the United States or in Europe, differ essentially from the descriptions of those said to be caused by the plant in the South American natives.* We believe that in no recorded cases has there been anything resembling the beatific visions and exhilarations described by Montegazza. Ordinarily, in the mildest cases of poisoning with us, there are great restlessness and nervous ex- citement, but no sense of beatitude ; rather a condition of terror. With this state come usually distinctly accelerated pulse, increased frequency of respiration, and, perchance, muscular twitchings or even mild con- vulsions. In the more severe cases of -poisoning the symptoms vary ; sometimes there have been nausea, vomiting, rapid, almost imperceptible pulse, great perspiration, and collapse with or without loss of conscious- ness ; in other cases the pulse has been slow and feeble, and sometimes pronounced cyanosis, with slow or almost arrested respiration, has been the most alarming manifestation. The pupils are usually dilated, but have been reported in some cases as ' ' contracted. ' ' After very large doses convulsions usually occur ; they are often violent and epileptiform ; not rarely, at times, at least, they are partial, and in many cases opisthot- onos has been pronounced. Consciousness rarely escapes ; usually it is * The belief of H. H. Rusby, that these differences depend upon alterations of the coca-leaf during its drying and transmission across the seas, has hardly been sustained (Therap. Gaz., 1888). DELIRIFACIENTS. 199 simply lost, but sometimes it is merged into a mania with hallucinations and delusions, which mania may become violent and even homicidal, as in a case reported by Mattison. Very small doses (one- to three-one-hundredths of a grain of cocaine) produce in the frog no other symptoms than some evidences of excitement. After doses of from one-tenth to one-fiftieth of a grain the frog becomes quiet, with an apparent increase, however, in the reflex activity, sometimes amounting to tetanus, followed by increasing palsy and failure of the respiration ; very large doses produce symp- toms of paralysis. In the domestic animals the symptoms vary. In the rabbit there is first a pecu- liar state of quiet, followed in a few moments by a condition of great excitement, in which the animal springs and jumps about. A few minutes later the rabbit again becomes quiet, and now, although trembling much, is so weak that he moves with difficulty. The tremblings increase until they merge in convulsive movements of the legs, while at the same time there is partial paraplegia ; pendulum movements of the head are very marked, and finally epileptiform convulsions appear, while simultaneously a peculiar tetanic rigidity seems to indicate spinal excitement. The lethal dose for a rabbit is put at a grain and a half per kilo. Dogs and cats are said to be more susceptible to the action of cocaine than is the rabbit, and to suffer similar symptoms, but especially with the dog the evidences of mental excitement are more pronounced. According to Von Anrep, after an injection of cocaine the dog will dance and leap, never standing still for a moment, and continually circling around the experimenter. The movements are not at all those of convulsions, but voluntary, and accompanied by every expression of joy and exhilaration. This may continue for hours, the animal then becoming gradually quiet, and passing finally into his normal condition. If instead of a moderate dose a toxic one has been given, there is first a period in which the animal is very restless but seems full of terror and anxiety ; the least sound frightens him, causing him to tremble and to drop his tail between his legs. He does not appear at this time to know his master. Rhyth- mical movements of almost all portions of the body accompany this state. Fifteen or twenty minutes later the mental condition alters, and the dog becomes appar- ently full of joyous excitement. He barks loudly, runs from one person to another, licking them, and giving all the characteristic signs of joy. After a few moments this condition gives way to one of increasing feebleness ; the dog gradually be- comes unable to move, rhythmical movements, cramps, and convulsive symptoms appear ; the pendulum-like swinging of the head gets very violent, and at last narcosis, with epileptiform convulsions, develops. It is evident that many of these symptoms are psychical. Nervous System. L. Dadd* 1 states that distinct histological changes can be recognized in the cells of the nerve-centres as the result of poison- ing with cocaine, and that these lesions are most marked in the cerebral cortex. B. von Anrep believes that the drug has a very distinct and peculiar influence upon the semicircular canals, thereby causing the peculiar pen- dulum-like motions of the head, the lack of coordination, and the rolling convulsions especially seen in doves. Spinal Cord. According to the researches of Von Anrep, the con- vulsive movements are of cerebral origin, and are arrested by section of the spinal cord ; but the experiments of L. I. Tumass 10 indicate that they do not arise in the psycho-motor centres of the brain-cortex, since 200 GENERAL REMEDIES. he found not only that the local application of cocaine lessens the irrita- bility of these centres, but also that during the convulsive stage of cocaine- poisoning the centres are less sensitive than normal. Danini, more- over, appears to have found that section of the cord does not prevent con- vulsions in the hind feet, and the experiments of Mosso show that when the upper cord is cut in the dog and the animal cocainized, the irritation of the nerve-trunk or of the surface will produce in a little while general muscular rigidity. Both Mosso and Von Anrep are in accord with other observers in stating that reflex activity is at first increased by cocaine, and the evidence seems to show that while the convulsive movements of the poisoned animal originate chiefly in the brain, yet there is a primary stage of excited reflex activity, the result of a direct action upon the spinal cord. The motor paralysis and the loss of reflex activity which finally occur in cocaine-poisoning are probably in part the result of an influence upon the nerves ; but that they are chiefly due to a direct seda- tive action upon the spinal cord seems to follow from the experiments of Mosso, who found that when he so bound the hind legs of the frog as to prevent the access of cocaine to the nerves, there was a rapid loss of reflex activity, and indeed a complete paralysis, at a time when both the motor and the sensory nerves were still intact. An observation made at a certain stage of the poisoning by Dr. Ott viz. , that irritation of the posterior column of the spinal cord produced no effect, while a prick of the anterior column was followed by the usual result indicates that there is the same difference in action upon the sensory and motor tracts as upon the corresponding nerve-trunks ; but Mosso' s experiments upon tritons led him to conclude that the power of conducting impulses efferently, or from the centre, is first lost in the spinal cord poisoned with cocaine. Nerves. Almost all observers agree that the sensory nerves after suf- ficient doses are finally paralyzed in cocaine-poisoning ; but Mosso " believes that the respiratory centre is more susceptible to the action of cocaine than are the sensory nerves, and certainly doses of the alkaloid not dangerous to life have no perceptible general effect upon the sensory nerves. The experiments of Nikolsky, of B. von Anrep, of Ott, and of Laffont seem to prove that the sensory paralysis is preceded by increased functional activity, which is in accord with the observation of Mosso, that in doses of 0.05 to o. i gramme cocaine increases in man the sensibility of the skin. According to Danini, the motor nerves in the frog remain irritable until after death ; but, according to Nikolsky, their functional activity is first increased and afterwards destroyed. Ott also asserts that co- caine depresses the motor nerves. Moreno y Maiz found that when he tied the iliac artery of a frog on one side and administered cocaine anteriorly, there came a time when irritation of the poisoned limb caused no movement, while irritation of the protected extremity pro- voked very distinct general reflexes ; at the same time there was dimin- DELIRIFACIENTS. 201 ished motility in the non-protected limb as compared with the pro- tected one : facts which, of course, indicate that the drug finally depresses both motor and sensory fibres, but that its action upon the motor is subordinate to that upon the sensory nerves. Ott also noticed that there is a time in the poisoning when irritation of the central end of a cut sciatic nerve produces no response, while irritation of its peripheral end causes muscular action, and thereby confirms the view that the drug affects the sensory earlier and more powerfully than the motor nerves. H. Alms found 12 that a five per cent, solution of cocaine in contact with the isolated ischiatic plexus of the frog caused absolute anaesthesia of the leg and apparent loss of motor power, the leg lying motionless and trail- ing behind. Nevertheless, strong irritation upon the front leg of the frog caused immediate movements which were shared by the cocainized hind leg, showing that the motor filaments were not paralyzed. The experi- ments of Alms indicate that the extreme peripheral filaments of the nerve are first affected, since at a certain period most severe irritation of the skin produced no pain in the poisoned rabbit, although the injection of irritating materials evidently caused violent pain. The discovery of Mosso, that the local application of cocaine sus- pends functional activity in motor nerves, has been confirmed by L. Popielski, 13 and it must be considered as demonstrated that cocaine is a paralyzant to both motor and sensory nerves, although it acts much more powerfully upon the sensory nerves. According to Verebe'ly and Horvdth 40 , the action of cocaine upon the nerve-endings is so pronounced that demonstrable changes can be noted after it has been applied locally. Circulation. The action of cocaine upon the circulation is in some details so complex that in spite of much work it is not yet fully understood, but in the main our knowledge concerning it is clear. The concordant experimental results obtained by Ott, by Von Anrep, by Vulpian, by Laborde, by Nikolsky, by Danini, and by Reichert 1 * show that the moderate dose of cocaine produces an increase in the arterial pressure. It is true that some of these experimenters employed only non-curarized ani- mals, but others practised curarization and artificial respiration, so that it must be acknowledged that whilst disturbance of the respiratory and muscular system, by the alkaloid may secondarily increase the blood-pressure, yet it has the power of directly increasing the arterial pressure. The fact that various experimenters have failed to obtain the increase of pressure just spoken of is in some cases to be ex- plained by their having used too large doses, all investigators agreeing that the too large dose of cocaine finally decreases pressure ; in other cases, when small doses of cocaine were employed (Berthold 15 ), it is probable that so much curare had been given that the drugged heart and blood-vessels were unable to respond to a new poison : certainly the evidence is overwhelming that cocaine directly increases blood-pressure. The experiments of Danini, of Berthold, and of Reichert are con- cordant in showing that after section of the spinal cord alone, or of the spinal cord and the vagi, cocaine does not distinctly increase the arte 202 GENERAL REMEDIES. rial pressure, proof that the chief cause of the rise of the arterial press- ure under the influence of cocaine is centric vaso-motor spasm. Concerning the action of cocaine upon the heart itself there is such conflict of testimony as to require further experimentation before positive conclusions can be reached, but the drift of the present evidence is to show that the small dose of cocaine moderately stimulates the heart, and that the large toxic dose finally depresses it. As showing the stimulant action of the small dose of cocaine, Mosso and H. G. Beyer, 16 as the result of their experimental studies, made in the one case on the cut- out frog's heart, in the other upon the isolated heart of the terrapin, found that the minute dose of the alkaloid increased the whole amount of force put out by the heart, as well as the power of the individual systolic contraction ; whilst Pachon and Moulinier, 17 in experiments with cocaine on the heart of the frog in situ, find that after a moderate dose of cocaine there is a hypertonicity of the heart due to a direct action upon the muscular fibres. Observers affirm that the heart of the mam- mal is arrested by the toxic dose in diastole, which is in accord with the statements of Yon Anrep and Nikolsky concerning the heart of the frog and of H. G. Beyer concerning that of the terrapin, diastolic arrest being affirmed by all these investi- gators. Pachon and Moulinier declare that the ventricles are arrested in systole, the auricles in diastole. According to these investigators, the arythmia of advanced cocaine-poisoning is really a rhythm which differs from the normal in that the con- tractions occur in regular groups ; later there is a dissociation of the auricular and ventricular rhythms. The fact that section of the spinal cord that is, separation of the general capillaries of the body from the vaso-motor centres largely or altogether prevents the rise of arterial pressure produced by cocaine indi- cates that the alkaloid has little or no direct influence upon the vessels themselves, but the matter is not as clear as appears at first sight. The evidence as to the facts is contradictory. Mosso found that when he ex- perimented with artificial circulation upon extirpated kidneys small doses of cocaine had no sensible effect upon the blood-vessels ; and Durdufi states that marked nar- rowing of the vessels of the rabbit's ear can be seen when cocaine is injected, but is prevented by previous section of the sympathetic. Contrariwise, H. G. Beyer found in experiments upon the terrapin that both large and small doses of cocaine produce contraction of the blood-vessels by a direct influence ; and Laffont experi- mentally reached the conclusion that one of the chief actions of cocaine is to con- tract the blood-vessels by affecting the nerve-endings in their walls. The results of the plethysmographic studies of Mosso namely, that in man therapeutic doses of cocaine cause contraction of the blood-vessels have no bearing upon the matter in hand, since such contraction might or might not be of centric origin. It should also be stated that in some of Reichert's experiments there was a slight rise in the arterial pressure produced by cocaine after section of the cord. The well-known constringing of blood-vessels by the local application of cocaine can hardly be explained except by attributing to the alkaloid the power of acting upon the blood-vessel walls. It should be noted that in such cases the cocaine is brought in enormous quantities and great concentration into contact with the blood-vessels ; and in view of the contradiction in the experimental evidence, the most probable con- clusion is that cocaine has direct relations with the muscle-fibres in the DELIRIFACIENTS. 203 arteriole walls, but that it acts so feebly upon them in comparison with its influence upon nerve-centres that even in general poisoning with the alkaloid the influence upon the blood-vessel walls is overshadowed by the much greater powers of the drug. The results of the studies made by various investigators with the direct application of cocaine to the heart lead to the conclusion that whilst small doses of the alkaloid feebly stimulate the viscus, toxic doses act as a depressant and finally as a paralyzant ; that cardiac depression is one of the causes of low arterial pressure in advanced cocaine-poisoning is further evidenced by the rapid and immediate fall in the pressure which occurs when cocaine is injected into a dog whose spinal cord has been cut and vaso- motor system paralyzed.* The opinion of Reichert, that widen- ing of the blood-paths by vaso- motor paralysis is the most important factor in the causation of lowered blood-pressure in advanced cocaine- poisoning, seems to be so far correct that the probabilities are that such widening of the blood-paths occurs. The testimony as to the action of the alkaloid upon the pulse-rate and upon the inhibitory nerves of the heart is so various that no positive con- clusions are warranted without further study. Von Anrep states that the pulse-rate is usually increased, but that this increase is not marked in rabbits, while in Ott's experiments upon dogs the pulse usually becomes slower. Von Anrep also states that the vagi are paralyzed by large doses of cocaine, while Ott, Nikolsky, Laffont, and Durdufi 18 declare that it does not affect the vagi, and Berthold states that previous section of the vagi has no effect upon the course of the symptoms caused by cocaine. Reichert found in an elaborate series of studies that by small doses of cocaine the pulse-rate is at first decreased, then increased, and finally decreased. In regard to the causes of the alterations of the pulse he came to the following conclusions : "Very small doses of cocaine decrease the rate by stimulating the cardio-inhibi- tory centres ; small to moderate doses increase the rate by depressing these cen- tres, and in some cases by depressing also the cardio-inhibitory ganglion ; large doses cause a transient decrease, followed by a rise or a permanent decrease, the de- crease being due to a depression of the accelerator or motor ganglion in the heart, and the increase to the factors before mentioned. The cardio-inhibitory centres are invariably affected, being primarily stimulated and secondarily depressed." Muscles. Although there is some contradiction of evidence, yet our knowledge of the effect of cocaine upon the striated muscles is sufficient for positive conclusions. Alms, Nikolsky, and B. von Anrep state that the striated muscles are not affected by the alkaloid, while Ott affirms that it acts upon them like veratrine, and is con- firmed in this by Buchheim and Eisenmenger. 19 The tracings given by Ott would appear to prove that the muscular contraction is prolonged by cocaine, and can hardly be accounted for by a condition which M. J. Rossbach and B. von Anrep allege to be produced, viz., a peculiar sensibility of the muscle similar to that pro- duced by curare, and, like it, caused by a lessening of muscle-tonus by paralysis of the peripheral nerve-endings. * See experiments of I. Ott, Toxicological Studies, 1874, 30. 204 GENERAL REMEDIES. The results obtained by Otffind such confirmation in the experiments of Berthold upon the effects of the local application of cocaine upon the frog's muscle, and in those of Mosso, who found that in the frog, the dog, and the man the excitability of the muscles is increased by small doses, and paralyzed by large doses of cocaine, that it must be considered established that cocaine is a muscle poison, stimulating and afterwards depressing the functional activity. This influence of the alkaloid is, however, probably too slight, as compared with its effects upon other portions of the organism, to be very apparent in general poisoning. Nevertheless, in the ergographic experiments of Benedicenti 20 cocaine both heightened muscular energy and increased resistance to fatigue,* whilst Mosso found that in man, when the muscles were exhausted by work and fasting, the exhibition of cocaine in the dose of a grain and a half more than doubled the response to stimuli. These experiments throw a peculiar light upon the assertions of travellers, that cocaine in the South American Indians enormously increases the power of with- standing fatigue. The present difficulty in the way of the full acceptance of the natural deductions from them is the fact that in America and in Europe cocaine has appeared to fail as a stimulant during fatiguing labors. Temperature. The rise of rectal temperature in cocaine-poisoning sometimes amounts to as much as 8 F. It is certainly not due to the convulsions, as it usually occurs before the motor disturbance, t In fatal cases it is followed by a fall, so that before death the temperature may become subnormal. In the calorimetrical experiments of Reichert, the rise of temperature was found to be due to a great increase in the heat production. Reichert " has further determined that after section of the spinal cord \ at its junction with the medulla, as well as after section of the crura cerebri, cocaine is powerless to produce rise of the temperature, and therefore concludes that the rise of temperature produced by cocaine is of cerebral origin, and is due to stimulation of the thermogenic centres in the cau- date nucleus and to motor excitement produced by stimulation of the cortical motor centres. Urinary Secretion Such varying results have been recorded by clinicians as to the effect of cocaine upon the amount of urinary secretion that its action is probably not constant. According to Bignon, 21 the single large dose may produce an anuria so prolonged as to bring on uraemic symptoms. There is some reason for believing that cocaine re- * Sobieranski believes, however, that the effect of cocaine is through the nerve-cen- tres (see Gazetta Lekarska, 1896, No. 4). t P. Langlois and Charles Richet have found that the temperature of the cocainized animal has a great effect in determining the amount of cocaine necessary to produce convulsions. The higher the temperature the smaller the dose necessary, and when the animal was kept at a temperature of 39 C., only tonic convulsions were produced. t The rise of temperature which has been noted by Mosso after section of the spinal cord may have been the result of imperfect division. DELIRIFACIENTS. 205 duces the nitrogenous elimination, but the experiments upon the subject are hardly sufficient to warrant the positive conclusion that the alkaloid checks protoplasmic waste. I. Ott and Atherton P. Mason w have found that when cocaine is taken habit- ually it not only lessens the urinary secretion but also markedly decreases the elimination of urea, whilst in three experiments Richard Fleischer determined that the alkaloid markedly reduces nitrogenous elimination. Mason experimented with very large therapeutic doses of cocaine taken during prolonged exercise, and states that his results were contrary to those previously reached by Gazeau. In Ott's experiments the urine, under the influence of cocaine, became full of calcium oxalates. Sugar and albumin have been frequently noted in the urine of poisoned animals, but Von Anrep affirms that their pres- ence is due to the prolonged asphyxia induced by the drug. Eye. When a watery solution of cocaine is dropped into the eye there occurs a slight contraction of the pupil, followed within a few minutes by dilatation. The first contraction is probably reflex and due to the irritation of the conjunctiva. The maximum dilatation for a four per cent, solution is usually reached about the end of the first hour ; an hour later it has sensibly begun to decline, and in from twelve to twenty- four hours the pupil returns to normal. The dilated pupil is to some extent responsive to light and to accommodation, the mydriasis can be rapidly overcome by eserine, and, according to Limbourg, 2 * increased by atropinization. The dilatation of the pupil is certainly due to a peripheral influence which appears to be a double one, namely, stimulation of the sympathetic nerve endings and paralysis of the oculo-motor endings. The experiments of Nikolsky, Holtzke, Limbourg, as well as of Scholer and Pfliiger (quoted by Limbourg), show that cocaine applied to the eye immediately after section of the sympathetic does dilate the pupil, although later, when suffi- cient time has elapsed for degeneration of the sympathetic fibres to occur, the alka- loid is powerless. This would appear to prove that cocaine dilates the pupil by stimulating the sympathetic nerve-endings ; but, according to Schultz, very strong solutions of cocaine will dilate the pupil after nerve degeneration has occurred, though weaker solutions fail to act. Further, Schultz found that when, in the cat, he extirpated the superior cervical ganglion on one side, waited a sufficient length of time for degeneration of the dilator nerves, and then applied cocaine to both eyes, he obtained a maximal dilatation on the unoperated side, but a medium dilata- tion on the operated side. Allowing the correctness of Schultz's experiments, the double action of cocaine appears to be demonstrated. Limbourg states that electrical irritation of the cornea may restore to such an eye the power of respond- ing to cocaine. Respiration. Small doses of cocaine increase distinctly the rapidity of the respiration, and in some cases also the depth (Von Anrep, Mosso, Danini, Ott, and Nikolsky). After toxic doses the respirations become at first rapid and more shallow, then irregular with interruptions, after each of which the respiratory movements begin deep and slow, but be- come more rapid and shallow until the next stand-still. As Mosso found 206 GENERAL REMEDIES. that after section of the vagi cocaine causes an enormous increase of the rapidity of the breathing and at the same time so modifies the rhythm that expiration is no longer quicker than inspiration, it must be con- sidered that the drug acts directly upon the respiratory nerve-centres as a respiratory stimulant. The first stimulant effect of cocaine upon the respiratory centres appears to be followed after fatal doses by a paralyzing influence which leads to death from asphyxia. Intestines. According to Von Anrep, the intestinal peristalsis is markedly increased by moderate doses. After large doses this increase is followed by great sluggishness deepening into paralysis. Tarchanoff states that coca increases the mucous secretions, but Von Anrep affirms that it decreases them.* SUMMARY. Cocaine is a cerebral stimulant, producing peculiar mental excitement, ending after large toxic doses in narcosis, with epi- leptiform convulsions, which are probably of cerebral origin. In the poisoning there is at first increased reflex activity, followed by paralysis of voluntary motion and of reflex activity, which are chiefly due to a direct action upon the spinal cord, the sensory side of the cord being probably more sensitive to the drug than the motor side. Toxic doses depress and finally paralyze the sensory nerves, and in a much less degree the motor nerves. Our present physiological knowledge estab- lishes the fact that cocaine in moderate dose is a mild stimulant, in over- dose a depressant, to the circulation, the primary rise being chiefly due to narrowing of the blood-paths by stimulation of the vaso-motor cen- tres. Upon the heart itself the moderate dose of the alkaloid acts pri- marily as a stimulant, increasing to a slight extent the amount of force put forth by the heart. There is also reason for believing that co- caine exerts a direct influence upon the coats of the blood-vessels, which is, however, so feeble as not to be of practical importance except when the cocaine is applied locally. The fall of blood-pressure pro- duced by the toxic dose of cocaine appears to be due to a direct depres- sion of the heart itself, aided by a widening out of the blood-paths, probably through paralysis of the vaso-motor centres. Upon striated muscles cocaine appears to have a peculiar though very feeble action, which is not manifested during poisoning by it. It has been asserted that cocaine acts as a powerful diuretic, but the drift of present evidence is to show that it has no definite influence upon the amount of urine secreted: the evidence available indicates that it decreases elimina- tion of urea. Upon the eye cocaine acts as an energetic mydriatic. It is a powerful stimulant to the respiratory centres, increasing the rapidity and fulness of the respirations, but if the dose be sufficiently large it after a time causes the respirations to become very shallow, and finally paralyzes the respiratory centres. Moderate doses are said to increase, large doses to paralyze, peristalsis. THERAPEUTICS. By its constringing influence upon the blood-vessels, as well as by its local effect upon the sensory nerves, cocaine is a valuable local remedy. In acute coryza a ten per cent, solution applied to the nostrils will sometimes afford permanent relief, but a combination of a four * M. E. Gley states (Compt.-Rend. Soc. Biol., iii. 560) that when cocaine is injected into the portal vein it produces comparatively little effect, and he believes that it is destroyed in the liver. This is criticised by Chouppe (Ibid.). DELIRIFACIENTS. 207 per cent, solution with bismuth (three drachms to the ounce of mucilage) is more generally useful. It should be applied by means of a dropper every three or four hours. In hay fever, in the peculiar irritated sore throat of advanced/^/^ww, in chronic laryngitis, in inflamed hemorrhoids , in fissure of the anus, and even in open cancer its application will often afford temporary relief. In some cases of dysentery with excessive nervous irritability of the rectum, cocaine suppositories are of great ser- vice. Cocaine is also sometimes useful as a local haemostatic in arresting nasal and other mucous membrane hemorrhages. For local use the two to ten per cent, solution may be employed, care being exercised not to use a possibly fatal dose of the drug. Internal Use. As an internal medicament cocaine is useful as a re- spiratory stimulant and as a tonic, especially to the circulation. It is largely used in the same class of cases in which strychnine is found to be available. Less powerful in its influence than is strychnine, it is espe- cially useful as an aid to that alkaloid. (See Respiratory Stimulants.) Its stimulant influence upon the cerebrum naturally led to the expectation that it would be of value in cases of depression of spirits and even of true melancholia. The results of our own experience, after thorough trial, however, are in accord with the generally expressed opinions of alienists, that it has no remedial value in any form of mental aberration. Some- times it appears to produce at first a temporary relief, but this does not continue ; and if the remedy be pushed, anorexia, restlessness, or other disagreeable symptoms usually demand its withdrawal. In neurasthenia and hysteria it is valuable only as a stimulant and stomachic, acting better in the form of the fluid extract than cocaine itself ; and in all these cases there is especially the danger of the formation of the cocaine habit. Large doses of the fluid extract are sometimes of service. In the form of large doses of the fluid extract, coca has appeared to us to be of service during the breaking off of the opittm habit, exerting some stimulant influence upon the nervous system, and restraining the tendency to diarrhoea and loss of appetite. Some European clinicians have found cocaine of service in the treatment of serous diarrhceas. It is undoubt- edly of value for the relief of excessive vomiting, especially when due to gastric irritation. Thomas D. Dunn 2 * states that hypodermic injections of one grain control the pain of migraine. Aschenbraidt 2D asserted that, in doses of 0.15 grain, cocaine was a valuable stimulant during forced marches ; but in a series of careful trials with it by the medical rowing crew of the University, it appeared to have no value, and the general experience seems to conform with this result. ADMINISTRATION. The official salt of cocaine (COCAINE HYDRO- CHLORIDUM, U. S. ) may be given in doses of one-sixth to one-half a grain (0.01-0.03 Gm. ) ; the cruder preparations of the drug are at present rarely used. The dose of the official fluid extract (FLUIDEXTRACTUM , U. S. ) is one-half to two fluidrachms (1.97.5 C.c. ). TOXICOLOGY. The number of cases of poisoning by cocaine is very 208 GENERAL REMEDIES. great, and although large doses have been recovered from, excessively violent symptoms have followed the use of smaller amounts. It is re- markable, also, that in many of these cases the drug has been employed for a local effect. The fatal cases, to the details of which we have had access, are those reported by Kolomnin, twenty-four grains into the rectum for local anaesthesia ; F. M. Thomas, four per cent, solution used locally for toothache, in unknown quantity ; Knabe, four per cent, solution, twelve drops given hypodermically to a girl of eleven years, death in forty seconds (for details, see J. B. Mattison 26 ) ; J. H. C. Simes," one drachm of twenty per cent, solution injected into the urethra, fol- lowed immediately by violent convulsions, ending in death in twenty minutes, autopsy proved that urethra was not ruptured. A fatal case is said to have been reported in Odontologie, 1890, x. Half an ounce of a two per cent, solution of cocaine injected into hydrocele and allowed to stay about a minute is said to have caused death (Paul Berger 28 ). O. H. Garland, 29 death said to have been produced by the application of twenty drops of a five per cent, solution to the gum. E. Pfister, 30 death caused by an unknown quantity of a twenty per cent, cocaine solu- tion injected into the urethra. On the other hand, large amounts of the drug have been recovered from. Von Ploss st reports twenty-two grains taken by an apothecary, by the stomach, with spontaneous recovery, although the urine was suppressed for twenty-four hours. In another case ten grains taken hypodermically in the course of five hours produced complete unconsciousness, excessive failure of circulation, slow respira- tion, recovery under treatment (J. S. Spear M ) ; E. Caldwell 35 reports recovery after the hypodermic injection of five grains, which produced convulsions with asphyxia. A case reported by W. Finlay 34 is interesting, because six grains given hypodermically to a pregnant woman lowered the pulse to 38 and the breathing to 5, but did not cause a miscarriage. Some of the most remarkable cases of poisoning by small quantities are those reported by T. H. Burchard, ten drops of a four per cent, solution injected hypo- dermically caused unconsciousness and apparent death in four minutes ; Myer- hausen, eight drops of a two per cent, solution upon the conjunctiva produced in a girl of twelve years violent symptoms ; Kennicott, a case of violent symptoms produced by cocaine in hay fever ; George T. Stevens, one in which four minims of a three and a half per cent, solution, given to a strong man, produced violent con- vulsions, followed by mania ; Grosholz, three drops of a four per cent, solution in the eye ; Frost, one drop of a one per cent, solution in the eye produced in a child of fourteen marked poisoning ; Ramsden Wood" reports violent poisoning with four minims of a twenty per cent, solution. A number of cases are on record in which very severe symptoms have been produced by one grain given hypodermically (see Mattison, Addinsell, 36 and Pitts") ; and it is plain that, although this dose has been used to a considerable extent, its employment is unjustifiable. The occasional effects of the local application of cocaine are very remarkable.* It is not safe to put upon mucous membranes amounts which if given hypodermically would be dangerous ; so that not more than three-quarters of a grain should be used locally. * In addition to cases mentioned, see Brit. Med. Journ., Nov., 1885; Deutsch. Med. Wochensch., No. 46, 1886; New York Med. Rec., 1886, ii. ; La Pratique Med., Jan. 1891 ; S. J., cclvii. 201. DELIRIFACIENTS. 209 The treatment of cocaine-poisoning must be largely symptomatic. When there is great cerebral and motor excitement, we have found chloro- form to act very happily. Partial anaesthesia may be maintained for some moments. If the symptoms do not yield to such medication, chloral may be cautiously exhibited. When .the toxic manifestations are syncopal, hypodermic injections of digitalis may be given, whilst alcohol and am- monia are exhibited by the mouth ; if circumstances favor, intravenous injections of ammonia might be justifiable. In some cases life has been apparently saved by artificial respiration. Intravenous injection of salt solution has been recommended.* Cases of cocainismus or chronic cocaine habit are not rare, but in the great majority of instances the victim is addicted to the use of more than one narcotic. Usually the cocaine has been taken as a substitute for, or aid to, morphine : in a number of cases the habit has been formed by the local use of the drug for hay fever. The symptoms are in no way char- acteristic ; dreaminess, apparent inability to attend to the ordinary duties of life, loss of reliability, promptness, and punctuality, varying mental aberration suggesting, but different from, that of paranoia, occurring in any case, should arouse suspicion. The paranoiac, unless greatly de- pressed, is usually egotistical, self-reliant, conceited ; the victim of co- cainism, in matters not connected with his habit, is usually even less self- assertive and more easily led than the normal individual. Magnam 58 affirms that a peculiar hallucination as to the existence of foreign bodies under the skin is characteristic. The will and the desire to reform are as weak as in the opium habit, and the greatest difficulty is usually to get the victim earnestly to desire reformation. The abrupt withdrawal of the narcotic is probably always safe ; thus, in a case in which fifteen grains were taken hypodermically daily, the immediate cessation of exhibition was followed by no greater disturbance than diarrhoea, dyspepsia, and nervous depression, which subsided in the course of two or three days. (For cases, see Grundlach ** and Mattison. 26 ) REFERENCES. ATROPINE. 8. WOOD A. J. M. S., April, 1873. 1. LEFORT L'Union M6d., Nov. 1871. 9. ALBERTONI . . . A. E. P. P., xv. 265. 2. ZELLER V. A. P. A., Ixvi. 384. 10. BOTKIN V. A. P. A., xxiv. 85. 3. FUBINI and BONANNI . U. N. M. T., 1892, xiv. n. MEURIOT . . . . De la Methode Physiol. 4. BEZOLD and BLOEBAUM . U. P. L. W., i. en Th&rap. et de ses 5. LANGENDORFF . A. G. P., 1886. Applic. a 1'Etude de la 6. GNAUCK Verhandl. Physiolog. Ge- Belladone, Paris, 1868. sellschaft, Berlin, 1881. 12. ERASER Tr. R. S. Ed., 1869, xxv. 7. BEYER A. J. M. S., July, 1885. 450. * Systemic Lavage for Poisons. Intravenous injection of normal saline solution as a treatment for acute poisoning has been experimented upon by Carlo Bozza ( Canadian Pract., 1898, xxiii.), who believes that it leads to rapid elimination and slow absorption, owing to fulness of the blood-vessels. He determined that the minimum fatal dose of cocaine given to dogs hypodermically is 0.025 gramme per kilo ; rising to 0.03 if hypo- dermoclysis is employed, and to 0.035 with lavage of the organism. 14 210 GENERAL REMEDIES. KEUCHEL .... In. Dis., Dorpat, if- OTT N. Y. M.J., 1883. REFERENCES. Continued. 4. HEILMANN . WOOD J. P., 1892. HEUBACH . . . . A. E. P. P., viii. ORLOWSKI .... Thesis, Warschau, 1891. VOLLMER . . . . A. E. P. P., xxx. UNVERRICHT . . B. K. W., 1896. WALTI A. E. P. P., 1895, xxxvi. HARLEY The Old Vegetable Neu- rotics, London, 1869. OTT and COLLMAR . T. G., Aug. 1887. JONES M. T. G., 1857. ROLLETT .... A. Op., xv. i. DIEGEL Arch. f. Mikros. Anat., 1870, vi. i. 26. BONDERS .... Accommodation and Re- fraction, New Sydney Soc- Ed., 584. 27. A. G. P., xxvi. 460. 28. BERNARD .... Physiol. et Pathologic du Systeme Nerveux, Paris, ii. 212. 29. WOOD P. M. T., i. 290. 30. HOPPE Die Nervenwirkungen der Heilmittel, Leipsic, 1856, ii. 179. 31. VALENTIN . . . . Versuch einer physiol. Pa- thologic der Nerven, Leipsic, 1864, ii. 368. 32. BORELLI Ed. M. J., Nov. 1871. 33. VON CARION . . . Der intraoculare Druck und die Innervations Verhaltnisse der Iris, Vienna, 1868. ENGELHARDT . . U. P. L. W., ii. 321. ROSSBACH and FROHLICH . Pharmak. Unter- such, Wiirzburg, i. 6. DA COSTA .... P. M. T., Feb. 15, 1871. HAMMERBACHER . A. G. P., xxxiii. 228. NORRIS A. J. M. S., Oct. 1862. M. T. G., Nov. 1856. London Pharm. Journ., 1871. 41. MOREL Ann. de la Soc. de Med. de Gand, 1873. 42. W. G. H., Feb. 1845. 43. CHAMBERS . . . Lancet, 1864. 44. REICHERT .... P. M. J., Jan. 1901. 45. MATHEWS . . . . A. J. P., 1901, iv. 482. 46. STRACHAM . . . L. L., 1901, i. 47. RAPHAEL . . . . D. M. W., 1899, xxv. , 48. WIECHOWSKI . . A. E. P. P., 1901, xlvi. 49. SCHULTZ .... A. A. P., 1898. HOMATROPINE. i. DE SCHWEINITZ and HARE . M. News, 1887, Ii. 731. STRAMONIUM. i. LAURENT . . . . De 1'Hyoscyamine et de la Daturine, Paris, 1870, Thesis. HYOSCYAMUS. i. HARLEY The Old Vegetable Neu- rotics. a. LAURENT .... Thesis, Paris, 1870. 3. SCHROFF .... Wb. G. A. W., 1865. 5. SHAW . . 6. RICHTER 7., RINGER . 1. WOOD, JR. . 2. WILCOX . . . . Beitr. zur Kenntniss der Physiol. Wirk. d. Hyos- cyamins, Jena, 1873. . . . J. N. M. D., vii. 27. . . . N. Cb., i. 294. . . . Pract., March, 1877. Lancet, 1879, i. 474. SCOPOLA. . . . T. G., April 15, 1901. . . . M. News, Aug. 31, 1901. HYOSCINE. 1. WETHERILL . . . T. G.,i. 199. 2. WOOD ...... T. G.,Jan. 18 3. GLEY and RONDEAU . C. R. S. B., 1887. iv. 56. 4. BALAGOPAL 5. WINNETT . Indian Med. Rec., 1894. West. Med. Rev., 1898, iii. 2IO. A. and N., iii. 539. U. M. M., i. 6. HUTCHINSON 7. CAREY 8. O'HARA ..... T. G., ii. 9. ROOT ...... T. G., ii. 10. WOOD ...... Amer. Med. 1905. 11. MAIRET and COMBEMALE . C. R. S. B. 1887. 12. KOCHMANN . . . Ther. Geg. 1903, v, 202. 13. CLAUSSENS . . . M. Dis. 1883. 14. KOBERT ..... A. E. P. P. 1887. CANNABIS IND1CA. 1. WOOD ...... Proc. Amer. Philosoph. Soc., 1869, xi. 226. 2. LAWRIE ..... Stille's Therap., i. 772. 3. ZEITLER ..... In. Dis., 1885. 4. HARE ...... T. G., 1887. 5. FRAENKEL . . . A. E. P. P., 1903, xlix. COCAINE. KOLLER . . , BOSWORTH . FEINBERG . , ARLOING . . ALBERTONI , DANILEWSKY . W. M. W., Nov. 1884. . N. Y. M. R., Nov. 15, 1884. . B. K. W., March, 1887. . Lyon M., May, 1883. . A. G. P., 1890, xlviii. . A. G. P., 1892, Ii. MORENO Y MAIZ . Thesis, Paris, 1868. BIBRA Die Narkot. Genussmittel, 1855- VON ANREP . . . A. G. P., 1880, xxi. TUMASS A. E. P. P., xxii. Mosso A. G. P., 1890, 557. ALMS A. Ph., 1886, Suppl. POPIELSKI .... Cb. P., 1896, x. REICHERT. . . . Am. Lan., May, 1891. BERTHOLD . . . . C. M. W., 1885, 435. BEYER A. J. M. S., July, 1885. PACHON and MOULINIER . C. R. S. B., 1898, v. DURDUFI . . . . D. M. W., 1887, 172. EISENMENGER . . Pflanzenstoffe, 2d ed., 885. U. N. M. T., xvi. 170. J. A.M. A., July, 1887. B. M. S. J., Sept. 1882. A. E. P. P., xxx. T. G., 1888. D. M. W., 1883, ix. 50. Med. R., 1887, i. BENEDICENTI , BIGNON . . . . MASON . . . . LIMBOURG . . DUNN . . . . . ASCHENBRAIDT MATTISON SIMES M. News, DELIRIFACIENTS. 211 REFERENCES. Continued. 28. BERGER . . 29. GARLAND . 30. PFISTER . . 31. VON PLOSS 32. SPEAR . . . 33. CALDWELL 34. FINLAY . . 35. WOOD . . . 36. ADDINSELL . B. M. S. C. P., 1891, xvii. Lancet, Nov. 1895. B. K. W., 1896, xxxiii. Husemann's Pflanzen- stoffe, 2d ed. . N. Y. M. R., 1885. . B. M. J., 1885. , Aus. M. Gaz., 1887, ii. . Aus. M. Gaz., Aug. 1886. . Lancet, 1888, i. 37. PITTS Lancet, 1887, ii. 38. MAGNAM . . . . N. C., 1896, 15. 39. GRUNDLACH . . . S. Jb., 1886, ccxii. 40. VEREBELY and HORV/TH . Cb. N., 1899, xviii. 41. DADD L. S., 1899. 42. WIECHOWSKI . . A. E. P. P., 1901, xlvi. 43. GLASENAP .... In. Dis., St. Petersburg, 44. REICHEKT . P. M. J., 1902. FAMILY V. EXCITO-MOTORS. IN this class are included such drugs as increase the reflex activity of the spinal centres, and thereby give rise to disturbance of motility. The only representatives of the class used by the practitioner of medicine are those drugs which contain strychnine as their active principle. NUX VOMICA NUX VOMICA. U.S. The seeds of Strychnos Nux-vomica, a middle-sized tree growing in the East Indies, whence the drug enters commerce. They^re circular, nearly flat disks, a little less than an inch in diameter, covered with very short, satin-like, grayish hairs ; internally they are tough and horny, and are possessed of an intensely bitter taste. They contain two alkaloids, strychnine and brucine, existing in combination with an acid, the so- called igasuric of Pelletier and Caventou, which, according to Huse- mann, is identical with malic acid. The U. S. Pharmacopoeia recognizes the extract (EXTRACTUM Nucis VOMICA), of which the dose is one-fourth of a grain (0.016 Gm.), equivalent to about one-twenty-seventh of a grain of total alkaloids ; the tincture (TiNCTURA Nucis VOMICA, U. S. ), ten per cent.; dose, from ten to fifteen minims (0.600.90 C.c. ), fifteen to twenty-five drops ; and the fluid extract (FLUIDEXTRACTUM Nucis VOMICA), which is required to assay one gramme of strychnine (not total alkaloids) one hundred cubic centimetres; dose, three minims (o. 18 C.c.), containing about one- twenty-third of a grain of alkaloids. It is usually estimated that strych- nine constitutes about forty per cent, of the alkaloids. Practically there is no qualitative difference between the medical action of strychnine and that of the cruder preparations of nux vomica, over which it usually should have the preference on account of definiteness of action. STRYCHNINA. U.S. As kept in the shops, strychnine is a grayish-white powder, but by slow crystallization from its alcoholic solution it may be obtained in octahedral or quadrilateral prisms. It is so bitter that it will impart a very intense bitter taste to twenty thousand times its weight of water. On account of its insolubility (one in about seven thousand parts of cold water) it is very rarely used in medicine, at least in the United States, the sulphate (STRYCHNINE SULPHAS, U. S. ) being universally EXCITO-MOTORS. 213 preferred, and being what is commonly meant in American writings when the word ' ' strychnine' ' is used. Strychnine sulphate contains about seventy-five per cent, of strychnine. The ordinary dose is from one-fortieth to one-twentieth of a grain (0.0016-0.0032 Gm. ).* PHYSIOLOGICAL ACTION. Local Action. The local action of strych- nine is that of a very feeble irritant ; upon the mucous membrane of the stomach it acts like a simple bitter. Absorption and Elimination. Strychnine is absorbed rapidly, whether taken by the mouth or by hypodermic injection. Several investigators have attempted to determine the comparative rate of ab- sorption of strychnine in different portions of the alimentary canal by isolating these different portions by ligatures and then injecting strychnine into them. After tying of the pylorus, Bouley and Colin J found that the absorption of strychnine was rapid in the stomachs of dogs and cats, whilst Tappeiner determined that in cats it was taken up very slowly. In two series of experiments, S. J. Meltzer 2 found that, after tying the cardiac and pyloric ends of the stomach, large doses of strychnine would remain in the stomach of the rabbit without producing any physiological effect, whilst under similar circumstances in the dog the gastric absorption was extremely slow and uncertain. Meltzer further determined that absorption takes place in the oesophagus somewhat more rapidly than in the stomach, whilst the alkaloid was taken up with great and about equal avidity in the small intestines, colon, and rec- tum. Although the method of investigation is open to the objection that the oper- ative procedure may seriously disturb the mucous membrane of the part, and consequently its absorbing power, it is probable that the results of Meltzer are sub- stantially correct. Strychnine has been detected by chemists in the blood, kidney, liver, heart, brain, spinal cord ; indeed, practically in all portions of the system. The statement of R. W. Lovett, 3 that it accumulates in the spinal cord, has been disproved by Ipsen and by Lesser.* It may be in excess in the organs concerned with absorption and elimination, as in the stomach, liver, f and kidneys, but seems to be nowhere else present in the body of the poisoned animal or man out of proportion to the amount of blood going to the organ. It is certain that strychnine escapes from the body to some extent unchanged, as it has been found in the urine by Peter von Rautenfeld, 5 by Wormley, 6 by Schauenstein, by Kratter, 7 and by Dixon Mann. Its elimination is prompt and rapid, as Ipsen asserts that it can be detected in * Thoinot and Brouardel (La Presse Med., 1898, i., Annex, 127) found that when strych- nine is macerated with the spinal cord and brain, or with potato starch, the toxicity is so far lost that double the ordinary fatal dose of the alkaloid is required to kill guinea-pigs. When the nerve-tissue mixture was filtered, the filtrate was without toxic action. The strychnine could, however, be recovered from any of the mixtures, and when separated was found to be physiologically active. The loss of toxicity is therefore not due to its destruction. The authors believe that the loss of activity is due to the strychnine being so fixed as to interfere with its absorption. Talc and charcoal were found to have the same properties as nerve-tissue to a slight degree. t Scruff and Lautenbach believe that they have proved that the alkaloid is destroyed, at least in part, in the liver ; a conclusion which is strongly combated by Chouppe and Pinet (Compt.-Rend. Soc. Biol., 1887, cv.), and is very doubtful. 2i 4 GENERAL REMEDIES. the urine five minutes after its absorption, and others have detected it in the urine half an hour after its exhibition ; and in various poisoning cases, fatal within two hours, it has been found in the urine. Kratter and Mann believe that they have proved that the elimination is complete within forty-eight hours. According to P. C. Plugge, 8 a portion of the alkaloid is converted into strychnic acid* General Action. According to the experiments of Borzi, 9 strychnine paralyzes the sensory organs of plants, but increases the tension (motor function) of the plants : solutions as low as I in 10,000 acted distinctly upon vegetable protoplasm, and when the plant was apparently killed by strychnine, chloroform or paraldehyde would restore its functional activity. Upon all animals strychnine probably acts similarly, but with great variations of power. According to Leu be, 10 it takes ten times as much strychnine to kill chickens as it does to kill other birds, weight for weight ; and among mammals the guinea- pig is very insensitive to it. It has also been asserted that on some monkeys it has but little influence (Boston Med. and Surg. Journ. , 1872). Very young animals are said to be quite insensitive to it.f The resistance of birds to the poison is attributed by Falck u partially to slow absorption and partially to a destruction of the poison in the body. When taken in quantities just sufficient to produce sensible physio- logical effects, strychnine in man induces a feeling of restlessness, per- haps accompanied by tremblings in the limbs and some stiffness in the neck and jaws. When a somewhat larger amount has been given, there may be general muscular twitchings and startings, with stiffness and stricture of the throat and chest ; formications or other abnormal sen- sations under the skin may or may not be present. After poisonous doses the symptoms come on usually in from fifteen to twenty minutes, rarely after an hour, with great suddenness ; sometimes the convulsions are preceded by partial spasms of the muscles of the extremities, but more often the patient is suddenly thrown down by a general tetanic spasm. In this the body is bent backward and rests upon the heels and the head, in a condition of opisthotonos ; the legs are rigidly ex- tended and the feet everted ; the arms bent and the hands clinched ; the eyes staring, wide open ; the corners of the mouth often drawn up so as to produce the risus sardonicus. The senses may be sharpened, but ringing in the ears and dimness of vision may be induced if the fits are severe. The face is at first pale, but, if the fit be sufficiently severe and protracted, it becomes livid from the interference with respiration. Con- sciousness is not affected, unless when asphyxia becomes so pronounced as to threaten death ; in such cases sometimes a period of insensibility * The theory that strychnine becomes fixed in certain tissues of the body, originally proposed by Widal and Nobecourt, has received considerable credence, but its correctness has certainly not been proven. For discussion of the whole subject, with experiments and literature, see paper of S. J. Meltzer and G. Langmann. 50 t See Arch.f. Ges. Physiol., 1884, xxiv. 530; also Behrend Lau (Elmshorn Inaug. Diss., 1886). EXCITO-MOTORS. 215 precedes dissolution, but generally the intellect is clear to the moment of death The muscles of the jaw are usually the last in the body to be affected, but trismus finally comes on in severe cases. We have seen death occur in this first convulsion in animals ; but Tardieu states that he knows of no such instance in man (compare case of Demme n ). After a time the paroxysm is at an end, the jaw drops, the muscles relax, and a period of calm comes on, to be succeeded by a second convulsion like the first. These convulsions are excited by the slightest touch, by a draught or breath of air, even by a loud sound ; but a firm grasp or hard rubbing of the muscles is frequently grateful. A slight rigidity is some- times manifest between the paroxysms, but no marked stiffness. The spasms are generally, but not always, very painful. There are often erections of the penis, and the faeces and urine may be passed involun- tarily. If the case terminates favorably, the convulsions gradually lessen in intensity, and fade away, leaving the patient exhausted, with a sore, tired feeling in the muscles. After death, post-mortem rigidity is devel- oped very quickly. Autopsies have revealed nothing but the usual con- gestive lesions of death from asphyxia, and, at times, indications of spinal hyperaemia. Cerebrum. So far as our present knowledge goes, strychnine has little or no influence upon the cerebral cortical centres. The stimulation of the special senses sometimes seen in the beginning of strychnine-poi- soning is probably, though not certainly, peripheral in its origin ; and consciousness is probably never directly affected by the drug. Spinal Cord. The spinal origin of the convulsions of strychnine has been demonstrated by a large number of experimenters. They occur after section of the spinal cord below the point of division. In Brown- Se"quard's experiments, confirmed by Martin-Magron and Buisson, when the spinal cord was severed just below the origin of the nerve supplying the fore legs of the frog, and the lower section of the cord isolated by cutting its blood-vessels, strychnine produced convulsions in the anterior part of the body, whilst the posterior segment of the body was quiet and re- tained its normal reflexes, although the blood was carrying strychnine to every part of it except the spinal cord. It has been proved by Van Deen, by Valentin, and by A. J. Spence * that when strychnine is placed upon the cut upper surface of the brain or spinal cord so that it will diffuse itself within the spinal cord without being carried by the cir- culation, convulsions appear in those muscles whose nerves have their origin near the point of application, and spread from muscle to muscle as the poison creeps through the cord. The accuracy of the statement * Some of the phenomena stated by Spence to have occurred are at present very diffi- cult to explain. Thus, he noted that as the poison travelled down the cord there was a time when irritation of the fore feet caused only spasm in them ; later in the experiment, irritation of the front feet caused spasm of both the front and hind feet, although irrita- tion of the latter did not produce other than normal reflex movements ; later still in the poisoning came a stage when irritation of the front legs was powerless to cause spasm in the hind legs, although irritation of the latter would now cause spasm in the former. 216 GENERAL REMEDIES. of Claude Bernard, 12 that when all the posterior nerve-roots are cut no convulsions occur, whereas, if a single afferent root remains, irritation of its nerve will cause general tetanic spasm, has been denied by Spitzka, but is probably correct. If so, it demonstrates that the reflex motor gan- glionic cells are incapable of originating an impulse, and in strychnine- poisoning are simply in such a condition of over-excitability as renders them exceedingly sensitive to slight irritations and causes them to re- spond most energetically to the feeblest stimulus, the convulsion always being therefore a reflex phenomenon. That the action of the alkaloid is upon the motor centres of the cord seems further to be demonstrated by the ingenious experiments of Van Deen, 13 who so divided all the tissues that the anterior portion of an eviscerated frog was connected with the posterior solely by the posterior columns of the cord. When one or two drops of a solution of strych- nine were placed in the mouth of the prepared batrachian, tetanus, con- fined to the anterior segment of the body, was developed ; and it was also found that while irritation of the posterior feet caused in them only ordinary reflex movements, in the front legs tetanic spasms were simul- taneously induced. Strychnine is evidently a powerful stimulant to the motor cells of the whole spinal tract up to the pons Varolii. Hare 48 found demonstrable histological changes in the cells of the anterior cornua. Biernacki 14 believes that the cortical portion of the pyramidal or motor tract does not share in the stimulation, because he has found that in the strychnized rabbit the psycho-motor centres in the brain are even less susceptible to stimulation than in the normal animal. Motor Nerves. After death from strychnine, the functions of the motor nerves are always found to be more or less impaired, so that gal- vanization of the nerve-trunk produces either very feeble contractions in the tributary muscles or none at all.* That the exhaustion produced by the excessive number of violent impulses which travel along the motor nerves during the period of strych- nic convulsions is a distinct factor in causing the loss of functional power in the nerve-trunk was proved in 1856 by Kolliker, 15 who found that when he cut the sciatic nerve in the frog and exhibited strychnine the divided nerve would respond to galvanic stimulation after all functional power had been lost in the nerve whose connection with the centres was intact. * See Matteucci ( Traitt des Phenomenes electro-physiologiques, Paris, 1844), Moreau (Comptes-Rendus Soc. de Biol., 1855), M. Ambrosoli (Gazette Medicate, 1857, 525), Wit- tich (Bericht d. Fortschritte d. Anat., 1857, 434), Kolliker ( Virc how's Archiv, 1856, x. 239), and Vulpian (Archives de Physiologic, Nov. 1870, 125). The statement of W. H. Klapp, that he has found in thirty-seven experiments the motor nerve unimpaired in the frog after death from strychnine (Journ. Ment. and Nerv. Dis., Oct. 1878), may depend upon the fact that in some species of frogs the nerves are extraordinarily refractory to the action of strychnine, or it may be that he employed such powerful stimuli that all appar- ent differences were lost. Sautesson found that strychnine acts twelve times more powerfully upon the nerves of Rana esculenta than upon those of JR. temporaria. S. Leduc believes that he has demonstrated that strychnine can be electrolytically carried into a human nerve and temporarily suspend its functional power ( C. R. S. B., 1902, liv.). EXCITO-MOTORS. 217 These experiments have been confirmed by Martin-Magron and Buisson, and must be accepted. Nevertheless, it has been demonstrated by Vul- pian, by E. Poulson, 16 by C. G. Sautesson," and others, that strych- nine has a direct paralyzing action upon the peripheral motor nerves. When the nerve has been divided, as in the experiments of Kolliker, it finally becomes paralyzed in strychnine- poisoning ; and Vulpian has found that if the doses have been properly adjusted the motor nerve after a time will regain in the poisoned frog its activity before stimulation of the spinal cord has altogether passed off, so that the history of such an experiment is, first, tetanus, then paralysis, due to the loss of power by the nerve-trunks, and then again a tetanus which gradually subsides into the normal condition. Further, as pointed out by Richet, and as we have frequently seen, if an enormous dose of strychnine be injected into the jugular veins of the dog, death immediately results practically without convulsion, it being possible by artificial respiration to maintain the circu- lation for a considerable length of time. Under these circumstances the motor nerves will be found to have entirely lost their power of responding to galvanic or other stimulation, although they may still be able to trans- mit sufficient afferent impulses from the spinal cord to produce slight but distinct choreic muscular contractions. Sensory Nerves. The afferent or sensory nerves appear not to be affected by strychnine. Martin-Magron and Buisson having tied all the tissues of a hind leg of a frog except the nerve, and injected strychnine into the body of the batrachian, found that at a time when convulsions had ceased in all portions of the body except the leg to whose nerve the poison had not had access, slight irritation of the poisoned foot would induce tetanic spasms in the protected leg, thus showing that though the motor nerves to which the strychnine had had access were completely paralyzed, the afferent nerves were still functionally active. Circulation. The full dose of strychnine produces a rise of the arte- rial pressure which is enormously increased during the convulsion, after which there is a very pronounced fall in the arterial pressure.* The pri- mary rise is not due to the convulsion, since it precedes the convulsion, and occurs in curarized animals. It is largely due to vaso-motor con- traction, since Mayer, 18 Klapp, 19 and Reichert 20 have all found that after paralysis of the dominant vaso-motor centres by section of the cord, strych- nine causes no rise at all,f or an exceedingly slight one, of the arterial pressure. The fall of the arterial pressure has been shown by Klapp and Reichert to be due, in part at least, to paralysis of the vaso-motor centres. By the intravenous use of very large doses of strychnine it is possible * See also Richter ( Zeitschrift f. ration. Med., 1863, xviii.), Denys (Arch.f. Exper. Path. Pharm., xx. 306), Kionka (Arch, de Pharmacod. interend., 1898, v.). t Schlesinger (loc. cil.) found after the division of the cord that the rise of arterial pressure caused by strychnine both absolutely and relatively exceeds that produced in the normal animal. This result we believe to have been due to imperfect section of the cord. For an elaboration of the reasons for this belief, see tenth edition of this treatise. 218 GENERAL REMEDIES. to produce immediate paralysis of those centres, with corresponding fall of the arterial pressure. Our knowledge of the cardiac action of strychnine is still imperfect. Although Lahousse believes that in any dose strychnine depresses the intra-cardiac ganglia, it is probable that the small dose has a stimulating influence upon the heart. In the experiments of I. Steiner, confirmed by Klapp, it was found that strychnine affected the isolated frog's heart much more markedly when it was placed upon the posterior than when it was placed upon the anterior face ; also that it acted much more promptly and severely upon the separated sinus venosus than upon the separated ven- tricles or auricles, leading to the natural conclusion that it acts especially upon the ganglia of the sinus. In regard to the action of the alkaloid upon the vagi there is much difference of statement by investigators. Carl Heinemann, Mayer, and Klapp all affirm that the heart under the influence of strychnine can be arrested by galvanization of the par vagum, but Martin-Magron and Buisson, E. T. Reichert and Lahousse, 21 state that the sufficient dose of strychnine paralyzes inhibition.* Reichert has found that the early effect of strychnine is to stimulate the peripheral inhibitory apparatus of the heart, but that if the dose have been sufficient this stimulation is followed by pronounced depression or even complete paralysis, f Blood. Harley found that blood shaken for twenty-four hours with air contained 11.33 parts of oxygen and 5.96 parts of carbonic acid; while blood treated in a precisely similar manner, except in the addition of strychnine, yielded 17.80 parts of oxygen and 2.73 parts of carbonic acid. Kionka 22 found that blood taken from the strychnized animal does not absorb oxygen with the avidity of normal blood, although no spec- troscopic changes could be discovered in it. Moreover, his analysis of blood gases shows during the dyspnoeic stage of the poisoning an extreme lack of oxygen without any excess of carbonic acid. Maurel 33 states that five centigrammes of strychnine sulphate are sufficient immediately to kill the leucocytes in one hundred grammes of blood, and that in poisoning by strychnine sulphate the death of the leucocytes and of the animals takes place at the same time.! * For the paper of Brunton and Cash showing that strychnine increases the " refrac- tory period" of the isolated frog's heart, see Proc. Roy. Soc., 1883. A consideration of this memoir would require an elaborate discussion of the minute points of cardiac physi- ology, and, as it would throw at present no light upon the practical use of the drug, is not entered upon. t According to Reichert, when the salt of strychnine is injected intravenously into the dog there is, first, a transient increase in the pulse-rate, due to the immediate overwhelm- ing action of the undistributed strychnine upon the inhibitory apparatus of the heart ; second, a lessening of the pulse-rate, due to slight stimulation of the pneumogastric end- ings ; third, a marked increase in the pulse-rate, due to pneumogastric depression ; and, finally, a decrease in the pulse-rate, the result of an influence upon the heart-muscle or its ganglia. Reichert determined that five milligrammes of strychnine per kilogramme of weight will paralyze the peripheral vagi in the dog. t The statement of Carl Heinemann, that the diminished frequency of cardiac move- ment and the diastolic pauses taking place in the heart of the strychnized frog occur after EXCITO-MOTORS. 219 Respiration. The injection of strychnine produced in the dog an ex- traordinary increase in the respiratory air-movement, which in H. C. Wood' s 24 experiments never amounted to less than seventy-five per cent. , and sometimes rose to three hundred per cent. On chloralized dogs the respiratory effects of the alkaloid were even more pronounced. Strychnine is among the most certain of the respiratory stimulants, its action upon the respiratory centres being evidently a portion of its wider influence upon the whole motor tract. Temperature. We know of no recorded temperature-curve in human poisoning, but in the lower animals there is usually a primary elevation of the temperature followed by a pronounced fall, both the rise and fall ap- parently being in greater or less measure independent of the convulsions. According to the experiments of Kionka, during both temperature periods, heat-production, and heat-dissipation are above the normal, but during the rise of temperature the increase in heat-production is greater than the increase of heat- dissipation, whilst during the period of falling temperature the overplus of heat- dissipation is greater than that of heat-production. Harnack * 9 confirms the results of Kionka, but has found also that irregularly at any time during the poisoning there may be a sudden arrest of heat-production without corresponding fall in heat-dissi- pation, so that the temperature of the animal rapidly descends. Anton Obermeier * 5 has found that in the rabbit strychnine causes a notable increase in the production of carbonic acid, i.e., of oxidation ; and U. Mosso 26 * affirms that even in the cura- rized dog a very pronounced rise of rectal temperature may be produced by strychnine. The final fall of temperature is due to the excessive dissipation of heat, which in turn is probably the outcome of vaso-motor paralysis. It would appear that the action of strychnine upon heat-production and heat-dissipation is independent of its convulsive influence, and is probably the outcome of some effect upon the central nerve-system, but we have not sufficient evidence to determinate the exact nature of this influence. Eye. The effect of strychnine upon the normal eye has been studied by Von Hippel 28 and Cohn, 29 with rather different results. They both, however, found the sharpness of vision increased. SUMMARY. In small therapeutic dose strychnine produces little apparent effect, but acts as a powerful bitter, increasing at the same time the general tone of the body. After large therapeutic doses there is probably a pronounced general stimulation and increase of bodily tone. The fullest permissible doses stimulate very powerfully the respi- ratory centres, and also slightly increase blood-pressure by stimulation of the vaso-motor centres, and probably also of the heart itself. Toxic cases produce violent reflex tetanic convulsions, -without loss of con- sciousness, by causing such excessive irritability and excitement of the ganglionic spinal cells that these cells respond overwhelmingly to section of the vagi, of course does not disprove vagi stimulation by small doses of the drug. It is entirely possible that the strychnine may diminish cardiac frequency, partly by vagi stimulation, partly in another way. * Denied, however, by M. C. Delezenne, 27 who states that in curarized animals the exhibition of strychnine is always followed by an abatement of the central temperature, which is often but not always accompanied by an increase in the temperature of the sur- face, which increase he explains by the supposition that the drug has the power of dilating the peripheral vessels. 220 GENERAL REMEDIES. the slightest stimuli ; they also lower the functional activity of the motor nerve-trunks by producing exhaustion and by a direct paralytic influence. Death occurring during a convulsion is due to cramp as- phyxia, and is usually immediately preceded by loss of consciousness ; death between the convulsions is the result of a paralytic asphyxia, produced in part by an exhaustion, and perhaps also a direct or second- ary paralysis, of the respiratory centres, and in part by a loss of func- tional power of the respiratory nerve-trunks ; upon the cerebrum and upon the sensory nerves the alkaloid exerts no demonstrable influence, unless it be that it stimulates feebly the special sense centres. There is also reason for believing that the toxic dose paralyzes the peripheral pneumogastric nerve and greatly depresses the heart itself and the vaso-motor system. The ozonizing power of the red blood-corpuscles appears to be lessened by toxic doses of strychnine. The absorption and the elimination of strychnine are rapid, the alkaloid escaping partly in the form of strychnic acid and partly unchanged. THERAPEUTICS. Clinical experience shows that strychnine is a pow- erful bitter, tonic, and stomachic, stimulating digestion and increasing the appetite, a conclusion which has been elaborately confirmed by S. F. Hamper, 30 who, using Ewald's test-breakfast, found that the drug in- creases the volume and digestive power of the gastric juice as well as the movements of the stomach. Strychnine is, however, more than a mere stomachic : it is a most useful tonic when there are general relaxation and loss of nerve-power. A portion of its value probably arises from ks action upon the spinal motor nerve-centres ; but in all likelihood it in- fluences other portions of the cord, affecting the vaso-motor centres, and most probably also the trophic centres. Be these things as they may, strychnine is the best of all tonics in general functional atony and relax- ation. Many years ago Trousseau taught that in certain cases of chorea minor the strychnine preparations are very valuable, and Morris Bene- dict 31 asserts that the remedy is useful against choreic movements. It is not probable that in such cases strychnine exerts any specific influence. H. C. Wood has experimentally proved that in choreic dogs it greatly increases the activity of the movements ; and any good which it may achieve in chorea minor is probably due to its tonic powers. The great influence of strychnine upon the function of voluntary motion early led to its use in cases of paralysis, often with the result of doing harm rather than good. It is very evident that it can be useful only when the paralysis is dependent upon, or at least accompanied by, a depressed state of the spinal motor centres. Whenever there is inflam- mation or irritation of these latter, strychnine may do great injury by in- creasing such irritation, and must never be employed. Like galvanism, in hemiplegia it can do only a very limited amount of good, and should not be exhibited until irritation from the clot has ceased. It is probably useful in many forms of lead paralysis, but when the symptoms resemble those of poliomyelitis i.e. , when there is a multiple paralysis with rapid wasting of the affected muscles and alterations of the electro-contractility EXCITO-MOTORS. 221 we have found strychnine pushed to the verge of poisoning extraordi- narily efficacious. The value of strychnine in amaurosis was first asserted by Nagel. 32 In atrophy of the essential nerve-structure experience has shown, however, that little is to be expected from it or any other remedy. To be of use the drug must, therefore, be used before the stage of atrophy has been reached. It is most useful when employed in cases of subsiding neuritis, when atrophy is imminent, as indicated by the increasing impairment of vision and the contraction of the fields for form and color. Its value in the toxic amblyopias is undisputed, especially where the toxic agent is tobacco or alcohol. The distressing headache so frequently present during the progressing atrophy of the optic nerves is often signally relieved by steadily increasing doses of strychnine or nux vomica, even although the advancing loss of vision is not arrested. The prompt action of the drug, secured by daily or twice daily hypodermic injections in the temple, seems to offer better results than other methods of administration. The physio- logic impression should be maintained by steadily ascending doses. Com- mencing with one-thirtieth of a grain, the dose can, within a few weeks, be increased to one-tenth or more, the dosage being controlled only by the tolerance of the patient, which varies greatly, a slight dryness or sense of constriction in the throat or twitching of the calves following the injection being the indications as to dosage. The acuity of vision and a widening of the fields may often be noted within an hour after the injection, which, however, subside to former conditions as the influence of the drug dis- appears. It must be said, however, that in most cases of serious optic neuritis the stage of atrophy is reached and progresses in spite of all known medical measures, but in some cases strychnine seems to maintain the nutrition of the parts involved until the stage of shrinking is at an end, and thus aids in preserving permanently some increment of vision. Strychnine in ascending doses is often of signal benefit in restoring the proper binocular balance in cases of insufficiency of the ocular muscles in debilitated patients, e.g. , after attacks of influenza. The strychnine should be given hypodermically in full and ascending doses sufficient to produce and maintain a distinct physiological effect. A widening of the field of vision and improved central acuity may often be noted after the injection, which, however, subsides as the physiological impression dis- appears. For a discussion of the value of strychnine as a respiratory stimulant, see Respiratory Stimulants, page 268. The alkaloid is extremely valu- able in acute or chronic diseases of the lungs whenever the respiratory function is failing. In long-standing bronchitis or winter cough, and in other obstinate pulmonic diseases with dilated right heart, the combina- tion of strychnine and digitalis yields most excellent results. Much advantage may often be derived, especially in feeble subjects, by adding strychnine to ordinary cough mixture. The value of strychnine in the treatment of the respiratory accidents 222 GENERAL REMEDIES. of anaesthesia, which was first pointed out in the address of H. C. Wood before the Berlin Congress in 1890, is now universally acknowledged. The drug has no less value in other similar acute respiratory poisonings. Very frequently the best results are obtainable by using it in combina- tion with other respiratory stimulants. In dyspepsia or constipation or diarrhoea, connected with atony of the visceral muscular coat, strychnine is a very valuable remedy. In various local paralyses, such as prolapse of the rectum, atonic retention of urine, atonic incontinence, and loss of voluntary motion in certain groups of mus- cles from pressure upon or temporary injury of the supplying nerve, it may be very useful. There is reason to believe that it sometimes does good in these cases by influencing the nutrition of the affected muscle or the peripheral nerves ; it should be injected into the affected part. Strychnine is also a serviceable remedy as a stimulant in cases of mental and physical depression due to prolonged excitement and over- work. J. H. Musser S3 asserts that during the strain of student-life before examinations it is especially valuable in preventing the development of asthenopia. Strychnine is an extremely serviceable remedy in the treatment of cardiac diseases with weakness of muscle. In mitral insufficiency we have seen it prolong life for years after the failure of digitalis, and when before its administration immediate death seemed inevitable. It should always be tried in cases of failing heart where digitalis disagrees, it not being possible at present to pick out those cases in which brilliant results are to be achieved by it. To be effective it must be given in rapidly ascending doses, the patient being kept, if necessary, for weeks and months on the verge of strychnine-poisoning, with distinctly heightened reflexes and some muscular stiffness. Clinical experience shows that it has no cumu- lative action, but that the patient becomes accustomed to its use, so that a grain a day may finally be given without any serious effects. In acute narcotic poisoning, in serious respiratory diseases, in chronic alcoholism, and in plumbic poliomyelitis, whenever strychnine is used for a very decided immediate effect much larger doses should be employed than have been heretofore used. These doses should be given hypo- dermically at intervals of from four to six hours, under the immediate care of a trained nurse or other equally skilful person, who should vary the dose according to the effect produced. In chronic neurasthenia ex- cellent results are sometimes obtained by slowly ascending doses carried over a period of one or two years. TOXICOLOGY. Sufficient has already been said in regard to the gen- eral symptoms of stiychnine-poisoning. It only remains to discuss the diagnosis. * This is especially important, because strychnine is frequently * A lesion found in one case by Moriz Rosenthal may possibly be characteristic. It consists of numerous small cross-rents in the heart-muscle, accompanied by small ex- travasations (Nen'enkrankheiten, 1870, 334). EXCITO-MOTORS. 223 used criminally, and because not rarely it is impossible for the chemist to detect it after death. The only disease with which a typical case of strychnine-poisoning seems to be readily confounded is tetanus, in its various forms of idio- pathic, traumatic, infantile, and hysterical. Cases of strychnine-poison- ing have, however, occurred in which the symptoms have appeared to point towards some cerebral disease or cerebral poisoning. Thus, in the case reported by Henry Pilkington, 34 the patient was found unconscious, surrounded by vomited matters, with excessively uneven pupils and an elevated temperature. After death both lateral ventricles were found to contain clots, and there can be little doubt that the high arterial press- ure during an early convulsion had produced an apoplexy which was the cause of the subsequent symptoms and death. It has been asserted that in fatal cases the duration of the attack will always distinguish be- tween natural tetanus and that produced by poison. Louis Starr, 55 how- ever, reports traumatic tetanus fatal in twelve hours after the first muscular twitchings, and within one hour and a half after the first convulsion ; and death from tetanus has occurred fifteen minutes after the reception of the injury (Jaccoud 36 ). The following table shows, we think, in as clear and brief a manner as possible the differences between traumatic or idiopathic tetanus (No. i), hysterical tetanus (No. 2),* and strychnic poisoning (No. 3). The refer- ences in column No. 3 are to authorities who affirm that the symptoms there given are peculiar to poisoning : No. i. Muscular symptoms usually commence with pain and stiff- ness of the back of the neck, sometimes with slight muscular twitchings ; come on gradually. Jaw one of the earliest parts affected ; rigidly and persist- ently set. No. 2. Commenced with blindness and weakness. Muscular symptoms com- menced with rigidity of the neck, which gradually " crept over the body," affecting the extremities last. Jaw rigidly set before a con- vulsion, and remained so be- tween the paroxysms. No. 3. Begins with exhilaration and restlessness, the special senses being usually much sharpened .f Dimness of vision may in some cases be manifested later, after the development of other symp- toms ; but even then it is rare. Muscular symptoms develop very rapidly, commencing in the extremities, or the convul- sion, when the dose is large, seizes the whole body simul- taneously.! Jaw the last part of the body to be affected : its muscles relax first, and, even when during a severe convulsion it is set, it drops as soon as the latter ceases, jj * Column No. 2 is from an actual case. See trial of Mrs. VVharton, New York Medi- cal Record, 1873. t Taylor, On Poisons, 683 ; Wormley, Micro- Chemistry of Poisons, 536. t Wormley, 536; Still, Therapeutics, ii. 148. \ Taylor, On Poisons, 134, 682 ; Wormley, 536, 540, 541 ; Tardieu, Sur V Empoisonne- ment, 924. 224 GENERAL REMEDIES. No. i. Persistent muscular rigidity, very generally with a greater or less degree of permanent opisthotonos, emprosthotonos, pleurothotonos, or orthotonos. Consciousness preserved un- til near death, as in strychnic poisoning. Draughts, loud noises, etc., produce convulsions, as in strychnic poisoning. May complain bitterly of pain. Eyes open, rigidly fixed, dur- ing the convulsion. No. 2. Persistent opisthotonos, and intense rigidity between the convulsions ; and after the con- vulsions had ceased the opis- thotonos and intense rigidity lasted for hours. Consciousness lost as the sec- ond convulsion came on, and lost with every other convul- sion, the disturbance of con- sciousness and motility being simultaneous. Desired to be fanned. Crying-spells, in which he " sobbed violently," and " cried like a child," alternated with the convulsions. Eyes closed. The spasms in the leg must have been partial, as the feet were crossed and toes inverted, which could not happen if all the muscles were involved, be- cause the muscles of eversion, being very much the stronger, would of necessity overcome the antagonistic muscles, and the feet be everted. No. 3. Muscular relaxation (rarely a slight rigidity) between the con- vulsions, the patient being ex- hausted and sweating. If re- covery occur, the convulsions gradually cease, leaving merely muscular soreness, and some- times stiffness like that felt after violent exercise.* Consciousness always pre- served during convulsions, ex- cept when the latter become so intense that death is imminent from suffocation, in which case sometimes the patient becomes insensible from asphyxia,! which comes on during the lat- ter part of a convulsion, and is almost a certain precursor of death. The slightest " breath of air" produces a convulsion. J: Patient may scream with pain, or may express great appre- hensions, but " crying-spells" would appear to be impossible. Eyes stretched wide open.fi Legs stiffly extended, with feet everted, || as the spasms affect all the muscles of the leg. Death from strychnine in man and other mammals mostly occurs in a convulsion, and under these circumstances is undoubtedly due to as- phyxia, caused by the unyielding, spasmodically contracted muscles. In man, death sometimes occurs not in a paroxysm, but during relaxation, and probably then is the result not only of the exhaustion following effort, but also of the direct action of the poison upon the respiratory centre and nerves. In frogs, death must occur from other causes, since a frog, as shown by Claude Bernard, will live for days after removal of its lungs, probably by breathing through its skin. The causes of death in the frog are not hard to find when the physiological action of the drug is known. The lymph and true hearts (Kolliker, Harley 37 ) are very much affected, but the chief factor is no doubt paralysis of the motor nerves. * Taylor, On Poisons, 134, 136, 682 ; Wormley, 536, 540, 541 ; Tardieu, 924, 938, 939 ; Husemann, Handbuch der Toxicologie, 168. t Wormley (ist ed.), 536; Taylor, Medical Jurisprudence, 331, 332; Wharton and Stille, Medical Jurisprudence, paragraph 757 ; Tardieu, 923 ; Stille, Therapeutics, 148. J Stille, Therapeutics, 148. # Ibid. ; Wormley, 536 ; Tardieu, 924. || Tardieu, 924 ; also other authorities, which we have neglected to note, and at present writing have not at hand. EXCITO-MOTORS. 225 Honigmann S8 reports a remarkable case, in which acute inflammation of the kidneys followed strychnine-poisoning. The minimum fatal dose of strychnine is probably something under half a grain ; the latter quantity has several times caused death, once in a man in twenty minutes ; 39 one- third of a grain given at intervals in fractional doses has produced such alarming symptoms as to indicate that in a single dose it might readily destroy life ; one-hundredth of a grain is said to have killed a child three and a half months old ; * but ten grains (Tschepke 41 ), twenty grains (A. E. Connor"), also twenty-two grains (George Gray 43 ) taken on a full stomach and retained two hours have failed to cause death, in each case probably on account of slow absorption.* The question as to the possibility of acquiring immunity to strychnine has become an important one in certain cases of alleged murder, and also has some bearing upon the practical use of the drug. Clinical experience undoubtedly favors the view that strychnine may be given continuously for months or years without any distinct immunity, and H. A. Hare 48 has been unable to produce in rabbits by ascending doses any distinct lessen- ing of susceptibility to the poison. In treating poisoning by strychnine, a chemical antidote should be at once administered, such as tannic acid or iodine or one of its soluble salts. As, however, the compounds formed in the stomach by these substances are not permanent, theoretically a quick emetic may sometimes be ad- visable. Potassium permanganate has the power of oxidizing strychnine, but its value as a practical antidote has not as yet been determined. For the lessening of the excitability of the spinal cord various spinal depress- ants have been from time to time recommended. No spinal depressant, however, which, like aconite or tobacco, is also powerfully depressant to the circulation, should be used. The remedies which may be employed are potassium bromide, chloral, f chloroform, and amyl nitrite. Alcohol has been strongly recommended by some authorities (Amagat, Stacchini) as antidotal ; and when the great muscular relaxation of drunkenness is remembered, it seems very probable that the commendation has some basis. Husemann has, however, shown that alcohol can scarcely be looked upon as a real antagonist to the alkaloid. The best treatment of strychnine-poisoning is apparently to be found in the conjoint use of chloral and potassium bromide, with, when convul- sions are very threatening, inhalations of amyl nitrite or chloroform. Half an ounce of the bromide with half a drachm to a drachm of chloral * In a preliminary investigation, William Salant (Amer. Med., Aug. 1902) failed to detect small quantities of strychnine which had been previously added to the contents of the large intestine of normal rabbits. Subsequently (Amer. Med., June, 1903), however, he proved that these strychnized contents were actively poisonous, and that therefore the failure to detect strychnine lay at the door of the chemical methods employed, and sug- gested a new method of looking for the alkaloid. The chief importance of this investi- gation is the side-light which it throws upon failures of chemists in cases of poisoning. t For detailed discussion of the relations of strychnine and chloral, with account of experiments by various investigators, see tenth edition of the present treatise. 15 226 GENERAL REMEDIES. may be given at once in a severe case ; and, if necessary, every twenty minutes afterwards two drachms of the first and fifteen grains of the second remedy may be exhibited. Chloroform or amyl nitrite should be given by inhalation whenever the convulsions are extremely severe, and if the patient cannot swallow, a drachm of chloral may be injected into the rectum, or, especially where respiration is very seriously affected, five minims of amyl nitrite may be given hypodermically. It is essential to remember that any disturbance of the patient may, when the symptoms are well developed, bring about a fatal convulsion. Thus, we have seen death occur in a convulsion caused by an effort to get the mouth open to give a remedy. Hence, unless the case is seen in the beginning, no attempt should be made to evacuate the stomach. Artificial respiration, which has been highly commended by some, cannot, we believe, ever be of service in human poisoning. Leube was, we believe, the first to demonstrate that forced artificial respira- tion in animals will not only very greatly lessen the production of convulsions by strychnine, but will also affect the final result of the poisoning. After considerable discussion, the accuracy of the results reached by Leube has been finally estab- lished. The method in which the forced respiration acts is at present unknown. It has been shown by W. J. Gies and S. J. Meltzer 46 that whilst artificial respiration completely suppresses the reflex irritability due to strychnine-poisoning, it does not distinctly affect the increased reflex irritability induced by section of the spinal cord : that the influence of the artificial respiration is not the result of any superoxidation of the blood seems to be proven by the fact discovered by Gies and Meltzer, that insufflation of the lungs of the animal with pure hydrogen gas has the same effect as artificial respiration. None of the ordinary methods of artificial respiration in man is sufficiently powerful to be of any value, whilst the manipulations of the physician would certainly tend to increase the strychnic spasm. The curious discovery of Leube is therefore of scientific rather than of practical value.* ADMINISTRATION. As a tonic, strychnine sulphate may be given in granule in doses of from one-fortieth to one-twentieth of a grain (0.0016- 0.0032 Gm. ). Whenever it is desired to push the remedy to its physiologi- cal limit, it should be given hypodermically in ascending doses until restless- ness, general excitement, muscular twitching, stiffness of the neck or legs, or other symptoms are manifested. In many cases of palsies, especially with trophicchanges in the muscles, the best effect seems to be obtained by inject- ing the strychnine salt directly into the affected muscle. If proper antiseptic precaution be taken, hypodermic injections do not cause local irritation. * Gies and Meltzer found that the animal under strychnine could be kept alive by insufflation of pure hydrogen for thirty minutes, without manifesting any signs of asphyxia, dyspnoea, or cyanosis. This is so absolutely destructive of the foundations of modern physiology that it is impossible to avoid believing there was some mistake or fallacy in the experimental technic. The literature of this subject is so thoroughly given in the paper of Gies and Meltzer that we content ourselves with adding Jochelsohn (Rossbach's Untersuchungen, \. 92). EXCITO-MOTORS. 227 BRUCINE. Strychnine clings so closely to brucine that the physio- logical actions attributed to brucine may be in truth caused by contami- nating strychnine. L. Wintzenreid l found that brucine acts as a stimu- lant to the spinal cord and a paralyzant to the motor nerves, but does not influence the cerebrum or the sensory nerves ; and that in the higher ani- mals, at first it increases the arterial pressure and afterwards lessens it, in large doses paralyzes the vagi, causes death by asphyxia, and in other ways acts like strychnine. The more recent experiments of Lauder Brunton 2 are in accord with the results obtained by Wintzenreid in show- ing that brucine causes spinal convulsions in mammals when injected di- rectly into the circulation. Brunton found, however, that when taken by the mouth it produces no symptoms, probably because it is excreted as rapidly as it is absorbed. In an elaborate study, Edward T. Reichert* reached the conclusion that the physiological action of brucine is pre- cisely that of strychnine, except that brucine is much less rapidly absorbed, is from forty to fifty times less powerful as a convulsant, is more poisonous to the sensory nerves, and is more uncertain in its effect upon bodily temperature. Further, brucine appears to have an action upon the volitional centres of the frog different from that of strychnine, pro- ducing a brief period of motor paralysis preceding the stage of spinal convulsion (Mays, Reichert).* Thomas I. Mays* found that brucine locally applied to the nerves of the frog rapidly produces a paralysis of the sensory fibres. This led him to test it as a local anaesthetic in man, and he asserts that a five or ten per cent, solution applied to the mucous membrane of the mouth caused rapid loss of sensibility ; also that a twenty per cent, solution applied to the back of the hand caused pro- nounced impairment of sensibility. Mays used this solution with excel- lent results for the relief of the itching of chronic pruritus. Ralph W. Seiss 5 and Charles H. Burnett have found that the application of a five per cent, solution in the local pruritus of inflammation in or about the external ear usually gives very marked relief. Burnett states that his results were far more satisfactory than those which he has obtained with cocaine. In using brucine as a local anaesthetic it is essential that it be chemically pure : the nitrate or the sulphate may be selected, and one drop of hydrochloric or sulphuric acid should be added to the solution for each three grains of the alkaloid salt. REFERENCES. STRYCHNINE. 5. RAUTENFELD . . In. Dis., Dorpat, 1884. 1. BOULEY and COLIN . Trait6 de Physiol. 6 - WORMLEY .... Micro-Chemistry, 2d ed. comparte, ii. 91. 7- KRATTKR . . . . W. M. W., 1882. 2. MELTZER .... J. Ex. M., i. ; A. J. M. S., 8 - PLUGGE Arch. d. Pharm., 1883. Nov. 1899. 9- BORZI A. I. B., 1899. 3. LOVETT J. P., ix. I0 - LEUBE A. A. P., 1867, 630. 4. LESSER Vierteljahrschr. f. gericht. " DEMME Syd. Soc. Year-Book, 1865- Med.,i898, xv.27and26i. '66,441. * For a research showing the comparative action of strychnine and brucine on differ- ent species of frogs, see Sautesson (Archivf. Exper. Path. u. Pharm., xxxv.). 228 GENERAL REMEDIES. 12. BERNARD . . . 13. VAN DEEN . . . 14. BlERNACK! . . 15. KOLLIKER . . . REFERENCE . Lemons sur les Substances Toxiques. . Physiol. de la Moelle 6pi- niere, 1860, iii. 130. . Th. M., xii. . V. A. P. A., x. IS. Continued. 33. MITSSER . . . . . T. G., ii. 10. 34. PlLKlNGTON . 35. STARR .... . . L. L., 1893, i. P. M. T , iii. 311 36. JACCOUD . . . 37. HARLEY . . . . . Path. Intern., i. 441. . . L. L., July 1856. 38. HONICMANN . 39- 40. 41. TSCHEPKE . . 42. CONNOR . . . 43. GRAY .... . . S. Jb., ccxxiii. 21. Guy's H. R., 1865, xi. 208. P. J. and'Tr., viii. 1010. . . D. K. C., 1861. . . O. M. R., 1879, 12. . . B. M. J., 1880, i. 477. 16. POULSON . . . 17. SAUTESSON . . 18 MAYER . . . A. E. P. P., xxvi. A E P P , 1894, xxxv. Med Jahrb d k k Geseli- 19. KLAPP . schaft d. Aerzte zu Wien, 1872, 112. J. N. M. D., Oct. 1878. 20. REICHERT . . . 21. LAHOUSSE . . . 22. KlONKA . . . . . T. G., April, 1892. . C. R. S. B., xci. . A. P. I., 1898, v. in. 44. FALCK .... . Cb. M. W.. 1800. XT. 45. DERBY B. M. and S.J., 1902, cxlvi. 508. 46. GIES and MELTZBR . J. Ex. M., 1902, vi. 107. 47. CARRARA .... Cb. Inner. Med., 1901. 48. HARK A. T. P.. IOOT. v. 23. MAURKL . B. G. T., March, 1892. 24. WOOD . J. P., 1892. 25. OEEKMEIER . . 26. Mosso . In. Dis., Erladgen, 1891. A. I. B., 1886. 27. DELEZBNNK . . 28. VON HIPPEL . . 29. COHN 30. HAMPER . . . Bull. Med. du. Nord, 1895, xxxiv. . Wirkung des Strychnins auf die normale und kranke Augen, Berlin, 1873- . W. M. W., 1873, No. 42. L. M R , Feb 1891 49. HARNACK . . . A. E. P. P.. IOOT. xlix. 50. MKLTZBR and LANGMANN . J. M. R., 1903, ix. BRUCINE. i. WINTZENREID . . In. Dis., Geneva, 1882. 2. BRUNTON . . . . J. Chem. S., 188. 3. REICHERT . . . . M. News, April, 1893. 4. MAYS T. P.. viii. 31. BENEDICT . . . 32. NACEL . . . . . W. M. W., 1891, xli. . Die Behandlung der Am- T C" '" Acn aurosen u. Amblyopeen mil Strychnin, Tubin- gen, 1871. FAMILY VI. DEPRESSO-MOTORS. UNDER this heading are considered certain drugs which are used for the purpose of lessening the activity of the spinal cord. They have, except in this particular, but little in common in their action, and must be studied individually. PHYSOSTIGMA CALABAR BEAN. U.S. An irregular, kidney-shaped bean, about an inch in length and three- fourths of an inch wide, the product of the Physostigma venenosum, a perennial woody creeper of Calabar, Africa, where the bean has been used by the natives as an ordeal test for criminals, witches, etc. , since time immemorial. It contains an alkaloid known as physostigmine, or eserine. E. Harnack and L. Witkowski 1 have described a powerful teta- nizing alkaloid, calabarine, which is sometimes abundant in commercial extracts of Calabar bean. It is probably a decomposition product from that alkaloid (see also Husemann 2 ). Isophysostigmine according to Ogiu 34 is similar in its action to physostigmine but more powerful. PHYSIOLOGICAL ACTION. Local Action and Elimination. No ap- parent irritant action occurs from therapeutic doses of Calabar bean or its alkaloid. Both absorption and elimination are very rapid. N. Teich and D. Schweder 3 have both found physostigmine in the urine half an hour after its ingestion. Although the alkaloid has been detected in various secre- tions by Dragendorff and his pupil Pauder, it chiefly escapes through the kidneys. Its effect upon the urinary secretion has never been studied, excepting in that Merson * states that it decreases the excretion of urea and other urinary solids in paresis. General Action. No sensible effects are perceptible after the full therapeutic dose of Calabar bean, except it be slight weakness and dis- like for muscular exertion. The symptoms produced by large doses are giddiness, lessened heart-action, great muscular weakness, with, in most cases, contraction of the pupil, and sometimes vomiting, and still more commonly purging, which may be very free. A pupil of Gubler took 0.15 grain of eserine sulphate, and suffered, after a time, nausea, giddiness, and intense muscular weakness, so that he could not stand ; three-quarters of an hour afterwards he vomited some of the solution mixed with bile, but his strength did not begin to return for two and a half hours. When an animal receives a small fatal dose of Calabar bean, after a time mus- cular tremors appear, and almost immediately the victim falls to the ground, or lies down, in a state of perfect muscular flaccidity. The pupils generally contract, 229 230 GENERAL REMEDIES. and the respirations become slow, irregular, and often stertorous. All reflex actions are almost at once diminished, and this diminution grows greater and greater, until it ends in their complete abolition. So long as the condition of the motor system allows of it, evidences of sensibility are manifested whenever the animal is in any way injured. According to dementi Papi, 5 the voice is completely lost. The mus- cular tremors persist during the whole period of paralysis, and, indeed, even after cessation of the respiration. They vary greatly in intensity, and in some cases are so severe (Eraser) as to simulate general convulsions. As the minutes go by, the rhythm of the respiration becomes more and more affected, and at last death takes place quietly, consciousness being preserved until the last few gasping respirations close the scene.* The pupils sometimes, but not always, dilate immediately after death. According to the experiments of Fraser, the bodily temperature is slightly elevated. After a small lethal dose of the poison, the fatal result is always due to failure of the respiration, and if the body be at once opened the heart is found still beat- ing ; indeed, it has been seen to continue to do so for one and a half hours after death ( Fraser) . If a very large amount of the drug be given, the animal falls almost at once, paralyzed, with only a few muscular twitchings. The pupils contract, and in a very short time the gasping respiration ceases. The heart is now found distended and passive, but often will contract under the stimulation of a galvanic current. Nervous System. Upon the cerebrum physostigmine has no per- ceptible influence. The paralysis and loss of reflex activity which it produces are undoubtedly due to a depressant action upon the motor cord. Thus, Fraser, Harnack, Witkowski, and others have found that if in the frog a peripheral nerve be protected by tying its artery and the batrachian be poisoned with Calabar bean, the paralysis in the protected limb occurs part passu with that in the remainder of the body. Again, Fraser divided the spinal cord of a frog, and then cut or tied all the blood-vessels going to the posterior section of it. After this, the animal was poisoned with physostigma, and while the usual symptoms developed themselves in the anterior portion of the body, reflex actions were unaf- fected in the posterior part. Further, Fraser 6 has found that when the poison is applied directly to the cord, fibrillary contractions, due prob- ably to a local irritant influence, are induced in the muscles supplied from below the point of application, but in a little while all movements cease, and even galvanization of the cord itself is unable to elicit response. It is asserted by several investigators that the extremely minute dose of physostigmine acts as a stimulant to the spinal cord. Although this may be true, it seems at present writing improbable, f * Kohler, Rossbach, and others have affirmed that Calabar bean produces a tetanic intoxication. A plausible explanation of these singular observations, and of many of the discrepancies of authorities, is to be found in the discovery of calabarine. Its discoverers state that it produces first a violent tetanus, and afterwards paralysis. It is plain how its presence in varying amounts in Calabar bean preparations would modify their action. The researches of Kohler, of Vintschgau, and of Rossbach and Frohlich are especially open to doubt, on account of their statements that Calabar bean tetanizes. It is very probable that the extracts used by them contained a notable percentage of calabarine. t Papi states that in frogs the stage of exaltation and reflex activity precedes the stage of depression. M. Vintschgau ( Stitzungsb. Math. Nat. Classe Akad. Wissen. Wien., 1867, Bd. lv., Abth. ii. 49) affirms that in a frog whose iliacs he had tied the poison pro- duced violent convulsions, which affected the protected legs, and must, therefore, have been of central origin. Two plausible explanations of this suggest themselves : first, DEPRESSO-MOTORS. 231 Nerves. Although there is reason for believing that physostigmine is capable of affecting both motor and sensory nerve-trunks, yet this action is so feeble as probably to take no part in the production of symptoms. The afferent nerves are less sensitive than the efferent, since Eraser has found, first, that the local application of a strong solution of the poison to a nerve kills the efferent or motor fibres before the afferent or sensory, although the functions of both of them are finally abolished ; second, that when the arteries in the left leg of a frog are tied, and the animal poisoned both with Calabar bean and strychnine, there comes a time when reflex movements are excited in the left leg by irritation of the right foot, although irritation of the left foot does not cause movements in the right leg, i.e., the impulse is able to travel up the poisoned nerve of the right leg but not down it. The extreme feebleness of the influence of physostigmine is shown by the fact that the frog's nerves are often active after death from Calabar bean (Laschkewich, 7 Vintschgau, 8 and Eraser) ; and Eraser has deter- mined that after the fatal result has been produced rapidly with physo- stigmine, the rate of conduction of impulse is as rapid in the nerve to which the poison has had free access as in one which has been protected by the tying of its artery. Loss of power in the motor nerves after poisoning by Calabar bean has been found in the frog only, and, further, only when the dose has been so small that the heart has continued to beat long after the cessation of res- piration, so that the nerves had been, as it were, macerated in a solution of the poison. Harnack and Witkowski deny that physostigmine has even this feeble influence upon the nerve-trunks. The loss of power is prob- ably in the termination of the nerve rather than in the trunk, for Eraser found that when all the blood-vessels supplying the gastrocnemius muscle were cut in a frog and the animal poisoned, at a certain time irritation of the crural nerve produced spasms of the gastrocnemius alone. Muscles. The continuance of the muscular movements after death indicates that they are due to a direct action of the drug upon the muscles. This conclusion is established by the experiments of Laschkewich, of Eraser, and of Leven and Laborde. 9 All of these investigators have noted that after death these contractions are increased by exposure to the air and by direct stimulation of the muscles ; and Eraser has found that they occur in the frog during life after section of the supplying nerve, and also in a muscle actually cut out of the body. Laschkewich has con- firmed the latter fact in the case of warm-blooded animals, and Leven and Laborde have proved that previous destruction of the lower end of that the physostigmine used contained calabarine or other active impurity ; second, the well-known fact that certain spinal depressants produce convulsions, or even excite re- flex action, by paralyzing reflex inhibition, or in some unknown way. The probability of the impurity of the alkaloid is increased by the assertion of Harnack that Merck's " cala- barinum purum" contains little or no calabarine. Schweder, however, asserts that pure physostigmine, in small doses, acts as a distinct stimulant to the cerebral, respiratory, and vaso-motor centres. 232 GENERAL REMEDIES. the spinal cord in a guinea-pig does not prevent the development of the muscular twitchings in the hind legs. Schweder contends that the action of the poison is not, however, upon the muscular structure itself, but upon the peripheral nerve-endings in the muscle, basing his conclusions especially upon the asserted fact, that previous hypodermic injections of atropine or curare prevent the development of rigidity in the snake poisoned with physostigmine. It is certain that the final paralysis pro- duced by Calabar bean is not of muscular origin, since at the time of death the contractility of the muscles is in no way diminished, but, on the contrary, Fraser has noted that loss of contractility and rigor mortis are greatly delayed in Calabar-bean poisoning. Circulation. In the mammal, after therapeutic and even toxic doses, the cardiac action of physostigmine is subordinate to its influence upon the nerve-centres ; but, as has been shown by Fraser, when overwhelm- ing doses of the poison are administered, especially if they be injected into the jugular vein, death results from syncope, or from consentaneous failure of the cardiac and the respiratory functions, and the heart is found arrested in diastole, flaccid, but, according to Fraser and to C. Arnstein and P. Sustschinsky, 10 responding, though feebly and uncertainly, to direct stimulation. In the poisoned frog the early contractions of the heart are slower and more forcible than the normal (Harnack and Wit- kowski) ; whilst the arrested heart is insensible to stimuli (Rossbach and Frohlich 11 ). When smaller doses of the poison are exhibited, there is slowing of the heart's action (Laschkewich, Fraser, and J. Tachau 12 ). Although, according to the experiments of Fraser, there is at first a slight fall of the blood-pressure, which is probably due, as he believes, to diminished pulse-frequency, yet, in spite of the continuance of the slow pulse, the arterial tension soon recovers itself, and remains for a long time much above the normal point, while at the same time the individual cardiac beats are greatly increased in strength (Fraser, Bezold and Gotz*). Finally, the arterial pressure falls far below normal, and the power of the heart is gradually extinguished. That the rise of arterial pressure must be largely the result of a stimu- lant action upon the heart or upon the vessel-walls is shown by the finding of Bezold and Gotz, that the arterial pressure still rises under the influ- ence of physostigmine after high-up section of the spinal cord ; and by that of Harnack and Witkowski, that when the vaso-motor centres are paralyzed with chloral, physostigmine causes a very decided increase of the arterial pressure. The facts that section of the vagi does not interfere with the production of the cardiac phenomena of Calabar bean, and that in the frog physostigmine acts in its usual way on the heart, although the brain and medulla have been destroyed (Vintschgau) ; also that * We have not seen the original paper of these authorities in the Centralblalt fur Med. Wissenschaft, 1867, but quote them from the paper of Arnstein and Sustschinsky. DEPRESSO-MOTORS. 233 when physostigmine is placed directly on the heart, or into one of its chambers, it causes a long diastolic pause, followed by contractions, inter- rupted by pauses, and finally by resumption of regular contractions, or else by diastolic arrest, the heart still retaining its power of responding in an embarrassed manner to stimuli (Fraser) would appear to demon- strate that physostigmine directly affects the heart. How far this in- fluence is upon the cardiac ganglia and how far upon the muscle-fibre has not been determined. It seems, however, probable that physostig- mine affects the cardiac muscles in the same way as it does the muscles of voluntary life. There is, however, much reason for believing that physostigmine affects the peripheral inhibitory apparatus, although the evidence is not entirely clear. Arnstein and Sustschinsky found in rabbits and also in guinea-pigs that the influence of galvanic irritation of the vagi upon the heart is much greater after than before poisoning with physostigmine, diastolic arrest being produced much more easily and continuing much longer than normal after the withdrawal of the stimuli. Moreover, after having completely paralyzed the peripheral cardiac vagi in the rabbit by large doses of atropine, they restored functional power to these nerves by injections of Calabar bean. If the accuracy of these experiments be ad- mitted, it must also be admitted that physostigmine is a powerful stimulant to the peripheral cardiac inhibitory apparatus. Kohler, however, using the frog, and Rossbach and Frohlich, using the rabbit, failed to resusci- tate the atropinized vagi by means of Calabar bean, but a negative result in such a case might be due to an improper proportion in the doses of the counter-poison, or to the atropine being employed in overwhelming amount. Physostigmine appears to have no paralyzing effect upon the vagi ; at least in warm-blooded animals these nerves are never paralyzed (Fraser, Arnstein and Sustschinsky, Harnack and Witkowski) ; and the loss of functional power which has been detected by Fraser, Rossbach and Frohlich, Harnack and Witkowski, in the vagi of the frog does not ap- pear until so long after the cessation of respiration that it is very probably a secondary result. That Calabar bean does not affect the cardiac inhibitory centres would seem to follow from the experiments of Arnstein and Sustschinsky, in which an injection of the drug through the carotid into these centres failed to affect at once the rate of the heart. The question as to the effect of physostigmine upon the blood-vessels cannot at present be positively answered. Evidence concerning it has been brought forward by Fraser and Harley in the form of observations made upon the web of the frog. We have already stated our belief that this sort of evidence is of very little value. In the present instance, as usual, it is entirely contradictory as given by different observers. (For details, see tenth edition of this treatise. ) The fact that the rise of arterial pressure produced by physostigmine 234 GENERAL REMEDIES. after section of the cord is not nearly so great as in an uninjured animal suggests, but does not prove, that the drug affects the vaso-motor centre. Analogy makes it probable that the muscular fibres in the coats of the vessels share the wide-spread muscular action of the poison, and that the peripheral contraction of the arteries is an efficient cause in producing rise of blood-pressure. In considering the general physiological action of the drug, it must not be forgotten that its influence upon the heart is entirely subservient to its influence on the nervous system,* and that death in the mammal occurs before the stage of cardiac palsy is reached, unless the drug be injected directly into the heart in overwhelming dose. Blood. According to Fraser, after death from physostigmine the blood coagulates slowly and loosely, and the red disks present various irregularities of outline ; it is probable that these changes are due to the long asphyxia, and that the poison does not directly affect the blood. Intestines. Intestinal peristalsis is primarily much increased by the action of Calabar bean (Westermann, 13 Papi, Fraser). After poisonous doses there is at first a stage of exceedingly active movements in the bowels ; then spasmodic tetanic contraction of the intestines occurs, so that their calibre is very much diminished ; and finally relaxation and dilatation take place. After death the vermicular movements are found very much lessened (Fraser) or altogether abolished (Tachau). The action of Calabar bean upon the intestines appears to be peripheral, due to contact of the poison in the blood with the muscular fibres or the nerve- elements in the walls of the bowels ; for Westermann found that extirpation of the cardiac ganglion had no effect upon the action of the drug, but that tying of the mesenteric and of the cceliac arteries, before poisoning, prevented any increase in the peristalsis. Secretion. Calabar bean probably increases intestinal secretion. Its action upon the salivary glands is often decided, and, according to Heiden- hain, is not prevented by atropine. Eye. The contraction of the pupil which is produced by Calabar bean is, without reasonable doubt, caused by a local peripheral influence. The fact that physostigmine will contract the atropinized pupil is relied upon by Schmiedeberg " to prove that the action of physostigmine is directly upon the iris muscle ; a deduction which seems unwarranted. As well argue that atropine acts upon the muscle because it antagonizes physostigmine. The closeness of the analogy between the pupillary action of atropine and that of physostigmine is seen in the fact that, like the former, the latter, as shown by the experiments of Ve'e and Leven 15 on chickens, does not affect the irides of birds. It is probable that the two alkaloids are directly antagonistic in their action upon the peripheral nerve-endings in the pupil. It has been held by various authorities that if galvanization of the sympathetic * For a discussion of the peculiar cardiac relations of physostigmine and muscarine, see the paper by Harnack and Witkowski. Those authors believe that Calabar bean sets in motion the heart arrested in diastole, not by paralyzing the cardiac inhibitory appa- ratus, but by stimulating the cardiac muscle. DEPRESSO-MOTORS. 235 fibres in the neck fails to expand a contracted pupil, the myosis must be due to paralysis of the sympathetic. Evidently, however, this is asserting too much, for, as pointed out by Griinhagen, 16 it is conceivable that an oculo-motor spasm can exist of such intensity that the antagonistic nerve is unable to dilate the pupil. The tes- timony as to whether galvanic stimulation of the sympathetic does or does not dilate the physostigminized pupil is somewhat conflicting. Schultz, 33 and Griin- hagen, each affirms that dilatation always occurs ; whilst, on the other hand, Gustav Engelhardt " has found that galvanization of the cervical sympathetic has no effect upon the physostigminized pupil. The experiments of Fraser, of Bernstein and Dogiel, and of Rosenthal 18 would seem to reconcile these differences, and, by their accord, to prove that under the maximum influence of Calabar bean the sympathetic nerve is powerless, while when the contraction is the result of a milder influence of the drug, stimulation of the sympathetic nerve will cause some dilatation.* Fraser, and also Engelhardt, have found that if the poles of a battery be applied directly to an iris even most profoundly contracted by physostigma, immediate dilatation occurs. If it be true that direct stimulation of the muscle-fibres of the iris causes dilatation of the physostigminized pupil, whilst stimulation of the sympathetic nerve fails of effect, it would appear that Calabar bean par- alyzes the sympathetic nerve-endings in the iris. On the other hand, the well-known force of the myosis indicates that it is not due simply to loss of power in the dilating fibres ; an indication which is corroborated by the fact that section of the cervical sympathetics will not produce a myosis as complete as that caused by physostigmine. It would seem, there- fore, that the whole influence of Calabar bean is a simultaneous stimula- tion of the oculo-motor nerve-endings and paralysis of the peripheral sympathetic nerve-endings. The observations of Rossbach and Frohlich, that overwhelming doses of physostigmine finally dilate the pupil, have been confirmed in cases of human poisoning (see Leibholz). It would seem, therefore, that when the alkaloid is in sufficient amount the primary oculo-motor stimulation is followed by oculo-motor palsy. SUMMARY. The dominant physiological action of Calabar bean is a persistent depression of the motor centres of the spinal cord, involving also the respiratory centres in the medulla, and producing loss of reflex action -with an increasing paralysis, ending in death from centric para- lytic asphyxia. Contraction of the pupil is usually seen in the poison- ing, and is always produced by the local application of the drug ; it is due to a peripheral influence and probably to paralysis of the sympa- thetic nerve-filaments with stimulation of the oculo-motor nerve-end- ings. The motor nerve-trunks are scarcely affected, but in slow poi- soning probably suffer some depression of function which especially affects their peripheral endings. Neither the cerebral cortex nor the sensory nerve nor the sensory nerve-centres are acted upon, unless secondarily in the latest stages of poisoning. Calabar bean acts as a * More recently Rossbach and Frohlich affirmed that galvanization of the sympathetic still causes dilatation, even when the action of the physostigmine is most vigorous. As it is scarcely conceivable that the various other investigators should have been so much in error, it is probable that Rossbach and Frohlich used such strong currents that they were directly transmitted to the iris. 236 GENERAL REMEDIES. stimulant directly either upon the muscle structure itself or upon the peripheral nerve-endings in the muscles. The influence of the drug upon the circulation is entirely subordinate. Early in the poisoning there is a rise of the blood-pressure, -which is in great part, if not altogether, due to a direct stimulation of the cardiac muscle or its contained ganglia, although it is probable (not proved) that there is some contraction of the blood-vessels, -which may be due to an influ- ence upon the muscle-fibre in the vessel-walls similar to that upon other muscle-fibres, striated and non-striated. We have no informa- tion as to the effect of the poison on the vaso-motor centre. Accord- ing to some authorities, the peripheral vagi are strongly stimulated. Intestinal peristalsis is greatly increased by the direct action of Calabar bean upon the muscular fibres or the peripheral nerve-endings in the intestinal -walls. The alkaloids of Calabar bean are rapidly absorbed, and are eliminated chiefly by the kidneys. THERAPEUTICS. The physiological action of Calabar bean has sug- gested its use in spasmodic affections, in atony of the muscular coats of the bowel, and in various diseases of the eye. The action of Calabar bean upon the spinal cord very early led to its use in spasmodic affections, and especially in tetamis. In the paper of B. Roemer 19 are collected forty-seven cases, of which twenty proved fatal. To these we are able to add the twenty whose references are given below,* making in all sixty-seven cases, with thirty-seven recoveries and thirty deaths, not a very flattering record. It is, however, proper to state, as affecting the value of these statistics, that much of the Calabar bean extract which has been offered in the market is practically inert, and in all probability in some of these cases the drug did not have a fair trial ; and that when especial care was taken by certain observers better results were achieved, although on so small a scale as to leave the issue in much doubt, f In trismus neonatorum, Calabar bean has been employed with results certainly no more encouraging than those obtained in tetanus. In chorea it has also been used by some practitioners with asserted advantage, but further experience hardly justifies its administration. 20 The physiological action of physostigmine upon the unstriped intestinal muscle-fibres has led to its employment in atony of the muscular coat of the bowels and other similar organs. V. Subbotin 21 has used the extract * FATAL CASES. Fenwick, one (Glasgow Medical Journal, 1869, 300) ; Franzolin, one (The Doctor, Oct. i, 1871) ; Laborde, one (British Medical Journal, June, 1872) ; Valdivieso, one (Philadelphia Medical Times, i. 455) ; Tyson, one (Ibid., 418) ; Johnson. one (Ibid., 372) ; one (London Lancet, 1874) ; Silbermann, one (Charier' s Thesis, 1881) ; Delaraarre, one (Paris Thesis, 1875); Richelot, one (These de Concours, 1875). RE- COVERIES. Fenwick, one (Glasgow Medical Journal, 1869,300) ; Newman, one (Medi- cal Examiner, July, 1869) ; W. W. Keen, one (Philadelphia Medical Times, i. 195) ; J. H. Packard, one (Ibid., 138) ; Cunningham, one (British Medical Journal, i. 1874) ; one (Cincinnati Lancet, Sept. 1878). All these cases were of the traumatic form of the dis- ease. Charier, one (Paris Thesis, 1881) ; Burnam, one (Lancet, Jan. 1881) ; Pooley, one (New York Med.Journ., Sept. 1878) ; Silbermann, one (Charter's Thesis, 1881). t For a favorable record, see Watson (Glasgow Medical Journal, N. S., 1869, i. 54) ; consult also London Practitioner, Sept. 1869- DEPRESSO-MOTORS. 237 with the happiest results in a case of chronic bronchial catarrh with in- tense dyspnoea, believed to be due to weakness of the bronchial muscular fibres, and also in one of apparently ' 'phantom tumor, ' ' with chronic in- testinal dyspepsia and catarrh. In constipation dependent upon relaxa- tion, and as an addition to laxative pills, we have found it very useful. A. Hiller " strongly endorses the value of the extract in chronic intestinal atony, after or during a catarrh, in the convalescence from fever, etc., and in constipation with flatulence, in meteorism, etc. Calabar bean has also been employed in strychnine-poisoning, and a recovery obtained after the ingestion of three grains of the latter alkaloid is reported by J. W. Keyworth. 2S In epilepsy, some trials have been made of the drug, but its value is very doubtful. Harnack and Witkowski have found that in epileptic guinea-pigs physostigmine causes a succession of fits lasting for hours and days. They have further noted a similar influence upon man. Atten- tion has also been called to the employment of Calabar bean as a galac- tagogue the extract being applied to the breast itself. The Use of Eserine in Diseases of the Eye.* The instillation of a drop of a one-quarter to one-half per cent, solution of eserine sulphate into the eye is followed by strong contraction of the sphincter of the iris and by spasm of the ciliary muscle which adapts the eye for the near point. Its action begins in about one minute, usually reaching its maxi- mum in from twenty to thirty minutes, and lasts from twenty -four to thirty- six hours. The intraocular tension is reduced, provided it has been raised above the normal point before the application of the drug. Eserine, when first instilled into the eye, is apt to produce twitching of the eyelids and sharp supraorbital pain due to its causing spasm of accommodation. It is used by ophthalmologists : First, to reduce abnormally high intraocular tension, particularly in glaucoma, and in those ocular conditions in which, other things being equal, it is desired to diminish the intraocular tension ; second, to prevent prolapse of the iris after simple cataract extraction, and sometimes to reduce a prolapse when this has occurred in the periphery of the cornea as the result of an operation or of a perforating corneal ulcer ; third, to limit the progress of deep ulcers near the margin of the cornea, because it is supposed to promote absorption through dilatation of the ciliary vessels and to check the sloughing process ; fourth, to counteract the effect of the milder acting mydriatics, for example, homatropine, especially in eyes in which their use has tended to raise intraocular ten- sion ; fifth, to overcome paresis of the ciliary muscle resulting from various diseases, for example, diphtheria, diabetes, syphilis ; sixth, to reduce the vascularization in certain types of keratitis, episcleritis, and scleritis, provided there be no associated iritis. Eserine too freely used, especially in hyperaemic eyes, is capable of causing slight iritis, the so- called eserine iritis. If the indications for a local anaesthetic are present * This section has been written by Professor George E. de Schweinitz. 238 GENERAL REMEDIES. in conjunction with those demanding a myotic, there is no objection to combining in the same solution eserine and cocaine, or eserine and dionine. ADMINISTRATION. Calabar bean is usually administered as an extract (EXTRACTUM PHYSOSTIGMATIS, U. S. ), the commencing dose of which is one-tenth to one-fifth of a grain (0.0065-0.013 Gm. ). The dose of the tincture (TINCTURA PHYSOSTIGMATIS ten per cent., U. S. ) is twenty to forty minums (1.25-2.5 C.c. ). The alkaloid is preferable, on account of its certainty. The salicylate (PHYSOSTIGMINE SALICYLAS, U. S. ) is preferable to the sulphate (PHYSOSTIGMINE SULPHAS, U.S.) as more permanent, the sulphate being very deliquescent. The thirtieth of a grain (0.002 Gm. ) of either the alkaloid or its salt may be considered to be the full dose. TOXICOLOGY. So far as we know, Calabar bean has not been used, either in Europe or in this country, with criminal intent. In Liverpool seventy children were accidentally poisoned at one time. 25 Many of the victims vomited spontaneously, and thus relieved themselves. Those brought to the hospital were in a state of extreme prostration and muscular relaxation. They appeared to suffer almost no pain, some of them, how- ever, saying that they had a ' ' belly-ache. ' ' Among some thirteen ex- amined, one had the pupils contracted. The only child who did not recover was excessively weak, and, crying out suddenly, was dead of syncope. The heart was found relaxed and flabby, both sides equally full of blood. Half a bean produced in a strong man 26 great muscu- lar weakness, tightness across the chest, temperature of 96.6 F. , very slow, intermittent, irregular pulse, and collapse, without vomiting, purg- ing, contraction of the pupils, or abdominal pain. Lodderstaedt 27 re- ports a hypodermic injection of one-half a milligramme of the physo- stigmine sulphate in a boy nine years old, followed in a quarter of an hour by violent headache, free sweating, salivation, slowing of the pulse, repeated vomiting, contraction of the pupils, and, finally, deep collapse, from which, however, the patient recovered. Two girls took between them o.i gramme (1.53 grains) of physostigmine, with the result of sudden unconsciousness, great redness of the face, muscular relaxation, vomiting, widely dilated, immovable pupils, and, on recovery of con- sciousness, violent abdominal pains, with pulse 60, and hard ; recovery after some hours (Leibholz 28 ). In 1864 Kleinwachter first used successfully atropine in Calabar bean poisoning, and thereby started much discussion and research. Bourneville M detailed in 1867 some experiments which seemed to show that there is a real antagonism between Calabar bean and the mydriatic, and in 1870 published five experiments upon guinea-pigs, which were very decisive in that a proved fatal dose of physostigmine was given in each case and recovery obtained by the use of non-lethal doses of atropine. In 1869 Roberts Bartholow, of Cin- cinnati, on the strength of a few really indecisive experiments, arrived at a con- clusion opposite to that of Bourneville. In an extremely thorough research, which might well serve as a model to any one studying the antagonistic action of poisons, Fraser 30 demonstrated that within DEPRESSO-MOTORS. 239 certain limits atropine may be relied upon as a counter-irritant poison to physostig- mine. He found that in the rabbit one-fiftieth of a grain of atropine could success- fully antagonize one and a half but not twice the minimum fatal dose of Calabar bean, one-fortieth of a grain of atropine could overcome two to two and a half times the minimum lethal dose of physostigmine, and three-fiftieths was sufficient for three times the minimum fatal dose. When four times the lethal dose of physo- stigmine was given to the rabbit, atropine was powerless to do good. In all these cases the atropine was given just before the administration of the Calabar bean. \Yhen the atropine was given five minutes after the physostigmine the largest dose of the physostigmine which could be combated successfully was three times the minimum fatal dose. No experiments were made by Fraser to test the value of physostigmine in atropine-poisoning. These experiments of Fraser * have been in some degree confirmed by the imperfect researches of Amagat. 31 The antagonism between physostigmine and pilocarpine is at least as great as that between atropine and pilocarpine. ( See article on Jaborandi. ) The practical deduction from the scientific and clinical evidence is that in any case of Calabar bean poisoning both of the antagonistic alkaloids should be used in doses proportionate to the amount of the poison ingested. J. Pal M asserts that physostigmine is an antidote to curare ; it being possible with it to bring about voluntary respiration in an animal which has been entirely paralyzed by the South American poison. We know of no experiments as to the value of curare in physostigmine-poisoning. POTASSII BROMIDUM POTASSIUM BROMIDE. U.S. Potassium bromide occurs in milk-white cubic or quadrangular pris- matic crystals of an acrid saline taste, freely soluble in water and slightly so in alcohol. When its solution is mixed with starch, and chlorine is added, a yellow color is developed. A bluish tint betrays contamination with an iodide. PHYSIOLOGICAL ACTION. Local Action. When a solution of the bromide is applied locally to the heart, it produces instantly marked lessening of its action, and, if in sufficient amount and concentration, even instantaneous diastolic arrest. 1 Upon the voluntary muscles it acts in a similar manner when similarly applied. If its solution be not too concentrated or abundant, however, the muscle of the frog is first thrown into a tetanic spasm, and Purser suggests that the tetanic symptoms seen in the frog poisoned by potassium bromide are due to this, action on the muscles. On the nerve- trunks, and also on the nerve-centres, the bro- mide acts, when applied locally, as a paralyzing poison (Amory, 2 Ringer and Morshead 3 ). It is, therefore, evident that potassium bromide in sufficient quantity is a poison to all the higher animal tissues. In general poisoning of animals by hypodermic injection of the bromide, this local action is often very manifest, and paralysis of the part into which the solu- tion has been thrown follows very rapidly upon the injection. Potassium bromide is distinctly irritating, and when in the form of powder it is affirmed to be somewhat caustic, and has been highly recom- mended for the destruction of excessive granulations, etc. 240 GENERAL REMEDIES. Absorption and Elimination. Potassium bromide is freely absorbed and circulates in the blood as a bromide. Elimination takes place to a certain extent through the skin, and probably largely through the intes- tinal mucous membranes, though the chief avenue is the kidney. P. Guttmann * has recognized bromine in the contents of the acne pustules of bromism ; Bill 5 detected the bromide in marked quantities in the faeces of men taking it ; and H. Quincke 6 found that when forty grains of sodium bromide were given to dogs with intestinal fistula, two and a half hours afterwards the intestinal juices were free from the bromide, which reappeared in them three to six hours later. The salt has been found by Voisin, Amory, Namias, Bill, etc., in the saliva and in the urine, and by Amory 7 in the perspiration. In the body of a man who died while taking it, M. Namias 8 found it in all the liquids, as well as in the brain, liver, spinal cord, lungs, etc. The rapidity of elimination seems to vary : thus, Amory recovered one-half of the amount ingested during the first, and one-third during the second, twenty-four hours, and Ware (Thesis of H. P. Bowditch) ob- tained a little more than half of the amount ingested in the urine of the succeeding thirty-two hours, while Bill was not able to get more than one-eighteenth of it during the first day. Bill has frequently found the bromide in the urine two weeks after the last dose had been exhibited ; and Rabuteau has seen its presence persist under similar circumstances for a month. According to T. Hondo, 10 when the diet is rich in sodium chloride the bromides are eliminated much more freely than when common salt is withheld. When a bromide is given continuously it accumulates in the body and may be found in every tissue, but, according to Doyon and Cazeneuve 9 (confirmed by Fere and Herbert 10 ), it is stored up in the nerve-centres much more largely than elsewhere. General Action. Potassium bromide administered to frogs in minute doses produces as a first result a tetanoid condition, in which there may be very marked opisthotonos. After a short time this stage of muscular excitement gives way to one of great muscular relaxation and total aboli- tion of reflex actions. Voluntary movements, however, often occur during this period, and the frog which has been lying limp and appar- ently dead will startle the observer by a sudden vigorous leap. This fact has been so frequently witnessed that there can be no doubt of its truth.* Very early in the paralytic stage the respiratory movements are affected, and they gradually grow less until their final arrest. When a very large dose of the bromide is given, death may be induced by paralysis of the heart (Albert Eulenberg and Paul Guttmann 11 ) ; but after a small toxic dose this viscus continues to beat long after the cessation of breathing. If the drug be given by an injection practised in the vicinity of the heart, sudden cardiac arrest always occurs. Upon mammals 12 (Eulenberg and Guttmann ") the bromide acts very much as upon frogs, inducing progressive paralysis, depression of tem- perature, and death by asphyxia when given in small poisonous doses ; * It is vouched for by the following observers : J. M. Purser (Dublin Journ, Med. Set., 1869, xlvii. 324) ; Lewisky aus Kazan ( Virchozv's Archiv, 1869, xlv. 191) ; J. V. Laborde (Archives de Physiol. Norm, et Palhol., 1868, i. 423, and Comptes-Rendus, 1867, Ixv.) ; Damourette and Pelvette (Bull. Thlrafi., 1867, Ixxiii. 249). DEPRESSO-MOTORS. 241 and great disturbance of the circulation, with finally diastolic arrest of the heart, when very freely administered. So far as we know, no fatal case of acute poisoning by potassium bromide is on record. In our own experience an ounce taken by mis- take by a young adult produced violent pain in the oesophagus, nausea with a little vomiting, great thirst, feeling of weight in the head, and ex- cessive sleepiness, which lasted for three days. In a case reported by Dougall 1S an ounce and a half taken within twenty-four hours was fol- lowed by coma, with weak pulse, cold extremities, temperature 96.8 F., total abolition of the reflex action, and general cutaneous anaesthesia, followed by excessive drowsiness interrupted by periods of talking de- lirium and by periods of rationality, the symptoms gradually subsiding during a fortnight. The results of the continuous employment of large doses of the bro- mide, however, demonstrate that it acts upon man as upon the lower animals. When it is taken with sufficient freedom to accumulate in the system, a conjunction of phenomena known as bromism arises. The cerebral symptoms are a sense of mental weakness, heaviness of intellect, failure of memory, partial aphasia, great somnolence, and depression of spirits. With these there may be decided impairment of the sensibility of the mucous membranes and of the skin, so that titillation of the fauces may be without effect, and, according to Puche, even heat applied to the skin calls forth no complaint ; Huette " has seen in some cases absolute anaesthesia of the sclerotic conjunctiva. The sexual function is abolished. There are also very generally fetid breath and an eruption of acne which may indeed be very severe. Of course, in any individual case of bromism many of these symptoms may be wanting ; but when the use of the remedy is persisted in, they all at last become developed in an intense degree. In the words of Edward H. Clarke : " The fetid breath becomes nauseous ; oedema supervenes on congestion of the uvula and fauces ; the whispering voice sinks into aphonia ; sexual weakness de- generates into impotence ; muscular weakness becomes complete paralysis ; reflex, general, and special sensations disappear ; the ears do not hear, nor the eyes see, nor the tongue taste ; the expression of hebetude becomes first that of imbecility, then that of idiocy ; hallucinations of sight and sound, with or without mania, pre- cede general cerebral indifference, apathy, and paralysis ; the respiration, without the stertor of opium or alcohol, i easy and slow ; the temperature of the body is lowered ; as the bromism becomes more profound, the patient lies quiet in bed, un- able to move or feel or swallow or speak, with dilated and uncontractile pupils, and scarcely any change of the color of his skin or face." Death has been attributed to the continuous use of the bromide in large doses. Thus, Hameau reports the case of a young woman who took four and a half pounds during the course of ten months, and while in a condition of cachexia, with yellowish skin, a copper- colored erup- tion upon the forehead, colic, gastralgia, insomnia, etc., suddenly be- came greatly prostrated, and had delirium with profuse sweats, followed . 16 242 GENERAL REMEDIES. by death in four days. Anton Eigner 15 details the case of a woman who took five pounds in less than a year, and while having very pronoun ed symptoms of bromism was seized with delirium and suffered from hal- lucinations of sight and hearing, saying that she was being poisoned, and finally died of pneumonia. In neither of these cases can it be considered probable that the bromide was the direct cause of death. Nervous System. The persistence of voluntary movement in the frog after the abolition of reflex actions shows that the influence of the drug is not chiefly exerted upon the cerebral centres of motor impulse, nor upon those cells of the cord which originate movement, but upon either the afferent nerves or those portions of the cord which transmit the impulse from these nerves to the cells presiding immediately over motion. This is confirmed by some experiments of Lewisky, in which it was shown that previous separation of the cord from the cerebrum had no influence upon the action of the bromide. Both he and Purser 16 also found that death occurred from small doses before the motor nerve-trunks and the muscles had lost their irritability (confirmed by Saisson 17 ). This being so, the question arises whether the paralysis be spinal or due to paralysis of the peripheral afferent nerves. There is an apparent conflict in the evi- dence upon this point. Eulenberg and Guttmann found that when access of the poison was prevented to one or more limbs by tying the arteries, reflex actions were abolished in these parts as rapidly as in others. Simi- lar results have been obtained by Lewisky, 18 by Roberts Bartholow, 19 by Purser,* and by Laborde. 20 The latter observer has also found that elec- trical stimulation of a nerve high up will cause violent spasms in the mus- cles directly supplied by it, although it may be unable to excite the slightest reflex tremor. On the other hand, Damourette and Pelvette assert a contrary result. Unfortunately, they do not give the details of their experiments. They state, however, that if the lumbar plexus of vessels be tied before the poisoning, the fore feet lose their reflex activity before the hinder. There are two possible methods of reconciling their results with those of the other observers. In some way the operation may have interfered with the circulation in the lower part of the cord, and consequently the poison have reached more freely the upper part of it and acted first upon it. Again, if the injection was, as is very probable, thrown into the anterior portion of the body, the poison may have reached the anterior extremities in so concentrated a form as to have acted, as it were, locally upon their nerves and muscles. The same observers in an- other portion of their memoir show that the solution's of these salts in the frog travel rapidly by imbibition ; and this and their local action seem to us to be the cause of the differences of experimental results. It seems well established that cutaneous anaesthesia in greater or less degree ac- companies the loss of reflex activity ; for, as Purser says, a poisoned * From the wording of his memoir, however, it is doubtful whether Purser performed the experiment himself. DEPRESSO-MOTORS. 243 animal quite able to jump submits to pinching, pricking, burning, etc., without moving. Eulenberg and Guttmann have seen the same thing in some rabbits. Damourette and Pelvette 21 have noticed a condition in which electrical stimulation of a nerve-trunk produced marked reflex action, although no excitement of the skin supplied by the afferent fibres of the nerve was capable of doing this, showing that the extremities of the sensitive nerves are affected before the trunks. The evidence is, we think, sufficient to prove that potassium bromide affects all parts of the nervous system of the lower animals, but that the cerebrum, the motor tract of the cord, and the efferent nerves are the last portions to be affected ; that the most sensitive to its action is the receptive portion of the cord, that which receives and transmits reflex impulses, and next to this, and perhaps almost equally susceptible with it, are the peripheral ends of the afferent nerves. Upon the cerebrum of the higher animals the bromides undoubtedly exert an influence, and the researches of Albertoni M have thrown much light upon the usefulness of the drug in epilepsy. That observer found that when administered to dogs the bromide depresses very markedly the power of the motor zone of the cerebral cortex to respond to stimuli, and to give forth, on decided irritation, epileptic discharges ; it was also dis- covered that this action of the bromide was much more decided when there had been a prolonged saturation of the system with the drug than after a single large or even toxic dose. According to the researches of A. Crisafulli, 31 the action of the bromides upon the cells of the cerebral cortex is so powerful that vacuolization and other demonstrable changes are produced by it. The intellectual symptoms of bromism show that in man the action of the bromide on the cerebral cortex is more marked than in the lower animals, on account, no doubt, of the higher cerebral develop- ment. The drug in other respects acts upon man as upon lower mam- mals, lowering the reflex excitability of his spinal cord, paralyzing the ends of the peripheral nerves, etc. According to the researches of B. Schulze, 23 there is under the influ- ence of the bromide a decided decrease in the elimination of phosphorus, an indication that the protoplasmic molecular changes in the nervous system are lessened by the drug. Circulation. It is well established that large toxic doses of the bro- mide exert a direct paralyzing action on the heart, lessening both the force and the frequency of the beat, and finally causing diastolic arrest.* J. G. Schouten M found that during the slow injection of a two per cent, solu- tion into the vena cava of a rabbit the cardiac systole grew slower, the diastolic pauses longer, and finally the heart stood still, exhibiting only fibrillary contractions of its walls. The same observer is, so far as we know, the only one who has made manometrical studies of the action of small doses of the drug. He found that such amounts of the bromide * For experiments upon the isolated frog's heart, see Med.-Chir. Trans., 1882. 244 GENERAL REMEDIES. administered hypodermically or by the stomach always produced in- creased pulse-frequency with lessened arterial pressure. It would appear, therefore, that even small doses of potassium bro- mide are directly depressant to the circulation. The fall of the arterial pressure is certainly largely of cardiac origin. It is probable, though not proved, that the vaso-motor system also shares the paralyzing influence of the drug. How far the base in potassium bromide is responsible for the cardiac action has never been determined. Temperature. In warm-blooded animals, toxic doses of potassium bromide lower very decidedly the temperature. There have been no calorimetric experiments to determine whether this fall of temperature is due to a diminished heat-production or an increase in heat-elimination. The relaxed condition of the vaso-motor system under the influence of the bromide favors the escape of heat, and it is probable that the fall of bodily temperature is due in part or altogether to an excessive loss of heat. Nutrition. The symptoms of bromism show that potassium bro- mide has a distinct influence upon the general nutrition of the body, and it would appear probable that on account of the potassium in it there would be an increase in tissue-waste. The results reached by investiga- tors are, however, distinctly conflicting, although in many ways they appear to be the a priori expectation. It should be further recognized that we have no knowledge whatsoever as to the general influence of bromine upon the tissue- changes. Rabuteau K found that while taking the bromide there was slight lessening in the daily elimination of urea. The experiment was, however, a single one, and the daily dose of the bromide was only fifteen grains, an amount so small as to have no determinate influence. H. Bill, in an elaborate study of the action of the bro- mides upon elimination, determined that there was a very decided decrease in the amount of carbonic acid thrown off from the lungs, but that the elimination of urea was not sensibly affected. On the other hand, the quantity of urine was usually increased, the coloring-matters invariably augmented, and the action on phosphoric acid varied : after smaller doses it appeared to be slightly increased. Schulze, whose article we have seen only in abstract, in an apparently very careful investiga- tion on his own person, found as the result of the ingestion of one hundred and fifty grains of bromide a day that the urinary secretion was greatly increased, the phosphorus diminished, the sulphur very much increased, and the nitrogen slightly increased. The experiments of Chittenden and Culbert 26 were made with the maximum dose of one hundred and fifty grains a day. They found diminished excretion of phosphorus, but a pronounced increase of urea. In Chittenden and Culbert's experiments ammonium bromide acted like potassium bromide, but more powerfully, so far at least as the urea was concerned.* * It has been asserted (Binz, London Pract., 1874) that potassium bromide owes its physiological and therapeutic powers solely to its base. This is plainly not the case, as the bromide is not largely decomposed in the system, and the symptoms caused by it are very different from those produced by potassium carbonate : in a later publication (Arch. f. Exper. Path. Tlierap., xiii.) Binz himself has shown that bromine vapor pro- duces in frogs effects in many respects similar to those caused by the potash salt. At the same time it is almost certain that the potash influences the system to some extent. DEPRESSO-MOTORS. 245 SUMMARY. When in sufficient concentration potassium bromide acts as a powerful depressant upon all of the higher tissues. It is absorbed rapidly and eliminated in all the secretions more slowly; so that when given continuously it accumulates and causes bromism, usually first manifested by fetid breath, acne eruption, sleepiness, mus- cular relaxation, and general depression. The portions of the human organism most sensitive to its influence are the whole cerebral cor- tex, the receptive side of the spinal cord, and the afferent peripheral nerve-endings. The influence of potassium bromide upon the circula- tion is subordinate to its action on the nervous system. In full dose, however, it is directly depressing both to the heart and to the blood- vessels, and we have no knowledge that it acts in any dose as a stimu- lant either to the heart or the vaso-motor system. The fall of temper- ature which has been noted, chiefly in the lower animals, after toxic doses of the bromide is in all probability due to extreme heat-dissi- pation, in turn the outcome of vaso-motor depression. THERAPEUTICS. Potassium bromide is employed by the therapeutist to quiet cerebral excitement when not inflammatory in its nature ; to lessen over-susceptibility of the spinal centres of reflex action, or of the periph- eral afferent nerves which lead to these centres ; and to subdue nervous excitement of the genital system. The bromides are contra-indicated by an excessive irritability of the gastro-intestinal mucous membrane ; when such condition exists they may provoke exhausting diarrhoea. Great exhaustion, and especially great nutritive exhaustion of the nerve-centres, is a centra-indication to their use. Thus, owing to the excitement that attends confusional insanity, i.e. , the insanities following child-birth, typhoid fever, surgical operations, etc., bromides are frequently administered in large doses, to the great detriment of the patient. We are well convinced that under such circumstances they greatly lower the nutrition and check recovery. In the same way, in cerebral softening, senile dementia, and allied dis- orders, they must be used, if at all, only with the greatest reserve. There are various forms of nervous excitement, or unrest, such as sometimes follow excessive intellectual toil, anxiety, and other nervous strain, or occur during convalescence from acute disorder, in which the salt now under consideration is very valuable. The same may be said of some forms of hysteria. In some cases of neuralgia the bromide affords great relief, but in the majority of cases it fails. It has seemed to us useless in neuralgia dependent upon anaemia or want of power ; and our experience agrees with that of Anstie, that it is especially useful in persons of good nervous power, muscular force, and activity of circu- lation. As an hypnotic, it is employed in wakefulness from nervous ex- citement and in delirium tremens, but is of very feeble power. G. Krosz (Arch./. Exper. Path. Therap., vi. 43), in three experiments upon man, found decided difference in the results produced by proportionate doses of potassium bromide and of sodium bromide. He attributes the lessening of reflex activity to the bromine (see also Steinauer, Vlrchow's Archiv, lix.). 246 GENERAL REMEDIES. The chief use of the bromide is to lessen motor activity. It is especially in epilepsy that it has attained a well-deserved reputation, doing far more good than all other remedies combined, sometimes ap- parently effecting cures, more commonly ameliorating the symptoms, _but occasionally failing entirely. There is no known method of distinguish- ing before trial with any certainty in what cases it will do good. The assertion of Trousseau, that it is least efficient in the mild form of the disorder known as petit mal, accords with our experience. The most brilliant results have, as a rule, been obtained in cases of not too long duration in which the fits were frequent and severe. The governing principle in its use is to try it in every case, increasing the dose until a mild degree of bromism is induced, and being guided by the results. The salt is also often efficacious in various reflex spasmodic neuroses : in the vomiting of pregnancy or of uterine diseases ; in the gastric con- vulsions of children ; and, according to J. T. Rothrock, in preventing the so-called urethral fever induced in very susceptible males by the intro- duction of the catheter or bougie, it is very useful. The physiological action of the salt seemingly indicates that it is one of the remedies best suited for the treatment of tetanus. Clinical experience certainly accords with this conclusion : in a table published in previous editions of this treatise were collected thirty-four cases of tetanus, nearly all traumatic, treated chiefly by potassium bromide, with but four deaths. Not less than a half-ounce of the salt should be exhibited in the day, and at night chloral should be used as an hypnotic. (See CHLORAL.) In strychnine-poisoning, Saisson has demonstrated the value of the bromide by experiments on animals, and Charles B. Gillespie '" and C. L. Bard 28 have each reported, under its use, recovery without vomiting after the ingestion of three grains of the alkaloid. In nervous excitement connected with the genital function, potassium bromide is often of value. When there is actual inflammatory disease, as in gonorrhoea, the drug frequently fails to effect the desired end. If, however, there be no organic lesion of the organs or of their nerve- centres, the continued dose will usually succeed to a greater or less extent. We have found the remedy effective in cases of semi- impotence from over- irritability of the organs causing emission too soon during attempted sexual congress. There is abundant evidence as to its value in nympho- mania. As an adjuvant to other physical and moral measures of relief, the salt may be used with satisfaction in men suffering from masturbation. In nervous symptoms occurring at the time of the menopause or compli- cating uterine disease, and in the peculiar train of morbid phenomena arising from the forced suppression of the sexual function in vigorous individuals of either sex to whom circumstances have denied marriage, the bromides have almost a ' ' unique power. ' ' Ch. Bernard ** affirms that potassium bromide in doses of from twenty to forty-five grains a day removes with marvellous quickness malarial enlargements of the spleen. DEPRESSO-MOTORS. 247 ADMINISTRATION. We have known half an ounce of the bromide to be taken at once without inducing any serious symptoms ; and in severe acute cases, as in tetanus and strychnine-poisoning, it is perfectly safe to administer two-drachm doses at short intervals, as the case may require. Almost all the indications for the use of the bromide are best met by the so-called continuous dose, i.e., by the administration of so much in the twenty-four hours until an effect is induced. In epilepsy, from one to two drachms (4-8 Gm.) may be exhibited daily (see page 246); although as little of the remedy as will suffice to prevent the recurrence of the fit must be used, yet any amount necessary to do this should be given, unless distinct bromism be produced before the paroxysms are arrested. The remedy must be exhibited in a freely diluted solution. In some cases it causes diarrhcea, which may generally be checked with small doses of opium. It is essential in epilepsy and other chronic dis- orders to persist in the continuous administration of the bromide, it may be for years ; and it is remarkable how rapidly the symptoms of long- continued bromism subside upon the withdrawal of the drug.* AMMONII BROMIDUM AMMONIUM BROMIDE. U.S. Ammonium bromide may be obtained in colorless crystals, but gen- erally occurs in a granular powder, which becomes yellowish on exposure. It has a saline, pungent taste, and is readily soluble in water, sparingly so in alcohol. When mixed with mucilage of starch, if chlorine- water be added it becomes yellowish brown ; a blue tint would indicate the pres- ence of iodine. PHYSIOLOGICAL ACTION. The physiological action of ammonium bromide has not as yet been fully investigated ; but our present knowl- edge indicates that in many points it resembles that of the corresponding salt of potassium, whilst in others it differs from the latter. According to N. Bistroff 1 when two decigrammes are administered to a frog, a period of quietude and lessened irritability is induced, which, after fifteen or twenty minutes, gives place to violent tetanic convulsions. Later, all excitability is lost, so that even burning calls forth no recognition ; the frog lies in whatever position it is placed in, the spasms become more violent, and death ensues. Similar phenomena have been witnessed also by Amory * in the rabbit and the guinea-pig, although in one of Amory's experiments the guinea-pig died without convulsions having been noted. The curious abolition of reflex action and of sensibility con- sentaneously with the occurrence of violent convulsions was noted fre- quently, and death seems always to have resulted from asphyxia. In the * Ch. Fere asserts that many of the disagreeable symptoms of bromism are due to its disturbance of the alimentary canal, and are prevented by the daily exhibition of four grammes of beta-naphtol and four grains of bismuth salicylate, which doses are borne for months without any inconvenience, usually with much benefit to the appetite and digestion (Nouv. Iconog. de la Salp&tr., 1890). 248 GENERAL REMEDIES. experience of Bistroff, moderate non-fatal doses produced only weakness and uncertain movements in the rabbit. Ammonium bromide appears to exert very little influence upon the peripheral motor apparatus. Amory has seen the nerves retain their power of conduction after having been placed in a " strong solution ;' ' and, according to Bistroff, muscles retain their irritability after soaking five minutes in a ten per cent, solution. According to the latter observer, the heart always continued beating after death from the drug, and the heart removed from the batrachian and laid in a ten per cent, solution did not in any degree lose its normal activity. Even a twenty per cent, so- lution dropped upon the bared heart produced only a momentary arrest of the ventricular systole. On the other hand, Purser asserts that the heart is soon arrested in diastole in poisoning by this salt, and that the nerves and muscles also lose their irritability sooner than after poisoning by potassium bromide. The subject certainly needs further investigation ; yet it seems to us probable that ammonium bromide exerts less influence upon the cardiac and other muscles than does potassium bromide, but that in other respects their actions are very similar. The experiments of Amory indicate that the ammonium salt affects temperature and acts on the capillaries in the same way as that of potassium, and that it is also eliminated in a similar manner. The experiments of Bistroff show that in the cat, at least, am- monium bromide -has no especial influence, as has been asserted, upon the superior laryngeal nerves. THERAPEUTICS. Ammonium bromide is capable of fulfilling all the indications for which potassium bromide is used, and is especially useful in epilepsy. (See Strontium Bromide.} SODIUM BROMIDE, U. S. , closely resembles in appearance potassium bromide, and has been supposed by Voisin to have very similar physio- logical and therapeutic properties. On the other hand, M. J. V. Laborde * states that in double the toxic dose of potassium bromide he has found that it does not produce any characteristic symptoms in the frog, the guinea-pig, or the dog, and leaves the animal perfectly healthy. By clinicians the drug has been used to a considerable extent. Mere- dith Clymer 2 asserts that it will arrest epilepsy without producing the unpleasant cerebral symptoms of bromism. He gives twenty grains three times a day. Hammond s asserts that in epilepsy it is in no wise superior to the potassium salt, but affirms that its hypnotic power is much greater. M. E. Decaisne, 4 as the result of the trial of the drug in twenty- seven cases {epilepsy, chorea, hysteria}, asserts that its action is the same as that of the potassium salt, except that instead of causing diarrhcea it constipates. Notwithstanding this testimony, our own experience is in accord with the physiological teachings, that sodium bromide, although not free from therapeutic value, is not equal to potassium bromide in subduing nervous excitation, and is in no wise superior to it. DEPRESSO-MOTORS. 249 LITHIUM BROMIDE, U. S. , was, we believe, first employed in medi- cine by Gibb, 1 who recommended it as gently toxic and sometimes diu- retic. He used it in very small doses. Attention was first called to its employment in nervous affections by S. Weir Mitchell, 2 who stated, as the result of his experience, that, when administered to the amount of half a drachm to one drachm daily, it acts in some cases of epilepsy after potassium bromide has failed, and that it is generally efficient in about one-half the dose of that salt ; also that its hypnotic action is much more decided. Clark confirms these observations ; but, according to our ex- perience, the drug has no especial value. STRONTII BROMIDUM. U. S. Strontium bromide occurs in colorless, odorless, very deliquescent crystals of a bitter saline taste, soluble in 1.05 parts of water. Strontium bromide shares the action of the other stron- tium salts upon the alimentary canal and of other bromides upon the nervous system. It is therefore an extremely useful remedy in the treatment of epilepsy. It yields its bromine, however, rather slowly to absorption, and we have found that it usually acts much better in con- junction with ammonium bromide than it does by itself. The mixture of the two bromides, also, is much better tolerated than is the ammonium bromide alone ; so that after long trials in many hundreds of cases of epilepsy we have reached the conclusion that the best possible results are in the majority of cases to be obtained by the administration of a mixture containing in each dose twenty grains of ammonium bromide, ten grains of strontium bromide, five grains of antipyrin, and three minims of Fow- ler's solution, given morning and evening. In individual cases the dose of the bromides in this mixture is to be increased or decreased, the in- tent being to use as small an amount of the bromides as possible to control the paroxysms, and under no circumstances to go beyond the production of mild bromism. As the bromides act by accumulation in the system, and as patients become very much disgusted by the long continuance of frequent doses, it is usually much better to give the drug in two large than in three smaller doses a day. CALCII BROMIDUM. U.S. Calcium Bromide is a white, granular, very deliquescent salt, of a sharp, saline taste, soluble in half part of water. It is undoubtedly effective in epilepsy, and, according to Germain Se'e, 1 is absorbed and eliminated rapidly, and acts favorably upon the digestion. Dose, ten to twenty grains (0.66 to 1.33 Gm. ), always given in solution. ACIDUM HYDROBROMICUM DILUTUM. U. S. Diluted Hydrobromic Acid, A clear, colorless, strongly acid, odorless liquid, which contains ten per cent, by weight of the gas, absolute hydrobromic acid. In the physiological studies of E. T. Reichert, 1 hydrobromic acid was found to produce a temporary elevation of the blood-pressure, which was attributed, without proof, to vaso-motor spasm of peripheral origin. Large doses 2 5 o GENERAL REMEDIES. were directly paralyzant to the heart and to a less extent to the voluntary muscles. Reflex action is suspended by the acid in the frog, and all portions of the spinal cord and nerves are depressed by the poison ; but Reichert presents experimental facts which indicate that the sensory por- tions of the cord and the sensory nerves are affected before the motor system by hydrobromic acid as they are by ordinary bromides. In a very thorough test of hydrobromic acid in a large number of hospital epileptics, made by H. C. Wood, it was found that hydrobromic acid in equivalent doses resembles potassium bromide in its therapeutic action, and is less apt to produce acne eruption or muscular depression. It was determined, however, that the acid is so irritant that the stomach will not bear full doses of it, and that it ought to be used only in combination. The official dose is one fluidrachm (4 C.c. ). Comparative Power of Bromides. It is probable that the activity of the bromide is in direct proportion to the amount of bromine which it contains. It is interesting, therefore, to note that the calcium bromide contains eighty per cent, of bromine ; the sodium bromide, seventy- seven and one-half per cent. ; the potassium bromide, sixty-seven per cent. ; the strontium bromide, sixty-five per cent. A drachm of dilute hydrobromic acid is equivalent to nine grains of potassium bromide. GOLD BROMIDE. The original assertion of Goubert, that gold bromide is exceedingly valuable in the treatment of epilepsy and migraine, was apparently experimentally confirmed by Shtcherbak, who found that the salt, in doses of o. I to 0.2 gramme per kilogramme, had a very pronounced effect in inhibiting the psycho-motor centres. It is plain, however, that one-eighth of a grain (8 Mg. ) of the gold bromide (Goubert's dose) contains too little bromine for that element to have any effect. A grain of the gold bromide given daily has produced in our experiences no perceptible effect in epilepsy. BROMOFORMUM. U. S. Bromoform. Formyl Bromide. This is a colorless liquid with an ethereal odor and sweetish taste, which, first brought forward in 1849 by Nunneley and Schuchard as an anaesthetic, was found too dangerous for use as such, but has been employed to a considerable extent internally in the treatment of whooping-cough and other diseases for which the bromides are used. It is probably broken up in the system, but its products are eliminated with great slowness. It is undoubtedly capable of acting like the bromide, but has no advan- tage over the older preparations and is distinctly more dangerous. W. Gerhardi * * has shown that bromoform is capable of producing wide-spread fatty degeneration in the lower animals. E. Kiwull * has collected twenty cases of poisoning by it ; the symptoms have been pallor, titubation, dilatation of the pupil, coma, heart- failure, and collapse. The dose for the adult is six or seven drops in capsules. Two substances, apparently parallel in that they are saturated solutions of bro- mine in oil and in that the bromine is stated to be in combination with olein, have been put upon the market by manufacturers, and are probably identical in their physiological influence. Bromolein is a clear, yellow, oily liquid, said to contain twenty per cent, of bromine in oil of sweet almonds. * See also Wien. Med. Jahrb., 1883, 497. For poisoning, see Times and Register, 1892; also Annals of Gyn&cology, 1896-97; Pest. Med.-Chir. Presse, 1897. DEPRESSO-MOTORS. 251 Bromipin is a similar liquid, prepared with bromine and sesame oil, and sup- plied to the market by the manufacturers in two strengths, one containing ten, the other thirty-three and one-third per cent, of bromine. According to Merck's report, thirty grains of the stronger bromipin are equal to fifteen grains of potassium bromide ; so that thirty grains of bromolein should be considered about equal to ten grains of potassium bromide. Of the weaker bromi- pin one-half ounce may be given as dose to the adult, representing theoretically twenty-four grains of bromide. These substances may be used hypodermically, or may be employed, diluted with oil, endermically. After either method of administration bromine soon appears in the urine. They have been recommended by various clinicians in epilepsy, insomnia, neurasthenia, and other diseases in which the bromides are commonly employed. The dose of either substance appears to be in direct proportion to the amount of bromine contained. CAMPHOR A MONOBROMATA. U. S. Monobromated Camphor or Bromated Cam- phor. This is a compound in which one atom of hydrogen in the camphor has been replaced by bromine. It occurs as a crystalline solid, or in large acicular crystals several inches long. Our present knowledge of the physiological properties of bromated camphor rests upon the work of Bourneville, 1 of Lawson, 2 of Pathault, 3 of Richard Peters, 4 and of Pellicani. 5 In frogs there is progressive loss of reflex excitability and of voluntary movement (Peters), which, according to Pellicani, is due to paralysis of the motor nerves. Death is caused by arrest of respiration (Peters). In mammals it produces violent convulsions, muscular weakness passing almost into paralysis, reduction of temperature (after small doses preceded by a rise Peters), great decrease in the rate of the respiration and of the pulse (with occasional periods of hurried respiration Peters), profound sleep or stupor, and finally death. Bourne- ville states that the blood-vessels of the eyes and ears are diminished in calibre. Upon man the drug probably acts as upon other warm-blooded animals ; in a case reported by M. Rosenthal, 6 forty-five grains of it caused tremblings, marked slow- ing of the pulse, and coma of six hours' duration. Bromated camphor was first introduced by Deneffe 7 as a nervous sedative, and as an antispasmodic, especially in delirium tremens, but is of little value ; it is still used in hysteria, and has an especial reputation in sexual excitement and. spermator- rhoea. It is taken with difficulty, and is apt to irritate the stomach. It is too irri- tant for hypodermic use. Dose, five to ten grains (0.3-0.6 Gm. ), in capsule or coated pill, and repeated as necessary. BROMOCOLL is a yellow, tasteless, odorless powder, said to contain twenty per cent, of bromine, ten per cent, of water, thirty per cent, of gelatin, and forty per cent, of tannic acid. According to the experiments of Brat l bromocoll is very resistant to gastric juice, but is readily dissolved with decomposition in the intes- tinal juices. It is alleged to act like the older bromides and to produce less dis- agreeable symptoms. Friedlander 2 experimentally determined that it depresses the irritability of the psycho-motor centres. Dose, thirty to seventy-five grains a day. BROMALIN {Bromethylformin} occurs in colorless scales or as a white powder, nearly tasteless and readily soluble in water. It has been used in epilepsy and therapeutically allied diseases, especially by J. Kollarits, 1 and found to have no advantages over the older bromine preparations. The dose is about half that of potassium bromide. For a resume of the physiological action of bromal hydrate, which is certainly valueless as a practical medicine, see the tenth edition of this treatise. 252 GENERAL REMEDIES. AMYL NITRIS AMYL NITRITE.* U. S. Amyl nitrite was discovered by the French chemist Balard in 1844, and the attention of physiologists was called to it in 1859 by Guthrie ; but it was not until 1865 that Richardson, of London, introduced it to the notice of the profession. It is a yellowish, oily, very volatile liquid, of a very penetrating, persistent, fruity odor, ' ' containing eighty per cent, of amyl (principally iso-amyl) nitrite." (U. S. P.). It is prepared by the action of nitric acid on amylic alcohol, or, as it is commonly called, fusel oil. PHYSIOLOGICAL ACTION. Local Action. Amyl nitrite has no irri- tating properties. It causes a progressive loss of functional power in every highly organized tissue with which it comes in contact. Nerve-centres, peripheral nerves, muscles of organic and voluntary life, all succumb to it alike. If the contact be not continued too long, the tissue may recover even after a total suppression of its function, a proof that the poison ex- erts no destructive chemical or devitalizing influence upon the tissues, such as that of sulphuric acid or veratria. Absorption and Elimination. Amyl nitrite is absorbed with extraor- dinary rapidity, especially through the lungs, and must also be eliminated from or destroyed in the system with great rapidity on account of the fugaciousness of its action. F. Rohrmann * believes that the nitrites undergo oxidation in the system, because he has found that when potas- sium nitrite is administered to the lower animals it appears in the urine as potassium nitrate. General Action. The most prominent symptoms induced when amyl nitrite is inhaled by a man in moderate quantities are a sense of great ful- ness and distention of the head, amounting at last to sev :re pain, and ac- companied by intense flushing of the face, a deep, labored respiration, and an exceedingly rapid, violent action of the heart. The succession of these phenomena is usually so rapid that often they seem to be simultaneous ; but it is said that the cardiac disturbance is sometimes very distinctly manifest before the other symptoms. It has been noticed by Peck and confirmed by Ladendorf that objects look yellow to a person fully under the influence of the drug. After poisonous doses the symptoms have been great pallor, usually dilatation but sometimes contraction of the pupils, excessive muscular relaxation, slow, scarcely perceptible pulse, haemoglobinuria, and irregular respiration. In the lower animals the first stage of the action is like that just described in man. After this the breathing becomes violently hurried and panting, progressive muscular weakness and diminution of reflex * Berloni's ether or tertiary amyl nitrite, a mixture of amyl nitrite and iso-butyl nitrite has been found by Lauder Brunton and T. J. Bokenham to act very much as does the ordinary amyl nitrite, except that its effects are somewhat more slowly developed and are more permanent. It is not proved to be more stable than the ordinary amyl nitrite and has no advantages over the latter. According to Dunstan, amyl nitrite of commerce is chemically a mixture of a and ft amyl nitrites, iso-butyl nitrite, ethyl nitrite, and propyl nitrite (St. Bartliolomew's Hospital Report, 28, 1892). DEPRESSO-MOTORS. 253 activity ensue, and finally death from failure of respiration, sensation, and consciousness being preserved almost to the last. A very peculiar symptom is that a long time before death both the arterial and the venous blood become of a nearly uniform chocolate color. Convulsions are some- times present ; but in our experience more often the animal is exceedingly quiet throughout the poisoning. Nervous System. The influence of amyl nitrite upon the cerebrum is very feeble, disturbances of intellection and of consciousness not being produced except by very decided toxic doses, and not being prominent symptoms of the poisoning. As was shown by H. C. Wood, 2 the lessen- ing of reflex activity and of voluntary motion which undoubtedly occurs in toxaemia from the agent now under consideration is chiefly spinal in its origin, since after death the nerves and muscles preserve, though in an impaired condition, their functional power. On the motor centres of the cord the nitrite acts as a direct and powerful depressant, at the same time that it exerts a similar but much less pronounced influence on the nerves and muscles, decreasing, but not destroying, their functional life. The diminution of reflex activity is never preceded by a stage of functional excitement. In some animals convulsions do occur, especially when the drug is administered by inhalation ; but they are in all probability cere- bral, not spinal, and due to the asphyxiating influence of the poison. Over the sensory nerves and centres amyl nitrite has but little power. They are among the last portions of the body to be affected, sensation being intact until near death : so that the drug is in no sense an anaes- thetic. Respiration. It is certain that the respiratory centres are greatly depressed by full doses of amyl nitrite, the breathing becoming both slow and shallow, and death finally occurring from centric paralytic asphyxia. Mayer and Friedrich assert that small doses of amyl nitrite increase the rapidity and depth of respiration by stimulating the respiratory centres ; but this remains at present doubtful, it being probable that the increased respiration is secondary to the disturbance of the circulation, as is asserted by Winkler. Circulation. Although the pulse may be much increased in frequency sometimes from the very beginning by amyl nitrite, the arterial pressure is diminished, and finally is reduced almost to zero, the fall of pressure occurring equally after section of the vagi as at other times. As the num- ber of heart-beats in the uninjured animal is increased rather than di- minished, while the strength of the individual beat is not perceptibly lessened, it is evident that, at least in the early stages of the poisoning, the diminution of arterial tension is not cardiac in origin, but must be due to dilatation of the capillaries. This conclusion is confirmed by an experi- ment of Brunton, who found that if the descending aorta were tied high up, no perceptible fall of pressure was produced by the inhalation of the amyl salt until very late in the poisoning, when the heart itself was acted upon by the drug ; also by the fact noted by Amez-Droz* and by Gaspy,* 254 GENERAL REMEDIES. that the vessels of the rabbit's ear and of the frog's web can be seen to dilate when the salt is inhaled.* In man the flushing of the face and of the retina, as noted by Charles Aldridge, 5 indicates that the nitrite acts locally, probably upon some centre, before it does generally, as general dilatation of the vessels causes pallor. An interesting question which here arises is, whether the dilatation is centric, due to an action on the vaso-motor nerve-centres, or peripheral, due to a direct action on the muscular coat of the arterioles. We be- lieve that it must be peripheral, and not centric, in its origin, since both in our own experiments and in those of Brunton it occurred after the arte- rioles had been separated from the vaso-motor centres by division of the cord. This fact appears to prove that the fall of arterial pressure is due to a direct paralyzing action of the drug upon the coats of the arterioles, a conclusion confirmed by our knowledge of the local action of the nitrite upon muscular tissue. Bernheim, however, asserts that this cannot be so, and that the dilatation must be solely due to an action upon the vaso-motor centres, because he found that gal- vanization of the cervical sympathetic still caused contractions in the vessels of the ear of a rabbit to which amyl nitrite had been given. As pointed out by Pick, 6 Bernheim's experiment does not warrant his conclusion. It only shows that the muscle-fibres in the walls of the vessels are not so completely paralyzed as to be unable to respond to very powerful stimuli. W. Filehne 7 also dissents from the view that the action of the nitrite is upon the vessels. It is very probable from the general sedative effect of the drug upon the motor centres that it acts also upon the vaso-motor centres ; and when the local flushings caused by small doses of the poison are borne in mind, this probability is greatly enhanced. Filehne affirms that when to animals, whose lungs are exposed, inhalations of the nitrite were given, the change of color was not nearly so great as in the ears, and that if the sympathetic had been destroyed in the neck of a rabbit, and amyl nitrite exhibited, the ves- sels on the unwounded side actually became larger than those of the opposite ear. The answer to these results is, that opening the chest must derange most profoundly the pneumonic circulation, and that all observations upon the comparative size of vessels are very apt to be mere guess-work when the change is slight. Moreover, in Schuller's 8 experiments, after destruction of the cervical sympathetic in a rabbit, inhalations of the nitrite produced still further dilatation of the vessels of the ear. Atkinson 9 and D. J. Leech 10 have each found that the nitrite enor- mously increases the flow of blood-serum which is being forced by a steady pressure through the decapitated tortoise, or through a recently excised kidney ; a solution i in 10,000 had a distinct effect in widening the blood-paths. In conclusion, it seems to us established that amyl nitrite does act locally on the coats of the arterioles, although it may at the same time influence the vaso-motor centres. * A noteworthy fact asserted by Amez-Droz is that after a long period of dilatation the vessels contract again, whether the inhalation be continued or not. We think the explanation of this is simply that, owing to the volatility of the nitrite, it soon all escapes from the dossil of lint on which it is placed for inhalation ; an explanation strongly con- firmed by a statement of Amez-Droz, that in these cases a new inhalation was followed by dilatation as before. Amez-Droz says only the arterioles dilate, but Gaspy found that both arterioles and veins were affected. DEPRESSO-MOTORS. 255 In man the pulse-rate is enormously increased by amyl nitrite. In animals the amount of the increase varies, but in the higher groups the rule appears to be increase of the pulse-rate, which is especially decided in the dog. Filehne has by a single very ingenious experiment apparently shown that the acceleration is due to a depressing influence upon the in- hibitory centres. He divided the par vagum in a rabbit, employed an electric current to the sever d nerves of sufficient strength to bring the pulse-rate to normal, and found that the amyl salt was powerless to affect the rapidity of the cardiac action. Certain experiments performed by Mayer and Friedrich " confirm that of Filehne. It is known that sudden asphyxia slows the pulse by exciting the inhibitory centre. Mayer and Friedrich found that this action is prevented by the inhalation of the amyl salt. Then, again, they found that when by compression of the arteries the blood was prevented from going to the head, the nitrite did not increase the rapidity of the pulse, and also determined that the reflex inhibitory slowing of the heart by irritation of a sensitive nerve is pre- vented by amyl nitrite. Further, in dogs with a powerful cardiac inhibi- tory apparatus the primary influence of the nitrite is more marked than it is in rabbits, whose pneumogastrics are very feeble. The sudden, thump- ing action of the heart which is so prominent in man when the nitrite is inhaled is therefore probably, at least in part, due to depression of the inhibitory apparatus. There is, however, as pointed out by Reichert, 12 some reason for believing that in small doses the nitrite acts primarily as a stimulant to the heart. Lauder Brunton long ago discovered that if the aorta be compressed so as to eliminate in great part the influence of the vaso-motor system, the nitrite causes a primary rise in the arterial press- ure ; and it is perfectly possible for an excessive heart-action to be more than neutralized, so far as the arterial pressure is concerned, by a vaso- motor depression, so that the immediate fall of pressure caused in the normal animal by the nitrite is not proof that the heart may not be stimu- lated. In G. A. Atkinson's experiments, i part of the nitrite in 20,000 produced a slight increase in the working power of the cut-out frog's heart ( Williams' s apparatus) ; i in 10,000 caused a rise for four or five minutes, followed by a fall ; smaller and larger amounts than these had either no effect or lessened the heart's action.* It seems, therefore, that our present physiological evidence justifies the belief that very small quan- tities of amyl nitrite primarily stimulate the heart, although it is demon- strated that in moderate or large amounts the drug respectively depresses or paralyzes the heart-muscle. Urine. F. A. Hoffmann 14 found that in the rabbit a hypodermic in- jection of o. n i to o. 1 1 3 gramme of the drug is enough to cause dia- * There is, however, still much uncertainty about the matter. D. J. Leech affirms that i in 10,000 always quickens and weakens the beat of the isolated frog's heart in a Roy apparatus. In a single experiment made with amyl nitrite on the isolated mam- malian heart, Bock 13 came to the conclusion that the amyl nitrite has no effect upon the heart itself. The experiment, however, does not seem to us sufficient, and the method employed is open to very grave objection. 256 GENERAL REMEDIES. betes. If twice this amount of the amyl salt is used, the sugar becomes very abundant in the urine, and continues to be present for from twelve to thirty hours. Consentaneously with the elimination of sugar there is a great increase in the amount of the urine. The occurrence of glycosuria in man has not been recorded ; it is produced by toxic doses only, if at all. Temperature. Amyl nitrite, in whatever way exhibited, if given in sufficient amount, reduces most remarkably animal temperature. We have seen a pigeon perfectly conscious although its temperature had been brought down by this agent some 13 F. This influence is as marked in fever as in the normal condition of the animal, and is independent of the nerve-centres, occurring after section of the cord, and even after death in those cases in which post-mortem rise or continuance of high temperature normally takes place. We have also experimentally deter- mined that it is associated with diminished excretion of carbonic acid. It must therefore be due to a direct arrest or check of tissue-changes or oxidation within, or without, the blood. The mouth-temperature in man is certainly sometimes elevated by the inhalation of amyl nitrite, but the rise is a very temporary one. W. A. Manassein and N. Sassezki l * found, in a number of studies upon normal and fevered men, that while the peripheral temperature was at first increased the rectal temperature was always reduced, and after a time the surface of the body grew cooler. The maximum reduction was reached in one to one and a half hours, and in a case of fever amounted to 3 C. The vapors of the nitrite have a very marked influence over oxida- tion outside of the body, as is shown by many facts, of which it is only necessary here to cite the extinguishment of glowing phosphorus by a few drops of the amyl salt diffused through the jar. It cannot be doubted that within the economy the same thing occurs. If, however, the arrest of oxidation were complete, instant death from suffocation would result. The true explanation of the symptoms evidently lies in diminution, not destruction, of oxidation. When an animal inhales amyl nitrite, the arterial and venous blood soon become of a nearly uniform hue, which resembles somewhat that of normal venous blood, but is quite distinct from it, having a chocolate tint. Moreover, this chocolate-colored blood does not assume the arterial hue when shaken with the air. The appearance of the chocolate color of the blood is due to the for- mation out of the haemoglobin of a new substance which Gamgee 16 be- lieved to be a nitrite-oxy haemoglobin, but which has been considered by most observers, on account of similarity of spectrum, to be the methaemo- globin of Hoppe-Seyler." Haldane, Makgill, and Mavrogordato " assert, however, that the spectra are not absolutely identical, and that the new compound is really a mixture of nitric-oxide-haemoglobin and haemoglobin. The action of the nitrites upon the red blood-corpuscles immediately suggests that they affect the animal economy by overpowering the haemo- globin of the blood and putting an end to oxidation. That they have DEPRESSO-MOTORS. 257 an influence upon the interchange of gases in the blood, and that this influence counts for much in their action, seems certain. On the other hand, it seems almost equally certain that the nitrites in therapeutic doses do not arrest, but only check oxidation, and that their influence upon the nervous system and circulation is independent of their haemic action. Gamgee showed conclusively that the new compound in the blood yields oxygen to a reducing agent, and that when nitrite blood is brought into contact with prepared guaiacum-paper it still oxidizes it, though not so actively as normal ; so that evidently the blood-corpuscles retain to a greater or less degree their power of yielding ozone to bodies desiring it, and are capable of exerting at least this por- tion of their respiratory function : further, when this ozone is given up and the oxyhaemoglobin changed into haemoglobin, so far as our present knowledge goes, the haemoglobin must absorb more oxygen before it can unite with the nitrite. Evidently, then, absorption of oxygen must take place ; evidently the blood-cor.- puscles must perform their respiratory function ; but evidently also they are greatly crippled and impaired in the rapidity and ease of its performance. Haldane, Makgill, and Mavrogordato found that when an animal is placed in oxygen gas, under a pressure sufficiently high to so saturate the serum of the blood with oxygen that it (the serum) was able to maintain life, ordinarily fatal doses of the nitrites failed to kill, although by increasing the amount of the nitrite death could be produced ; evidence that the influence of the nitrites upon oxidation is an important but not a sole factor in their toxic influence. Further, Gamgee showed that potassium and other nitrates act upon the blood as do the nitrites, yet the symptoms caused by them are very different from those produced by the nitrites. It is also sure that various drugs in toxic doses check oxidation, but do not cause the same symptoms as are produced by the nitrites ; finally, when arrest of oxidation in the body is caused by substituting oxygen by an inert gas, such as nitrogen, the symptoms are essentially different from those of nitrite-poisoning, the brain and con- sciousness being always affected before the spinal centres, whereas under the influ- ence of amyl nitrite the contrary occurs. In sufficient dose amyl nitrite is poisonous to the white corpuscles ; Atkinson has found that i in 1000 kills the corpuscles in from fifteen to twenty minutes. SUMMARY. The dominant physiological action of amyl nitrite is upon the spinal cord and the circulation. Under its influence arterial pressure falls from paralysis of the blood-vessels, chiefly due to a direct action upon the muscles in their walls. At the same time the vagi-centres are paralyzed and the heart is stimulated directly or indirectly, the number and force of its contractions being in- creased, this period of stimulation after moderate doses gradually subsiding into the normal state, but after toxic doses passing into one of cardiac paralysis, -with a final arrest in diastole, -which is due to a direct action upon the heart-muscle or contained ganglia. Paral- ysis of motion and loss of reflex activity, prominent phenomena of advanced poisoning, are due to a direct action upon the motor side of the spinal cord. Death results finally from paralysis of the respiratory centres. By a direct action upon the red blood-corpuscles the haemo- globin is converted into a new compound, probably methaemoglobin. The fall of the bodily temperature is probably the result of lessened oxidation. Locally applied in concentrated form, amyl nitrite paral- yzes all higher tissues. 17 258 GENERAL REMEDIES. THERAPEUTICS. Amyl nitrite is employed to meet indications which are very closely in accord with its known physiological action. It should be remembered, however, that its influence is all over in from ten to twenty minutes after its ingestion, and it is therefore a remedy useful only in cases of crises or fugacious conditions. It may be employed in all cases in which it is desired to dilate the capillaries. During the algid stage of an ordinary intermittent fever it will put an end immediately to the chill, but does not affect the development of the hot stage. It might possibly be of service in the algid stage of a pernicious malarial fever. Led by the evidences of arterial spasm in the sphygmographic tracings in a case of angina pectoris, Lauder Brunton in 1867 suggested its use in that disease. As the pathology of these cases of heart-pang is not defi- nitely made out, it seems useless to speculate how the nitrite acts in many cases ; but there is abundant evidence of its value in relieving almost instantly agony which has resisted all other treatment. This ap- pears also true whether valvular disease or merely functional disorder exists. Foster 18 has found the drug of great service in aortic insuf- ficiency with excessive hypertrophy and severe frontal headache. The violent cardiac action which is produced by the inhalation of the nitrite has led to its employment as a cardiac stimulant, and it has been much commended by various clinicians in all forms of sudden heart- failure^ even when such failure is dependent upon fatty degeneration or other disease of the heart itself. The direct stimulant influence, if it exist at all, of amyl nitrite upon the heart is, however, of the briefest duration, and if the least overdose of the drug be given, passes into cardiac de- pression. The zone between stimulation and depression of the heart by the nitrite is so narrow that the greatest care must be exercised whenever there is any cardiac disease, or whenever the heart is violently depressed by such a poison as chloroform. Although Reichert states that he has seen the blood -pressure and pulse-wave, which had been depressed almost to zero by ethylene bichloride, greatly increased by amyl nitrite, in an elabo- rate series of experiments made by H. C. Wood with chloroform no such effect could be obtained, and in recorded cases of cardiac failure in anaes- thesia the amyl salt has failed. Its use should always be tentative. Its physiological action would indicate that it should be of service in all cases of spasm of the capillaries, of the bronchial tubes, and of the muscular system generally. Accordingly, Oscar Berger 19 and others have used it with very good effect in migraine with capillary contraction. Amyl nitrite is of very great value for the purpose of relaxing spasms ; it will usually abort a paroxysm of asthma, but in practice it will be found that the asthmatic patient becomes so rapidly accustomed to the use of the drug as to make it of comparatively little value. In a fully formed paroxysm of epilepsy it must be used with caution, because the pa- tient's condition will obscure its early effects ; but in the status epilepticus, when there is an almost indefinite repetition of the fits, the remedy may be of great use in stopping the convulsions. When there is a notable in- DEPRESSO-MOTORS. 259 terval in ordinary epilepsy between the aura and the convulsion, the latter can usually, if not always, be entirely prevented : the patient should carry a small vial containing a few drops of the drug or so-called ' ' pearls' ' (minute flasks, each containing five minims, which are to be broken in a handkerchief), and should inhale the amyl salt so soon as the aura is felt. S. Weir Mitchell 20 calls attention to the value of the nitrite as an aid in diagnosing those occasional cases of nervous disorder in which petit mal is simulated by attacks really due to passing congestion of the nerve- centres. He asserts that in these cases amyl nitrite instead of arresting the paroxysm increases its severity. In nervous spasmodic dysmenorrhcea, it is stated by various authorities that inhalation of amyl nitrite will sometimes bring immediate relief, two to six drops being given when the pain comes on, and repeated pro re nata. As' was first pointed out by William F. Jenks, 21 the nitrite is most effective in arresting puerperal convulsions, but if the convulsions occur shortly after parturition the use of the nitrite is attended by the greatest danger of producing uterine relaxation and serious or even fatal post- partum hemorrhage. Amyl nitrite is a very valuable remedy in the treatment of tetanus and of strychnine -poisoning. In the experiments of St. Clair Gray, 22 which have been substantially confirmed by Hobart A. Hare, 23 although one- quarter of a grain of strychnine was found to be sufficient to cause death in an immediate convulsion in the rabbit, no decided symptoms whatever were induced in two rabbits by the subcutaneous injection into each of half a grain of strychnine with ten drops of the nitrite. During a par- oxysm of cramp asphyxia from strychnine, the poison of tetanus, or other similarly acting cause, the nitrite should be given hypodermically, the lack of respiratory movement interfering with its absorption through the lungs. TOXICOLOGY. We know of no deaths recorded from amyl nitrite, though very alarming symptoms have resulted in various cases. Ten minims of a ten per cent, solution, hypodermically injected, are said to have been followed by two successive furious epileptic convulsions, each preceded by arrest of respiration and of the heart's action, to which arrest they were probably due. * Three drachms caused no other symp- toms than violent vomiting. One drachm occasioned great weakness, cya- nosis, and very feeble, slow, intermittent pulse. Two drachms caused vomiting within five minutes, great weakness of the pulse, slow respiration, temperature below 95 F. , semi-coma, with haemoglobin, but no sugar or blood-corpuscles, in the urine for twelve hours ,after the poisoning. The best treatment for the poisoning would consist in favoring vomit- ing by apomorphine or other agents, and the use of artificial respiration and hypodermic injections of strychnine and digitalis. That there is * Strahan (Journ. Ment. Set., xxx. 252), J. Roesen (Centralb.f. Klin. Med., 1888), George E. Shoemaker (Med. News, 1893, i.), and Stansfield (Brit. Med. Journ.). 260 GENERAL REMEDIES. between the latter drug and a nitrite, so far as the circulation is con- cerned, direct antagonism has been shown by C. R. Marshall," who found that, in accordance with the doses used, the vaso-dilator influence of the nitrite would put an end to the high pressure caused by digitalis, or that digitalis would elevate the lower blood-pressure of the nitrites, or that the two drugs would just counteract each other, and that digitalin would overcome the diastolic cardiac arrest produced by the nitrite, or the nitrite, if in excess, would overcome the systolic arrest of the frog's heart produced by digitalin. ADMINISTRATION. As already stated, the method of administration usually employed hitherto is inhalation, from one to three or five drops being placed on a handkerchief and held near the mouth or nose, the handkerchief being removed so soon as a sense of fulness of the head is experienced. We have given it by the mouth, dropped upon a lump of sugar and taken instantly in doses of two or three drops. There is not at present sufficient evidence to enable us to decide as to the maxi- mum amount of the drug which it is safe to give. In a case of cholera, D. B. Smith 25 exhibited hypodermically two drachms in the course of an hour and thirty-six minutes without inducing any serious symptoms, and a dose of a dessertspoonful has been recovered from, 26 emetics being given. Used with care, the nitrite, although a very rapidly acting and powerful agent, seems to be safe, since we have never seen either in man or in the lower animals any sudden or unexpected action, any influence out of proportion to the amount given. It must be borne in mind that the symptoms generally increase in intensity for a minute or two after the withdrawal of the drug from inhalation. ETHYL NITRITE. It is not to be doubted that all of the nitrites de- pend for their physiological activity on their acid-radical, and that most of them have similar physiological properties. This has been shown to be true of ethyl nitrite (Richardson 1 and Leech 2 ). Leech asserts that the ethyl nitrite has the great advantage over the amyl salt of greater per- manency of action, the effect of the single dose lasting from a half to two hours. He highly commends in asthmatic bronchitis a solution, which he states to be stable, composed of three parts of ethyl nitrite, five of glycerin, and ninety-two of absolute alcohol ; dose, thirty to ninety minims (2-6 C.c. ). SODIUM NITRIS. U. S. It has been demonstrated by E. T. Reichert l that the general physiological action of sodium and of potassium nitrite is indistinguishable from that of amyl nitrite, except in being much less rapid and more permanent. (See also G. A. Atkinson. 2 ) Doses of six to ten grains in man sufficed to raise the pulse to no or 120, with flushing of the face and intra-cranial throbbing ; the symptoms usually began in twenty minutes and lasted several hours, and were in no case disagreeably severe. Eructations of a phosphorus-like taste were nearly DEPRESSO-MOTORS. 261 always present. Ten to fifteen grains have produced complete muscular relaxation, livid lips, headache, etc., lasting three hours. Twenty grains of the commercial sodium nitrite have been given without serious effect, but of a pure article, either of the sodium or the potassium nitrite, the dose is three grains (o. 2 Gm. ) ; five grains have produced serious symp- toms. 3 The dose may be repeated every two hours, cautiously. SPIRITUS GLYCERYLIS NITRATIS. U. S. Spirit of Glonoin, a one per cent, alcoholic solution of glonoin trinitrate or nitroglycerin, is a clear, colorless liquid, having the odor and taste of alcohol. As very minute quantities are capable of producing violent symptoms, great care should be exercised in tasting it or in applying it to the skin. Moreover, if any considerable quantity of it be spilled, the evaporation of the alcohol is liable to be followed by a dangerous explosion. Full therapeutic doses of the spirit of glonoin cause in man giddiness, constriction, or other abnormal sensations in the head, often amounting to severe headache, choking in the throat, sometimes nausea, and rapid cardiac action, with lessened arterial pressure. After toxic doses there is great failure of the heart's action. A single drop is said to have caused insensibility, and in the case of Mr. Field, 1 who took two drops, loss of consciousness and of the pulse at the wrist was complete. J. Noer 2 attributed the follow- ing symptoms in a woman to the use of ten-drop doses of the alcoholic solution of nitroglycerin. The pulse was slow, intermittent, and very irregular, the pupils dilated, the urine scanty and containing considerable pigment. There were also pain in the region of the heart, intense head- ache, sense of constriction around the forehead, and great weakness of the muscles. Lauder Brunton and Tait 3 have found that upon blood- coloration, arterial pressure, nerve-centres, and muscles nitroglycerin acts very much as does amyl nitrite. This similarity of action between nitro- glycerin and the nitrites has been confirmed by Murrell and Matthew Hay, 4 also by A. Henocque, 5 and is remarkable, as nitroglycerin may be regarded as glyceryl nitrate. It has been shown, however, by Hay, that during its alkaline decomposition it yields nascent nitrous acid, and it can scarcely be questioned that this acid is developed in the blood and acts upon the system. Amblyopia is said to have resulted from prolonged exposure to the fumes of nitroglycerin (Hogg 7 ). The effect of nitroglycerin is certainly more prolonged than is that of amyl nitrite. The statement of Korczynski, 6 that the maximum effect of a dose in man is reached in from three to five minutes, whilst the influ- ence is dispersed in three-quarters of an hour, is as accurate as can be made. Nitroglycerin has come into great favor for all conditions in which amyl nitrite has been employed. In angina pectoris, in cardiac failure, in asthma, in ur&mia, and in puerperal eclampsia it may be sub- stituted for amyl nitrite with advantage whenever any persistency of action is desired. It is also very largely used in cases of habitual high arterial pressure, especially in arterial fibrosis in which the increased peripheral 262 GENERAL REMEDIES. resistance is developing or has produced increased cardiac power. Even its action is, however, too fugacious to be of much service in these cases, and it should be administered every hour when a decisive effect is wanted. In some cases of acute apoplexy with high arterial pressure it might be of great service. The dose is one to two minims (0.06-0. 12 C.c. ). Erythrol Tetranitrate. A crystalline solid which, when pure, is colorless, but which is prone to decomposition and to become yellow. It is a violent explosive whose trituration has caused death. It is slightly soluble in water, but readily in alcohol. Its physiological action appears to be entirely parallel to that of glonoin, excepting in that its influence is less powerful and is much more prolonged. In man its effects are said not to be apparent in less than half an hour and to last for more than an hour. It has been especially recommended in the treatment of angina pectoris. As its alcoholic solution is explosive, it should always be used in tablets, whose preparation requires great care. Dose, from one-half to one grain (0.03- 0.064 Gm.). LOBELIA. U. S. The leaves and tops of the indigenous herb Lobelia inflata. The dried plant has a slight irritating odor and a taste at first scarcely per- ceptible, afterwards burning, acrid, and attended by a flow of saliva. Proctor discovered the alkaloid lobeline, which was long believed to be liquid, until J. U. and G. G. Lloyd obtained it in broad, colorless, odor- less, and tasteless crystals.* PHYSIOLOGICAL ACTION. The symptoms produced by large doses of lobelia in man are nausea, soon followed by violent vomiting, accom- panied by intense prostration, as is shown by feeble pulse, cold sweats, pale skin, and great muscular relaxation. Purging may or may not occur. Numerous cases of fatal poisoning by it have been recorded. The symptoms are those above mentioned, intensified ; in some cases vomiting does not occur, and it is especially under these circumstances that fatal effects have been noted. Burning in the fauces and oesophagus, and epigastric distress, in addition to the intense prostration, bordering upon collapse and finally merging into complete collapse, with coma, stupor, muscular tremblings, and in some cases convulsions, precede the fatal termination. In mammals the symptoms produced by lobelia are : slowing and irregularity of the respiration ; progressive failure of the muscular power ; violent vomiting in those animals which have the power of vomiting ; dilated, fixed pupil ; convulsive seizures ; fall of the bodily temperature, and death from asphyxia, the heart con- tinuing to beat after the failure of respiration, the dominant physiological action of the drug being its influence upon the respiratory centres. When given to the frog, lobeline produced failure of voluntary movement, with distinct loss of coordination and disturbances of respiration. Unless the dose has been too large, there is pri- mary increase of the reflex activity, which, however, sinks below the normal until it is lost. * The Messrs. Lloyd also assert that there is a second alkaloid in lobelia, but the researches of Dreser 1 render it probable that this second alkaloid is a derivative from lobelime. DEPRESSO-MOTORS. 263 All experimenters seem to be in accord in concluding that the final paralysis caused by lobelia is due to a direct paralyzing action upon the motor nerves. Berstein called attention to the fact that the spinal cord of the frog is usually supplied with blood from the anterior spinal artery, and that by thorough and complete section of the cord the lower segment is cut off from the general circulation. Experimenting in accordance with this, Dreser J found that the increased reflex activity produced by lobelia was confined to the anterior section of the cord and tributary muscles, and concludes that lobeline is a direct spinal stimulant. Respiration. The researches of Dreser seem to show that both the respiratory centre and the vomiting centre in the medulla oblongata are primarily excited by lobeline ; hence the vomiting, and hence, also, the increase not only in the rate of the respiration, but in the amount of air taken in and out from the lungs, as observed by Dreser. This condition of excitement is followed by paralysis of the respiration, which after very large doses may come on abruptly, even within two or three minutes after the injection of the poison. According to Dreser, the paralysis of the motor nerves, noted in the frog, is of little importance in the mammal, the respiratory centre being so susceptible to the drug that it is paralyzed before the nerves. Dreser also found that there is a peripheral palsy of those vagus filaments which have influence upon the bronchial muscles. Circulation. According to Ott 2 and Afanasieff, 3 lobelia produces a rise of the arterial pressure, which in Ott's experiments was not prevented by previous high-up section of the spinal cord, and must, therefore, be due to an action either of the heart or of the muscles in the arterial walls. Because he found that no rise of pressure is produced by lobelia in the nicotinized rabbit, Ott concludes that the alkaloid is a stimulant to the arterial walls. On the other hand, in the experiments of Afanasieff, lobeline caused in the frog's heart a period of increased work, followed, if the dose were large enough, by loss of power ending in diastolic arrest. In the later stages of lobeline-poisoning the arterial pressure falls progres- sively, so that it is probable that lobelia first stimulates and afterwards paralyzes both the heart and the arteries. A very important point to be noted is that the action of lobelia upon the circulation is entirely subordi- nate to its influence upon the nerve-centres, especially upon respiration, and is, therefore, of no value to the therapeutist. TOXICOLOGY. The symptoms of lobelia-poisoning have been suffi- ciently described. The treatment should consist in washing out the stomach with plenteous draughts of a warm solution of tannic acid, in the free exhibition of opium, alcohol, ammonia, strychnine, and digitalis, and in the use of external stimulation by dry heat, frictions, mustard, etc. , precisely as in poisoning from veratrum viride. THERAPEUTICS. The former use of lobelia as an emetic, and for the purpose of relaxing spasm in various diseases, has been entirely super- seded by more effective and less dangerous remedies. Lobelia remains, however, a valuable drug in the treatment of asthma, or acute bronchitis 264 GENERAL REMEDIES. with bronchial spasm, in which it may be given in small repeated doses at long intervals, or in severe attacks every few minutes until nausea is induced. An infusion (one ounce to a pint) has been strongly recom- mended as a local application in the eczema produced by the Rhris toxi- codendron, or "poison-vine. ' ' The dose of the tincture (TINCTURA LOBE- LI^E ten per cent., U. S. ), as an expectorant, is twenty to forty minims (0.61.2 C.c. ) ; in the paroxysm of asthma, one-half to one fluidrachm (2-4 C.c.) every half-hour until nausea is induced. That of the fluid extract (FLUIDEXTRACTUM LOBELIA, U. S. ) is, as an expectorant, one to five minims. According to S. Nunes, 4 from five to forty centi- grammes of lobeline may be given a day, but in any case the first dose should not exceed one-fortieth of a grain, to be increased pro re nata. GELSEMIUM. U. S. The root of Gelsemium sempervirens, \hzyellow or Carolina jessamine, a beautiful climbing plant of the Atlantic Southern United States, distin- guished by its large, axillary, very fragrant, clustered blossoms and perennial dark green leaves. The very light, fibrous, dirty yellowish root has a bitterish taste, and contains an alkaloid, Gelsemine, in combi- nation with Gelseminic Acid, both discovered by Wormley. PHYSIOLOGICAL ACTION. Absorption. The alkaloid gelsemium is rapidly absorbed and is eliminated unchanged by the kidneys. General Action. There is a wide range of susceptibility in man to the influence of gelsemium, some individuals being profoundly influenced by a dose which has no perceptible effect upon another person. After the smallest active dose (five to fifteen minims of the fluid extract), the only symptom is languor ; with it may be a little lowering of the force and frequency of the pulse. When a somewhat larger amount is ingested, to the languor are added dizziness and disturbance of vision, with, in some cases, a pain over the brows. Ringer and Murrell * state that the pupil is contracted, but this is probably an inconstant result. After toxic doses of the poison the muscular weakness is extreme, and in several cases 2 the flexors of the arms have been especially affected. The disturbance of sight is now very marked ; double vision, or partial or even complete blindness, may exist ; the pupil is widely dilated and immovable ; the external rectus muscle is weakened, sometimes sufficiently to produce a marked internal squint ; the eyelid droops, and is raised with difficulty or falls in paralytic ptosis. If the patient is able to walk at all, the gait is staggering ; the jaw drops, articulation fails ; the general sensibility is much impaired ; the respiration slow and labored ; the pulse feeble and thready ; the skin bathed in a cold sweat ; the bodily temperature greatly lowered. Sometimes drowsiness is felt after moderate doses of the poi- son, but consciousness may be preserved in the midst of very severe symptoms, although in all the fatal cases whose record we have met with it has been lost before death. The drug acts very promptly, symp- DEPRESSO-MOTORS. 265 toms usually appearing in about twenty minutes after its ingestion, and beginning to subside in two or three hours. Gelsemium produces in the lower animals symptoms similar to those which it causes in man, with the exception that convulsions are very generally developed. The convulsions are not always present, but they have been observed in the frog, pigeon, cat, rabbit, and dog. The loss of voluntary power precedes the con- vulsions, and in the careful experiments of Ringer and Murrell upon frogs it was found that the cord was rapidly exhausted by repeated irritations, so that convul- sions could not at once be induced. Bartholow states that in the rabbit, cat, and pigeon the convulsive movements are backward, sometimes amounting to complete somersaults. Nervous and Muscular Systems. Cerebrum. The retention of con- sciousness until very late in the poisoning, both in man and in the lower animals, shows that the drug has very little power over the higher cerebrum, although the drowsiness and the final loss of consciousness prove that it is not entirely devoid of such influence. The convulsions are not cerebral, as is proved by their occurrence in the pithed frog (Ringer and Murrell), and below the point of section in mammals with divided spinal cord (Taylor 8 ). Both the convulsions and the paralysis in poisoning by gelsemine are spinal. Their development is not affected by tying an artery before poi- soning, so as to protect a limb (Bartholow, 4 Ringer and Murrell 5 ) ; more- over, the afferent and motor nerves and muscles preserve their functional activity until death.* The convulsive stage of gelsemine-poisoning is preceded by exaggerated reflex activity (I. Ott 6 ), so that gelsemine ap- pears to cause spinal motor excitation followed by spinal motor paralysis. The most plausible explanation of these phenomena is (in accordance with the doctrine of spinal inhibition, see page 172) that gelsemine is a depressant and, finally, paralyzant to both the spinal inhibitory ganglia-cells and to the spinal motor nerve-cells, but attacks primarily inhibition ; so that in the first stage of its poison- ing excessive motor activity results from the paralysis of spinal inhibition, whilst in the final stage there is a true motor paralysis due to a direct paralysis of the motor nerve-cells. Ringer and Murrell, however, conceive that there are in gelsemium two active, antagonistic substances, one a tetanizant,t the other a paralyzant ; but in their own experiments, and in those of Ott, gelsemine believed to be pure produced convulsions. Ott, however, found gelsemic acid so much more pow- erful in its convulsive action than the alkaloid as to suggest the correctness of Ringer and Murrell's hypothesis. * Ott, Bartholow, Ringer and Murrel. (For details, see eighth edition of this treatise.) fin confirmation of this, A. R. Cushny {Arch, fur Exper. Pathol., 1892, xxxi.) finds that there are two bases in gelsemium, to one of which he gives the namegelse- min, the other gelseminin. Gelsemin, he finds, produces in the frog violent spinal ex- citement with increase of the reflexes, followed by paralysis due to an action upon the nerve-endings. Gelseminin is the more active of the two, producing a paralysis by direct action upon the spinal centres and having also a curare-like paralytic influence upon the nerve- trunks. 266 GENERAL REMEDIES. Dr. Bartholow says that ' ' it [gelsemium] acts also on the sensory portion of the cord, producing at last complete anaesthesia ; but this effect in warm-blooded animals and in man is toxic only, and follows the paralysis of the motor functions." This may be correct, but, so far as we know, has not been experimentally proved. Respiration. Gelsemium usually kills by a paralysis of respiration. According to the researches of Burdon Sanderson and of Ringer and Murrell, immediately after the ingestion the extent of the respiration, but not its rate, is increased ; very shortly, however, both rate and depth enter a condition of progressive palsy ending in death. The respiratory changes are the product of a direct action upon the respiratory centres, being uninfluenced by previous section of the vagi. Circulation. The action of moderate doses of gelsemium upon the circulation is not pronounced, but the toxic dose depresses both the pulse- rate and the pressure. As this occurs after previous section of all the cardiac nerves of the spinal cord (Ott 7 ), it is probable that the poison exerts a direct influence upon the heart. How far or in what way it affects the arterial system we have no knowledge. Eye. Ringer and Murrell affirm that decided non-toxic doses of the drug cause contraction of the pupil. However this may be, marked dila- tation of the pupil is a very constant symptom in the poisoning, and the local application of gelsemine to the eye produces violent mydriasis, with paralysis of accommodation. It would seem probable that the mydriasis is due to an action upon the periph- eral nerve-ending in the eye. The palsy of the external rectus and the ptosis indi- cate that such action is paralytic, so that it is a probable conclusion that peripheral oculo- motor paralysis is the cause of the dilatation of the pupil. The falling of the jaw and the loss of the power of articulation indicate that all the motor nerves of the head are acted upon by the poison. SUMMAHY. The characteristic symptoms of gelsemium-poisoning are progressive muscular "weakness, double vision, dilated pupils, squint, ptosis, and dropping of the jaw. The chief physiological action of the remedy seems to be depression of the motor spinal cord, including the respiratory centres ; the depression apparently being preceded by a stage of stimulation. The effect of the remedy upon the circulation is not pronounced, but toxic doses depress directly the heart and arterial pressure. THERAPEUTICS. Gelsemium was originally employed as an arterial sedative and febrifuge in the malarial fevers of the South, and subse- quently in other sthenic fevers. It appears in some way to depress the bodily temperature, but certainly possesses no controlling influence over the arterial system at all comparable to that of veratrum viride and aconite. Bartholow commends it highly in pneiimonia and pleuritis ; its influence for good in these disorders would seem, however, to be chiefly associated with its power of lessening the rapidity of respiration and increasing the tendency to perspiration. It does not appear proba- ble that any advantage to be derived from it will counterbalance the dan- DEPRESSO-MOTORS. 267 gers attending its employment in the large doses required. In asthma, spasmodic laryngitis, whooping-cough, and nervous cough, in which it is also recommended by Bartholow, its employment seems more plausible, as in these cases there is a distinct spasmodic element. The testimony to its value in cases of trigeminal, ovarian, and other neuralgias is strong. How it does good in these disorders is as obscure as is the nature of the neuralgias, and in our hands it has usually failed. The marked effect of the drug upon the facial nerves would appear to indicate its employment in facial neuralgias, and especially in facial spasmodic affections. In acute mania the drug may be employed in full doses as a calmative. TOXICOLOGY. I. Ott has collected six cases of fatal poisoning, a teaspoonful of the fluid extract being the smallest amount that has caused death in the adult. Wormley believes that his chemical examina- tions have shown that in one fatal case the fluid extract ingested could not have contained more than one-sixth of a grain of the alkaloid. The treatment of gelsemium-poisoning should be conducted on gen- eral principles. Our present knowledge does not indicate that morphine and gelsemium are physiological antagonists, but George S. Courtright 8 asserts that they have such relation, and details a case in which recovery occurred after the ingestion of from one to two teaspoonfuls of the tinc- ture, one and one-half grains of morphine having been given hypoder- mically and one grain by the mouth. ADMINISTRATION. The dose of the fluid extract (FLUIDEXTRACTUM GELSEMII, U. S. ) is five minims (0.3 C.c. ) every two hours until con- stitutional effects are produced ; of the tincture (TiNCTURA GELSEMII ten per cent., U. S. ), fifteen to thirty minims (1-2 C.c.). TABACUM. Tobacco is no longer recognized by the United States Pharmacopoeia, and is not at present used in practical medicine. We shall here discuss it very summarily, referring the reader to the tenth edition of this treatise for an elaborate study of its physiological action. Tobacco depends for its activity upon the presence of an alkaloid, nicotine, a poison of such intensity that it has caused death in three minutes. The fatal dose of nicotine has not been made out. One-thirty- second of a grain will cause serious symptoms ; one-seventh of a grain has been recovered from. The symptoms produced by tobacco in those unaccustomed to its use are horrible nausea and vomiting, giddiness, intense malaise, with weakness, followed, if the dose has been sufficient, by burning pain in the stomach, purging, free urination, extreme giddiness passing into delirium, a rapid, running, and finally imperceptible pulse, cramps in the limbs, absolute loss of muscular strength, a cold, clammy skin, and finally complete collapse, terminating in death. In the lower animals, especially in the frog, to the symptoms com- monly seen in man are added violent convulsions, which are of spinal origin and are followed after a time by paresis, which is probably also in part of spinal origin, although it has been demonstrated that tobacco is 268 GENERAL REMEDIES. a powerful depressant to the motor or efferent nerves ', acting primarily upon their peripheral filaments. The afferent or sensory nerves are much less affected than the motor, but are probably also depressed. The sympa- thetic ganglia are first stimulated and then depressed by nicotine. To these actions are probably due the increase of saliva and other secretions caused by small doses and the lessening of gland activity produced by large doses. Upon the voluntary muscles the drug has no action. Upon the circulation nicotine has a very distinct influence, producing first rise and afterwards fall of pressure. The rise of pressure is certainly in part due to stimulation of the cardiac muscles or ganglia, but prob- ably is also in part the outcome of peripheral contraction of the vessels ; and it is further probable that the final paralysis is due to a double depressing influence upon the heart and the arterial walls, although these points have not been distinctly proved. Upon the pupil nicotine acts as a myotic, probably paralyzing the peripheral ends of the sympathetic, and almost certainly stimulating the oculo-motor nerves. The only use now made of tobacco in medicine is in the preparation of ointments for painful hemorrhoids, and in the form of a strong wash for pruritus. Its free external use is always accompanied by danger, and has caused death. The dose of tobacco is five grains (0.32 Gm.), in infusion. TOXICOLOGY. A large number of deaths have resulted from the medicinal use of tobacco, Husemann J stating that no less than ten fatal cases have been caused by tobacco enemata alone. Copland '* has seen a clyster containing half a drachm produce death. Even smoking has caused an acute fatal poisoning. Melsens affirms that the smoke of half an ounce of strong tobacco contains sufficient nicotine to prove fatal.* In the only case of criminal nicotine-poisoning on record, an unknown amount of the alkaloid was forced into the mouth of the victim, causing death in from three to five minutes.* The treatment of tobacco-poisoning consists in washing out the stomach, the free administration of ammonia and alcohol, the hypodermic use of moderate amounts of strychnine, and the employment of such external measures as dry heat, rubbings, etc. If these fail, artificial respiration should be maintained. The excessive use of tobacco produces in some persons serious nervous disturbance, such as insomnia, irritability, general feebleness ; the most characteristic symptom is a peculiar irregularity of the heart's action, often accompa- nied by distinct intermissions. Amaurosis is also sometimes present, f * For a number of cases, see Still's Therapeutics, ii. 374. t The diagnosis of tobacco amblyopia depends upon the history of the abuse of the drug, the failure to improve with optical therapeutics, and the presence of a scotoma, usu- ally oval in shape and negative in character, particularly pronounced for red and green, while the periphery of the field of vision remains unaltered. If, in addition, there is a quadrant-shaped patch of atrophic pallor in the nerve-head, the diagnosis becomes still more certain. Atrophy of the nerve may result, but in many cases there is no structural change, as the symptoms may go off in a few hours (De Schweinitz's Toxic Amblyopia). DEPRESSO-MOTORS. 269 Jonathan Hutchinson * affirms that he has seen this amaurosis recovered from by the use of opium and champagne without the abandonment of the habit of smoking. We have seen impotence as the only distinct symptom of chronic tobacco-poisoning. CONIUM. U.S. The U. S. Pharmacopoeia recognizes only the full-grown fruit, gathered while green, of Conium maculatum. The plant is umbelliferous, a native of Europe, but naturalized in the United States. The dried leaves have a strong heavy odor, increased by the addition of an alkali, and resem- bling somewhat that of mice. They are bi- or tripinnate, and very much incised. The fruits are one to two lines long, roundish-ovate, striated, with five crenated ribs on the outer sides of the easily separable halves ; the odor is that of the leaves. The active principle is Conine, a yellow- ish, oily, liquid alkaloid, highly volatile, of a strong odor similar to that of the urine of mice, and of a very acrid taste. It is freely soluble in alcohol and in ether, and slightly so in water, with which it forms a hydrate, and it coagulates albumin ; when exposed to the air it under- goes decomposition, becoming first brown, afterwards resinous ; heat accelerates the change. PHYSIOLOGICAL ACTION. Local Action. Upon the mucous mem- branes conium acts as an intense irritant. In a concentrated form it is probably fatal to all highly organized tissues, Christison having proved this to be true in regard to the muscles which are not influenced by the alkaloid taken internally. It is absorbed with great rapidity, and escapes through the system chiefly if not solely through the kidneys. Zaleski and Dragendorfl have found it abundant in the urine during the first twelve hours of the poisoning ; Prevost has seen the urine of poisoned ani- mals cause in a frog the characteristic general palsy, and in a doubtful case of poisoning this physiological test might decide the diagnosis. General Action. Full physiological doses of conium produce in man quietude, languor, and muscular weakness. After toxic doses the weakness becomes extreme, forcing the patient to the horizontal position, or causing him to stagger or fall from weakness of the legs when he at- tempts to walk. This weakness has in some cases been attended by burning in the mouth, fauces, or stomach, nausea, vomiting, and with a sense of pressure or even with severe frontal pain. As the case pro- gresses consciousness is preserved, but the paralytic symptoms become everywhere pronounced. The pupils sooner or later dilate ; * amblyopia from paralysis of accommodation, diplopia from irregular weakness of the ocular muscles, and ptosis are almost universally present, and the voice may be weakened to a whisper or lost. Sensibility is maintained to the end. Free salivation or free sweating sometimes occurs. * The experiments of Poehlmann (quoted by Husemann 1 ) show that very grave symptoms may be induced and yet the pupils remain natural ; but sooner or later they probably always dilate. 270 GENERAL REMEDIES. The circulatory phenomena are very subordinate ; though the pulse- rate may at first fall, later it becomes more rapid. Consciousness is usually preserved until the last, but may be lost in asphyxial coma some minutes before death, which results from paralysis of respiration. We have met with accounts of but four fatal cases of such character. In one, that of the mistress of Dr. Hermann Jahn, killed in a few minutes by from ten to fifteen drops of the alkaloid (quoted by Husemann), violent palpitation of the heart is said to have been a prominent symptom. The chief symptom in the second case * was universal paralysis, with total failure of voluntary movement and of the voice before consciousness was lost. Convulsive movements were present very late in the case. Sensation appeared not to be lost until death was at hand. The third case 3 was that of a medical electrician, suffering from blepharo-facial spasm, who took, beginning four hours after the last of a previous series of divided doses of a fluid extract amounting to one hundred and eighty drops, at 4.10, 4.40, and 5.15 P.M. fifty minims (one hundred and fifty in all) of " Squibb' s fluid ex- tract." The first dose produced dizziness and muscular relaxation; the second, great muscular weakness, inability to stand, and thickening of speech, without relief of the spasm ; the third, immediately, some nausea, and tremors about the chest. At 6.10 there were nausea, intense muscular weakness, partial ptosis, diplopia, and great difficulty of speech ; the pulse was 60. Shortly after this the man became unable to speak or to swallow. He made signs for electricity, and, on being asked whether the chemical or the faradic current, indicated the latter, and also the place of application of the electrodes, but was unable to hold one of the latter. Shortly after this, on being raised up, he dropped dead. A fourth case, in which a child five years old died of asphyxia preceded by coma and paralysis as the result of taking a drachm of chloroform-water containing five grains of the extract of conium, is recorded. 4 In mammals conium produces symptoms parallel with those observed in man, and it probably acts similarly upon all vertebrates. In frogs convulsions are rarely if ever present ; in birds they are occasionally so ; in mammals they are more frequent, thus, Ihmsen saw them in twelve out of twenty-three experiments ; they are chiefly clonic, but tonic spasms do occur in the hind legs. As the legs are usually affected before the arms in man, so in quadru- peds the hind extremities are usually paralyzed first. The respiration is generally much affected, and the heart continues to beat after its cessation. Spinal Cord. The exact influence of conine upon the spinal cord cannot yet be considered absolutely determined, but it is most probable that the poison has a feeble depressant action. Verigo 5 asserts that it is a powerful spinal depressant, and Pelvette and Martin- Damourette 6 say that it acts as an excitant. Lautenbach, in carefully investigating the subject, failed to obtain, under any circumstances, evidences of excite- ment of the cord ; he did succeed in producing loss of reflex activity when the nerve was protected by tying the artery in the limb, but, as in all but two of fifty-two experiments the reflexes in the protected limb were not greatly reduced until just before death, it is plain that any action upon the spinal cord is unimportant and dominated by the more powerful peripheral influences of the poison.* * The experimental results obtained by A. D. Davidson and D. Dyce Brown (Med. Times and Gazette, July, 1870), which have been cited as favoring the absurd theory of DEPRESSO-MOTORS. 271 Nervous System. Cerebrum. The retention of consciousness and all the mental faculties almost up to death in conium-poisoning shows that the drug has but little influence upon the general cerebral cortex. Ac- cording to Lautenbach, 7 the convulsions which occur in the lower animals are, however, of cerebral origin, since after division of the cord they were confined to those portions of the body situated above the section. They are probably asphyxial or of other secondary character. Nerves. In 1856 Kolliker 8 announced that the paralysis of conine- poisoning is due to paralysis of the efferent or motor nerves, a conclusion which has since been abundantly confirmed. Kolliker demonstrated that in the poisoned frog immediately after death the galvanic current applied to the nerve is powerless to induce contractions ; that if by tying the aorta access of the poison be cut off from the hind legs, there is a stage of the poisoning in which galvanic stimulation of the nerve of the front leg fails to affect the tributary muscles, although it does produce reflex contractions in the hind legs ; proof that the anterior afferent nerves and the spinal cord still retain func- tional activity after this activity has been lost in efferent nerves reached by the poison. These experimental results have been confirmed by Funke, 9 by Guttmann, 10 and by Pelvette and Martin- Damourette.* The latter observers extended the series by severing in a frog all the tissues at the upper part of the thigh except the nerve, and found that when a batrachian so prepared was poisoned with conine, after the paralysis was complete in all portions of the body to which the poison had access, after stimulations of the poisoned nerves were powerless to excite contraction in the tributary muscles, the leg which had been protected from the action of the conine upon it responded not only to irritations applied to its nerve, but also to stimuli placed upon distant portions of the body. These same observers also noted that when conine and strychnine were given simultaneously to a frog from one of whose sciatic nerves the circulation (i.e., direct access of the poison) was cut off in either of the manners spoken of, they produced by their conjoint action a com- mingling of paralysis in all other parts of the body with violent tetanic spasms in the protected leg, a commingling explainable only on the supposition that the conine paralyzed all the motor nerves to which it had access through the circulation. These experiments upon the frog have been confirmed by B. F. Lautenbach, 11 Verigo, A. W. Hofmann, Prevost, H. Schultz, 12 and Fliess," whilst Hayashi and Muto 17 have shown that, although the nerves of purely voluntary motion are acted upon in the mammal by conine, the phrenic nerve, at least in the rabbit, is even more suscep- tible to its influence. It has been generally believed that conine does not affect the sensory nerves, but the evidence appears to show that this is not correct ; only that the action upon the sensory nerves is so much less decided than that upon the motor fibres that it counts very little in the general influence of the drug. In 1875 Gubler 1 * called attention to the local influence of conium in benumb- ing the cutaneous sensibility, and Lautenbach found that when he tied the abdomi- Harley that the corpora striata are especially affected by the drug, evidently depended upon an arterial anomaly said to be common in the leg of the cat. * M. Tiryakan (Compt.-Rend., Ixxxvi. 1344) has affirmed that absolutely pure conine does not affect the nerves, but M. Prevost (Arch. Physiol. Norm, et Path., 1880, vii.) has shown that chemically pure conine bromohydrate has this action. 272 GENERAL REMEDIES. nal aorta and left axillary artery in the frog, and then injected a dose of conine into the abdomen, irritation of the leg whose nerve was not protected from the poison failed to cause reflex movements at a time when irritation of the protected nerves produced reflex actions in distant parts of the body. Muscles. All observers agree that in conium-poisoning the muscles themselves are not affected. Pupil. The pupil is generally dilated by conine ; but both Von Praag 15 and Verigo assert that the phenomenon is not constant, at least in animals. The ptosis of conium-poisoning indicates that the dilatation of the pupil is due to oculo-motor paralysis. The known action of the drug upon nerve-trunks indicates that this paralysis is peripheral, a con- clusion corroborated by the experiments of I. Hoppe 16 and of Lautenbach, each of whom found that when conine is dropped into the eye of an ani- mal it causes at first contraction, apparently due to the intense irritation, and afterwards dilatation, of the pupil. Temperature. Verigo, Von Praag, and others affirm that lethal doses of conium cause a decided lowering of temperature ; but Lauten- bach asserts that the drug decidedly increases the temperature both when in therapeutic and when in toxic doses. Circulation. No sufficient investigation has as yet been made upon the action of conine upon the circulation. Lautenbach states that the arterial pressure falls immediately after the injection of conine, and after- wards rises far above the normal point, and that the pulse is at first accelerated, but afterwards retarded. The secondary rise of pressure is probably due to asphyxia. The primary pulse-acceleration is ex- plained by the observation of Pel6nard (confirmed by Prevost) that the pneumogastrics are paralyzed before the motor nerves. Prevost finds that the heart itself is scarcely affected by the poison. SUMMARY. The chief symptom of poisoning by conium is a failure of voluntary and involuntary movement, the result of a progressive paralysis of the motor nerves. The cerebrum is not affected, hence consciousness is preserved to the last. The pupil is dilated by a periph- eral paralysis of the oculo-motor nerve. The sensory nerves and the spinal cord are probably feebly depressed. It is probable that the alka- loid does not directly act upon the circulatory apparatus except to paralyze the pneumogastrics. THERAPEUTICS. The paralytic action of conium naturally suggests its use in spasmodic affections ; and accordingly it has been tried in chorea, in paralysis agitans, in whooping-cough, and in other diseases of similar nature. Although it seems not to have met with continued favor, and is but little used, it may be employed when life is threatened by the mere convulsive actions, which it will sometimes temporarily sus- pend. In maniacal and hysterical excitement, the drug in full doses is said to produce a highly favorable condition of calm and relaxation ; and in the treatment of the insane, conium is much used by some alienists. DEPRESSO-MOTORS. 273 Conium was formerly employed to relieve pain or as a deobstruent and alterative in chronic glandular or arthritic diseases, and even in can- cer, but for these purposes has passed entirely out of vogue. The belief that it possesses alterative qualities does not seem to be well founded. ADMINISTRATION. The preparations of conium are exceedingly un- certain in their action. Conine itself is very prone to undergo sponta- neous change, although its hydrobromate is said to be a stable crystalline salt; dose, one-twentieth to one-twelfth of a grain (0.003-0.005 Gm. ). The dose of the extract is one grain (0.06 Gm.) ; of the tincture, one- half fluidrachm (2 C.c.) ; of the fluid extract (FLUIDEXTRACTUM CONII, U. S. ), one to two minims (0.06-0.12 C.c.) : all of which must be ad- ministered in increasing doses until some effect is experienced. Of these preparations the last is certainly the best. TOXICOLOGY.* Sufficient has been said about the symptoms caused by conium. After death from it no distinctive lesions are to be found, only the usual indications of death from asphyxia. The treatment con- sists in the immediate evacuation of the stomach and the exhibition of tannic acid, the tannate formed is, however, probably more or less poisonous, with the use of external heat and of internal stimulants : artificial respiration should steadily be maintained so long as there is the faintest indication of cardiac action. No physiological antidote is known ; but strychnine and other respiratory stimulants should be used. REFERENCES. PHYSOSTIGMA. i. HARNACK and WITKOWSKI . A. E. P. P., v. and x. 301. 3. HUSEMANN . . . A. E. P. P., 1878, ix. 434. 3. SCHVVEDER . . .In. Dis., Dorpat, 1889. 4. MERSON Journ. Ment. Science, Jan. 1875. 5. PAPI S. Jb., cxlii. 287. 6. FRASER Tr. R. S. Ed., xxiv. 7. LASCHKEWICH . V. A. P. A., 1866, xxxv. 294. 8. VINTSCHGAU . . W. A. W., 1867, lv., Abt. ii. 49. 9. LEVEN and LABORDE . S. Jb., cxlvi. 136. 10. ARNSTEIN and SUSTSCHINSKY . U. P. L. W., Theil ii. 86. 11. ROSSBACH and FROHLICH . Pharmakol. Un- tersuch., i. 56. 12. TACHAU A. Hk., 1865, 70. 13. WESTERMANN . . S. Jb., cxxxviii. 290. 14. SCHMIEDEBERG . Grundriss d. Arzneimittel- lehre, Leipzig, 1895, 109. VEE and LEVEN . C. R. S. B., 1865, 161. GR(JNHAGEN . . . V. A. P. A., xxx. 521. U. P. L. W., ii. 526. A. Ph., 1863. St. L. M. S. J., 1873, 367. B. G. T., Ixxxix. 85, 541. A. K. M., 1869, v. 285. 15- 16. 17- 18. 19- 20. 21. SUBBOTIN ENGELHARDT ROSENTHAL . ROEMER . 22. HlLLER . . . . 23. KEYWORTH . . 24. 25- 26. 27. LODDERSTAEDT 28. LEIBHOLZ . . . 29. BOURNEVILLE . 30. FRASER . 31. AMAGAT . 32. PAL . . . 33. SCHULTZ 34. OGIU . . . Charite-Aanalen, 1883, 235. . Gl. M. J.,n.s., 1869,1.54. B. M.J., 1876, ii. 554. M. T. G., Oct. 1864, 406. St. Bartholomew Hosp. Rep., 1879, xv. . B. K. W., 1888. . Vierteljahrsch. f. Gerichtl. Med., Berlin, 1892. . Revue Photog. d. Hdpi- taux, 1870. . Tr. R. S. Ed., 1870, 71. . J. de Th., 1876. . Cb. P., 1900-01, xiv. . A. P., 1898. . Ther. Geg. 1904. POTASSIUM BROMIDE. 1. V. A. P. A., xli. 101. 2. AMORY Physiol. and Therap. Action of Bromide of Potassium, Boston, 1872, 3. RINGER and MORSHEAD . J. A. P., xii. 71. 4. GUTTMANN . . . V. A. P. A., Ixxiv. 5. BILL A. J. M. S., July, 1868. 6. QUINCKE .... A. Ph., 1868, xxxv. 158. 7. AMORY B. M. S. J., Oct. 1868. 8. NAMIAS . . . C. R. S. B., Ixx. 282. " According to H. Hayashi and K. Muto, the minimum fatal dose of conine for rabbits, intravenously given, is between fifteen and twenty milligrammes. 18 274 GENERAL REMEDIES. REFERENCES. Continued. 9. DOVON and CAZENEUVE . l.yon M., 1889, Ix. 10. FER and HERBERT . C. R. S. B., 1891, iii. 11. EULENBERG and GUTTMANN . V. A. P. A., 1867, xli. 12. B. G. T., Ixxiii. 256. 13. DOUGALL . . . . Gl. M.J., Feb. 1893. 14. HUETTE C. R. S. B., 1850. 15. EIGNER Wien. Med. Presse, 1886, No. 25. 16. PURSER D. J. M. S., 1869, xlvii, 324. 17. SAISSON S. Jb., cxliii. 17. 18. LEWJSKV . . . . V. A. P. A., 1869, xlv. 191. 19. BARTHOLOW . . . Biomides, Providence, 1871. 20. LABORDE . . . . A. de P., 1868, 423. 21. DAMOURETTK and PKLVETTE . B. G. T., 1867, Ixxiii. 249. 22. ALBERTONI ... A. E. P. P., xv. 256. 23. SCHULZE . . . . Z. B., 1883, xix. 301. 24. SCHOUTEN .... A. Hk., 1871, xii. 97. 25. RABUTEAU .... Gaz. Hebdom., 1869. 26. CHITTENDEN and CULBERT . S. L. C. Y. 27. GILLESPIE . . . . A. J. M. S., Oct. 1870. 28. BARD P. M. T., June, 1871. 29. BERNARD .... The Clinic, Sept., 1874. 30. HONDO B. K. W., 1902, xxxix. 31. CRISAFULLI . . . G. I. M. P., 1899. AMMONIUM BROMIDE. 1. BISTROFF . . . . A. Ph., 1868, 723. 2. AMORY Bromide of Potassium and Bromide of Ammonium, Boston, 1872. SODIUM BROMIDE. 1. LABORDE .... Robin's Journal, 1868, 560. 2. CLYMER N. Y. Med. World, Oct. 1871. 3. HAMMOND. . . . N. Y. M. J., Dec. 1871. 4. DECAISNE . . . . C. R. S. B., 1870. LITHIUM BROMIDE. 1. GIBB British Asso. for the Ad- vancement of Science, 1864. 2. MITCHELL . . . . A. J. M. S., Oct. 1870. HYDROBROMIC ACID. i. REICHERT . . . . B. M. S. J., civ. 505. CALCIUM BROMIDE. i. SEE B. A. M., 1892. BROMOFORM. 1. GERHARDI .... In. Dip., Bonn, 1891. 2. KIWULL C. B. I. M., 1902. CAMPHORA MONOBROMATA. 1. BOURNEVILLH . . Prog. M., 1874. 2. LAWSON Practitioner, 1874, 1875. 3. PATHAULT .... Bromure de Camphor, Paris, 1875. 4. PETERS S. Jb., ci. 126. 5. PELLICANI . . . . S. Jb., ci. 6. ROSENTHAL . . . S. Jb., ci. 127. 7. DENEFFH .... Presse M. B., 1871. BROMOCOLL. i. BRAT T. M., xv. 1901. i. FRIEDLANDER . . T. M., 1901. BROMALIN. i. KOLLARTIS . . . S. Jb., Bd. cclxxvii. AMYL NITRITE. 1. ROHRMANN . . . Z. P. C., V. 233. 2. WOOD A. J. M. S., July, 1871. 3. AMEZ-DROZ . . . A. de P., Sept. 1873, 467. 4. GASPY V. A. P. A., Ixxv. 310. 5. ALDRIDGE . . . . West Riding Lunatic Rep., i. 187. 6. PICK C. M. W., 1873, No. 55. 7. FILEHNE .... A. G. P., ix. 478. 8. SCHULLER . . . . B. K. W., 1874, No. 25. 9. ATKINSON . . . . J. A. P., 1888, xxii. 10. LEECH L. L., 1893, i. 11. MAYER and FRIEDRICH . A. E. P. P., v. 63. 12. REICHERT . . . . N. Y. M. J., July, 1881. 13. BOCK A. E. P. P., 1898, xli. 14. HOFFMANN ... A. P., 1872, 747. 15. MANASSEIN and SASSEZKI . St. Petersburg Med. Wschr., 1879, iv. 392- 16. GAMGEE Philos. Trans., 1868, 589. 17. HOPPE-SEYLER . Z. P. C., ii. and iii. 54. 18. FOSTER B. M. J., 1874, i. 77. 19. BERGER Allg. Med. Central-Zeit- ung, May, 1871. 20. MITCHELL. . . . P. M. T., v. 553. 21. JENKS P. M. T., 1872, ii. 404. 22. GRAY Gl. M. J., 1871, 188. 23. HARE B. M. S. J., Nov. 1884. 24. MARSHALL . . . J. P., 1897, xxii. 25. SMITH L. M. R., Oct. 1873. 26. Amer. Journ. Pharmacy, 1881, 137. 27. HALDANE, MAKGILL and MAVROGORDATA . J. P., 1897, xxi. ETHYL NITRITE. 1. RICHARDSON . . Brit, and For. Med.-Chir. Rev., July, 1867. 2. LEECH Med. Chron., 1869, ix. SODIUM NITRITE. 1. REICHERT . . . . A. J. M. S., Ixxx. 180. 2. ATKINSON . . . . J. A. P., 1888, xxii. 3- L. L., 1883, ii. 945. SPIRIT OF GLONOIN. 1. FIELD B. M. J., 1880, i. 406. 2. NOER T. G., 1887, 459. 3. BRUNTONand TAIT . St. Barthol. Hosp. Rep., xxii. 140. 4. HAY ........ Pract., xxx. 422. 5. HENOCQUE . . . C. R. S. B., 1883, v. 669. 6. KORCZYNSKI . . . S. Jb., cxciii. 132. 7. HOGG Aus. M. Gaz., Oct. 1901. LOBELIA. 1. DRESER A. E. P. P., 1889, xxxvi. 2. OTT B. M.S. J., 1875; P.M. T., vi. 3. AFANASIEFF . . . L. M. R., Aug. 16, 1886. 4. NUNES S. Jb., ccxxix. GELSEMIUM. i. RINGER and MURRELL . L. L., 1876, i. 83. a. B. M. S. J., 1869, iii. 185; 1879, ci. 18. 3. TAYLOR Richmond and Louisville Med. Journ., 1875, 606. DEPRESSO-MOTORS. 275 REFERENCES. Continued. 4. BARTHOLOW . . . Pract., v. 202. 5. RJNGER and MURRELL . L. L., 1875, ii. 908. 6. OTT P. M. T.,vii. 289. 7. OTT P. M. T.,v. 691. 8. COURTRIGHT . . Cincinnati Lancet and Ob- server, 1876, 693. 1. HUSEMANN 2. COPLAND . 4. HUTCHINSON I. HUSEMANN TOBACCO. . . Handb. d. Toxicol., ii. 483. . . Diet, of Pract. Med., art. Colic. An. d'H., 1861, ii. . . M. T. G., 1884, i. 40. CONIUM. . . Die Pflanzenstoffe, 269. Edinb. Med. and Surg. Journ., 1845. 3. 4. 5. VERIGO 6. PELVETTE and 7. LAUTENBACH . 8. KOLLIKER . . . 9. FUNKE 10. GUTTMANN . 11. LAUTENBACH 12. SCHULTZ . . 13. FLIESS 14. GUBLER 15. VON PRAAG . Sanitarian, June, 1875. P. J. and Tr., xvi. 102. S. Jb., cxlix. 16.' MARTI N-DAMOURETTE . A. G. M.,6s., vi. 89. . Proc. Acad. Nat. Sciences, Phila., 1875. . V. A. P. A., x. 228. Sb. G. W., Leipzig, 1859, xi. 23. . B. K. W., 1868. . P. M. T., v. . S. Jb., cxlix. 16; cxcv. 119. A. Ph., 1882, in. B. G. T., 1875. . Journ. f. Pharmacodyn., i. 16. HOPPE ...... Nervenwirk. der Heilmit- tel, Leipzig, 1855. i. 17. HAYASHI and MUTO . A. E. P. P., xlviii. FAMILY VII. RESPIRATORY STIMULANTS AND DEPRESSANTS. FORMERLY the effect of a drug upon the respiration was universally estimated by its influence upon the rate of the respiratory movement. If this were increased the drug was spoken of as a respiratory stimulant ; if it were decreased the drug was a respiratory depressant. It is evident, however, that a drug may increase the rate and yet so diminish the extent of the respiratory movements that the amount of air taken in and out of the lungs would by it be absolutely decreased. Consequently, as was first clearly shown by H. C. Wood, the only proper test as to the effect of a drug upon the respiration is the amount of air moved by the lungs under its influence. (See Journal of Physiology, 1892.) It is worthy of note that the respiratory centre is anatomically a por- tion of the motor tract of the spinal cord ; and this seems to be carried out by its physiological relations with drugs, apparently all substances which are stimulant to the motor side of the spinal cord being centric respiratory stimulants, and those which are depressant to the motor side of the spinal cord being centric respiratory depressants. The drugs which are practically used as respiratory stimulants are ammonia, caffeine, atropine, cocaine, and strychnine. For the discussion of these drugs as individual remedies, the reader is referred to the respective articles upon them. Certain comparisons, however, may well be here instituted. H. C. Wood has found that ammonia is too fugitive in its action and too violent in its local influence upon the mucous membranes to be of practical value as a respiratory stimulant. In contrasted ex- periments atropine appeared to be the most powerful in its influence on the normal animal, but strychnine apparently had more power in assert- ing its influence against opposition. Thus, although atropine seemed to stimulate respiration more than did strychnine in the normal dog, yet in the chloralized dog the effect of strychnine was distinctly greater than that of atropine. Cocaine was found to be, as a respiratory stimulant, about half-way between atropine and strychnine. Another result reached was that it was possible to get greater effect by the consentaneous use of two drugs than by one alone. Thus, in the heavily chloralized dog, strychnine given up to the point of in- cipient tetanus could only raise the respiratory function to a certain height ; whereas injections of cocaine, without affecting the tetanoid con- 276 RESPIRATORY STIMULANTS AND DEPRESSANTS. 277 dition, would increase the air-movements perhaps to the normal or even above it. A practical deduction from this is that in all cases in which respiratory stimulation is urgently needed, at least two alkaloids should be used. In diseases such as pneumonia or suffocative bronchitis we have found that the alternate use of cocaine and strychnine gives the best results ; a dose of each remedy may be given every four hours, the patient receiving one or the other every two hours. In most respiratory diseases the collateral effects of atropine interfere very greatly with its use. On the other hand, in narcosis, especially from opium, the awaken- ing influences of the drug upon the cerebral cortex lend to it especial value ; so that usually in narcotic poisons the combination of atropine and strychnine is probably better than that of cocaine and strychnine. In all cases of severe narcosis the alkaloidal salts should be used hypodermically. ASPIDOSPERMA QUEBRACHO. Aspidosperma is the bark of an evergreen South American tree, Aspidosperma Quebracho-bianco. It contains at least six alkaloids, aspidospermine, aspidosper- matine, aspidosamine, quebrachine, hypoquebrachine, and quebrachamine. The as- pidospermine of commerce (amorphous aspidospermine) is not a pure principle, but probably contains all the alkaloids of the bark. According to Merck & Co., it consists principally of aspidosamine. PHYSIOLOGICAL ACTION. The general physiological action of aspidosperma has not been carefully enough studied to permit definite conclusions concerning its effects. It would seem that the various alkaloids have entirely different effects upon the system and in some respects are even antagonistic ; thus, Schiffer l has found that the extract of quebracho-bianco causes in the rabbit general muscular weakness with greatly diminished reflexes and increased frequency in breathing. Eloy and Huchard * found that aspidospermine, quebrachine, and hypoquebrachine produced violent convulsions, which were followed, when the dose was large, by paralysis. According to Penzoldt, 8 aspidospermine produces complete motor paralysis in the frog, with slowing of the pulse. Respiration. Penzoldt * was the first to describe the marked action of que- bracho upon the respiration. He described the effect produced in a dog as dyspnoea. In an elaborate research by Wood, Jr. , and Hoyt 5 on the effects of the com- mercial aspidospermine, it was shown that this substance produces a marked increase in both rate and depth of the respiration, the amount of air moved being augmented in some cases four hundred per cent. Secondary depression was produced only by doses large enough to kill, and in these cases the stage of diminished respiratory activity was very short. Blood. Penzoldt noted that the blood in the veins as well as in the arteries after the administration of aspidosperma had a bright red hue, and attributed the increase in the respiration to a dyspnoea brought about through the inability of the corpuscles to give up their oxygen. Wood, Jr., and Hoyt, however, believe that the change in the blood is the effect rather than the cause of the increased breathing. They were unable to find any spectroscopic change in the blood, either in the poisoned animal or when the aspidospermine was added to the blood outside of the body ; they were unable to note any diminution of the oxidation power of the aspidospermine blood towards guaiac, and finally they noted that if the animal was asphyxiated the blood assumed the venous hue all over the body. Circulation. According to Wood and Hoyt, commercial aspidospermine pro- duces a marked temporary fall of the blood-pressure, which was permanent if the 278 GENERAL REMEDIES. dose had been large. During the period of low blood-pressure, it was found that irritation of the central end of the vagus produced a rise of pressure, showing that the vaso-motor system was not paralyzed. As the pulse was not slowed, it would seem probable that aspidospermine lowers the blood-pressure by a depressant action on the cardiac muscle. Temperature. Penzoldt found that, although quebracho had but little effect on the temperature of the normal animal, in a dog with septic fever it caused marked diminution in the temperature. In clinical experiments, however, it did not seem to exercise such effect in human fevers. THERAPEUTICS. Aspidosperma has been used with asserted good results in various forms of respiratory embarrassment, as asthma, emphysema, and bronchitis. It is even stated that it will relieve urcsmic and cardiac dyspnoea. The commercial amorphous aspidospermine may be given as representing prob- ably the whole effects of the drug, in doses of from one-eighth to one-half grain (0.008-0.03 Gm.) ; the dose of the fluid extract is a quarter to one Huidrachm (1-4 C.c.) ; of the solid extract, one to three grains (0.065-0.194 Gm.). REFERENCES. ASPIDOSPERMA. 3. PENZOI.DT . . . . B. K. W., 1880, jtvii. 565. 1. SCHIFFER .... A. Ph., 1883, 249. 4- PENZOLDT . . . . B. K. W., 1879. xvi. 269. 2. ELOV and HUCHARD . A. de P., 1886, vii. 236. 5- WOOD, Jr., and HOYT . U. P. M. B., Sept. 1903. ORDER II. CARDIANTS. FAMILY I. CARDIAC STIMULANTS. THE term cardiac stimulants is here used to designate a number of medicines which, when given internally, increase the power and force of the circulation, and are used by the physician for such purposes. There are some substances which are heart-stimulants in reality, but which possess other properties in so great a degree as to overshadow their cardiac relations, and are therefore not used by the physician to affect the circulation. Such medicines are considered in connection with those powers which give them their clinical value, and are not included in the present class. Some of the members of the present class are slow in their operation, some rapid. Some produce increase in the pulse- rate, some lower it. It is evident, then, that no general indications can be laid down for their use, but that medicines so diverse must be studied individually. AMMONIA. Ammonia is a colorless, irrespirable, highly irritant gas, of a strong alkaline reaction, extremely soluble in water. It is obtained upon a large scale as a waste product in the manufacture of coal-gas, and is official in watery and alcoholic solutions and in various salts. PHYSIOLOGICAL ACTION. Local Action and Elimination. In solu- tion, ammonia is a very powerful irritant and even escharotic, producing, if kept in contact with the skin, blistering, and finally sloughing, and causing the most serious disturbances of mucous membranes which it reaches. This local action is sufficient to interfere with its absorption, and it is difficult to produce distinct constitutional symptoms with it in man. Its volatility and the extreme fugaciousness of its action would seem to indicate its elimination by the lungs ; but Feltz and Ritter * were not able to find it in the breath of poisoned animals, and Magnus has appar- ently demonstrated that it will not pass through the alveolar walls, Bence Jones 2 believed that ammonia is oxidized in the system because he found that its administration increases the acidity of the urine and also the amount of nitric acid. The theory that some portion of the ammonia is, in conjunction with carbonic acid, converted into urea is held by some physiologists.* General Action, When ammonia is injected into the veins of animals in considerable quantities, it causes violent convulsions, with remarkable disturbances of the respiration, followed, if the dose has been large enough, * This theory is of such purely physiological interest that it is dismissed with the fol- lowing key to the literature : Arch. f. Exper. Path. u. Pharm., ii., viii., x. 125, x. ii. 77; Zeitschr.f. Physiolog. Chem., ii. 29, iv. 36; Zeitschr.f. Biol., xiv. 279 280 GENERAL REMEDIES. by death in a very short time.* Billroth 8 states that the temperature falls enormously in animals poisoned with ammonia. Cerebrum and Spinal Cord. Ammonia has no effect upon the cere- brum. The tetanus produced by it in the lower animals is accompanied by great increase of the reflex activity (Funke 4 ), and is certainly of spinal origin, since it occurs below a section of the spinal cord (Lange, Formanek) and is not prevented by tying the artery of a limb (Funke). It would therefore appear that the toxic dose of ammonia is a powerful stimulant to the motor spinal cord. Upon the sensory cord it seems to have little or no action. Respiration. The intravenous injection of ammonia causes in the animal a great acceleration of the breathing, which after large doses may be preceded by temporary arrest of respiration in expiration. The cause of this arrest is uncertain, Funke observing it after section of the vagi, while in the experiments of Lange it was always absent. Section of the vagi, however, does not interfere with the increased rapidity of the breathing, the change from the deep breathing of divided vagi to the extremely rapid respiration of ammonia-poisoning being colossal (Funke). Further, Binz 5 has found that the increase of the respiratory rate in chlo- ralized rabbits is accompanied by a great increase in the amount of air breathed. Ammonia is, therefore, a powerful direct stimulant to the respiratory centres. Circulation. The intravenous injection of ammonia both in normal and curarized animals is followed by an immediate fall in the blood- pressure, which gives way to a very decided rise if the dose has not been too large. If, on the other hand, an overwhelming amount of ammonia or one of its salts is employed, the fall of blood-pressure continues until the arrest of the heart in diastole. When the dose has been sufficient, this cardiac arrest is immediate. In the experiments of Lange and of Forma- nek, the primary fall of blood-pressure occurred after section of the spinal cord, also after ligation of the aorta ; without doubt it is due to the direct action of the concentrated drug upon the heart. The rise of pressure which is the characteristic effect of the moderate dose of ammonia must be due to a stimulating action upon the heart or upon the peripheral vessels, since, according to both Lange and Formanek, it occurs after previous section of the cord. The experiments of Formanek, in which it was shown that if the thoracic aorta were temporarly ligated, ammonia still distinctly elevated the blood-pressure, demonstrate that the drug acts upon the heart directly, but it is probable that the muscle-fibres of the arterioles are also affected ; so that the conclusion must be reached that ammonia is a primary stimulant both to the heart and to the muscle-fibres of the arterioles, although when in overdose it is a paralyzant to both heart and arterioles. * F. Lange (Archiv f. Experiment. Path. u. Pharm., ii., 368), V. Feltz et E. Ritter (Journal de r Anatomic et de la Physiol., 1874, 326), and Funke (Pfiuger's Archiv, ix. 426). CARDIAC STIMULANTS. 281 In regard to the action of ammonia upon the pulse-rate, the evidence is somewhat discordant. All observers seem to be in accord that the pulse is for a time increased in rate, which increase in rate, according to Lange, does not occur after section of the spinal cord, and according to Formanek, 7 is prevented by extirpation of the stellate ganglion of the sympathetic. The increased rate appears, therefore, to be due to a stimu- lating influence upon the cardiac accelerators. Formanek has found that at the time of the highest pressure there is marked slowing of the pulse, which is prevented by section of the vagi, and which he concludes, there- fore, to be due to stimulated inhibition.* According to Feltz and Ritter, the blood of a dog killed by ammonia is incapable of absorbing oxygen, and contains much less than the normal amount of gas, whilst the red disks resist the action of acetic acid to a markedly abnormal degree. THERAPEUTICS. Externally, ammonia is much used as a constituent of irritating liniments, and, on account of its efficiency and cheapness, is very valuable. By inverting a watch-glass full of the stronger water of ammonia upon the skin, a blister may be raised in a very few minutes ; but, as the effects of the application are apt to be severe, the use of it is justifiable only under rare circumstances. Internally, the chief indication for the use of ammonia is failure of tlie heart ' s action. The more sudden and purely functional this is the more efficacious is the remedy, which should in such cases be not only administered by the stomach, but also inhaled through the nostrils, as the local action of the irritant vapor upon the mucous membrane has a very arousing influence. When the failure of the circulation depends upon a slow and persistent cause, as in adynamic fevers, ammonia is not generally useful, but may be employed as an adjuvant to alcohol in the crisis of the disorder. As a stimulant, ammonia may be useful in poison- ing by venomous serpents, but the statements that have been made that it is antidotal to venom have no foundation. (For detailed discussion, see the tenth edition of this treatise. ) In failure of the heart from anaesthetics f or other poisons, animal or vegetable, in stidden collapse in disease, as is sometimes seen in the ex- anthemata, in cholera, and not rarely in pernicious malarial fever, \ or after surgical operations or injuries, hypodermic injections of ammonia have seemed to be in a number of reported cases of very great service. * Formanek believes that the vagi are directly stimulated, but his tabulated experi- ments seem to show that the reduction of the pulse-rate is inconstant, and it is possi- ble that it is a secondary result due to high blood-pressure. t Ringer (Practitioner, xxvii.) finds that ammonia added to the frog's heart depressed with chloroform, iodoform, etc., has a pronounced effect in re-establishing its action. t See Zuelzer (Revue de Therap. Med.-Chir., July i, 1872). ? See Indian Med. Gaz., June i, 1872; Med. Times and Gaz., Nov. 1872; Chicago Med. Journ., 1872; London Med. Record, 1873, i. ; L'Abeille Med., Aug. 1874; Berlin. Klin. Wochenschrift, No. 24, 1874; Archives Gen., 1874, ii. ; Lancet, 1879, ii. 158; New York Med. Rec., xv. 532. 282 GENERAL REMEDIES. It is probable that in many of these instances the injections have largely acted as local irritants, reflexly exciting the heart. From fifteen to twenty-five minims of the aqua ammoniae fortior, diluted with four times its bulk of water, should be thrown directly into a vein of the arm, and repeated in fifteen minutes if necessary. Ammonia appears to have a tendency to act upon the mucous mem- brane of the lungs, and its salts are used as stimulant expectorants in adynamic pectoral inflammations, as in typhoid pneumonia. As a stimu- lant antacid, it is frequently of service in cases of headache from gastric acidity. TOXICOLOGY. Ingested in large amount, ammonia acts as a violent corrosive poison, the symptoms of its constitutional action being en- tirely lost in those caused by its local influence. Violent pain in the mouth and fauces, in some cases intense burning in the larynx with sense of choking and great difficulty of breathing and rapid asphyxia ; more commonly violent abdominal pain, vomiting, bloody purging, and other symptoms of gastro-enteritis, mark its escharotic effects. Death from redema of the larynx may occur within five minutes. More usually the fatal result is wrought out more slowly, with collapse and sometimes con- vulsions secondary upon the local effects'. In some cases symptoms of impending suffocation, resulting in death from asphyxia, have occurred, and at the autopsy intense redness and congestion of the bronchial mucous membrane have been present, due no doubt to the irritant's having found its way into the bronchi. The intellect may be clear to the very moment of death, or stupor, and finally coma, may be developed. If the victim survive for a few hours, recovery usually occurs, but the convalescence is commonly protracted, and permanent ill-health may result from the de- structive lesions produced by the poison. These lesions are to be found not only in the respiratory and gastro-intestinal tracts, but also in the kidneys. 8 The treatment of poisoning by ammonia consists in the neu- tralization of the ammonia as soon as possible by vinegar or other dilute acid, and the meeting of indications as they arise. If the oedema of the glottis be threatening, tracheotomy should at once be performed. ADMINISTRATION. There are four official preparations of uncombined ammonia, namely, AQUA AMMONITE FORTIOR, U. S. (Stronger Water of Ammonia), contains twenty-eight per cent, of gaseous ammonia, sp. gr. 0.897 ; AQUA AMMONITE, U. S. (Water of Ammonia), ten per cent., sp. gr. 0.958; SPIRITUS AMMONITE, U. S. (Spirit of Ammonia); and SPIRITUS AMMONITE AROMATICUS, U. S., or Aromatic Spirit of Harts- horn. To reduce the strength of the first of these preparations to that of the second or third requires the addition of one and eight-tenths measures of water. The aromatic spirit contains both ammonia and its carbonate. For hypodermic use a water of ammonia or a solution of the ammonium carbonate is to be preferred. Dose of the water or either spirit, twenty-five drops to a teaspoonful (1.5-3 C.c. ), properly diluted. Ammonium Carbonate (AMMONII CARBONAS U. S.), is the best CARDIAC STIMULANTS. 283 preparation for continuous use. It occurs in white, translucent, fibrous masses, which on exposure become opaque and efflorescent, parting with ammonia and passing into a bicarbonate. It is soluble in four and a half times its weight of water, and may be given in solution in doses of from five to ten grains (0.3-0.6 Gm. ), repeated pro re nata. The effects of a single dose upon the system probably do not last over one hour. Ammonium Nitrate (AMMONii NITRAS, U. S., 1890) is used for the preparation of nitrous oxide ; Ammonium Chloride (AMMONII CHLO- RIDUM, U. S. ) will be considered under Expectorants ; Ammonium Iodide (AMMONII IODIDUM, U. S. ) under Alteratives. CAMPHORA CAMPHOR. U. S. Camphor is obtained in China, Japan, Cochin China, the Sunda Islands, etc., by boiling the comminuted wood of the root, stem, and branches of the Laurus Camphora, and skimming off the camphor as it rises to the surface of the water when cooled. This camphor is then partially purified by sublimation, and comes into commerce as crude cam- phor, which occurs in grains of a whitish or pinkish color, and is finally purified by sublimation with lime.* Refined camphor (or, as it is commonly called, camphor) occurs in disks or hemispherical bowl-like translucent masses, of a fibrous or granu- lar fracture. Its taste is hot and peculiar ; its odor very strong and char- acteristic ; it is volatile, inflammable, tough, but readily pulverized on the addition of a few drops of alcohol ; melts at 347 F. ; is soluble in one thousand parts of cold water, f in one part of strong alcohol, and still more soluble in chloroform ; thrown upon water, a granule of camphor floats, and exhibits a rotatory movement. PHYSIOLOGICAL ACTION. Local Action, Absorption, and Elimina- tion. Camphor, though primarily a local irritant and stimulant, probably has a narcotic action on nerve-endings in the mucous membrane, in this way relieving intestinal spasm. It is slowly absorbed and in great part or altogether oxidized in the organism, probably changed first into cam- pherol, and being excreted in the urine as campho-glycuronic acid, and amido-glycuronic acid (Schmiedeberg and Meyer 1 ). General Action. The ordinary dose of camphor (five to ten grains) produces when taken internally a feeling of warmth in the stomach, with in some cases a sense of slight exhilaration 'and quietness, and some, but usually not a pronounced, acceleration of the pulse. In doses of from twenty to thirty grains it causes lassitude, giddiness, lessening of the * Borneo camphor, yielded by the Dryobalanops Camphora, is very highly valued in the East, but does not reach this country. Stockman has found that both it and the Ngai camphor of China act on the organism like camphor. See Pellicani. 17 A number of other camphors, such as Camphor- Cymol Bornylamin, Amido- Camphor, Campherol, have been examined by various investigators, and found to resemble true camphor very closely in their physiological action. t By rubbing the camphor up with magnesia in water, the latter can be made to take up much more than one part in one thousand. 284 GENERAL REMEDIES. pulse-rate, preceded in some cases by a brief period of excitement. After poisonous doses (thirty to sixty grains) the symptoms, which are toler- ably uniform, are as follows : faintness, headache, vertigo, confusion of ideas, burning pain in the stomach, dyspnoea, delirium, spasms deepening into violent convulsions, coma, with complete insensibility and absence of all reflexes ; the pulse, at first full and quick, later becomes small and sometimes slow ; the skin is cool, pale or livid, generally bedewed with sweat. Glycosuria has been noted by Stockman. Sudden unconscious- ness, with or without convulsions, has been in some instances the first manifestation of the action of the poison, and in any individual case many of the symptoms detailed above may be wanting. Upon the lowest forms of life camphor acts as a very feeble germicide ; to the articulates it is a violent poison ; in the frog it produces stupor with primary- paral- ysis ; in birds, according to Menghini, it causes stupor or delirium, with epileptiform seizures ; and in mammals vomiting, violent convulsions, coma, and death, appar- ently from asphyxia, follow its ingestion. Nervous System. The only evidences that the small dose of camphor has any influence upon the intellectual centres is the slight quietness which it sometimes produces in man. The convulsions which are caused by the toxic dose are certainly of cerebral origin, since C. Weidemann, 2 Hoff- mann (quoted by Weidemann), and Gottlieb* have shown that they do not spread to the lower segment of the body after section of the cord ; and R. Stockman 4 has found that in the rabbit they do not occur after removal of the cerebral cortex. The convulsions may be the outcome of irritation of the psycho-motor centres in the cerebral cortex, but the possible methods of production of epileptiform convulsions are not suffi- ciently worked out to warrant positive conclusions. That the toxic dose finally produces cerebral paralysis is shown by the coma which is so fre- quent a symptom of camphor- poisoning. Spinal Cord and Nerves. The action of small doses of camphor upon the spinal cord is still unsettled, but it is probable that in therapeutic doses the drug acts as a stimulant. The toxic dose of camphor depresses the spinal cord, and, as was first shown by Weidemann, 2 later the motor nerve-trunk, beginning with their peripheral endings. In the frog the regular course of paralytic symptoms produced by camphor are, first, loss of voluntary movement, the reflexes being intact ; second, loss of reflexes, the muscles still responding when the motor nerves are stimulated ; third, loss of function in the motor nerves, the muscles responding still to direct stimuli. It is probable that the loss of the power of voluntary movements is due to paralysis of the psycho-motor centres, although it may be the outcome of some interruption of the power of the cord to carry impulses from these centres to the motor cells in the cord. According to the experiments of Binz, 6 Grisar, 7 and Gottlieb, small doses of camphor increase reflex activity by a direct action upon the motor side of the spinal cord, but the experiments of Stockman 4 appear to have yielded a different result, so that there is uncertainty in the matter. CARDIAC STIMULANTS. 285 Muscles Upon the muscles themselves camphor exerts a very feeble influence. Locally applied to the muscles in the form of solution or vapor, a notable effect is produced, but in general poisoning this is not evident. In experiments of Cesare Rossi, 8 made with a Mosso's ergograph, camphor given internally seemed to distinctly increase the energy and endurance of the human muscle, but in other cases it entirely failed to manifest any such power ; so that if it have any direct action as a muscle stimulant, such action must be feeble and uncertain. According to the experiments of Meyer, 5 the absence of convulsions in camphor- poisoning in the frog cannot be explained by paralysis of the spinal cord or motor nerves, since before these conditions are developed the brain is profoundly affected ; nor does the local application of camphor to the brain in the frog produce convul- sions. Meyer believes, with probable correctness, that the absence of convulsions is due to the rudimentary development of the cerebral system in the frog. Respiration. According to Stockman and Binz, 9 camphor increases the rate of respiration greatly ; and Lewin 10 found that the amount of respired air moved was markedly increased in the rabbit by it. It would appear, therefore, that the moderate dose of camphor is a respiratory stimulant, and as there is probably some stimulation of the cord by the drug, the inference is that such stimulation is due to an action upon the respiratory centres. The asphyxia of advancing camphor- poisoning indicates that the respiratory centres finally share with the other motor centres of the spinal cord the paralyzing influence of the overwhelming dose of the drug. Circulation. Although there has been much positiveness of statement in regard to the action of camphor upon the circulation in various works of pharmacology, our knowledge of its action is really incomplete and uncertain. It has been directly shown by the concurrent experimental results of Heubner " and Harnack and Wittkowski, 12 Weidemann, Umpfen- bach, 1J Maki, u and Stockman that the drug decreases the rate and in- creases the energy of the contractions of the isolated frog's heart,* and it may be considered established that upon the frog's heart camphor acts as a stimulant. The statement of Heubner, that camphor will re-excite the movements of the frog's heart when arrested by muscarin, has been abundantly confirmed. Harnack and AVittkowski found that the atropine increases the contraction-rate of the cam- phorized heart, that stimulation neither of the vagus nor of the sinus are able to arrest cardiac contraction, and that muscle paralyzants like the soluble copper salts and apomorphine do stop the heart's beating. f Bohme M found that camphor is capable of causing the heart arrested by chloral to recommence beating. The question whether the drug acts upon the muscle or upon the ganglia is still unan- swered, and certain actions of camphor upon the frog's heart are not easily explained. * The contrary results of Alex. Lewin were probably due to the use of overwhelming: doses, in such doses camphor certainly being a cardiac depressant. t In repeating Harnack and Wittkowski's experiments Stockman failed to get satisfactory results. 286 GENERAL REMEDIES. Thus, in Maki's experiments with Williams's apparatus, some minutes after the application of the camphor the blood-pressure fell below the norm, to rise very shortly under very powerful pulsations of the heart. Then the blood-pressure would sink, to rise again in a little while, and again to sink. This alternation would occur several times. These experiments of Maki have apparently not been confirmed, but are especially interesting in relation with the periodic rise and fall of blood-pressure which has been noted in mammals by Weidemann and others. The action of camphor upon the heart of the frog indicates that it is a cardiac stimulant in the mammal, but the direct positive proof of this is not at present satisfactory. At times camphor, when injected in small doses directly into the circulation of a mammal, increases the arterial pressure, but this increase is never constant or persistent and is often absent, the characteristic effect of the camphor being depression of the arterial pressure. It is of course possible for a drug to stimulate the heart and yet so widen out the blood-paths as to produce no rise of the arterial pressure, and Stockman reached the conclusion that camphor depresses the vaso-motor centres and probably produces a vascular dilatation which masks the increased action of the heart, a conclusion which is in accord with the statements of both Maki and Lewin, that in chloralized animals, when the vaso-motor centres are deeply paralyzed, camphor elevates the pressure ; but in Lewin' s experiments, when the action of the chloral was profound, the pressure failed to rise under the influence of the camphor ; and H. Winterberg 15 determined that camphor does not raise the arterial pressure when chloral is given sufficiently to certainly paralyze the vaso-motor centres. Further, all attempts to demonstrate the stimulating action of camphor upon the more or less isolated heart of the mammal have so far yielded contradictory results. Gottlieb obtained an apparent stimulating influence from the camphor, but Winter- berg, using the method of Langendorff for cardiac isolation, failed entirely, except in two experiments, to get any evidence whatever of cardiac stimulation. Selig- man 21 although showing in some cases stimulation, was unable to demonstrate any constant influence on the normal mammalian heart but found that camphor was ca- pable of restoring coordinate beats to a heart thrown into fibrillary contraction.* The primary rise of arterial pressure sometimes produced by camphor is probably due to cardiac stimulation. Depression of the blood-vessel system is the characteristic effect of the full dose of the drug. It is still uncertain how far this action is centric or peripheral. Various observers have noted that the local application of camphor causes local hyperaemia, believed to be due to a direct action of the camphor upon the blood- vessels, and it seems probable that Stockman is correct in believing that the fall of pressure is due to a centric action on the vaso-motor centres, , and that Winterberg is also correct in believing that the chief action of * Rosenstein, in his research, concluded that camphor has a stimulating influence upon the heart, though a very fleeting one. With borneol, Pellicani " obtained fall or periodical oscillations of pressure. Lewin was only able to obtain a fall of the arterial pressure, and Gottlieb reached the conclusion that probably camphor increases the capability of the heart to respond to stimuli, so that, whilst the normal systole is not altered, in pathological condition there is such an increased excitability that the heart is capable of great efforts. CARDIAC STIMULANTS. 287 camphor is peripheral. In other words, it is probable that camphor depresses both the walls of the arterioles and the vaso-motor centres. As is shown by Weidemann, during the convulsive stage of camphor-poisoning there is a marked rise of the arterial pressure, which, however, may be prevented in great measure by curarization and artificial respiration, and is therefore evidently chiefly due to the convulsions and disturbances of breathing. In the curarized animal Weidemann found that camphor caused remarkable periodic alternating elevation and fall of the arterial pressure, which are prevented by section either of the cord or vagi, but whose nature Weidemann did not determine. Stockman found that, at least with Borneo camphor, such action is extremely inconstant, and Winterberg has demonstrated that when the curarization is complete the oscillatory phenomena are absent, so that they are probably due to obscure spasmodic move- ments. Sexual Function. Camphor has been largely praised by some med- ical practitioners as a sexual stimulant, by others as a sexual depressant. Almost invariably, however, it has been administered in combination with other more potent drugs, to which any apparent influence of the remedy has probably been due. There is certainly no experimental and appar- ently no sufficient clinical reason for believing that camphor acts more de- cidedly upon the sexual centres of the spinal cord than it does upon other nerve-cells of the same region. SUMMARY. Camphor causes convulsions through its effect upon the brain ; the therapeutic dose probably has a quieting influence on the cerebral cortex. In large doses it acts as a depressant to the motor cord, -whilst the small doses are probably stimulant. It is a stimulant to the respiratory centres, and probably to the cardiac mus- cle, but does not greatly raise the blood-pressure on account of its widening the blood-vessels, probably both peripherally and centrally. THERAPEUTICS. Camphor is very frequently given internally as an an- tispasmodic, to quiet restlessness and ' ' nervousness. " It is also employed in certain painful affections seen in those persons who are especially liable to the condition of the nervous system just mentioned : thus, it is often useful in nervous headaches and dysmenorrhcea. Indeed, in the latter disease, either alone or combined with opium in bad cases, it is a most valuable drug, but must be given freely. In diarrhoea not dependent upon inflammation, in nervous diarrhoea, in cholerine, and even to some extent in cholera, camphor is an efficient remedy, allaying intestinal pain and spasm, and also checking intestinal secretion. It enters into a large proportion of the popular cholera-mixtures. In sudden cardiac failure and in adynamic conditions it has been largely used, especially in Germany ; but whilst it probably has distinct value when given hypodermi- cally, it ought not to be relied upon to the exclusion of more potent drugs. According to Schilling, thirty grains a day may be given hypodermically in the profound adynamia of acute endocarditis, typhoid fever, pneumonia, etc. , with the happiest result. The use of large doses of camphor in 288 GENERAL REMEDIES. abnormal sexual excitement, and in chordce, has about passed out of vogue, which also is true of its employment in severe convulsive disorders such as whooping-cough, epilepsy, and puerperal convulsions.. In hysterical convulsions, as in other phenomena of similar origin, camphor is a useful antispasmodic. Externally, camphor is much used in liniments as a stimulant applica- tion for bruises, sprains, etc. TOXICOLOGY. Although camphor has in many cases produced very alarming symptoms, over two hundred grains of it have been taken with- out permanent result, and the recorded fatal poisonings are very few. The only ones known to us are adult, quantity unknown ; 18 sickly infant, ten grains ; 19 child two years old, unknown amount ; M fatal abortion produced by three drachms.* ADMINISTRATION. Large doses (ten to fifteen grains) of camphor are best administered in emulsion, because when given in this way, being very finely subdivided, they create as little irritation as possible, and are rapidly absorbed ; smaller doses may be given in pill. For hypodermic use a ten per cent, solution in olive oil should be preferred. As an anti- spasmodic, the Camphor Water (AQUA CAMPHORS, eight-tenths of one per cent. , U. S. ) is usually preferred ; its dose is half a fluidounce to two fluidounces (15-60 C.c. ), but, when a decided effect is desired, the Spirit of Camphor (SPIRITUS CAMPHORS ten per cent. , U. S. ) is more effec- tive ; its dose is fifteen to thirty minims (1-2 C.c.). For external use are official the LINIMENTUM CAMPHORS (camphor one part, cotton-seed oil four parts, U. S. ) and the LINIMENTUM SAPONIS, or Soap Liniment, U. S. , a mild liniment very popular either by itself or as the basis of more stimulating preparations. The Oil of Camphor occurs in our market as a reddish or yellowish-brown liquid, having a strong odor of camphor, and a hot, camphoraceous taste. It con- tains camphor in solution, and is probably equivalent to it in physiological action, except that it is locally more stimulating, and preferable in intestinal disorders. Dose, five to ten drops (0.3-0.6 C.c.). ACIDUM CAMPHORICUM, U. S. Camphoric Acid is produced by boiling cam- phor with concentrated nitric acid. It occurs in small white, acicular or scaly crys- tals, free from odor, of a feebly acid taste, sparingly soluble in cold, freely in hot, water, also in alcohol, ether, and fatty oils. It was originally proposed by Fiir- bringer J as an antiseptic of practical value for the disinfection of the intestinal canal, and in the treatment of tuberculosis and ammoniacal cystitis : as first noticed by Wittkowski it is a very valuable antihydrotic in the night-sweats of phthisis ; how it acts in these cases has not been determined. Max Reichert, Niesel, and other physicians have found it very serviceable as a local application in the treat- ment of tubercular and other catarrhs of the upper and lower air-passages. According to Bohland,* camphoric acid is rapidly eliminated, the whole of a * Cases, Edinburgh Med. Journal, May, 1873 ; The Clinic, March, 1873 ; Wiener Medizinische Presse, 1874, 258; Berlin. Klin. Wochens., Sept. 1873-74; Trans. Land. Clin. Soc., 1874, 27; London Lancet, 1876, ii. 71; British Med. Journ., Feb. 1875, 1877, i. 607, Sept. 1895; June, 1896; St. Petersburg Med. Wochens., 1897, xiv. CARDIAC STIMULANTS. 289 single dose escaping from the kidneys in the course of five hours unaltered. In cys- titis, fifteen grains ( i Gm. ) may be given three or four times a day ; for night- sweats, fifteen to thirty grains may be administered at bedtime, or, when the sweat occurs late in the night, the dose may be divided, the patient being wakened to take the last dose after midnight. Gastric irritation and even vomiting have been noted after thirty grains, and Niesel saw severe renal irritation in a patient who had taken in four weeks fifty grammes. Oxycamphor This oxidation product of camphor is a white, crystalline powder, soluble to two per cent, in cold water ; is alleged to have a calmative action upon the respiratory centres whilst strengthening the cardiac muscle and the central and peripheral vaso-motor nervous system. It has been used with asserted excellent results in dyspnoea from cardiac weakness, and from tubercular and other chronic diseases of the lungs. Dose, eight to sixteen grains (0.5 to i Gm.) two or three times a day. (See M. R.,i897, 1899, 1901). ALCOHOL. U. S. ALCOHOL ABSOLUTUM, U. S. (Absolute Alcohol), i. 5 by mouth) ; Phila. Med. Times, xiii. 328 (a decoction of aconite, amount unknown, Tinct. digitalis in drachm and half-drachm doses, by mouth). In a successful case treated by Elliot (Lancet, 1878, ii. 917) amyl nitrite freely inhaled seemed to do great good : a fluidounce of a concentrated aconite liniment was thought to have been taken. Ammonia injections were unsuccessful in a case re- ported in the Australian Med.Jotirn., 1879, i. 283. G. H. Tuttle (Boston Med. and Surg. Journ., 1891, cxxv.) has reported recovery after seven and a half drachms of the tinct- ure, under the free hypodermic use of brandy and digitalis, the same remedies with tincture of nux vomica being given internally, and auxiliary measures used. CARDIAC DEPRESSANTS. 385 should be used hypodermically with great boldness, tempered with cau- tion. Ammonia may be injected into the veins, if it be found practicable. The patient must be kept upon the back, with the feet a little higher than the head, and external heat be used freely to maintain temperature. La- borde and Duquesnel affirm that in the lower animals death after a usu- ally fatal dose of aconitine can be prevented by artificial respiration ; and in a case of human poisoning, if the heart's action were at all sustained, and the respiration failing, Sylvester's method or forced artificial respira- tion might be resorted to. ADMINISTRATION. Aconite is never used in substance. Dose of tincture of aconite (TINCTURA ACONITI ten per cent., U. S.), three to fifteen minims (o. 18-1.0 C.c. ), repeated every one to three hours pro re nata, its effects being always watched. Fleming 1 s tincture is a stronger preparation (ten and a half ounces to a pint). Dose of extract, one-quarter to three-quarters of a grain (0.016-0.049 Gm. ); of fluid ex- tract (FLUIDEXTRACTUM ACONITI, U. S. ), one to two minims (0.06- o. 1 2 C. c. ) . The tincture or the fluid extract of aconite is very frequently added to stimulating and anodyne liniments. Owing to its varying purity and composition and its extraordinary activity, aconitine should rarely be used in practical medicine. The dose of the official ACONITINE is given in the U. S. Pharmacopoeia as TSTS grain (0.00015 Gm. ). ACIDUM HYDROCYANICUM HYDROCYANIC ACID. Pure hydrocyanic acid is a colorless, transparent, volatile, inflamma- ble liquid, giving rise to giddiness and headache when smelled, and having, it is said, a burning, bitter taste. So poisonous is it that when inhaled it causes death, and it must be handled with the greatest cau- tion : smelling and tasting it are excessively dangerous proceedings. It is, indeed, an imperative rule that no one should experiment with an- hydrous prussic acid alone, or under any circumstances in summer, or in a warm room, or in an apartment whose open windows and doors do not admit of a free draught of air. The chemist Scheele, the discoverer of prussic acid, is believed to have been killed by the inhalation of the fumes of this material, whose poisonous properties were first pointed out by the Berlin apothecary Schrader in 1803. The anhydrous acid is soluble in water and in alcohol, but is never kept in the shops, and is not official. Hydrocyanic acid of common medical parlance is the official Dilute Hydrocyanic Acid (ACIDUM HYDROCYANICUM DILUTUM, U. S. ), a color- less, watery solution, containing two per cent, of the anhydrous acid. Its odor and taste are the familiar ones of peach-kernels and bitter almonds ; its reaction is faintly acid. As it has a great tendency to undergo spon- taneous decomposition, especially under the influence of light, it should be kept in well-stopped, dark-colored bottles. PHYSIOLOGICAL ACTION. Local Action. Absorption and Elimina- tion. Hydrocyanic acid appears to be free from irritant properties, but 25 3 86 GENERAL REMEDIES. is a universal depressant poison, capable, when in sufficient amount, of paralyzing all higher tissues, and having, when applied locally, an espe- cially powerful influence upon sensory nerve-endings. It is absorbed with almost instantaneous rapidity through all mucous membranes. Con- cerning its fate in the body we have no knowledge except that it is either destroyed or eliminated with the greatest rapidity, so that its action is extremely fugacious. General Action. The symptoms produced by prussic acid in man are so rapid in development and course that usually the patient is dead or convalescent before seen by the physician. The ordinary therapeutic dose produces no distinct manifestations ; after the toxic dose the symp- toms come on suddenly. In a moment or two the individual falls to the ground insensible and convulsed, the respirations arrested or occurring at long intervals, the eyes salient, the pupil dilated, the mouth covered with bloody froth. If the dose be sufficiently large, death may occur in three or four minutes ; if less has been taken, deep insensibility, tetanic or clonic convulsions, dilated pupils, a bloated countenance, cyanosed surface, set jaws, and irregular respiration constitute the chief symp- toms. The breathing is mostly convulsive, with deep, forcible expira- tions, but in some cases it has been stertorous. Death results from as- phyxia. After small toxic but not lethal doses of prussic acid, giddiness, lightness of the head, nausea, a quick pulse, and muscular weakness are the chief symptoms. After a full dose of the strong anhydrous prussic acid, the lower animal gasps once or twice, and then instantly falls in a tetanic or clonic convulsion, or else drops mo- tionless and powerless upon its side, heart and lungs ceasing almost at once. After a smaller toxic dose the signs of asphyxia at once manifest themselves, and grow more and more intense, until they end in total arrest of respiration. The heart beats irregularly, often at first slowly and strongly, with intervals of suspension of movement, but always becoming weaker and more rapid in its action, until, after the breathing has ceased, its efforts gradually die away. Ordinarily, three distinct stages are apparent : a first, very brief one, of difficult respiration, slow cardiac action, and disturbed cerebration ; a second, convulsive stage, with dilated pupils, violent convulsions, unconsciousness, loud cries, vomiting, often spasmodic urina- tion and defecation, erections, etc. ; and a third period, of asphyxia, collapse, and paralysis, sometimes interrupted by partial or even general spasms. The slow form of the poisoning follows the exhibition of the poison in an amount just sufficient to kill. After the ingestion of such a dose, no phenomena are offered for some seconds ; then the breathing becomes labored and the pulse slow and full. The animal perhaps cries out, and muscular tremblings rapidly grow into clonic and tonic convulsions, which continue at intervals until the third stage that of col- lapse is developed. When the third stage is developed, the anaesthesia is marked, affecting first the hind legs, but finally spreading to all parts of the body, and even being complete in the widely dilated pupil. Death finally results from failure of respiration. Recovery may occur even after the conjunctiva has lost its sensibility ; the return to life by a subsidence of the symptoms is usually rapid, so that generally in from one-half to three-quarters of an hour the animal will be eating as though nothing had happened. Coullon, however, noted persistence of paralysis, in some cases, for days. CARDIAC DEPRESSANTS. 387 Blood. Prussic acid has a very decided influence upon the blood, which may after death be found uniformly of a bright arterial or a deep venous hue. F. B. Vietz, 1 E. L. Schubarth, 2 J. F. Sobernheim, 3 Coze,* Claude Bernard, and others all affirm that when an animal is killed abruptly with hydrocyanic acid the blood in the veins and right heart is of a bright arterial hue. In 1844, how- ever, J. R. Bischoff * affirmed that in man and in mammals killed with prussic acid nothing could be found but dark venous blood in either artery or vein, an ob- servation which has been since confirmed. The explanation of these discrepancies was first given by W. Preyer, 6 and subsequently confirmed by Carl Gaethgens ; T directly after the administration of the poison, in the mammal the venous blood be- comes almost immediately of a bright arterial hue, which, however, rapidly darkens until all the blood of the body is venous. If the mammal dies suddenly from car- diac paralysis during the first stage of the poisoning, this excessive arterialization may be found after death, and in cold-blooded animals, the bright color persists for many hours (Preyer). If, however, life is more prolonged, the blood grows dark. According to Gaethgens, the scarlet venous blood of the first stage of the poisoning shows clearly the absorption bands of oxyhaemoglobin under the spec- troscope, whilst Preyer has demonstrated that the dark blood of the advanced stages of the poisoning gives only the lines of reduced haemoglobin. There has been much discussion as to the cause of these changes in the blood. Hoppe-Seyler believes that the scarlet venous blood of the first stage of the poison- ing is due to the suspension of the power of the red blood-corpuscles to yield up their oxygen. Carl Gaethgens determined that during this first stage there is a limited elimination of both carbonic acid and oxygen from the lungs. At the same time the percentage of carbonic acid in the expired air is less, and that of oxygen is greater, than in the normal air, showing that in some way the conversion of oxygen into carbonic acid is interfered with. It is clear that during the first stage of prussic acid poisoning oxidation is arrested. That this arrest of oxidation is due, as believed by Hoppe-Seyler, to the action of the poison upon the red blood-cor- puscles seems to us improbable, since it has been proved by Gaethgens that when the experiments are prolonged there comes a time when more than the normal amount of carbonic acid is eliminated, a fact in accord with the excessive carboni- zation of the blood which occurs in the later stages of protracted hydrocyanic acid poisoning. In the advanced stages of the poisoning the red corpuscles must, there- fore, be functionally very active. As first discovered by Hoppe-Seyler, 8 and afterwards confirmed by Preyer, when hydrocyanic acid is added to blood outside of the body there is produced a new substance giving rise to new spectroscopic lines and without ozonizing power, the so-called cyanohesmoglobin. It has been determined by Schonbein that hydro- cyanic acid destroys the ozonizing power of living vegetables, such as roots, fungi, etc. , and also of blood to which it is added outside of the body. In regard to the latter fact some confirmation has been afforded by Harley, who found that the dark blood taken forty-eight hours after death from the subject of prussic acid poisoning, shaken with air, and allowed to stand, yielded gas containing about twenty per cent, of oxygen, eighty of nitrogen, and no carbonic acid. It is proved that the dark blood of prussic acid poisoning, shaken with the air, assumes the red arterial hue, and Lecorche" and Meuriot 9 have shown that artificial respiration will produce the same result in the poisoned animal. On the other hand, it has been spectro- scopically proved that there is no cyanohaemoglobin in the blood of the poisoned animal, the haemoglobin existing in the blood either as haemoglobin or oxyhaemo- globin (Preyer, Laschkewitsch, 10 Hiller and Wagner 11 ). 388 GENERAL REMEDIES. The facts just epitomized would seem at first sight very strong evi- dence of the correctness of the theory of Hoppe-Seyler, that hydrocyanic acid in the first stage of the poisoning paralyzes the ozonizing power of the red blood-corpuscles ; but it seems very difficult to see how a sub- stance should in the first stage of poisoning paralyze the ozonizing power of the red blood-corpuscles and in the next stimulate such power so that the blood should become dark and loaded with carbonic acid. Further, it has been shown by Preyer that the excessive oxygenation and the sub- sequent excessive carbonization of the blood are not peculiar to hydro- cyanic acid poisoning, but are equally present after the exhibition of sul- phuretted hydrogen, and even after mechanical closure of the mouth and nose. It is possible that a heightened arterial pressure producing an in- creased rapidity of circulation may cause the blood to pass too quickly through the capillaries to allow time for the usual changes ; but this has not been proved, and at present it must be acknowledged that we are ignorant as to the immediate cause of the blood-changes in these cases. Alterations in the form of the corpuscles of the blood have been sug- gested as the cause of the changes of the color, Ernst Geinitz having found that both in the frog and in the mammal prussic acid distorts the blood-corpuscles. On the other hand, in the observations of Preyer, although such alteration of the blood-corpuscles could be produced in mammalian blood outside of the body, yet in blood drawn immediately after death from prussic acid the corpuscles offered their usual character ; a fact confirmed by Hiinef eld. 12 * Whatever may be the cause of the changes in the blood, the experi- ments of Lewisson 13 would appear to prove that the action of the poison on the nervous system is a direct one, and not due to these changes in the vital fluid, for the observer mentioned found that prussic acid acted upon the bloodless ' ' salt frog' ' as upon the normal batrachian. Action on the Heart. The action of hydrocyanic acid upon the heart varies according to the dose. In sufficient amount and concentration it produces instantaneous diastolic arrest, which is either permanent or reoccurs after a few slow feeble beats (Preyer, and Lecorch6 and Meuriot). As early as 1826 Krimer found that prussic acid placed directly upon the heart of the frog produces arrest of its beat and loss of its muscular irri- tability. Preyer has confirmed this, and it would seem to be proved that the cardiac arrest spoken of above is due to a direct action upon the * According to E. Ray Lankester (Pftiiger's Archiv, 1869, 492), when blood is shaken with cyanogen gas, and allowed to stand for two or three hours, the spectrum-changes are exactly the same as after similar treatment of blood with CO. The compound of cyanogen and hsmatin (Cy,Hb) offers not only the identical spectrum of CO,Hb, but also, like the latter, is unaffected by reducing agents. After the blood stands awhile, ac- cording to Lankester, the spectrum of hydrocyanic acid (H,CN) becomes visible in it, and the Cy,Hb undergoes conversion into the cyanohaemoglobin (Cy,Hb) of Hoppe- Seyler. Any one desirous of investigating this subject more deeply than can be done in a work like the present should consult especially the papers by Hoppe-Seyler ( Virchow^s Archiv, xxxviii., and scattered through the Med.-chem. Unterstichungen), by Harley (Lond. Phil. Trans.. 1865, 706), and by Preyer (Pflilger's Archiv, 1868, 395). CARDIAC DEPRESSANTS. 389 heart-muscle or its contained ganglia, yet that after cardiac death from prussic acid the heart responds to galvanism. The cardiac results of the exhibition of small non-toxic doses are, according to Preyer, simply slowing of the heart's action. Preyer and Laschkewitsch agree as to the action of large, but not enormous, doses. At first there is a sudden prolonged diastolic arrest of the heart, followed by an augmentation in the rapidity of the cardiac action, and after this a diminution of the rate, to the normal number in cases of recovery, to cardiac stand-still in cases of death. Both Preyer * and Laschkewitsch found that after section of the vagi the pri- mary diastolic arrest of the heart did not occur. Jos. Lazarski " has also found that the slowing of the pulse by moderate doses of hydrocyanic acid is prevented by previous section of the vagi. It would seem, there- fore, proved that small doses of prussic acid stimulate the cardiac inhibi- tory nervous centres. Boehm and Knie 15 noted that large doses of the acid caused slowing of the pulse whether the vagi were cut or not, and in this have been confirmed by Lazarski. This slowing would seem to be due to a direct action upon the muscle or the intra-cardiac ganglia, as Lazarski found that the cardiac accelerator nerves are not paralyzed. Moderate doses of prussic acid seem to produce a primary very brief but great rise in the arterial pressure, followed by a fall to or below the normal. This primary rise has been noticed by Boehm and Knie, by Wahl, 16 by Rossbach and Papitzky, 17 and by Lazarski. It does not seem to be altogether the result of the asphyxia produced by the acid, as it is recorded by Boehm and Knie as occurring when artificial respiration was used, and Lazarski has confirmed this. All observers agree that it is followed, if the dose of the poison has been large enough, by a profound sinking of the arterial pressure. Lazarski found that galvanization of a sensitive nerve has no effect at this time upon the blood-pressure : so that we must consider that hydrocyanic acid primarily stimulates very briefly the vaso-motor system directly or indirectly, and afterwards paralyzes it. Respiration. Hydrocyanic acid acts directly upon the respiratory cen- tres as a depressant, so that in poisoning by it the respiratory movements are lessened from the beginning, and becoming more and more distant finally cease before the heart's action is arrested. Preyer found that, after division of the vagi, normally lethal doses did not kill, and that when death was brought about by the exhibition of larger doses it was by cardiac arrest. From this he deduces the conclusion that the prime respiratory action of the poison is upon the peripheral ends of the vagi. Preyer's experiments have been partially confirmed by Lecorch6 and Meuriot ; but Boehm and Knie have in a series of experiments found that section of the vagus has no influence upon the respiratory action of the poison, and in this have been confirmed by Jos. Lazarski. Even if investigations had proved the correctness of Preyer's experi- ments, his conclusion could not be considered established, because we know so imperfectly the normal relations of the pneumogastrics to respiration. Moreover, * Preyer (loc. cit., 93) has also noted the same absence in curarized animals poisoned by hydrocyanic acid. 390 GENERAL REMEDIES. Joseph Jones 18 found that while to kill an alligator by the administration of prussic acid required a considerable length of time, its application to the medulla produced within one minute a most powerful expiration, ending in permanent contraction of the muscles of respiration and collapse of the lung. In the experiments of H. Ha- yashi and K. Muto" 7 doses of 15 milligrammes per kilogramme of potassium cyanide caused in the rabbit fatal paralysis of respiration at a time when the phrenic and motor nerves were still excitable. Action on Muscles, Nerves, and Nerve- Centres. Kolliker 19 has found that in frogs dead of prussic-acid poisoning both nerve-trunks and muscles are unexcitable, or that the muscles respond very feebly to direct stimulation. He also showed that protecting the nerve-trunks by tying their supplying artery prevented any loss of function in them when the animal was poisoned, and that the conclusion of Stannius, 20 that prussic acid applied locally to the nerves has no effect upon them, was due to his having used on the nerve employed for com- parison a fluid almost as deadly as the prussic acid. The experiments of Kolliker are in agreement with those of Stannius, that the muscle dies very much more quickly in the solution of the acid than does the nerve, losing its excitability in from seven to eight minutes. This rapid destruction of muscular irritability by the local application of prussic acid was, we believe, first noted by Coullon in 1819. Yet it is most probable that when given internally prussic acid acts almost as rapidly upon the nerve-trunks as upon the muscles, since Kolliker noted that in some cases galvanization of the nerve was incapable of causing contractions in the tributary muscles, although the latter responded feebly to direct stimulation. This fact has been experimentally corroborated by Funke. 21 Upon the peripheral sensitive nerves prussic acid, if in sufficient con- centration, acts as a paralyzant. Kolliker found that if the leg of a strychnized frog, whose heart had been cut out to prevent absorption, was put in a four per cent, solution of prussic acid, in a very short time irritation of the immersed skin ceased to produce convulsions. From the slowness with which, in Kolliker' s experiments, the nerve- trunks were affected in frogs poisoned by hydrocyanic acid, it seems probable that he is correct in his conclusion that in these batrachians the poison first paralyzes the brain, then the reflex centres of the spinal cord, and afterwards the motor nerves. But we have not met with any experimental evidence in regard to the order in which prussic acid affects the nervous system. According to Kiedrowski* (quoted by Preyer), in frogs it first paralyzes the gray, then the white substance of the brain, and the early disappearance of reflex * We have, unfortunately, been unable to obtain access to the original paper of E de Kiedrowski. Even Preyer appears to know it only in abstract. According to him, it was published in 1858, at Breslau, as a dissertation, under the following title : De quibusdam experimentis quibus quantum vim habeat acidum hydrocyanicum in nervorum systema cerebro-spinale atque in musculos systematis vertebralis probatur. CARDIAC DEPRESSANTS. 391 movements is not due to spinal palsy, but to destruction of the functional power of the peripheral afferent nerves. Preyer also states that the conclusions of Kie- drowski rested upon the following experimentally proved fact, which, if accurate, seemingly renders them logically inevitable. When a frog is poisoned with prussic acid, and afterwards with strychnine in properly proportioned doses, there is a stage at which slight irritation of the afferent nerve-roots causes violent general tetanic spasms, although the most intense peripheral irritation fails to elicit response. It is a question of interest to decide as to the cause of the convul- sions in poisoning by hydrocyanic acid. We have found that they do not occur after section of the cord in parts below the point of section, and that they are therefore cerebral in origin. It is probable that the convulsions are secondary, asphyxial, or due to disturbance of circulation. Laschkewitsch, who opened the thorax of a rabbit so as to expose the heart, maintained artificial respiration, and administered prussic acid ; directly after arrest of the heart had commenced the convulsions came on ; also in the earlier observation of Coze, 2 " the convulsions did not occur until directly after the arrest of the circulation. In frogs poisoned with hydrocyanic acid, convulsions do not take place. Preyer states that after section of the vagi convulsions do not generally happen in mammals, but if artificial respiration be performed they come on. SUMMARY. When in sufficient concentration hydrocyanic acid is a powerful depressant poison to all the higher tissues. It is absorbed immediately, and acts at once, but so fugaciously that its influence is over in a few minutes. In poisoning by it death usually occurs through centric paralysis of the respiration, but the depression of the heart's action is pronounced, and diastolic cardiac arrest sometimes takes place simultaneously with or even before cessation of breathing. It first stimulates, then paralyzes the vagi ; it first stimulates, afterwards paralyzes the vaso-motor system. Upon the nerve-centres it has a most pronounced depressing influence, and it is also a paralyzant to the nerve- trunks and to the muscles themselves. There is some reason for suspecting that after the small toxic dose of hydrocyanic acid the paralytic stage is preceded by a very brief stage of excitement, with centric increase of the respiratory activity, rise of the arterial pressure (caused by an influence upon the vaso-motor centres and perhaps upon the heart), and slowing of the pulse from stimulation of the cardiac in- hibitory centres. Outside of the body hydrocyanic acid attacks the red blood-corpuscles, forming a new compound, cyanohaemoglobin ; but the occurrence of this change during life in hydrocyanic acid poi- soning is doubtful. THERAPEUTICS. Our knowledge of the physiological action of prussic acid does not lead to a belief in its wide applicability to the relief of disease, and we think that clinical experience has demonstrated that it is of little value except in meeting three indications : first, to allay cough ; second, to relieve irritation of the gastric nerves ; third, to allay irrita- tion of the peripheral sensitive nerves. Prussic acid has been used very largely to allay cough, either itself or in the form of potassium cyanide. Owing to the extreme fugaciousness 392 GENERAL REMEDIES. of its action, it is, however, of very little real value for this purpose. It is not probable that the effect of any therapeutic dose of the acid lasts over twenty minutes, or of the cyanide over forty-five minutes. There can be, on the other hand, no doubt as to the value of prussic acid in certain stomachic affections, especially nervous vomiting and gas- tralgia. When the pain is accompanied by decided dyspeptic symp- toms, the remedy will sometimes succeed, but more often fails. Even in the most favorable cases it does not always afford relief ; and as the relief when it does occur is immediate, or at least is very soon apparent, it is useless to persist long in the exhibition of the remedy. In these cases its action is probably local, as it certainly is when the acid is em- ployed to relieve itching in prurigo and other cutaneous diseases. For this purpose it is used as a wash (one- half to one fluidrachm in one fluid- ounce) ; but great care must be taken to avoid constitutional effects, especially when there is any abrasion of the skin. Very serious results are said to have been caused by its absorption when carelessly used in skin diseases. Prussic acid has been commended as an arterial sedative ; but unless given in dangerous doses it has no such action. TOXICOLOGY. The symptoms of prussic acid poisoning have already been mentioned : those of most value from a diagnostic point of view are the sudden occurrence of unconsciousness, the violent convulsions, the general paralysis, the peculiar character of the breathing, expira- tion being prolonged and forced, and the rapid results. The odor of prussic acid upon the breath is very often, but by no means always, present. When distinct, it is, of course, of great diagnostic value. Leaving out of sight the cyanides, the only poison with which prussic acid could well be clinically confounded is nitrobenzol. The distinc- tion is often very difficult, large doses of the latter substance killing almost as quickly as prussic acid and inducing analogous symptoms. Caspar advises that after death the body be left open, exposed to the air, as the odor of prussic acid disappears rapidly, while that of nitro- benzol is persistent. The diseases with which the poisoning may be confounded most readily are some forms of apoplexie foudroyante, and sudden failure of the heart's action. The diagnosis may, during life, be almost impossible. It has been asserted that stertorous breathing does not occur in prussic acid poisoning ; but it has been present in several reported cases.* An autopsy, however, ought generally to ena- ble the physician to determine whether the case has or has not been one of prussic acid poisoning, if the symptoms during life are known. A curious case of temporary hemiopia, apparently caused by the fumes of hydrocyanic acid, is reported. The period at which death may occur after the ingestion of the poison is set down by Lonsdale at from one to fifty-five minutes ; but a case has * See Taylor's Medical Jurisprudence, Philadelphia, 1873, 363. CARDIAC DEPRESSANTS. 393 been observed by Hilton Fagge, 24 in which the fatal result was put off for at least an hour and a quarter after the ingestion of hydrocyanic acid. After death the body often presents a livid surface, bloated countenance, fixed glassy eyes with dilated pupils, and clinched fingers ; sometimes it offers nothing worthy of note except excessive rigidity, and the face may be very pale. When opened, the odor of prussic acid is generally, but not always, emitted ; the mucous membrane of the stomach is very com- monly found much congested, and the dark or cherry-colored liquid blood usually everywhere fills up the veins. The heart is soft and flaccid. The treatment of poisoning by prussic acid is of little avail. Of the several chemical antidotes which have been proposed, hydrogen dioxide is the most practicable.* But such is the rapidity of absorption that the case is usually terminated before the antidote can be obtained. The asserted physiological antagonism of atropine has been disproved by Keen' 25 and by Boehm and Knie. The stomach should, if possible, be emptied or washed out with a thirty per cent, hydrogen dioxide solution if at hand, and the hypodermic use of atropine and strychnine as respiratory stimulants might be tried ; the inhalation of the vapors of ammonia, and the free exhibition of ammonia by the mouth and by injection into the veins, may be practised. Artificial respiration has been found very suc- cessful by Preyer, and by Boehm and Knie, in animals, and should always be assiduously practised. Next to it in importance is the use of the alter- nate cold and hot douche, about a half of a small bucketful of cold water and the same quantity of very hot (115 F. ) water being dashed upon the chest in rapid succession. There is considerable experimental evidence to show that the sodium hyposulphite is capable of following prussic acid, cyanides, nitrobenzole, and other nitrites into the system and there decomposing them, but we know of no case in which the antidote has been used upon man. As, however, it is harmless it might well be given hypodermically. f ADMINISTRATION. The dose of the dilute prussic acid ( ACIDUM HY- DROCYANICUM DILUTUM, U. S. ) is one to three drops (0.06-0. 18 C.c. ). Potassiiim Cyanide (POTASSII CYANIDUM, U. S. ) occurs in white, amorphous, opaque masses, having the odor of prussic acid and a taste of similar character, but somewhat alkaline. It is deliquescent, and readily soluble in water. When potassium cyanide is taken into the stomach, the acids there present convert it into prussic acid, and the same change probably occurs, although more slowly, even when the salt is injected directly into the blood-vessels. The physiological, therapeutical, and toxicological prop- erties of this salt are similar to those of prussic acid. J Death, however, * See E. Merck, Merck's Arch., 1900, ii. 94. t See S. Lang, A. E. P. P., 1895, Bd. xxxvi. ; J. F. Heymans and P. Masoin, A. I. P., 1897, iii, fasc. i and 2; R. Verbrugge, A. I. P., v., fasc. 3 and 4; and J. Meurice, A. I. P., vii., fasc. i and 2. % Poisoning has occurred from the inhalation of the vapors of the cyanide and from absorption through the hands (Brit, and For. Med.-Chir. Rev., July, 1876, 231). 394 GENERAL REMEDIES. does not occur so soon as from hydrocyanic acid, and insensibility is sometimes not manifested for several minutes. Five grains of the salt have caused death but fifty grains have been recovered from. (See Mc- Kelway. 28 ) Dose : one-twelfth to one-tenth of a grain (0.005-0.006 Gm. ). Silver Cyanide (ARGENTI CYANIDUM, U. S. ) is a white insoluble powder, wnich is used solely for making prussic acid. Cyanogen Gas has been studied physiologically by B. Bunge. 18 He finds that it kills by paralyzing the centres of respiration, but that it is less powerful in its influence than is hydrocyanic acid, and causes only very feeble convulsions. Bitter Almonds (AMYGDALA AMARA, U. S. ) yield a volatile oil, Oleum Amygdala Amarce, Oil of Bitter Almonds ; of a yellowish color, bitter, acrid taste, with a strong odor of prussic acid. This volatile oil consists of benzoic aldehyde contaminated with various substances, of which the most important, prussic acid, has been present to such an extent that two drachms of the commercial oil are said to have caused death in ten minutes. Very properly, under the name of Benzal- de/iydum, U. S., Benzaldehyde, the pure benzoic aldehyde, produced synthetically or obtained from natural oils, has been recognized in the last edition of the U. S. Pharmacopoeia, fhis is a colorless, strongly refractive liquid, having a bitter odor and a burning taste. The official oil and benzaldehyde are very seldom used ex- cept as flavoring agents. VEGETABLE ACIDS. Although most of the official vegetable acids differ so much from the other substances considered in the present class as not to be poisonous except in enormous doses, and although they are never used to produce a profound impression upon the circulation, yet, since they have, or at least are believed to have, the power of lowering the force of the cardiac movements to some extent, and since they are so commonly believed to have a tendency to depress animal temperature as to be usually spoken of as refrigerants, the present seems to us a fitting place for their con- sideration. In experiments made by W. H. Gaskell, 1 similar to those described in the article on digitalis (see page 300), it was found that while alkalies contracted the arterioles of the frog, acids * caused a dila- tation, probably by paralyzing the muscular coats. Acids also dimin- ished the activity and power of the frog's heart. ACIDUM TARTARICUM TARTARIC ACID. U.S. Tartaric acid occurs in large, hard, transparent, six-sided prisms, which are pyro-electric and phosphorescent when rubbed in the dark, are nearly free from odor, have a very sour taste, and are very soluble in water. In the shops the acid is almost always kept in the form of powder. Tartaric acid is the acid of the grape, and occurs in grape- juice as potassium bitartrate. When the juice undergoes fermentation and alcohol is developed, the acid salt, not being soluble in the newly * Lactic acid, however, appears to have been the only one used, and it does not seem certain that the results of experiments would be the same with all acids, as is stated in Gaskell's generalization. CARDIAC DEPRESSANTS. 395 formed menstruum, precipitates, collecting as a dark mass in the wine- casks, whence it is sent into commerce under the name of argol or tartar. PHYSIOLOGICAL ACTION. In powder or concentrated solution tar- taric acid is a very decided irritant, capable of producing, when taken internally, violent cesophageal and gastric burning, vomiting, and, it may be, fatal gastro- enteritis.* Mitscherlich states that three or four drachms suffice to kill a rabbit, the evident symptoms being great weakness of the heart's action, difficult and slow breathing, and steadily increasing pains, with slight convulsions before death. According to Devergie, it requires nearly half an ounce to kill a dog when given by the stomach ; but Pommer (quoted by Husemann) asserts that one gramme (15.34 grains) in- jected into the crural vein of a dog will produce death. Concerning the action of therapeutic doses of tartaric acid we have no definite information. General clinical experience, in accord with the experiments of Bo- brick.t who found that very large doses render the heart's action weaker and slower, indicates that the drug is a very feeble cardiac depressant. It is probably partially burnt up in the body and partially eliminated by the kidneys. W6hler,f in his ex- periments, found it in the urine in the form of calcium tartrate, while Buchheim f and Piotrowski t could find only a very small percentage of the ingested acid in the urine, and conclude that it is mostly destroyed in the body. Munch * finds that when tartaric acid or citric acid is given it soon appears in the urine. H. Bence Jones * has found that both citric acid and tartaric acid cause a pronounced increase in the acidity of the urine of persons taking them, and are apt also to give rise to the presence of free uric acid in the excretion. Unfortunately, Jones did not attempt to determine whether the increased acidity was or was not due to the presence of the vegetable acid in the urine. THERAPEUTICS. Tartaric acid is rarely used in medicine, citric acid almost always being preferred. It may, however, be employed whenever it is desired to render the urine acid, in doses of ten to twenty grains (0.6-1.3 Gm. ). TOXICOLOGY. There are, we believe, but three fatal cases of tartaric acid poisoning on record : one reported by Devergie,* one by Taylor, 4 in which death took place nine days after the ingestion of an ounce of the poison dissolved in half a pint of water, and one 5 in which half an ounce of the acid was supposed to have been taken. The treatment of tartaric acid poisoning consists in the free exhibition of magnesia, of lime, of potassium or sodium carbonate, or of any article, such as soap, contain- ing an alkali in a suitable shape, which may be at hand. The after-treat- ment is that of toxic gastro-enteritis. ACIDUM CITRICUM CITRIC ACID. U. S. Citric acid is the acid of lemon- and lime-juice. It occurs in rhom- boidal prisms, of a sour, almost corrosive, taste, extremely" soluble in water. * Case reported in the Brit. Med. Journ., for June, 1893, in which the supposed dose was one hundred and eighty grains. Symptoms : diarrhoea, violent abdominal pains becoming more and more marked, followed by fever, delirium, and death on the seventh day. At the autopsy violent inflammation of the whole of the gastro-intestinal tract was found. t All these are quoted by Husemann (Die Pflanzenstoffe}. We have not seen the originals. 396 GENERAL REMEDIES. PHYSIOLOGICAL ACTION. Citric acid in concentrated form is actively irritant, but, according to Mitscherlich, is less so than tartaric acid, since its concentrated solution has no action upon the sound skin. Serious poisoning by it is extremely rare, and we know of but one recorded fatal case (H. Kionka). 3 Piotrovvski (quoted by Husemann) took, in six hours, thirty grammes, an hour later fifteen grammes, and an hour later thirty grammes, or nearly two ounces and a half in all, with the induction of no more serious symptom than vomiting. In Kionka's case, a girl in order to produce abortion took an unknown quantity of citric acid, and was brought dying into the hospital with the only clinical record that she had vomited greatly. Nine thousand four hundred and fifty-two grains of citric acid were collected from her gastro-intestinal tract. Marked evidences of violent gastritis were present, with gross evidences of hepatic degeneration. In the experiments of Maass 4 citric, acetic, and tartaric acid were found to have very little influence on frogs unless in large quantities. Hugo Schulz l states that citric acid is an active antiseptic, a five per cent, solution being sufficient to preserve small pieces of meat for two weeks ; one part in a thousand was fatal to paramecia. THERAPEUTICS. Lemon-juice (Succus LIMONIS, U. S. ) is a valuable remedy, but how or why it acts is at present entirely unknown. According to the analysis of H. Bence Jones, 2 lemon-juice contains about twenty-six grains of free citric acid and less than two grains of potassium citrate to the ounce, but neither citric acid nor any of its known salts act in disease as does the juice of the fruit. M. Schmitt found lemon-juice in very large dose increases the flow of urine, but at the same time markedly diminishes the elimination of urea and of acids. The chief and most important use of lemon-juice is in the cure and prevention of scurvy. During the dis- ease three or four ounces may be given three times a day. As a prophy- lactic against the disease, lemon-juice is simply invaluable ; but it is absolutely necessary that it be of good quality. It may be prepared for long voyages in one or two ways : first, boil the juice slightly, strain, allow to cool, pour into bottles up to their necks, fill the vacant space above with pure olive oil, cork tightly, and keep the bottle upright ; second, add ten per cent, of brandy, and bottle as before. In acute rheumatism, benefit may be derived from the free use of lemon-juice, as originally proposed by Rees, of London. One or two ounces of it may be given four or five times a day ; but it is certainly less efficacious than the alkalies. In catarrhal jaundice and in habitual torpor of the liver the free administration of lemon-juice often aids in effecting a cure. In fevers, lemonade is a very refreshing and useful refrigerant drink. ACETUM VINEGAR. The physical properties of vinegar are too well known to need de- scription here. That best suited for medicinal use is in this country pre- pared from cider, and should have a trace of the taste of cider. Vinegar CARDIAC DEPRESSANTS. 397 may be substituted for lemon-juice as a basis of an acidulous drink in fever when the lemon-juice is not to be had ; but as an antiscorbutic it is certainly very much inferior to it, and has not, that we are aware of, been tried in rheumatism. Acetic Acid* (AciDUM ACETICUM, U. S.) is a colorless liquid, having a pungent odor, free from empyreuma, and an intensely acid, corrosive taste. It contains thirty-six per cent, of the monohydrated acetic acid, and has a specific gravity of 1.047. Glacial or Absolute Acetic Acid ( ACIDUM ACETICUM GLACIALE, U. S. ) is now official. It is a colorless liquid, crystallizing at 59 F. , remaining solid at temperatures below 60 F. , and actively escharotic, in a measure, no doubt, owing to its prop- erties of dissolving gelatin and gelatinous tissue and of effecting a partial solution of albuminous matters. Dilute Acetic Acid ( ACIDUM ACETICUM DILUTUM) is officially prepared by the addition of five parts of water to one 'part of acetic acid, and should have the specific gravity of 1.008. Dilute acetic acid or its equivalent, vinegar, acts upon the skin as a powerful stimulant and astringent, causing contraction of the vessels and great whiteness, so that it is often very useful as a topical application in various forms of dermatitis, especially sunburn, and also in bruises and sprains. We have found it, diluted with from one to four parts of water, a very grateful drink in hcematemesis, and very effective in arresting the flow of blood. Diluted with "two or three times its bulk of water, it is occasionally employed as an injection against seat-worms ; but the infu- sion of quassia is preferable. The use of acetic acid as a caustic will be spoken of under the head- ing of Escharotics. TOXICOLOGY. Acetic acid in any of its more concentrated forms is a corrosive poison, and death has been produced by it in at least one case (Orfila 1 ). The symptoms resemble those caused by mineral acids, and the treatment is exactly similar, neutralization by an alkali or its car- bonate, or by some substance, such as soap, containing an alkali, and the meeting of indications as they arise. Oxalic Acid ( ACIDUM OXALICUM) has been asserted J to be a valuable emmenagogue, but it is chiefly known to the profession as a poison. In 1874 Rabuteau 2 announced that in oxalic acid poisoning the nerves and muscles are not affected, and that therefore the acid acts upon the nerve- centres. This has been confirmed by the elaborate researches of R. Kobert and B. Kiissner, 3 who find that it paralyzes the respiratory, vaso-motor, and other motor spinal centres. It is also a cardiac poison, arresting the heart in systole.* The acid is eliminated by the kidneys. As a poison, oxalic acid figures in two forms : that of simple oxalic acid, * ACETOXUM, U. S. Acetone. Pyroacetic Spirit. This substance, which mixes in all proportions with water, alcohol, and ether, is recognized in the last U. S. Pharmaco- poeia on account of its large use in pharmacy as a solvent for fats, resins, and various active principles. It is not used in practical medicine. 398 GENERAL REMEDIES. and that of the acid potassium oxalate, or salt of sorrel, or essential salt of lemons, as it is variously termed in common parlance. The symptoms produced are a hot acrid taste experienced during the swallowing, a burning in the gullet, soon extending to the stomach, intense abdominal pain, vomiting of highly acid, greenish, blackish-brown or bloody mucus (rarely of arterial blood), collapse, livid surface, cold skin, entire pros- tration of strength, small, irregular pulse, stupor, unconsciousness, some- times convulsions, 5 and finally death. In some cases the gastric symp- toms are very prominent ; in others they are nearly wanting, and the chief manifestations are collapse and such nervous symptoms as almost complete general paralysis, numbness, and finally stupor ; indeed, the patient may suddenly fall unconscious immediately after the ingestion of the poison. 6 In pregnant women abortion or at least death of the foetus usually occurs. According to Taylor, the smallest quantity which is known to have caused death is one drachm. An ounce usually proves fatal, but has been recovered from. After death the coats of the stomach are found softened and swollen, and sometimes perforated. 7 Rabu- teau affirms that the blood is everywhere scarlet ; but this is certainly not always the case (Taylor 8 ). In 1879 Kobert and Kiissner discov- ered that oxalic acid will produce in the lower animals not only oxaluria and albuminuria with tube-casts, but also glycosuria.* In 1883 Sarga- neck discovered sugar in the urine in human poisoning, and the recent investigations of Kobert have shown that in rabbits and cats even non- poisonous doses of the acid cause the appearance of a fermentable sugar in the urine. It would seem, therefore, that glycosuria should hold an important place among the diagnostic symptoms of the poisoning. Ac- cording to Kobert and Kiissner, a pathognomonic post-mortem lesion is the incrustation of the urinary tubules with crystals of oxalates. In poisoning by oxalic acid, the immediate administration of an antidote is of the utmost importance. As the potassium and sodium oxalates are poisonous, neither potash nor soda is available ; but, fortunately, lime or chalk is a perfect antidote to oxalic acid, forming the excessively insolu- ble calcium oxalate. As time is a matter of so much importance, very often it is best simply to scrape "whitewash" off a wall, a ceiling, a fence, or wherever it may be at hand, rub it up hastily with water, and admin- ister it freely. The after-treatment is that of toxic gastro-enteritis. As an emmenagogue, oxalic acid has been used in all forms of amen- orrhcea with asserted great success. It is said also to be an active aborti- facient, but as such is certainly extremely dangerous. The dose usually given is half a grain three or four times a day, but F. W. Talley has reported serious poisoning as produced by this amount. Oxalic acid is a powerful germicide. According to O. Loew, 9 the one per cent, solution of the neutral potassium oxalate is very active in the destruction of infusoria, whilst Howard A. Kelly 10 asserts that potassium * Kobert has made the very important observation, that the extract of Syzygium jambolanum will control the glycosuria produced by oxalic acid. CARDIAC DEPRESSANTS. 399 permanganate and oxalic acid afford the only known practical method of perfectly disinfecting the hands of the surgeon.* REFERENCES. CARDIAC DEPRESSANTS. 1. WOOD P. M. T., iii. 2. La Nazione, Aug. 1872. 3. FOTHERGILL. . . B. M. J., 1873. ANTIMONY. 1. ACKERMANN . . 2. SENTZ 3. RADZIEJEVVSKI . 4. NOBILING . . . 5. SOLOWEITSCHYK 6. RICHARDSON . . 7. BRINTON .... 8. Mosso 9. MAYERHOFER . 10. HUSEMANN . . 11. SALKOWSKY . . 12. TAYLOR .... 13- 14. 15. MASOIN .... . V. A. P. A., xxv. 531. . In. Dis., Dorpat, 1853. .A. A. P., 1871. . S. Jb., cxl. 24. . A. E. P. P., xii. 440. . L. L., 1856, i. . L. L., 1853, ii. 599. ^ . S. Jb., clxix. 236. . Notlmagel's Arzneimittel- lehre, Berlin, 1870, 219. . Toxicologie, 853. . V. A. P. A., 1865, xxxiv. 78. . Guy H. R., Oct. 1857. Taylor's Medical Jurispru- dence, 1873, 309. N. V. M. R., xxiv. 401*. . A. I. P., 1902, ii. VERATRUM VIRIDE. 1. WOOD P. M. T., iv. 2. Amer. Journ. Pharmacy, 1865. 3. M.S. Rep., xl. 372. 4. BLAKE Amer. Med. Weekly, 1874, No. 20. 5- P. M. T., xiv. 863. ARNICA. 1. B. M. S. J., Jan. 1875 ; Ann. de Dermal, et de Syph., 1886, vii. 2. HARE B. M. S. J., Jan. 12, 1888. 3. BALDING L. L., Dec. 1870. 4. B. G. T., Ixxvi. 5. L. L., Nov. 1864. 6. THORN Virginia Med. Monthly, Sept. 1883. ACONITE. 1. CASH and DUNSTAN . Tr. R. S. London, 1898, cxc. 243. 2. HARLEY St. Thomas Hosp. Rep., v. 3. BOEHM and WARTMAJJN . Arbeit. Physiol. Wiirzburger Hochschule, 1873- 4. LIEGKOIS and HOTTOT . J. de P., 1861, 520. RINGER and MURRELL . J. P., i., No. 4. PLUGGE .... V. A. P. A., Ixxxvii. 410. MACKENZIE . . . Pract., xx. 100. GUILLAUD . . . . A. de P., 1875. EWERS A. E. P. P., 1873, i. LABORDE and DUQUESNEL . Des Aconits, Paris, 1883. ACHSCHARUMOW . A. A. P., 1866. MATTHEWS . . . J. Ex. M., ii., No. 5. LEWIN PragerVierteljahrs.,cxxxi. NUNNELEY. . . . Proc. Roy. Soc., London, 1870. BRUNTON and CASH . St. Barthol. Hosp. Rep., 1886, xxii. REICHERT .... P. M. T., 1881, 105. STEVENSON . . . Guy H. R., 3 s., xxvi. 308. BASSOT Thesis, Lyons, 1889. Ln6TE and VIBERT . An. d'H., April, 1892. HYDROCYANIC ACID. 1. VIETZ Med. Jahrb. d. k. k. Oes- terreiches Staat., 1814, ii. 2. SCHUBARTH . . . Horn's Arch. f. Med. Erfahrung, 1824. 3. SOBERNHEIM . . Handb. d. Prakt. Toxicol- ogie, Berlin, 1838. 4. COZE Gazette M6d. de Paris, 1849. 5. BISCHOFF .... Ueber Vergift. nebst Ver- such. an Thieren, mit Blausaure, etc., Wien, 1844- 6. PREYER Die Blausaure, Bonn, 1870. 7. GAETHGENS . . . Hoppe-Seyler's Med. Chem. Untersuch., Ber- lin, 1866. 8. HOPPE-SEYLER . V. A. P. A., xxxviii. 475. 9. LECORCHE and MEURIOT . A. G. M., 6 s., xi. 10. LASCHKEWITSCH . A. A. P., 1868, 652. 11. HILLER and WAGNER . L. L., 1877, ii. 933. 12. HtJNEFELD . . . Der Chemistnus in d. thierisch. Organis., Leipzig, 1840. 13. LEWISSON . . . . A. A. P., 1870 352. 14. LAZARSKI .... Wien. Med. Jahrb., 1881, 441. 15. BOEHM and KNIE . A. E. P. P., ii. 137. 16. WAHL De Vi et Effectu Hydro- cyanato, etc., Bonn, 1865. 17. ROSSBACH and PAPITZKY . C. M. W., 1877, 640. * The exact method practised, by Kelly is as follows : i. Scrubbing the hands, with especial attention to the nails, not more than one millimetre in length, for ten minutes in water frequently changed, at about 40 C. (104 F.). 2. Immersion of the hands in a solution of potassium permanganate, made by adding an excess of the salt to boiling dis- tilled water, until every part of the hands and lower forearms is stained a deep mahogany red or almost black color, followed by transfer to a saturated solution of oxalic acid until completely decolorized and of a healthy pink color. This decolorization is accompanied by a sense of warmth, due to chemical reaction, and a sharp stinging wherever there is any abrasion of the epidermis. 3. Washing off the oxalic acid in warm sterilized water. 400 GENERAL REMEDIES. REFERENCES. Continued. 18. JONES . . . . 19. KOLLIKER . . 20. STANNIUS . . 21. FUNKE . 23- 24. FAGGE 25. KEEN 26. BUNGE .... 27. HAYASHI and 28. McKehvay . . . . N. Y. M. R., ii. 459. . . V. A. P. A., x. 272. . . A. A. P., 1858, 95. . . Sb. G. W., Leipzig, 1859, xi. 28. B. M. J., 1884, i. 409. . . Guy H. R., 1868, 259. . . Proc. Acad. Nat. Phila., 1869. . . A. E. P. P., xii. 71. MUTO . A. E. P. P., xlviii. . . A. J. M. S. 1905 cxxix, 684. Sci., 1902, VEGETABLE ACIDS, i. GASKELL . . . . J. P., iii. 49. TARTARIC ACID. i. MUNCH . . Arch. d.Vereins. f. getnein. Arbeit., 1863, 370. 2. JONES M. T. G., 1854, ix. 408. 3. DEVERGIE .... An. d'H., 1851, ii. 4. TAYLOR Medical Jurisprudence, London, 1873, 230. 5. Med. Press and Circular, Nov. 1880. CITRIC ACID. 1. SCHULZ D. M. W., 1883, ix. 398. 2. JONES M. T. G., 1854, ix. 3. KIONKA A. S. Z., 1903, ix. 4. MAASS Th. M., 1903, xvii. ACETIC ACID. i. ORFILA Toxicologie, ii. OXALIC ACID. 1. G. H. M. C., xxiii. 128. 2. RABUTEAU .... Gazette M6d., 1874,92. 3. KOBERT and KUSSNER . V. A. P. A., Ixxviii. 109. 4. Les Nouveaux Rem&des, 1886, ii. 290. 5. Guy H. R., 1838, ii ; Dub- lin H. R., 1818, ii. 6. . Guy H. R., 1874. 7. Ed. M. J., July, i86i,vii. 8. TAYLOR Med. Jurisprud., i. 224. 9. LOEW Sitzb. d. Gesellsch. f. Morphol. und Physiol., 1892, viii. 10. KELLY Amer. Journ. Obstetrics, 1891, xxiv. ORDER III. NUTRIANTS. FAMILY I. ASTRINGENTS. ASTRINGENTS are those drugs which cause contraction of living tis- sues. That they do not act, as has been supposed, either by coagulating albumin or by calling into action the muscular function is demonstrated by the transitoriness of their effects, and by the fact that they influence tissues containing no muscular fibre. Every living soft tissue appears to possess a normal degree of condensation, which may be departed from on either hand : when this happens, in the one case the part is said to be relaxed, in the other to have its tonicity increased, or to be astringed. The action of astringents is always a local one, i.e. , produced not through the intervention of the nervous system, but by direct contact with the part affected. A pure astringent should be capable of doing nothing beyond inducing contraction ; but in reality there is scarcely such a drug. Astringents are, when applied too freely, irritants. The concordant experimental results reached by M. Rosenstein * and by R. Heinz 2 show that medium solutions of tannic acid, alum, and the salts of lead, zinc, iron, copper, and mercury contract the blood-vessels by a direct action. When, however, the solutions are too strong, according to Heinz, this contraction is followed by dilatation. Both experimenters state that the silver nitrate is the most powerful in its influence, pro- ducing an almost permanent contraction. According to Rosenstein, acids cause dilatation of the capillaries. The clinical results obtained by the use of astringents in the treatment of inflammation can hardly be due to their action upon the blood-vessels, but seem to find more appropriate explanation in the discovery of Heinz, that, locally applied, they decidedly check the out-wandering of the white blood-corpuscles, probably, as he thinks, by modifying the wall of the blood-vessel. The chief indication for the use of an astringent is the existence of relaxation. Local relaxation is commonly due to previous over-excite- ment. Thus, a throat is relaxed after over-use, or after inflammation. Astringents are more efficient as local than as general remedies, but in cases of inflammation care must be taken to use them in such a way that they shall not act as irritants. Applied too soon or too vigorously, they may do harm. These remarks are scarcely applicable to some of the mineral astringents, such as lead and silver nitrate, which really 401 402 GENERAL REMEDIES. appear to have sedative properties, and may with care be used advan- tageously in all stages of inflammation, whenever there are distention and relaxation of the blood-vessels, although the general action of the part be that of nutritive excitement. Closely allied to relaxation is over-secretion, and astringents are con- stantly used to check morbid discharges. Indeed, these discharges are often simply the result of relaxation. Thus, A'sp has experimentally proved that division of the intestinal nerves and consequent paralysis and relaxation of the vessels are followed by free watery secretion. In such cases the indication for astringents is very plain. But when a morbid discharge represents a high degree of inflammation, the same care must be practised in the use of astringents as in treating other local inflammations. Especially is this true since free secretion is often nature's method of relieving local inflammation. Thus, when abnormal alvine discharges are dependent upon intestinal relaxation, astringents are most valuable, but when they are dependent upon enteritis or colitis, astringents may do harm. If the morbid discharge by its profuseness endangers life, as in serous diarrhoea, astringents are urgently demanded. Very rarely, if ever, are these discharges other than paralytic in their origin ; even, however, if they be due to over-action, an astringent may be necessary to check their excessiveness. Another indication for the use of astringents is to check hemorrhage, and the same general reasoning is applicable to this as to the other indi- cations. Hemorrhage dependent upon over-action demands other treat- ment than by astringents. Sometimes in these cases it is necessary, however, to check the hemorrhage at all hazards, and then astringents may be used in conjunction with other measures, although they may be to some extent contra-indicated. Some of the astringents are employed locally to check hemorrhage due to traumatic or other ruptures of ves- sels. In such cases the astringents are employed as styptics, and do not act so much by their astringency as by coagulating the albumin of the blood and thus forming a clot and mechanically arresting the flow. Under certain circumstances there seems to be a general relaxation or loss of tone throughout the whole system, which may be best met by a consentaneous use of tonics and astringents. VEGETABLE ASTRINGENTS. The active principle of the vegetable astringents is tannic acid, and as it is almost their sole therapeutic principle and represents them very closely, it seems proper first to consider it, and afterwards to point out any especial therapeutic virtues the crude drugs of the class may possess. ACIDUM TANNICUM TANNIC ACID. U.S. There are two generic varieties of tannic acid, the gallo- and the kino- tannic : of these the former yields, upon exposure to the air in a moist ASTRINGENTS. 403 state, gallic acid, the latter a gelatinous, inert substance. They are further distinguished by the color of the precipitates which they yield with the persalts of iron ; gallo-tannic acid producing a blue-black, kino- tannic a green-black color. The official tannic acid the gallo-tannic acid is obtained by treating powdered galls with washed ether, which on standing separates into two strata, the upper of which is ethereal and contains chiefly the coloring- matter and other impurities. The lower watery stratum contains the tannic acid, which is recovered by evaporation. Commercial tannic acid is a light, feathery, non- crystalline powder, of a yellowish-white color, a faint odor, and an astringent, somewhat bitter taste. When absolutely pure, it is colorless and free from odor or taste other than that of astringency. Its reaction is strongly acid, and it unites freely with both organic and inorganic bases. It is very freely soluble in water, even more so in glycerin, somewhat so in dilute alcohol, scarcely at all in absolute alcohol, and not at all in ether free from water. With salts of the alkaloids it produces a whitish precipitate (tannates), very soluble in acetic acid ; with persalts of iron, a black (bluish or greenish) precipitate. PHYSIOLOGICAL ACTION. Applied locally, tannic acid is a very powerful astringent, causing contraction, and in the case of a mucous membrane, great dryness. Sometimes, when it is used very freely, its irritant influence seems to overcome its astringent action, and we have seen diarrhoea result from its administration. Several experimenters (Rosenstein, 1 Fikentscher 2 ) have denied that it causes contraction of the blood-vessels, because when they applied it to the exposed mesentery of a " Cohnheim frog," stasis of the blood, with dilatation of the vessels, not preceded by contraction, occurred. Daniels, 3 however, using rabbits, obtained different results, and Lewin has shown that the method of ex- perimentation was faulty. Clinical experience proves that tannic acid applied to relaxed mucous membranes affects their whole substance. Absorption and Elimination. Although it was formerly believed that owing to the activity with which tannic acid coagulates albumin it was incapable of absorption, under certain circumstances a small amount of an alkaline tannate may be absorbed and circulate in the blood ; but although a small portion of it may get into the blood as a tannate, what is absorbed is chiefly various decomposition products. Gallic acid has been found in the urine after the administration of tannic acid, but according to Morner the amount is less than one per cent, of the tannic acid ingested. When given in large amounts it mostly escapes absorp- tion, and passes out with the faeces unchanged. Thrown rapidly into the blood, tannic acid causes a fatal thrombosis ; but Lewin * asserts that when it is injected slowly and in moderate quantities the re- sulting albumin tannate is held in solution by the alkaline carbonates. He has also discovered that while tannin, in five per cent, solution, precipitates peptones out of watery solution, it is powerless in the presence of hydrochloric acid. As- 4 o 4 GENERAL REMEDIES. suming the correctness of the investigations of Lewin, it is plain that tannic acid, when put in the stomach in small doses, must to some extent be absorbed unchanged. Lewin also asserts that it is, at least in part, eliminated unaltered, as he has fre- quently recovered it from the urine. At the same time it seems very probable that most of the tannic acid is converted into gallic acid, either in the stomach before absorption or subsequently in the system, since in the viscera of a rabbit poisoned with it, Schroff 5 found only gallic acid ; and according to Clarus, 5 the greater part of ingested tannic acid can be recovered from the stools as albumin tannate or as gallic acid. The recent researches of Stockman 6 afford a possible reconciliation of the results of Lewin with those of the the older observers. Stockman finds that when tannic acid is given to the lower animals only a trace of it appears in the blood, while gallic acid can be obtained in abundance from the urine, with occa- sionally a small amount of tannic acid. If, however, sodium tannate be given, tannic acid appears in abundance in the urine, with a little gallic acid. The expla- nation offered by Stockman of this is probably correct, namely, that tannic acid is usually converted in the stomach into an albuminous tannate, which is dissolved with great difficulty in the intestinal juices, so that time is afforded for the con- version of the tannic into gallic acid, whereas an alkaline tannate is absorbed at once and rapidly eliminated unchanged. Wohler and Frerichs have also found gallic acid with pyrogallic acid in the urine after the exhibition of tannic acid. After its conversion and absorption tannic acid still possesses astrin- gent properties. Lewin has shown that in frogs poisoned with it the muscles are shortened and narrowed, and when loaded stretch less and recover their original length more nearly than do normal muscles. Kuchenmeister 7 and Hennig state that in poisoned cats the spleen is notably diminished in size and increased in firmness ; and Lewin has found in rabbits that tannic acid causes primary arrest of the urinary secretion, followed by a marked increase of the flow. THERAPEUTICS. As tannic acid undergoes in the system partial con- version into gallic acid, the latter is to be preferred to it when the part to be acted on can be reached only through the circulation. As a local application, tannic acid is much more powerful than gallic acid. Lo- cally applied it may be used to overcome relaxation, as in spongy gums, mercurial sore mouth, hemorrhoids, and chronic sore throat. To check hem- orrhage it may be used whenever the source of the flow can be reached directly, as in epistaxis, h&matemesis, hemorrhage from the bowels, etc. To arrest excessive secretion it may be employed locally in leucorrhoea, diarrhea, old abscesses, chronic ulcers, excessive perspiration, osmidrosis, and various diseases of the skin. It is also often very useful for the pur- pose of hardening parts exposed to friction, as in cases of sore nipples and tender feet. TOXICOLOGY. Tannic acid can scarcely be called poisonous ; although Rollet reports the case of a young girl in whom a very large quantity of it induced severe gastric and abdominal pains, with obstinate vomiting and constipation, fever, and general malaise. Both Schroff and Judell assert that eighty grains of it cause no symptoms of importance in the rabbit. ASTRINGENTS. 405 As an antidote it is useful in tartar emetic poisoning, forming an in- soluble antimony tannate. It is also the best chemical antidote for the poisonous alkaloids ; but, as the compounds it makes with them are slowly dissolved by the fluids of the alimentary canal, it must always be followed by emetics and cathartics. ADMINISTRATION. When given to act on the stomach, as in hsema- temesis, tannic acid should be in powder, ten to twenty grains (0.6-1.2 Gm. ). When the bowel is to be influenced, as in diarrhoea, the drug should be administered in pill, three to five grains (0.2-0.3 Gm.), so that, if possible, it may pass the pylorus undissolved. For local use the glycerite of tannic acid (GLYCERITUM ACIDI TANNICI, U. S. , twenty per cent. ) may be employed, or the ointment (UNGUENTUM ACIDI TANNICI, U. S., twenty per cent.), or the troches (TROCHISCI ACIDI TANNICI, U. S., one grain each). Tannic acid enters into styptic collodion (CoL- LODIUM STYPTICUM, U. S. , twenty per cent.). TANNIC ACID COMPOUNDS. A number of compounds of tannic acid have come into vogue, some of them of great practical value. TANNALBIN. Tannin albuminate. This is a light-brown powder, insoluble in water or the gastric juice, but decomposed by the alkaline juices of the intestines with the liberation of its constituents. It is tasteless, odorless, and non-irritant. It is a very valuable remedy in the treatment of intestinal catarrh and relaxation requiring the use of an astringent, acting immediately, persistently, and effectively, and affording in many cases an excellent combination with bismuth subnitrate. It has been recommended also in renal conditions associated with an excessive dis- charge of albumin. Dose, twenty to forty grains, in powder (1.2-2.5 Gm.). TANNACOL. Gelatin tannate. A tasteless, odorless powder, probably identical in its therapeutic application to tannalbin, although Rosenheim 8 affirms that it is superior in that it is less apt to be affected by the gastric juice, and is of greater uniformity of constitution. Dose, fifteen to thirty grains (1-2 Gm. ). TANNOPINE. Tannon. A combination of tannic acid and urotropin, which is said to contain eighty-seven per cent, of the acid, and, passjng unchanged through the stomach, to undergo decomposition by the alkaline juice of the alimentary canal. It has been strongly recommended by Schreiber 9 and other clinicians in the treat- ment of all forms of diarrhoeas requiring an intestinal astringent. Dose, ten to fifteen grains (0.8-1 Gm.). TANNOFORM. The tannoforms are combinations between tannins and formal- dehyde. Commercial tannoform is the condensation product of gallotannic acid and formaldehyde. It is a light, pinkish-white powder, which is believed to be decom- posed by the alkaline juices of the intestines with the setting free of tannic acid and formaldehyde, and to act, therefore, as an astringent and germicide. It has been very highly recommended by numerous practitioners in tuberculous and other diar- rhoeas requiring an astringent, both in adults and in children, given in doses of one- half to one grain (0.03-0.06 Gm. ), in capsules, three times a day. There is also much testimony as to the value of tannoform as an external remedy. A dusting-powder composed of one part of tannoform to two of talc, well rubbed into the skin of the body morning and evening, is stated by Strassburger 4 o6 GENERAL REMEDIES. and others to be very efficient in the preventing of night-sweats. An application of dilute alcohol should be made to the skin just before the use of the tannoform. According to K. Ullmann, confirmed by F. Merz, tannoform is extremely efficient in hyperidrosis of the feet ; a foot-bath should be used just at bedtime and a powder, composed of one part of tannoform and two parts of talc, should be well rubbed in between the toes and over the feet, daily for eight days. The effect is said to last many weeks. Tannoform has also been used as a local remedy in various external ulcerations, also eczemas, and other affections of the skin. ACIDUM GALLICUM GALLIC ACID. U. S. Gallic acid is a white, powdery substance, in fine acicular prisms, sol- uble in one hundred parts of cold water, in three parts of boiling water, and freely soluble in alcohol and in ether. Its taste is acidulous and astringent. According to the usual method, gallic acid is prepared by the ex- posure of moistened powdered nutgalls in a warm place for a month. A species of fermentation, with the development of a peculiar fungus, is said to occur, during which oxygen is absorbed, carbonic acid is evolved, and glucose and gallic acid are produced. M. Sacc 1 has, however, denied this, affirming that the change is simply one of hydration, tannic acid being an anhydride of gallic acid. Tannic acid also may rapidly be con- verted into gallic acid by the action of dilute sulphuric acid. Gallic acid produces with persalts of iron a bluish precipitate, with lime- water a whitish precipitate, changing to blue and then to violet or pur- plish, all of these precipitates being gallates. It does not coagulate gel- atin or albumin, and is, therefore, not a styptic. As an astringent it is less powerful than tannic acid. It escapes from the body through the kidneys. THERAPEUTIC ACTION. Gallic acid is not nearly so efficient as tan- nic acid, when applied locally, but should always be preferred when the part is to be reached through the medium of the circulation. It is useful as an astringent in hemoptysis, hczmaturia, colliquative sweats, etc. It has been recommended in bronchorrhcea and in the profuse expectoration of chronic phthisis. In our hands, however, it has completely failed in the latter affections. In Bright 1 s disease, when there is an abnormally large secretion of highly albuminous urine, it may lessen very materially the excretion of albumin. ADMINISTRATION. The dose of gallic acid is ten to thirty grains (o. 6-2 Gm. ) in capsules or powder, repeated pro re nata. GALLA GALLS. U. S. Galls are vegetable excrescences which are produced by the deposi- tion of the ova of insects. They occur on almost all kinds of plants, even on fungi, but the official gall is developed on the Quercus lusitanica by the act of the fly Cynips gallae tinctorise. There are in commerce two varieties of galls, derived chiefly from the Levant. The blue or green galls are globular, solid bodies, from the size of a pea to that of a hick- ASTRINGENTS. 407 ory-nut, externally smooth, or more commonly marked with large tuber- cles. They are the young galls which have been gathered before the ova of the fly have hatched, or before the caterpillar has eaten out the interior of its birthplace. The white galls are large, light, hollow bodies, with a hole, through which the Cynips has escaped after having fed upon the interior during its whole larval life. They contain but little tannic acid, and are of comparatively little value. THERAPEUTICS. The sole value of galls is as the source of tannic acid. As galls, they should not be used in medicine ; the tincture (TINCTURA GALL^E twenty per cent., U. S.) and the ointment (UN- GUENTUM GALL^E twenty per cent. , U. S. ) are still sometimes used but are inferior to preparations of tannic acid. GAMBIR. U. S. Under the name of catechu the U. S. Pharmacopoeia of 1 890 recognized the extract of Acacia catechu. It occurs in masses of various shapes, or in small fragments, of a dull reddish-brown color, and having a bitterish, astringent, and, after a time, sweetish taste. At present the U. S. Pharmacopoeia concurs with the British in recognizing only gambir or pale catechu. The extract of the Uncaria gambir occurs in small cubes, about an inch in diameter, lighter than water, pale yellowish within, deep yel- lowish or reddish-brown externally. Both gambir and true catechu con- tain kino-tannic acid and are powerful astringents. Dose, for diarrhoea, twenty to thirty grains (1.5-2 Gm. ). Dose of the compound tincture (TINCTURA GAMBIR COMPOSITA five per cent., U. S. ), one to three fluidrachms (4-12 C.c.) ; the troches (TROCHISCI GAMBIR, U. S. ), contain one grain each. KINO KINO. U. S. The inspissated juice of Pterocarpus marsupium and of other trees. It occurs in small, irregular, angular, shining, reddish, brittle fragments, of a bitterish, highly astringent, and, after a time, sweetish taste. There are four varieties, the East India, West India, Botany Bay, and African. Of these, the first is common, the second rare, and the last two are never seen in our market. Kino contains kino-tannic acid, and its therapeutic powers are identical with those of catechu. Dose, twenty to thirty grains (1.5-2 Gm. ) ; of a tincture (TINCTURA KINO five per cent., U.S.), one to four fluidrachms (4-16 C.c.). H.3EMATOXYLON H-dEMATOXYLON. U. S. The heart- wood of Haematoxylon campechianum, or logwood-tree, a native of Central America, a dense, heavy wood of a deep reddish- brown color, containing, besides kino-tannic acid, a crystalline principle, Hamatin or Hcematoxylin, which when pure is yellow, but readily yields red or purple dyes. According to F. Combemale,* haematoxylin is capa- * Bull. Gen. de Therap., 1894, cxxvii. 408 GENERAL REMEDIES. ble of causing a fatal intoxication, commencing with rigors and fever and ending in vomiting, anuria, coma, and collapse. Haematoxylon is a mild, efficient astringent, valued on account of its sweetish taste. It is readily taken by children, but is sometimes objected to on account of the staining of the diapers by the blood-red stools which it produces. Dose of extract (EXTRACTUM H^EMATOXYLI, U. S. ), ten to thirty grains (0.65-2 Gm. ). The following formula offers an efficient and elegant remedy for diarrhceas of relaxation ; the proportions may be varied to suit individual cases. R Ext. haema- toxyli, jii ; Acid, sulph. aromat., f giii ; Tinct. opii camph., f ^iss ; Syrupi zingib- eris, q. s. ad f % vi. M. Dose, a tablespoonful, properly diluted. KRAMERIA RHATANY. U. S. The roots of Krameria triandra, of Peru, and of Krameria ixina, of northern South America. Rhatany contains kino-tannic acid and is a powerful astringent, similar in virtue to kino and catechu, but is never administered in powder. Dose of the extract ( EXTRACTUM KRAMERIA, U. S. ), five to ten grains (0.3-0.6 Gm. ) ; of the tincture (TINCTURA KRAMERIA twenty per cent., U. S. ), half to one flui- drachm (2-4 C.c. ) ; of the fluid extract (FLUIDEXTRACTUM KRAMERIA, U. S. ), twenty minims (1.25 C.c.). HAMAMELIS HAMAMELIS. U. S. Under the names of Hamamelidis cortex and Hamamelidis folia, the U. S. Pharmacopoeia recognizes respectively the bark and twigs, and the leaves of the Hamamelis virginica. There is no reason for believing that the two drugs differ in physiological or therapeutic properties except that the cortex is probably the stronger of the two. Originally in the form of a proprietary remedy, subsequently in the official prep- aration, Hamamelis has been enormously used in the United States as a local embrocation for bruises and sprains, also as an application to inflamed mucous membranes. It has been carefully studied by various chemists, but no active prin- ciple has been found in it except tannic acid and traces of a volatile oil. According to researches of W. Straub 1 its tannic acid taken into the stomach is converted into gallic acid, and as such eliminated ; although when injected intravenously it in part escapes with the urine unchanged. Under the name of Hamamelin two substances are sold in commerce, one greenish and the other brownish ; the first probably derived from the leaves of the plant, the second from the bark, each containing tannic acid. That the volatile oil of hamamelis is not a factor in any therapeutic activity of the drug seems to be shown by the fact that a very concentrated distil- late was found by H. C. Wood to have the same action upon frogs as the same amount of distilled water. The therapeutic value of distilled preparations of hama- melis would appear, therefore, to depend upon the alcohol which they usually con- tain, the rubbing with which they are applied, and the faith with which they are received by the patient. Fluidextractum Hamamelidis Foliorum, U. S., may be used in doses of one-half to two fluidrachms (2-8 C.c..), as an internal astringent in varicose veins, diarrhoea, hemorrhoids, etc. Aqua Hamamelidis, U. S., Water of Hamamelis, used as an embrocation, may be taken internally in doses of two fluidrachms (8 C.c.). QUERCUS ALBA, U. S., and QUERCUS TINCTORJA are the inner barks of the trees whose names they bear, the white and the black oak respectively. The latter is a rough, yellowish-brown bark, which is used in dyeing, under the name of ASTRINGENTS. 409 quercitron. On account of its imparting readily its color, it is rarely, if ever, employed in medicine. White oak bark also stains, but not nearly so deeply as does black oak bark, and, containing a large percentage of gallo-tannic acid, is used as a means of making cheap astringent infusions for baths, vaginal washes, etc., also in powder for poultices. The dose of the fluid extract (FLUIDEXTRACTUM QUERCUS, U. S. ) is thirty minims (2 C.c.). ROSA GALLICA, U. S., is the dried petals of the half-opened flowers of the hundred-leaved rose. They are of a deep red color, of a pleasant astringent taste, and contain a small percentage of gallotannic acid, red coloring matter, and a trace of volatile oil. Sulphuric acid changes their infusions or tinctures to a bright red color. They are almost destitute of therapeutic virtues, but their preparations, except the fluid extract, are used as elegant vehicles. The U. S. Pharmacopoeia recognizes a fluid extract (FLUIDEXTRACTUM ROS^E U. S. ), a honey (MEL ROS^E twelve per cent.), a confection (CONFECTIO ROS.E, U. S.), and a syrup (SYRUPUS fluid extract, 12.5 per cent). ROSA CENTIFOLIA, U. S., or Pale Rose, contains little tannic acid, with a vola- tile oil, and is used simply on account of its pleasant odor : out of it are prepared rose-water (AQUA ROS.S:, U. S. ) and the very elegant, bland emollient ointment, cold cream (UNGUENTUM AQU^E ROS.E, U. S. ). GERANIUM, U. S., is the rhizome of Geranium maculatum Linn., an indigenous herbal plant. It contains a large percentage of gallotannic acid, and has been used, especially boiled in milk, in the diarrhoea of children. Dose, twenty to thirty grains (1.2-2 Gm.). Dose of the fluid extract (FLUIDEXTRACTUM GERANII, U. S. ), thirty minims to a fluidrachm (2-4 C c.). RHUS GLABRA. U. S. The fruit of berries of the sumach contain a very large percentage of tannic and malic acids. They are not used internally, but their fluid extract (FLUIDEXTRACTUM RHOIS GLABR^E, U. S. ) affords a very superior gargle in anginose affections. It may be diluted with from two to four parts of water, and potassium chlorate added to saturation. AGARIC. Under the name of Agaric various species of fungi belonging to the genus Boletiis have been employed from time to time in medicine. Of these the white agaric, or purging agaric of writers, is obtained from Boletus laricis, the fungus of the European larch. It contains a whitish, very bitter acid, variously known as agaric acid, or agaricinic acid, slightly soluble in cold water, moderately so in hot water. According to the researches of Hofmeister, 1 agaric acid has upon the lower animals very little influence except in arresting the secretion of sweat by paralyzing the peripheral nerves of the sweat-glands. Both the impure extract, known in commerce as agaricin, and agaric acid have been extensively used for the purpose of arresting colliquative sweats, and in our experience have proven valuable remedies. The only untoward effect ever produced, even by the largest dose, is irritation of the gastro-intestinal canal. Two to five grains (0.13-0.3 Gm. ) of the agaricin may be given three times a day, commencing with the smaller dose and increasing. According to Hofmeister, the dose of the pure acid is from one- sixteenth to one-third of a grain (0.004-0.02 Gm. ). COTARNINE HVDROCHLORATE. Stypticin. This salt, which is obtained by oxidizing narcotine, occurs in yellow crystals, readily soluble in water and alcohol. Falk * found that cotarnine caused in frogs paralysis by depression of the motor side of the spinal cord, and in warm-blooded animals acts as a depressant both upon the cerebral cortex and motor-cord, causing narcosis with paralysis. He further determined that it has no direct influence upon the circulation ; and that upon the respiration it acts as a primary stimulant and secondary depressant, 4 io GENERAL REMEDIES. causing death by central asphyxia when given in toxic dose. Abundant clinical evidence has been published to show that cotarnine is a valuable remedy, as first stated by Freund, in menorrhagia as well as in pulmonic and other internal hemorrhages. It is said, also, to be a powerful local haemostatic. Cotarnine gauze, or absorbent cotton saturated with cotarnine, has been greatly praised by dentists and surgeons. As Mohr * in his experiments with the drug failed to produce uterine contrac- tions it seems probable that cotarnine arrests hemorrhage by some sort of astringent action, or by directly affecting the blood ; but further physiological investigation is imperative for decision. In excessive menstruation half a grain may be given three or four times a day for four days before the expected discharge ; the dose being increased to one grain when menstruation appears. In haemoptysis three grains may be administered at once subcutaneously, and repeated in half an hour if required. MINERAL ASTRINGENTS. ALUMEN ALUM. U. S. (POTASSIUM ALUM.) Owing to the cheapness of ammonia the double salt of alumina and ammonium has been largely substituted for the true alum, which contains potash and is alone recognized by the U. S. Pharmacopoeia. The physi- cal qualities of the two salts are identical, but the ammonia alum, when triturated with lime, betrays its nature by the evolved gas. Alum occurs in octahedral colorless crystals, which are often aggregated into large masses. Its taste is astringent, acidulous, and sweetish. It is soluble in nine parts of water at 59 F. and in one-third part of boiling water. It is slightly efflorescent, and when heated parts with its water of crystallization and is converted into a white powder (ALUMEN EXSICCATUM, U. S. , or Dried Alum}. The alkalies and their carbonates, lime, magnesia, and its car- bonate, potassium tartrate, and lead acetate are incompatible with alum. PHYSIOLOGICAL ACTION. According to the statements of G. B. Wood and A. Stille, alumina can be detected in the urine of persons to whom alum has been given, so that it or its derivatives must find a way into the blood. Locally, it is when in dilute solution a powerful astringent ; when in concentrated form, irritant ; as dried alum, mildly corrosive. Given in large dose to the lower animals it produces violent gastro-intestinal irrita- tion, and is capable in man of causing death, preceded by violent vomiting, bloody purging, and haematuria. (Case, Kramolik 1 . ) One ounce and five drachms of burnt alum caused death in eight hours.* THERAPEUTICS. Internally alum is of no value in practical medicine, except it be in colica pictonum, in which it is asserted by authority that it is a valuable remedy even though there be no lead in the primes -vice to be precipitated by it as a sulphate. As a local drug it is of especial value as a styptic by virtue of its powerful coagulative influence on albumin; and we have known it usefully given by atomization in hemoptysis. It is sometimes used in various anginas and other inflamed conditions of the mucous membrane, but is so irritant and attacks so strongly the teeth as to greatly lessen its value. In colliquative sweats, sponging at bedtime with alum-water, or, still better, the taking of an alum-water bath, will often materially aid in re- ASTRINGENTS. 411 storing the lost tone to the skin. In chronic ulcers with exuberant spongy granulations, and in certain conditions of conjunctivitis, alum curd is often applied with benefit. When it is desired to exert an astringent action upon the internal organs, alum is not nearly so useful as other members of the class. As a mechanical emetic it is too uncertain to be of much value. Astringent dose, ten to twenty grains (0.6 Gm. ) ; emetic dose, a teaspoon- ful of the powder for a child, a tablespoonful for an adult. Alum curd may be made by dissolving two drachms in a pint of milk, and straining, or by rubbing the alum with white of egg. Dried alum is sometimes used as a very mild escharotic for the destruction of exuberant granulations in ulcers. ALUMINII SULPHAS. U. S. Aluminum sulphate. This substance usually occurs in flattened crystalline cakes, of a sour-sweetish, somewhat astringent taste and acid reaction. It is soluble in twice its weight in water. It is an irritant active astringent, with some germicidal power. Its solution, in strength varying from half an ounce to the pint up to saturation, has been used as a local application for foul ulcers^ leucorrhcea, and other allied diseases. In solid form, or even in satu- rated solution, it is very feebly caustic. ALUMINII HYDROXIDUM. U. S. Aluminum hydroxide. Aluminum hydrate is a white, amorphous, odorless, tasteless, permanent powder, insoluble in water and alcohol, which has been used as a feebly astringent, desiccant powder in inflam- matory conditions of the skin. PLUMBUM LEAD. When a soluble salt of lead is applied to a part in not too concen- trated solution, it acts as an astringent and sedative. Owing to the con- traction of the vessels which is induced, the tissue becomes blanched, and any inflammatory action which may be present is remarkably affected. When in concentrated solution, the mildest preparations of lead are capa- ble of acting as irritants, increasing or even originating inflammation. When the salts of lead are taken internally in therapeutic doses, no decided symptoms are generally induced, except a diminution of the se- cretions, especially of those of the alimentary canal. Sometimes, when full therapeutic doses are exhibited, a slight lowering of the frequency and force of the pulse * is said to result, but we have never witnessed this. The insoluble are much less irritant than the soluble lead prepa- rations. TOXICOLOGY. Acute lead-poisoning is usually produced by a soluble salt, notably the acetate ; f but a case reported by Freyer l shows that white lead and other insoluble preparations may act as violent and even fatal irritant poisons. When the acetate is ingested in toxic dose, the first symptom is usually a persistent, sweet, somewhat metallic taste ; this in a few minutes is followed by vomiting, which may or may not be preceded by nausea. The matters vomited are often milky white, from * See Laidlaw's Observations (quoted byStill), Therapeutics, second edition, i. 177. t According to Husemann (Handbuch der Toxicologie}, the poudre de succession, so famous during the reign of Louis XIV., was composed chiefly of lead acetate. 412 GENERAL REMEDIES. the presence of lead chloride. A severe burning persistent pain in the abdomen now comes on, and is accompanied by a craving for drink. There may be obstinate constipation, or diarrhoea may ensue : in either case the stools are generally black from the sulphuret of lead. In certain cases a state of collapse is developed ; the pulse falls to 40 or 50 per minute, the voice is lost, the face is deadly pale, the lips are livid, and syncope seems imminent. In other instances the nervous symptoms may predominate, or they may accompany those of disordered circulation : cramps in the calves of the legs, severe neuralgic pains in the extremi- ties, paralysis and anaesthesia, vertigo, stupor, may any or all of them be present. In fatal cases, coma, with or without convulsions, finally develops. A distinctive mark of lead-poisoning, which occasionally is present very early, is the blue line upon the gums. After death inflam- mation of the alimentary mucous membrane is sometimes, but not always, found. One ounce of lead acetate, subacetate, or nitrate may take life. The treatment of acute lead-poisoning consists in the evacuation of the stomach, the exhibition of sodium or magnesium sulphate, and the meeting of the indications as they arise. The Epsom and Glauber's salts act as chemical antidotes, by precipitating the insoluble sulphate of lead, and also, if in excess, empty the bowel of the compound formed. To allay the gastro-intestinal irritation, albuminous drinks should be given and opium freely exhibited. Subacute and chronic lead-poisoning are almost always accidental, and occur most frequently among those whose occupation exposes them to daily contact with some compound of the metal ; manufacturers of white lead, painters, glaziers, and similar artisans furnish the greater number of victims. They may be seen, however, in persons of all conditions of life, for although neither food nor drink is often purposely adulterated with lead, yet it is frequently introduced into the system accidentally along with those necessities. Lead pipes are habitually used for the con- veyance of water, and when the water contains salts of lime, even in minute proportion, no evil results, because through the decomposition which ensues insoluble coatings are deposited on the inside of the pipes.* When the water is pure, no such reactions occurring, the lead is slowly dissolved in the form of a carbonate, and poisoning may result. Poi- soning has also frequently resulted from the employment of cosmetics and hair-dyes, from the internal or external medical use of lead prepa- rations, 2 from cooking bread with painted wood,* from imperfectly burnt pottery, 4 from habitually biting silk thread which rascally manufacturers often load with lead to give weight to it,f from lead bullets retained * For an elaborate article on the chemical relation of water to lead, see Schmidt's Jahrbiicher, cxliv. 279. t Chronic lead-poisoning is produced much more frequently by insoluble than by sol- uble compounds of lead, but it is probable that any saturnine preparation may cause it. Thus, lead chromate has killed numbers of people. (See Med. News, ii. 1887; also Therap. Gaz., iv.). ASTRINGENTS. 413 in the body (Vucetio 5 ), and from diachylon used as an abortifacient (Ransom 64 ), etc. That form of lead-poisoning in which colic is the most decided symp- tom is often spoken of as subacute. After some days of malaise and wretchedness, or sometimes very suddenly, the victim is taken with abdominal colicky pains, which increase in intensity until they become very severe. They are constant, with occasional exacerbations, are some- times dull, sometimes sharp, are generally described as twisting, and seem to centre around the umbilicus. Very often there are repeated retching and vomiting. The walls of the abdomen are retracted, rigid, knotted ; the bowels are obstinately costive ; the tongue is contracted and whitish, the appetite gone, and the thirst sometimes excessive. Neuralgic pains in the thorax and in the extremities are of frequent occurrence. In some cases the conjunctiva is distinctly icteroid. This condition, which is known as colica pictonum, or lead colic, may after a time abate, and the patient convalesce ; more usually, however, the attacks recur from time to time, becoming gradually less severe and dis- tinctive, and the patient gradually passes into chronic lead-poisoning. Occasionally the colic increases in severity ; sometimes the course of the disease is interrupted by various violent accidents. The cases of chronic lead-poisoning vary so much in their symp- tomatology as almost to baffle concise description. It has seemed to us that the symptoms can best be studied by arranging the cases in groups, but it must be remembered that in nature not only do these groups shade into one another, but also that there are all kinds of mixed cases, cases which offer simultaneously or successively symptoms of two or more of these various groups. The first group contains the great bulk of cases of chronic lead-poi- soning, at least as seen in this country. The symptoms consist of failure of health, more or less digestive disturbance, and double wrist-drop, i.e. , paralysis of the extensor muscles of each hand. Not rarely, the only noticeable symptom is the wrist-drop, the general health seeming to be very good. The true nature of such cases can usually be at once recognized by the bilateral character of the wrist-drop, cerebral and pressure paralyses being almost invariably unilateral. We have seen, however, bilateral pressure palsy, and also one or two cases of unilateral plumbic wrist-drop, due to a local absorption of lead, in artisans who had one hand much of the time in a preparation of the metal. Similar cases have been recorded by Manouvriez. 6 * The wrist-drop may exist alone, but not rarely there is with it anaesthesia of the affected part, or some- times of the shoulders or other unparalyzed portion of the body. When the paralysis is complete, the electro-contractility of the muscles is in great part or altogether absent. The rarer forms of chronic lead-poisoning may be divided into the cerebral, the periphero-spinal, and the nutritive. See also La France Med., 1882, i. 829. 4 i 4 GENERAL REMEDIES. In the cerebral cases should be included those which are commonly spoken of as encephalopathia saturnina, or saturnine cerebritis* In cerebral cases of lead-poisoning the violent brain symptoms may develop with great suddenness, or may be preceded by some days of headache, giddiness, sleeplessness, disturbed vision, strabismus, tinnitus aurium, psychical aberration, or other prodromes of brain disturbance. Delirium, which is among the chief mani- festations of the fully formed condition, may be mild, but is often maniacal ; stupor may replace or alternate with it ; and violent epileptiform convulsions, ending in coma, are not infrequent. These convulsions are usually the precursors of death, but recovery may occur even after the most severe symptoms. 8 Without the development of such severe symptoms, headache, loss of memory, giddiness, somnolence, hemianaesthesia, disturbance of the special senses, aphasia, monoplegia, hemiplegia, or multiple cerebral palsies may occur during chronic lead-poisoning. Death, preceded by severe cerebral symptoms, may take place without organic lesion ; but usually, when focal symptoms have been present, local- ized alteration of brain structure, secondary to diseases of the cerebral vessels, or to chronic inflammation of the brain or its membranes, can be detected. Some- times the cerebral symptoms are uraemic ; indeed, true plumbic encephalopathy and plumbic uraemia from contracted kidney may coexist. Again, the more serious affection may be masked by a saturnine hysteria, since cases have been reported by Charcot and by Dutil in which hysterical hemianaesthesia, amaurosis, anosmia, loss of sense of taste, and other cerebral symptoms have been the outcome of a major hysteria due to chronic lead-poisoning. Such cases as these probably occur only in individuals of previously hysterical temperament, and must be extremely rare in persons not of the so-called Latin race. Disturbances of vision are so frequent and so marked in lead-poisoning as to deserve special mention. They have been classified by de Schweinitz as follows : 1. Transient amblyopia, without ophthalmoscopic change. 2. Amblyopia without fundus lesions, or with congestion of the nerve-head, and with central scotomas analogous to those caused by other toxic agents. 3. Optic neuritis, or neuro-retinitis, either specifically due to lead or secondary to changes in the brain or kidneys. 4. Optic nerve atrophy, either consecutive to a plumbic papillitis or retrobulbar neuritis, or due to a primary effect of the lead on the visual organ. 5. Various types of retinitis, vasculitis, and perivasculitis, either primarily due to lead or secondary to nephritis. Strabismus from muscular paralysis is sometimes of saturnine origin.! The second group of cases of chronic lead-poisoning consists of those in which the nerve-symptoms apparently originate below the cerebrum. In the present group belong cases such as have been reported by Putnam, by Tisier, by Raymond, and by G. L. Walton, in which the phenomena resemble those of locomotor ataxia, except in the presence of tenderness over the nerve-trunks, preservation of the tendon reflexes, or some other atypical symptoms. We have seen several cases in which the symptoms resembled those of an acute polio- myelitis, consisting chiefly of wide-spread paralyses with rapid wasting of the * George F. Crooke 7 reports a case in which lead plaster taken for the production of abortion caused not only miscarriage, but also fatal brain lesions, preceded by choked disks, albuminuria, and convulsions. t For discussion of details, see Beau (Arch. Gen., 1848), Manouvriez (Arch, de Physiol. Norm, et Palholog., 1870, 411 ; 1876, 762), A. De Cours (De V Hemianczsthesia saturnine, Paris, 1875), Proust (Progres Mid., 1879, vii. 546), Debove (Ibid., 99, 117), and Alex. VVestphal (Archiv fur Psychiat., 1887-88, xix.). ASTRINGENTS. 415 muscles. These cases usually can be differentiated by the presence of violent neuralgic pains, paralysis of the bladder and rectum, or other atypical symptoms. Similar to these cases are those spoken of by G. Lyon, 9 in which a rapid general paralysis spread from part to part, until at last aphonia and dyspnoea, and even death from asphyxia, resulted. Severe intractable chorea has been produced by lead. Oscar Buber 10 calls attention to the form of irregular lead palsy in which the paralyzed muscles are affected with peculiar slow, worm-like, and occasion- ally painful contractions. Disturbances of sensation may occur in lead-poisoning ; anaesthesias are, perhaps, not very rare, and violent neuralgic pains, probably due to neuritis, may be the chief manifestation. In a case of H. C. Wood's in which the diagnosis was confirmed by finding lead in the drinking-water and in the urine of the patient, the symptoms were intense general pruritus, with violent neuralgic pains shooting through the rectum and the urethra, coming on at night and producing an insomnia which appeared to be unconquerable. The lesion is often peripheral, and the very rapid pulse seen in some cases may be due to disease of the vagi, which Prevost and Binet u have found degenerated. The third group of cases comprises those in which the poison chiefly expends itself upon glandular or visceral organs, or in producing wide- spread nutritive changes. It would seem that almost any of the vital structures may undergo degenera- tion. Potain 12 reports a case of saturnine cirrhosis of the liver ; while Valence 1S and Claisse and Dupre" u call attention to plumbic parotiditis, which may take the form of a slowly progressive chronic hypertrophy of the gland, with dryness of the mouth, or of a distinct sclerosis, or there may be .ulceration of the orifice of Steno's duct and obstruction. Rudolf Maier 15 has found in poisoned animals atrophic de- generations of the intestinal glands and walls. Sailor K found in twelve cases of saturnism a constant reduction in the secretion of hydrochloric acid. Of great frequency and importance are the lesions produced by lead in the kidneys. It must be remembered that temporary albuminuria may occur in lead- poisoning without serious implication of the kidneys ; while, on the other hand, fatal nephritis may exist when there js no albumin in the urine ( LanceYeaux 1B ) . A persistent low specific gravity of the urine in lead-poisoning is a symptom of the utmost gravity. Geppert " confirms the observation, previously made by Olivier, that in temporary plumbic albuminuria many isolated kidney epithelial cells may often be found in the urinary sediments ; and it is evident that a persistence of this condition must end in chronic renal disease. After death, which may be induced by uraemia, the kidneys are found contracted, granular, with excessive development of the fibrous tissue (followed by contraction) and great thickening of the walls of the blood-vessels : these changes are identical with those of contracted kidney pro- duced by gouty and other irritant poisons. As Ellenberger and Hofmeister have shown that the lead is chiefly eliminated by the kidneys, the frequency of plumbic nephritis is easily explained ; but it is not readily perceived why it is so frequently associated with an arthralgia whose course and lesions closely simulate those of chronic gout. Garrod (1859), Dickinson, LanceYeaux, Rosenstein, Leyden, 18 and other authors have reported so many cases of this association of renal and gouty manifestations that it can scarcely be doubted that the plumbism is the cause of the gouty symptoms, and not simply a complication of gout.* There are certain cases of lead-poisoning which do not conform to any of the types as yet given. * Consult Deutsch. Med. Wochenschrift, 1883, 185, 351 ; 1884, 129 ; also Paul Musehold (Die Bleivergiflung, Berlin, 1883). We have ourselves seen one case. 416 GENERAL REMEDIES. Among these very irregular cases may be mentioned those reported by E. Levy, 19 in which acute asthma was produced by the inhalation of the dust of white lead. Again, chronic saturnine asthma is sometimes seen in feeble, narrow-chested people. James J. Putnam 20 calls attention to the fact that in lead-poisoning of children the legs and feet are commonly paralyzed. Pagliano 21 has reported a case of saturnine facial palsy. It has been abundantly proved both by clinical experience and by experiments made upon the lower animals that in chronic lead-poisoning the metal may pass through the placenta into the fcetus, causing its death, with sub- sequent abortion.* As any of the obscure manifestations of lead-poisoning may exist, and even prove fatal, without a distinct history of other more characteristic phenomena, great care is sometimes necessary to avoid being misled, and not rarely the true nature of saturnine epilepsy or of saturnine albuminuria is overlooked. Hence the importance of the blue line upon the gums where they join the teeth, which is very common in persons suffering from lead-poisoning. It is said to be the result of a formation of lead sul- phide in the walls of the capillaries. As was first pointed out by J. J. Putnam, 22 chronic lead-poisoning may exist without this blue line upon the gums. Under such circumstances, if the symptoms be obscure the diag- nosis can be established only through a chemical examination of the urine.f The practitioner should see that the urine which is to be sent to the chemist for examination be slightly acidified, that directly after passing it be put in flint-glass bottles, and that it be at least a quart in quantity. From a diagnostic point of view an extremely important ob- servation, if it be confirmed, is that of Deroide and Lecompt, 23 who assert that there is in the urine of saturnine patients uroh&matoporphyrine, a red pigment, soluble in ether, water, and alcohol, which can readily be recognized by the spectroscope. In those cases of lead-poisoning which pursue a slow course to death the paralysis involves after a time the extensors of the lower as well as of the upper extremities, epileptic paroxysms occur at intervals, racking pains shoot through the limbs, points of cutaneous anaesthesia appear, and often albuminuria aids in producing the fatal issue. Gradually the patient becomes more and more cachectic, general cedema and the whitened skin betray the increasing anaemia, the paralysis extends from muscle to muscle, locomotion becomes impossible, and, if a convulsion or other accident do not close the scene, death at last takes place from loss of power in the respiratory muscles. Plumbic anaemia is probably due, at least in part, to a direct action of the lead upon the blood or the blood-making organs. According to Malassez," the red blood-corpuscles during the anaemias are not only diminished in number, but also increased in size. Sabrazes and Bourret 62 have found in the blood of a case of serious acute lead-poisoning normoblasts, basophilic, granular, and polychromatic * See Constantine Paul (Archiv Gtn., 1860, xv.), Legrand and Winter (Compt.-Rend. Soc. Biolog., 1889), and B. Annino (Schmidt's Jahrb., ccxliv., No. n). t For an elaborate discussion, see leading article in Therap. Gaz., Dec. 1887; Ibid., iii. 813, and iv. 92. ASTRINGENTS. 4*7 cells , also neutrophilic, polymorphonuclear leucocytes. In chronic lead-poison- ing, Moritz 6J found granulation of the basophilic erythocytes, and was able to pro- duce such a change in lower animals. After death lead has frequently been detected in almost all of the tissues. Heubel 25 found most of it in the bones, and less in the muscular than in the nervous system. Chatin 26 obtained from the cervical spinal cord three in one hun- dred and fifty parts. In the studies of Ellenberger and V. Hofmeister '" the liver and kidneys were found to contain the most, lead, after them the bones, then the nerve-centres, and finally the flesh. Prevost and Binet found the lead in all the tissues, but believe that it especially accumulates in the kidneys.* G. N. Pitt 28 re- ports finding over forty-seven grains of the lead sulphite in nine inches of the colon. The electro-muscular contractility is affected very early in lead-poi- soning, and may be lost before the voluntary movements. It is stated by M. Raymond that the short extensor of the thumb preserves its func- tion when all the other extensor muscles are paralyzed. The paralyzed muscles are finally exceedingly wasted, and their structure may be so totally destroyed that scarcely a single striated fibre can be found. The nerve-trunks are lessened in size, in many of their tubules the medulla has been replaced by fatty granules, and in some cases every trace of the tubules has disappeared and the nerve has been reduced to a fibrous cord. *A question of the most serious importance, which at present we are not able to answer positively, is as to whether sclerosis, neuritis, and other chronic affections of the nervous system which have been reckoned as idiopathic or of unknown origin are not frequently the outcome of an entirely latent lead-poisoning. In a remarkable paper, J. J. Putnam, of Boston ( Trans. Assoc. American Physicians, ii.), describes cases entirely apart from recognized types of lead-poisoning, in which the metal was found in the urine. These cases may be grouped as follows : i. Trembling of hands ; sense of coldness and numb- ness in toes ; lancinating pains in legs ; fatigue on exertion. 2. Marked progressive spastic paraplegia, with myosis and pupillary reactions ; ataxia and some atrophy of hands. 3. Progressive weakness and stiffness in legs, with diffused and almost universal pains ; marked tremor. 4. Temporary pain in chest, with slight dyspnoea ; progressive numb- ness, heaviness, and weakness in legs. 5. Numbness in feet and legs, with impairment of strength ; tremor of hands and tongue ; some wasting of small muscles of hands ; tem- porary retention of urine. Closely connected with this subject is the question whether lead may not be for a length of time in the system and appear in the urine without doing injury to the health. In a paper (Boston Med. and. Surg. Journ., 1890, cxxiii.) Putnam brings forward more facts, whose import is at present very doubtful. In an examination of the urine of sixty-eight persons, presenting no evidences of any dis- arrangement of health, lead was found in the proportion of about seventeen per cent., while the urine of thirty-six persons suffering from chronic and subchronic affection of the nerves, nerve-centres, and spinal cord contained lead in the proportion of fifty per cent. In the last group were cases of tremors with debility, of chronic multiple neuritis, multiple sclerosis, spastic paraplegia, muscular atrophy, epilepsy, sciatica, digestive dis- orders, etc. (Bost. Med. and Surg. Journ., 1889, cxxi.). One cannot help suspecting that, owing to defective water-supply, Bostonians are especially prone to contain lead. For a minute description of various forms of lead palsy, see Le Salurnisme, Meillere, Paris, 1903. 27 4 i8 GENERAL REMEDIES. According to the researches of DegeYine, 29 the first appearance of change in a nerve-trunk consists in the myeline becoming broken up into blocks, and the nature of the change is a commingling of a parenchymatous and an interstitial neuritis, which both De"ge"rine and Vulpian have traced upward as far as the anterior spinal roots. Lance'reaux, 30 Westphal, sl Friedlander, 32 and others may be cited as having found very distinct peripheral lesions in lead-poisoning. Whether these lesions begin in the nerve or in the muscles cannot be considered as determined. Bird- sail ss reported a case of what he believed to be a plumbic myositis, and Gourbault 34 describes primary alteration in the nerves, similar to those seen after section, as occurring in poisoned guinea-pigs, while Debove and Reaut 35 describe the first changes as resembling those of subacute myositis, and Friedlander emphatically asserts that lessening in the size of the muscular fibres and multiplication of the muscular nuclei precede the nerve-degeneration. On the other hand, Vulpian, 36 Monakow, 37 Oeller, 38 and a number of other observers* have noticed structural changes (poliomyelitis, capillary hemorrhages, etc.) in the spinal cord of men dead of plumbism ; while Popow M found that when guinea-pigs were rapidly poisoned (six to eight days) with lead there was produced a central myelitis, which first affected the large cells of the gray matter, and afterwards involved the white matter, the peripheral nerve-filaments remaining normal. There is, however, no real contra- diction, as Popow believes, between his observations and those of Gourbault, 40 for the latter poisoned his animals very slowly (six months), and it is not im- probable that the rapidity of the poisoning had an influence upon the seat of the lesion. As already stated, the symptoms of plumbism may exactly simulate those of general poliomyelitis, and both De'ge'rine and Leopold Stieglitz 41 found degen- eration of the motor cells. Karl Schaffer 42 believes that two sharply separated forms of degeneration of the nerve-centres occur in chronic lead-poisoning, one consisting of a minutely granular destruction of the protoplasm, the other of the homogenization of the contents of the cell. The evidence at present indicates that lead is capable of producing a peripheral neuritis, and also a centric poliomyelitis, which may or may not coexist in an individual case ; the probabilities being in favor of a peculiar peripheral neuritis, as the primary lesion of ordinary plumbic wrist-drop (see paper by Schultze, 4 * also Prevost and Binet). Hemor- rhages into the nerve-centres sometimes occur." There seems to be no doubt that lead really affects the nutrition of almost all of the higher tis- sues. In saturnine encephalopathy changes have been found in the gan- glionic cells as well as in the neuroglia, with stenosis of capillaries and general shrinkage of the cortex (see O' Carroll 45 ). Marked alterations are not rare in the kidneys and other glandular organs, and general fibrosis of the blood-vessels is probably more or less developed in every slowly fatal case of chronic poisoning (case, Fisher 46 ). The excretion of lead with the gall is very active, but it is probable that it chiefly escapes from the body with the urine. The elimination seems to be capricious, and much affected by potassium iodide and by other influences.* The treatment of chronic lead-poisoning evidently arranges itself under three indications : first, to prevent the ingestion of more of the poison ; second, to aid in the elimination of that in the system ; third, * For references, see Arch. f. Psychiat. und Nervenkr. , xvi. 447. f See Melsens, 47 Pouchet, 48 Annuschat, 49 and Pouchet. 50 ASTRINGENTS. 419 to relieve symptoms and restore lost functions. In lead colic the last two indications are met by purgatives, to which opium should be added to relieve pain. It is often necessary to use the most powerful drastics, such as croton oil ; but senna, salts, and other of the milder cathartics should always be tried first. Alum, it is asserted, acts in some unknown way as a specific in lead colic, and from twenty to sixty grains of it may be given four or five times a day ; but our experience is not favorable to its use. In the more chronic forms of lead-poisoning, to fulfil the second indication baths of potassium sulphuret should be employed, and potassium iodide be administered internally.* As the result of special investigation, Oddo and Silbert 51 conclude that the elimination of lead through the skin in chronic lead-poisoning is important, that it is facilitated by injections of pilocarpine, and that the sulphur baths are valuable in the treatment of chronic lead-poisoning. The bath should be given (A. Eulenburg 52 ) in a wooden tub, two or three times a week, and should contain six or seven ounces of the salt. The patient, during the half-hour of his continuance in it, from time to time should be well rubbed with a coarse towel. On coming out he is to be thoroughly washed with warm soapsuds. The dose of the iodide should be from fifteen to twenty grains, administered after meals, in dilute solution. A case is reported M in which galvanic baths were used successfully, the patient being placed in the bath and the positive pole of a twenty-eight-cell battery applied to the nape of the neck, the negative to the feet. When severe cerebral symptoms arise, treatment is of little avail, and should be largely ex- pectant, f In cases of lead-poisoning in which the symptoms resemble those of acute poliomyelitis we have used ascending doses of strychnine with most extraordinary results, rapidly deepening paralysis being almost at once controlled. It is essential that the strychnine be pushed to the point of systemic intolerance. It is best to administer it by the mouth, or if used hypodermically it should be given at least twice a day. It may possibly prove of value in other acute forms of lead palsy. * As the result of a careful series of analyses, J. D. Mann (Brit. Med. Journ., 1893, }.) concludes that in chronic lead-poisoning there is a great fluctuation in the elimina- tion of lead, that potassium iodide has no real effect in increasing the elimination, that lead is eliminated from the intestines even more freely than from the urine, and that the previous contrary results obtained by investigators have been due to chance coincidences of the iodide treatment with increase of the lead excretions from other cause. He recom- mends especially general massage, and confirms to some extent the assertion of Tedes- chi, that this massage increases remarkably lead elimination. t It seems doubtful whether the sulphur baths really aid elimination, but we have seen good follow their use. It has been denied that the iodide acts ; but cases are reported in which lead was not in the urine before, and was after the administration of the drug (see Brit. Med. Journ., 1880, ii. 1034). Moreover, John Marshall ( Therap. Gaz., iv. 97) has shown by actual experiment that potassium iodide in solution has an action on the insoluble lead carbonate and phosphate, with the formation of a soluble lead com- pound, double lead and potassium iodide ; and therefore, if lead taken into the sys- tem be deposited in the tissues as insoluble carbonate or phosphate, these latter com- pounds, on the administration of potassium iodide, will be decomposed, with the produc- tion of a soluble lead compound, and consequently a more rapid elimination of the lead will occur. 420 GENERAL REMEDIES. The local use of electricity is exceedingly important to restore the lost function of nerve and muscle. When the faradic current elicits a response, it should always be employed ; but in some cases M the con- tinued current retains its power after the induced has lost all its influence. The rule is always to apply that current which causes contraction ; if both fail, the continued current should be used, the poles being reversed at intervals of four or five seconds. The electrical stances should be tri- weekly, each lasting about fifteen minutes, and they should be persevered in for months. We have seen great improvement in a case which for the first four months yielded no results ; indeed, long after voluntary move- ment had in great measure returned, no form of electricity would cause contraction of the affected muscles.* PHYSIOLOGICAL ACTION. The symptoms of acute lead-poisoning are chiefly due to its local irritant action, but those of chronic poisoning are of wider significance. How the lead is absorbed to produce them is uncertain, probably as an albuminate. All the compounds of lead and albumin as yet discovered by the chemist are, however, precipitated by alkaline carbonates, and cannot, therefore, exist in the blood. The symptoms of chronic lead-poisoning are probably in great part secondary to the structural alteration produced by the drug, lead being a poison to all forms of protoplasm. Why in one case one set of organs should be attacked and in another case a different portion of the body is a mystery. The nephritis which is so common a result is no doubt connected with the effort to eliminate the poison from the system. The chief research we know upon the effects of lead upon the lower animals is that of Ernest Harnack, 55 who employed the compound of lead and ethyl first discovered by Loewig. When this is injected into animals in large quantities it causes a rapidly fatal train of symptoms evidently due to the action of the compound itself. When, however, the introduction into the system has been slow, a chronic poisoning is produced by the lead set free in the blood and tissues. Under these circumstances a constant symptom in both dogs and rabbits is diarrhoea, due to a violently increased peristalsis, with, in the dog, occasional attacks of colic. Harnack found that in dogs the lead ethyl produces violent ex- citement, with chorea, convulsions, etc., evidently due to an exciting or irritant action upon the cerebrum, and believes that this explains the saturnine cerebral cases sometimes seen in man. The chief symptom of the poisoning in frogs was a progressive palsy of mus- cular origin. The muscle became exhausted on repeated galvanization much more rapidly than is normal, and after death was incapable of undergoing complete post- mortem rigidity. The peripheral nerves appeared to have escaped entirely. The heart-muscle snared the fate of the voluntary muscles. The muscular action of the * M. Semmola (Bull. Acad. de Meet., 1892, xxviii.) asserts that chronic plumbism can readily be cured by the elimination of the metal from the urine under the influence of a constant galvanic current. He applies the positive pole upon the tongue and the negative pole over the region of the kidneys for a while ; later, places the positive pole upon the sides of the vertebral column and the negative pole upon the abdomen, keeping up the application for five to twenty minutes each day, using a current from one hundred to one hundred and fifty milliamperes. He affirms that in cases in which no lead could be found in the urine, after three or four days of treatment the lead could readily be detected and that its quantity gradually increased. ASTRINGENTS. 421 poison was excessively pronounced in rabbits, but was feeble in dogs and cats. Different results have, however, been arrived at by H. von Wyss, 56 who found that the loss of reflex activity, etc., in the frog was not prevented by tying an artery so as to protect the leg from the poison, and that the protected muscle lost its power of responding to electrical stimulation just as fast as did the one reached by the lead. He concludes, therefore, that the paralysis is of centric origin. Curci 57 is stated to have proved that lead exerts an irritant influence upon the peripheral branches and ganglionic centres of the pneumogastric. According to the researches of Ellenberger and Hofmeister, in the sheep toxic doses of lead greatly depress the elimination of urea. , The pulse in lead colic is usually very hard and tense. Sphygmo- graphic studies made of it by August Frank M and Ernest Bardenhewer w have been thought to indicate a condition of general arterial spasm, and have given rise to the theory that the colic is caused by intestinal anaemia from vaso-motor contraction. Harnack, however, found that in dogs and rabbits the lead ethyl has no action upon the vaso-motor system and does not produce spasm of the vessels. Moreover, he determined that both the diarrhoea and excessive peristalsis produced in dogs were arrested by atropine, which ought to promote rather than lessen vaso-motor con- traction. Lead colic in man is probably due to a spasmodic contraction of the intestines so powerful as to arrest peristalsis, and to so press upon the blood-vessels as to force the blood from the abdomen into the general circulation.* The following preparations of lead are official in the United States Pharmacopoeia : PLUMBI OXIDUM LEAD OXIDE. U. S. Litharge, which is prepared by blowing air through melted lead, occurs in small yellowish or orange-colored scales, which are insoluble in water and alcohol, but are soluble in acetic or dilute nitric acid and in a warm solution of the fixed alkalies. It is occasionally used as a desiccant astringent powder for ulcers, but its chief employment in medi- cine is in the making of EMPLASTRUM PLUMBI, or Lead Plaster, U. S. , which consists chiefly of lead oleomargarate. Lead plaster occurs in grayish, cylindrical rolls, which become adhesive at the temperature of the body, and, spread upon kid, is sometimes used as a protective to parts exposed to pressure, or to superficial ulcers or abrasions. EMPLAS- TRUM RESIN^E, or Resin Plaster, U. S. , or adhesive or sticking plaster, is made by incorporating resin with lead plaster, and, spread upon linen, is much used in surgery for mechanical purposes. EMPLASTRUM SAPONIS, or Soap Plaster, U. S. , is made by the addition of soap to lead plaster. It is employed chiefly as a protective. PLUMBI ACETAS LEAD ACETATE. U.S. Sugar of lead occurs in transparent, acicular, often aggregated, crys- tals, of a sweet, styptic taste. It is soluble in water, to which it usually * Bardenhewer affirms that pilocarpine given hypodermically will relieve simultane- ously the pulse and the colic. 422 GENERAL REMEDIES. imparts a slight milkiness. From its solution it is precipitated black by sulphuretted hydrogen, white by soluble carbonates, chlorides, and sul- phates, and bright yellow by potassium iodide. It is also incompatible with the mucilage of slippery elm, but scarcely so with that of flaxseed or of pith of sassafras. THERAPEUTICS. A solution of lead acetate is used very largely in acute external inflammations as a sedative and astringent lotion. Although chemically incompatible, it is frequently combined very ad- vantageously in these cases with opium. As a too concentrated solution acts as an irritant, the strength for use on the skin should not exceed ten grains to the ounce. In diseases of the eye it is condemned by oculists, because when there is any abrasion of the cornea it is very prone to deposit an opaque film. Internally, lead acetate has been employed very largely in hemor- rhage ; indeed, George B. Wood M commends it as the most valuable of all astringents in hemoptysis. We think it is now, however, rarely given for this purpose. Its chief use at present is in diarrhoea. On account of its sedative properties, when the purging is attended by inflammation it is the most serviceable of all the astringents ; and, owing to the prompt- ness of its action, it is also very valuable in cases with profuse serous discharges. Dose, two to five grains (0.13-0.32 Gm. ), in pill, repeated pro re nata. LIQUOR PLUMBI SUBACETATIS. U. S. The Solution of Lead Subace- tate, or Goulard' s Extract, as it is sometimes called, is a colorless limpid liquid, of a sweetish, astringent taste. When exposed to the air, it rapidly absorbs carbonic acid and deposits lead carbonate, the neutral acetate being left in solution. In its action upon the human organism, Goulard's extract resembles very closely the simple lead acetate ; but it is never used internally. Externally, it is a favorite application in cases of sprains or bruises, as well as in superficial inflammation. For this purpose it requires dilution, and from a fluidounce to four fluidounces of it may be added to a pint of water. When used upon a raw surface, the strength should not be so great. The Diluted Solution ( LIQUOR PLUMBI SUBACETATIS DILUTUS, U. S., strength four per cent.) is too weak to be of value. PLUMBI CARBONAS, or Lead Carbonate, is a heavy, white, tasteless powder, insoluble in distilled water, but slightly soluble in water contain- ing carbonic acid. It is used solely as an external sedative application. Rubbed up with linseed oil, it constitutes white lead paint, and in this form, or in that of the ointment (UNGUENTUM PLUMBI CARBON ATIS, U. S. 1890), it is a most efficient dressing for fresh burns. Care must be taken in its use, however, when a large surface is involved, as lead colic has been caused by its absorption. ASTRINGENTS. 423 PLUMBI NITRAS, U. S., or Lead Nitrate, occurs in white, nearly opaque, octahedral, very heavy crystals, soluble in two parts of water at 59 F. , and in o. 75 part of boiling water ; almost insoluble in alcohol. It is used chiefly as a disinfectant. Dissolved in water, it forms Le- doyeri s Disinfectant Solution. It acts by decomposing the sulphuretted hydrogen, itself being converted into a lead sulphide. It is said to attack actively the soldering of pipes. 61 Lead nitrate is frequently used in onychia maligna. The dead part of the nail should be cut away, and the powdered nitrate thickly sprinkled over the surface ; after a few days the slough separates, leaving a clean surface, upon which the new nail usually soon forms. Sometimes more than one application of the remedy is required. BISMUTHUM BISMUTH. The metal bismuth is never used in medicine in its simple or metallic form. BISMUTHI SUBCARBONAS, U. S. BISMUTH SUBCARBONATE, U. S. , a white or yellowish-white powder, tasteless and odorless, totally insoluble in water, soluble with effervescence in dilute nitric acid, contains not less than fifty-two per cent, of bismuth oxide ; BISMUTHI SUBNITRAS, or BISMUTH SUBNITRATE, U. S. , a heavy white powder, odorless, with a faint acid taste, and a decidedly acid reaction when applied to moistened litmus-paper, almost insoluble in water, soluble without effervescence in nitric acid, contains not less than eighty per cent, of bismuth oxide. The complicated official processes for the making of salts were designed to get rid of the arsenic, which contaminates all the bismuth ores of Europe. Of late years the South American bismuth has been introduced into com- merce, and, as it contains no arsenic commercial bismuth preparations are now pure. PHYSIOLOGICAL ACTION. The actions of bismuth subcarbonate and subnitrate are so exactly similar that they can practically be considered as one. Orfila and others of the older observers attributed to bismuth violent irritant properties, reporting severe symptoms and even death after its ingestion. These results were, however, due not to the bismuth, but to the arsenic with which it was contaminated. The soluble prepa- rations of bismuth are, it is true, active irritant poisons (see BISMUTHI CITRAS), but the insoluble subcarbonate and subnitrate, when pure, have practically no irritant influence. It was formerly denied that they are dissolved at all in the alimentary canal, but it is now certain that they are very slowly absorbed and as slowly eliminated. Harnack * affirms that the metal has been found by Orfila in the liver, spleen, and urine, and by Lewald in the milk. Bergeret and Mayen9on ~ state that when bismuth subnitrate is administered the metal can always be detected, after a few hours, in the urine. They have also discovered it in the serous exuda- tion of dropsy, and have proved that when a few grains of the salt men- tioned are given to rabbits, in from twenty to thirty minutes it can be found in the urine, kidneys, spleen, blood, and muscles, and even eight days after the administration can be detected in all the tissues. Five 424 GENERAL REMEDIES. days after the exhibition of a gramme of the subnitrate to a man they found traces of the metal in the liver and kidneys ; but the analysis of the body of a woman dead sixty-two days after the ingestion of two grammes yielded negative results. E. S. Wood 3 also has detected bis- muth in the urine four weeks after its last exhibition. The discovery by Theodore Kocher 4 that the most insoluble bismuth preparations are actively antiseptic led to their use in surgery, and to the further discovery that when applied in very large quantities to extensive wounded surfaces they are capable of yielding so much bismuth to absorption as to produce a poisoning, which is characterized by acute stomatitis, sometimes gangrenous, with a peculiar black discoloration of the mucous membrane, usually beginning upon the borders of the teeth, but spreading over the whole mouth, followed by an intestinal catarrh with pain and diarrhoea, and in severe cases with desquamative nephritis, as shown by albuminous urine and epithelial tube-casts.* That bismuth is capable of acting as a poison in the lower animals has been abundantly proved by the experiments of F. Balzer 5 and of P. Dalchd and E. Ville- jean, 6 which show that, whether given by the mouth or hypodermically, repeated large doses of it produce gradual failure of strength, a peculiar stomatitis, and evi- dences of gastro-intestinal irritation, with death from exhaustion. Balzer states that the stomatitis which it causes differs from the stomatitis of ptyalism in the tendency to rapid gangrenous change ; and also that the bismuth is eliminated with the saliva, bile, and urine, but has a distinct tendency to accumulate in the tissues. THERAPEUTICS. It is stated (by means of the Roentgen rays in the living animal,-and by means of the microscope in animals killed) that after the administration of bismuth, it maybe demonstrated that the insoluble prep- arations of bismuth gradually spread themselves over the gastro-intestinal mucous membrane, and undergo slow conversion into the black oxide of bismuth, f Experimental science, therefore, is in accord with the con- clusion previously reached by clinicians, that by virtue of their physical and chemical properties these bismuth preparations act as protectives to the mucous membrane, and especially by their slow change and absorp- tion not only exert an antiseptic influence, but have a peculiar persistent sedative, astringent action. They are, therefore, of great service in the treatment of irritations and inflammations of those mucous membranes with which they can be brought in contact. Thus, they are useful to allay vomiting dependent upon gastric irritation. In simple neuralgic gastric pain following eating, especially when occurring in feeble, badly nourished subjects, bismuth is often of great service ; and even in car- cinoma it may palliate by alleviating pain and vomiting. In Pyrosis it is sometimes successful ; in gastric and enteric catarrhs it is a standard remedy. In the simple diarrhoea of irritation and in the chronic diarrhoea of camps the bismuth preparations are often very efficient ; and in the chronic bowel complaints of children, especially as seen in the summer * For cases, see Kocher, also Petersen (Deutsches Med. Wochcnschr., June 20, 1883). t Consult Cenlralblall f. innere Medizin, 1894, S. 2. Also, Inaug. Dis., Jena, 1893. ASTRINGENTS. 425 season, given with pepsin, they are almost invaluable. Bismuth is a very serviceable topical remedy in the treatment of mucous inflammations and of ulcers to which it can be applied directly. Thus, in the beginning of a gonorrhoea, the injection every two hours of a mixture containing thirty grains of bismuth to the ounce usually brings immediate relief ; in a simi- lar way it may be employed in leucorrkcca and in acute coryza. In Ger- many it has been to some extent used as a surgical dressing. ADMINISTRATION. In order to get the best attainable results from the use of bismuth subnitrate it is necessary to vary the dose and method of administration. In stomachic affections from five to fifteen grains may be given preferably when the stomach is empty, in order that the bismuth may be distributed as closely as possible over the gastric mucous membrane. In intestinal diseases from fifteen grains to a drachm (1-4 Gm. ) may be exhibited in capsule from one to two hours after meals at a time when the gastric contents are escaping through the pylorus. Chil- dren bear proportionately very large doses : thus, five to ten grains may be given to a two-year-old infant. BISMUTHI CITRAS. U. S. The insoluble bismuth citrate is not used in medicine, but has been introduced into the Pharmacopoeia for the pro- duction of the soluble BISMUTHI ET AMMONII CITRAS, U. S. We know of no recorded cases of poisoning by this salt, which, however, is probably capable of acting as a corrosive poison. According to Feder-Meyer * the Bismuth and Ammonium Citrate causes in rab* bits violent tremblings with diarrhoea, accompanied after large doses by disturbance of the sensibility and of coordination, tetanic cramps, altered respiration (in the beginning accelerated and superficial, afterwards becoming slow), continual lower- ing of the blood-pressure, and death. The same observer noticed in chronic poi- soning similar symptoms with albuminous urine and after death fatty degeneration of the liver, heart, and renal secreting structure. Similar observations were made by Mory, 8 who states that the death in mammals is the result of cardiac paralysis, and that in the advanced stages of chronic poisoning, when the blood-pressure is very low, it is not elevated by stimulation of the splanchnic nerves nor by asphyxia. W. Steinfeld 9 has obtained in the frog from the administration of bismuth ammonio- citrate and ammonio- tartrate peculiar tremblings of the voluntary muscles with prolongation of contraction upon stimulation with the galvanic current, and slow- ing of the heart's beat, also after sufficient doses paralysis of nerves and muscles ; effects which he attributes not to the bismuth, but to the acids of the preparations. He states that the proper symptoms produced by the metal appear only after some hours, and consist of motor excitement with reflex cries which are due to irritation of the medulla oblongata. In acutely poisoned mammals he noticed vomiting and purging, convulsions with loss of power, slowing of the pulse, and sinking of the blood-pressure, believed by him to be all of centric origin. In chronic poisoning there was loss of certainty of movement with cardiac depression followed by in- creasing paralysis, usually ending in death without convulsions. In his studies upon absorption and elimination he found that the ammonio-citrates and ammonio- tartrates are quickly eliminated through the kidneys, so that, as a rule, after from ten to fifteen hours they can no longer be found in the blood, tissues, or urine. 426 GENERAL REMEDIES. THERAPEUTICS. The ammonio-citrate of bismuth in small dose is actively stimulant, astringent, and, probably, germicidal. In large dose it is a violent irritant. It has none of the peculiar properties which grow out of the insolubility of the subnitrate, but is more astringent, and has been used in chronic diarrhoea and in the acute diarrhoeas of relaxation. Dose, two to five grains (0.13-0.32 Gm. ) in dilute watery solution, re- peated every three to six hours pro re nata. BISMUTH OXYIODOGALLATE or AIROL is a grayish-green, non-irritating, tasteless, odorless powder, containing about two parts of bismuth to one part of iodine. When brought in contact with a surgical surface it turns red from the liberation of iodine. According to the studies of Carl S. Haegler it is in its bactericidal properties about equivalent to iodoform, the products of its surgical decomposition being, as in the case of that drug, active germicides. Injected into the lower animals in doses of from one to three grammes per kilo, it causes clonic convulsions, with coma, nephritis, and fatty degeneration of the liver. Theoretically the toxic dose should produce the combined symptoms of iodine and bismuth-poisoning, but in Haegler's " exper- iments the symptoms rather resembled those caused by bismuth, and in a case reported by Aemmer, 12 symptoms of bismuth-poisoning followed the injection into the cavity of an abscess of nine and one-half fluid drachms of the ten per cent, glyce- rin solution. Haegler took fifteen grains of airol in the course of three days with- out the production of any disagreeable symptoms. It has been largely used as a substitute for iodoform on account of its lack of odor. It may be employed for the making of antiseptic gauze or similar dressings, or applied directly as a dry powder ; as a salve of ten to twenty per cent, with lard or vaselin free from water, or be in- jected in ten per cent, glycerin solution in tubercular or other abscesses, or used in the form of suppositories made with cacao-butter in metritis, vaginitis, etc. Brun's Paste, much used in various skin diseases and ulcerations, consists of airol one part, mucilage and glycerin each two parts, kaolin sufficient to make a soft paste. BISMUTHI SUBGALLAS. U. S. Bismuth Subgallate. Dermatol. This is a dry, yellowish-saffron or bright-yellow powder, odorless, tasteless, insoluble in ordinary menstruum, containing from fifty-two to fifty-five per cent, of pure bismuth oxide. It is believed by many practitioners to add to the general local influence of the in- soluble bismuth preparations the astringent powers of gallic acid. Originally pre- pared by Heintz and Liebreich 10 as a substitute for iodoform, it has come quite largely into use in the treatment of eczema and other skin diseases and in surgical dressings. It is not, however, a true substitute for iodoform ; is but a very feeble germicide, and both externally and internally acts as do other insoluble preparations of bismuth, for which it may be substituted in gastro-intestinal diseases, in doses of from ten to thirty grains (1-2 Gm.). BISMUTHI SUBSALICYLAS. U. S. Bismuth Subsalicylate. A whitish, amor- phous or crystalline, odorless, tasteless, insoluble powder, containing from sixty-two to sixty-four per cent, of bismuth oxide. It has been much used in diarrhoeas under the belief that it is slowly decomposed in the intestines with the elimination of salicylic acid. We have never been able to perceive any difference between its action and that of the more ordinary insoluble salts of the metal. Dose, ten to twenty grains (0.65-1.3 Gm.). CERII OXALAS. U. S. Cerium oxalate of the U. S. Pharmacopoeia is a white powder, insoluble in water, alcohol, and ether, but soluble in sulphuric acid. It is a mixture of ASTRINGENTS. 427 the oxalates of cerium, didymium, praesodymium, lanthanum, and other rare earths. It has been employed in medicine quite largely for the relief of vomiting, especially when dependent upon pregnancy or other forms of uterine disturbance. Its action on the economy has not yet been made out, but it may be tried with some hope of success in cases of nervous or dyspeptic vomiting. The dose is one to three grains (0.06-0.19 Gm.), in pill, three or four times a day. ZINCUM ZINC. ZINCI SULPHAS Zinc Sulphate. U.S. White Vitriol occurs in irregular white masses, the pure zinc sulphate in minute, transparent, four-sided, prismatic crystals, which effloresce slightly in dry air, and are soluble in 0.6 part of water at 59 F. , and in 0.2 part of boiling water, also soluble in about three parts of glycerin ; insoluble in alcohol. The taste is styptic and peculiar. THERAPEUTICS. Zinc sulphate is in weak solution a stimulant as- tringent, in concentrated form an active irritant. Emetic dose, thirty grains (2 Gm. ). In doses of one grain (0.06 Gm. ), it has been given in pills as a stimulant astringent in chronic diarrhoea with ulceration. TOXICOLOGY. Zinc sulphate in large doses acts as an irritant poison, producing violent vomiting, colicky pains, diarrhoea, prostration, etc. The symptoms which it causes are almost identical with those produced by the corresponding salt of copper. Alkalies and their carbonates are the chemical antidotes to it, producing insoluble precipitates. Eggs and milk should also be exhibited, and the symptoms treated as they arise. Chronic zinc-poisoning, if it really exists at all, is very rare, and the metal seems to be used with impunity in cooking-utensils. Schlockow 1 affirms that zinc-smelters rarely live to be over forty-five years of age, dying sometimes of catarrh of the bronchial or alimentary mucous mem- branes, or, in other cases, of a peculiar nervous affection, which commences with burning superficial pains, exalted sensibility, and reflex activity in the legs, and afterwards puts on still more clearly the features of myelitis ; and A. Sacher * finds that intravenous injection of very large doses of zinc salts produces paralysis of the voluntary muscles. ZINCI OXIDUM VENALE. Commercial zinc oxide is a snow-white powder, obtained by burning the metal in the air. It should be used only in pharmacy. The pure oxide ( ZINCI OXIDUM, U. S. ) is a yellow- ish-white powder, insoluble in water, but soluble without effervescence in dilute acids. THERAPEUTICS. Zinc oxide is used externally as a mildly astringent, slightly stimulant, and desiccant application in skin diseases and to ulcers. When given continuously in small doses it is believed to act as a tonic and alterative upon the nervous system. It has also been commended as an astringent in chronic catarrhal diarrhoea of adults and infants, and has been largely used in epilepsy and in chorea. Dose, one-half to two grains 428 GENERAL REMEDIES. (0.03-0.12 Gm.). The ointment (UNGUENTUM ZINCI OXIDI, U. S., one part to four of benzoinated lard) is useful in various skin diseases. ZINCI CARBONAS PR^CIPITATUS. U.S. Precipitated zinc carbonate is intended to replace the old impure native carbonate, calamine. It is made by. precipitating the zinc sulphate by the sodium carbonate. It is a white powder, closely resembling in its medical properities zinc oxide. ZINCI ACETAS. U. S. Zinc acetate occurs in white, micaceous crystals, which effloresce in a dry atmosphere and are very soluble in water. The taste is astrin- gent and metallic. The zinc acetate resembles in its physiological and therapeutic qualities the sulphate, but is probably somewhat less active. It is chiefly used in collyria (one to two grains to one fluidounce), and as an injection (one to twenty grains to one fluidounce) in gonorrhoea. ZINCI BROMIDUM. U. S. This is a white deliquescent powder of a saline me- tallic taste. In full doses it is an irritant emetic but has been chiefly used in epi- lepsy. Its value is doubtful. Dose one to two grains (0.06-0.13 Gm) . CUPRUM COPPER. CUPRI SULPHAS COPPER SULPHATE. U.S. Copper sulphate occurs in blue, transparent, slightly efflorescent, rhomboidal prisms, or their fragments. It dissolves, at 59 F. , in about 2.6 parts of water and in 0.5 part of boiling water ; almost insoluble in alcohol. With ammonia its solution precipitates a bluish-white cupric hydrate, which redissolves when an excess of the alkali is added, forming a rich deep blue solution. PHYSIOLOGICAL ACTION. In very dilute solution the copper sul- phate acts locally as a stimulant and mild astringent ; in a more concen- trated form it is an irritant ; in powder it is a very mild caustic, which is scarcely capable of destroying sound tissue. The salts of copper in suf- ficient amount are poisonous to all forms of protoplasm. Coupin T found that 0.0055 P er cent, solution of soluble salt of copper will prevent ger- mination of wheat : that copper compounds affect violently the genera] nutrition in animals is shown by the production of fatty degeneration by them (see Ellenberger and Hofmeister). According to Falck, 2 the cupric sulphate causes in the lower animals great depression of temperature, with progressive general paresis, ending in death, apparently from failure of respiration. When the copper salt was given hypodermically, vomiting was not produced ; although when it was exhibited by the mouth, emesis was very violent and persistent. THERAPEUTICS. Cupric sulphate is occasionally used for its local effect in chronic enteritis and colitis, with ulceration, but is rarely of value. It was at one time much employed in the treatment of organic nervous diseases, but has fallen into deserved desuetude. Forty years ago Men- dini recommended it in the treatment of chlorosis with amenorrhcea, a use which has been revived from time to time and has recently been com- ASTRINGENTS. 429 mended by Liegeois. 13 A. F. Price 15 claims that cupric sulphate in doses of one-thirtieth of a grain three times a day greatly enhances the power of the mercurials in syphilis. Dose, one-eighth to one-quarter of a grain (0.008-0.016 Gm. ) in pill. The chief value of the so-called blue stone is as an external appli- cation. When applied in solid form to ulcers, it destroys flabby granu- lations and exerts a powerful excitant influence. Its solution acts more feebly, and is sometimes employed as a dressing for indolent idcers, but more frequently as a stimulant and alterant to mucous membranes, as in granular conjunctivitis and urethritis. In 1904 Moore and Kellerman of the U. S. Department of Agriculture stated that copper sulphate even in minute quantities is capable of destroy- ing both algae and typhoid bacilli. According to Gildersleeve w i part in 1,000,000 is sufficient to kill all typhoid germs in water in three hours although other microorganisms seem more resistant. This property de- pends probably on the disassociation of the ions, for metallic copper seems to be more efficient than any of its salts. Stewart " found that water inoculated with typhoid bacilli and kept in copper vessels contained none of these organisms after three hours and comparatively few of the other forms of bacteria, and Kraemer 18 has shown that copper foil placed in the water has the same effect. It does not seem probable that the minute quantity of copper present in these circumstances (about i part to 4,000,000) can exercise any very deleterious effect on the system especially as much of it becomes united with the organic matters and pre- cipitated. When large amounts of foreign substances are present in the water copper is so much less efficient in its germicidal powers, that accord- ing to both Fowler 19 and Doty 20 it is of no Tactical value. TOXICOLOGY. The symptoms of acute copper-poisoning generally come on in about a quarter of an hour, but may be postponed for from one to two hours. They consist of violent vomiting and purging, accom- panied by very severe colicky pains. The matters vomited are greenish or bluish, the stools glairy, mucous, and at times bloody. There is a very strong taste of copper in the mouth, and often constant expectora- tion ; excessive salivation and bronchial secretion are stated by Galippe * to be characteristic. Death may occur in a few hours, preceded by con- vulsions, paralysis, delirium, anaesthesia, and other symptoms of great nervous disturbance, seemingly as the result of a direct action of the poi- son upon the nervous system. Sometimes a tendency to syncope is very marked, and as both L. Schwarz* and W. Filehne 5 have found that toxic doses of copper salts paralyze the heart in the lower animals, cardiai death probably occurs in human poisoning. The urine is usually les- sened or suppressed. Black urine, due to the presence of haemoglobin without unaltered blood- corpuscles, has been noted ; in this case, after death all the tissues were found stained with altered blood, and evidently destruction of the blood was an important factor in the fatal result ; 6 fatty degeneration of the liver was also found. If the patient survives 430 GENERAL REMEDIES. for twenty-four hours, jaundice nearly always shows itself. After this, profound depression with nervous symptoms may develop and end in death ; but not rarely a favorable issue results, in which case the symp- toms of gastro-intestinal inflammation with fever develop themselves. The copper is said to be eliminated more freely with the salivary and intestinal secretions than with the urine (Galippe). As the action of the cupric sulphate is exceedingly rapid, any anti- dote to be of avail must be given at once and act quickly. In the poi- soning milk, eggs, or other albuminous substance should be exhibited im- mediately, freely, and repeatedly.* Soap or a fixed alkali may be used. The yellow prussiate of potash, when pure, is harmless, and precipitates instantly an insoluble compound of copper from solutions of its salt. When it is to be had in time, it may therefore be used as an antidote to the sulphate. The treatment of copper-poisoning after the administration of the antidote consists in meeting the indications as they arise ; opium should be used freely. When death occurs, the results of gastro-intes- tinal inflammation are usually found ; sometimes the intestine has a decided bluish tint, and occasionally submucous ecchymoses occur. In exceptional cases, it is said, there are no evidences of inflammation in the alimentary canal, f Fatty degeneration of the liver has been noted in man. There has been much discussion as to whether there is or is not a chronic copper poisoning among workers in that metal. The chief symp- toms which have been described as present are coppery taste in the mouth, gastro-intestinal irritation with pain, anaemia, progressive emacia- tion, cough, and nervous disturbances with tremors. The green discolor- ation upon the gums or teeth, which was first pointed out by Clapton, 7 has been noted by Taylor, by the Committee of the London Clinical Society, 8 and various other observers. It is, however, not constant, and may exist in persons who show no other evidences of poisoning. Accord- ing to Kurth, 12 it really consists of a greenish or olive discoloration on the front of the teeth, and is due to the staining of the tartar, since when the teeth are perfectly clean there is no staining. It is probable that most, if not all, of the symptoms of the chronic poisoning noted in workers in copper are due to the local action of the copper dust upon the various mucous membranes, an explanation which is rendered more probable by the fact pointed out by Kurth, and also by Lewin, 14 that workers in copper often have their hair colored green. * No time should be lost in attempting to separate the yolk from the white of the egg, but the egg should be broken into a bowl as quickly as possible, a little water added, and the whole stirred up and exhibited. t For a fatal case of repeated poisoning by copper, with much information of value to chemical experts, see La France Mid., September, 1874, abstracted in Half- Yearly Com- pendium, January, 1875. Bournevette and Yvon (Revue Scienttfique, 1874, 859) found two hundred and ninety-five milligrammes of metallic copper in the liver of a woman who had taken the ammoniacal sulphate three months previously. Minute quantities of cop- per exist in the normal human body (Bull. Therafi., xciii. 88). ASTRINGENTS. 431 When copper is given to the lower animals in continuous sufficient dose it pro- duces loss of appetite, failure of digestion, diarrhoea, and other evidences of gas- tro-intestinal catarrh ; with marked evidences of disturbances of the nutrition, such as emaciation, failure of the heart, and with a progressive paralysis and failing respi- ration ending in death. After death alterations of the blood and wide-spread fatty degeneration have been noted by numerous observers.* According to Von B6kay, 9 the muscles are very early affected, cloudiness of their protoplasm and disappearance of their cross-striation coming on. The liver and kidneys, how- ever, are especially attacked : in the beginning there are hyperplasia of the con- nective tissue and subacute nephritis, followed by fatty degeneration and finally atrophy. Although Galippe and Burcy and also Ducom 10 affirm that copper is almost without influence upon dogs, and Galippe " fed himself for one month on food containing a large amount of copper without causing any symptoms of intoxication, it is certain that whilst very minute quan- tities of copper may be taken internally habitually without producing injury, larger doses may slowly and insidiously work out fatal conse- quences. The matter is important because the metal is habitually used in the canning of vegetables, French peas, beans, etc. , owing their at- tractive color to their treatment with copper, which can be chemically recognized in them. The possibility of injury from such food has been repeatedly investigated by French and Belgian commissions, and the general verdict has been that no harm is produced. The fact that twenty millions of cans of these food-articles are con- sumed every year, and that after thirty-six years' continuance of the custom it has not been clearly established that harm is done, indicates that in the amount used the vegetables containing copper are not poisonous. It is plain that the freedom from injury depends upon the minuteness of the amount of copper ingested ; the Italian law does not allow more than 0.05 gramme of copper per kilo of food, but the researches of Tschirch would indicate that a food containing this amount of copper, if very freely taken, might do harm.t ARGENTUM SILVER. ARGENTI NITRAS SILVER NITRATE. U.S. This is a heavy anhydrous salt, crystallizing in translucent, shining, rhombic plates, and having a styptic, metallic, corrosive taste. It is solu- ble, at 59 F., in 0.6 part of water, in twenty-six parts of alcohol, in o. i part of boiling water, and in five parts of boiling alcohol. For external use the crystals are melted and run into moulds, where they harden into round, grayish, brittle sticks, about the size of a goose-quill, and having a radiated crystalline fracture. These constitute the official ARGENTI NITRAS Fusus. As only the pure salt will make well-formed crystals, the * Falck (Deutsch, Klinik, 1859, x i-)> Ellenberger and Von Hofmeister (Arch.Wissen. Prakt. Thierheilk., x. 228), W. Filehne (Deutsch. Med. Wochen., 1893, xxi.), De Moor, Von B6kay (Pester Med.-Chir. Presse, 1897, 33), Baum and Seeliger (Archivf. Thier- heilk., 1897, xxiii., 1898, xxiv.), and Trolldenier (Archivf. Thierheilk., 1897, xxiii. t For discussion upon the subject, see De Moor (Archives de Pharmacodynamie, 1895, i.) and Tschirch ( Toxicologie und Hygiene, Stuttgart, 1893). 432 GENERAL REMEDIES. impure products are always manufactured into the fused nitrate, which should therefore not be employed internally. When silver nitrate, either in substance or in solution, is exposed to the conjoint influence of light and of even a minute portion of organic matter, it turns black, and is converted into an insoluble substance, which has been believed to be metallic silver, but is more probably an oxide. For this reason the white stains which it first makes when applied to living tissues soon blacken. PHYSIOLOGICAL ACTION. Local Action. Silver nitrate coagulates albumin, and, when applied in its pure state to living tissues, acts as a caustic, coating them over with a white almost membranous film. The caustic action is, however, not a deep one, because penetration of the salt into the tissues is soon prevented by the thick and tough skin or stratum which is formed. When applied in a dilute solution it acts as an astringent, constringing the vessels and overcoming relaxation. Its local action, however, is not simply that of an astringent, but is certainly peculiar and apparently alterative to nutrition. It is also a very active germicide. Absorption and Elimination. It is evident that in the stomach sil- ver nitrate cannot long maintain its integrity. Bogolowsky ' has found that when the nitrate is added to a peptone it is readily dissolved, and that the solution formed does not coagulate albumin.* That in this or in some other analogous form silver is absorbed is proved by its having been found in various internal organs and by the discoloration which follows its protracted use : argyria of authors. When it is exhibited for a long continuous period, the skin often acquires a peculiar bluish slate color, which may become very dark, and in decided cases the conjunctiva and even the mucous membrane of the mouth are involved. The silver is found in all the tissues of the skin below the rete Malpighii f (Frommann, 2 Riemer, 3 Neumann 4 ). E. Harnack 5 asserts that in all recorded cases of argyria at least thirty grammes of the salt have been taken. The staining of the skin is always preceded by a dark discolor- ation of the mucous membrane of the mouth and gums. Both Heller and Orfila failed to detect silver in the urine of animals taking it ; but probably it is eliminated, though slowly and in very small quantities, by the kidneys. General Effects. As silver is never given for an immediate therapeu- tic action, its acute physiological action is of less interest to the therapeu- * For recent studies of this character, see Isidore Neumann (loc. cit.), also A. von Fragstein (Berlin. Klin. U'ochen., 1877, 294). t In an elaborate study of the organs of a case of argyria, Riemer detected the silver in the glomerules of the kidney, the intima of the aorta, the choroid plexus, and the mesen- teric glands. He believes that it is never deposited inside the cells, and that the silver preparation is reduced in the intestines, and the fine particles of the silver carried in the blood and lymph. Gerschun (Arbeiten aus Physiolog. Inst.zu Dorpat, x.) coincides with Riemer in affirming that the silver is deposited outside of the cells, but O. Loew (Pfi tiger's Archil', xxxiv. 603) asserts that it occurs inside of the renal endothelial cells. Jahn (Beitrdge z. Patholog. Anal., xvi.) states that the unstriated muscular fibres and the elastic tissue have a special power of reducing silver. ASTRINGENTS. 433 tist than to the toxicologist, and the detailed symptoms of its poisoning are considered under the head of toxicology. In general these symptoms consist of those of gastro-enteritis with violent disturbance of the nervous system, due to a direct action of the poison upon the cerebrum and the spinal cord.* Although the circulation is profoundly affected, death ap- pears to take place from centric paralysis of respiration. By an elaborate series of experiments Charles Rouget 6 has shown that upon all animals from a crab to a dog the soluble salts of silver act as a poison, causing in mammals vomiting and purging, and in them and the lower animals violent dis- turbance of the motor functions, as shown by paralysis and convulsions, and of the respiration, ending finally in death by asphyxia. This is in accord with the obser- vations of other investigators. Rabuteau and Mourier affirm that the almost instan- taneous death which Charcot and Ball first noted as following the injection of a large dose of silver nitrate into the veins is due to a direct paralyzing influence of the drug upon the muscle of the heart. Rouget has never seen this form of death follow the hypodermic or internal administration of the poison, the heart always continuing to beat for a greater or less length of time after the cessation of respira- tion, and also retaining its irritability. As already stated, both convulsions and paralysis are present in acute silver- poisoning. The convulsions are severe, generally tetanic, and according to Rouget are plainly reflex. A peculiarity noted by Rouget is the persistence of the convul- sions after the complete abolition of voluntary movements. Curci 7 affirms that they are due to excitation of the motor tract of the cord, and that this is preceded by a similar influence upon the sensory tracts. The death is due, in argyria, to cessation of the respiration ; Rouget even states that he has witnessed the suspension of the latter function in the frog while the activity of the reflex movements was much beyond normal. In the dog and in the full-grown cat this asphyxia is accompanied by an outpouring of mucus in the lungs, pulmonary congestion and oedema being found on post-mortem examination. Two theories have been propounded as to the cause of the asphyxia : one, that it is simply due to the choking up of the lungs by the congestion and the excessive secretion whose origin is an altered state of the blood ; a second, that both the asphyxia and the lesions in the lungs have their origin in a direct action of the poison upon the nerve-centres. The first view has been especially supported by Krahmer and by Rabuteau and Mourier. Unfortunately, we have not seen the original papers of these physicians ; but, according to Rouget, the basis of the argument of Krahmer is simply the ecchy- moses which he found in horses dead of the poison, while that of Rabuteau and Mourier is the fluidity of the blood after death, and the existence in it of granules which, on account of their solubility in ammonia, were believed to be silver chlo- ride. The French observers were, however, almost certainly mistaken in their belief that these granules were silver chloride, since ammonia dissolves haematin as freely as it does the chloride. In 1864 Charcot and Ball 8 made a series of experiments in which a silver salt that did not coagulate albumin was injected directly into the blood. They noted not only the respiratory embarrassment, but also that the hinder extremities were suddenly paralyzed, and concluded that both the asphyxia and the lung trouble were due to an affection of the central nervous system. In 1869 Bogolowsky, of * Orfila and other of the earlier observers experimented upon it by injecting it directly into the veins of animals. When exhibited in this way, it must, by coagulating the albu- min of the blood, produce thrombi, to which the subsequent symptoms are in greater or less measure to be ascribed. This method of experimentation can, therefore, throw but little light upon the action of silver nitrate when taken into the stomach. 28 434 GENERAL REMEDIES. Moscow, studied the action of a peptone of the nitrate when used hypodermically. He found, on examination of the blood of a poisoned animal, that the spectrum analysis betrayed nothing abnormal ; that the red corpuscles appeared paler and their outline more delicate than normal ; and that the white corpuscles were natural. On the other hand, Rouget examined microscopically the blood of animals poisoned with silver nitrate, and found it perfectly normal. The only conclusion to be drawn from all this seems to us to be that at present there is no proof whatever that the symptoms of acute silver-poisoning are due to alterations in the blood : that the embarrassment of respiration is not due to local lesions in the lungs is abundantly shown by the experiments of Rouget, who found that while in all animals these respiratory symptoms are very prominent, in only a few species are decided pul- monic lesions found after death. From all these facts we think it highly probable, if not altogether certain, that the theory propounded by Charcot and Ball is correct. That the motor disturbance is centric, not peripheral, in its origin is shown by the fact noted by Rouget, that the muscles and nerves preserve their excitability after the arrest of the respiration. We know of very few, if any, cases of chronic poisoning with silver salts in man (see foot-note, page 437); the following summary epitomizes the results of chronic poisoning in the lower animals. The action of the drug when exhibited continuously for a length of time in large doses has been investigated by Bogolowsky upon dogs and rabbits. He found that it produced loss of appetite, wasting, slight lowering of bodily tempera- ture, diarrhcea, diminution of the quantity of urine passed, with increase of its specific gravity and often with the presence of albumin, and transitory paralysis. How far some of these symptoms were due to the direct constitutional action of the poison and how far to derangement of the digestion dependent upon its local influence is perhaps an open question. The local action was avoided, however, as much as possible, by the use of an albuminate or of the double phosphate of silver and sodium, which does not coagulate albumin. Comparative examinations of the blood showed that the haemoglobin was diminished by more than one-third. The blood was also rendered very aplastic, as was betrayed by the constant tendency to the formation of ecchymoses. As some one has suggested that the silver in these cases replaces the iron of the blood-corpuscles, Bogolowsky made a chemical ex- amination of the latter, but failed to find any traces of silver in them, no doubt because it was not there. The solid tissues were found, after death from chronic argyria, to be in an advanced stage of degeneration, which especially affected epithelial structures. The first change was swelling and opacity of the cells, with obscuration of the nucleus. After this came fatty degeneration, fatty globules in the cell, destruction of nucleus, and finally of the cell itself. The liver and kidneys were profoundly influenced, as was also the muscular structure, especially of the heart. These results obtained by Bogolowsky have been in the main corroborated by A. V. R6zsahegzi. 9 THERAPEUTICS. The results of the chronic poisoning by silver are in every way so closely analogous to those produced by antimony, arsenic, copper, and other metallic poisons as to show that silver belongs to that class of drugs which in some way markedly affects the general nutrition. It cannot, however, be called an alterative, as at present we know of no application of its power to the needs of practical medicine. The only advantageous use of silver in therapeutics is for its local action either upon the surface of the body or upon those mucous mem- branes that can be reached directly by the drug. ASTRINGENTS. 435 As a simple caustic, the salt may be used whenever a superficial action only is required : for reasons already given (page 432), it is use- less whenever it is necessary to produce a deep eschar. As a caustic alterative, it is applied in solid form to many ulcerated surfaces, for the purpose of destroying superficial diseased tissue and of substituting, when the eschar separates, a healthy for an unhealthy action. As an antiphlogistic, silver nitrate acts not only as an astringent, but also as a germicide. In the various inflammations of the mucous membranes, such as conjunctivitis, faucitis, laryngitis, urethritis, etc. , it is used very frequently, not only in the stage of relaxation, but also in the beginning of the attack. In conjunctivitis, the solution employed should not, under ordinary circumstances, be stronger than one or two grains to the ounce ; and it should not be used at all if any corneal ulceration exists, since a deposit of silver is liable to occur and to produce opacity. In faucitis, the strength of the solution may vary from thirty to sixty grains to the fluidounce. In ordinary cases of sore throat, the application once a day or every alternate day is generally sufficient. It is best made by means of a good-sized camel' s-hair brush, each part of the inflamed surface being distinctly touched, and not the whole simply daubed or slopped over by means of a very large brush or a sponge probang. In severe cases it may be necessary to use the solution twice a day. Even a satu- rated solution can scarcely be looked upon as caustic to the more robust mucous membranes. Carl Seller J0 states that while solutions of silver nitrate of less than sixty grains to the ounce cause pain when applied to the throat, solutions of one hundred and twenty to two hundred and fifty grains act as local anaesthetics, relieving soreness, and usually arresting acute inflammations at once, if applied in the first twenty-four hours, before inflammatory exudation has occurred. In laryngitis, the solution may contain from ten to twenty grains to the ounce, and should be applied with a brush by the aid of the laryngo- scopic mirror. An attack of urethritis may sometimes be aborted in its forming stage by the injection of a strong solution (twelve grains to one fluidounce) of the salt ; but the practice is of doubtful expediency, since when it fails it greatly aggravates the trouble. When chronic gonorrhoea is strictly localized to a small spot in the posterior urethra, installation of from five to ten minims of a solution of the strength of five to ten grains to the fluidounce is often serviceable. When the inflammation is more diffused, irrigation with a weaker solution is preferable ; at first i to 5000 may be employed, and the strength gradually increased to even i to 500. Freely applied to the skin of the whole finger, silver nitrate will some- times abort a commencing felon, or, applied to the scrotum, an epididy- mitis. Internally, silver nitrate is exceedingly useful in stomachic and to a less extent in enteric diseases, exerting no doubt a purely local influence. 436 GENERAL REMEDIES. In that form of dyspepsia characterized by the vomiting of large quanti- ties of yeasty fluid, it has yielded in our hands better results than any other remedy ; and the same may be said of chronic gastritis and of gas- tric idcer. The rules of administration are identical in these three dis- eases. In the first place, regulation of the diet is imperative : if the case be a bad one, all eating of meals should be suspended, and the patient receive every two or three hours a cup of sweet milk, with sound toasted bread broken up and thoroughly softened in it. In order to wash off as much as possible the mucous membrane of the stomach, and to neutralize the acids of the stomach, forty-five minutes before the meal fifteen to twenty grains of sodium bicarbonate should be ex- hibited in a tumblerful of hot water, and ten minutes later a quarter of a grain of silver nitrate should be given in pill form. The use of cold water at meals should be absolutely forbidden, and in very serious cases, when all food is rejected by the stomach, it is sometimes advisable to allow absolute rest for two or three days to that viscus, the patient being fed by the rectum, and only a little water and pills of silver with opium being taken by the mouth. Under these circumstances,, the return to the usual method of taking food must be very gradual, at first only a tablespoonful each of milk and of lime-water being administered every hour. In chronic enteritis or colitis, silver nitrate is sometimes of service, especially if there be ulceration. For its constitutional effects silver nitrate is used solely in diseases of the nervous system. It was formerly given in epilepsy, but it has passed out of use. In chronic inflammations of the spinal cord, whether affect- ing chiefly the posterior columns and constituting locomotor ataxia, or the anterior and giving rise to paraplegia, it is still employed, but is of doubt- ful value. TOXICOLOGY. The symptoms produced by the ingestion of large doses of silver nitrate are partly gastro-intestinal and partly cerebro- spinal. In some instances the one series of phenomena predominate, in others those of the other class. In a case 11 at the Hopital St. -Louis in 1839 the symptoms were insensibility, violent convulsions, dilated pupils, and, when consciousness was partially regained, intense gastric pain : complete restoration of consciousness did not occur until eleven hours after admission, and the coma returned at intervals during several days. Vertigo, coma, convulsions, great muscular weakness, and paralysis, with intense disturbance of respiration, are in these cases the manifesta- tions of disturbed innervation, whilst the abdominal symptoms are those of gastro-enteritis. The diagnosis can generally be made by the discolor- ations of the lips and skin at first white, afterwards black and by the blackish or brownish vomit ; when the customary antidote has been given, both vomit and stools are generally white and curdy. After death the stomach and bowels are found corroded, often ecchymbsed and with patches of a white or grayish color. Poisoning by silver nitrate ASTRINGENTS. 437 is not common, and we know of but three fatal cases, one in 1837 (Taylor"), one in 1861, a woman killed by fifty grains in solution in di- vided doses, and one in 1871, a child destroyed by a piece of the solid stick three-quarters of an inch long, in spite of the use of the antidote (Scattergood 13 ). The treatment consists in the administration at once of large amounts of common salt, alkaline carbonates, or soap, the chemical antidotes, the constant use of large draughts of milk, and the meeting of symptoms as they arise. The fatal dose of silver varies very much, according, no doubt, to the presence of substances capable of decomposing it in the stomach. Thirty grains have killed, and recovery has taken place after the ingestion of an ounce (case, Husemann 14 ). Chronic argyria, or discoloration of the skin by silver, is usually unaccompanied by disturbances of health, although in severe cases the discoloration affects not only the skin, lips, gums, and sclerotic, but even the internal organs, such as the liver, spleen, and kidneys. It is there- fore not due, as has been thought, to the silver chloride, since the latter becomes dark only under the influence of the light, but to a deposition of silver itself or of its oxide.* S. Krysinski 15 found the granules in almost every tissue of the body, and states that they are an organic compound of silver, the exact nature of which has not yet been determined. The minute quantity of the metal present is shown by the analysis of Versmanns, 16 who in 14.1 grammes of dried liver found only 0.0068 gramme of metallic silver (0.047 P er cent.), and in 8.6 grammes of dried kidney 0.053 gramme (0.61 per cent.). Greater or less success has been asserted for various treatments in argyria, but in general they are equally futile. Rogers states that blistering will lighten the color very much, and Eichmann asserts (Husemann) that he has cured two cases by the use of potash baths and of soap baths, each four times a week. The older au- thorities commend the use of potassium iodide internally. L. P. Yan- dell 17 has reported two cases in which large doses of the iodide were given for many months for syphilis, and the mercurial vapor-baths used at the same time for the same purpose, with the result of a complete cure of the argyria. The fading was gradual. ADMINISTRATION. The silver nitrate should always be given in pill, and, when it is desired to obtain its constitutional influence, after meals, during the process of digestion ; but when its local action on the stomach is required, it should be administered one or two hours before meals ; and if the intestines are to be reached, the pill should be enclosed in two thick capsules. The administration of silver nitrate should not extend over a longer time than two months without a protracted intermission. The dose is one-quarter of a grain (0.016 Gm. ). * According to R6zsahegzi, Hermann has seen one case in which preceding the dep- osition of the silver there were malaise, emaciation, failure of memory, singing in the ears, -deafness, and spasms of the ocular muscles. 438 GENERAL REMEDIES. ARGENTI NITRAS DILUTUS, U. S. , is a white or grayish, solid sub- stance, often in crayons, composed of two parts of potassium nitrate with one part of silver nitrate. It may be used as a very mild caustic. Silver Oxide. (ARGENTI OXIDUM, U. S. ) An olive-brown powder, very slightly soluble in water ; has no other local action than that of a very feeble astringent, but has been commended in pyrosis in doses of a grain (o. 6 Gm. ) in pill, three times a day, on an empty stomach. It was originally incorrectly affirmed that it is incapable of producing chronic argyria, and that it is therefore superior to the nitrate in chronic nervous diseases, in which diseases it is, however, valueless. Silver Cyanide (ARGENTI CYANIDUM, U. S. ) is used solely for the preparation of hydrocyanic acid. Silver iodide, formerly official, has been used as an alterative, but is of very doubtful value. A large number of preparations of silver have been recently proposed for use in practical medicine but have not yet become official. The most important of these preparations are as follows : ALBARGIN. Gelatose Silver. This compound of silver and gelatose is a yel- lowish, bulky powder, dissolving readily in cold or warm water, and containing fifteen per cent, of silver. It affects albumin slowly, but may be used with cocaine provided the double solution be freshly prepared at the time of administration. It should be kept in amber-colored bottles. It was introduced by Bornemann, 23 to be used in a one to two per cent, aqueous solution in gonorrhoea. ARGENTI ACETAS. Silver Acetate. This has been especially recommended by Zweifel M in a one per cent, solution for the treatment of ophthalmia in new-born children. ARGENTI CITRICUM. SILVER CITRATE. Itrol. A dry, odorless powder, solu- ble with difficulty in water, has been recommended as intensely poisonous to the gonococcus and non-irritant to the urethral membrane. The injection of from i : 4000 to i : 8000 solution is said to produce no pain even in acute gonorrhoea, and may be practised four times a day. The remedy has also been used in chronic cystitis. ARGENTI LACTAS. SILVER LACTATE. Actol. This substance is soluble in fifteen parts of water, and may be used in very strong or saturated solution for the disinfection of infected wounds. It is decomposed at the point of application, but is said to form soluble compounds, so that it is able to find its way deeply into the tissues. One gramme has been given hypodermically without serious symptoms, except some burning. The application of the pure powder to an affected surface is asserted to produce only moderate and brief pain. ARGENTOL. A yellowish powder which readily splits up into oxyquinoline and metallic silver ; it has been recommended by Cipriani as efficient, in diarrhoea, as an astringent, intestinal antiseptic of which fifteen grains ( i Gm. ) may be given safely in twenty-four hours, if necessary. It has also been used surgically in the strength of i to 300 to 1000. ARGYROL. Silver Vitellin. This albuminous compound of silver occurs in dark-brown hygroscopic scales, very freely soluble in water, and containing about thirty per cent, of silver. These solutions keep well and are not irritant. At the time of this writing argyrol is probably the most popular of all the recent prepara- ASTRINGENTS. 439 tions of silver in the treatment of gonorrhceal infections of all kinds. In injections the strength of the solution should usually be from one to five per cent., although on occasion stronger solutions are usually well borne. For irrigation, solutions of i : 2000 to i : 500 are employed. Even the stronger solutions are said not to pro- duce unpleasant symptoms. Argyrol is much used by dentists in gingivitis and mouth infections. LARGIN. This compound of silver and albumen is a whitish-gray powder, soluble to about ten per cent, in water, freely soluble in blood serum, not precipi- tated by albumen, and containing n.i per cent, of silver. It has great penetrating power when brought in contact with tissue, and has been highly praised by a number of German clinicians as a germicide in the treatment of gonorrhoea and other infectious inflammations. It is said to be pre-eminently satisfactory in the gonorrhoea of women. In man, one-quarter to one per cent, solution, gradually increased to two per cent. , may be used. In women, the parts should be irrigated with the one-half to one per cent, solution, after which a five per cent, largin bougie may be held in position by a cotton plug for fifteen minutes, and the part again irrigated with a five per cent, solution of largin. This treatment should be repeated every day for one week, subsequently every second or third day only. In infectious conjunctivitis and in catarrhal corneal ulcers, Welander especially commends the use of gelatin tablets containing one per cent, of largin. ARGENTI SULPHOPHENAS. Silver Sulphocarbolate. Silberol. Introduced by Zanardi as a substitute for silver nitrate, this substance has been considerably used in gonorrhoea, and as a surgical germicide, especially in connection with the eye. It is asserted that the two per cent, solution is well borne by the conjunctiva, and that when used as a substitute for silver nitrate silberol must be employed in twice as concentrated a solution. ARGENTUM SOLUBILE. Soluble Silver. Colloidal Silver. Collargol. allotropic form of silver, discovered by M. Carey Lea 19 in 1891, occurs as a bluish or green-colored mass. It makes with water a deep red solution, which is precipi- tated by the addition of salt solutions. Soluble silver was originally employed by Cred^ as a non-poisonous germicide, to be used for internal medication in various affections, such as septiccemia, diphtheria, and tuberculosis. At first he exhibited it by inunctions, forty-five grains at one time for the adult, but later gave five to ten grammes of the one per cent, solution hypodermically or intravenously.. Theharm- lessness of these intravenous injections has been confirmed by Muller," who also affirms that in septic diseases collargol may be given with as much trust as antitoxin in diphtheria. The value of the remedy is, however, very doubtful. The experi- ments of George Brunner 25 have shown that collargol is precipitated by gelatin or bouillon ; that it is not soluble in blood serum although it remains dissolved if the solution of it be mixed with the serum ; that the germicidal properties of it are very feeble, twelve hours' contact with the one per cent, solution of it being required to kill most pathogenetic bacteria ; that when given subcutaneously or intravenously it has no apparent effect upon animals, and that granules of silver can be found later at the places of injection : finally, that whether given with infected matter or in- jected after the material, in the lower animals it has no influence over the processes of infection or upon the bactericidal power of the blood. The chills and other constitutional disturbances which were formerly produced by the intravenous injec- tions of collargol were probably due to the presence of impurities in the solutions used, and the whole drift of present evidence is to show that collargol probably never circulates in the blood to any extent, and that it is physiologically inert. ARGONIN. Argentum Casein. An albuminous preparation of silver, readily soluble in warm or albuminous water, has been highly recommended in inflam- \44<> GENERAL REMEDIES. mations due to gonococci. Its ten per cent, solution is said to produce no pain ; even in acute cases it may be used freely. ICHTHARGAN. Silver-thio-hydrocarbo-sulphonate. This compound of silver and ichthyol contains about thirty per cent, of silver and fifteen per cent, of sulphur. It is a brown amorphous powder, readily soluble in water, glycerin, and. dilute alcohol, but insoluble in absolute alcohol ; and is precipitated from its solution by sodium chloride and albumin ; the latter precipitate, however, being redissolved by an excess of albumin. It is stated to add to its germicidal and antiphlogistic influences a distinct locally anaesthetic power. According to the researches of Aufrecht, 27 ichthargan is much more destructive to gonorrhceal, pyogenic, diphtheritic and typhoid germs than is either colloidal silver or protargol, its one per cent, ointment being as active as the fifteen per cent, of collargol. According to H. C. Wood, Jr., 28 this preparation does not differ essentially in its physiological action from the ordinary salts of silver. When injected into a vein it produces a fall of the blood-pressure from cardiac weakness. After death the lungs are found congested and filled with a frothy fluid. In the frog it acts as a depressant to the spinal cord, and when locally applied as a paralyzant to muscle-tissue. Both Aufrecht ** and Wood, Jr., have found that ichthargan is much less toxic than is silver nitrate. According to the former it requires four times the fatal dose of the nitrate, while according to Wood, Jr. , the fatal dose of the nitrate for the frog is one-tenth that of the silver ichthyolate. Ichthargan is being very largely used in gonococcal and other infective diseases of the mucous membranes ; also in various infected ulcerations and skin diseases. It has been especially commended in various forms of rhinitis, tonsillitis, laryngitis, and other affections, chronic and acute, of the upper respiratory mucous membrane, either applied in spray of the glycerin solution varying from four to ten per cent. , or less freely in solutions up to twenty per cent. No irritation is produced except after the strongest applications. The strength of the ichthargan solution varies in gonorrhoea from i : 500 to i : 3000 for injections ; from i : 2000 to i : 5000 for irrigation ; one to three per cent, in instillations. In the gonorrhoea of women most excellent results are said to follow packing the vagina with tampons saturated with a solution : one to five parts of ichthargan, five of water, and one hundred of glycerin ; a five to ten per cent, ointment may also be employed. In chancroids the powder of ichthargan, full strength or diluted, may be used. In trachoma, gonorrhceal, and other infective conjunctivitis, the one to three per cent, solution may be applied with a brush ; i : 1000 used as a wash. In eczema, ulcerations, phlegmons, vaginitis, and lymphangitis, the ointment, varying from one to fifteen per cent., is advised, well rubbed into the adjacent thoroughly cleansed healthy skin, and also applied directly to the affected surface if it be exposed. Ichthargan has also been administered internally with asserted and excellent results for the relief of gastritis, and especially of gastric ulcers. Dose, one- twentieth to one-eighth of a grain in half an ounce of water on an empty stomach. Intravenously ichthargan has been used experimentally in various septic dis- eases, such as septic endocarditis, septic&mia, etc. It is stated that injections of o.oi to 0.02 gramme per kilo (one-sixth to one-third grain per two and a half pounds) may be given without risk. At present there is no sufficient evidence as to the value of the treatment. PROTARGOL. The chemical combination of silver and protein occurs as a fine, yellowish powder, readily soluble in cold water. Its solution is precipitated by albumen, by dilute solutions of sodium chloride, or by dilute acids and alkalies. It is said to contain eight per cent, of metallic silver, and was originally proposed by Professor Niesser as having the antiseptic properties of the silver salts, and being able to penetrate tissues on account of its not coagulating albumen. According to ASTRINGENTS. 441 the experiments of Petitjean, Athanasion, and Comparesco, the injection of protargol into the jugular vein of the dog produces in a very few minutes a fatal pulmonary oedema, probably due to deposition of silver and consequent mechanical obstruction. Protargol has been much used in gonorrhcca, infective conjunctivitis of various forms, as well as in infected wounds. In gonorrhoea in the female, one to two per cent, solutions of protargol are used as vaginal douches, and the half per cent, solution injected into the urethra. When the neck of the cavity of the uterus is affected bougies containing five per cent, of protargol, with starch and gum, are intro- duced into the uterus. Then a tampon saturated with a ten per cent, protargol glycerin is placed in front of the neck ; this should be done daily for a week. In acute gonorrhoea of the male, injections of half of one per cent, solution may be given three times a day, the strength rapidly increased to one per cent. ; the injec- tions to be held in the urethra from five to thirty minutes. In infected wounds a lengthened application of the five per cent, solution may be made, or the powder itself used by dusting, or a ten per cent, ointment applied. REFERENCES. ASTRINGENTS. 1. ROSENSTEIN . . . Rossbach's Pharmakol.Un- tersuch., Wiirzburg, ii. 2. HEINZ V. A. P. A., 1889, cxvi. TANNIC ACID. 1. ROSENSTEIN . . . Rossbach's Pharmakol.Un- tersuch., Wiirzburg, 1875. 2. FIKENTSCHER . . In. Dis., Erlaiigeii, 1877. 3. DANIELS In. Dis.. Bonn, 1864. 4. LEWIN V. A. P. A., Ixxxi. 74. 5. SCHROFF; CLARUS . Husemann's Die Pflan- zenstoffe, 1005. 6. STOCKMAN . . . . B. M J., Dec. 4, 1887. 7. KUCHENMEISTER . Arch. Physiol. Heilk., 1851,493- 8.' ROSENHEIM . . . B. K. W., xxxvi. 9. SCHREIBER . . . D. M W., 1897. GALLIC ACID, i. SACC Chem. News, July 24, 1871. AGARIC. I. HOFMEISTER . . A. E. P. P., 1889. COTARNINE HYDROCHLORATE. i. MOHR Ther. Geg., 1905, vii. 361. ALUM. 1. KRAMOLIK .... P. M. C. P., 1902, ii. 2. L'UnionMed.,i873,No.64. LEAD. 1. FREYER Z. Mb., 1881, i. 2. S. Jb. ccxlix. 3- Prog. M., 1877, 349. 4. S. Jb., cxliv. 279; P. M. T., iv. 241,483. 5. VUCETIO .... Allgem. Wien. Mecl. Zeit- ung, 1897, xlii. 6. MANOUVRIEZ . . L' Intoxication Saturnine, Paris, 1874. 7. CROOKE L. L., 1898, ii. 8. Charite-Annalen, ix. 159. 9. LYON Gaz. des H6pitaux, 1889. 10. BUBER Neurol. Centralbl., 1897, xvi. 11. PREVOST and BINET . R. M. S. R., 1889, ix. 12. POTAIN La Semaine Med., 1888, viii. 13. VALENCE .... Thesis, Nancy, 1888. 14. CLAISSE and DUPRE . La Presse Med., Paris, 1897, iv. 15. MAIER V. A. P. A., xc. 16. LANCEREAUX . . Trans. Internal. Med. Con., 1881, ii. 191. 17. GEPPERT . . . . Z. K. M., v. 161. 18. LEYDEN Z. K. M., 1884, 881. 19. LEVY S. Jb., clii. 250. 20. PUTNAM B. M. S. J., Feb. 1893. 21. PAGLIANO .... Marseille Med., 1891, xxviii. 22. PUTNAM Trans. Amer. Neurol. Ass., 1883. 23. DEROIDE and LECOMPT . L'Echo Med. du Nord, 1898, ii. 24. MALASSEZ . . . . A. de P., 1874, 50. 25. HEUBEL Virchow and Hirsch's Jahrbiicher, 1871, i. 316. 26. CHATIN C. R. S. B., 1862, iv. 84. 27. ELLENBERGER and HOFMEISTER . Arch. f. Wissen. u. Prakt. Thier- heilk., x. 216. 28. PITT Trans. Path. Soc., London, 1891, xlii. 29. DGERINE . . . . C. R. S. B., 1880. 30. LANCREAUX . . Gaz. M6d. Paris, 1862 ; 1871. 31. WESTPHAL . . . Arch. f. Psychiatr., iv. 776. 32. FRIEDLXNDER . . V. A. P. A., Ixxv. 24. 33. BIRDSALL . . . . N. Y. M. R., March, 1882. 34. GOURBAULT . . . Prog. M., 1880. 35. DEBOVE and REAUT . Prog. M., 1876, 151. 36. VULPIAN Maladies du Syst. Ner- veux, 1879. 37. MONAKOW .... Arch. f. Psychiat., x. 495. 38. OELLER Festschrifl d. Aerzll. Verein Miinchen, 1883. 39. POPOW V. A. P. A., xciii. 351. 40. GOURBAULT . . . A. de P., 1873. 41. STIEGLITZ .... Arch. f. Psychialr., 1892, xxiv. 42. SCHAFFER .... Ungar. Arch. f. Med., 1893, xi. 442 GENERAL REMEDIES. REFERENCE 4;. SCHULTZE .... Arch. f. Psychiatr.. 1885, xvi. 809.. 44. Prog. M., xii. 827. 45. O'CARROLL . . . B. M. J., 1893, i. 46. FISHER A. J. M. S., 189*. civ. 47. MELSENS . . . . Ann. Phys. et Chim., xxv. 48. POUCHET . . . . A. de P., xii. 74. 49. ANNUSCHAT . . . A. E. P. P., x. 50. POUCHET . . . . A. de P., 1879. 51. ODDO and SILBERT . Rev. de Md., Paris, 1892, xii. IS. Continued. 5. FILEHNE . . . . D. M. W., 1893, xxi. 6. N. V. M. R., xxi. 567. 7. CLAPTON . . . . M. T. G., June, 1868. 8. LONDON CLINICAL SOCIETY . Transactions 1870, 13. 9. VON BOKAY ... P. M. C. P., 1897, 33. 10. DUCOM A. de P.. 1877. iv. i8t. ii. GALIPPE C. R. A. S. Ixxxiv 718. 12. KURTH . . . , 13. LlEGEOIS . N. Y. M. R., 1900, Iviii. 14. LEWIN . . . D. M. W., 1900, xxvi. 15. PRICE ..... . N. Y. M. R., 1903. 53. L. L., 1876, ii. 53. 54. Meyer's Electricity, N. Y., 1869, 284. 55. HARNACK A. E. P. P., 1878. l6. GlLDERSLEEVE 17. STEWART . . iv KRAEMER . . 19. FOWLER . . . A. J. M. S., 1905, cxxix. 757. . . A. J. M. S., cxxix. 761. . . A. J. Pharm., 1906, 140. . . Journ. Roy. Army Corps., v. 391. , . N. Y. M. R., 1905, Ixvii. 90. 56. VON WYSS V. A. P. A., xcii. 5- CURCI G H M C 1883 552 Gaz d. Ospitali, March, 1883. 58. FRANK D. A. K. M., xvi. 422. i. BOGOLOWSKY 2. FROMMANN . 3. RIEMER SILVER. V. A. P A 1869 xlvi 413 59. BARDENHEWKR . B. K. W., 1877, 126. 60. WOOD Therapeutics, i. 158. . . V. A. P. A., xvii. 135. 61. Report on Hygiene, U. S. Navy, 1879. 62. SABRAZESand BOURRET . Cb. I. M., 1902. 63. MORITZ D. M. W., 1901, xxvii.; 4. NEUMANN . . 5. HARNACK . . 6. ROUGET ... . . Medizin. Jahrbiich., 1877, 369- . . Arzneimittellehre, 1883, 410. . A. de P., 1873, 356. also P. M. W., 1901, xviii. 64. RANSOM B. M. J., 1900, i. 65. SAILER J. A. M. A., 1905, xliv. 1515. BISMUTH. i. HARNACK .... Arzneimittellehre, 1883 383- 2. BKRGERET and MAYKNCON . J. A. P., 1873, 242. 8. CHARCOT and f 9. RdzSAHEGZI . . 10. SEILER .... IALL . Gaz. Med., 1864. . A. E. P. P., ix. 295. . J. A. M. S., i. 266. ii. 12. TAYLOR .... 13. SCATTERGOOD . 14. HUSEMANN . . 15. KRYSINSKI . . Beck's Medical Jurisprud., Phila., 1863, i. 675. . Med. Jurisprudence, 2d ed., 1.319. . B. M. J., May, 1871. . Toxicologie, Berlin, 1862, 868. . . L. M. R., Aug. 16, 1886. Ass., 1883, 23. 4. KOCHER Volkmann's Klin Vor- trage, No. 224. 5. BALZER C. R. S. B., 1889. 6. DALCHE and VILLEJEAN . B. G. T., 1888, Ivii. 7. FEDER-MEYER . In. Dis., Wiirzburg, 1879. 16. VERSMANNS . . 17. YANDELL . . 18. 19. LEA V. A. P. A. 1859 xvii . . Amer. Pract., June, 1872. P. M. T., vi. 204. . Amer. Journ. Science, 1889, 10. HEINZ and LIEBREICH . G. M. P., 1891. 11. HAEGLER . . . . C. B. S. A., 1895. 12. AEMMER C B. S A 1897 xxvi : 20. CREDK xxxvii. 479. .A. K. C.. 1807. Iv also 1903, Ixix. 21. CHANEVANT and ROSTERNAK . C. R. S. B., 1903, Iv. 22. NlESSER . . . - T. W.. 1807. ZINC, i. SCHLOCKOW . . . D. M. W., 1879, 208. 2. SACHER Thesis, Dorpat, 1893. COPPER, i. COUPIN C. R. A. S., 1898, cxxvii., 400. 2. FALCK D. KL, 1859, xi. 23. BORNEMANN . 24. MC'LLER .... 25. BRUNNER . . . 26. ZWEIFEL . . . 27. AUFRECHT . . 28. WOOD, JR. . . 29. AUFRECHT . . 30. FALK . . . Ther. Geg., 1901. . D. M. W., 1902. . Fort. M., 1900, xviii. . Cb. G., 1900. . . Merck's Annual Report, 1902. . . N. Y. M. J., April, 1903. . . Deutsch. Med. Wochen., 1900, xxvi. . T. M.. 1806. x. 3. GALIPPE Etude toxicol. sur la Cuivre, Paris, 1875. 4. SCHWARZ . . A. E. P. P.. iSos. xxv. FAMILY II. TONICS. MINERAL TONICS. FERRUM IRON. U.S. SINCE iron constitutes a necessary integrant portion of the red blood- corpuscles, it is a food rather than a medicine. A large proportion of the various articles of ordinary diet contain a trace of it, and it must undoubtedly find entrance with the food into the blood. Although a great amount of work has been done by chemists upon the absorption and elimination of iron, the results have been so imperfect, contradictory, and difficult of explanation that they are at present of very little use to the clinician. Iron is probably at all times in the urine in minute quan- tities. Among the older chemists, Quevenne taught that the exhibition of the salts of iron had little influence upon the amount of iron in the urine, whilst Becquerel found that the increased elimination of iron commenced directly after the first taking of a ferruginous preparation, and, though varying notably from day to day, continued on the whole until the end. Among the later chemists, Bunge, of Basel, believes that no salts of iron are absorbed into the blood, and that the value of the iron in chlorosis is due to its local action on the gastric juices. His theory is that in chlorosis there is a great poverty of gastric juice, with an excessive formation of alkaline sulphides ; that these alkaline sulphides decompose the absorbable albuminous iron compounds of the food, and render them, like ordinary salts, incapable of absorption ; and that the ordinary iron preparations occupy the alkaline sulphides, and allow the albuminous iron compounds to be absorbed. Bunge bases his theory upon the experimental results obtained by himself and by Hamburger, 1 which he believes prove, first, that in the healthy subject the continued administration of iron does not raise the red blood-corpuscles or haemoglobin ; second, that when iron is given it does not increase the amount ex- creted in the urine. The researches quoted later in this article (page 416) throw, however, the gravest doubt upon the theory of Bunge. Moreover, it is directly opposed by the research of Carl Th. Moerner, 2 who finds as the result of the study of urinary indican, etc., during the administration of iron, no reason for believing that the salts of iron act as intestinal antiseptics. The researches of certain Dorpat investigators and of Peter Robert Berry, epitomized below, would also appear to prove that the Pharmaco- 443 444 GENERAL REMEDIES. poeial preparations of iron, when taken into the organization, are not ab- sorbed, a conclusion, however, which, for reasons given a little later, cannot be accepted. Nicolai Damaskin, Johann Kumberg, Chr. Busch, and Eugen Stender, work- ing with and under the immediate supervision of Robert, of Dorpat, found, first, that the presence of iron can be demonstrated in normal filtered or unfiltered urine, both quantitatively and qualitatively ; that the elimination of iron does not cease, as has been affirmed, during fasting in man ; and that the administration of an official preparation of iron does not cause iron to disappear from the urine : second, that the iron exists in the urine in two portions, one in the morphological elements, nor- mal and pathological, of the urine, the other dissolved in the urine itself ; it being doubtful whether the iron is or is not simply in the coloring-matter of the urine, but it being certain that this iron in solution is in some very permanent combination, as it resists even heating of the urine with muriatic and nitric acids : third, that the normal relation of the iron in the morphological elements to that in solution ap- pears to be from one to seven to one to eight : fourth, that the daily elimination of iron in the urine is scarcely one milligramme, but is subject to much variation, ac- cording to nourishment, etc. ; in sickness attended by destruction of the blood, or with increase of the morphological elements of the urine, the elimination of the iron increases, but the presence of biliary coloring-matter in the urine has no in- fluence upon it : fifth, that when iron and sodium citrate is injected subcutaneously into man, in the dose of one milligramme per seven kilogrammes of weight, forty per cent, of the iron escapes in the urine unaltered, such injections being, however, attended by distinct danger of renal irritation, so that hypodermic injections of iron should be given in very minute doses only : sixth, that the administration of the ferrous citrate or of the saccharated iron carbonate by the mouth, in doses of one hundred milligrammes a day, or the rubbing into the skin of the same prepa- rations, does not perceptibly alter the elimination of iron ; so that positive proof is still wanting that this and similar preparations of the Pharmacopoeia are taken up by the human organism, although Kunkel reached opposite results upon animals. In Busch's experiments it was found that either pure or impure haemoglobin, given internally, moderately increased the elimination of iron from the urine. Peter Robert Berry * in a micro-chemical study failed to detect in the intestinal walls of the animal the iron whieh had been exhibited shortly before. Notwithstanding all the laboratory evidence just summarized, every clinician knows that almost any one of the ordinary preparations of iron is capable of increasing the amount of iron in the blood in chlorosis, and until some plausible reason other than that which is natural namely, that the iron acts after absorption is given, it remains highly improbable that iron is unabsorbed. The conclusion that the human body is capable of absorbing iron from the Pharmacopoeial preparations has, moreover, recently received so much of experimental corroboration that it would appear to be an established truth. In the first place, Socin * has shown that it is scarcely possible to determine the question of iron absorption by the simple comparison of the iron ingested and eliminated. In the second place, the chemists upon whose work so much has been presaged studied the renal elimination of iron only ; whereas the metal escapes even more freely through the intestinal tract than through the kidneys. Thus, Gott- lieb, feeding dogs on food practically free from iron, was able to obtain from the TONICS. 445 faeces nearly ninety-seven per cent, of iron which had been subcutaneously injected. He also demonstrated that twenty to sixty-five per cent, of the injected iron could at a certain time be found in the liver. Carl Jacob! 5 found that after the intra- venous injection of iron, renal elimination ceased in the dog in from two to three hours, after which fifty per cent, of the injected iron could be recovered from the liver. Zaleski 6 affirms that iron is especially eliminated by the liver. In the third place, there is direct proof of absorption. Kunkel 7 for eight weeks fed two dogs upon milk, giving to one of them iron in addition, and bleeding each dog equally from time to time. After the killing of the dogs the blood and the various organs of the body were carefully analyzed, and it was found that iron was in distinct excess in all the organs of the dog to which the metal had been given, and that in the blood there was one and a half times as much of the iron, and in the liver eight times as much, as in the similar tissues or organs of the dog used for control. Justus Gaule 8 detected chemically iron in the lymph coming from the thoracic duct of a rabbit into whose stomach a dilute solution of the ferric chloride had been in- jected. Quincke 9 not only proved that iron is excreted from the mucous mem- brane of the large intestine, but also that absorbed iron can be detected in the walls of the duodenum, a fact which has been confirmed by Hall, 10 by A. Hoff- mann, 11 and by Hare. 12 Hall further discovered that if the feeding of a carnivo- rous animal with iron had been long continued, the metal could be detected in the pulp-cells of the spleen and in the hepatic acini around the central vein. The conclusion of Hall, that iron occurs in the human system in two forms, one a fixed organic combination, haemoglobin, the other an inorganic or a very loose organic combination, is very plausible. According to Hall, it is the second combi- nation whose amount in the system continually varies with that of the iron taken into the alimentary canal. Spurred on by the theory that the inorganic preparations of iron are not absorbed, pharmaceutical chemists have put forth many organic prep- arations. Of these, dried blood or an impure hemoglobin was naturally the first to be exploited. Bunge suggested a ferruginous nucleo-albumin obtained from egg-yolk, to which he gave the name of hcematogen ; whilst Schmiedeberg and Marfori, 13 under the name of ferratin, commended a proteid compound containing from four to eight per cent, of iron, which is affirmed to be the form in which iron exists in the liver, and out of which in the body the haemoglobin is directly made. There is, however, neither clinical nor experimental evidence indicating that ferratin is supe- rior to the older compounds. Hochhaus and Quincke u found that ferra- tin and the older compounds could be traced through the duodenum into the mesenteric glands with equal facility ; and in an elaborate study on the absorption and elimination of the iron, Cloetta 15 was unable to per- ceive any difference between organic and inorganic preparations of iron in relation to their building up of the blood. When, in anaemia, there is need of more supply of material for the manufacture of blood-corpuscles, the immediate usefulness of iron is very explicable ; but in most cases of serious anaemia, even when that anaemia is of the chlorotic type and is relieved by the use of iron, there has been no lack of ferruginous food ; so that it is probable (not proven) that medicinal iron has a direct stimulant influence upon those organs which produce the red blood-corpuscles. 446 GENERAL REMEDIES. Miiller " has found that in dogs rendered anaemic by repeated bleeding and a diet as free as possible from iron that the administration of an inorganic salt of iron increased the number of nucleated corpuscles in the blood. It would seem, there- fore, that iron has a direct stimulant influence upon the formation of red blood-cells in the bone marrow. The question whether or not iron acts as a stimulant to the blood- making organs is closely connected with the question as to the effect of iron upon healthy individuals. It was formerly believed that the proper administration of the metal to healthy man would produce an excess of the red blood-corpuscles, but more recent investigations, whilst somewhat discordant and not conclusive, have unsettled this belief. The experiments of Nasse lf upon dogs are in favor of the older view, while, those of E. C. Cutler and E. H. Bradford are in opposition to it.* The first ob- server, giving iron with fat, noted not only an increase of bodily weight, but also that the specific gravity of the blood rose from 1052 to 1060.8, and the amount of the metal in the blood from 0.477 to 0.755 P er thousand parts, both the result of increase in the corpuscular element. Cutler and Bradford experimented upon man, using the tubes of M. Malassez, the result being slight diminution of the red blood- disks. As, however, the experiments were only two in number, and the subjects not under complete control as to conditions of life, these observations can hardly be considered conclusive. It appears to be a well-established fact that one of the functions of the red blood-corpuscles is to convert oxygen into ozone, which is the efficient form of the element in the system (see A. Sasse 17 ). The iron oxide outside of the body cer- tainly possesses an ozonizing power similar to that of the red disk. Thus, a spot of iron mould i.e., iron oxide on linen will in time destroy the fabric. The reason of this is the corroding action of the ozone which is slowly generated by the iron oxide. From a similar cause a fleck of rust on a bright surface of steel will steadily enlarge and deepen. It would seem a priori probable that in the blood iron acts as it does out of the body. If this be so, by increasing oxidation an increase of the iron in the blood should cause elevation of temperature and increased elimination of urea. The studies of W. Pokrowsky 18 have shown that, in cases of anaemia, after the exhibition of iron the temperature does rise, even when in the beginning it was not below normal, and that simultaneously there is an increase in the daily elimination of urea ; and the experiments of Botkin, as quoted by Sasse (we have not seen the original), establish the same fact in regard to healthy men. The in- creased oxidation cannot be due simply to an increase in the number of the red corpuscles, for while the latter accrue slowly, Pokrowsky found that the tempera- ture sometimes rose within five hours after the exhibition of the first dose. From the evidence just educed it would seem that iron increases the ozonizing power of the blood. THERAPEUTICS. Leaving out of consideration those cases which may be spoken of as instances of "accidental anaemia," i.e., anaemia due to hemorrhage, poison, starvation, or other temporary cause, which has * V. H. Meyers and F. Williams (Arch. f. Exper. Path. u. Pharm., xiii. 76) have studied the effects of enormous doses of the iron and sodium tartrate upon the lower animals. Both frogs and mammals are killed by it, the symptoms in warm-blooded ani- mals being vomiting, purging, great fall of the blood-pressure, muscular weakness, and finally coma and death. The experiments show that the heart is not much affected, but the vaso-motor system and the spinal motor centres are paralyzed. TONICS. t 447 passed off or is removable, and in which iron may be given as an aid to the rebuilding of the blood, we find that practically the anaemias are divided into two sets : those in which there is a pronounced lessening in the percentage of haemoglobin in the blood but not a corresponding lessening in the number of red blood-corpuscles, and those in which the red blood -corpuscles are greatly diminished in number. The first class of cases is typified in chlorosis, the second in the essential anaemias. Of the value of iron in chlorosis there can be no doubt. Thus, Simon 19 reports a case of chlorosis in which, under the steady use of iron for sixty-four days, the globulin increased from 30.86 parts to 90.80 parts per thousand, and the haemoglobin from 1.431 parts to 4.598 parts per thou- sand ; and Cutler and Bradford ' J0 have obtained confirmatory results with Malassez's tubes. In most cases of essential anamia with great lessening in the number of red blood-corpuscles, typified by leukamia and per- nicious an&mia, iron is of no service whatever. Unfortunately, the line between the two sets of cases of anaemia is in nature not so sharp as it can be made in treatises, and we have seen cases presenting a chlorotic form of anaemia, in which the anaemia failed to be affected at all by iron or any other treatment, remaining almost as persistent and unconquer- able as the blood-lesion of leucocythaemia. Almost all the preparations of iron are more or less astringent, and when in the blood very probably exert a direct influence upon the tissues, contracting them not merely by increasing their tone, but also by acting on their vital contractility. The preparations of iron may be divided into those which are soluble and those which are insoluble in water. At first sight it would appear that the former class of preparations would be those most readily ab- sorbed. The experiments of Quevenne have, however, demonstrated that solubility is, so far as iron is concerned, no evidence of absorbability. Quevenne asserts that the reduced iron yields the largest percentage to the gastric juice, and, as it is nearly free from astringency, it is one of the best of the chalybeates for use in pill form : but little, if any, inferior is the saccharated carbonate. If a soluble preparation be desired, the ammonic or potassic tartrates are very unirritating. When freely given, almost all preparations of iron form in the intestines sulphides, which blacken the faeces. There are persons in whom iron produces headache : this can in some cases be obviated by the use of laxatives. The observations of M. Petit, N. A. Bubnow, 21 etc., that the iron preparations in large doses inhibit the digestive processes, throw some light upon these cases. Our experience is that gouty or rheumatic patients bear iron badly, and that sometimes its exhibition seems to aggravate the arthritic symptoms. The chief centra-indications for the use of iron is the existence of plethora or of catarrhal disease of the gastro-intestinal tract. The peculiar actions of certain salts of iron will be considered under their respective preparations. 448 GENERAL REMEDIES. FERRUM REDUCTUM. U. S. REDUCED IRON. FERRI PULVIS, Iron by Hydrogen, Quevenne 1 s Iron. This substance is made by exposing ferric oxyhydrate at a white heat to the action of hydrogen, which takes away the oxygen and leaves metallic iron. It occurs as a light, iron-gray, tasteless powder, which should be completely dissolved by dilute sulphuric acid without yielding the odor of sulphuretted hydrogen, and when touched with a lighted taper should ignite and burn to the brown iron oxide. If it be black, or if it fail to answer the tests given above, it is impure ; and indeed, as offered in the shops, not rarely it is entirely spurious. Reduced iron is an efficient chalybeate, very free from astringency. Dose, two to five grains (0.13-0.3 Gm. ), in pill, capsule, or chocolate lozenge. FERRI HYDROXIDUM. U. S. FERRIC HYDRATE. The Hydrated Oxide of Iron, made by precipitating ferric sulphate with ammonia, is a reddish-brown powder, which is used solely as an antidote to arsenic. For antidotal purposes ferric hydrate should be freshly prepared, and should be so moist as to constitute a magma. Its virtues are deteriorated by age, even when it is kept under water, and are entirely destroyed by drying. If the solution of the ferric sulphate be not at hand in an emergency, the chloride will yield just as useful a product, and sodium carbonate or, better still, magnesium carbonate, may be substituted, if circumstances necessitate it, for the ammonia. The precipitate falls at once, and may be washed by putting it in a piece of muslin, squeezing out the original fluid, and then pouring on some fresh water. As the ferric hydrate is perfectly innocuous, it should be very freely administered when used as an antidote, especially since it acts only when in excess. A tablespoonful may be stirred up in water and taken at once, the dose being repeated several times if necessary. The FERRI HYDROXI- DUM CUM MAGNESII OXIDO, U. S. , differs from the ferric hydrate in con- taining magnesia, which is substituted in excess for the ammonia as a precipitant. As magnesia is not at all irritant, and is itself antidotal to arsenic, the latter preparation offers decided advantages over the older antidote. It should be given freely. FERRI CARBONAS SACCHARATUS SACCHARATED FERROUS CAR- BONATE. U. S. This greenish-gray powder is made by precipitating a solution of the ferrous sulphate by sodium bicarbonate and adding sugar in sufficient quantities. During drying, sugar is kept constantly present in large amount, so as to prevent the absorption of oxygen, and the consequent conversion of the ferrous carbonate into the ferric oxide. This carbonate is a very good chalybeate, nearly free from astringency. Dose, three to five grains (0.2-0.3 Gm. ), in pill. Griffith' s Mixture (MiSTURA. FERRI COMPOSITA, U. S.) contains the ferrous carbonate and TONICS. 449 myrrh, and has been much used in an&mia with amenorrhcea in doses of from one to two tablespoonfuls (15-30 C.c. ). FERRI SULPHAS FERROUS SULPHATE. U. S. Ferrous sulphate occurs in transparent, efflorescent, rhombic prisms of a pale bluish-green color and a metallic styptic taste. It is also official in a granular form (FERRI SULPHAS GRANULATUS). It is a very decided astringent, and in a concentrated form and sufficient amount acts as an irritant poison, producing vomiting, purging, and gastro-intestinal inflammation.* Ex- ternally its solution (five to twenty-five grains to the fluidounce) has been used as an astringent lotion, especially in erysipelas. As a simple cha- lybeate the ferrous sulphate should never be used. In chronic diarrhoea it is sometimes employed as a tonic astringent. Dose, one to two grains (0.06-0.12 Gm. ) ; in the form of the dried sulphate (FERRI SULPHAS EXSICCATUS, U. S. ), one-half to one grain (0.03-0.06 Gm. ). LIQUOR FERRI SUBSULPHATIS SOLUTION OF FERRIC SUBSUL- PHATE. U.S. MONSEL'S SOLUTION. The solution of the subsulphate (of the sesquioxide) of iron (often incorrectly called solution of the per- sulphate of iron) is a very active astringent and blood-coagulant : being also only slightly irritant, it is perhaps the most efficient of the styptics, but must in hemorrhage, to be efficient, be applied directly to the part. In h&matemesis five minims (0.3 C.c.) of it may be given in from one to two ounces of water, repeated if necessary. The atomization of its watery solution (from five to twenty drops to the ounce) often acts well in hemoptysis. The pulverization of the liquid should be complete, and the inhalation, which should last for five to twenty minutes, may be repeated at intervals of an hour or longer. In diphtheria Monsel's solu- tion is very valuable applied freely, of full strength or diluted pro re nata, to the throat every three to twelve hours. In overdose Monsel's solu- tion is an irritant poison ; the antidote is soap or an alkaline carbonate. The Solution of Ferric Sulphate ( LIQUOR FERRI TERSULPHATIS, U. S. ), owing to its irritant action, is used only to make the ferric prepa- rations. TINCTURA FERRI CHLORIDI. U. S. Tincture of Ferric Chloride. This preparation contains the ferric chloride, hydrochloric acid, and alcohol, and, from the reactions of the last two ingredients, chloric ether. It is a reddish-yellow liquid, actively chalybeate, very astrin- gent, and possessed of peculiar properties, some of which may be due to the ether in it. Decidedly diuretic and escaping through the kid- neys, it directly affects the genito-urinary mucous membrane. It is much used in chronic Brighf s disease and combined with tincture of * In a case reported in the N. Y. Med. Journ., xxxviii. 401, the early symptoms, as stated by the patient, were chiefly nervous : little confidence can, however, be reposed in the patient's report of symptoms or of the amount ingested. 29 450 GENERAL REMEDIES. cantharides in gleet. In erysipelas it is constantly employed with remark- able results, controlling the disease in a manner not yet understood. Analogy has suggested its employment in other adynamic affections, such as diphtheria and pyaemia, but its value in these diseases is much more doubtful. It is so destructive to the teeth that except in the tooth- less its use as a gargle is unjustifiable ; and even in its ordinary thera- peutic use, by the employment of a tube, etc. , the teeth should be pro- tected as far as possible. Dose, ten to thirty drops (0.6-2 C.c. ) as a chalybeate three times a day, in erysipelas every two or three hours. The orange-yellow, crystalline, deliquescent Ferric Chloride (FERRI CHLORIDUM, U. S. ) is rarely used. Liquor Ferri Chloridi, U. S. , Solu- tion of Ferric Chloride, should contain twenty-nine per cent, of the anhy- drous salt. It is an acid, irritant, reddish-brown liquid, of which the dose is two minims (0.15 C.c.). SYRUPUS FERRI IODIDI. U. S. The Syrup of Ferrous Iodide is a transparent, greenish liquid, of a sweet, ferruginous taste. It deposits no sediment on keeping, and should not affect the color of starch. If it strikes a blue color with the latter substance, it contains free iodine. The syrup of ferrous iodide is a favorite remedy in those cases of anaemia in which there is a distinct scrofulous taint. It is believed to possess the peculiar alterative powers of iodine, conjoined with the tonic properties of iron. It is much used in scrofulosis occurring in anaemic children ; but it certainly possesses no advantages over a ferruginous tonic and iodine when given separately but simultaneously. Dose, for a child two years old, five to ten drops (0.3-0.6 C.c.) ; for an adult, thirty to forty minims (2-2.5 C.c.). As it affects the teeth very seriously, it should always be freely diluted when taken, and the mouth should be well washed after its administration. FERRI IODIDUM SACCHARATUM. U. S. 1890 Saccharated Ferrous Iodide is a yellowish-white or grayish powder which represents the chem- ical and medical properties of the corresponding syrup, being prepared by a parallel process. It may be substituted for the syrup in doses of from two to five grains (0.13-0.3 Gm. ), given in pill form. FERRUM DIALYSATUM. Dialyzed Iron is a clear, neutral, nearly tasteless, dark red liquid, prepared by dialyzing a solution of the chlo- ride of iron. Its exact chemical composition is uncertain, but it is so- unstable that a precipitate is at once produced by minute quantities of alkalies, almost all soluble salts, and many organic substances. Owing to- ils tastelessness and its freedom from astringency it was for a short time much used as a chalybeate in doses of from twenty to forty drops (1.2- 2.5 C.c. ), but the ferric oxide which results from its immediate precipita- tion in the stomach is a very feeble substance, and the preparation has almost passed out of vogue. It may, however, be used as an antidote TONICS. 45i to arsenic. Doses of a tablespoonful (15 C.c. ) may be given every five or ten minutes pro re nata* There are five official Iron Citrates, each soluble in water. Two of these (FERRI CITRAS and FERRI ET AMMONII CITRAS) occur in gar- nety scales, and are simply mild chalybeates. Dose, five grains (0.3 Gm. ). The Iron and Quinine Citrate (FERRI ET QUININE CITRAS), in transparent scales, varying from reddish brown to yellowish brown in color, and Soluble Iron and Quinine Citrate (FERRI ET QUININE CITRAS SOLUBILIS, U. S. ), each containing twelve per cent, of alkaloid, may be given in doses of five grains (0.3 Gm. ) or more. The Iron and Strych- nine Citrate ( FERRI ET STRYCHNINE CITRAS) contains one per cent, of strychnine, f Dose, two grains (o. 125 Gm. ). FerriHypophosphis, U. S. , is almost insoluble. Dose, eight grammes. There are two official Iron Tartrates (FERRI ET AMMONII TARTRAS and FERRI ET POTASSII TARTRAS), each occurring in garnety scales, and each soluble in water. Dose, five grains (0.3 Gm. ). The Ferrous Lactate (formerly official) occurs in greenish-white crystalline crusts or grains, soluble in forty parts of water. It is a good chalybeate. Dose, five grains (0.3 Gm. ). Soluble Ferric Phosphate (FERRI PHOSPHAS SOLUBILIS) and Soluble Ferric Pyrophosphate (FERRI PYROPHOSPHAS SOLUBILIS) are excellent preparations, occurring in apple-green scales, completely soluble in water, and nearly free from astringency and ferrugi- nous taste. Dose, five grains (0.3 Gm. ). Ferric Ammonium Sulphate (FERRI ET AMMONII SULPHAS, U. S. ) occurs in octahedral crystals of a pale violet color : it is freely soluble in water, is very astringent, and is often useful in atonic leucorrhcea, in doses of five grains, three times a day. MANGANESE. The Manganese Dioxide (MANGANI DIOXIDUM PRECIPITATUM U. S. ), and the Manganese Sulphate (MANGANI SULPHAS, U. S. ) have been supposed to possess therapeutic properties similar to those of iron. The metal manganese certainly exists in the blood, but its salts have failed to gain the confidence of the profession, although highly recommended by Harmon, of Belgium, and by P6trequin * as an adju- vant to the chalybeates. In Garrod's 2 experiments upon anaemia the preparations of manganese failed to be of service. According to C. C. Gmelin, the sulphate acts as a powerful cholagogue on the lower animals, and Thomson states that it is a purgative to man in doses of one or two drachms. Leand 3 affirms that the manganese oxide is therapeutically equivalent to the preparations of bismuth excepting in that it does not constipate, and that it may be used with advantage in gastralgia, py- rosis, and similar stomachic derangements. Dose, five to fifteen grains (0.3-1 Gm.). * See Phila. Med. Times, viii. 104, 151, 335. t The alkaloidal compounds with iron are very ineligible preparations, because they do not allow the practitioner to vary the proportionate doses of the two ingredients. 452 GENERAL REMEDIES. MINERAL ACIDS. Sulphuric, hydrochloric, nitric, and nitro-hydrochloric acids, when in concentrated form, rapidly destroy all organic tissues, and are, therefore, corrosives, hydrochloric acid being the feeblest. Owing to its abstraction of the element of water from the carbon of organic tissues, sulphuric acid blackens organic matter at the same time that it destroys its texture ; nitric acid stains organic tissue a deep yellow color ; nitro-hydrochloric acid produces a somewhat similar but much less pronounced discoloration. In the detection of poisoning by one of these agents the color of the stain upon the person or clothing is often of great assistance. Holes made in the linen by one of these acids are to be distinguished from those made by fire or mechanical violence by the pulpy character and acid reaction of the edges. The general symptoms of poisoning by mineral acids are similar, and depend for their severity especially upon the amount and the concentra- tion of the dose taken, although sulphuric and nitric acids are more power- ful than is hydrochloric acid.* Death from collapse has resulted in two and a half hours, but months may be required in the working out of the fatal result. The symptoms are immediate pain in the mouth, gullet, and epigastrium, violent vomiting (after sulphuric acid the matters may be tarry), and rapid collapse marked by cold wet surface, feeble pulse, and suppressed voice. The mind is usually clear until very late in the poisoning. After a small dose the chief symptoms may be connected with the upper digestive passages. Thus, Maukopff has recorded suppurative parotitis largely due to the closure of the duct of Steno. Ulceration of the larynx or oesophagus has frequently been noted. Desquamative nephritis may be developed several days after subsidence of the first symptoms. In a case of sulphuric acid poisoning recorded by Maukopff, the urine which had ceased to be albuminous on the third day became so again on the twentieth, with a simultaneous development of casts contain- ing blood-corpuscles ; after death tubular nephritis was found. Another symptom noted by Maukopff was intercostal neuralgia. After death, destruction of the oesophagus, stomach, or air-passages is usually found, the color of the slough black after sulphuric, yellow after nitric acid being characteristic. Probably in all cases in which death does not take place too early, wide-spread degeneration of proto- plasm takes place. A. D. Kazowsky, 1 has found that this involves the cells of the heart-ganglia, which undergo parenchymatous swelling, fol- lowed by necrosis of the cells and vacuolization not only of the nuclei but also of the general protoplasm. When the dose has not been sufficient to kill, protracted illness from local organic alterations usually results. * Cases of sulphuric acid poisoning (Med. Times and Gaz., 1863, i.). TONICS. 453 The treatment of a case of acid-poisoning consists in the immediate administration of soap, chalk, whitewash, magnesia, or other available antidote. Notwithstanding Christison's condemnation of the alkaline carbonates as too irritating, they should be used unhesitatingly in dilute form if immediately at hand. ACIDUM SULPHURICUM. U. S. SULPHURIC ACID. Oil of Vitriol | is, when pure, a colorless, heavy liquid which on exposure to the air rapidly absorbs moisture. The official acid has a sp. gr. 1.826. Concentrated sulphuric acid is not rarely used as an escharotic, for which purpose it is mixed with finely powdered charcoal so as to form a paste. Appropriately diluted, it has been employed as a stimulant and astringent lotion in venereal and other indolent ulcers. Internally, sul- phuric acid is very useful as an astringent in colliquative sweats (night- sweats} and in profuse serous diarrhoeas. We have used it with great advantage in the sudden serous vomiting and purging of infants known as cholera infantum. It has been employed with advantage in cholera, and a remarkable series of observations by R. G. Curtin * at least furnish good reason for further testing its powers as a prophylactic against this disease. The facts recorded by Curtin are as follows. A very severe epidemic of the disease ceased in the Insane Department of the Philadelphia Almshouse within twelve hours after the lunatics were all put upon the free use of sulphuric acid lem- onade, the only new case after this being in a man who refused to use the prophy- lactic. Two days after the use of the sulphuric acid was stopped two new cases occurred, and the epidemic was again arrested by the use of the acid. In the sur- gical wards of the Hospital Department the acid was used from the beginning of the epidemic ; and these wards, although in no way isolated, were the only parts of the institution unvisited by the disease. The sulphuric acid probably acted by producing an excessive acidity of the alimentary canal, it being well assured that the cholera organism will develop only in an alkaline condition of the alimentary tract. Thus, the dog, whose digestive tract is highly acid, resists the action of the bacillus unless an alkaline carbonate be freely given, when choleraic symptoms appear after the administration of the cholera organism. Sulphuric acid was formerly used in hemorrhages, but is now rarely employed. It is, we think, much less efficacious than are some other reme- dies. In acute lead-poisoning the dilute acid is an efficient antidote, and in white lead works the free use of sulphuric acid lemonade by the em- ployees is said to be advantageous as a prophylactic against the chronic poisoning. ADMINISTRATION. Sulphuric acid should be given properly diluted, and with the requisite precautions to prevent its injuring the teeth. It is * It is very probable that other acids are equally antidotal to the cholera germ, since Richard P. Strong found that the addition of one per cent, of citric acid to water infected with the cholera germ made it safe to drink. It was noted further that a large Philippine lemon, containing forty cubic centimetres of juice, was equivalent to 2.74 grammes of citric acid. Report Government Laboratories, Philippine Islands, Sept. i, 1903. 454 GENERAL REMEDIES. best administered in the form either of the dilute (AciDUM SULPHURI- CUM DILUTUM ten per cent, by weight, U. S. ; sp. gr. 1.070 ; dose, fifteen to thirty drops (1-2 C.c. ) or of the aromatic sulphuric acid (AciDUM SULPHURICUM AROMATICUM about twenty per cent, by weight, U. S. ). The last preparation contains alcohol and aromatics. Its dose is from ten to twenty drops (0.6-1.3 C.c.), well diluted. ACIDUM HYDROCHLORICUM. U. S. Hydrochloric Acid is a color- less aqueous solution of hydrochloric acid gas, having the specific gravity of 1.158 and containing 31.9 per cent, by weight of the gas. The yel- lowish tint of commercial hydrochloric acid is due to the presence of ferric chloride, organic matter, or other substance. Hydrochloric acid, being the normal digestive acid of the stomach, is often advantageous in cases in which chronic indigestion is connected with the failure to secrete acid in the stomach, and the combination of it with strychnine, bitter tonics, and aromatics is often serviceable. In the so-called " Swedish plan" of treatment of typhoid fever, hydrochloric or other mineral acid is given in very large quantities. Although the method was at one time much in vogue, it has no justification in results, and is to be avoided. The local use of hydrochloric acid in diphtheria, made famous by Bretonneau, has deservedly gone into oblivion. As a poison, hydrochloric acid is the most feeble of its class, recovery having occurred after the ingestion of an ounce.* ADMINISTRATION. The acid is best given in the form of the official ACIDUM HYDROCHLORICUM DILUTUM (ten per cent.; sp. gr. 1.049). Dose, ten to thirty drops (0.6-2 C.c.), properly diluted. ACIDUM NITRICUM. U. S. Nitric Acid is a liquid of the specific gravity of about 1.403, which as first made is colorless, but by exposure to the light acquires a yellow tint. It oxidizes all the common metals except gold, and is exceedingly corrosive to living tissue, which it stains an indelible yellow. When diluted it converts most animal and vegeta- ble substances into oxalic, malic, or carbonic acid. When taken internally in small amount, nitric acid acts as a stimulant upon the glandular system of the alimentary canal, and in serous diar- rhoea appears to exert an astringent influence. Nitric acid is frequently used as a powerful escharotic in cases of chancre, venereal or other warts, hospital and other acute gangrenes. In many instances in which formerly it was relied upon it has been replaced by antiseptic measures. In its employment care should be taken to protect the sound tissue by oil or, still better, by a layer of soap. It may be applied by means of a splinter of wood, or, if it is to be used more freely, by a little mop. When it has penetrated as deeply as is desirable, washing the part with warm soapsuds will prevent further action. * See Boston Medical and Surgical Journal, xv. TONICS. 455 Internally, nitric acid has been used in low fevers, but with very doubt- ful advantage. In dyspepsia, in chronic hepatic congestion, in the oxalic acid diathesis, and in the dyscrasia of constitutional syphilis nitric acid has been employed with advantage, but is much inferior to nitro-hydro- chloric acid. In 1826 Hope asserted that ACIDUM NITROSUM has a specific action in serous diarrhoea, including the sudden acute diarrhoeas of hot climates, and in the chronic dysenteries originating under similar circumstances. The formula he employed is as follows : R Acidi nitrosi, fsji ; Misturae camphorae, f^viii ; Misce, et adde Tinct. opii, gtt. xl. S. A fourth part to be taken every three or four hours. Under the name of Hope's Camphor Mixture a preparation similar to this has been much used, but nas gradually lost the confidence of the profession, chiefly, we believe, because on theoretical grounds the original formula has been departed from. The Nitrous Acid oi the shops ( ACIDUM NITROSUM, Edinburgh Pharmaco- poeia) is an orange-red liquid, which may be looked upon as a solution of nitric oxide in nitric acid. When it is diluted with water it is after a short time converted into simple nitric acid. For this reason it has been customary to substitute nitric acid for the Acidum Nitrosum of Hope's original formula. It should be noted, however, that the latter provided only sufficient of the remedy to last a few hours, and, as the reaction which has been spoken of requires some time for its perform- ance, we do not think that theory in truth warrants the change. Practically we have failed with the new formula, when immediate relief was afterwards obtained by the use of the medicine prepared according to the old plan. Made in this way and used while fresh, Hope's Camphor Mixture is a very efficient though disagree- able remedy in serous diarrhoeas connected with disordered secretion of the liver and other glands of the alimentary canal. ADMINISTRATION. Dose, from five to twenty drops (0.3-1.2 C.c. ); of the ACIDUM NITRICUM DILUTUM, U. S. (ten per cent. ; sp. gr. 1.054), from fifteen to sixty drops (1-4 C.c.). ACIDUM NITRO-HYDROCHLORICUM. U. S. Nitro- Hydrochloric Acid is made by mixing nine parts of nitric acid with forty-one parts of hydro- chloric acid. If the acid be sufficiently strong, an orange-colored liquid will be formed with the evolution of intensely irritating vapors. After standing for a length of time, the red color of freshly mixed nitro-hydro- chloric acid changes to a golden yellow. It is in this state that the U. S. Pharma- copoeia directs the acid to be used. By longer standing the golden yellow becomes lemon yellow, and the odor of chlorine is almost entirely lost. These changes are hastened by light, but will occur in the dark and in well-stopped bottles. Although the golden-yellow acid is directed by the Pharmacopoeia, yet careful clinical studies have convinced us that the acid acts much more efficiently when freshly prepared and of a deep red color. In some cases it has seemed to us useful only when in the latter form. The lemon-yellow acid is comparatively inactive. The remedial value of nitro-hydrochloric acid depends chiefly upon the power which it possesses to a much greater degree than any other of the mineral acids of influencing the action of the liver and other 456 GENERAL REMEDIES. glandular organs of the alimentary canal. Originally proposed by Scott, of Bombay, in the chronic hepatitis of hot climates, it has been used with great success by Annesley, Martin, and other famous India surgeons. The remedy would seem not to be indicated in hepatitis with high fever and a tendency to rapid suppuration so much as in the slower form of the affection, which normally ends in chronic enlargement and induration of the viscus. Both in the habitual congestion of the liver and in the milder affection known as biliousness, whose pathology is probably a torpid con- dition of the small glands of the alimentary mucous membrane as well as of the liver, nitro-hydrochloric acid has yielded in our hands most excellent results. That the remedy does act upon the liver is proved by the fact that in these cases it sometimes produces violent bilious diarrhoea. When jaundice depends upon obstruction or upon any of the severer organic diseases of the liver, the acid is of little if any use ; when, however, the jaundice depends upon torpor of the liver, or even when it is catarrhal in origin, the remedy may be of great service. Even in the early stages of cirrhosis, while the liver is still enlarged, nitro-hydrochloric acid should be tried, as in some cases apparently of this character great benefit has been derived from its use. In those forms of chronic diarrhcea in which the disease is really an intestinal dyspepsia, nitro-hydrochloric acid may be of great service. As the effect of the acid is not a sudden one, it is evident that it acts in these cases not as an astringent, but by restoring the normal digestive power. There is a morbid condition, oxaluria, probably dependent upon de- fective primary assimilation, in which the chief symptoms are general malaise, a feeling of weakness, a lack of elasticity, and a very great de- pression of spirits, with the crystals of calcium oxalate generally present in the urine, and in which nitro-hydrochloric acid produces in a few days a surprising revolution. As a " blood-purifier' ' the acid has been employed in constitutional syphilis and in various ulcerative skin affections. In these diseases it no doubt does good by improving digestion and increasing glandular action, but there is no reason to believe that it is a direct alterative. ADMINISTRATION. For reasons which have already been given, when nitro-hydrochloric acid is administered internally it should be freshly pre- pared ; and, as the changes which have been spoken of take place more rapidly when the acid is mixed with water, the official dilute nitro-hydro- chloric acid, twenty-two per cent. , is an ineligible preparation. As light hastens its deterioration, the strong acid should always be kept in a dark bottle with a glass stopper. Directly after mixing the acids the evolution of gas may be so great as to necessitate its being allowed to escape. After six or eight hours, however, the bottle should be closely stopped. The dose of the strong acid is from five to eight drops (0.3-0.5 C.c. ), properly diluted, and taken through a tube after meals. In chronic hepatic diseases the external application of the acid appears TONICS. 457 to give even better results than its internal use. In India, according to Sir Ranald Martin, the bath is used as follows. Take Hydrochloric acid f^iii, Nitric acid f .$ii, Water f 3v. Mix. Two gallons of water and six fluidounces of the above mixture suffice for a bath, which will keep fit for use during three days, provided half a fluidounce of acid and a pint of water are added morning and evening. The bath must of course be given in wooden or earthenware vessels, and if it becomes necessary to warm it only a portion should be heated and the rest then added. In urgent cases the whole body may be im- mersed in the bath ; but generally a foot-bath is preferable, the inside of the thighs and arms and the hepatic region being at the same time sponged. The bath should be repeated twice daily, lasting each time for ten or fifteen minutes. We have had no experience in this method of using nitro-hydro- chloric acid, but have derived great benefit from the application of the acid over the hepatic region. A large piece (eight by ten inches) of spongio-piline, or of canton flannel (several layers), should be wrung out in a lotion of a strength varying, according to the irritability of the patient's skin, from one to three fluidrachms to the pint, and applied over the right hypochondrium, and covered with a piece of oiled silk sup- ported by a bandage. The application sometimes causes a prickling sensation, and after a time may produce a profuse local sweating. The dressing may be left on from half an hour to an hour, and be repeated three or four times a day : some patients can wear it almost continuously. LACTIC ACID (AciDUM LACTICUM, U. S., seventy-five per cent, of absolute lactic acid). W. Preyer, s conceiving that sleep is due to the presence in the blood of the results of tissue-change, among which is lactic acid, experimented with it and its soda salt, and announced that they acted as powerful soporifics upon both man and the lower animals. According to his statements, with the sleep came deep, slow respiration, and lessening of reflex activity and of the bodily temperature. It has, however, been shown * that the hypnotic powers of lactic acid and its salts are very feeble and uncertain. The large doses used also are very prone to produce irritation of the alimentary canal, and Senator noticed the pro- duction of rheumatic pains. From three to nine drachms (12-36 Gm.) of the sodium lactate may be given at a dose. REFERENCES. TRnKr 5- JACOBI A. E. P. P., xxviii. 3. 6. ZALESKI A. E. P. P., xxiii. 1. HAMBURGER . . Z. P. C., 1879, " 7- KUNKEL A. G. P., Ixi. 2. MOERNER . . . . S. Jb., ccxxxix. 227. 8. GAULE D. M. W., 1896, xxii. 3. BERRY S. Jb., ccxxxvi. 9. QUINCKE . . . . A. E. P. P., 1896, xxxvii. 4. SOCIN Z. P. C., 1890-91. 10. HALL A. A. P., 1896. * E. Mendel (Deutsch. Med. Wochenschr., 1876. No. 17), Erler (Centralbl. f. Med. Wissens., 1876, 658), Fischer (Land. Med. Record, 1877, 193), Lothar ( Virchow's Archiv, Ixvi. 120), and Senator (Berlin. Klin. Wochenschr., 1877, 537). 458 GENERAL REMEDIES. REFERENCES Continued. 11. HOFFMANN . . . V. A. P. A., 1895, cli. 12. HARE Arch. f. Verdauungs Krank., 1898. 13. SCHMIEDKBERG and MARFORI . A. E. P. P., xxix., xxxiii. 14. HOCHHAU s and QUINCKE . A. E. P. P., 1896, xxxvii. 159. 15. CLOETTA .... A. E. P. P., 1897, xxxviii. 161. 16. NASSE L. M. R., 1877, 498. 17. SASSE Vierteljahr. f. prak. Heilk., 1866, ii. 18. POKROWSKY . . . V. A. P. A., xxii. 19. SIMON Animal Chemistry! Lon- don, 1845. 20. CUTLER and BRADFORD . A. J. M. S., 1878, 78. 2T. BUBNOW . 22. MiJLLER . . Z. P. C., vii. . V. A. P. A., 1901, 164, 436. MANGANESE. 1. PETREQCIN . . . Nouvelles Recherches du Manganese, Paris, 1852 ; B. G. T., March, 1852. 2. GARROD M. T. G., 1863. 3. LEAND Gl. M. J., Jan. 1865. MINERAL ACIDS. 1. KAZOWSKY . . . Centralb. f. Allg. Path. u. Path. Anat., 1894, v. 2. CURTIN P. M. T., iii. 649. 3. PREYER C. M. W., 1875, 578. FAMILY III. ALTERATIVES. THERE are employed by practitioners of medicine, to affect certain -diseases most intimately connected with the processes of nutrition, vari- ous substances which do not, at least in the doses commonly used, pro- duce any very obvious symptoms. It is to medicines of this character that the name of Alteratives has been applied, because when adminis- tered they seem simply to alter morbid processes. Speculation has been rife as to the mode in which alteratives influence the body ; and as the accepted pathology has been humoralistic or otherwise, so has it been strenuously argued that they act upon the vital fluid, or upon the solids of the body. The term " purifying of the blood" has been especially applied to their action, and is sufficiently suggestive of their function as viewed from the pathologi- cal stand-point of the old humoralist. What we know of the action of these medi- cines at present amounts to this, that they modify the nutritive processes of the body. To deny, as has been done, the existence or value of medicines of this class because we cannot tell why mercury relieves syphilis or why potassium iodide cures rheumatism is as absurd as to deny the existence of the syphilitic and the rheumatic dyscrasia because we do not know their ultimate nature. PHOSPHORUS. U.S. Phosphorus is a translucent, when pure nearly colorless, but usually slightly yellowish, highly inflammable elementary body, which is taste- less, but possessed of a peculiar alliaceous odor. It is insoluble in water, sparingly soluble in ether, absolute alcohol, and the oils, freely so in chloroform. It takes fire at 100 F. , and melts at 111.2 F. In the shops it is in cylindrical sticks, covered with a whitish layer, and having when cut a waxy consistence and lustre. It occurs in several allotropic forms, red phosphorus, black phosphorus, and the crystallized metallic phosphorus of Hittorf, whose physiological properties have not been investigated. PHYSIOLOGICAL ACTION. Absorption and Elimination. It has of late years been demonstrated that phosphorus passes into the blood as phosphorus, and not in the form of phosphoric acid or other compound. In cases of poisoning in men the breath is said to be sometimes distinctly phos- phorescent, and in animals Bamberger has found phosphorus in the blood, and Husemann and Marme in the liver two or three hours after its ingestion. W. Dyb- kowsky 28 has detected it in the blood and liver ten hours after its ingestion, and other observers have demonstrated its presence in almost all of the tissues. It seems probable that to some extent it finds entrance into the circulation by being 459 460 GENERAL REMEDIES. dissolved in the various fatty matters contained in the alimentary canal. At the temperature of the body, however, it yields abundant vapors, and Bamberger has demonstrated that these readily and rapidly pass through animal membranes. He has found that defibrinated blood, when separated from the fumes of phosphorus only by an animal membrane, rapidly becomes saturated with the poison. Dyb- kowsky has confirmed this, and it cannot be doubted that in a similar manner living blood absorbs the poison from the alimentary canal. W. Dybkowsky's research renders probable the theory of Schuchardt w that the phosphorus is converted to some extent in the alimentary canal, but much more largely in the veins, into phos- phuretted hydrogen, and that some of this compound and some of the phosphorus itself is oxidized in the venous blood, so that phosphoric acid, besides phosphorus and phosphuretted hydrogen, is emptied into the arterial blood ; further, that the last two compounds are oxidized at the expense of the arterial blood and the tis- sues it feeds, and that the poisoning is due to this deprivation of oxygen. For the details of the experiments upon which these conclusions rest we must refer the reader to the original memoir. * According to Plaice, 38 phosphorus is not found in free condition in these cases in the urine. The physiological action of phosphorus in therapeutic doses is prob- ably entirely different from that which it exerts when in larger amounts. It is a constituent of most of the more important tissues, and is especially abundant in the nerve-centres, upon whose nutrition it is believed by many to act as a stimulant. So far as the nervous system is concerned, this assertion rests upon clinical observation ; but Wegner l (confirmed by S. Miura and W. Stoeltzner 2 ) has experimentally demonstrated such an action upon the bony tissues. When adult animals are fed upon minute doses of phosphorus the spongy tissue in the long and short bones becomes thickened and the compact tissue more dense. After a time new tissue is deposited upon the inside of the shafts of the long bones, in some instances until the marrow cavity is obliterated. The action upon the bones of growing animals is even more marked. Phosphorus was at one time believed to be a diffusible stimulant, and it possibly may exert such an influence. In the acute nervous exhaustion of typhoid pneumonia we have once or twice seen it apparently act favor- ably in this way. For reasons to be already adduced (see page 459), it is certain that in poisonous doses phosphorus enters the blood in its elemental form. Wegner advances the following reasons for believing that thera- peutic doses act as phosphorus upon the bony tissues. First, no similar action can be obtained from phosphoric acid unless from eight hundred to one thousand times the proportional dose be given. Second, the newly formed tissue is at first gelatinous. Third, there is no excess of phosphates in the bone. Fourth, when the food is deprived of lime the same new tissue arises, but remains in a soft, gelatinous state. THERAPEUTICS. The chief use of phosphorus in medicine is as a nutrient tonic to the nervous system. In all cases of chronic nervous * M. Lecorch (Archives de Physiologic Normale et Pathologique, 1868, i., 1869, ii.) believes that phosphorus acts in the blood as phosphoric acid, but does not establish his opinion. For a discussion of this, see Dybkowsky's paper. ALTERATIVES. 461 exhaustion, whether involving the cerebral or the spinal centres, it is of great value ; even when the symptoms strongly suggest organic disease, as in threatening cerebral softening or myelitic paraplegia from excessive venery, it is often of service. It has been strongly extolled in neuralgia due to nervous exhaustion. It is probable that it may be of value in some cases of impaired vitality, although the nervous system be not obviously implicated. H. Eames 3 states that he has obtained great benefit from its use in obstinate skin affections, such as lupus, acne, and psoriasis. S. R. Percy* has used it successfully for repeated furuncular eruptions. It has also been asserted to be useful in cataract* On account of its marked influence on the development of bone, Wegner suggested its use in osteomalacia and in rickets, and thereby started a large amount of clinical experimentation and a considerable clinical literature, in which there is some contradiction : the general re- sult, however, has been to establish the value of the drug in rachitic cases, especially in those in which there is a tendency to osteoporosis. As large doses as can be borne without derangement of the digestion should be given. TOXICOLOGY. The ingestion of a fatal dose of phosphorus is not followed by any sensible effects for some time. After, however, from three to twelve hours a sense of weakness and of general wretchedness manifests itself, and in a large proportion of the cases (according to Lewin, eighty-eight per cent.) is accompanied, or soon followed, by vomiting. With the emesis there is nausea, and in most cases the patient soon complains of abdominal pain, the severity of which, how- ever, never equals that of corrosive poisoning. The matters vomited consist of food, mucus, and bile. During the first eight or ten hours they often smell strongly of phosphorus, and are luminous in the dark. The vomiting may persist during the whole attack, but generally ceases on the second or third day, to reappear with the subsequent jaundice, when coffee-colored vomit from exuded blood is ejected. The pain, which in most cases abates with the vomiting, often spreads from the epigastrium over the whole abdomen, and in rare instances is parox- ysmal. If it reappear in the latter stages, it is apt to affect especially the right hypochondrium, and is associated with decided tenderness in the region named and in the epigastrium. In the very acute cases of phosphorus-poisoning a primary condition of pronounced cardiac weakness, passing into paralysis, may be present ; f in the subacute cases the heart-muscle undergoes so much degeneration that a slowly developed but progressive cardiac weakness is produced and may be the cause of death. * Tavignot (Revue de Therapeutique Medico-Chirurgicale, August and September, 1871) and Gioppi (Giornale d' Oftalmologia, abstract in N. Y. Medical Record, 1873). t See especially J. Pal (Jahrb. d. Wiener k. k. Krankenaushalten, 1896, ix. 43). 462 GENERAL REMEDIES. The tongue is whitish or abnormally red, sometimes furred. There are generally fever, loss of appetite, and thirst. Maukopff has noted a morning and evening temperature of from 37 C. to 39 C. and from 37.4 C. to 39.8 C. respectively. Later in the poisoning there is very often a remarkable fall in the temperature, which is generally, but not always, a precursor of death. The lowest point we have seen noted was 31.2 C. (88.2 F. ) some hours before death.* In some cases fever is altogether absent, or comes on just before death, f The stools are at times normal in character and frequency, but there is general diarrhoea or constipation, with flatulence. Late in the attack the passages are in 'most cases very light clay-colored, or even whitish, and exceptionally they are bloody. In some cases they are phospho- rescent. Jaundice comes on in from thirty-six hours (cases reported by Mau- kopff 5 and by Tiingel 6 ) to five days (Lebert and Wyss 7 ) after the inges- tion of the poison. In most cases it appears first in the conjunctiva, but sometimes the urine gives previous warning of its approach. In some cases there is with it a decided and palpable increase in the size of the liver, which may pass, if the patient live long enough, into an equally apparent lessening of the bulk of that viscus. The severe nervous symp- toms are rarely, if ever, developed until after the jaundice, although early in the attack there are not infrequently anxiety, headache, giddiness, and dreamy unquiet sleep, or even sleeplessness. The more pronounced nervous symptoms consist of delirium, which may be wild and is very frequently erotic, with somnolence ending in coma and death, occasion- ally preceded by convulsions. According to Taylor, the latter are a cer- tain sign of approaching dissolution. Very generally partial spasms and fibrillary contractions of the voluntary muscles occur, although there is always, in not too rapid cases, progressive paresis of the voluntary mus- cles. Death is usually put off beyond twenty-four hours, yet it has occurred in a child in four hours and in an adult in seven 8 hours ; also in nine 9 hours. The patient may suddenly succumb to collapse and cardiac paralysis, but more commonly dies comatose from a gradual failure of respiration and circulation. If recovery occur it is by a gradual amelioration of the symptoms, and the health of the patient is apt to be impaired for some time, the most marked disturbances usually being the digestive and nervous symptoms. Apparently desperate cases will sometimes convalesce unex- pectedly, and Tiingel states that a favorable issue may take place even after violent delirium. The urine is almost always much affected by the poison. Very com- monly it is scanty or albuminous, and sometimes it contains sugar. J As * Battmann (Archiv der Heilkunde, 1871, 257). t Concato (Sydenham Soc. Year- Book, 1869-70, 454)- % In only six of one hundred and forty-one consecutive cases of phosphorus poisoning in the Medical Clinic of Prague was sugar found in the urine (Zeitschr. f. ALTERATIVES. 463 was first pointed out by Munk and Leyden, 10 after jaundice has set in, bile-acids, as well as biliary coloring-matter, are always to be found in the urine. Not infrequently a cloudy sediment consisting in part of epithe- lial cells, often tinged with bile, is deposited. Oswald Kohts n and other observers have found leucin and tyrosin in the urine of dogs poisoned with phosphorus, and undoubtedly these substances may occur. Wohl- gemuth 39 has found besides these bodies arginin in the urine of a rabbit poisoned with phosphorus. The albuminuria generally follows, but may precede the icterus. A very remarkable and apparently con- stant constituent of the urine is sarcolactic acid. Fat has been found in the urine inside of renal epithelial cells, and also as free globules (Schultz 12 ). Aberrant Poisoning. In some instances phosphorus-poisoning presents symptoms quite different from the typical array. Death may take place in a few hours, and in such cases jaundice is not generally present. 13 Zeidler reports a death in forty-two hours, from suppression of urine, with collapse and erotic de- lirium. In a case of Bellinger's u the chief symptoms were vomiting, pain and tenderness over the abdomen, great weakness of pulse, gradually developed pa- ralysis of the legs, and death, without jaundice, in four and a half days. The autopsy revealed hemorrhagic effusion between the membranes and the spinal cord, and also into the sheaths of the proximal portions of the spinal nerves. In women, fatal doses of phosphorus very commonly produce a bloody pseudo- menstrual discharge, or, when pregnancy exists, abortion. M. Miura 15 has found in the foetus of poisoned rabbits structural changes similar to those of the mother. Sub-acute phosphorus-poisoning is said sometimes to be manifested by sym- metrical gangrene of the extremities. (See W. K. W., 1901, No. 52.) Post- Mortem Appearances. The post-mortem lesions found after death from phosphorus-poisoning are quite characteristic, consisting of wide- spread fatty degenerations involving practically all of the organs, but especially marked in the gastro-intestinal mucous membrane, the liver, and the kidney. As was first pointed out by Virchow, 16 there is universally a gastro-adenitis, which causes the gastric mucous membrane to become thickened, opaque, whitish, grayish, or yellowish-white. This gastro-adenitis is not due to a local action of the phosphorus, because it occurs when the poison is introduced through other chan- nels than the mouth. The duodenum and intestines suffer similar changes. The liver is generally very much enlarged, friable, and light-colored ; some- times it is mottled, .and sometimes portions of it are deeply stained with bile.* The cells are gorged with fat-globules, f and in some cases there are small-celled inter- Heilkde. N. F., ii. 8 u. 9, p. 339, 1901). As originally stated by von Jaksch, the sugar is probably of secondary origin, due to the alterations of the liver. * According to researches made by Emile Rousseau in the Pathological Laboratory of the University of Pennsylvania, the first anatomical changes in the liver occur in the centre of the lobules around the hepatic vein. t A. Lebedeff (Arch. f. Physiol., 1883, xxxi. n) believes that the fat in the liver is not produced by degeneration of the hepatic tissue, but has simply been transported there from the subdermal regions. He bases this opinion upon his own observations, first, that the phosphorus fat has the same chemical constitution as has subdermal fat ; second, in a dog which had been fed with linseed oil and then poisoned with phosphorus, the liver was loaded with linseed oil. This evidence is of very little value, because on the one 464 GENERAL REMEDIES. stitial thickenings due to hyperplasia of the trabecular tissue. The gall-bladder may be full or empty. In protracted cases the liver undergoes atrophy, with destruction of its secreting cells. According to the researches of Arthur Heffter, 17 the percentage of lecithin in the liver, which is fixed in health, is greatly lessened in phosphorus-poisoning. The kidneys, especially in their cortical portion, suffer a degeneration similar to that of the liver, the epithelium becoming enlarged, granular, fatty, and finally undergoing destruction. The voluntary and cardiac muscles, the spleen, the lungs, and probably all the tissue, partake of the universal fatty degeneration * which Wegner has shown to involve even the minute arterioles. The nervous system does not escape. As long ago as 1880 Danillo declared that he had found a myelitis in phosphorus-poisoning, and Gurrieri 18 has dis- covered in the poisoned dog degenerations of various portions of the spinal cord ; whilst it has been shown by Uziemblo t that profound alterations take place in the retina, which becomes o^dematous, with marked alterations in the vessels, hemor- rhagic extravasations, and necrotic degeneration of the nervous cells. The blood is often profoundly affected, | becoming very dark, more or less completely losing its power of coagulation, and apparently suffering also in its corpuscular elements ; ecchymoses are almost universal, and haematin crystals are occasionally found in the viscera. The ecchymoses occur in all parts of the body, but are apt to be especially pronounced in the mediastinum and the serous membranes. Schiff 19 has found that in dogs, after death from phosphorus, the blood does not pass into the veins, but remains in the arteries. O. Silbermann * states that thrombi are formed in the blood-vessels ; and it has been shown by G. Puppe that these are very common in slow cases of the poisoning, and are of fatty nature. It should be remembered that although some or all of the lesions which have just been described are usually found in the bodies of persons dead of phosphorus-poisoning, it is possible for the poison to take life very rapidly and leave no trace of its influence, there being not even hand the linseed oil probably accumulated in the dog's liver before the poisoning and simply remained over, and on the other hand there is no proof that fat produced by de- generative changes necessarily differs in composition from other fat. The fact that the liver and other organs are destroyed in phosphorus- poisoning may be considered proof that the fat is formed out of the affected tissue ; although this seems contrary to the allegation of Bergeat ( Gesellsch. f. Morph. u. Physiol. Miinchen., 1888), that in very emaciated animals the phosphorus-poisoning may run its course without the formation of fat. * For full discussion of the pathology of phosphorus-poisoning, see H. Lebert and O. VVyss (Archives Gen., September, 1868), Otto Bellinger, also O. Kohts (Deutsches Archiv f. Klin. Med., 1869, v.). Ziegler (Beitrage Path. Anat., ii.), G. Kronig ( Virchow's Archiv, 1887, ex.), Aufrecht (Deutsch. Arch. Klin. Med., 1897, Iviii.), HansSchmaus (Miinchener Med. Wochensch., 1897, xliv., also 1898, xlv.), Hans Schmaus and Arthur Boehm (Arch, f. Path. Anat., 1898, clii.). See also Schmidt's Jahrbiic her, cclvii., 94. t See Uziemblo ( Die Pathologischen Alterationen der Retina bei Phosphovergiftung, Monographic, St. Petersburg, 1892, Russisch), also Julius Steinhaus (Beitrage zur Path- ologischen Anatomic und zur Allgemeinen Pathologie, xxii.). J Mayr states that when very large doses of the poison have been taken the blood and even the urine (?) may be phosphorescent (Canstatfs Jahresbericht, 1862, v. 123). Otto Taussig, as the result of a series of blood studies in phosphorus-poisoning, reaches the somewhat remarkable conclusion that in man, usually at about the acme of the symptoms, there is either a suddenly developed or a slowly produced increase of the red blood-cor- puscles, without an increase of the haemoglobin of the blood and with a distinct lessening of the leucocytes, whereas in the rabbit there is no alteration in the amount of haemoglobin or number of red disks, but a plain increase of the white corpuscles ; and in chickens there occurs an enormous destruction of the red disks, with a marked leucocytosis (Archiv f. Exper. Path. u. Pharm., 1892, 30). See Corin and Ansiaux ( Viertelj.f. gerichtl. Med., 1894, vii.). ALTERATIVES. 465 sarcolactic acid in the urine (see case reported by Paltauf 21 ). According to the researches of W. W. Podwyssotsky, 22 in rapid cases the first change in the body consists in the formation of little whitish-yellow ne- crotic foci in the liver. The anatomical changes in the liver in phos- phorus-poisoning are sufficient to confirm the statements of Schultzen and Riess, that in the poisoning there is arrest of glycogen and sugar formation. The elimination of bile acids in the urine shows that the jaundice of phos- phorus is caused not by an arrest of secretion, but by an occlusion of the biliary passages and consequent resorption of the bile.* O. Kohts has apparently demon- strated that the occlusion is most frequently due to the duodenitis involving the common duct, so as to obliterate its lumen by the swelling of the mucous membrane. In some cases, however, it is probable, as believed by Wyss, Alter, and Ebstein, that a catarrhal inflammation of the minute gall-ducts is the cause of the jaundice, and also that the result is in part effected through pressure upon those ducts by the swelling of the glandular and trabecular tissue. f It is proper to state that Demar- baix 23 and Willmart 24 insist that the icterus is not really hepatogenous, but haemic in origin, chiefly because they have found haematoidin in the urine. This fact, how- ever, proves only that the blood is altered by the poison : it does not disprove the liver origin of the jaundice. Acute phosphorus-poisoning so closely resembles yellow atrophy of the liver that their clinical distinction is sometimes difficult, nay, impossi- ble. Distinct phosphorescence in the breath, vomit, or stools would, of course, be direct evidence of poisoning. This phosphorescence, however, very often cannot be detected : according to Vetter, 25 it can be rendered more evident in the vomit, stools, etc. , by acidifying with sulphuric acid and warming in a shallow dish. When death ensues during the first week of phosphorus-poisoning, the enlarged liver affords a distinctive proof of poisoning ; but when the case is more protracted, the atrophied liver of phosphorus cannot be distinguished from that of the natural dis- ease. Phosphorus-poisoning usually develops more abruptly than does acute yellow atrophy, and the primary disturbance of the stomach is more severe, whilst the lull of the symptoms is more complete. The clinical differences, however, between various cases of either affection are greater than those which have been relied upon as separating the two affections. Kohler has asserted that oxymandelic acid in atrophy of the liver replaces the sarcolactic acid of phosphorus-poisoning, and * E. Stadelmann (Archivf. Exper, Path. u. Pharm., 1888, xxiv.) states, as the result of his experiments made upon dogs, that so far as the secretion of bile is concerned three stages can be made out. In the first stage there are irritation of the liver and increase of the formation and excretion of biliary coloring-matter ; in the second stage the gall be- comes mucous and cloudy, and the production and separation of biliary coloring-matter are lessened (it is in this stage that the icterus begins) ; in the third stage the gall becomes again clear, dark, and more rich in biliary coloring-matter, so that the normal excretion of biliary coloring-matter is notably surpassed. t For an elaborate discussion of the cause of jaundice, see Kohts's paper (Deutsches Archiv f. Klin. Med., \. 168) ; also that of Bellinger (Centralbl. f. die Med. Wiss., 1869, and Deutsches Archivf. Klin. Med., 1869. v.). 30 466 GENERAL REMEDIES. stress has been laid upon the asserted facts that in the natural disease leucine and tyrosine are present in abundance in the urine, while in the poisoning they are absent. In yellow atrophy, however, tyrosine is not infrequently absent from the urine and leucine present in very small amount, while both principles may be present in phosphorus-poisoning.* In regard to the acids in the urine, very careful chemical analysis would in any case be necessary to determine their presence, and sufficient evi- dence is certainly not yet forthcoming to show that either of them is really characteristic. Chemical examination is therefore absolutely neces- sary in all medico-legal cases, f According to M. Poulet, 26 phosphorus is eliminated as hypophosphoric acid, and the poisoning can be recognized by heating the urine with nitric acid to calcination. If hypophosphoric acid be present, as dryness is reached the mixture suddenly bursts into a flame like a packet of matches. The cause of death in phosphorus-poisoning is probably the wide- spread structural alterations, as the experiments of A. Hauser 27 indicate that the poison does not act by inhibiting life processes. The indications for treatment in phosphorus-poisoning are very evi- dent. It is plain that no medication can influence the terrible organic lesions induced, and that the primary object must be to prevent the ab- sorption of the poison. Emetics and purgatives are, therefore, of prime importance. The necessity of the persistent use of evacuants is shown by the finding of phosphorus by Starck 28 in the stools three and a half days, and in the vomit two days, after the ingestion of the fatal dose. As phosphorus is soluble in oils, no fatty matters should be allowed either in the food or in the medicines. As an emetic, copper sulphate shoztld always be chosen. The minute particles of phosphorus adhere so closely to the ali- mentary canal that they cannot be dislodged by mechanical means, and an antidote is urgently demanded. For the purpose of oxidizing the poison, Duflos suggested calcined magnesia and chlorine-water, and Scherer the chlorinated lime ; but in practice these substances have been found of no value, on account of the slowness of their action. The oil of turpentine, originally proposed by Andant* 9 as an anti- dote to phosphorus, J has been largely used by experimenters, with apparently contradictory results, which, as is now known, were due to the employment of different varieties of the oil. * Cases (Wiener Med. Presse, 1872; Schmidt's Jahrb., clxix. 127, cxcv. 123). Ossi- kovsky believes that the principles appear habitually about the sixth day of the poison- ing, when the liver is still enlarged. t For discussions of the diagnosis between yellow atrophy and phosphorus-poisoning, see Kohler (Syd. Soc. Year-Book, 1870, 455), Schultzen and Ries (Annalen des Berlin. Krankenhauses, 1869, xv.), and especially I. Ossikovsky (Wien. Medizin. Presse, 1872, xiii., abstracted in Schmidt's Jahrb., cliv. 15). For cases in which the question was legally raised, investigated, and discussed, see Schmidt's Jahrb., cxli. 167 ; Syd. Soc. Year* Book, 1832, 430; Annales d' Hygiene, Jan. 1869. J For cases, see Gazette ffebdomadaire, 1874; Schmidt's Jahrbiicher, clxix, 126; Med. Times and Gaz., 1876, ii. 461. ALTERATIVES. 467 There are in European commerce three varieties of turpentine, the rectified, the German, and the French. Jonas 30 found that while the pure oil has no effect upon phosphorus, the acid French oil forms with it a crystalline, spermaceti-like mass. This is soluble in ether, alcohol, and alkaline solutions, and has received the name of turpentine-phosphoric acid. It is said to be eliminated by the kidneys unchanged, and to exert no deleterious influence. The elaborate experiments of Vetter on dogs and rabbits gave results in accord with these facts, for he found the rectified and German oils to be of no value in phosphorus-poisoning, while the crude acid French oil was distinctly antidotal. Kochler, however, asserts that when the German oil has not been rectified for some time, it acts upon phosphorus. He believes that the oil acts partly by oxidizing the poison and partly by converting it into the harmless turpentine-phosphoric acid. One part of the oil must be given for o.oi part of the phosphorus. 31 Case of recovery. 32 See also Bene. 33 Ordinary American oil of turpentine and Canada balsam are of no value in phosphorus-poisoning. As was pointed out by Eulenburg and Guttmann, 34 and subsequently by Bamberger, 85 phosphorus in a solution of a soluble salt of copper becomes immediately black, owing to the formation of a phosphide of the metal. Bamberger also asserts that, while this change is very rapid, that induced by turpentine is a slow one, and, from an elaborate series of experiments upon animals, concludes that copper is much the more valu- able and certain antidote. Antal appears to have been the first to use potassium permanganate as an antidote to phosphorus, and in a series of experiments upon dogs E. Q. Thornton 36 found it much superior to cupric sulphate. Hydrogen dioxide appeared in Thornton's experi- ments to be valueless. In human poisoning cupric sulphate should be given in dilute solution, three grains every five minutes until vomiting is induced. After this the potassium permanganate should be freely admin- istered, or, as was successfully done by Hajinos, the stomach may be washed out with its solution ; later, the magnesium sulphate or citrate may be given as a quickly acting purge, and symptoms met as they arise.* * We have allowed the text to stand as in the old edition because of the present uncertainty as to the comparative values of the use of copper sulphate and potassium permanganate. In the United States phosphorus-poisoning is very rare : we have not met with more than one or two reported cases. In Continental Europe, however, prob- ably on account of the difficulty of obtaining poisons through the restrictions of the law, phosphorus is perhaps the most used of any poison for the purpose of suicide. Thus, out of forty cases of attempted self-murder, brought to the Prager clinic between 1889 and 1895, in thirty-nine the phosphorus contained in the heads of matches had been employed (Fr. Lanz, Berl. Klin. Wochensc.hr., 1895, xxxiii.). Formerly the treatment at the clinic consisted in washing out the stomach with warm water until the smell of phosphorus dis- appeared ; then continuing the washing with water containing copper sulphate and cal- cined magnesia, and following up by giving internally copper sulphate and oil of turpen- tine ; also large doses of sodium bicarbonate. Since 1893, when the Antal method was introduced, the plan has been to wash out the stomach with large quantities of one-eighth per cent, solution of the permanganate ; then administer one litre of the one-half per cent, solution, at the same time giving a purgative ; on the following day giving large doses of sodium bicarbonate with the oil of turpentine. The mortality per cent, of the cases before the change of treatment was 36.6 ; since the change of treatment, 41 .6 a result which is not favorable to the newer method. 468 GENERAL REMEDIES. Chronic Poisoning. Match-makers and other artisans who are ex- posed by their occupations to the fumes of phosphorus suffer from chronic poisoning, which is especially distinguished by the occurrence of ne- crosis of the upper or lower jaw. It occurs chiefly in those artisans who have bad teeth, and the experiments of Wegner have demonstrated that the necrosis of the jaw is due to the local action of the vapor of phosphorus.* Wegner found that when rabbits were kept in an atmosphere full of the fumes of the poison no necrosis ever occurred, unless, by means of an unsound tooth or an artificial wound, the atmosphere had access to the bone. If such access were, on the other hand, allowed to any bone of the body, periostitis and subsequent necrosis resulted. Further, when rabbits received continuously small doses of the phosphorus by the mouth, no necrosis occurred even after wounds which laid bare the bones. ADMINISTRATION. A useful preparation of phosphorus is the elixir (ELIXIR PHOSPHORI, U. S. , 1890), one drachm containing about one- sixty-fifth of a grain (o.ooi Gm. ) of phosphorus. Dose, twenty to forty minims (1.2-2.5 C.c. ). Phosphorated oil (OLEUM PHOSPHORATUM, U. S. 1890) contained one-hundred-and-fifteenth of a grain of phos- phorus to the minim. Dose, one to three minims (0.003-0. 1 8 C.c. ). Each pill of phosphorus (PiLUL^E PHOSPHORI, U. S. ) contains about one hundreth of a grain (o. 0006 Gm. ) The dose of phosphorus may be set down as from the one-hundredth to the one-fiftieth of a grain, increased unless gastric disturbance is pro- duced. J. A. Thompson affirms that he has given one-fourth of a grain every four hours without injury. Anstie says that he has seen slight poi- soning produced by three-fourths of a grain taken in seven days in divided doses. It is always wiser to have a freshly made preparation, as phos- phorus in solution or in pill is very prone to undergo oxidation. ZINCI PHOSPHIDUM. Zinc Phosphide has been largely used, with asserted good results, as a substitute for phosphorus. According to the researches of Vigier, 37 it would seem that the phosphide yields its phos- phorus within the economy, probably to form a phosphuretted hydrogen. He found that it killed rabbits more quickly than did a corresponding dose of phosphorus, and that both symptoms and lesions were identical in the two cases. The phosphide should be given in pill or granule. Dose, one-twentieth to one-twelfth of a grain (0.003-0.005 Gm.). Seguin recommended doses of one-sixth to one-fourth of a grain (0.016-0.01 Gm.). ARSENI TRIOXIDUM. U. S. ARSENIC TRIOXIDE. White Arsenic, Arsenic, or Arsenous Acid, as first prepared by sub- limation from the ores, is in transparent masses, but on keeping becomes * In the manufacture of matches, Phosphorus sesquisulphide, PiSs, has been largely substituted for yellow phosphorus, and is believed to be only slightly toxic. For a study of it, see C. G. Santesson (V. V. N. K. I. M., July, 1902). ALTERATIVES. 469 milk white externally. It is soluble in water, has a vitreous fracture, is odorless, of a faint sweetish taste, and volatilizes without fusion " at a temperature of 424.4 F. " When it is put upon red-hot iron it emits a garlicky odor, owing to its being first reduced to a metallic state and then volatilized. PHYSIOLOGICAL ACTION. Local Action. When in concentrated form arsenic is a powerful though slowly acting escharotic, and even when well diluted is a violent irritant. Although a violent poison to all forms of life, it acts proportionately so much more powerfully upon the higher than upon the lower organisms that it cannot be classed among the prac- tical germicides. Johannsohn and Schaefer and also Boehm ' state that it exerts no influence upon non-organized ferments, either vegetable or animal, such as amygdalin, pepsin, and pancreatin. Absorption and Elimination. Although when arsenic is taken into the stomach in lumps it may be absorbed so slowly as to escape in part through the alimentary canal, when it is taken in powder, and especially when it is in the form of the soluble salt, it is absorbed with rapidity. It is so readily taken up that its free external use and its employment as an escharotic are accompanied by distinct danger. Six cases are on record in which severe or fatal poisoning has been produced by the introduction of it into the vagina.* It is eliminated chiefly by the kidneys, but it is thrown off freely when in toxic amount by all the excretory glands and mucous membranes, especially by those of the gastro-intestinal tract. M. G. Bouchet and Lewald in independent researches found arsenic in notable quantities in the milk of nursing women, f Unterberger has detected it in the ali- mentary canal of animals poisoned by injection into the vein. M. Chatin has found it in the serosity of a blister, Bergeron and Lemaitre ' 2 in the sweat, and Taylor 3 in the contents of the stomach of a child poisoned by its application to its scalp. The single dose escapes rapidly from the body, elimination being usually com- plete in from a few hours to three or four days. When in large amount it may remain long in the body. Flandin and Danger* failed, three days after the last dose, to detect arsenic in the bodies of animals to which fifteen grains had been given daily ; and in a child killed in two days by an arsenical pigment, none of the metal could be found in the body. 5 In the great majority of instances, however, there is no trouble in find- ing arsenic in the bodies of those poisoned by it, and Steinhauser 6 reports a case in which it was detected in the remnants of a corpse that had been buried for twenty- two years. Further, it would appear that the failure to find arsenic has often de- pended upon the lack of delicacy in the chemical operations. Using the chemical method devised by Charles R. Sanger, E. S. Wood 7 has been able to detect arsenic in the urine ninety-three days after the taking of a single toxic dose, and from sixty to eighty days after mild courses of Fowler's solution. * See A. Haberda ( Wien. Klin. Wochenschr., 1897, x. 9, 201). t See American Practitioner, 1887. 470 GENERAL REMEDIES. General Action. As arsenic is never used in medicine for an acute effect, the chief interest to the therapeutist centres around its physiological action when given in small doses ; yet it seems necessary here to take cognizance of the physiological action of large amounts of the poison.* Nervous and Muscular System. Arsenic acts powerfully upon the nerve-centres, and to a distinctly less extent upon the nerve-trunks. In the frog arsenic acts as a paralyzant of the nerve-centres. W. Sklarck, 2 * of Berlin, states that the small dose causes in the frog cessation of voluntary movement, with complete loss of sensibility to chemical and mechanical irritants at a time when the animal will struggle actively to recover its position if laid upon its back. Tying of the iliac artery had no effect in preserving motion or sensibility in the protected leg. It would appear, therefore, that the cessation of voluntary motion was due to a complete paralysis of the centres of common sensation, probably up to the per- ceptive centre in the brain ; the frog, placed upon his back, being induced to struggle into the normal position by sensations received either through the special senses or possibly through the muscular sense. The researches of Ringer and Mur- rell K upon frogs yielded very different results from those just described, they found that the symptoms of poisoning came on only after the lapse of some hours, and that paralysis of voluntary motion preceded that of sensation and reflex action. Ringer and Murrell suggest that these differences of result depend upon the time of year at which the frog was experimented on. Circulation. The toxic dose of arsenic greatly lessens the rate and force of the pulse-beat and markedly lowers the blood-pressure. Sklarck found that in the isolated frog's heart arsenic produces slowness and fee- bleness of pulsation, ending in a diastolic arrest, after which immediate galvanic or mechanical irritation caused imperfect systolic movements. It would appear, therefore, that the toxic dose of arsenic is a direct cardiac depressant ; but as both Cunza and Unterberger 26 have found that in ar- senical poisoning the heart persists in its movements after the cessation of respiration, it is evident that arsenic is more powerful as a respiratory than as a circulatory poison. Further, as demonstrated by Unterberger, the lowering of the arterial pressure in arsenical poisoning is very largely due to a vaso-motor paralysis. Thus, Unterberger found that in an animal under the influence of the poison neither galvanization of a sensory nerve nor of the vaso-motor centre in the upper cord had any influence upon the force of the blood-current. Galvanization of the splanchnics had no effect upon the arterial pressure, apparently showing that the vaso-motor palsy was peripheral ; but Unterberger found, to his astonishment, that stimulation of the cervical sympathetics had the usual effect upon the vessels of the rabbit's ear. Supposing these observations to be correct, there are only two seem- * The theory of Binz and Schulz, that arsenous acid acts by taking from protoplasm oxygen, so as to be converted into arsenic acid, and afterwards yields this oxygen to oxidize the protoplasm, and then repeats the process, seems to be so illy supported that in regard to it the reader is simply referred to Arch.f. Exper. Path. u. Pharm., xi., xiv., xxxvi., xli. ; also Brit. Med. Journ., 1882, ii. 1135. Dogiel's theory, that arsenic unites chemically with the albuminous principle, is more probable. (See Trans. International Congress, 1884, i., 134.) ALTERATIVES. 471 ingly possible methods of reconciling them : either the drug acts upon the peripheral vaso-motor nerves in the abdomen and not upon the same nerves in the neck, or else there is during arsenical poisoning such depression of the power of the cardiac muscle that narrowing of the blood-path does not have the usual effect. Unterber- ger found that compression of the abdominal aorta was followed by a great rise of pressure, and therefore he believes that the heart in arsenical poisoning has not lost its power. Some complicated transfusion experiments which he made indicated differently ; so that while his proposition that arsenic paralyzes the peripheral vaso- motor nerves of the abdomen and not those of the head may be considered proba- ble, it certainly is not proved. It would be a very easy matter to decide the ques- tion by dividing the splanchnic nerves in a poisoned animal : if the reduction of the arterial pressure be really due to an abdominal vaso-motor paresis, section of the splanchnic should have no effect on it. Tissue- Change. Schmidt and Stiirzwage believe that arsenic mark- edly influences tissue- change, because they found in rabbits a decided diminution in the excretion of carbonic acid and of urea during the use of minute doses of the poison. Fokker, 27 however, was unable to per- ceive in three experiments that daily doses of from .15 to .075 grain of arsenic to a dog had any effect upon the elimination of urea, and Kos- sell and Gaethgens,* 8 in two experiments, have noted a very decided increase of the elimination of urea produced by toxic doses of arsenic in the dog. The experiments of Chittenden and Cummins w are in accord with the early results of Stiirzwage, as they found that in the case of rabbits arsenous acid has a tendency to diminish the elimination of car- bonic acid. The evidence which we have at present is not sufficient to warrant a positive opinion, but it indicates that small doses of arsenic check tissue-change and decrease nitrogenous elimination, while large toxic doses have the opposite effect. Blood. As arsenic is frequently used in various forms of anasmia much interest is attached to its effect upon the formation of blood-corpuscles. Stockman and Charteris 3 ~ have found that repeated small doses of arsenic cause an increase in the formation of the leucoblastic cells of the bone marrow, with consequent stimulation of the formation of white blood- corpuscles, but without marked change in the number of red cells. Larger doses produced a hyaline degeneration of the bone marrow with a decrease in the number of both white and red cells. Skin. The changes in chronic arsenical-poisoning, especially as shown in the epidemic which occurred in Manchester, in 1900, as the result of contaminated beer, bear out the conclusions of clinical experience, that arsenic has a marked effect upon the nutrition of the skin. According to Brook,* 8 the most characteristic changes in the skin in this epidemic were the deposit of pigment and stimulation in the growth of the epithe- lium, similar changes occurring also in the modified dermal tissues, such as the finger-nails. Action of Small Doses. Minute quantities of arsenic may be given for a long time without perceptible effect. When the dose is increased, active manifestations of gastro-intestinal irritation may appear, such as 472 GENERAL REMEDIES. loss of appetite, nausea, abdominal pain or uneasiness, diarrhoea, and perhaps sympathetic headache. By the use of frequent small doses these symptoms may generally be avoided, and what may be termed the constitutional action of arsenic be obtained. The earliest sign of this is generally a puffiness about the eyes, at first visible only in the early morning, but soon increasing into decided oedema, which after a time may lose its local character and general anasarca develop. This ana- sarca, as was, we believe, first pointed out by S. Weir Mitchell, 30 may or may not be preceded or accompanied by the presence of albumin and of tube-casts in the urine. Beyond the production of the symptoms spoken of, arsenic should never be pushed in medicine. THERAPEUTICS. When arsenic is administered in small repeated doses, it may act as a stomachic, by slightly irritating the stomach and thereby provoking an appetite ; and in certain cachexias it increases the muscular strength and the general vigor. The history of arsenic-eating indicates that the drug has some positive tonic influence over nutrition; and although the increase of strength and of blood caused by its use in cachexias may be due to some indirect action of the drug, for example, to a removal or overcoming of the morbific agent of the disease, and a consequent allow- ing of the recuperative powers of the system so assert themselves, there is much reason for believing that the drug does act as a direct stimulant to nutrition. All that we know of the effect of arsenic upon the system throws only enough light on its therapeutic action to enable us to class it as an alterative, a modifier and often an improver of nutrition. After very much discussion* it seems to be established that many of the Sty- rian peasants use arsenic habitually in large quantities ; the young girls to beautify their complexions and enhance their charms ; the men with the belief that it will increase their "wind," endurance, and sexual powers. The best authorities state that the arsenic-eating is practised chiefly in the northern and northwestern parts of Styria : that the white arsenic is preferred, the yellow commercial article being sometimes taken ; the native red arsenic, or orpiment, very rarely ; and that the commencing dose is about 0.22 grain, which is very slowly increased to 0.62 grain avoirdupois. f Among the diseases which clinical experience demonstrates are espe- cially benefited by the use of arsenic is chronic malaria. No one would at present think of employing the drug in acute remittent fever, or even in acute intermittent, unless under very peculiar circumstances. It is in those cases which have resisted quinine, in which the paroxysms have become irr.egular, returning at long intervals, and in which the anaemia and the general nutritive disturbance are even more prominent than the *SeeVogt (Lehrbuch der Pharmacodynamik, Aufl. iii. i.), Charles Heisch (Pharm. Journ. Trans., 1859 and 1860, i. 556; British and Foreign Med.-Chir. Review, xxix. 144), and C. Maclagan (Edinb. Med. Journ., 1864, 203; Edinb. Med. and Surg. Journ., 1871, xvi. 569). t Maclagan says that in one case of suspected poisoning in Styria the prisoner was acquitted on the ground that the deceased was an arsenic-eater. (See also Wiener Klin. Wochensch., 1812, v.). ALTERATIVES. 473 febrile disorder, that arsenic is especially valuable. In these cases it should be administered with sufficient boldness, very generally in con- junction with iron. George B. Wood recommended that the first doses should be as large as the system will endure, so as to make a decided impression at once. When the ague paroxysms are frequent it is per- haps well to employ this plan ; but when it is the cachexia rather than the active disorder that is to be combated, it is preferable to commence with small doses and to increase them until some constitutional symptom is produced. In ordinary intermittent, after the paroxysms have been broken up by quinine, it is very well to place the patient upon a prepara- tion of arsenic and iron, as a prophylactic against their return. When, in ordinary intermittent fever, for any cause quinine cannot be admin- istered, arsenic may be employed. In these cases, as already intimated, the first doses should be large, so as to make an immediate impression; from five to ten minims of Fowler's solution, properly diluted, maybe given every two or three hours until some decided symptom is produced. When the stomach refuses the remedy, it has been recommended by Boudin to give it by the rectum, which he affirms will often bear even a grain of the acid. Not more than a third of this amount should, however, be used as a commencing dose. In malarial intermittent neuralgia, arsenic may be employed as a very useful adjuvant to the antiperiodic alkaloids. K. M. Downie 31 calls attention to the value of arsenic as a prophylactic against malaria. His trials were not numerous enough to be conclusive, but so far as they go they indicate that arsenic is even superior to quinine. It is alleged that arsenic injected directly into the growth is an effec- tive remedy in lymphatic tumors, especially in the affection known as malignant lymphoma* In various skin diseases arsenic is a valuable remedy. According to Duhring it affects the epidermis generally by its influence upon nutrition. It is more commonly useful in those skin diseases involving the superficial strata of the integument. As it is a stimulant it should ordinarily not be employed in the acute inflammatory stages of skin disease, when there is burning, itching, and rapid cell change. Its greatest use in skin diseases is in the chronic conditions, as in psoriasis and in eczema, especially of the chronic squamous and papular varieties, and where the disease is superficially seated. Pemphigus is generally favorably influenced and often relieved or cured by its use. It should be prescribed cautiously but fearlessly, large doses usually being required. It is the most reliable remedy for this disease. In lichen it is usually employed with great advantage, especially in lichen planus, in the rare lichen ruber of Hebra, and in allied diseases. Occasionally it may be given with benefit in chronic urticaria. * See Wien. Med. Wochenschrifl, 1871 ; Archiv f. Klin. Chir., xviii. ; Strieker's Jahrb., 1877. 474 GENERAL REMEDIES. It may prove of value in certain cases of acne and comedo, especially in chronic small papular acne, in neurotic cases. In certain glandular hypersecretory diseases, as seborrhcea and hyperidrosis of neurotic origin, it is also useful. Before prescribing it the digestive tract should be care- fully looked into, and if disordered in the slightest degree should first be rectified. This observation holds good for its use in all diseases of the skin. In morphoza, alopecia areata, and other atrophic diseases it is also sometimes of value. If improvement follows its use it is usually best to allow the patient to continue with the treatment for some time after all symptoms of the disease have disappeared. Arsenic is a very valuable remedy in the treatment of chronic bron- chitis, and is often of the greatest service not only in chronic pneumonia, or so-called fibroid phthisis, but even in true tubercular phthisis when the course is very slow and chronic. In asthma it may be given internally and also used locally. (See EXPECTORANTS. ) In certain nervous diseases arsenic acts very favorably, in some un- known way. In chorea it has acquired a deserved reputation. In this affection iron and other tonics are generally indicated and may be given consentaneously with the arsenic. It is best, however, to administer the latter separately, as the dose must be steadily increased until oedema or other manifestations betray a decided action. Arsenic has from time to time been strongly recommended in whooping-cough, non-malarial neu- ralgia, and simple gastralgia, or gastric neuralgia, Arsenic is of value in those forms of chronic rheumatism in which potassium iodide is commonly employed. It is often advantageous to alternate, administering one of these alteratives for three or four weeks, and then the other for the same length of time. In rheumatic gout, or rheumatoid arthritis, it has been highly extolled. TOXICOLOGY. When a single dose of arsenic of just sufficient size to be felt is ingested, colicky pains, diarrhcea, and perhaps nausea result. After a very large toxic dose, in from one-quarter to three-quarters of an hour an intense burning pain is felt in the oesophagus and stomach, soon spreading to the whole belly, and often accompanied by a sense of constriction at the throat and an acrid, metallic taste. In a very short time violent vomiting and purging come on. The matters rejected are at first mucous, and variously colored by the contents of the primae viae ; but they soon become bilious, often yellowish or greenish, and finally serous, with mucoid flakes and a greater or less amount of blood. As the case progresses the symptoms mentioned increase in intensity, and to them are soon added others of different nature. The thirst is excessive ; the urine is suppressed ; the extremities are icy cold ; the pulse is small, feeble, and frequent ; the rapid and labored respiration is very much embarrassed and painful from the abdominal tenderness ; the surface is dark and cyanosed ; violent cramps add their torture ; exhaustion deepens into collapse ; convulsions or coma ensue, and death occurs in from five to twenty hours. ALTERATIVES. 475 In another set of cases, when the dose has been smaller, or the sub- ject less susceptible, the termination is not reached so soon. After symp- toms, similar to but less violent than those just described, have lasted from a few hours to one or two days, a remission occurs ; the purging and vomiting grow less frequent, or perhaps intermit ; even the abdominal tenderness may in great measure disappear ; but the persistent thirst, cold extremities, and albuminous urine show that the danger is not past, and after a time the case puts on a more alarming aspect. Fever develops, the tongue becomes dry and red, the belly very tumid, the abdominal pain more severe, dyspnoea and cyanosis occur, the face is swollen, nervous symptoms, tremblings, cramps, and convulsions appear, and finally an icy coldness pervades the frame, and death occurs in from two to six days. The mind is generally clear to the last. An eruption very frequently appears, sometimes as early as the second day, sometimes not until the fifth. Its character is various : thus, it may be petechial, urticaria-like, papular, vesicular, or pustular.* Such are the ordinary phenomena of acute arsenical-poisoning ; but anomalous cases are not very rare. Immediate profound collapse, with- out abdominal pain, is said to have been the chief manifestation in some cases. We have seen heavy sleep as the most marked symptom, the sleep, however, being interrupted at intervals by wild outcries and writh- ings, evidently the outcome of abdominal pain, although no statement could be obtained from the patient. Again, serous purging may be the chief symptom, and arsenical-poisoning has been mistaken for cholera, not only during life, but also on the post-mortem table, f When arsenical-poisoning is not fatal the convalescence is apt to be slow and interrupted by various disorders. Prominent among these are affections of the alimentary canal, due to the structural changes produced by the poison. Nervous symptoms are common, and may affect the motor or sensory sphere separately or together. In some cases they have developed very suddenly. 8 We have seen anaesthesia of the feet as the only symptom ; motor paralysis may exist alone, but it is usually ac- companied by anaesthesia, hyperaesthesia, loss of temperature-sense, great feeling of coldness, or other disorder of sensation, and not rarely exces- sive pain, which may be aching or lancinating. Occasionally there are severe cramps. Normal sensibility is usually regained before normal motility. Of one hundred cases of arsenical paralysis collected by Imbert-Gourbeyre, 9 in more than half all the extremities were affected ; about one-fourth were paraplegic ; in the remainder there was hemiplegia or local palsy. Most frequently the paralysis was not pronounced above the elbow or knee. The lamed muscles are usually sensitive to pressure J * See Imbert-Gourbeyre (Moniteur des Hopit., 1857), also A. Huber (Zeitschr. Klin. Med., 1888). t See Virchow's Archiv, 1870, 1. t Consult C. Gerhard (Sitzungsb. Physik. Med. Gesellsch. Wiirzburg, April, 1882), Renner (Ueber ein Fall von chron. Arsenvergift., Wurzburg, 1876), W. P. Mclntosh 476 GENERAL REMEDIES. and undergo rapid atrophy, losing very early their electro-muscular con- tractility, or presenting the " reactions of degeneration." The tendency towards more or less complete recovery is remarkable. We have seen recovery when the muscular remnants on the wasted limbs had for many months been unable to respond to any form of electric current ; and out of Imbert-Gourbeyre's one hundred cases all got well except three. N. Popoff I0 found, in dogs killed in a few hours by a dose of arsenic, the spinal cord inflamed; after slower poisoning there were masses of "exudate" in the neighborhood of the blood-vessels, and in very protracted cases the walls of the spinal arterioles were found to be thickened and the large cells of the gray matter profoundly altered. The protoplasm first became opaque and granular ; the nuclei L,:L\V fainter and fainter, and disappeared ; vacuoles appeared, and encroached more and more on the shrunken body of the cell, which finally melted down. In the elaborate experiments, however, of C. Alexander 11 upon rabbits, the spinal cord was found to be healthy, but the nerve-trunks were in a condition of degenerative atrophy, and the muscles themselves had undergone changes which were believed to be the result of coagulation-necrosis. That arsenic is capable, in man, of producing a myelitis especially affecting the multipolar cells of the cord is shown by the autopsy reported by Erlicki and Rybalkin, 12 in which case there was no tenderness of the nerve-trunks. There appear to be, therefore, two forms of arsenical paralysis, one due to myelitic change, the other to a wide-spread multiple neuritis, the diagnosis between the two being made by the presence or absence of nerve-tenderness. It is very probable that in some cases both lesions are present.* In some of these cases trophic changes are pro- nounced : thus, we have seen a growth of hair several inches long cover the wasted limbs. If in any case of arsenical paralysis there were no sensory disturbance, the probabilities would be very strong that the lesion was a toxic poliomyelitis. We know of no general studies upon the blood of human beings poisoned with arsenic, f S. Betteman 12 has shown that in the rabbit in subacute arsenical-poisoning there is a marked lessening in the number of the red blood-corpuscles and in the per- centage of haemoglobin, without any distinct change in the general percentage of leucocytes, although the lymphocytes increase and the eosinophile cells decrease. Late in the poisoning nucleated red blood-corpuscles may be found in the circu- lating blood. The most obvious lesions found after death from acute arsenical-poi- soning are those of severe gastro-enteritis, but often there is also a wide- spread granular or fatty degeneration of the tissues. (TV. Y. Med. Record, Feb. 1885, 145), Seguin (Journ. Nerv. and Ment. Diseases, Oct. 1882, vii. 665), and C. K. Mills ( Trans. College of Physicians of Philadelphia, 3d series, vi. ; Archives de Physiol. Norm, et Path., 1884, iv.). * See also Wiener Klin. Wochensch., 1891, iv. t For spectroscopic study of the effect of arsenic upon the coloring matter of the blood, see Centralblatt, 1868, 609. It is interesting here to note that arsenic, antimony, phosphorus, and ammonia act very similarly, if not identically, upon the blood- ALTERATIVES. 477 The gastric mucous membrane is usually swollen, maculated with patches of a deep crimson or more commonly brownish-red color, and is often softened and covered with a diphtheritic exudation, but is rarely ulcerated. Perforation is exceedingly uncommon. The mucous membrane of the upper part of the small intestine, and sometimes of the whole of it, is in a condition similar to that of the stomach. In some cases the lesions very closely resemble those of cholera, as was first pointed out by Virchow. 14 In the microscopic examination of a cadaver whose bowels were filled with a "rice-water" fluid, that observer found in the intestinal contents epithelial flakes and the fungus described by Klebs as pecu- liar to, and, indeed, the cause of, cholera. The epithelial cells of the mucous mem- brane were choked with granules, many of them in an advanced stage of fatty degeneration ; the interstitial tissue was full of large round granulated cells ; the solitary glands and Peyer's patches were very much swollen. These facts have been confirmed by Hoffmann. 15 The gastro-intestinal lesions produced by arsenic are not due solely or largely to its immediate local effect, since they occur equally when the animal is killed by injection of the poison into a vein. The local influence of the drug is, however, probably not altogether lost, since Unterberger found that a larger dose was required to kill an animal by venous injection than by exhibition by the mouth. Curious and at present unexplainable anomalies occur in the distri- bution of the gastro-intestinal inflammation, and autopsies have been reported in which the stomach has altogether escaped. M. Karajau 16 reports a case which had been mistaken during life for acute atrophy of the liver ; Fr. Grohl and Fr. Mosler 17 one in which they found fatty or granular metamorphosis of the glands and epithelium of the stomach or intestines, of the cardiac muscle, of the diaphragm, of the cortical portions of the kidney, and, to a slight extent, of some of the voluntary muscles ; I. I. Pinkham 1B one in which the liver, kidneys, and epithelial lining of the peptic glands were almost destroyed ; similar lesions have also been reported by M. V. Cornil 19 and by Frol. 20 As was first pointed out by Salkowsky 21 when animals are poisoned by a small dose of arsenic, so as to live from three to six days, the liver * becomes much enlarged and very fatty. On microscopical examination, the cells on the exterior of each acinus are natural ; those in the centre in the most advanced stages of de- generation. The kidneys are similarly affected, their tubes choked up with fat- globules, their epithelium almost completely destroyed. The muscles of the heart and diaphragm are also compromised. In frogs poisoned with arsenic the epidermis peels off from the derm, as was first noted by Ringer and Murrell, and Emily A. Nunn " has found that the influence of the poison is first manifested in the under portion of the epidermis, the degener- ation progressing from the derm outward. In some cases of arsenical-poisoning yellow patches, believed to be due to the formation of arsenical sulphides, have been noted on the mucous membrane of the stomach and intestines. Similar yellow de- posits were found by Chunilal Bose ' 2Z on the endocardium. It is prob- able that in these cases the sulphide is formed after death by the aid of putrefactive gases. * Salkowsky also noted that early in both arsenical and antimonial poisoning the glycogenic function of the liver is abolished. Podwyssotsky finds that the first change produced by overwhelming doses of arsenic consists in the formation of necrotic foci in the liver (St. Petersburg Med. Wochensch., 1888). O. Silberman believes that during life thrombi form in various portions of the body (Archil' f. Path. Anat., cxvii.). For further discussion see Ziegler (Beitrage Path. Anat., ii.), also M. Wolkow (Archiv f. Path. Anat. u. Phys., 1892, cxxvii.). 478 GENERAL REMEDIES. The symptoms of acute arsenical-poisoning resemble so closely those of cholera nostras that without the knowledge of the taking of the poison, or chemical analysis of the excretions, a positive diagnosis may be im- possible. The abdominal pain is, however, usually more severe than in the natural disease. Death usually results in acute arsenical-poisoning in from eighteen hours to three days ; but Taylor reports a case in which it occurred with tetanic symptoms in twenty minutes, and life has been protracted until the sixteenth or even the twentieth day. The effects of the arsenical solu- tions, such as Fowler's, are more rapid and severe than are those of the solid drug. Tardieu places the minimum lethal dose at from ten to fifteen centigrammes (1.54-2.31 grains.) W. C. Jackson * 3 records a case of recovery, under the early use of emetics, after an estimated dose of two ounces had been taken ; and E. D. Mackenzie 14 gives an account of a man who swallowed an unknown quantity of arsenic in lumps, and received no treatment for sixteen hours, yet recovered after passing per anum one hundred and five grains of arsenic in two masses. On the other hand, death has resulted from the use of very small amounts. Taylor asserts that the smallest fatal dose hitherto recorded is two grains. Lachese J5 affirms that six milligrammes (0.09 grain) will produce decided but not serious symptoms, and that from one to three centigrammes (0.154-0.462 grain) are poisonous, and from five to ten centi- grammes (0.77-1.54 grain) fatal. The escapes from death after the ingestion of large amounts of arsenic have, without doubt, depended upon its being, as in the cases above narrated, in an insoluble form. Chronic arsenical-poisoning is often difficult of diagnosis ; the symp- toms are usually both local and constitutional. When the poison has entered the system through the respiratory tract the local irritation will be shown by dryness of the throat, coughing, and other evidences of chronic bronchitis or severe laryngo-bronchial catarrh. When the poison has entered the system through the alimentary tract, loss of appe- tite, with frequent vomiting and violent diarrhoea, are common. The general symptoms consist of depression of spirits, irritability, insomnia, giddiness, failure of memory, sometimes marked mental failure. Accord- ing to Reynolds, 39 in the epidemic which was caused by arsenical beer, involvement of the nerve-trunks was very common. There was in these cases marked disturbances of sensation, paraesthesia, and partial anaes- thesia, although complete anaesthesia was rare. There may be muscular tremors or stiffness ; vertigo or other disorders of equilibrium are some- times seen, whilst violent neuralgic pains, with numbness of the extremi- ties, marked tenderness of the nerve-trunks, and other results of periph- eral neuritis, are not rare. In most cases of chronic arsenical-poisoning without a history the congeries of symptoms is, however, sufficient only to arouse suspicion and to call for a chemical examination of the urine. It should always be remembered that a peripheral neuritis is usually due to the presence of some poison, and that a group of wide-spread atypical symptoms not characteristic of any distinct disease is usually either toxic or diathetic. ALTERATIVES. 479 Sometimes in acute, more frequently in chronic, arsenical-poisoning, or as the result of long-continued medicinal use of the drug, certain dis- orders of the skin appear.* Of these, herpes zoster seems to be the most frequent ; it probably is the result of an arsenical neuritis. Another common skin affection is erythromelalgia, the painful red swelling of the epiderm. In protracted cases there is frequently thickening of the horny tissue in the palms of the hands and soles of the feet, which occasionally extends up the limb. The formation of transverse ridges across the nails, the result of the hyperkeratosis has also been noted. The deposit of pigment in the skin and mucous membranes is an almost constant symp- tom, while there have been noted a number of other changes in the skin, such as erythematous and desquamatous eruptions, urticaria and subcutaneous oedema, vesicular eruptions, bullse, papules, pustules and ulcers, purpura, shedding of the hair and nails, and keratosis. In artisans who work in copper local arsenical poisoning is not very rare. Ulcers about the roots of the nails are generally the first trouble in these cases, but after a time eczematous or papular eruptions appear, and even subdermal erysipelatous inflammation is developed. Very com- monly to these local symptoms are added, after a time, the usual phe- nomena of chronic arsenical poisoning. In the arts, preparations of arsenic are largely used as pigments ; f and, excepting the manufacturers of arsenical compounds, it is almost ex- clusively those who are accidentally exposed to the deleterious influence of these pigments that suffer from chronic arsenical poisoning. The poisonous colors are of various hues, and, being very cheap, and remark- able for their purity of tone and their permanence under exposure to light, are much used by paper-makers. Scheele's Green copper arsenite contains fifty-five per cent., by weight, of arsenous acid ; and Schweinfurt Green the aceto-arsenite fifty-eight per cent. Paper coated with them has been largely used not only as hangings, but even as wrappings for confectionery and other edibles. The arseni- cal dyes are not all green, but may be in almost any hue ; they are largely due to the use of arsenic in the manufacture of magenta and other aniline colors. E. S. Wood, 33 of Harvard, has shown that in different parcels of the same goods one * See Berlin. Centralblatt, 1868; Deutsche Klinik, 1874 ; Schmidt's Jahrb., clxv. ; Deulsch. Archiv Klin. Med., 1899, xliv. ; Boston Med. and Surg.Journ., cxviii., cxix., cxx., cxxi., cxxii. ; Berlin Thesis, 1892; Ann. Dermal, el Syph., iv. ; Vierleljahr. f. Derne., Wien, 1897, xi. ; Ann. de Dermatol. el de Syph., 1897, viii. 4, 345; Monals. f. Prakt. Dermatol., 1897, xxiv. 3, 137. t For an excellent report upon this subject, see Report of the Slate Board of Health of Massachusetts, Jan. 1872, where it is stated that from five hundred to seven hundred tons of arsenical pigment were manufactured in 1862 in England alone. Fatal chronic arsenical poisoning from working in aniline dyes is reported in Strieker's Jahrb., 1877, 501. F. C. Shattuck (Med. News, 1893, Ixii.) reports a number of cases in which the symptoms have been gastro-intestinal irritation, anaemia, dermatitis, redness of the con- junctiva, puffiness under the eyes, headache, irritation of the upper air-passages, albumi- nuria with casts and blood, and peripheral neuritis. The number of cases of chronic ar- senical poisoning detected in and about Boston, contrasted with the rest of the world, is something remarkable, and is scarcely to be accounted for by the alleged superior acute- ness of the Boston physicians. A further difficulty of the subject is that arsenic has been detected in the urine of many normal Bostonians. 480 GENERAL REMEDIES. will contain arsenic and the other not, because the aniline dyes are sometimes con- taminated with arsenic and are sometimes free from it. These poisonous colors are by no means confined to wall-paper. Sweetmeats have been colored with them : pasteboard boxes, artificial flowers, tarlatan dresses, India muslins, cretonnes, walls of dwellings, shelves of groceries, toys of children, and various other articles have been made the vehicles of death, so that hundreds of cases of poisoning have resulted from the use of these pigments, which ought to be banished by the strictest laws. In most cases it is probably the minute dust, which is separated mechanically and diffused through the room, that produces the fatal result ; but poisoning has occurred when the arsenical paper was covered over with another paper. Hambers has made elaborate chemical researches upon the air of these apartments, and be- lieves that he has demonstrated that some arsenic escapes in the form of arsen- iuretted hydrogen. Not rarely the poison has been taken directly into the stomach, especially by children. TREATMENT As arsenic in large doses generally induces vomiting, it is rarely necessary in poisoning to evacuate the stomach by artificial means. If free emesis, however, have not occurred, a prompt emetic, such as mustard or zinc sulphate, should be at once exhibited, and very generally the stomach should be well washed out by large draughts of warm water, with salt, if necessary for the return of the water. With the emetic, or sooner, if possible, the antidote should be administered. The most certain antidote is the freshly precipitated ferric hydrate, which forms with arsenous acid a very insoluble compound. The antidote must be freshly prepared, and must be given in great excess ; according to the experiments of T. and H. Smith, of Edinburgh, at least eight grains of the iron being required for the conversion of one grain of the arsenous acid. In practice, any of the official ferric solutions that of the chloride being gen- erally preferred, as most readily procured should be neutralized by sodium car- bonate or preferably by magnesia, and a portion of the precipitate given at once, stirred up in hot water. The remainder of the antidote, having been hastily washed by emptying it on to a piece of muslin or in a filter, pouring water on it and allowing it to drain, should be administered very -freely, indeed indefinitely, as it is en tirely harmless. H. Kohler, 36 of Halle, has made an elaborate series of chemical, physiological, and clinical experiments upon the comparative antidotal values of the saccharated ferric oxide and the freshly precipitated ferric hydrate. His results indi- cate that the former preparation is the better ; but, as the efficiency of the hydrate has been so frequently proved at the bedside, further testimony is desirable before it is superseded, especially since the other ferric preparation is not official with us, and is not so readily prepared on the spur of the moment as is its fellow. Dialyzed iron has been used with very good results, but it is much better to precipitate it, just before administration, with a small amount of ammonia or other alkali. Mag- nesia, freshly calcined or freshly precipitated from a solution of its salts, is an anti- dote of some avail in arsenical-poisoning, but is decidedly less efficient than the iron oxide. The best form of the iron antidote is probably the Ferric Oxide with * Magnesia (FE.RRI OXIDUM HYDRATUM CUM MAGNESIA, U. S. ), Arsenical Antidote of the German Pharmacopoeia. It is made by precipitating the solution of ferric sulphate by magnesia. In emergencies, Monsel's ALTERATIVES. 481 solution, tincture of the ferric chloride of iron, or other of the ferric preparations, may be substituted for the tersulphate. In arsenical-poisoning castor oil should be administered for the pur- pose of expelling the poison from the bowels, and demulcent drinks, opium, stimulants, dry external heat, and rubbing should be employed as called for by the symptoms. When there is a tendency to suppression of urine, very large draughts of feebly alkaline water should be given as frequently as the stomach will bear. The chief indications in chronic arsenical-poisoning are to remove the patient from the exposure and to treat symptoms as they arise. Post-mortem Imbibition. Owing to the extensive use of embalming with liquids made either directly from arsenical preparations or from commercial chemicals which habitually contain arsenic as an impurity, it is becoming extremely difficult in criminal legal practice, as it occurs in the United States, to prove death from arsenical-poisoning. Although the subject is somewhat aside from the main motif of the present volume, its importance seems to require a brief authoritative con- sideration, the details of which may be found in recent works on toxicology. The old belief that the finding of arsenic in the brain or organs distant from the abdo- men was proof that the poison had been administered during life, and had been scattered by absorption * and not by imbibition, is absolutely incorrect. The qualitative distribution of arsenic in the body is of very little service in most cases in determining the question as to whether the poison has been given before or after death. Arsenic which has been injected into the thorax or into the abdomen, after death, may be found subsequently in the brain and other distant parts of the body. More respect should be given to the quantitative distribution of arsenic. It is naturally to be expected that more arsenic should be found in the parts adjacent to the points of injection than in distant portions of the body ; and that the position of the body, through the force of gravity, should influence the distribution of the poison. Thus, if the corpse has lain upon the back more arsenic should be found in the back tissues than in those in the upper portions of the body ; if on the left side more poison should be found in the left than in the right kidney. Nevertheless, when a body has lain for many weeks after post-mortem arsenicaliza- tion the laws of diffusion assert themselves against the law of gravity. To be of any value whatever the quantitative chemical study of the different organs must have been made with the greatest care and attention to details, not only chemical but also physical. The whole organ must have been used or reduced to a common pulp, a portion of which has been analyzed. Moreover, the quantita- tive differences must be most pronounced, or, as it has been well stated by Mann, " must be absolute not relative ; the left kidney must contain arsenic and the right none ; it is not enough that the right kidney shall contain less than the left ; such a difference is compatible with vital absorption." Except under rare circumstances, as when the body has been buried only a few days after embalming, so that there has not been time for the processes of imbib- ition to carry the poison throughout the organs, the expert is not justified in assert- ing from quantitative evidence that the poison has been taken during life : the im- perilling of life by overconfidence of statement is not a rare crime in American courts. To-day is as true as ever that at present the dictum of Witthaus and of Tor- sellini, that it is impossible in most cases to distinguish with positiveness by chemical * In this paragraph the word " absorption " is used technically to indicate the taking up of the poison during life; " imbibition " to indicate the passage of the poison from tissue to tissue after death. 31 482 GENERAL REMEDIES. analysis between absorption and imbibition, or, in other words, whether the poison has been put into the body before or after death.* ADMINISTRATION. The beginning dose of arsenic is one-thirtieth of a grain (0.002 Gm. ), which should be given in pill after meals, and be slowly increased until a perceptible influence, or the desired therapeu- tic effect, is obtained. In many cases {chorea, lymphoma, intermittent fevers, etc. ) it is necessary to push the remedy until decided evidences of poisoning are secured : in this case a liquid preparation should be selected. The following are the official preparations of arsenic : LIQUOR POTASSII ARSENITIS. U. S. Fowler 1 s Solution (one per cent. ) is nearly colorless and odorless, with a faint taste of the compound spirit of lavender, which is in it. Dose, five to ten drops (0.3-0.6 C.c. ) in a wineglassful of water after meals, to be increased and used with the same precautions as arsenic. SODII ARSENAS. U. S. Sodium Arsenate occurs in transparent, slightly efflorescent, soluble crystals, and is solely used in making the LIQUOR SODII ARSENATIS, U. S. Solution of Sodium Arsenate (about four and a half grains to one fluidounce) is equivalent to Fowler's Solution. LIQUOR ACIDI ARSENOSI. U. S. Solution of Arsenious Acid is in strength and therapeutic use equivalent to Fowler's solution. ARSENI IODIDUM. U. S. Arsenic Iodide. This is an orange-red, crystalline solid, wholly soluble in water and entirely volatilized by heat. It has been used as an alterative, and also as an external application in lupus and chronic tubercular affections. CACODYLIC ACID. Cacodylic acid is chemically di-methyl-arsenic acid. Several of its salts have been employed in medicine as substitutes for arsenic. It has been claimed for these preparations that they are much less poisonous than the ordinary arsenical preparations, and can be used freely without danger of causing unpleasant symptoms. It would seem that their low degree of toxicity depends upon the fact that the arsenic is so firmly bound up in the composition that it is liber- ated in the body only in very small quantities, since the experiments of Heffter 1 indicate that only about two or three per cent, of sodium cacodylate is destroyed in the body and eliminated as arsenic. It is therefore probable, as claimed by Heffter, that the cacodylate is not active as such but only through the liberation of free arsenic. This view is also held by Fraser, 2 who has used the remedy in a number of cases of chorea, eczema, leukemia, and chlorosis without special result. The remedy has been especially lauded by Gautier, 3 who has employed it in various forms of tuberculosis with asserted good results. Sodium cacodylate has been used as a substitute for arsenic in all the conditions in which this remedy is useful, in doses of one-quarter to one grain (0.016-0.06 Gm.). In chlorosis and other forms of anaemia the cacodylate of iron is preferred, and may be given in the same dose. According to Gautier it is always preferable to give the remedy subcutane- ously. Under these circumstances a five per cent, solution may be employed, of which one c.c. (15 minims) may be given at a dose. * American readers see especially Medical Jurisprudence and Forensic Medicine and Toxicology, by Witthaus and Becker. Also Text-book of Legal Medicine and Toxicology, by Peterson and H aines. Also Forensic Medicine and Toxicology, by Dixon Mann. ALTERATIVES. 483 ATOXYL. Meta-arsenic-anilid. This is a white, odorless powder, soluble in twenty per cent, of hot water, and containing thirty-seven and six-tenths per cent, of metallic arsenic. According to Blumenthal it is forty times less poisonous than arsenic acid, but as its physiological, toxic, and remedial properties are probably in direct proportion to the amount of arsenic eliminated in the system, it does not seem probable that it has any advantage over the older preparations of arsenic. It is claimed, however, to lend itself especially well to hypodermic medication ; according to Schild, three to fifteen minims of the twenty per cent, solution may be given hypodermically for five days, subsequently on alternate days. Schild believes that it is especially liable to act upon the heart, and considers cardiac weakness a centra-indication to its use. HYDRARGYRUM MERCURY. U. S. Local Action. The local effect of mercurial preparations varies from complete inertness to an active escharotic influence, so that each prepa- ration must in this regard be studied by itself. Absorption and Elimination. All preparations of mercury yield them- selves or the mercury in them to absorption, and after absorption to elimi- nation. The metal has been found in the blood,* in the urine, in the serum of blisters, in the saliva, in the faeces, in the pus from ulcers, in the seminal fluid, in the milk of nursing women, indeed, in every conceivable secretion and in every tissue. Heller found it in the aborted foetuses of salivated women, and Mayen9on and Bergeret in the urine of a baby whose nurse was taking calomel ;' and each of these observations has been con- firmed by Wellander. An enormous amount of work has been done to determine how rapidly mercury is eliminated, and whether when given internally it is all thrown out of the system. The result of all this labor seems to us to prove that the single dose of mercury does not remain in the system, but that when the drug is administered constantly for a length of time elimination does not keep pace with absorption, so that the mercury ac- cumulates in the tissues. Moreover, the elimination takes place irregu- larly and intermittently, for reasons that at present cannot be made out. Further, there does not appear to be any limit of time during which stored-up mercury may remain in the body ; indeed, all the evidence points to the possibility of mercury being deposited in the tissues in such form that it is practically inert and has no influence upon the system ; liable, however, under certain agencies, to be set free and to exert its power upon the general nutrition, f * Cantu, Jourda, Andouard, Fourcroy (quoted by Stille) ; Gmelin (Bull, de Therap., xiii.) ; Byanon (quoted by Mayencon and Bergeret); Salkowsky ( Virchow's Archiv, xxxvii. 347); Salkowsky (loc. cit., 347); Mayenfon and Bergeret (Robin's Journal de T Anatomic, 1873) ; Klinik (Detroit. Me d. Jour n., May, 1877). t The rate of absorption of mercury is of course affected by the choice of preparation and by the method of administration. Wellander (Ann. Dermatolog., vii. 413) has found mercury in the urine fourteen hours after its application to the human skin and one hour after its subcutaneous administration. Mayencon and Bergeret found that when one centigramme of corrosive sublimate was given hypodermically to a dog, the urine for the next twenty-four hours contained mercury, afterwards none. When a centigramme was 484 GENERAL REMEDIES. PHYSIOLOGICAL ACTION. When a mild, unirritating preparation of mercury is introduced into the system so as to produce constitutional effects, the first symptoms of its action are to be looked for in the mouth. In the mildest degree these symptoms consist of a slight fetor of the breath, and some soreness of the teeth when knocked forcibly together or struck with a key. Mercurial fetor of the breath is generally the first indication that the drug is affecting the system, and is sooner or later accompanied by a disagreeable metallic taste. If the use of the mercury be persisted in the gums become swollen, soft, and spongy, bleeding on very slight abrasion, and there is a decided increase in the secretion of saliva. Beyond this point the therapeutist is never justified in carrying the use of the drug.. If it be done, the local symptoms in the mouth increase in severity, the tumefied gums become inflamed, very vascular, and marked by a dark red line at the junction of the teeth ; the tongue is also swollen, sometimes enormously, protruding from the given daily for ten or twelve days, the urine contained mercury for four or five days after the cessation of medication. In their last series of experiments, rabbits received the drug, and were killed at different intervals : in half an hour the metal could be found in all the tissues, the liver and kidneys containing most of it ; in four days, or even in a shorter time, mercury given in a single dose was all eliminated, and could not be found in the tissues. The evidence in favor of the storing up of mercury in the system is overwhelming. In 1880 Vajda and Paschkis ( Ueber den Einfluss Quecksilbers, Wien) stated that they found the metal in the urine in different cases, six months, one year, two years, and even twelve and thirteen years after the mercurial course. Mayencon and Bergeret found that the exhibition of potassium iodide forty-eight hours after the cessation of a mercurial course, when the urine was free from mercury, would bring about the immediate elimi- nation of mercury. Sigismund has detected quicksilver in the urine of patients as long as thirteen years after taking the medicine ; but Schuster (Zeitschr.f. Klin. Med., 1884, vii.) asserts that these patients were habitues of a room in which inunctions were constantly being made, and that under these circumstances there is sufficient diffusion of the mercury to produce a very sensible effect in those breathing the air. Apparently, however, using all precaution and having the patient carefully watched, H. Stein ( Wiener Klin. Wochens., 1890) has obtained weighable amounts of eliminated quicksilver from the urine four weeks after its inunction. (See also Viertelj. f. Dermal, u. Syphilis, 1882; Annales de Der- mal, et Syphil., 1882, iii.). Schuster has found it in the faeces three months after the ces- sation of a mercurial course ( Viertelj. f. Dermal, u. Syphilis, ix. 307) ; indeed, he believes that it is thrown off more freely and constantly by the intestines than by the kidneys. He also asserts that elimination is completed six months after the cessation of an ordinary mercurial course (Journ. of Cutan. Med., i. No. 12, ii. No. 9). According to Gola (A. I. P. T., 1900, viii. 203) when the kidney elimination is great the intestinal output is small and vice versa. In an elaborate memoir on the elimination of mercury, Balzer and Klumpke (Revue de Medecine, 1888, viii.) state that extraordinary exacerbations and remissions occur in the elimination during treatment, that Michaelowsky and Souchow have shown that the effect of potassium iodide is small, but that Stepanow has proved that the hot-air baths increase enormously the elimination. It appears to be established that in these cases of long continuance the mercury escapes not only through the kidneys, but is also excreted by the salivary glands as well as by the intestines, and hence its con- tinuing elimination may be overlooked by the chemist, who simply studies the urine. (See paper by Stein and Kronfeld, Wiener Med. Wochen., 1890.) Method of Preparing Tissues for Microscopic Detection of Mercury. J. Almkvist (S. J., Bd., cclxxx., p. 177) soaks the freshly cut pieces for eight or ten hours in a solution of sulphuretted hydrogen, containing four per cent, of nitric acid, producing a yellow precipitate of mercuric sulphide ; subsequently he hardens in alcohol or other fluid not containing iodine, and cuts. ALTERATIVES. 485 mouth, whose closure it may entirely prevent ; the teeth are loosened in their sockets ; the saliva is enormously increased in quantity and altered in quality, forming great, ropy, viscid masses, which pour over the thick- ened lips ; the parotid glands, and even the submaxillary, are very much enlarged and tender. Severe ptyalism may be accompanied by marked fever, and nephritis is a not uncommon occurrence. Loss of the teeth, extensive ulceration of the soft parts, and even necrosis of the jaw-bones have occurred, and death from exhaustion resulted, or the patient strug- gled through to recovery, seamed and disfigured for life. In these cases passive hemorrhages often recur again and again, and may contribute largely to a fatal result. During severe ptyalism emaciation goes on rapidly, and seems to especially affect imperfectly organized tissues, so that exudations very generally rapidly disappear. The disturbance of nutrition is further shown in some cases by the occurrence of ulcers upon the extremities. The blood suffers very decidedly, becoming more fluid and watery than normal and having its power of coagulation impaired. According to the researches of Wright, its solid constituents are notably diminished, including albumin, fibrin, and the red corpuscles, and it con- tains a large quantity of a fetid, fatty material. These observations of Wright have been confirmed upon animals by Wilbouchewitch, 1 and by I. Hughes Bennett. Although large doses of mercury lower the general nutrition and de- stroy the crasis of the blood, it is probable that when given in very minute doses it has tonic properties. In 1869 Liegeois 2 asserted that the subcutaneous injection of very minute doses of quicksilver produces in healthy men an increase of their bodily weight, and in 1876, in two experiments, E. L. Keyes 3 found that not only was the bodily weight increased, but, as determined by actual count, the number of the red corpuscles was decidedly augmented. ' Hermann Schlesinger* has laboriously experimented upon rabbits and dogs. All other conditions being similar, those rabbits which received the mercury increased in weight a little more than did those to which mercury was not given, but the augmentation of the red blood-disks was distinctly greater in the mercurialized animals. With dogs the results were more decided, both bodily weight and blood-corpuscles increasing much faster in the animals to which mercury was given. I. Hughes Bennett had previously obtained results similar to those quoted, and Schlesinger thinks that it must be considered proved that very minute continuous doses of mercurials tend in the normal animal or man to increase distinctly the weight of the body and the richness of the blood, but that it is scarcely proper to call them tonic, as in his belief they act by hindering oxi- dation and restricting waste, and not by aiding in reconstruction, a conclusion which is purely theoretic and unproved. In some cases of syphilitic anaemia the effect of mercury in increasing the number of red blood-corpuscles is very marked. This effect is, however, to be attributed to the antisyphilitic influence of the remedy rather than to any specific action on the blood-making organs. (For elaborate paper, see L. Gaillard. 8 ) The ordinary symptoms of mercurialization have been sufficiently described, but there are on record various anomalous cases. In some instances the chief symptoms of mercurialism have been cutaneous. 4 86 GENERAL REMEDIES. The usual eruption is a polymorphic erythema, resembling more or less that of scarlet fever. In rarer cases the eruption may be distinctly erysipelatous, with sub- dermal cedematous swelling. Sometimes it takes the form of urticaria, or even of a roseola ; a very severe eczema, becoming finally pustular, has in some cases been pro- duced, most frequently as the result of an inunction ; whilst mercurial pemphigus and purpura have both been recorded. Usually the eruption is fugacious, being followed in two or three days by more or less desquamation, but very grave cases have been recorded in which there has been a universal dermatitis, with great swelling of the face and extremities, excessive desquamation, followed by thickening and infiltra- tion of the subdermal tissues, excoriation, violent fever, disturbance of the respi- ration, and death ; or, if the patient survive, months of illness (see M. A. Morel- Lavalle"e. 6 Sometimes the influence of mercury falls almost exclusively upon the nervous system, and produces a peculiar train of paralytic phenomena. Nervous mercurialism occurs chiefly when mercurial vapors find entrance through the lungs, and is most frequently seen in workers in the metal. It is gen- erally the result of long exposure ; but that it may be produced in a very short time is proved by the case, related by Christison, of two barometer-makers who slept one night in a room containing a pot of mercury upon a stove. One was severely sali- vated, the other was affected with a shaking palsy which lasted all his life. Accord- ing to Sigmond, 7 the attack of mercurial palsy, which is sometimes sudden, some- times gradual, begins with unsteadiness and shaking of the extremities and of the muscles of the face, which movements interfere with walking, speaking, or chewing ; the tremors become frequent, nay, almost constant ; ' ' every action is performed by starts." If the exposure be continued, sleeplessness, loss of memory, and death terminate the scene. A peculiar brownish hue of the whole body, and dry skin, generally accompany the disease. In its first attack it may be mistaken for St. Virus's dance ; in its latter stages, for delirium tremens. According to Noel Gue'neau de Mussy, 8 these two forms are distinct varieties rather than different stages of mercurial tremors. In the latter the affection simulates paralysis agitans in its shaking movements ; in the former the motions are violent, and occur independently of the will of the patient, even when he is lying quietly in bed. In a case reported by L. Langer, 9 the electro-contractility of the affected muscles was much heightened. Paralysis from chronic mercurial poisoning is said to be not a rare affection among artisans and miners who are in their daily occupation exposed to contact with the metal or its fumes. The subject has been thoroughly discussed by M. M. Letulle, 10 to whose paper the reader is referred for a collection of recorded cases and for details. In a case reported by Sigmond, symptoms similar to those of chronic lead-poisoning, including wrist-drop, followed repeated mercurial inunctions. In some cases mercurial paralysis takes the form of multiple palsy, or of a brachial or crural monoplegia, or of an obscure local palsy, as in a case re- ported by Kiissmaul, in which there was aphonia from paralysis of the laryngeal muscles. Almost invariably the loss of motor power is accompanied by an anaes- thesia, which may be wide-spread or may be in isolated islets, or may take the form of hemiansesthesia. The loss of sensation is very rarely absolute ; simple loss of the thermic sensibility or analgesia may exist alone. Partial anosmia or amblyopia may show that the nerves of special sensation are affected. Neuralgic pains may be the permanent result of a mercurial exposure, and epilepsy and even insanity, most frequently of the melancholic type, are stated to have been so produced. According to Letulle, trophic changes are not common, the paralyzed muscles not undergoing atrophy, and retaining their normal relations to the galvanic and faradic currents. When the thighs are affected the knee-jerk may entirely disappear. Guinon " describes violent hysteria following upon chronic mercurial intoxication. ALTERATIVES. 487 In some cases exposure to the vapor of mercury, or even its persist- ent medicinal use, has resulted in the production of a state of the system somewhat resembling scurvy, characterized by great anaemia, emaciation, and general loss of power, with loss of the hair, aching pains in the bones and joints, oedema, fetid breath, diarrhoea, and generally disordered secretions. This is the so-called mercurial cache xia* There is some reason for believing that the pancreas is especially affected by mercury. Thus, in a case related by Copland, a woman after excessive salivation experienced deep-seated epigastric pain and heat, with nausea, thirst, and fever, and voided thin stools containing liquid resembling salivary fluid. At the post-mortem the pancreas was found weighing four ounces, red, congested, and with its duct dilated. In re- gard to the action of mercury upon the liver, see PURGATIVES. The experiments of I. Brauer 12 and of V. Tirelli 13 show that in the lower ani- mals very large doses of mercurials have a powerful depressing influence upon the central nervous system, and may produce death by respiratory paralysis ; that when smaller doses are given a condition of nervous ex'citement is produced, with in- crease of the tendon-reflexes, followed by partial paralysis and ataxia ; and that in chronic poisoning by very small doses continuously administered a degeneration of the nervous system takes place, probably beginning in the anterior motor cells of the spinal cord. This degeneration appears, however, not to be characteristic of the mercurial poisoning, but to be similar to that produced by phosphorus, arsenic, and various other poisons. Little attention has been paid to local mercurial poisoning, but A. W. Foot M has reported the production of paralysis of the muscles of the hand and forearm by contact with the red mercury iodide during the rubbing of cattle with a salve containing it. It is asserted that in some peculiar persons the external, and even the internal, use of small amounts of mercurials will produce violent eczema or other skin-eruptions (Alex- ander 15 ). The constitutional action of mercury shows that it has relations to the nutrition of the whole body. The alterations in the blood, the wasting, the perverted functions of nerves and of glandular tissues, the various skin eruptions, all point to a profound influence upon the whole organism. After death from such irritant preparations of mercury as corrosive sublimate, violent diphtheritic colitis is the ordinary lesion, and, as was first shown by Salkowsky, structural alterations abound in the kidneys, accompanied by a peculiar deposit of calcium phosphate : that the renal lesions may be produced by the non-irritant preparations of mercury has been shown by B. Silva, 16 who has found true desquama- tive nephritis in dogs to which calomel had been given. Felix Klem- perer 1T discusses the literature of the subject fully, and concludes that the successive changes in the kidneys are : excessive hyperaemia, parenchy- matous nephritis, hemorrhagic nephritis, with wide-spread degeneration * For an interesting paper in regard to mercurialism in looking-glass makers, see article by Wollner {Munch. Med. Wochen., July, 1892). 488 GENERAL REMEDIES. of the epithelium, and in about one-half of the cases deposits of chalky material. Virchow 18 states that the coexistence of distinct renal chalky deposits with diphtheritic hemorrhagic colitis justifies the diagnosis of corrosive sublimate poisoning, but Klemperer affirms that this condition can be produced by bismuth and some other poisons. The later re- searches of E. Lentert'Med to a similar conclusion, namely, that the calcification of the kidneys makes the diagnosis of corrosive sublimate poisoning very probable but not assured. The calcification of the kid- neys, which is often accompanied by true calcareous deposit in the tubules, and which may be sufficient to cause the kidney structure to cry out under the scalpel, was attributed by Prevost 20 to the decalcification of the bones ; a theory which seems to have been disproved by Klemperer (confirmed by Paul Binet 21 ). According to our present evidence, it does not seem probable that mercury increases the nitrogenous waste. It is true that Hermann von Boeck, 22 in a case of mercurialization in a man, found that there was a very slight increase in the elimination of nitrogen during the mercurial periods, but H. Schroder, 23 and Guttenberg and A. Gurber, 24 in experiments made upon rabbits, obtained an absolute decrease in nitrogenous elimina- tion during mercurial poisonings. THERAPEUTICS. The use of mercury in affections of the liver and of the alimentary canal is fully discussed in another portion of this treatise ; and, although the drug has been used for almost innumerable purposes in times past, it seems here only necessary to speak of its action as an antiphlogistic and as an antisyphilitic. Antiphlogistic Action. The use of mercury in inflammation origi- nated towards the close of the last century with Robert Hamilton, and soon became universal in England and America. It is a matter of regret that no sufficient analyses of the blood of ptyalized persons have been made to determine exactly what are the changes produced in the vital fluid by mercury. The indications are, however, very strong that chief among them is a lessening of the amount of fibrin. As is well known, increase of the haemic fibrin is one of the most characteristic effects of inflammation : consequently, theory, instead of being opposed to the antiphlogistic use of calomel, affords at least some grounds for the belief that there is more or less antagonism between the processes of mercu- rialization and of inflammation. All important evidence as to the antiphlogistic value of mercurials at present available is clinical, and even of this it seems impossible to find much that is very exact and of such nature as to exclude possible fallacies. It is the enormous mass of testimony that overrides the proba- bility of fallacy. It is the general judgment of the profession, founded upon the thousand daily observed bedside facts, that endorses the use of mercury as an antiphlogistic. In other words, our knowledge of the value of mercurials in inflammation at present is clinical rather than experi- mental, empirical rather than scientific, but it seems scarcely possible ALTERATIVES. 489 that it is not correct. There is one inflammatory affection iritis which, from its anatomical relations, is completely visible at all stages ; and the effects of the drug upon its processes have been noted from day to day hundreds of times. Oculists are, we believe, agreed that when there is a marked tendency towards the exudation of lymph in this disease, mer- cury should be exhibited until ptyalism is induced. Of all inflammations, those of the serous membranes seem to be most allied to iritis ; and it is exactly in the condition above spoken of, where there is a tendency to fibrinous exudations in pleuritis, peritonitis, and pericarditis, that mercury is so constantly employed with so good an effect. In parenchymatous inflammations, especially \\\ pneumonia and in hepatitis, mercury has been used with asserted advantage by many practitioners, but its value is certainly more questionable than in serous inflammations. In pseudo-membranous angina or laryngitis, and in true diphtheria, the mercurials are very useful remedies ; they should be given in small repeated doses, preferably in the form of dry calomel pow- ders, it being probable that the good effect is at least in part due to the diffusion of the mercurial over the diseased surface and the consequent antiseptic influence. There is much doubt as to the exact advantageous- ness of mercurials in endocarditis ; but, as it is extremely important, if possible, in that disease, to prevent exudation, and as mercury is the most efficient known agent for effecting this, it should be administered freely and at once. In whatever disease a mercurial is administered as an antiphlogis- tic, it should be given during the stage of exudation, and to facilitate the absorption of the newly organized lymph after it has ceased to be thrown out. In the majority of cases mercury given for its constitu- tional effects should be combined with opium, to prevent its acting on the bowels. Calomel should not be used in adynamic inflammations, or where the exudation is serous rather than fibrinous. In puerperal peritonitis it has been strongly advocated by some and as strongly condemned by others, simply because there are two varieties of the disease, the sporadic or tfhenic, and the epidemic or asthenic ; and in the one both bleeding and calomel are strongly indicated, while in the other they are effective only for evil. Mercury as an Anti syphilitic. The literature concerning the use of mercury in the treatment of syphilis is so enormous as almost to defy analysis ; through the discussion, however, has finally been reached practi- cal unanimity of professional opinion, the only points of difference being as to details of ' ' how' ' and ' ' when' ' the mercury should be employed. Whenever a venereal ulcer offers the characteristics of a true chancre, mercury should be exhibited. Many practitioners believe that it is wiser for diagnostic purposes, in all cases of doubt as to the character of the primary sore, to withhold the mercury until secondary manifestations appear. Under any circumstances, so soon as the diagnosis of syphilis 490 GENERAL REMEDIES. is clearly established, mercury should be employed in some form or other. Our own practice is in the beginning of the treatment to push the mercury to the point of mild ptyalism, i.e., to the production of slight evidences of constitutional drug action, and then to continue the medicine persistently in small doses for at least eighteen months, in- creasing the dose up to mild ptyalism if at any time there should be a recrudescence of the symptoms. In tertiary syphilis mercury is to be used cautiously. It is not, how- ever, the mere length of time that has elapsed since the infection, but the condition of the patient, that guides the judicious practitioner. So long as there is no decided cachexia, if the patient has not recently been through a mercurial course, mercury should be freely used when the local lesion threatens to kill directly or to produce organic changes in a vital organ. Thus, a gumma in the heart-wall, in the upper spinal cord, or in some vital brain-region may imperatively demand active mercurialization. We have twice seen a patient slowly recovering from brain-syphilis under the influence of the iodides die by the accident of an epileptic arrest of respiration. In these cases the more rapid resolution of the gummatous masses by mercury, had that drug been exhibited, would in all proba- bility have prevented the fatal fit. In hereditary syphilis a prompt mer- curial impression offers the best chance of relief. At any stage of syph- ilis some caution and judgment should be used in the administration of mercury. As was shown by Keyes, the small dose of mercury in infected patients frequently acts distinctly in increasing the number of red blood-disks. Wilbouchewitch found that the mercurial when first exhibited increased the number of red blood-corpuscles in syphilitic patients, but after a time appeared to produce anaemia. Whatever preparation be employed, it should be so administered as to cause only signs of the constitutional action in the mouth. It is never necessary to ptyalize the patient severely. There are various methods by which this may be done. That most frequently employed, because most con- venient, is the administration of small doses of calomel or blue pill by the mouth : from one-fourth to one- half grain of calomel, or twice as much of the blue mass, combined, if necessary, with opium, to prevent its action upon the bowels, may be given three times a day, and increased if required. Instead of the internal use of the mercurial, the system may be brought under its influence by inunctions. In practising inunctions it is essential to remember that when mercury is applied to a hairy surface it is very prone to cause a troublesome irri- tation, due to inflammation about the hair-follicles. Indeed, the contin- uous application of the mercurial to almost any surface of the body will cause finally an eczematous eruption. Further, when the skin is in thor- oughly good condition it absorbs much better than when it is irritated. The frequent use of the hot baths seems also to aid in the absorption, and possibly also in the elimination of the mercury ; and the good effects ob- tained at the Arkansas and other thermal springs largely depend upon ALTERATIVES. 491 the frequent employment of the hot bath with the free use of the mer- curial. It is therefore usually better to have the inunction practised in the evening, after the patient has had a prolonged bath ; and in cases of great urgency the baths may be repeated two or three times a day, so as to produce free sweating, and the inunction practised, it may be, twice a day. In order to avoid irritation of the skin, a regular order should be maintained in the application, as follows : first day, inner side of both upper arms ; second day, inner side of both thighs ; third day, inner side of both forearms ; fourth day, inner side of both legs ; fifth day, upon both groins ; sixth day, upon the back ; seventh day, recommence the series. The advantage of inunction is that the digestion is less apt to be dis- turbed than when the drug is exhibited by the mouth ; * the disadvantages are the greater or less publicity which it entails, the trouble which it in- volves, and its apparent dirtiness. In private practice it is rarely prac- tised except in the case of infants, when the mercurial ointment is rubbed into the abdomen and armpits, or often simply smeared upon the flannel roller or binder which usually envelops the body. The mercurialization of the nurse, with the object of affecting the child, is unjustifiable, unless the nurse and the nursling are alike diseased : indeed, to allow a syphilitic child to feed at the breast of a healthy woman is a crime. Mercury may be used hypodermically, often with great advantage, in the treatment of syphilis. The search after novelties by clinicians and chemists has led to the invention of very many new preparations and the production of a very large literature, which was summarized in previous editions of this work, and is discussed in great detail in current mono- graphs on syphilis. As the result of much experience, however, we are confident that the whole matter can be summed up in a single sentence, namely, that no mercurial preparation has any distinct advantage over corrosive sublimate for hypodermic administration ; and that the great mass of the proposed preparations, including all those which contain cal- omel, are much more dangerous than is the corrosive chloride. From one-sixteenth to one-eighth of a grain of the bichloride should be injected deeply into the muscles of the back or of the thigh daily or every other day, according to the needs of the case ; care being exercised to see that the part is well rubbed immediately after the injection, so as to dispel the local accumulation of fluid, and that injections are not given on successive days in places near to one another. In some cases very pronounced pain * The action of inunctions is usually very mild and tractable, but Von Sackur (Berl. Klin. Wochensch., 1892, xxix.) has reported a case of death in six days, preceded by symptoms of violent irritation of the stomach, the intestines, and the kidneys, with furious gangrenous ptyalism, apparently produced by a single inunction with mercurial ointment. Ludwig, of Vienna, in an examination to determine the distribution of mercury given by inunction, found that it was most abundant in the kidneys, liver, and spleen ; then in the alimentary canal (least in the stomach and most in the large intestine). In the muscles the amounts were variable, in the cerebrum never sufficient to be weighed (Internal. Klinisch. Rundschau, 1892, vi.). 492 GENERAL REMEDIES. is produced ; this can be overcome, however, by injecting one-quarter of a grain of cocaine immediately before the injection of the mercurial into the same spot. The advantages of hypodermic medication are the rapidity and power of influence, the cleanliness, and the avoidance of gastro-intestinal irritation. Mercury is sometimes administered in secondary syphilis in the form of fumigations. The patient is placed upon a chair, and surrounded by a large blanket or, better, india-rubber cloth, so arranged as to fit tightly around his neck above, and below to encompass the chair. The mer- curial preparation is placed upon a metal plate, heated by a spirit-lamp, beneath the chair, and the fumes are allowed to fill the space around the patient inside of the blanket. The heat produced generally causes the patient to sweat profusely, and in from fifteen minutes to half an hour the lamp should be withdrawn and the patient allowed to cool off, and after a time be put to bed and wrapped up in blankets, with the deposit of mercury still adhering to the skin. The fumigation may be practised every other night, or at longer intervals, and is believed by some to be especially useful in cases of secondary skin eruptions. Calomel, black oxide, and cinnabar are the preparations generally used ; care must be exercised that the patient do not breathe the fumes. In advanced secondary and tertiary syphilis the mercurial iodides, given by the mouth, are often very useful, but the combination of the corrosive sublimate and the potassium iodide is in many cases still more efficient. Usually not more than one-twelfth of a grain of the bichloride should be exhibited, three times a day. It appears to be established that certain disagreeable and, perchance, serious effects may be produced by mercurials when freely and continu- ously used in the treatment of syphilis, against which the practitioner must be on his guard. The most important of these is nephritis, with its consequent albuminuria. According to Heller, 25 the safest method of mercurialization, so far as the kidneys are concerned, is by the hypoder- mic employment of corrosive sublimate ; the most dangerous, probably, being the use of inunctions. A very rare complication which has been attributed to the mercury is polyneuritis, which has especially been noted after the very free use of mercurial inunctions.* ADMINISTRATION. The following preparations contain metallic mer- cury : UNGUENTUM HYDRARGYRI. U. S. Blue, or Mercurial, Ointment is made by triturating mercury with suet and lard until the metal is extin- guished, /.om our present knowledge it seems almost impossible to say posi- tively in which form the active principle occurs in nature, since the com- plicated processes involved in the isolation in either instance might be sufficient to cause the slight difference in their formula. Practically, how- ever, it would seem that both adrenalin and epinephrin represent the physiological activity of the suprarenal capsules. Dreyer 5 found the active principle of the suprarenals in the vein coming from the suprarenal capsule, and that stimulation of the splanch- nics increased the amount present in the blood. From these experi- ments it would seem that the active principle of this vein is the product of a true glandular secretion. This is confirmed by the observation of Pettit, 6 that the adrenals are affected by glandular poisons, as pilocarpine, in the same manner as are the other glands of the body. Langlois 7 concludes from his experiments that there must be more than one active substance in the gland ; a view which is also adhered to by Corona and Moroni. 8 It would seem that one of the functions of the glands is to destroy toxic substances. It seems established that the adrenal bodies contain a considerable amount of neurin, a toxic substance resulting from katabolism of nervous tissue, and that this substance appears in the urine of persons suffering from Addison's disease ; and Albanese has shown that animals are less resistant to neurin after extirpation of their adrenals. Boinet 9 (confirmed by J. E. Abelous 10 ) has found that this applies also to atropine and nicotine. Langlois and Charrin " discovered that the repeated injection of certain toxins in sublethal doses produced an hypertrophy of the supra- renal capsules ; but that instead of being physiologically more active, such hyper- trophied glands lose their reaction towards ferric chloride and also their effects on the blood-pressure. The fact that the hypertrophied glands affect the circulation less than do the normal is very strong evidence that the circulatory poison is not the same principle as the antitoxic substance.* * An interesting confirmation of the fact is the observation of Caussade" that the glycerin extract of the suprarenals when injected continuously produces an hypertrophy of the suprarenals precisely as do other toxic bodies ; suggesting that the gland destroys its own secretion when in excessive amount. 540 GENERAL REMEDIES. PHYSIOLOGICAL ACTION. Local Action. Locally applied the ex- tract of the suprarenals acts as a powerful constrictor of the blood-vessels. It has of itself no local anaesthetic properties, but when used in con- junction with cocaine, enhances the powers of that drug, probably by its action on the blood-vessels. Elimination. The active principle of adrenals is very rapidly de- stroyed or eliminated in the system, since the effects do not last much over ten or fifteen minutes. Cybulski discovered that the urine of ani- mals poisoned with suprarenals is capable of producing a rise in the blood-pressure, and therefore believed that the active principle is elimi- nated by the kidneys. Ott and Harris 13 confirm this fact, but assert that it can be shown only after enormous doses have been given. It would seem, therefore, that only a part of the drug is eliminated by the kidneys. Langlois u found that maceration with the liver destroyed the active prin- ciple of the gland, that ligation of the hepatic vein prolonged the duration of its effect, and that when injected into the portal vein the suprarenal had comparatively small influence upon the circulation. This last fact has been also noted by Carnot and Joserand, 15 who further determined that injection into the femoral artery likewise destroys the activity of adrenalin. It would seem, therefore, that it is largely oxidized in the liver and mus- cular tissue. Erhmann 33 believes, however, that adrenalin is neither eliminated nor destroyed, because he finds remaining in the blood after the pressure has fallen to the normal more than sufficient of the principle to act as a circulatory stimulant, and because the blood of such an animal is capable of causing a rise of pressure in another animal. General Effect. The most manifest action of suprarenal bodies is upon the circulation, so that after the exhibition of anything like the therapeutic dose the only symptoms produced are connected with the circulation. Toxic doses of the extract caused in the frog progressively increasing loss of power without a true paralysis, which seems to be of spinal origin, since Gourfein and Oliver and Schafer find that after ordinary toxic doses the nerve-trunks and muscles preserve their activity up to death ; on the other hand, Vincent 16 asserts that the suprarenal extract is a muscle- poison, producing, when given to the frog in overwhelming doses, a pecu- liar rigidity similar to that brought about by veratrine. According to Abel 17 and Abbott, 18 epinephrin kills by arrest of the respiration. This paralytic effect upon the respiratory centres is preceded, if the dose has not been too large, by an enormous increase in the rate of the breathing. The lethal dose for a rabbit, according to Abel, is about ten milligrammes. The injection of the suprarenal extract or its active principle has been shown by a number of observers to produce glycosuria. Croftan 19 found in the suprarenal extract a diastatic ferment which was capable of producing glucose from glycogen, but Hurter and Richards 20 have shown that Takamine's adrenalin does not affect solutions of glycogen, although it causes the occurrence of sugar in the urine. ALTERATIVES. 541 They attribute this effect to an action on the pancreas, since they found degenera- tion of the islands of Langerhans after adrenalin-poisoning. Patton" determined that adrenalin was capable of causing the formation of sugar from the proteids after the destruction of the carbohydrates of the body; the glycosuria he therefore regarded as a true diabetes. Nutrition. Although the effect of suprarenal feeding on nutrition seems to be of minor importance, it has been abundantly proven that either the dried capsules or adrenalin is capable of producing glycosuria. This is accompanied with an increased amount of sugar in the blood and appar- ently disappearance of glycogen from the liver (see Paton 36 ). Drummond 37 has shown that adrenalin is capable of giving rise to acute parenchymatous nephritis. Circulation. After the intravenous injection of the suprarenal extract or its active principle, there occurs a maxked rise of the blood-pressure accompanied by a slowing of the pulse. When the blood-pressure has reached its maximum, the pulse becomes rapid. According to Cyon," this increase in the rate of the pulse is brought about by a heightened excitability of the accelerator centre. Amberg has shown that the slowing of the pulse is not dependent upon a rise of the blood-pressure as is claimed by Gearheart, 23 but is due to a stimulation of the inhibitory centre, being abolished either by section of the vagi or the injection of atropine. The rise of the pressure is not prevented by division of the splanchnics (Cyon) nor of the spinal cord (Oliver and Schafer). Meltzer and Meltzer 24 and Josue 25 have shown that the division of the sympathetic does not prevent the constriction of the vessels in the ear of the rabbit on the corresponding side. In fact, according to the former in- vestigators, the contraction was more marked on the side whose nervous influences had been destroyed than on the other side. Gottlieb w has determined that the vessels of an isolated kidney which had previously been dilated with chloral hydrate were contracted by the suprarenal extract. The pulmonary-pressure, according to both Velich and Gearheart, is slightly elevated by the adrenals. Ott and Harris 1S have found that adrenalin applied externally to the isolated frog heart produce a temporary decrease of both force and rate followed by an increase in the same, and Gottlieb has found that the isolated mammalian heart is also stimulated by the suprarenal extract. With very large doses the rise of pres- sure is followed by a gradual fall to the zero point, the heart ceasing in diastole. From the results of these observers it would seem that epinephrin stimulates the muscular walls of the heart and of the blood-vessels or else, as Gottlieb believes, their contained motor ganglia and the cardiac inhibi- tory centres. A remarkable effect, first demonstrated, we believe, by Josu6, and confirmed by Kulbs 34 , Erb 35 and others, is atheroma and even calcifica- tion of the arteries following the repeated injections of adrenalin. Kulbs has demonstrated in the rabbit not only hardening of the walls, but aortic aneurism which, in one case ruptured with fatal hemorrhage. This oc- curred after thirty-one injections given twice a day. According to Erb these changes are dependant upon a direct toxic influence on the muscle-fibers of the vessel walls. Besides the lesions in the arterial walls, 542 GENERAL REMEDIES. pulmonary oedema has been reported by Kulbs and others as a secondary result of the use of adrenalin. THERAPEUTICS. There is at present considerable clinical as well as experimental evidence to show that the extract of the suprarenal capsule is of value in the treatment of Addison' s disease. It is plain, however, that when the lesion of the adrenals is cancerous or tubercular, supplying artificially to the system an active principle prepared by those bodies cannot affect the progress of the local disease and therefore cannot bring about a cure. The most important therapeutic use of this drug depends upon its influence upon the blood-vessel walls when locally applied. It is used to counteract the vascular engorgement in the treatment of various inflam- mations of the mucous membranes, as rhinitis, pharyngitis, conjunctivitis and the like. According to Konigstein "" and De Schweinitz, the retinal vessels are not affected when the drug is instilled into the eye. It does not dilate the pupil * nor influence accommodation. It seems to possess the power of penetrating the skin and of whitening the hyperaemic skin of chronic eczema, It is difficult to say precisely what value this method of treatment has in acute inflammation. De Schweinitz 28 is of the opinion that, although the application of the suprarenal solutions will produce a blanching of the inflamed part, it does not hasten the cure of the dis- ease, and Kyle has seen cases of acute coryza made decidedly worse by the treatment. In liay fever it frequently gives good results, but in many cases fails entirely to relieve the symptoms. On account of its local vaso-constrictor action it is also of use in controlling local hemor- rhages, as epistaxis, hczmatemesis, enteric hemorrhages in typhoid fever. Various authors recommend it for the purpose of preventing hemorrhage during operations on the throat and eye. As pointed out by Kyle, 29 operations done under adrenalin ischaemia are likely to be followed by post-operative bleeding. Its effect in constricting the blood-vessels is not likely to make it of any value as a styptic in internal hemorrhages. Carnot and Joserand M have shown that if injected intravenously it does not produce visceral haemostasis. Moreover, these authors find that its action as a local styptic differs very markedly in different portions of the body. Thus, when injected in the kidneys it has no haemostatic action at all ; much less power when applied to the intestines or stomach, than in the nose. Suprarenal extract, and its active principle, have been suggested and to a certain extent used, as circulatory stimulants in conditions of sudden circulatory failure, especially in shock during operation. The ex- treme fugaciousness of its action makes it, however, even in these acute * Meltzer, Ott, and Harris assert that after section of the cervical sympathetic it does dilate the pupil. ALTERATIVES. 543 conditions, of comparatively little value, and the effects of its repeated use in causing arterial and pulmonary oedema, render its repeated use very dangerous. We have seen patients whom, we believe, were being killed by confidence in this drug as a circulatory stimulant. Internally it has been recommended by Cohen for the relief of asthma and hay fever, and by Floersheim Sl in endocarditis, but it is extremely doubtful if it is of value in either of these conditions. Schafer 32 recommends its employ- ment in uterine hemorrhages, as does also Floersheim. The former believes that it controls the hemorrhage by stimulation of the uterine muscle. ADMINISTRATION. Locally the suprarenal gland may be used in the form of a watery extract of from five to twenty per cent. Adrenalin may be applied in strengths varying from i to 100 to i to 10,000, either by atomizer or by tampon. Internally the dried suprarenals (GLANDULE SUPRARENALES Sicc.9 3. 31- 32. WOOD, JR. . 33 MAX and SORGE . Vierteljahrs, f. gericht. Med. 1905, xxix. 85. IODIPIN. . \VlNTERNITZ . . M. M. W., 1903. . SCHUSTER .... W. M. P., 1901, xlii. . NAEGELI . . . . A. A., 1901, xliv. IODINE. . LEUCH C. K. M., 1890. , HARNACK . . . . B. K. W., 1882. . SCHULZ .... Sitzungs d. Physik. Med. Soc. Erlangen, 1894-98, 26-30. TAYLOR Amer. Journ. Syph. and Derm., 1873. SEE L. M. R., i. 777. , EHLERS Ann. de Derm, et Syph., 1890. ROSE Nothnagel's Arzneimittel- lehre, Berlin, 1870, 252. CULPEPER . . . . T. G., 1888, iv. HOYGES and BINZ . A. E. P. P., x. 229, xlii. 114. TROUSSEAU . . . B. A. R. B., xxv. WOLF B. K. W., 1886, 580. KAMMERER . . . V. A. P. A.,lix. 467, Ix. 527. ROSE V. A. P. A., xxxv. SEE and LAPICQUE . B. A. M., 1889, xxii. ZEISSL Z. K. M., xxvii. ZEISSL Wien. Med. Presse, 1898, xxxix. PREVOST and BINET . R. M. S. R., 1890. VON BOECK . . . Z. Bi., 1869, iii. 393. JONES Beale's Archives, i. DUCHESNE .... In. Dis., Paris, 1885. HENRIJEAN and CORIN . A. Pharm., 1896, ii. HAIG L. L., 1893, i. DA COSTA . . . . A. J. M. S., Jan. 1875. SQUIER M. News, 1891, lix. WALLACE . . . . Liverpool Med. Surg. Rep., 1871. MARSHALL . . . T. G., Feb. 1888. ANTEN A. E. P. P., 1902, xlviii. LESSER A. D. S., 1903, Ixiv. STOCKMAN and CHARTERIS . B. M. J., 1901, ii. BESNIER B. M. S. H., xx. BJELOGOLOWY . . A. V. K., Bd. x. IODOFORM. ZELLER Z. P. C., viii. 70. HOYGES A. E. P. P., x. 405. - Continued. RUMMO A. de P., 1883, 144. FLOUCAUD .... Thesis, Montpellier, 1872. KREVET Th. M., 1888, ii. KRONACHER . . . M. M. W., 1887, xxxiv. 546. LUBERT Fort. M., v. 343. HEYN and DROVSING . Fort. M., v. 33. OLSEN Norsk Mag. for Legevi- densk, 1886. KONIGE Th. M., April, 1887. SATTLER .... Fort. M., v. 362. BRUNS Th. M., May, 1887. ELSBERG .... P. M.T., 1873, iv. 4. LANGENSTEIN . . W. M. W., 1882, xxxii. 1051. 5. CZERNY W. M. W., 1882, xxxii. 180. SAMTER and RETZLAFF . T. G., 1889. ROBERT A. I. P. T., 1901, viii. ANSCHUTZ . . . . B. K. C., 1900, xxviii. 233. IODOL. MAZZONI . . . . B. K. W., 1885. MARCUS B. K. W., 1886. PAH i In. Dis., Berlin, 1886. LANGENSTEIN . . T. G., 1887, 768. PICK Viertelj. f. Derm. u. Syph., 1886. CERVESATO . . . B. K. W., 1889, xxvi. ARISTOL. NEISSER B. K. W., 1890, xix. QUINQUAUD and FOURNIOUX . C. R. S. B. 1890. THIOSINAMINE. VON HEBRA . . . M. P. D., 1893, ix. SUKER M. A., 1902. COD-LIVER OIL. CAMPBELL .... Brit, and For. Med.-Chir. Rev., 1856, xvii. 21. NAUMANN .... A. Hk., 1865, 536. BERTHE L'Union M6d., 1856, x. BUCHHEIM . . . . A. E. P. P., iii. GAD A. A. P., 1878. HARE B. M. S. J., cxvi. 279. RANDOLPH and ROUSSEL . P. M. T., xiv. 239. BOUILLOT .... Compt.-Rend. Acad. Sci., 1892, cxv. CALCIUM CHOSSAT ROLOFF HAUBNER . . . . VOIT HEGAR BOKER PERL RIESELL . 9. TEISSIER DUSART PlORRY . 12. BODDAERT . . PHOSPHATE. C. R. A. S., xiv. V. A. P. A., xlvi. 302. S. Jb., cli. 138. Z. Bi., xvi. 198. S. Jb., cli. S. Jb., cli. V. A. P. A., lxxiv54. Hoppe - Seyler's Med.- Chem. Untersuch., 318. Le Mouvement M6d., Sept. 1875- A. G. M., 6 s., xv. Journ. de Chim. Med., 1863, ix. A. Pharm., 1895, ii. COLCHICUM. ALBERS D. Kl., 1856, xxxvi. ROSSBACH .... Pharmak. Untersuch., ii. FERRER U. M. M., i. PASCHKIS . . . S. Jb., cci. 232. ALTERATIVES. 555 REFERENCES. Continued. 5. BIRD Urinary Deposits, Phila., 1859, 354- 6. HAMMOND .... Proc. Acad. Nat. Sci., Phila., Dec., 1858. 7. LEWINS Edinburgh Med. Surg. Journ., 1841, Ivi. 200. 8. MACLAGAN . . . Edinburgh Journ. Med. Sci., 3 s., xiv. 24. 9. GARROD M. C. Tr., 1858, xli. 348. 10. PATTON B. M. J., 1886, i. 11. SCHULZ Wien. Med. Presse, 1897, xxxviii. 31. 12. WOOD U. S. Dispensatory*, I3th ed., 1504. 13. TAYLOR Med. Jurisprud., 2d ed., i. 14. KRAHMER .... Journ. f. Pharmakod., ii. -15- B. K. W., 1877, 107. SARSAPARILLA. BOCKER ..... Journ. f. Pharmak., ii. 23. JAMBUL. Th. M., 1893. CHRISTY ..... P. J. and Tr., 1888. BINZ ....... Verhandl. Cong. f. innere Med., Weisbaden, 1886. GELATIN. DASTRE and FLORESCO . C. R. S. B., 1896, ii. 668 ; iii. 243. CAMUS and GLEY . C. R. S. B., 1898, v. 1041. LANCEREAUX and PAULESCO . B. A. M., 1898, 578. WOOD, JR ..... Am. Med., 1902, iii. 729. FREUDWEILER . . Cb. I. M., July 7, 1900. SCHWABB .... Th. M., 1900, xiv. 312. HAHN ...... M. M. W., 1900, 1459. ZIBELL ..... M. M. W., 1901, 1646. KEHR ...... M. M. W., 1900, 181. LEMOINE .... Th. M., 1900, 284. MANICOTIDE and CHRISTODULO . K. T. W., 1899, vi. 696. BERTiMoand BESDETNOFF . Merck's Report, 1900, 105. LANCEREAUX . . B. A. M., 1898, 353. Ther. Geg., 1900, ii. 397. ROCCHI ..... M. M. W., 1900, 1613. MOLL ...... W. K. R., 1904, xviii. 580. THYROID BODY. BAUMANN . . . . Z. P. C., 1895, xxi. GOTTLIEB . . . . D. M. W., 1896, xxii. WORMSER . . . . A. G. P., Ixvii. 505. Roos ...... M. M. W., 1896, xliii. LEVY ...... D. M. W., 1896. HILDEBRANDT . . B. K. W., 1896, xxxiii. BAUMANV and GOLDMANN . M. M. W., 1896. FRANKEL .... Aertzl. Central. Anzeiger, 1895- HUTCHINSON . . B. M. J., 1896, i. BALLET and ENRIQUEZ . Med. Mod., 1895, vi. HERTOGHE . . . B. A. R. B., 1896. VAMOSSY and VAS . M. M. W., 1897, xliv. HASKOVEC . . . W. M. B., 1895, xviii. ; A. I. P. T., 1901, viii. 167. OLIVER and SCHAFER . J. P., 1895. OTT ....... Med. Bull., 1898, xx. 89. BELL ...... Phys. and Surg., 1898, xx. 39- PERRY ...... N. Y. M. R., 1896. 18. MOSKLY M. News, 1898, Ixxii. 353. 19. SCHOLZ Centralbl. f. innere Med., 1895, 104. 20. RICHTER .... Centralbl. f. innere Med., 1896, 65. 21. MAYER D. M. W., 1896, xxii. 22. Roos Z. P. C., 1896, xxi. 23. GLUZINSKI and LIMBERGER . Centralbl. f. in- nere Med., 1897, xviii. 4. 24. DAVID Zeitsch. f. Heilk., 1896, xvii. 439. 25. SCHONDORFF . . A. G. P., 1896, Ixiii. 423. 26. IRSAI, VAS, and GARA . D. M. W., 1896, xxii. 27. MAGNUS-LEVY. . S. Jb.,ccliii. 19; D. M.W., 1896, xxii. 28. SCHONDORFF . . A. G. P., 1897, Ixvii. 395. 29. BETTMANN . . . B. K. W., 1897, xxxiv. 30. JAMES B. M. J., Aug. 4, 1894. 31. POYES B. K. W., 1900, xxxvii.300. 32. BERGMANN . . . S. Jb., 1897, ccliii. 18. 33. GOULD B. M. J., 1898, ii. 34. DOBROWSKY . . . Ann. d. Kinderheilk., 1896, xxi. 35. DIABALLA and ILLYES . A. E. P. P., 1897, xxxix. 273. 36. LEPINE Lyon M., 1896, Ixxxii. 37. MURRAY Annals of Surgery, 1900, xxxi. 696. SUPRARENAL CAPSULES. 1. OLIVER and SCHAFER . J. P., 1895, xviii. 2. SZVMONOWICZ and CYBULSKI . Cb. P., ix. 3. LANGLOIS . . . . C. R. S. B., 1896, 10 s., iii. 4. ABEL Johns Hopkins Hosp. Bull., July, 1897. 5. ABEL A. J. P., 1899, ii.. No. 3; Bericht. d. Deutsch. Chem. Gesellsch., 1903, xxxvi, 1839. Journ. Biol. Chem. 1905 i. 6. DREYER A. J. P., 1899, ii. 203. 7. PETTIT C. R. S. B., 1896, 10 s., iii. 322. 8. CORONA and MORONI . Rif. M., 1898, xiv. 433. 9. BOINET C. R. S. B., 1896, 10 s., iii. 364- 10. ABELOUS . . . . C. R. S. B., 1895, 10 s., ii. 11. LANGLOIS and CHARRIN . C. R. S. B., 1896, 10 s., iii. 14. 12. CAUSSADE . . . . C. R. S. B., 1896, iii. 67. 13. OTT and HARRIS . T. G., 1903, xxvii. 378. 14. LANGLOIS . . . . A. de P., 1898, x. 124. 15. CARNOT and JOSERAND . C. R. S. B., 1902, liv. 1472. 16. VINCENT . . . . J. P., 1892, xxii. in. 17. ABEL Z. P. C., 1899, xxviii. 318. 18. ABBOTT J. M. R., 1903, iv. 329. 19. CROFTAN .... Am. Med., 1902, iii. 113. 20. HURTER and RICHARDS . M. News, 1902, Ixxx. 201. 21. PATON . . . . J. P., xxix. 286. 22. CYOS A. G. P., 1899, Ixxiv. 97. 23. GEARHEART . . . A. E. P. P., 1900, xliv. 161. 24. MELTZER .... Am. Med., 1903, v. 216. 25. JOSUE C. R. S. B., 1903, Iv. 30. 26. GOTTLIEB . . . . A. E. P. P., 1899, xliii. 27. KONIGSTEIN . . . Wien. Med. Presse, 1897, xxxviii. 857. 28. DE SCHWEINITZ . T. G., 1902. xxvi. 433- 556 GENERAL REMEDIES. 29. KYLE T. G., 1902. xxvi. 438. 30. CARNOT and JOSERAND . C. R. S. B.. 1903, liv. 1346. 31. FLOERSHEIM . . M. News, 1902, Ixxx. 17. 32. SCHAFER . . . . B. M. J., 1901, i. 1009. 33. EHRMANN .... A. E. I'., P., 1905, liii. 97. 34. KCI.BS A. E. P. P., 1905, liii. 140. 35- ERB A. E. P. P., liii. 173. 36. PATON J. P., 1904, xxxi. 92. 37. DRUMMOND . . . J. P., xxxi. 89. PITUITARY BODY. 1. OLIVER and SCHAFER . J. P., 1895, xviii. 2. CYON A. G. P., 1898, Ixxiii. 3. HOWELL J. Ex. M., 1898. 4. SCHIFF 2. K. M., 1897, xxxii., Suppl., 284. 5. MAIRET and Bosc . A. de P., 1896, 100. SPLEEN, i. CLARK Ed. M. J.. 1898, iii. 152. THYMUS GLAND, i. MACKENZIE . . . A. J. M. S., 1897, cxiii. ANTITOXINS. 1. VON RUCK .... Journal of Tuberculosis, 1903, v. 165. 2. MUSSER U. M. M., March, 1900. 3. GOODRICH .... Annals of Surgery, Dec. 1897. REFERENCES. Continued. TSUZUKI A. I. P. T., 1901, viii. 19. 5. BEHRING . . . . D. M. W., 1900, xxvi. 29. 6. LOEB Ann. Otol. Rhin. Laryng., June, 1905. SNAKE-POISON. 1. PHISALIX and EERTRAND . C. R. A. S., 1894. cxviii. 356 ; 1895, cxxi, 754- 2. CALMETTE . . . C. R. S. B., 1894, 10 s., i. in ; Ann. de 1'Inst. Pas- teur, 1895, ix. 225. 3. MITCHELL and REICHERT . Publications of the Smithsonian Institute, 1886. 4. MCFARLAND . . . J. A. M. A., Dec. 14, 1901. 5. NOGUCHI . . . . U. P. M. B., 1904, xvii. 154. 6. FRASER B. M. J., 1896, i. 957. LECITHIN. 1. WOOD, JR U. P. M. B., 1902. 2. DANILEWSKY . . C. R. S. B., 1897, iv. ; C. R. A. S., 1896, cxxiii. ; A. G. P., 1895, Ixi. 3. SERONO A. I. B., 1897, xxvii. 4. CLAUDE and ZAKY . R. T., 1901, Ixviii. 5. GILBERT and FOURNIER . C. R. S. B., 1901, liii. 6. LANCEREAUX and PAULESCO . B. A. M., 1901, xlv. FAMILY IV. ANTIPERIODICS. CINCHONA. U.S. THE U. S. Pharmacopoeia formerly recognized three varieties of Cinchona, namely, Cinchona Flava or Yellow Cinchona, Cinchona Pal- lida or Pale Cinchona, and Cinchona Rubra or Red Cinchona. At present, under the general heading of Cinchona, it recognizes the bark of all species of the genus yielding when assayed by the official process not less than five per cent, of the alkaloids and two and five-tenths per cent, of quinine. The genus Cinchona contains numerous species, yielding quinine and its congeneric alkaloids, indigenous to the western and northern portions of South America, where they grow upon the slopes of the Andes, at an altitude of from five to ten thousand feet. Formerly the only cinchona known to commerce was collected by the cascarilleros, or woodmen, and exported in large bundles or bales, usually covered by raw hide (jseroons). The natural commerce, however, in the quinine barks has almost disappeared under the conjoint influence of excessive production by cultivation and reckless destruction of the original for- ests. At present the world's market is supplied with the cinchona barks chiefly from plantations in the Himalaya Mountains, in Ceylon, and in Java. For a full account of this most important industry the reader is referred to the very able article by H. H. Rusby in the United States Dispensatory. CHEMICAL CONSTITUTION. Besides tannic, kinic, and kinovic acids, and other important substances, the cinchona barks contain quinine and quinidine, cinchonine and cinchonidine. Out of these alkaloids quinicine and cinchonicine are readily formed artificially, but, so far as is known, they do not exist in nature. There are therefore two isomeric alkaloidal groups : quinine, quinidine, quinicine ; cinchonine, cinchonidine, cinchonicine.* The official preparations of Cinchona are the fluid extract (FLUID- EXTRACTUM CINCHONA, U. S. ), dose, thirty minims (2 C.c. ), and the compound tincture (TINCTURA CINCHONA COMPOSITA, U. S. ), Hux- Aant's tincture, dose, one to three fluidrachms (4-7 C.c.). * Out of the quinine alkaloidal groups have been formed by chemists various isomeric alkaloids. For physiological study of these, see Archiv Physiol. Norm, et Path., 1893, v - 557 558 GENERAL REMEDIES. QUININA QUININE. U. S. This alkaloid was first distinctly separated from the other ingredi- ents of f he bark by Pelletier and Caventou in 1820. When quinine is precipitated by an alkali from a solution of its salt, it usually falls as a hydrate, which may be crystalline. By sufficient heat the hydrate is melted and the water is driven off. On cooling, the alkaloid, now free from water, forms a white, opaque, crystalline mass. The neutral, official quinine sulphate ( QUININE SULPHAS, U. S. ) oc- curs in light silky crystals, soluble in seven hundred and forty parts of cold or in thirty of boiling water, readily soluble in alcohol, very freely so in acidulated solutions, nearly insoluble in ether. Therefore, when it is administered either by the subcellular tissue or by the rectum the alkaloid should be given in the form of the bisulphate and in distinctly acidulated water. The authority mentioned found that one thousand parts of blood which was defibrinated and deprived of its gases at a temperature of 36 C. dissolved in an hour only 0.398 part of pure quinine. Water saturated with carbonic acid gas dis- solves the quinine sulphate pretty freely ; and Kerner also experimentally deter- mined that when a neutral solution of a salt of quinine is added to a very dilute so- lution of sodium carbonate no precipitate occurs. It would appear, then, that the quinine is held in solution in the blood by reason of the loosely combined car- bonic acid gas in that fluid. PHYSIOLOGICAL ACTION. Local Action. Quinine is distinctly irri- tant to the mucous membranes, but has little or no influence upon the sound skin. As stated as long ago as 1765 by Pringle, the cinchona bark itself is distinctly antiseptic.* More recent researches have demon- strated that quinine is actively germicidal, and that in the proportion of one part to three hundred it will preserve for a long time flesh, meal, milk, butter, urine, albumin, etc., and will check very markedly the alcoholic fermentation in honey or in syrup. According to the experiments of Binz, the larger infusoria, such as Paramecia and Colpoda, are killed by a solution of quinine of the strength of i in 800 immedi- ately, of i in 1000 after some minutes, of i in 20,000 after some hours. Upon the ordinary mould Penicillium, upon Vibrios and Bacteria, as well as upon the higher infusoria, quinine acts with a similar fatality. In the case of the Vibrios and Bacteria a decidedly stronger solution than the one mentioned is required to quiet movement. Bochefontaine found that a solution of one per cent, was needed for a vigorous rapid action, and that some active granules could even be found in it after three days. The fact that fungi will appear after a time in an ordinary solution of quinine sulphate demonstrates that at least upon some of the lower organ- * Mayer, Pavisi, Hallier (Das Cholera-Contagium, Leipsic, 1867), Herbst, Polli, and especially Binz ( Virchow's Archiv, 1869, xlvi. 68; and Untersuchungen uber das Wesen der Chininwirkung , 20). ANTIPERIODICS. 559 isms it has some, but comparatively little, influence, although on others it acts with much power. Absorption and Elimination. Owing to its insolubility in simple water or alkaline solutions, quinine can enter the body with rapidity only under circumstances in which it is exposed to the solvent power of acids. Taken into the stomach, the quinine salt is dissolved by the acid gas- tric juice ; but if it be not absorbed at once, passing into the intestines it is liable to be precipitated by the alkaline juices and the bile .acids. That a considerable portion of ingested quinine can be recovered from the faeces has been proven by Kerner 1 and other chemists. It is probable, however, that some of this fecal quinine has been absorbed and subsequently cast out by the liver as a very insoluble biliary salt, since Albertoni and Ciotto ** found that when they injected quinine into the jugular vein it failed to appear in the bile, although when given by the mouth it was freely eliminated with that secretion. Quinine is eliminated chiefly through the kidneys,* escaping in large part unchanged, but probably in part undergoing alteration, f According to Briquet, 1 quinine may generally be found in the urine half an hour after the administration of a large dose. Its removal, according to the researches of Binz, goes on slowly, for it is stated that in six experiments only a little more than two-thirds of the ingested quantity was excreted in the first forty-eight hours. Further, De Renzi, 3 Yvon, and Dietl 4 have found it in the urine six r seven days after the ingestion of the last dose. It is probable that some of the quinine is elimi- nated through other channels than the kidneys, since Binz had found it in the saliva of a poisoned dog, and Landerer 5 states that he has detected it in the urine, sweat, tears, milk of nursing women, and in the serum of dropsical effusions, while Al- bertoni and De Renzi found it abundant in the bile when it had been taken by the mouth, but not when it had been given hypodermically. Merkel 97 discovered that in the dog from eighty-six to eighty-eight per cent, of the quinine escaped unchanged from the kidneys, the remainder being converted into new substances. F. K. Kleine 98 determined that 29 per cent, escaped through the urine in twenty-four hours, the elimination being at its height in about six hours after the taking of the drug. As the blood is alkaline, a priori it would be expected that the qui- nine salt would be precipitated in the blood ; that this does not occur is, according to the researches of Kerner, due to the solvent power of the carbonic acid in normal blood. * See analyses of Landerer (Repertorium fur Pharmacie, 1836, xxv.), of Dietl ( Wiener Medizinische Wochenschrift, 1852), of Briquet, of Binz, and of De Renzi (Bull. Therap., xci. 45). t G. Kerner (Pfliiger's Archiv fur Physiologic, 1870) asserts that the quinine as ex- creted is in an amorphous, uncrystallizable form. He also has discovered in the urine of persons taking quinine a peculiar substance, sometimes amorphous, sometimes in acicular prismatic crystals, free from bitter taste, possessing the quinine inflorescence, which he believes to be a derivative formed in the body from the ingested alkaloid. He has not been able to get this substance in such quantity as to analyze it or further examine it, but has produced a principle (dihydroxyl-quinine) which he believes to be identical with it by acting on quinine with the potassium permanganate. An elaborate series of experiments have shown that the dihydroxyl-quinine is physiologically inert. This dihydroxyl-quinine must be produced in small amount, if at all, as there is abundant evidence that quinine is largely excreted as quinine (see Pharm. Journ. and Trans., ix. 1255. 5 6o GENERAL REMEDIES. The question as to the rate and completeness of the elimination of quinine is one of great practical importance. It is evident that it is both absorbed and eliminated more rapidly when it is given in solution or in the form of the acid salt than when taken in pill 6r capsule. Under favorable circumstances, with the dose not too large, it is probable that absorption is practically complete within two hours after the taking of the quinine into the stomach, so that the maximum effect of the single dose is probably reached in from one to two hours. Thau determined that from a third to somewhat less than half of the ingested quinine escapes from the body in the first six hours, and that in the first twelve hours about three-fourths are excreted. Welitschkowski 6 found an elim- ination of sixty-five per cent, the first day and twenty-five per cent, the second day. Prior gives the second day as the usual final limit of elimina- tion. We think it more than probable that after a few doses the alkaloid is practically eliminated in forty -eight hours, but that when it has been given continuously, or when kidney disease or great feebleness of circulation exists, the system may contain a notable amount of the quinine for a longer period. The researches of Welitschkowski are in accord with those of Jiirgensen and Thau in showing that in cardiac and renal disease and in low fevers elimination proceeds very slowly, more of the alkaloid being thrown off in the second than in the first six hours after its inges- tion. General Effects. The first symptoms of cinchonism, as produced by full therapeutic doses (ten grains) in man, are usually ringing in the ears, slight fulness in the head, and perhaps some deafness. With the use of larger doses these symptoms are intensified : the deafness is very marked, disturbed vision may exist, and the flushed face, with a sense of distention in the head, may point towards a cerebral congestion, which is in some cases relieved by spontaneous epistaxis. In decided cin- chonism, giddiness and staggering in walking are very common. After toxic doses, severe headache, delirium, stupor, complete deafness and blindness, dilated pupils, embarrassment of respiration, great weakness, convulsions, paralysis, and finally collapse may result, either comatose or delirious. Quinine deafness usually passes off rapidly, but may be permanent. In the lower animals large doses of quinine frequently cause violent epilepti- form convulsions. Given to dogs in sufficient quantity, it produces restlessness, followed by muscular tremblings, which have been compared to those of paralysis agitans, loss of power deepening into more or less complete paralysis, great dysp- noea, and cerebral symptoms, such as anaesthesia, blindness, stupor, or violent de- lirium, dilated pupils, coma, and convulsions. When the drug is introduced by the stomach, vomiting generally occurs, and at times diarrhoea also.* Death has been *See F. M. Melier (Mi-moires de V Acadi-nrie, 1843, xii. 722), William O. Baldwin (Amer. Journ. Med. Sci., April, 1847), and P. Briquet ( Traite therap. de Quinquina, Paris, 1855). ANTIPERIODICS. 561 shown by Heubach to be produced, at least in the lower animals, by a failure of the respiration.* A close physiological study of quinine can best be made by investi- gating its effects upon the different systems of organs seriatim, and this shall now be done. Cerebrum. According to the experiments of Briquet, a solution of quinine sulphate injected into the carotid will in some cases produce meningitis. In doing this, it is evident that the salt acts as an irri- tant to the membranes of the brain rather than as a nervous stimulant : indeed, experimental evidence proving that quinine is a cerebral stimu- lant seems to us to be wanting. The chief proof that the alkaloid does act as a nervous stimulant lies in the fact that persons who have been taking it regularly for some time will occasionally, upon the sudden with- drawal of their daily dose, manifestly be less active without than with it. Briquet may be right in his belief that in small doses it acts as a nervous stimulant, but the proof of his correctness at present is clinical rather than experimental. When given in toxic doses to the lower animals, probably all of the cinchona alkaloids produce epileptiform attacks. J. Jakoubowich 7 has noticed such effect with quinine in dogs, and it has been pro- duced with cinchonidine in various animals. Chirone and Curci found that in the pigeon this action of cinchonidine is prevented by ablation of the cerebral hemi- spheres, but Albertoni 8 objects with much force that these observers gave the pigeon the alkaloid too soon after the ablation, while it was still profoundly affected by the shock and hemorrhage of the operation. Albertoni found that, if the pigeon is allowed to recover, the cinchonidine is capable of causing convulsions ; also that in dogs with the motor zone of the cerebral cortex destroyed, the alkaloid causes epileptiform attacks, and that therapeutic doses do not increase the excitability of the cerebral cortex in the dog. The production of convulsions in the lower animals is of great inter- est in connection with the fact noted for quinine by Brown-Sequard and confirmed by Albertoni as regards cinchonidine, that in epileptics the attacks are rendered decidedly more frequent by the cinchona alkaloids. The present evidence indicates that this increase is not due to an influ- ence upon the cerebral cortex, but can hardly be considered sufficient to be conclusive. In very large doses quinine without doubt abolishes the functions of the cerebrum. Louis Dupuis 9 found that reflex action may be normal in poisoned dogs and rabbits, although there is complete loss of sensibility : if this be correct, the toxic dose of quinine must paralyze the perceptive centres in the cerebrum. * The present is perhaps as suitable a place as any to notice certain researches upon the relations of alkaloids to protoplasms. The relation between medicinal substances and the tissues upon which they act is certainly a very close one, and very probably is chem- ical in its nature. Rossbach (Pharm. Untersuch.,\. iii.) found that various alkaloids sensibly modify the properties of albumin, and believes that they form a chemical com- pound with it. Under the influence of the poison the albumin coagulates at a much lower temperature, and is deprived of its affinity for ozone. The alkaloids also precipi- tate the albumin from its ozonized solution. 36 562 GENERAL REMEDIES. Special Senses. The disorders of special senses caused by quinine are due to an action upon the peripheral sense organs ; an action which is probably directly exerted upon the nerve-structure involved, and is not a secondary result of changes in the circulation of the organ, although it is still believed by many authorities that the drug acts directly upon the aural and retinal circulation. In regard to the aural action of quinine, Roosa 11 affirms that large doses of quinine cause congestion of the blood-vessels of the middle ear, and in our own observation in persons suffering from unilateral chronic inflammation of the middle ear, small doses of quinine will produce tinnitus aurium of the diseased ear without affecting the sound ear. Again, the fact, long since pointed out by Kirchner, 10 that in the lower animals killed with quinine, very great congestion of the middle internal ear and the labyrinth, with bloody exudation and in some cases hemorrhage, are present after death, has been abundantly confirmed ; but Wittmaack, 9 * as the result of his experimental investigations, believes that these changes are not caused directly by the quinine, but are the result of the long drawn out suffocation which precedes death. Wittmaack further finds that the ganglionic cells of the cochlear ganglion are very distinctly altered by the poison, the anatomical changes being demonstrable four hours after the taking of the fatal dose. He was also able to detect alterations in the protoplasm in these cells, as the result of chronic poisoning with quinine. Analogy would indicate that as in the retina so also in the peripheral aural apparatus, the first effect of quinine upon the circulation is a spasm of the vessels, but at present there is no proof of this. The evidence still indicates (not demon- strates) that quinine does cause congestion of the peripheral nerve aural apparatus, but whether this is or is not preceded by a period of ischaemia, and whether it is primary or secondary to the action of the drug upon the nerve-endings them- selves, is undetermined. More or less complete amblyopia may be produced by quinine and end in permanent loss of sight.* In most of the numerous recorded cases the amount of quinine ingested has been very large, but we have seen in one individual twelve grains of quinine repeatedly produce temporary blindness. The disturbance of vision may come on abruptly or gradually. When fully developed it is usually accompanied by dilatation of the pupils, absence of the light reflex, and imperfect response to accommodative effort. There have also been noted nystagmus, divergent strabismus, anaesthesia of the conjunctiva, and increased ocular tension. When the blindness is not complete there is usually pronounced contraction of the field, or, in rare cases, scotomata. The disturbance of vision may subside with the specific action of the drug, but it may persist for days or months, or even permanently. The color-sense is probably first affected ; certainly it usually does not recover itself until after the return of central vision. The ophthalmoscopic ex- amination commonly, but not always, has revealed pallor of the optic disks, with excessive lessening in the size of the retinal vessels ; indeed, in some cases there has been complete obliteration of the vessels of the optic nerve. Graefe has, how- * According to Rogers (Journ. Amer. Med. Assoc., 1889), one or two hours after the ingestion of twenty grains of cinchonine sulphate there can usually be observed paresis of accommodation, which may increase until it becomes almost complete. It seems hardly possible that this phenomenon, if an habitual one, could have been overlooked by other observers. ANTIPERIODICS. 563 ever, noted quinine blindness with normal ophthalmoscopic appearances, whilst Dickinson describes congestion of the retina and choroid, and Gruening M and Mellinger 87 record hyperaemia of the disk. The pathogenesis of quinine amaurosis in dogs has been studied by Brunner, De Schweinitz, 88 Burabaschew, 89 De Bono, 90 Holden, 91 and Druault. 9 * The visual disturbances are due to a degeneration of the ganglion cells of the retina and the optic nerves, which, with the tracts, finally become completely atrophic. The primary lesion is in the nuclei of the cells, where it may be demonstrated ten hours after the injection of the drug. The breaking down of the least resisting elements of the inner retinal layers the ganglion cells and nerve-fibres is commonly believed to be caused partly by a lessened blood- supply due to spasm of the retinal vessels and partly by a direct action of the drug on the protoplasm of the cells. An ascending atrophy of the optic nerve follows. The spasm of the retinal vessels has been attributed to an action of the drug on the vaso-motor centres, which is unlikely, and to its influence on the vessel walls or on the peri vascular vaso-motor plexus. De Bono's theory, that paralysis of the neuro-epithelium of the retina causes the amaurosis, has not been confirmed.* Spinal Nerves and Centres. Schlockow was the first to notice a stage of increased reflex activity produced in the frog by quinine ; its existence was subsequently denied by A. Eulenburg, 12 but has been reaf- firmed by H. Heubach 13 and by David Cerna, 14 who agree in finding that it occurs only after very minute doses. In his investigations made in the laboratory of the University of Pennsylvania, Cerna found that this stage of excitement is probably caused by a stimulant influence upon the pe- ripheral sensory nerves, as it did not occur when the abdominal aorta was tied previous to the exhibition of the alkaloid. Two facts, first pointed out by T. A. Chaperon, 15 have been so abundantly substantiated that we must accept them as established. They are, that in small doses quinine causes in the frog a lessening of the reflex activity, which is removed by section of the medulla, and in large doses it produces a permanent palsy of reflex activity. The only explanation of the first lessening of reflex activity which is at present plausible is that it is due to stimulation of Setschenow's centre. Sedgwick 16 combats the theory just spoken of ; he believes that the inhibition of the reflexes is such as occurs when a sensitive nerve is galvanized, and is the result of a stimulation of the peripheral afferent cardiac pneumogastric nerve-end- ings by the quinine. He bases his theory chiefly on the fact which he has discov- ered, that atropine prevents the primary inhibition of reflexes by quinine. This is, however, readily explainable without the adoption of the theory of Sedgwick, and the results which he obtained after division of the pneumogastrics are scarcely in accord with his theory. The cause of the permanent influence upon reflex activity has not yet been accurately determined, but there is reason for supposing that pe- ripheral sensory nerve-endings are first paralyzed. * For discussion of the subject, with resume of the literature, see Toxic Amblyopias, George E. de Schweinitz, 1896, and Norris and Oliver's Diseases of the Eye, 1900, iv. 832 ; for case of blindness lasting twenty-one days, see Brit. Med. Journ., 1886, i. 823. 564 GENERAL REMEDIES. Chaperon and Wild found that the motor nerve-trunks are unaffected, but this does not prove that the spinal centres are paralyzed, especially as Wild's experi- ments seem to show that the nerve-endings in the muscles are attacked. (See below. ) A. Eulenburg asserts that voluntary movements persist after reflex actions, and that the quininized frog will turn into its normal position when laid upon its back, although ordinary reflex actions are completely abolished. This, if correct, certainly shows that it is either the sensory nerves or the receptive centres of the cord whose paralysis by quinine puts an end to ordinary reflex movements. So that, accepting the various results reached by experimenters, it is probable that in frogs quinine first excites and then paralyzes the peripheral sensitive nervous system. Muscles. According to the experiments of H. Robert, 17 very large doses of cinchonine, and probably therefore of quinine, lessen the excita- bility of the muscles. This is confirmed by the experiments of R. B. Wild, 18 who finds that solution of quinine i to 1000 brought in contact with the isolated muscles of the frog diminishes the irritability of the muscle and alters to some extent its relations with stimulation. The peripheral nerve-endings appear to be more sensitive than is the muscle, for when a solution of i to 4000 was employed, galvanization of the nerve failed to elicit a response, although the muscle contracted when the current was applied to it directly. Abdominal Organs. Upon the stomach and intestines quinine acts very much as does a simple bitter. In moderate doses it stimulates diges- tion and increases the appetite ; in large doses it not infrequently causes nausea and vomiting. When there is any morbid irritability of the mucous membrane of the stomach or bowels, its irritant action is often very marked, and its continued use in large doses has been known to cause gastritis. The statement of Piorry, 19 that a large dose of quinine would produce a distinct immediate lessening of the size of the spleen in cases of inter- mittent, appears not to be correct. Several observers * have stated that the exposed spleen of an animal can be seen to contract when quinine sulphate is injected into the stomach, veins, or cellular tissue ; but other investigators f have failed in their attempts to produce this asserted contraction. The experiment necessitates such abnormal exposure of the organ that only a very pronounced and very constant diminution could estab- lish the assertion that quinine produces contraction of the spleen, and our present knowledge indicates that the alkaloid has no immediate decided influence on the size of the organ. Organs of Circulation. Briquet, who first studied closely the action of quinine upon the circulation, found that in large doses it lowers the * Piorry (Archives Generates de Medecine , 1847), Pages (Gazelle Medicate, 1846), Kuchenmeister (Archiv fur Physiol. Heilkunde, x.), Mosler (Pathologic der Leukaemie, Berlin, 1872, 451), and Jerusalimsky ( Centralblatt f. Med. Wissen., 1876, 476). The latter observer believes the contraction to be caused chiefly by an action on the peripheral splenic nerves and muscles. t Magendie ( Gaz. Med., 1847), and especially L. T. Bochefontaine (Recherches experi mentelles a la Contractilitt de la Rate, Paris, 1873). ANTIPERIODICS. 565 arterial pressure in the lower animals. The experiments have been confirmed by various observers, notably by Schlock ow, 20 A. Eulenburg, and Cerna. It has been abundantly proved that the alkaloid thrown into the jugular vein, introduced into the coronary artery, or in any way brought in contact with the heart, lessens the force and frequency of the pulsations, and finally produces diastolic arrest ; also that this result is not influenced by separation of the mammalian heart from the nerve- centres, and occurs in the cut-out frog's heart. In man, very large doses of quinine (thirty to sixty grains) lower the force and frequency of the pulse ; a pulse-rate of 40 has been noted, and in reported cases of quinine-poisoning the pulse has been imperceptible at the wrist. Under the latter circumstances the pulse-rate may be increased, but the cardiac force is reduced to a minimum. The evidence is conclusive that both in man and in the lower animals quinine in sufficient amount is a powerful depressant to the heart-muscle or ganglia. * Schroff 21 found that in the quininized animal neither galvanization of a sensitive nerve nor asphyxia was able to produce vascular contraction and rise of blood-pressure, and Jerusalimsky 22 asserts that in frogs dila- tation of the vessels can be seen.f Further, Kobert, experimenting with the excised organs of the warm-blooded animals, and Wild, ex- perimenting with the tortoise, prepared according to the method of Ste- vens and Donaldson, have found that very weak solutions of quinine sulphate (i part to 5000) cause enormous dilatation of the vessels, with consequent increased rapidity of passage through them of liquid under pressure. It is probable, therefore, that the_/a// of the arterial pressure in poisoning by quinine is in part the result of an action upon the vessels. J Both Schroff and Jerusalimsky noticed that the fall of arterial pressure produced by quinine is preceded by a rise of the pressure, accompanied by an increase of the cardiac action. This observation has been con- firmed by G. S6e and Bochefontaine ; 2S but no observer seems to have shown that the rise of pressure is more than a temporary phenomenon. See and Bochefontaine affirm that the increased cardiac action continues some time after the pressure begins to fall. The primary rise of pressure may be the result of a stimulant action upon the vaso-motor centres, as Jerusalimsky found that it was not produced after division of the cord. It is not improbable that it is due to disturbances of respiration. Jerusa- limsky attributes the increase in the pulse-rate to paralysis of the in- * Pantellejeff (Centralbl.f. Med. Wissensch., 1880, xvii. 529) states that atropine will cause the heart arrested by quinine to recommence its action. t M. Chirone believes that by quinine the heart is arrested in active dilatation. The theory is very improbable. See Rivista Clinica di Bologna, abstracted in Journ. de Physiol. Norm, et Patholog., 1876, 844. Heubach, in a series of experiments on the influence of galvanization of a sensitive nerve upon the circulation after the exhibition of quinine, failed to detect any paralyzant action of the drug, although in some of his experiments the reflex activity was paralyzed. J When, in Wild's experiments, the action of quinine was maintained for a length of time, the dilatation was finally followed by contraction, which contraction was in all prob- ability the outcome of a post-mortem rigidity. 566 GENERAL REMEDIES. hibitory apparatus, a view which is supported by the assertion of Cerna that previous section of the pneumogastric prevents the quickening of the pulse-rate. We have never been able to perceive any depressant action upon the circulation in man after ordinary therapeutic doses (three to five grains) of quinine, and we believe that in tonic doses quinine produces no percep- tible sedation of the circulation, but that the largest antiperiodic doses have a distinct influence.* Blood. According to Bonorn and Arvedi, to Magendie, to Mon- neret, to Melier, and to Baldwin, in animals killed with quinine the blood is found to be dark, defibrinated, fluid, and incapable of forming a clot. Briquet, however, denies that this alteration of the blood is constant, or even common, in quinine-poisoning, as he found it in only four out of twenty-three dogs so sacrificed ; and he believes that it is merely an ac- cident dependent upon the method of death, a conclusion which has been confirmed by H. A. Hare. In a series of analyses Briquet found that the continued use of quinine augments the proportion of fibrin, but lowers that of the red corpuscles. In 1867 f Binz announced the fact that quinine added to human blood in the proportion of i part to 4000 immediately checks and in a short time arrests the amoeboid movements of the white blood-cells. Con- firmation of this has been furnished by Scharrenbroich, 24 by Kerner, 25 by Geltowsky, 26 and by Jerusalimsky. The minimum effective strength of the solution has been found to vary in different species of animals, and even in different individuals of the same species. It is a matter of great interest to determine whether quinine acts in the living organism as on the stage of the microscope ; and, to settle this point, Binz " has experimented according to the method of Cohnheim. He found that when the mesentery of curarized frogs to which quinine had been given was exposed upon the stage of the microscope, no accumulation of white blood-cells in the small ves- sels, or passage of them out into the tissues, occurred upon irritation ; or, if after a time these phenomena commenced, they were at once checked by a small hypo- dermic injection of the alkaloid. When the inflammatory process had already com- menced in a " Cohnheim frog," an injection of quinine would cause the out-wan- dering of the corpuscles to cease, and would bring about a gradual clearing of the white cells from the choked-up vessels. Binz further took two young cats and, after poisoning one of them with quinine, examined their blood. In the blood of the unpoisoned animal the white cells were far more abundant than in that of the poisoned cat. From these facts Binz deduced the conclusion that quinine acts de- structively in the system upon the white blood-corpuscles, in the same way as when they are out of the body. George R. Cutter 28 and H. A. Hare 29 have experimen- tally confirmed the effect of quinine in preventing the extrusion of white blood- * Some studies have been made upon the action of the drug on the capillaries of the brain, but the evidence is contradictory and insufficient. Consult Psychological and Medico-Legal Journal, 1875, 33; also Archives of Medicine, i. 33. f Archiv fur Microscop. Anatomie, 1867, iii. Consult also Experimented Unter- suchungen uber das Wesen der Chininzvirkung, Berlin, 1868 ; Virchow's Archiv, 1869, xlv. 137; Berlin. Klin. Wochenschrift, Nov. 1871. ANTIPERIODICS. 567 cells from the frog's mesentery, and A. Martin 30 has also found that the action of the drug is apparent in the centre of parenchymatous organs, such as the liver. The correctness of the original observation of Binz, that quinine checks the out-wandering of the white blood-corpuscles in the irritated mesentery of the Cohnheim frog, must be considered as established, but the question as to whether the failure of the blood-corpuscles to escape from the irritated vessels is due to the arrest of their amoeboid movements by the quinine is not so easily answered. Schwalbe * could detect no difference in the blood of a cat before and after poisoning by quinine ; and the experiments of Geltowsky upon frogs and guinea-pigs have yielded similar results : in all his animals after fatal poisoning by the alkaloid the movements of the white corpuscles were very active. In a series of experi- ments H. A. Hare found that the vessels in the cinchonized frog were much more contracted and had their walls much thicker than in a corresponding frog without quinine. This contraction of the vessels is thought by Hare to be the result of a direct action exerted by the drug upon the muscular coat of the arterioles. It is certain that the alkaloid reduces very markedly the force of the heart. The theory that quinine prevents the out-wandering of the blood-corpuscles by lessening the force which is driving the corpuscles and at the same time increasing the resistance of the capillary walls, seems to us, however, scarcely sufficient ; moreover, E. Maurel 9S has found that when the minimum fatal dose of quinine is given to the rabbit the leucocytes take on the rounded form which is characteristic of the early stage of the quinine action in drawn blood. The present evidence makes it probable that the toxic dose of quinine has a demonstrable action upon the white blood-corpuscles, but that therapeutic doses have no apparent influence. Upon the red blood-cor- puscles quinine exerts a distinct influence in inhibiting their functional activity. When blood is drawn from the body and allowed to stand, acid is developed in it (see Zunst, 52 ). Binz sl believes that this development of acid is due to oxidation, and by an elaborate series of experiments has determined that quinine (also berberine sulphate and sodium picrate in almost as great degree) inhibits these changes very greatly. These experiments are in accord with the previous ones of A. Schulte : ss the facts may, therefore, be considered proven. If ozonized oil of turpentine be dropped into an alcoholic solution of guaiac resin, no alteration of color occurs ; but if a drop of blood be added, the blue appears at once, i.e., the blood acts as a carrier of ozone from the turpentine to the resin. Binz has found that quinine, even in so small an amount as i part in 20,000, has a perceptible influence in preventing this. Similarly, when sodium car- bonate is thrown into a dilute watery solution of indigo sulphate until the reaction is decidedly alkaline, and a little blood, and subsequently ten drops of ozonized turpentine, are added, a green color begins at once to develop, and in a little while passes into the clear yellow of isatin. In this case also the blood acts as a carrier of ozone ; and Binz and his pupil, Ransone", 84 have determined that quinine also inhibits this action, one part of it added to a thousand of the mixture delaying the change of color for an hour. In these experiments Binz used a large number of different salts of quinine, and found that they acted identically. He further demon- * Quoted by Kerner (Pfliiger's Archiv, i. 203). 5 68 GENERAL REMEDIES. strated that the action of the alkaloid was on the red blood-corpuscles. He also found that in young cats to which he had given a very large but not fatal dose of quinine the freshly drawn blood affected the tincture of guaiac much less than it normally should. According to Maurer one per cent, of a quinine salt added to fresh blood rapidly destroys the red disks. There is no sufficient evidence to show that the action of quinine upon the blood has any close relation to its general action on the organism. It is not probable that the antipyritic influence of quinine is due to depression of the ozonizing power of the red disks, and so far as the white blood-corpuscles are concerned Binz has shown that quinine affects all animal germinal matter ; and it is probable that the protoplasm of the nervous system, being more specialized than that of the white corpuscles, is more susceptible to the influence of the alkaloid. Moreover, various drugs attack the white and the red corpuscles and do not otherwise act as does quinine. Binz states that both conine and camphor act more forcibly upon the white cor- puscles out of the body than does quinine, and T. Lauder Brunton and Theo. Cash M have found that morphine, veratrine, and codeine check the ozonizing power of the blood, while digitalin, picrotoxin, and caffeine increase it. Each of these principles has its own peculiar physiological action, differing from that of quinine and the other alkaloids. It seems absurd to attribute such diverse physiological actions to the one common property of the group, and we think that we must con- sider the antozonizing power of quinine as simply one of its functions, and not as the basis of its relations with the human organism. Uterus. In 1871 Monteverdi 36 announced that quinine is an active uterine stimulant, but in so doing brought forward nothing that was novel. As long ago as 1855 John S. Wilson " called attention to the uterine action of quinine, and in 1860 reasserted his belief, which in the meanwhile had been con- firmed by J. H. Rich; in 1858 Jos. J. West* 8 wrote: "Many regard the use of quinine as dangerous and even criminal in any disease in pregnant women. The belief of these persons is that this substance exercises a direct influence upon the uterus, causing powerful contractions and expulsion of the foetus. And to support this notion they are ready to bring forward innumerable instances of abortion after its use, of cases of sudden suppression relieved by a prompt use of the same remedy." He then goes on to say that these abortions, etc., were due to the in- termittent fever, and not to the drug. Surely this is enough to show that the oxy- tocic action of quinine was believed in many years ago by our Southern practitioners. The answer to the question, Has quinine ecbolic qualities ? should be made out in three different directions. First, Is there any evidence of quinine producing abortion in healthy women or in females of the lower animals ? Second, How strong is the evidence of its producing abortion in women suffering from ague ? Third, What is the evidence in regard to the action of quinine during labor ? In regard to the first of these sub-questions, the only affirmative evidence we have met with is in the experiments of Rancillia, 89 who saw abortion in two bitches ANTIPERIODICS. 569 follow the administration of from six to nine grains of quinine : as the pups in one case were already dead before the administration of the drug, it would seem that this investigation was not on such a scale as to be at all conclusive. Moreover, we have given quinine to two pregnant cats, in one case in sufficient quantity to cause death, without disturbing the products of conception. Furthermore, we have met with no evidence that quinine is capable of inducing abortion in healthy pregnant women. Sayre's 40 case is certainly no proof whatever that quinine will originate labor, as labor had commenced under the influence of the hot and cold douche and other measures employed before the quinine was given. Chiara, 41 of Milan, has fur- nished very strong evidence that quinine is incapable of originating uterine contrac- tions in healthy pregnant women. In his public service, two doses of a gramme (15.34 grains) each were given without effect daily for two successive days to eight women, all in the eighth month of pregnancy. It being necessary to cause abortion, one gramme was given daily to one woman for seven days, and to another for three days, without, in either instance, any effect, so that the labor had to be brought on in the usual manner. On the whole, we believe that the first question must be answered quinine is incapable of producing abortion during quiet pregnancy. In answer to the second sub-question, some evidence has already been adduced to indicate that abortion may be so caused, but it is opposed by much stronger facts. To evidence already quoted may be added the assertion of Walraven* 2 that he has frequently seen the exhibition of quinine followed by abortion, the record of two cases of such character by Burt, tt and no doubt the affirmations of others which we have not seen. Opposed to this, however, is the overwhelming fact that the great body of the profession have for centuries been giving quinine in one form or other to pregnant women indiscriminately, and if abortion had been produced it must have been noted long ago. Further, direct testimony is not wanting. Malaria often in- duces abortion, and Erwin, 44 James C. Harris, 16 and A. Russwurm ** testify from per- sonal experience that quinine will arrest abortion from such cause. J. A. Ashford, 47 Beauchamp,* Rooker,* J. S. May,* and A. d'Arcourd have given quinine to hun- dreds of pregnant women, suffering from malaria, in large doses without disturbing the uterus. Other testimony might be adduced ; but it is incredible, in the face of daily experience, that even the largest therapeutic doses of quinine are abortifacient in malarial fevers or in health. In regard to the third sub-question, f it seems to us proved that qui- nine in full doses (ten to twenty grains) is a stimulant to the uterine con- tractions during labor. The pains it produces so exactly simulate the natural ones as to indicate that they are not so much caused by a specific action of the drug as by its arousing the general nervous forces of the system. Be this as it may, most of the leading accoucheurs of Philadel- phia and of New York are accustomed to rely upon quinine in cases of uterine inertia from exhaustion. J * See American Practitioner, 1870. t For details of the evidence the reader is referred to the third edition. Consult also Practitioner, xvii., xviii., xix. J Certain experiments of Wild (Brit. Med. Journ., 1887, ii.) suggest that the quinine may act directly upon the muscle-fibres of the uterine walls. He found that when the 57 o GENERAL REMEDIES. Voluntary Muscles. C. G. Sauterson, 48 in a series of experiments upon both cold- and warm-blooded animals, has found that quinine acts directly upon the muscle-fibres, increasing the susceptibility and power of the muscle, but, especially in the cold-blooded animal, causing it to become fatigued more readily than normal. Nutrition. Ranke was the first to notice that quinine produces a great decrease in the elimination of uric acid, and thereby provoked many in- vestigators to the making of researches. Ranke was confirmed by H. V. Bosse 49 and by G. Kerner. The latter ob- server found that, when about nine grains of quinine were taken in divided doses during the course of the day, the urea was decreased not quite one-eighth, the uric acid to a little less than one-half, the kreatinine was slightly increased, and the nitrogenous material decreased about one-ninth. When a very large dose (thirty- eight grains) was taken in the morning, the urea and the kreatinine were each de- creased about one-fourth, as was also the collective nitrogenous material ; the phosphoric acid was lessened about one-fifth, and the uric acid about four-fifths. Zuntz (quoted by G. Strassburg 50 ) found that twenty-five grains of quinine reduced his elimination of urea nearly forty per cent. A. Schulte also found that 1.8 grammes of quinine depressed the elimination by the kidneys thirty-nine per cent ; yet in the experiments of Unruh 51 the action of the alkaloid in depressing urea elimination was not constant, and in the trials of H. Oppenheim 52 the excretion of urea was actually increased. Nevertheless, the experiments, upon the dog, of Rabuteau 83 and of Hermann von Boeck 54 bear strong evidence to the fact that quinine does decrease the elimination of urea. Considering all the evidence, and especially the rather recent very elaborate studies of Prior, K we are warranted in believing it established that quinine powerfully depresses the elimination of the nitrogenous excre- tory principles. That such decrease is due to diminished formation, and not to lessened elimination, seems proved by the fact that in Prior's experiments there was no increase of nitrogenous excretion beyond the normal following the omission of the quinine. It seems, therefore, to be established that quinine has a direct or indirect depressing influence upon the tissue-changes of the human organism. Contrary to what might have been expected, Strassburg, in an elab- orate series of experiments, found that quinine had no decided effect upon the elimination of carbonic acid either in healthy or in fevered rabbits. These observations of Strassburg are opposed by those of Bock and Bauer, 56 who found that in cats large doses of the alkaloid cause in the first stage of their action lessened carbonic acid production, but that when the convulsions appear the carbonic acid is increased as the result of the increased muscular activity. R. H. Chittenden 57 found that fatal doses of quinine given to fasting rabbits had no decided effect upon car- solution of quinine sulphate, i part to 1000, was brought in contact with the isolated oesophagus of the frog, the oesophagus first shortened, and afterwards lengthened be- yond its normal limit, the change probably being, as believed by Wild, due to stimulation first of the weak longitudinal muscular fibres, and later of the more internal stronger cir- cular fibres, as the quinine penetrated the coats. The muscle-fibres of the oesophagus are similar to those of the uterus. ANTIPERIODICS. 571 bonic acid production until just before death, when both the animal tem- perature and the excretion of carbonic acid fell distinctly. On the other hand, small doses of quinine seemed to cause a gradual falling off in the carbonic acid elimination. Although the evidence is somewhat contra- dictory, it indicates that any action of quinine upon carbonic acid elimi- nation must be very feeble and uncertain. THERAPEUTICS. At present our estimate of the value of quinine in disease, an'd our knowledge of its therapeutic use, rest solely upon clin- ical observation, although recent discoveries have enabled us to frame a very plausible explanation of the method by which it overcomes malarial disease. On account of its power of arresting or preventing putrefactive fer- mentation by killing the microscopic entities which produce such changes, Binz has recommended quinine in the so-called septic diseases. The chief evidence which he produces is in some ten experiments made upon dogs and rabbits. In each of these experiments two similar animals were poisoned with putrescent liquids, and to one of the pair quinine was freely administered. In two cases the cinchonized animal recovered, while its fellow perished ; in three ex- periments neither of the animals died ; and in the other five trials the cinchonized animal lived from two to twenty-four hours longer than the other. These experi- ments are certainly too few and indecisive to prove in any degree Binz's view. To us they indicate very strongly that quinine has no such influence over the dis- ease as he believes. If living germs in the blood were really the cause of the septic symptoms, and if quinine killed such germs, its action would be as manifest and as unmistakable as it is in intermittent fever. The results of Binz's experiments seem to us to agree with the em- phatic teachings of clinical experience that quinine has no direct specific influence in pycemic, septic, or exanthematous diseases. Before the introduction of modern antipyretics the question as to the power of quinine of lowering bodily temperature was extremely im- portant, but at present it is enough to know that as an antipyretic quinine is of very inferior power. Unless given in enormous toxic doses, quinine does not lower bodily tempera- ture in health. It is alleged, however, by G. Kerner and Jiirgensen that it will largely prevent the rise of the bodily temperature which normally occurs from ex- ercise, and it is asserted by various clinicians that it does not affect the tempera- ture in fever. C. Liebermeister 58 came to the conclusion that quinine given in doses of from twenty to forty-five grains in one hour is, in typhoid fever, a very active and certain antipyretic, a conclusion also reached by the Committee of the London Clinical Society. 59 Naunyn and Quincke 60 found that sometimes quinine prevented the develop- ment of fever after the division of the spinal cord in animals, but in other cases failed to do so. Binz 61 has achieved similar results : he says that if the conditions of the fever are too favorably constituted the effect of the quinine fails thoroughly. The drift of our present clinical evidence seems to indicate that qui- nine exerts in febrile disease a decided antipyretic action, which is espe- 572 GENERAL REMEDIES. cially manifested during those stages of disease in which the natural ten- dency is towards a lowering of temperature. In exanthematous diseases, etc. , after the use of the cold bath twenty grains of the alkaloid are often efficacious in delaying the return of the excessive fever. As a simple tonic, quinine is largely used, especially in combination with iron. We are not entirely convinced that it is of much more value in simple debility than is quassia or other simple bitters ; but if, as is prob- able, it be true that quinine lessens to a very great extent the elimination of nitrogen, i.e. , the consumption of tissue, the general practice is well founded. Hare, 62 as the result of observations made upon himself, be- lieves that quinine has a distinct action in increasing the formation of the red blood-corpuscles. If this be correct, it must have especial tonic value. When administered in very large doses, quinine, as has been already shown, acts as a powerful depressant, and as such it has been used by Briquet and other French physicians in rheumatism. As much as sixty or seventy grains a day have been given, and it is beyond dispute that under the influence of these heroic doses the symptoms of inflammatory rheumatism have often rapidly abated ; but the method has found little favor out of France, and is less efficient and more dangerous than other plans of treatment now in vogue. In inflammatory rheumatism, after the acute symptoms have abated, when the patient shows evident signs of weakness, especially if there be profuse sweating during sleep, fifteen grains of quinine daily are often of great service. Conceiving the theory that choreic movements may be due to weak- ness of the spinal inhibition, H. C. Wood some years ago injected quinine into the veins of choreic dogs, and found that the movements were at once arrested by comparatively small doses of the alkaloidal salts. This led him to make trial of the remedy in the chorea of childhood, and as the result of much experience it has been determined that the drug in some cases of this affection is of great value. There are certain cases in which enormous doses are borne without the production of cinchonism : thus, we have given in a month to a child ten years old one thousand grains of the quinine sulphate without causing tinnitus aurium or other disagreeable effect, but with the result of curing a chorea which had resisted all treatment for nearly two years. In our experience in the disease, when there is no tolerance of quinine no benefit is achieved by its admin- istration, but when the quinine is tolerated in large dose its use is com- monly most beneficial. Led by the results obtained in chorea, the chief of H. C. Wood's clinic at the University Hospital, Charles S. Potts, con- ceived the belief that incontinence of urine might in many cases be the result of failure of inhibition, and on trial found that very large doses of quinine often put an end to this most annoying symptom, a result which we can confirm from our own experience. The chief value of quinine is as an antiperiodic. There is at present no doubt that the alkaloid does good in all forms of malarial fever by directly affecting the malarial plasmodium or organism. ANTIPERIODICS. 573 Quinine in its relations to malarial fever may be considered, first, as a prophylactic; second, as a curative agent The value of the daily use of quinine to persons exposed to a malarial atmosphere has now been thoroughly tested in all portions of the world. In North and South America, in Europe, in Africa, and in India the pro- phylactic powers of quinine have been tried on the largest scale in connec- tion with the military and naval services, and the testimony is unanimous in favor of the drug. A single citation will serve to illustrate this fact. J. B. Hamilton M reports the case of a battery of one hundred and thirty-five men, quartered at Jubbulpore, East Indies, in the same barracks with an infantry regiment. Each of the artillerists received three grains of quinine every other day : to the infantry none was given. The result was that while three hundred out of the five hundred men of the regi- ment were sick at one time with malarial disease, at no period was more than four per cent, of the battery affected. The dose of quinine as a prophylactic may be considered as two grains in the morning and three in the evening. In intermittent fever, when there is sufficient time, it may be well to precede the quinine by a mercurial or other purge. If the expected par- oxysm be so near that there is not sufficient time for the action of the purgative, the antiperiodic should be administered without previous prep- aration of the patient. The value of purgatives in obstinate intermittents, as an adjuvant to quinine, is often overlooked, although in some cases the employment of purgatives, and of such diuretics as cream of tartar, seems to be almost essential for the successful use of the antiperiodic. \& penurious fever i or malignant malarial poisoning \ no time should be lost after the first paroxysm in getting the patient cinchonized, as it may be uncertain whether the attack be of the quotidian or of the tertian type. At least sixty grains of the alkaloidal salt should be administered during the first twenty-four hours ; in very severe types of the disease even larger doses than these are necessary, less than seventy-five grains of the drug sometimes being unable to suppress the disease. In remittent or bilious fever it may often be advisable to give purga- tives and febrifuges before the quinine. As soon as the remission has appeared, the exhibition of quinine should be begun. Local inflamma- tions or even severe cerebral symptoms occurring during a remittent fever are no centra-indications to the use of the specific. When gastritis exists, other channels of entrance than the stomach should be employed, on account of the local irritant action of quinine. When the symptoms in remittent fever are severe and seemingly continuous, it may be not only proper but necessary for the saving of life to exhibit quinine freely during the period of fever. In large doses the alkaloid is probably antipyretic as well as antiperiodic, and we do not know of any theoretic or clinical objection to its use during the period of fever. 574 GENERAL REMEDIES. In malarial intermittent neuralgia, as in all other forms of abnormal manifestations of malarial disease, quinine is efficient, although it is usually necessary to administer it in large doses (thirty to forty grains at intervals). In neuralgia which, although not dependent upon malaria, assumes the intermittent type, quinine will often temporarily set aside the par- oxysmal attacks, and sometimes effect a cure. The same fact may be stated in broad terms as true of all non-malarial intermittent affections. In the great majority of such cases, unfortunately, the action of the quinine is only temporary, and any controlling power is soon lost. Ordinarily the best method of treating a case of intermittent fever is to give the patient a full mercurial purge, and after it has acted, to begin the exhibition of the drug about eight hours before the expected par- oxysm, in doses of five grains every two hours until from fifteen to twenty grains are taken ; care being exercised to see the quinine is in such form as to secure prompt absorption. In cases of persistent or chronic intermittent fever, quinine is often administered in moderate doses day after day, but we are convinced that it is better to use the remedy in large doses at intervals than to administer it continuously in smaller amounts. In this climate fifteen grains of quinine a day will usually put an end to a mild intermittent, but the paroxysm will be very apt to recur, even if six grains of the alkaloid be afterwards given daily for some weeks. We believe it is better to administer from twenty to twenty-five grains in the beginning, sufficient to produce very pronounced cinchonism and to arrest the disease at once. The full physiological effect of the drug should then be maintained for two or three days, and no more quinine given except at certain intervals. The paroxysms have un- doubtedly a great tendency to return on the seventh day after their arrest, and every seventh day for some weeks full cinchonism should be produced. If the observation of Councilman, that large doses of quinine entirely destroy the malarial organism, be correct, the practice just spoken of has a foundation in scientific as well as in empiric observation. The general clinical experience, that it is best to administer quinine so that the last dose will be given about two hours before the development of the paroxysm, is confirmed by the various experiments which have been made upon the relation of quinine to the malarial paroxysm. (See Golgi. 95 ) Monaco and Panichi 96 believe, as proven by their experiments, that the results obtained are not due to the quinine acting more powerfully upon the young forms of the parasite liberated by the processes of segmentation just before the febrile outbreak, but are due to the facts that quinine remains in the blood during the fever, and that the old parasites present during the febrile stage are more susceptible to the action of the quinine than are the younger forms, even though the latter be not protected by the red blood-disks. Local Use of Quinine. The effect of quinine upon the lower organ- isms has suggested its local use in various disorders supposed to depend upon the presence of such entities. Thus, Henke, 64 finding some pecu- ANTIPERIODICS. 575 liar motile cells in the sputa of whooping-cough, employed inhalations of quinine with asserted good results. Henke was not, however, the first to suggest either this fungoid pathology of whooping-cough or the use of quinine. Binz 65 in 1870 asserted that quinine had a specific action in whooping-cough, provided it was given in large doses in solution, so as to come in contact with the mucous membrane in its passage through the pharynx; and in 1871 Letzerich 66 announced that whooping-cough was due to a fungus in the lung. Dawson 6I has confirmed the value of the method of Binz ; but, if the fungoid theory be as we do not believe true, the plan of Henke must certainly be the better one. The use in hay-fever, as recommended by Helmholtz, of a weak tepid solution (one to three grains to one fluidounce), as nearly neutral as possible, freely applied to the nasal mucous membrane, has not achieved general recog- nition, and any influence which the alkaloid has in either whooping-cough or hay-fever probably depends on its direct influence upon the mucous membranes. In the later stages of gonorrhoea the topical employment of its solution (five to ten grains to one fluidounce) may be serviceable.* Hypodermic Use. Owing to its local irritative action, and the in- solubility of its ordinary salts, quinine does not lend itself well to hypo- dermic medication. Great local disturbances, abscesses, ulcers, and even tetanus, 69 have followed the injection of the sulphate under the skin. Many of these manifestations, however, were undoubtedly due to lack of proper asepsis. Further, in severe pernicious malarial affections, promptness of action is of the greatest importance, and many of the German practitioners believe that, hypodermically given, quinine acts much more favorably as an antipyretic than when given by the mouth. Qidnine sulphate may be used hypodermically dissolved in a solu- tion of tartaric acid. Quinine bisulphate (QuiNiN^E BISULPHAS, U. S. ) is soluble in ten parts of water, and is preferable to the ordinary sulphate. One gramme (15 grains) of Quinine hydrochlorate (QuiNiN^E HYDRO- CHLORIDUM, U. S. ) maybe dissolved in i c.c. of boiling water, and does not precipitate until the temperature reaches 100 F. For hypodermic injection it is better to dissolve the quinine salt, I gramme in 2 c.c. of water, and give in two injections of i c.c. each if ten grains are required. According to Gagglio, confirmed by Aufrecht, 99 urethan increases the sol- ubility of quinine so that the following formula is permanent at ordinary room temperature: Quinine hydrochlorate, 0.5; urethan, 0.25; distilled water, add 5 c.c. Quinine hydrobromate (QuiNiN^E HYDROBROMIDUM, U. S. ) is soluble in ten per cent, of water containing twenty-five per cent, of alcohol, and its solution has been used to a considerable extent hypo- dermically. QUININE SALICYLAS. U. S. Quinine salicylate is often very * Walerian Sokolow affirms that the local application of quinine to wounds has a very remarkable effect upon the granulation tissue, a similar effect being produced by the ad- ministration of the drug by the mouth. (For details, see Inaug. Dissert., 1891, abstracted in Schmidt's Jahrb., 1802.) 57 6 GENERAL REMEDIES. effective in subacute muscular and neuritic rheumatism, or in the sub- siding stages of acute rheumatism. It may be given in doses of five grains (o. 3 Gm. ) three or four times daily. ADMINISTRATION. Ordinarily quinine is used in the form of the sulphate. The powder should be given in capsules, the pill, and espe- cially the sugar-coated pill, being prone to become hard and uncertain in its solubility and action. If immediate action is required the solution may be used, the solubility of the salt being guaranteed by the addition of one drop of dilute sulphuric acid to every grain of the salt. The quinine hydrochlorate is as efficacious as the sulphate, and more soluble. Contra-indications. On account of its irritant properties, quinine must be used with caution when there is irritability or inflammation of any part of the gastro-intestinal tract. It is strongly contra-indicated by inflam- mation of the middle ear, and may greatly and permanently increase dulness of hearing. The statement of M. Friedmann 70 that ergotin, and that of W. B. Dewees n that chloral greatly lessens the tinnitus aurium produced by quinine and salicylic acid need confirmation. Irritability of the bladder or other portion of the genito-urinary tract centra-indicates the use of quinine : hence it is often badly borne by old men. It is even asserted that it will in some persons cause hsematuria.* TOXICOLOGY. The general symptoms produced by toxic doses of quinine have been sufficiently discussed. Owing to personal peculiarities or idiosyncrasies, quinine sometimes causes manifestations entirely unlike those ordinarily seen. Thus, in a case reported by A. Erlenmeyer," the symptoms simulated those of strychnine-poisoning, f In some persons a few grains of quinine given internally produce wide-spread erythema and subdermal cedema, affecting it may be the whole body, but usually most pronounced in the face, and accompanied by pronounced disturbances of the nervous system and circulation, the symptoms usually subsiding in from a few hours to a few days, and sometimes being followed by desqua- mation of the cuticle. * In certain regions of country persons suffering from malarial poisons have inter- mittent attacks of haematuria, or probably, to speak more correctly, of methaemoglo- binuria, in which the haematuria has been attributed by many practitioners to the influence of the quinine sulphate. The facts, however, that quinine never produces methaemo- globinuria in healthy individuals, that the attacks are accompanied by chill, fever, and sweat, following, according to Carreau, absolutely-the course of the paroxysm of inter- mittent fever, and that, though quinine is used everywhere, the methaemoglobinuria occurs only in certain localities, certainly seem to prove that the attacks are really due to a peculiar form of malaria and not to the quinine. The most elaborate account we have met with is that published in Guadeloupe, in 1891, by J. Carreau (La Mlthlmoglobinurie Quinique, 1891 ; see also Bull. Soc. de Mid. Pratique de Paris, 1891 ; Arch, de Mid. Navale, 1896, Ixv., 1897, Ixvii. ; Bull. Therap., xcvii.) ; Pispiris (Le Progres Mid., 1891, xix.) affirms that in some cases of malarial fever not only the internal administration but also external friction of the quinine sulphate will provoke serious gastro-intestinal hemorrhage. It does not, however, appear probable that the quinine in his cases was the cause of the bleeding. t For cases, see Brit. Med. Journ., 1869, ii. ; Berlin. Klin. Woch., 1877, 294 ; Phila. Med. Times, x. 166 ; N. Y. Med. Record, xxi. 627. ANTIPERIODICS. 577 The importance of these idiosyncrasies was shown in a case in our own prac- tice, in which two grains given by the mouth produced a furious general urticaria, with great subdermal swelling and cardiac depression of the most alarming charac- ter ; according to B. D. Titlow, violent general erythema involving the lymphatics was produced by one-third of a grain of quinine. Miccich6 74 reports the death of an adult caused by the hypodermic injection of seven and seven-tenths grains (one- half gramme), the symptoms being great paleness of the surface, small, frequent pulse, high fever, severe nervous depression, increasing stupor with delirium, great dyspnoea, jaundice, haematuria, and anuria. Death occurred on the seventh day. Both during life and at the autopsy the evidences of great destruction of red blood- corpuscles were apparent. Purpura has also been ascribed to the alkaloid. 75 Cheval- lier T6 describes a peculiar affection of the skin, etc., as occurring among workers in the bark. Fatal instances of poisoning by quinine are rare in literature, but Husemann " has made a collection of cases in which death has been attrib- uted to the alkaloid, not always, in our opinion, with correctness. The minimum fatal dose is not known, but must be very large. Clapton 78 details a case in which a soldier took at one dose an ounce of the sulphate, stirred up in some water, without the induction of any more serious symp- tom than a mild stupor ; a similar case is mentioned by Lente, on the authority of Woodhull ; and a third is recorded by Taussig. 79 R. G. Wharton 80 records a case in which during thirty-six hours a half-ounce was taken without vomiting and with- out ill effect. We cannot help suspecting that in all of these cases much of the drug passed through the intestines without absorption. In the famous case of Bazire, five ounces taken in the course of ten days caused death. Quinine tannate* although not official, has been used to some extent, and is not altogether inefficient. It has the great advantage of not being disagreeable to the palate, but is less active and less certain than the more soluble salts of the alkaloid, and is also much slower in its operation. If given at all, it should be in doses one-third greater than those of the sulphate. QUINIDINJE SULPHAS. Quinidine sulphate occurs in long, shin- ing, silky, acicular crystals, soluble in one hundred parts of water at 59 F. It probably closely resembles quinine in its physiological and therapeutic properties, and is a moderately efficient antiperiodic ; the dose is about one-third larger than that of quinine. CINCHONINjE SULPHAS CINCHONINJE SULPHATE. U. S. The pure alkaloid cinchonine crystallizes in prisms and needles. The official cinchonine sulphate is in short oblique prisms of a very bitter taste, soluble, at 59 F. , in sixty-six parts of water, more freely in boiling water, readily soluble in alcohol. * For an elaborate discussion of the therapeutic value of this salt see Bulletin de f Academic, Paris, 1872. 37 578 GENERAL REMEDIES. PHYSIOLOGICAL ACTION. Conzen (quoted by Husemann) has found that the action of cinchonine on infusoria and on fermentation is simi- lar to but weaker than that of quinine, and that on the movements of the white blood-corpuscles its influence seems transient. It is stated that it is eliminated unchanged and rapidly, the great bulk of it being thrown off in the first twenty-four hours. According to the experiments of Laborde 81 and Bochefontaine, 82 toxic doses cause in the lower animals more violent epileptiform convulsions than do the corresponding doses of quinine. In Bochefontaine' s experiments the relative strength of cincho- nine to quinine was about 10 to 16, in Bernatzik's (on dogs only) as 4 to 5. De Schweinitz has found that cinchonine produces amaurosis in the dog, as does quinine. THERAPEUTICS. As an antiperiodic, cinchonine exerts a similar in- fluence to quinine, but is probably about one-third weaker than that alka- loid, and must be used in correspondingly larger dose. J. B. Hamilton affirms as the result of experiment that cinchonine as a prophylactic against malaria is even superior to quinine. As a tonic we have never been able to perceive that cinchonine acts differently from quinine. CINCHONIDIN^E SULPHAS. U. S. Cinchonidine sulphate occurs in white, silky, lustrous needles or prisms, odorless, of a very bitter taste, soluble in seventy parts of water, freely soluble in acidulated solutions. It polarizes to the left, and is not fluorescent. According to Se"e and Bochefontaine, 85 cinchonidine produces in the lower animals symptoms similar to those caused by quinine, except that the convulsions are less severe. A boy aged five years took one hundred and twenty-eight grains in solution during six hours without vomiting. There were then convul- sions followed by great collapse, fall of temperature, pulselessness (with seventy-four cardiac beats per minute), dilated pupils, muscular relaxa- tion, and, finally, death ; consciousness was preserved to the end.* PHYSIOLOGY AND THERAPEUTICS. Cinchonidine acts similarly to quinine, but is less powerful, doses one-third greater being required. The assertions made by various clinicians, that it produces less disagree- able symptoms than does quinine, have not been confirmed. De Segrais 88 has found the bromohydrate given hypodermically in doses of four to six grains (0.26-0.4 Gm. ) very efficacious. CINCHONAMINE. This alkaloid was discovered by Arnaud 84 in the Cuprea bark from Colombia, probably the product of Remijia pedunculata and Remijia Purdieana. In poisonous doses it produces violent convulsions in the dog, with fall of the arterial pressure. It also arrests the heart in diastole, and increases especially the secretion of the salivary glands. (Se"e and Bochefontaine. ) Its influ- ence upon man has not, so far as we are aware, been studied, but its botanical an J chemical relations make it probable that it resembles quinine in its physiological and therapeutical properties. * See N. Y. Med. Journ., 1884, xxxix. ANTIPERIODICS. 579 WARBURG'S TINCTURE. This is a dark brown liquid, prepared in accordance with a very complicated formula,* which has obtained an extraordinary reputation in India and other tropical countries in the treatment of severe remittent and malig- nant malarial fevers. The testimony is so strong as to its remarkable and almost certain efficiency that it cannot be questioned, and entitles the tincture to rank above all other remedies. The method of administration is as follows. The bowels having been freely opened, a half-ounce of the tincture is given undiluted, all drink being withheld, and at the end of three hours a second half-ounce is in similar manner exhibited. Soon after the last dose a profuse and very aromatic perspiration sets in, and convalescence is usually secured. The remedy is also commended in one-drachm dose in acute nervous exhaustion and collapse without organic disease. QUININE ESTERS. A number of the esters of quinine have been ex- amined pharmacologically, and some of them have found their way into practical use. Among these compounds acetylquinine has been con- demned on account of its taste ; benzoylquinine and phosphorylquinine are stated by M. Overlach 100 to be practically inert. The esters which have been put upon the market as of value are as follows : ARISTOCHIN. Neutral carbonic quinic ester. This tasteless, pinkish-white, amorphous powder, soluble in alcohol, ether, chloroform, or glycerin, insoluble in water, is said to contain ninety-six per cent, of quinine. According to Stursberg, 101 after its ingestion, quinine appears in a short time freely in the urine. It probably is effective as an antiperiodic, but has been chiefly commended in whooping-cough of children, given in doses of from one to four grains three times a day. EUQUININE. The ethyl carbonic ester of quinine has been highly commended as a substitute for quinine, and as having the advantage of being practically tasteless and of producing a less severe tinnitus aurium. The tinnitus aurium is, however, almost certainly a test of the amount of active quinine in the circulation ; that euquinine is absorbed very slowly and eliminated very slowly is indicated by the studies of F. K. Kleine, who was unable to obtain from the urine more than seven- teen per cent, of the quinine contained in the ingested euquinine. It does not, therefore, appear probable that euquinine is as efficient as quinine, but it has been commended highly in all forms of malarial disease, also in whooping-cough, chorea, an&mia, general debility, and, indeed, in all affections for which quinine is gener- ally employed. According to Luigi de Carlo, combined with benzonaphthol it is especially effective in those forms of malaria accompanied by intestinal affection. From fifteen to thirty grains may be given in the course of the twenty-four hours. RHEUMATINE. Salicylate of salicyl-quinine occurs in white, tasteless needles ; sparingly soluble in water. It has been especially commended by Overlach in the treatment of rheumatic neuritis. It is affirmed also to relieve the lancinating pains of tabes, and may be given in doses of fifteen grains up to a drachm in the course of twenty-four hours. SALOOUININE. This quinic ester of salicylic acid occurs in colorless crystals, insoluble in water, but soluble in alcohol and ether. It contains fifty per cent, of quinine. Overlach alleges that it does not cause cinchonism ; it is, therefore, prob- ably as an antiperiodic very feeble, a conclusion which is confirmed by the fact that * For formula, see United States Dispensatory, i8th ed. 580 GENERAL REMEDIES. F. K. Kleine was only able to recover during the twenty-four hours from two to seven per cent, of the quinine contained in an ingested dose of saloquinine. Never- theless, saloquinine has been most highly commended as an antiperiodic, as an anti- pyretic in fevers, and as an analgesic and antirheumatic in neuralgias, neuritis, and similar conditions. It has usually been given in the single dose of thirty grains. In sciatica and various neuralgias the dose may be repeated within the twenty-four hours. The absorption of the drug appears to be very slow, so that in typhoid fever thirty grains of it, administered directly after the cold bath, begins to exert its influence about the time the effect of the bath is passing off. METHYLTHIONIN^ HYDROCHLORIDUM METHYLENE-BLUE. U. S. Medicinal methylene-blue is to be carefully distinguished from the dye- stuff, which is a mixture of the chloride of zinc and tetramethylthionine, and contains various impurities of which the most important is arsenic. When intended for internal use the drug must be free from arsenic and zinc. Parenski and Blatteis l attribute the various unpleasant symptoms nausea, vomiting, strangury, and the like which have been reported, to the confusion of the medicinal with the dye methylene-blue. Absorption and Elimination. Methylene-blue is readily absorbed from both the subcutaneous tissues and mucous membranes of the ali- mentary tract, appearing in the urine, according to Achard and Cas- taigne, 2 within half an hour after its hypodermic injection. Although the bulk of the drug ingested probably escapes with the urine, the bluish saliva and faeces observed by Ehrlich and Leppmann s would indicate that other glands share in its elimination. In a number of morbid conditions the urine does not become dis- colored after the administration of methylene-blue. Achard and Castaigne, believing that this was due to failure of elimination, suggested the remedy as a test for the permeability of the kidney and reported a number of cases of nephritis tending to support their position. Subsequently, however, Voisin and Hauser* showed that if this colorless urine be warmed, or if acetic acid be added to it, the blue color will appear. Achard and Castaigne, 5 in reply to this, expressed the opinion that methylene-blue was eliminated in part unchanged, and in part as a colorless chromogenic substance, and that the diseased kidney permitted the passage of the latter but not of the methylene-blue itself ; they give, however, no indication of the chemical nature of this chromogen. General Action. Very little is known concerning the physiological action of methylene-blue. According to Combemale and Francois 6 doses of 0.4 gramme per kilo produced in the dog vomiting, purging, and diuresis. These observers found that in the guinea-pig o. 3 gramme per kilo caused muscular weakness, greatly accelerated respiration, and death. After death there was widespread staining of the tissues, especially marked in the nervous system. The blood was chocolate-colored and contained methaemoglobin. THERAPEUTICS. In 1890 Ehrlich and Leppmann called attention to the analgesic action of methylene-blue, reporting several cases of neural- ANTIPERIODICS. 581 gic and rheumatic pains relieved by it. Combemale and Francois found that while in simple neuralgia it was frequently of service, in neuritis and central nerve-pains it was of little value. Although numerous other authors have confirmed the statement that methylene-blue possesses some analgesic action, the drug seems to be uncertain in its effect, and has no advantage over the newer aniline derivatives.* As an antiperiodic, methylene-blue deserves a position of high rank, rivalling quinine in the treatment of malaria. In four hundred and twenty-five cases collected by H. C. Wood, Jr., 7 in which it was the sole drug employed, there were 85 per cent. (362) of recoveries. Both Rosin 8 and Iwanoff 9 have shown that it exerts a direct, destructive action on the plasmodium malariae. The latter observer states that this effect is most marked in the adult forms of the protozoon, in this contrasting strongly with quinine (correct (?); see p. 572, small print), and that the crescent type, notoriously resistant to cinchona, is easily destroyed by methylene-blue. Since it exerts no irritant influence on renal structure methylene-blue has been recommended especially in the so-called black- water fever. Whenever in a malarial disease quinine is contra-indicated it is the most serviceable substitute we possess. Austin Flint (1895), impressed with the results obtained from the use of methylene-blue in cases of chyluria, suggested its use in gonorrhoea, concluding from its action on the genito-urinary tract that it would prove to be a valuable remedy in that affection. The results obtained at the hands of many clinical observers do not, however, confirm this opinion, experience showing that where the remedy is employed alone, and not in combination with well recognized antiblenorrhagic drugs, it has no effect whatever in lessening the urethral discharge. The property which the drug possesses of coloring the urine is, moreover, a distinct disadvantage, as it prevents the physician from drawing proper conclusions regarding the natural appearance of the urine. Methylene-blue may be set down as a mild genito-urinary antiseptic of some value in chronic cystitis and pyelitis. f ADMINISTRATION. In the treatment of malarial diseases with methyl- ene-blue it is necessary to continue the use of the drug for some time after the cessation of symptoms on account of the liability of relapse. From two to three grains (0.1-0.2 Gm. ) may be given every three hours for ten days, and after this, three grains three times a day for a fortnight longer. In gonorrhoea the usual dose is two or three grains (0.1-0.2 Gm. ) three times a day. The remedy may be conveniently given in pill form, but preferably enclosed in gelatin capsule to avoid the staining of the fingers and lips. The patient should always be warned of the probable discoloration of the urine. * The theory of Ehrlich that methylene-blue acts as analgesic by staining the axis cylinders has been shown by Combemale and Francois to be untrue, for while it is pos- sible to stain living tissue with the drug, doses far in excess of those used are necessary. f This paragraph was written by Prof. H. M. Christian. 582 GENERAL REMEDIES. EUCALYPTUS. U. S. Of the Australian genus Eucalyptus,* which comprises about one hun- dred and thirty-five species of evergreen trees, the U. S. Pharmacopoeia recognises only E. globulus, whose leaves are official, but allows the oil of eucalyptus (OLEUM EUCALYPTI, U. S. ) to be distilled from fresh leaves of various species of the genus. Neither the dried leaves nor their fluid extract (FLUIDEXTRACTUM EUCALYPTI, U. S. ) are themselves used in medicine. From the various species of Eucalyptus are prepared in Australia an umber of volatile oils, and also the Eucalyptus Gum of the British Pharmacopoeia. The so-called red gum, which occurs in commerce in kino-like grains or masses, contains nearly five per cent, of tannic acid, and is much used in making astringent lozenges. Most of the eucalyptus oils are composed very largely of eucalyptol or of phellandrene. The oils containing phellandrene were thrown out by the revisers of the U. S. Pharmacopoeia, evidently under the impression that the active physiological portion of the oil is eucalyptol. Concerning the physiological action of phellandrene, however, we have no knowledge. Oil of eucalyptus is a colorless or faintly yellowish liquid, having a characteristic somewhat camphoraceous odor and a spicy, disagreeable taste. Dose, ten to fifteen minims (0.6-0.9 C.c. ), in capsules. Its active principle ( EUCALYPTOL, U. S. ) is to be preferred to the oil as more con- centrated and uniform in action. Dose, five to ten minims (0.3-0.6 C.c.). All the virtues of Eucalyptus probably reside in the volatile oil, which is in greatest abundance in the leaves, f PHYSIOLOGICAL ACTION. Local Action. Absorption and Elimi- nation. The oil of eucalyptus is decidedly irritant, large doses causing burning in the mouth and fauces, with increased secretion of saliva, fol- * Attention was first called by Labillardiere in 1792 to the value of the Eucalyptus globulus, but it was not until 1860 that M. Ramel commenced the culture of the tree in Paris and induced the Prefect of the Seine to order its cultivation on a large scale. Since that time it has been largely introduced into Europe, Algeria, South Africa, and California, and in some of these countries planted forests are now growing and spreading. The tree is remarkable for combining extreme hardness of wood with a rapidity of growth asserted to be about five times that of our ordinary trees ; it is also affirmed that shingles made of it are fire-proof. Its capability for absorbing and evaporating water is extraordinary, and to it has been attributed the freedom of Australia from malarial climatic influences. In- deed, it is stated that a tree will evaporate ten times its weight of water in twenty-four hours, and numerous examples are given in which swamps in Europe and Algeria have been rapidly converted by it into dry ground. It is believed to destroy malaria not only by draining the soil, but also by yielding balsamic exudations to the air; however this may be, there is at present very strong evidence as to its power of rendering infected districts healthy. As the consideration of this subject belongs to hygiene rather than to therapeu- tics, the reader is referred for detailed information to the following memoirs : Regulus Carlotti (L' Eucalyptus, son Rang parmi les Agents de la Matters Medicale, Ajaccio, 1872), M. Gimbert (L' Eucalyptus Globulus, son Importance en Agriculture, en Hygiene, et en Medecine, Paris, 1870), Waterer {Bulletin de la Societe d'Acclimatation, 1872; London Medical Record, Dec. 1873; London Lancet, 1877, ii.). Under the name of Eucalypsinthe , a liqueur distilled from the leaves of the euca- lyptus has appeared in European commerce. t It has been affirmed that the leaves of Eucalyptus contain also an alkaloid ; but Rabuteau (Bull. Therap., Ixxxiii. 549) has demonstrated that this is an error. ANTIPERIODICS. 583 lowed very soon by a feeling of warmth in the stomach. It is absorbed from the alimentary canal, and is probably eliminated by the lungs, skin, and kidneys. In the experiments of Binz, the day after the ingestion of seventy-five drops the breath smelt of the drug and the perspiration of amylic alcohol ; the urine began to have the odor of the oil an hour and a half after its ingestion, and continued to have it for thirty-six hours. Gimbert 1 states that the odor imparted to the urine resembles that of violets, and is very similar to that caused by turpentine. Binz affirms that upon the lower infusoria the oil acts even more powerfully than does qui- nine, and its general antiseptic properties are decided (Gimbert). General Effect. The constitutional effect of the same dose of the oil appears to vary considerably in different individuals ; but the following summary comprises the facts as nearly as may be. After the ingestion of from ten to twenty minims, a period of mental and physical activity is often apparent, followed by a feeling of calm and serenity. After large doses irritation of the digestive organs sometimes shows itself by loose stools or even by vomiting. In exceptional cases even the moderate dose may produce violent cardiac palpitation and intense headache and fever, all these symptoms probably being due to gastric irritation. Large amounts of the oil cause marked depression, with slowing and afterwards quickness and weakness of the pulse, general asthenia, sub-normal temperature, blunting of sensation, and finally profound loss of muscular power with stupor, deepening into unconsciousness, and accompanied by loss of the reflexes, and contracted reactionless pupil. In anomalous cases the symptoms produced by the oil of eucalyptus differ from the typical character. Thus, in an old man who took eighty drops, the power of motion almost disappeared ; the man also affirmed that he lost for the time being all sense of the presence of his limbs, so that he was unconscious of possessing them when he shut his eyes, although his intellect was perfectly clear throughout. In a case reported by Alfred Neale, 2 a little over half an ounce of the oil of eucalyp- tus is said to have produced death in fifteen hours in a healthy boy : the only re- corded symptoms were violent dyspnoea with collapse.* Upon the lower mammalia the oil of eucalyptus appears to act precisely as it does on man. According to the experiments of Gimbert, the hypodermic injection of the oil is immediately followed by a period of excitement, seemingly in great measure due to the intense local irritation ; after about half an hour, if the dose has been sufficiently large, the animal begins to stumble and totter in walking, the breathing grows more and more slow and irregular, the limbs give way, the ears droop, the muscular weakness becomes profound, and death, preceded often by partial convulsions, occurs through failure of respiration. Death appears to be produced by the fatal dose through asphyxia. According to the experiments of Gimbert (confirmed by Binz), the motor nerves and the muscles are not affected, so that the failure of motion and reflex activity is probably due to a depression of the motor side of the spinal cord and of the medulla. According to Hermann Schlager, the * As a quart of very bloody serum was found in the pleura cavity, and as the boy was not seen professionally until he was in articulo mortis, doubt attaches to this case. 584 GENERAL REMEDIES. hypodermic injection of the oil produces a temporary rise of temperature, probably as the result of the local irritation, but after toxic doses the temperature falls decidedly. Schlager 3 also states that the large dose of the oil causes a marked lessening of the arterial pressure, whose coming on is not affected by previous section of the vagi, by atropinization of the heart or by section of the cord. It would appear, therefore, that the oil of eucalyptus directly depresses the heart or the peripheral ar- teries. As in Schliiger's experiments the force of the isolated frog's heart was distinctly depressed by the drug, the latter must be a direct cardiac depressant. Mosler 4 affirms that in dogs whose spleens were exposed, injections of tincture of the leaves of eucalyptus produced a decided con- traction of the viscus. According to Gimbert, the excretion of urea is enormously increased by the drug. THERAPEUTICS. The oil of eucalyptus has some power as an anti- periodic, but is much inferior to the cinchona alkaloids and to methylene- blue, and should be used only in cases in which for sufficient reasons these remedies cannot be employed, or as an adjuvant to them. Joseph Keller 5 used it in four hundred and thirty-two cases, of which two hun- dred and ninety-three had suffered from previous attacks. Of the tertians 75.57 per cent., of the quartans 70 per cent., and of the quotidians 67.89 per cent, yielded to the remedy. He recommends it as especially valuable in obstinate cases in which quinine has been taken again and again. Lorinser, 6 Haller, 7 Bohn, 8 Carlotti, Cortan,' Gimbert, Gubler, Tristany, 10 of Spain, J. H. Musser," and others, bear testimony to the power of Eucalyptus in malarial diseases ; while Brudell, 1 * Seitz," and Papillon " affirm it to be of little or no value. Oil of eucalyptus is one of the best stimulating expectorants that we possess : in both acute and chronic bronchitis it may be exhibited when there is free secretion. Children bear it very well. According to A. F. Galbraith Faulds, 15 it is valuable in some forms of glycosuria. Dose of oil or of eucalyptol three to ten minims every three to five hours. REFERENCES. CINCHONA. 14. CERNA P. M. T., x. 493. 1. KKRNER A. G. P., 1870, iii. 93. 15. CHAPERON . . . . A. G. P., 1869, 295. 2. BRIQUET .... Traite therap. de Quin- 16. SEDGWICK . . . . J. P., iii. 22. quina, Paris, 1855. 17. ROBERT A. E. P. P., xv. 49. 3. DE RENZI . . . . B. G. T., xci. 45. 18. WILD B. M. J., 1887, ii. 4. DIETL W. M. W., 1852. 19. PIORRY A. G. M., 1847. 5. LANDERER . . . Repertorium f. Pharmacia, 20. SCHLOCKOW . . . De Chini Sulfavici, etc., 1836, 1839, 1842. Bratisl., 1860. 6. WELITSCHKOWSKI . St. Petersburg Med. 21. SCHROFF .... Med. Jahrb., 1875. Wochensch., 1876. 22. JERUSALIMSKY . . C. M. W.. 1876, 476. 7. JAKOUBOWICH . .Rev. d. Sciences Med., 23. SEE and BOCHEFONTAINE . C. R. A. S., xcvi. 1873. 267. S. ALBERTONI . . . A. E. P. P., xv. 278. 24. SCHARRENBROICH . In. Dis., Bonn, 1867. 9. DUPUIS L'Action Physiol. de Qui- 25. KERNER Pract., vii. 321. nine, Paris, 1877. 26. GELTOWEKY . . . Pract., vii. jo. KIRCHNER .... Sitzungsb. d. Phys. Med. 27. BINZ V. A. P. A.. 1869, xlvi. 138. Gesellsch., Wurzburg, 28. CUTTER Psychol. Med.-Legal Jour- 1881, 161. iial. Feb. 1875. 11. ROOSA A. J. M. S., 1874. 29. HARE P. M. T., xv. 43. 12. EULENBURG . . . A. A. P., 1865. 30. MARTIN In. Dis., Gicssen, 1868. 13. HEUBACH . . . . C. M. W., 1874, 674. 31. BINZ A. E. P. P., 1873, i. 57. ZUNST In. Dis., Bonn, 1886. SCHULTE . . . . C. M. W., 1871. RANSONE .... In. Dis., Bonn, 1871. BRUNTON and CASH . St. Barthol. Hosp. Rep., xviii. 269. MONTEVERDI . . Ann. et Bull, de la Soc. de M6d. de Gand, May, 1871. WILSON Southern Med. and Surg. Journ., 1855, 341 ; Sept. 1860. WEST Savannah Journ. of Med., i. 19. RANCILLIA . . . L'Union Med., 1873. SAVRE American Practitioner, 1871, 260. CHIARA L'Union Med., Nov. 20, 1873. WALRAVEN . . . B. M. S. J., 1873. BURT Med. and Surg. Rep., 1870. ERWIN . . . . St. L. M.S. J., March, 1872. HARRIS American Pract., 1872. RUSSWURM . . . American Pract., 1871, 127. ASHFORD .... Nat. Med. Journ., Oct. 1871. SAUTERSON . . . A. E. P. P., 1892, xxx. BOSSH In. Dis., Dorpat, 1862. STRASSBURG . . . A. E. P. P., ii. 343. UNRUH V. A. P. A., 1869, xlviii. 227. OPPENHEIM . . . A. G. P., 1880, xxxiii. 446. RABUTEAU . . . . B. G. T., Ixxv. 475. VON BOECK . . . Untersuchungen iiber die Zersetzung d. Eiweisses, etc., Munich, 1871. PRIOR A. G. P., xxxiv. 237. BOECK and BAUER . Z. Bi., x. CHITTENDEN . . S. L. P. C. Y., ii. 223. LIEBERMEISTER . D. A. K. M., 1867, iii. LONDON CLINICAL SOCIETY . Transact., 1870, iii. 201. NAUNYN and QUINCKE . A. A. P., 1869. BINZ Pract., 1870, 4. HARE B. M. S. J., cxiv. 73. HAMILTON . . . Indian Med. Gaz., Nov. i, 1873- HENKE D. A. K. M., xii. 630. BINZ Amer. Journ. Obst. and Dis. of Women, iii. LETZERICH . . . Amer. Journ. Obst., etc., iv. 761. DAWSON Amer. Journ. Obst., etc., 1873- ALBHRTONI and CIOTTO . B. G. T., xc. 403. L. L., 1876, i. FRIEDMANN . . . Wien. Med. Presse, 1884. DEWEES U. M. M.. 1890. ERLENMEYER . . Centralbl. f. Nervenheilk., June, 1890. TITLOW N. Y. M. R., 1898, liv. MICCICHE . . . . S. Jb., ccxlix. B. M. S. J., cix. 587. CHEVALLIER . . Gaz. des H6p., 1850. HUSEMANN . . . Th. M., Jan. 1888. CLAPTON . . . . M. T. G., April. 1864. TAUSSIG Stillg's Therapeutics, i. 507- WHARTON . . . . A. J. M. S., April, 1844. LABORDE . . . . C. R. S. B., 1882, iv. ANTIPERIODICS. REFERENCES. Continued. 82. 585 BOCHEFONTAINE . C. R. A. S., XCvi. 503. 83. DE SEGRAIS . . A. G. M., xvii. 711. 84. ARNAUD . . . . C. R. A. S., xciii. 85. SEE and BOCHEFONTAINE . C. R. A. S., c. 86. GRUENING . . . N. Y. Eye and Ear Infirm. Rep., 1897, v. 6. 87. MELLINGER . . Klin. Monatsbl. f. Augen- heilk., 1887, xxv. 57. 88. DE SCHWEINITZ . Toxic Amblyopias, 1896; also Ophthal. Rec., 1898, vii. ; Ibid., 1899, viii. 610. 89. BARABASCHEW . Archiv f. Augenheilk., 1891, xxiii. Heft 2. 90. DE BONO .... Archiv di Ottal., 1894, ii. 171-227; Ibid., 1899, vi. 398. 91. HOLDEN .... Transact. Amer. Ophtha). Soc., 1897-98, viii. 405. 92. DRUAULT .... Recherches sur la Patho- gnie de 1'Amaurose Quinique, Paris, 1900. 93. MAUREL .... A. M. Ex., 1903, xv. 94. WlTTMAACK . . A. G. P., 1903, XCV. 95. GOLGI Rend Inst., Lombardo, xxv. 96. MONACO and PANICHI . A. I. B., 1900, iii. 97. MERKEL . . . . A. E. P. P., 1902, xlvii. 98. KLEINE Z. H. I., xxxviii. 99. AUFRECHT . . . T. M., 1903. 100. OVERLACH . . . C. I. M., 1901. 101. STURSBERG . . . M. M. W., 1902, xlix. METHYLENE-BLUE. 1. PARENSKI and BLATTEIS . Th. M., 1893, vii. 16. 2. ACHARD and CASTAIGNE . B. S. M. H.. 1897, xir. 637. 3. EHRLICH and LEPPMANN . D. M. W., 1890, xvi. 493. 4. VoisiNand MAUSER . G. H. M. C., 1897, xliv. 493- 5. ACHARD and CASTAIGNE . B. S. M. H., 1897, xiv. 1128. 6. COMBEMALE and FRANCOIS . C. R. S. B., 1890, ii. 468; 1891. iii. 300. 7. WOOD, JR. . . . Tr. P. C. M., Nov. 9, 1904. 8. ROSIN D. M. W., 1893, xix. 1068. 9. IWANOFF . . . . D. M. W., 1901, xxvii. 291. EUCALYPTUS. 1. GIMBERT .... A. G. M., 1873, xxi. 141. 2. NEALE Australian Med. Gaz., 1893, xii. 3. SCHLAGER ... In. Dis., Gottingen, 1874. 4. MOSLER . . . . D. M. W., 1872, x. 160. 5. KELLER . . . . W. M. W., 1872, xxii. 6. LORINSER . . . W. M. W., xix., xx. 7. HALLER . . . . W. M. W., xxvi. 8. BOHN B. K. W., 1872. 9. CORTAN . . . . Montpellier Medical, May, 1872. 10. TRISTANY . . -Buchner's Repertorium, 1870, xix. 11. MITSSER . . . . T. G., 1886, 369. 12. BRUDELL . . . . B. G. T., May, 1875. 13. SEITZ Bayer. Aerztl. Intell. Blatt., 1870. 14. PAPILLON ... G. H. M. C., 1872. 15. FAULDS G. M. J., 1902. FAMILY V. ANTIPYRETICS. UNDER the term Antipyretics are to be considered certain remedies which are used in practical medicine for the purpose of reducing bodily temperature in fever. Most of these remedies conjoin to their antipy- retic properties the capability of relieving pain which is not due to inflam- matory or other distinctly local diseases or traumatism. Some of them are actively antirheumatic. The different members of the class vary greatly in the activity of what may be termed their secondary properties, some of them being used in reality almost entirely as antirheumatics or analgesics, their antipyretic powers being inferior for practical purposes to those of other members of the group. The method in which antipyretics reduce fever temperature has not been thoroughly worked out, but it is probable that they exert their in- fluence by an action upon the thermogenetic or thermo-inhibitory centres. On the other hand, it is possible that they have such immediate influence on the chemical processes in the various tissues of the body as to directly affect the production of heat. The question as to whether it is better in fever to reduce the excessive temperature by the administration of an antipyretic, or by the use of the cold bath, is one to which at present a positive answer cannot be given. So far as our present knowledge goes the antipyretics produce greater disturbances in the general functions of the body than is caused by what we may call the mechanical abstraction of heat. Further, the fever process itself is a disturbed condition of the nutrition, which is by no means thoroughly comprehended. In the administration of an anti- pyretic we are attempting to modify for the better a morbid process of whose real nature we are ignorant by the use of a powerful drug of whose action we have not definite knowledge. The use of the antipyretics is at present empiric, and in our lack of knowledge the cold bath would seem to be a safer remedy than the drug. The greater convenience of anti- pyretics, however, exerts a constant pressure for their use by the physi- cian, and little by little confidence in them seems to be growing. Our own belief is that in minor cases of fever the antipyretic is often superior to the cold bath because of its greater ease of application, but that in the severe cases of fever, especially when there is a tendency to persistent adynamia, the best results are to be achieved by relegating antipyretics to the class of adjuvants, employing them in moderate dose simply for the purpose of assisting the cold bath, and of prolonging its influence. 586 ANTIPYRETICS. 587 ACIDUM SALICYLICUM SALICYLIC ACID. U. S. Salicylic acid occurs in long acicular crystals or in the form of a white, dull powder, of a peculiar pungent odor, and a mild, peculiar taste, accompanied by a transient sense of numbness. It is soluble at 25C ., in about three hundred and seven parts of water and in 2.1 parts of alcohol. PHYSIOLOGICAL ACTION. Local Action. Absorption and Elimina- tion. Pure salicylic acid is so actively irritant to mucous membranes that its less irritant compounds are universally preferred in practical medicine. It is absorbed rapidly through mucous membranes, and also to a less ex- tent through the skin when applied in alcoholic solution (Drasche 1 ), or in the form of a soluble compound. It circulates as a sodium or other sali- cylate. Many of its insoluble compounds, such as strontium salicylate, bismuth salicylate, etc., undergo slow decomposition in the alimentary canal, yielding their salicylic acid to the alkaline intestinal juices, and subsequent absorption. Salkowski * pointed out that salicylic acid in the blood probably exists in the form of the sodium salt. Binz s supposes that the acid is liberated in the blood by the carbonic acid formed in the tissues. The only basis for this theory consists in the fact that by passing carbonic acid gas through a solution of sodium phosphate, carbonate, and salicylate, agitating with ether, and separating and evaporating the latter, crystals of salicylic acid are obtained. It is evident that if in the blood changes take place similar to those which occur in this solution, salicylic acid should be yielded to ether shaken with the blood of an animal poisoned with the drug. Feser and Friedeberger found that unless enormous doses of the drug were injected into the blood so as to produce immediate violent convulsions and death, the vital fluid of the poisoned animal yielded nothing to ether. In Kohler's 4 experiments, when salicylic acid was dissolved in normal blood no acid was yielded to ether ; but when the blood of asphyxia i. y experimenters to be preserved at a time when the lower portion of the nervous apparatus is distinctly affected. According to Bokai, 10 antifebrin paralyzes motor nerve-endings of the frog's muscles in a manner similar to curare, and when brought in contact with the muscle itself for a suf- ficient length of time destroys its capability of contraction. In the poi- soned animal, however, just before death the muscles respond actively, although irritation of motor nerve-trunks fails to elicit response. Circulation. Usually when antifebrin is given to patients with fever there is a fall in the pulse-rate corresponding to the fall of temperature. The size of the pulse is also reduced, and it may even become thready. Weill has found that, injected into the frog, the drug causes at first an acceleration of the heart' s beat, with apparent increase in the force of the impulses, followed after a time by slowing and irregularity of contraction. In the earlier stage the size of the pulse-wave is increased and the re- spiratory curve is more accentuated ; later the pulse-oscillations diminish and become irregular and quickened, and if the dose has been large enough the manometric writing resembles that produced by asphyxia. In the earlier stages of the action there is a slight rise in arterial pressure. The cyanosis of antifebrin-poisoning has been thought to be due to the formation of methaemoglobin and Stewart 20 reports two cases in which the blood had the characteristic chocolate color, although no spec- troscopic examination seems to have been made. On the other hand in cases of poisoning with marked cyanosis both Freund 11 and Stengel 21 were unable to detect anything abnormal in the blood by spectroscopical examination. The blood changes do not appear to be characteristic ; Stewart reports marked reduction of the number of red cells but in one of Stengel's cases the corpuscles were 6,000,000. Herczel states that * See also Medical News, Ixxii. 791. ANTIPYRETICS. 613 the red corpuscles do not adhere in rouleaux, that they are somewhat granular, and that, when the drug is given to dogs for a length of time, the blood is less alkaline than normal, and contains in its serum dissolved coloring- matter. According to Lepine and Aubert, 12 the oxygen of the blood is distinctly decreased. Nutrition. Kumagawa found that while small doses had no definite effect, large doses enormously increased the nitrogenous elimination ; but in Lepine' s experiments the results varied, there being sometimes an in- crease and sometimes a diminution, while H. C. Taylor 13 obtained a slight increase : so that it is impossible at present to say what is the action of the drug upon protoplasmic chemical activity. According to Kumagawa, antifebrin exerts a strong antiseptic influ- ence upon intestinal changes, decreasing the bacteria in the intestines, and the urinary indican. Temperature. The only information we have concerning the method by which acetanilid lowers bodily temperature is furnished by the experi- ments of H. A. Hare and E. M. Evans. 1 * It is not sufficient for a posi- tive conclusion, but indicates that in fevered animals antifebrin produces a fall of the temperature by decreasing heat-production. In fifteen experiments upon normal animals, which in nearly all cases were allowed to run free, Hare obtained a distinct fall of temperature from antifebrin, a result confirmed by Evans, but not in accord with the results of Cahn and Hepp, who found that antifebrin had not a constant influence upon the temperature of the normal animal. Hare, employing the calorimeter of H. C. Wood, found that in the normal animal heat-dissipation and heat-production were variously affected, in some cases being notably increased, in other cases notably decreased, arid in others not distinctly altered. Evans, employing the D'Arsonval calorimeter, also reached various results. In eleven experiments heat-dissipation was decreased nine times, while heat-production was increased four times and decreased five times. In ex- amining the records of the calorimetric experiments made by Hare and Evans on the normal animal, we find that not only did the rectal temperature not fall under the influence of antifebrin, but in nearly every instance there was a very distinct rise, amounting in some cases to over a degree. It is evident, therefore, that these experiments cannot be used to explain how antifebrin reduces temperature when it does cause a fall. The attempt to reason how a certain result is produced by a remedy from experiments in which that result was not produced is necessarily futile. In Hare's experiments made upon dogs in which fever was caused by the injection of pepsin, antifebrin failed to produce any constant fall of the bodily temperature, probably because the dose was not large enough. In the calorimetric studies heat- production was usually decreased, but sometimes it was increased, an assertion which is also true of heat-dissipation. These experiments must likewise be laid aside, because there was no fall of temperature caused by the antifebrin. In Evans's experiments with fever produced by the injection of albumose, the antifebrin nearly always caused a distinct reduction of temperature. In the calorimetric studies the results obtained were constant, there being in each of the six consecutive experiments a decrease in both the hourly heat-dissipation and the hourly heat-production, the amount of decrease seemingly bearing some relation to the fall of temperature. Il is plain that a decrease of heat-dissipation would have a natural tendency to ele- vate bodily temperature, and therefore the fall of temperature must have been due to the decrease of the production, which in turn gave rise to the decrease in the heat-dissipation. 614 GENERAL REMEDIES. THERAPEUTICS. The therapeutic use of antifebrin is exactly parallel to that of antipyrin. Some practitioners prefer it on the ground that it is less liable than is antipyrin to produce collapse, painful skin lesions, or other disagreeble effects, but it is certainly capable of causing fatal acute or chronic poisoning. According to Sembritski 16 it acts very badly on pregnant or nursing women. Lepine " affirms that it will relieve not only the fulgurant pains of spinal disease, but also the tremors produced by multiple sclerosis, and is often useful in epilepsy. Dose, five to fifteen grains (0.3-1 Gm.). Acetanilid affords a useful surgical dressing, and has the superiority over iodoform of being free from odor, and perhaps of being more anal- gesic. It is frequently employed with equal amounts of boric acid, finely powdered, in the treatment of minor infected wounds. The powder may be freely used, or an ointment of from ten to forty per cent, strength; in vaginitis or urethritis a mixture (twenty to forty grains to one fluid- ounce) with gum-arabic water may be injected. The free external use is not entirely devoid of danger, as cases have been reported of collapse with intense cyanosis and subnormal temperature produced by the sur- gical use of the drug.* Toxicology. The symptoms of acute poisoning by antifebrin are vomiting, muscular weakness, cyanosis, coldness of the extremities, sub- normal temperature, profuse sweating, disturbances of respiration, fixed dilated pupils, rapid irregular heart action, ending in collapse and cardiac death. In some cases an impaired consciousness has not been present until very late in the poisoning ; in others a complete unconsciousness has been a comparatively early symptom. The urine may be dark owing, it is said, to haematoporphyrin (methaemoglobin?). Leucocytosis with nucleation of the red blood-corpuscles has been noted. Sixty grains of it are asserted to have caused death, but have been recovered from after the most alarming symptoms. (See Doll, quoted by Biach, also P. Brown. 18 ) Marichaux 15 details a case in which four grains caused in a child collapse, with complete unconsciousness, ending in recovery. In chronic poisoning the most pronounced symptoms are anaemia and cyanosis ; gastric disturbance, failure of the general nutrition, rapid, feeble heart action, and distinct enlargement, without tenderness, of the spleen have been noticed. There is not only great decrease in the number of the red blood-corpuscles and in the percentage of haemoglobin, but also marked increase in the number of the white blood- cells, with nucleation of the red blood-corpuscles (see Stengel and White 19 ). ACETPHENETIDINUM. U. S. Acetphenetidin, or Phenacetin, an acetyl derivative of para-amidophenol , * See Phila. Polyclinic, 1897 ; Atlantic Med. Weekly, 1898 ; and Med. and Surg. Rep., 1897, Ixxvi; P. M. /., Sept. 1901. ANTIPYRETICS. 615 crystallizes in tasteless, colorless needles, slightly soluble in water, more so in alcohol. Phenacetin is eliminated by the kidneys, probably entirely altered, phenetidin appearing in the urine. According to Muller, 1 this change must take place after absorption, since both the gastric and pan- creatic secretions are without effect on the compound. O. Hinsberg and A. Kast a have found that when given to dogs in doses of fifteen-hun- dredths to two-tenths of 'a gramme per kilo phenacetin has no effect, but in very large doses it causes vomiting, irregular gait, hurried respiration, and somnolence, followed by general cyanosis and discoloration of the blood, due to the formation of methaemoglobin. The therapeutic dose of phenacetin produces no symptoms, but the toxic dose is said to cause violent vomiting, great cyanosis, chocolate- colored urine, yellow discoloration of the body, leucocytosis, and death (Kronig). Mahnert 3 states that the muscular weakness produced by phenacetin is of spinal origin, and that in massive doses the drug is antagonistic to strychnine, also that both respiration and heart are para- lyzed by it. According to the same observer it is chiefly eliminated un- changed ; and the urine gives a positive Trommer's reaction, although containing no sugar. Ledoux 4 asserts that in doses of o. 5 gramme per kilo phenacetin causes a fall of the blood-pressure ; but as he used an alco- holic solution his results are not entirely reliable. H. C. Wood, Jr. , and H. B. Wood 17 found that the drug, given intravenously suspended in water, had absolutely no effect on blood-pressure. Doses of o. 5 gramme per kilo killed by arrest of respiration ; which can, perhaps, however, be attrib- uted to the mechanical influence of undissolved particles. Frogs allowed to swim in a saturated aqueous solution of phenacetin in four hours became totally paralyzed, the motor nerves and muscles retaining their irritability. Ott 5 found that phenacetin pronouncedly decreases heat-production with- out producing distinct alteration of blood-pressure, and, therefore, probably acts as an antipyretic by lessening the heat-production through an influence upon the nervous system. According to Falcone and Gioffredi 10 changes in the cerebral cortical cells can be demonstrated in animals killed with phenacetin. THERAPEUTICS. Phenacetin has been largely used as an antipyretic, and for the relief of pains of such character as antipyrin is employed against. Large amounts of it can apparently be taken without serious result. In a case reported to us by E. C. Wagner, one hundred and twenty grains were taken in twelve hours without the production of any symptoms. The only serious case of poisoning by it that we know of is that reported by Hollopeter, 6 in which a woman took twenty-two and a half grains in six hours, producing collapse with marked lividity, great dyspnoea and restlessness, cold perspiration, and slightly dilated pupils, ending in recovery. There can be no doubt of the efficiency of phenacetin, and it would appear that it more rarely produces unpleasant symptoms than antipyrin, though urticaria has been noticed after its exhibition (Mahnert). If the 616 GENERAL REMEDIES. statements of Crombie 7 and of Hirschfelder " that it acts more gradually than other antipyretics, and that its influence does not reach its maximum for three or four hours be correct, phenacetin is probably the most valu- able of the antipyretics, especially as it seems to be the least poisonous. At present it is probably the most used of its class. Dose, from ten to twenty grains (0.65-1.3 Gm. ). Phenacetin is highly commended by M. H. Lee 9 as a local antiseptic dressing. PHENOCOLL HYDROCHLORIDE. Phenocoll occurs in white needle-like crys- tals ; it is made by the action of glycocoll upon phenetidin. Its hydrochloride is a white, finely crystalline powder, very soluble in water. Physiological Action. The action of phenocoll upon the animal organism is not very marked, Von Mering having found that twenty-three grains of it will not produce any pronounced symptoms in the rabbit. According to Isaac Ott, the toxic dose produces, in the frog, paralysis of both the motor and sensory functions of the spinal cord, with death from diastolic arrest of the heart ; in rabbits, quietude, partial paraplegia, and cyanosis, with acceleration of the respiratory movement and depression of temperature and of the arterial pressure. David Cerna and William S. Carter determined that the influence of phenocoll upon the circulation is exceed- ingly feeble. The fall of the arterial pressure caused by enormous doses occurred after section of the spinal cord and of the pneumogastrics ; so that it must be con- cluded that phenocoll, when in sufficient amount, is a cardiac depressant. The action of smaller doses was not made out. The pulse was found by Cerna and Carter to be primarily decreased by inhibitory stimulation, then increased by in- hibitory paralysis, and finally diminished by direct action upon the heart. The same investigators affirm that phenocoll has no action upon the blood, but the correctness of this seems to be challenged by the cyanosis which has been noted both in man and in rabbits. In experiments made upon animals with fever, Cerna and Carter found that the fall of temperature produced by phenocoll is due to an enormous reduction of heat-production, heat-dissipation being practically not altered. As the result of some evidently not elaborate chemical studies, P. Balzer 1 states that phenocoll very distinctly increases the nitrogenous elimination : the cor- rectness of this is very doubtful. Phenocoll is rapidly absorbed and almost as rapidly eliminated. According to Cohnheim, it may be detected in the urine from one to nine hours after its inges- tion. It is probably in part oxidized in the system, since the urine after its free administration becomes of a dark, reddish-brown color. It is possible, however, that this color is due to indican and biliary substances, both of which have been found in the urine. THERAPEUTICS. In 1891 Hertel and Herzog* stated that phenocoll rarely, if ever, produces gastro-intestinal irritation or other disagreeable symptoms, that its antipyretic action is quick and never accompanied by any depression, and that the free sweating which is apt to occur with it may readily be prevented by minute doses of atropine. Both Hertel and Herzog assert that phenocoll is a valuable remedy in acute and chronic rheumatism. The first reports regarding the antipy- retic action of the drug have received wide confirmation, and it would seem that phenocoll is one of the safest, promptest, and most efficient members of its class. On the other hand, it has been stated that in rheumatism and as an analgesic in ataxic or other nerve pains it is inferior to the older remedies. These results may, however, have been due to a too timid use of the phenocoll, as it is affirmed by some clinicians that five grammes or seventy-seven grains of it are usually re- quired to have an effect in rheumatism, whilst most writers give the dose as much smaller than this. In rare instances it produces vomiting, but we have met with no reports of human poisoning by it. The ordinary dosfe may be set down as twelve to fifteen grains (0.78-1 Gm. ), in solution or capsule. ANTIPYRETICS. ' 617 EXALGINE. Methylacetanilid occurs in needles or long tablet-like crystals, almost insoluble in cold water, freely soluble in hot water. When given to man in full, non-poisonous doses, it produces slight amblyopia and vertigo, accom- panied in some persons by vomiting, tinnitus aurium, headache, drowsiness, and vaso-motor disturbances, such as sweating. After large doses cyanosis is pro- nounced, but no eruption upon the surface of the skin seems as yet to have been noticed. No fatal poisoning by it has been reported, but in a case of A. C. Hart- ley's eighteen grains in divided doses produced a general motor paralysis, with dyspncea, intense pallor, dilated pupils, and pronounced palpitation of the heart. In a second case, two doses of three grains each produced in a boy fourteen years old a sudden almost lethal heart-failure, with dilated pupils and dyspnoea. In a case reported by Gillespie there were violent convulsions.* According to Brigonnet, hypodermic injections of exalgine cause in the lower animals violent epileptiform convulsions, profuse salivation, cyanosis, disturbance of breathing, fall of temperature, and alteration of the blood, which becomes dark prune-colored and contains an abundance of methaemoglobin. The muscles at the seat of the injection are said to be locally paralyzed, and although small doses increase slightly the blood-pressure, after the toxic dose the pressure suddenly falls. The urine does not become albuminous nor bloody. Exalgine has been used as an antipyretic, but to a very much larger extent as an analgesic, and is said also to be useful in chorea and polyuria. According to Moncorvo, as an analgesic it has at least five times the power of antipyrin. Dose, three to six grains (0.2-0.4 Gm. ), not more than twelve grains being exhibited in the twenty-four hours. Moncorvo gives the dose for a child five years old as one and a half grains (0.09 Gm. ). SALIPVRIN. Antipyrin Salicylate is a white, coarsely crystalline, odorless, slightly sweetish powder, readily soluble in alcohol. It is commended by Guttman and Kollmann as an active antipyretic and anti rheumatic, which rarely produces toxic symptoms, although an eruption resembling that of antipyrin has been noted; the color of the urine is not affected, but tests show the presence of a salicylate. Kollmann states that it sometimes vomits, and that the daily dose should never exceed forty-five grains (2.9 Gm. ), and should always be less than this in the be- ginning, as some individuals are intolerant of it. Salipyrin has been used to a con- siderable extent in all forms of rheumatism, in influenza, in various fevers, in migraine, and in the whole class of diseases in which its component constituents have been found to be useful ; also locally in coryza. The usual dose is from seven to fifteen grains (0.45-1 Gm. ), in capsule or tablet, repeated every three or four hours, but some clinicians prefer a single large dose of forty-five grains (2.9 Gm. ). PYRAMIDON. Dimethylamidophenyl-dimethylpyrazolon. This is a yellowish- white, crystalline, almost tasteless powder, soluble in ten per cent, of water. It was introduced by Filehne J as a remedy having an action similar to that of antipyrin. It appears to be absorbed readily, and, according to M. Jaffe, 2 is in part eliminated unchanged in the urine, in part converted into the red substance, rubaronic acid, and in part changed into a substance which is colored deep-blue by ferric chloride, and is, probably, antipyrylurea. Its general physiological activities have not been worked out, but G. Ssadkowski f is said to have experimentally determined that it has a powerful action upon the heart and blood-vessels, increasing the arterial ten- *See also Bull, de Therap., March, 1891 ; and Brit. Med. Journ., Feb. 1890. t Ssadkowski (Russkij Wratsch, 1902, No. 18.) We have not seen the original paper, nor yet a satisfactory abstract. 6i8 GENERAL REMEDIES. sion, so that in cases of tuberculosis of the lungs with already heightened arterial pressure, it may produce haemoptysis, and is, therefore, contra-indicated. Pyramidon has been used to a considerable extent as an antipyretic and as an analgesic. The reports as to its value as an antipyretic in typhoid and other low fevers are somewhat contradictory, various clinicians having expressed strong sen- timents in its favor, claiming that though it acts more slowly its influence continues much longer than does that of the older antipyretics. Other observers assert that it is more prone than are antipyrin and phenacetin to produce excessive sweating and collapse. It has been especially praised in migraine, neuralgia, and all the pains of the character for which phenacetin and antipyrin have been previously used. According to Roth, pyramidon is a useful drug in acute rheumatism, though of little value in chronic cases. Albrecht has found it of value in asthma. The dose is twelve grains dissolved in water or taken in capsules, and may, when it is neces- sary, be repeated up to thirty-six grains in the twenty-four hours. Three compounds of pyramidon have been put upon the market, the camphor- ate, the bicamphorate, and the salicylate. It is affirmed that the presence of camphoric acid markedly lessens the tendency of pyramidon to produce sweating without interfering with its antipyretic action. In the bicamphorate the anhydrotic influence is so great that the drug has been strongly recommended in the night sweats in phthisis. Pyramidon salicylate appears to be inferior in the treatment of rheumatism to the older salicylates, though it may be employed in subacute and chronic cases in times of excessive pain. The dose of any one of these preparations is seven and a half to twelve grains (0.5-0.75 Gm. ), repeated as necessary. In tuberculosis, with excessive sweating, it is advised to give two doses a day of eight grains each. THERMOL. Acetyl-salicyl-phenetidin. This substance is a white, crystalline, odorless, tasteless powder, which is affirmed to be a harmless and active antipyretic and analgesic, and as such has been used to a considerable extent in the treatment of typhoid fever, neuralgia, dysmenorrhcea, migraine, etc. ; also as an antispasmodic in whooping-cough. Dose, three to fifteen grains. PYROSAL. Antipyrin salicyl-acetate. PHENOSOL. Salicyl-acetic-acid-phenet- idide. These compounds, which have been proposed and to some extent used as antirheumatics and antineuralgics, are asserted to be broken up into their con- stituents in the alimentary canal and to exert the influence of these constituents upon the human system. Pyrosal is said to contain about fifty per cent, of anti- pyrin and about thirty-six per cent, of salicylic acid ; phenosol about fifty-seven per cent, of phenacetin and forty-three per cent, of salicylic acid. They have been given in doses of seven grains (0.5 Gm. ) from two to six times in the twenty-four hours (see D. M. W., 1898). REFERENCES. SALICYLIC ACID. 1. DRASCHE . . . . Cb. C., 1876. 2. SALKOWSKI . . . B. K. W., 1875, 297. 3. BINZ Pract., xxvi. 443. 4. KOHLER C. M. W., 1876, 553. 5. FARSKY Sb. G. W., Ixxiv. ii. 6. FLEISCHKR . . . Med. Centralb., 1876, 628 7. Mosso A. E. P. P., xxvi. 8. MUSSY B. G. T., xiii. 318. 9. BALZ A. Hk., xviii. 60. 10. BYANOW Cb. C., 1877, 809. 11. STUART Pract., xviii. 425. 12. WOLFBERG . . . D. A. K. M., xv. 403. 13. ROBIN L. M. R., 1877, 151. 14. SEE B. A. M., 1877, 697. 15. REISS B. K. W., 1875,674. 16. QUINCKE . . . . B. K. W., xix. 710. 17. KRUEG Wien. Med. Presse, 1886, xxvii. 405. 18. GIBSON and FELKIN . Pract., 1889, xlii. 19. LABORDE ... . B. G. T., xciii. 276. 20. DANEWSKV . . . Arb. d. Pharm. Lab. Mos- kau, i. 190. 21. LIVON Marseille Med., 1890. 22. MARACLIANO . . Z. K. M., 1884. 23. OLTREMARE . . . Thesis, Paris, 1879. 24. FAVAL Thesis, Lyon, 1887. 25. HAIC M. C. Tr., 1888, Ixxi. ANTIPYRETICS. 619 REFER ENCES. Continued. 32. WOLFSOHN . . . C. M. VV., 1877, 30. VIRCHOW . . . . Z. P. C., vi. SALOME Med. Jahrb. Aerzte Wien, 1885. iv. KUMAGAWA . . . V. A. P. A., 1888, cxiii. TAUSK and VAS . S. Jb. . ccxxxvi. BOHLAND .... Centralb. f. innere Med., 1896, xvii. SCHREIBER and ZANDY . D. A. K. M., 1899, Ixii. 242. FURBRINGER . . Zur Wirk. des Salicyl- saures, Jena, 1875. GEDL C. M. W., 1876, 403. NORTH Pract., xxiii. 184. JUSTI Cb. C., 1876,629. EWALD Pract., xvi. 200. HARK T. G., iii. 450. BUTT L. M. R., 1876, 193. STRICKER . . . . B. K. W., 1879, xiii. HUBER T. G., 1887. Journ. Med. de Paris, Aug. 1892. KOLBE A. E. P. P., iv. MEYER and KOLBE . Journ. f. Prakt. Chem., xii. FRENCH COMMISSION . B. A. M., 1886, xvi. HODARA Monats. f. Prakt. Derm., 1896, xxiii. STOKVIS Atti d. XI. Congr. Med. Internazionale, 1894, iii. PINKHAM .... Trans. Mass. Med.-Leg. Soc., Boston, 1887. JUVET N. Y. Med. Gaz., 1867. GALLAHER. . . . Phila. Med. Exam., 1852. WOOD and HARE . T. G., 1886, 73. LINOSSIER and LANNOIS . B. G. T., 1896. WIECHOWSKI . . A. E. P. P., 1902, xlviii. GOODBODY . . . . J. P., xxv. MOREIGNE ... A. M. Ex., 1900, xii. A. of Op., 1890, xxv. ,7. GIFFORD .... A. O. R., 1902, xi. ; also Tr. A. O. S., 1899. 58. FROMAGET and LAFFE . Ann. O., 1897, cxviii. GLYCOSAL. i. BLOCK T. M., Sept. 1903. AMYLII SALICYLAS. i. LYONNET . . . . R. T., Ixviii. ASPIRIN. 1. SINGER A. G. P., 1900, Ixxxiv. 2. LIESAN D. M. W., 1900, xxvi. SALICIN. I. HUSEMANN . . . Pflanzenstoffe, 903. a. SCARPETTI . . . Rif. M., 1898, 805. 3. MACLAGAN . . . L. L., 1876, i. ANTIPYRIN. 1. FILEHNE Z. K. M., 1884, vii. 641. 2. SAINT HILAIRE .Journ. Laryngol., Otol., etc., 1892. 3. HAGK Robert's Jahresb., 1885. 4. PINZANI Centralb. f. d.ges. Therap., Aug. 1890. 5. FIEUX S. Jb., cclvii. 6. FERRET and GIVRE . Le Bull. Med., Aug. 1891. 7. MARAGLIANO . . Kobert's Jahresb., 1885. 8. CAPITAN and GLEY . C. R. S. B., 1887, iv. 9. IWANOFF .... A. G. P., 1887, Suppl. 10. SPITZ Th. M., 1887. 11. BRIGGS L. M. R., March, 1891. 12. SPITZER Centralb. fur Therap., 1890, viii. IV ARDUIN Thesis, Paris, 1885. 14. DEMME Fort. M., 1884, ii. 657. 15. COPPOLA . . . . Kobert's Jahresb., 1885,314. 16. SIMON and HOCK . Johns Hopkins Hosp. Bull., 1890. 17. BLUMENEAU ... St. Petersb. Med. Woch.. 1887. 18. BATTEN and BOKENHAM . B. M. J., 1889, i. 19. CHOUPPE .... Sem. Md., July, 1887. 20. LEPINE Lyon M., liii. 21. DEVRAUX-ARMAND . Thesis, Nancy, 1885. 22. CASIMIR Thesis, Lyons, 1886. 23. CERNA and CARTER . New Remedies, 1892. 24. FAVAL Thesis, Lyons, 1887. 25. BIACH Die Neuren Antipyretica. 26. CROLAsand HAGOUMENG . Lyon M., 1889. 27. WOOD, REICHERT, and HARE . T. G., ii. 803. 28. DESTREE .... Journ. de M6d. Clin. de Pharm., 1888, Ixxxvi. 29. MARTIN Ott's Modern Antipyretics, 1891. 30. GOTTLIEB . . . . A. E. P. P., 1889, xxvii. 31. GIRARD R. M. S. R., 1887, vii. 32. GOTTLIEB . . . . C. M. W., 1888. 33. CHITTENDEN and CUMMINS . S. L. P. C. Y., ii. 34. UMBACH A. E. P. P., xxi. 35. CAZENEUVE and VISBECK . Lyon M., 1892. 36. Roux and RODET . Lyon M., 1892. 37. VON NOORDEN . B. K. W., 1884, 523. 38. PRIBRAM Prager Med. Woch., 1884. 39. SONNENBERGER . Th. M., 1888, ii. 40. FEENY L. L., 1889. 41. CLEMENT .... Lyon M., 1891. 42. SAINT-PHILLIPPE . Journ. de M5d. de Bor deaux, 1891. 43. GUIBERT Sem. M6d., 1891. 44. VERNEUIL .... Sem. Md., 1891. 45. YOUNG N. Y. M. R., 1890. 46. SCHVVABE .... Deutsche Med. Zeit., 1890 47. BARRS L. L., Feb. 28, 1885. 48. LAWROW .... Z. P. C., 1901, xxxii. ACETOPYRIN. i. BRAUN W. K. W., 1900, No. 39. a. MEITNER .... St. P. M. W., 1900, xx. EUPYRINE. 1. OVERLACH .... C. I. M., 1900. 2. PORGES W. M. Bl., 1901. ACETANILID. 1. FROTHINGHAM and PRATT . A. J. M. S., 1895, ex. 2. CAHN and HEPP . Prog. M., Jan. 1887. 3. PAVAI VAJNA . .Ceritralbl. fur ges. Therap., 1887. 4. KUMAGAWA . . . V. A. P. A., 1888, cxiii. J. JAFFE and HILBERT . Z. P. C., 1887-88, xii. 6. HUGHER . . . . C. B. S. A., 1887, xvii. 7. HARE T. G., 1887. 8. HERCZEL . . . . W. M. W., 1887, 730. 9. WEILL B. G. T., cxii. 150; Thesis, Paris, 1887. 10. BOKAI D. M. W., Oct. 1887. n. FREUND D. M. W., 1888, xiv. 62O GENERAL REMEDIES. REFERENCES. Continued. 12. LEPINE and AUBERT . Gaz. Md. de Stras- 4 bourg, 1887, i. 13. TAYLOR S. L. P. C. Y., Jan. 1889. 14. EVANS T. G., 1887. 15. MARICHAUX . . . D. M. W., 1889, xv. 16. SEMBRITZKI . . . Th. M., 1889, iii. 17. LEPINE Lyons M., 1886, xlvi. 18. BROWN A. J. M., Dec. 1901. 19. STENGEL and WHITE . U. P. M. B., 1903. 20. STEWART . . . . J. A. M. A., 1905, xliv. 1725. 21. STENGEL . . . . J. A. M. A., xlv. 243. ACETPHENET1DINUM. 1. MULLER B. K. W., 1888, 613. 2. HINSBERG and KAST . Centralb. f. ges. Therap., April, 1887. 3. MAHNERT . . . . D. M. W., :888, xiv. LEDOUX Rev. de Med., Paris, 1892, xii. 5. OTT J. N. M. D., 1888, xv. 6. HOLLOPETER . . M. News, 1889. 7. CROMBIE .... Pract., 1889, xliii. 8. HIRSCHFELDER . D. A. K. M., 1888-89, *lv. 9. LEE Memphis Med. Monthly, 1892, xii. 10. FALCONE and GIOFFREDI . A. I. B., xxxiv. 11. WOOD, JR., and WOOD . U. M. M., July, 190x3. PHENOCOLL. 1. BALZER Th. M., 1892. 2. HERTEL and HERZOG . D. M. W., 1891. PYRAMIDON. 1. FILEHNK . . . . B. K. W., 1896. 2. JAFFE I. B. I. M., 1902. CLASS II. LOCAL REMEDIES. FAMILY I. STOMACHICS. STOMACHICS are drugs which especially affect the mucous membrane and other coats of the gastro-intestinal tract so as to increase functional activity. A simple bitter is a substance of vegetable origin and of a bitter taste, which has no influence upon thegeneral system, but markedly affects the stomach as a stimulant. Borissow u found that the introduction of tincture of gentian into the mouth in conjunction with the presentation of food produced a greater flow of gastric secretion than did the food alone. He believes that this action is a reflex one, depending on the bitter taste. Simple bitters probably influence, however, not only the peptic glands but also the muscular fibres, since Paul Terray J found that the movements of the excised stomachs of dogs, kept in a warm salt solution, were in- creased in the order of naming by extract of gentian, cetrarin, condurangin, extract of taraxacum, quinine, and extract of quassia. Cetrarin was remarkable for its influence upon the intestinal movements. Although simple bitters may, by increasing the amount of food taken, affect the general nutrition of the body, they are essentially locally acting drugs. Probably all bitter vegetable substances are stimulants to the gastric mucous membrane, but in many of them, as in morphine and strychnine, such power is overshadowed by other inherent properties. Some of these active bitter vegetable substances are indeed employed on account of their influence upon the alimentary tract, notably quinine and strychnine, but in others of them, like morphine, the local is entirely swallowed up in the general influence. By virtue of their irritant action the simple bitters produce, when in overdoses, nausea, and may even cause active irritation of the gastro-mucous membrane. They have also some tendency to affect the bowels. They are essentially irritant, and are contra-indi- cated by inflammation or over-sensitiveness of the alimentary mucous mem- brane. They are especially indicated by loss of appetite, when such loss of appetite is the outcome of a depressed condition of the stomach, but when it is the result of gastro-inflammation they will do harm. A second class of stomachics are the so-called dramatics, which depend for their activity upon the presence of a volatile oil. They differ from the simple bitters in being more powerful but less permanent as local stimulants. (See page 623.) A third class of drugs contain both volatile oil and bitter principle, and unite the properties of the aromatics with those of the simple bitters. These are the so-called aromatic bitters. 621 622 LOCAL REMEDIES. SIMPLE BITTERS. QUASSIA. U.S. The wood of Picraena excelsa, a large tree, native of Jamaica. This wood is light both in density and color, somewhat resembling that of the tulip-tree, but distinguished by its intensely bitter taste. It is kept in the shops in billets and in raspings. The active principle is Quassin, an intensely bitter, neutral, crystalline principle. Simaruba, the bark of the root of Simaruba officinalis, also contains quassin, and may be substituted for quassia. PHYSIOLOGICAL ACTION. Quassia can hardly be said to be poison- ous to man, the largest doses producing in the adult only gastric irrita- tion, but F. Venn* has reported a case in which in a young child the injection into the rectum of a decoction representing two ounces of quassia was followed almost immediately by vomiting, stupor, relaxation, and collapse, ending in death. According to I. Hoppe," quassin, when given to frogs in doses of one grain, will produce weakness, convulsions, respira- tory and cardiac failure, ending in death. Locally, quassin is a distinct irritant. In man, five milligrammes of the pure crystalline form notably increased the secretion of bile and of urine, and caused some looseness of the bowels and stimulation of the bladder ; whilst fifteen milligrammes produced violent frontal headache, burning pains in the oesophagus and throat, nausea, vomiting, vertigo, excessive nervous restlessness, diar- rhoea, and very frequent micturition, but diminished renal secretion. 4 THERAPEUTICS. Quassia is probably the most active of all the simple bitters, and may be used whenever such remedies are indicated. In cases of seat-worms in children, a strong infusion of quassia (two ounces to one pint) affords a most harmless and efficient injection. Its exhibition should be preceded by an enema of simple water, after a stool, so as thoroughly to wash out the rectum and allow access to every fold of the rectal mucous membrane. The official preparations are a tinc- ture (TINCTURA QUASSIA twenty per cent., U. S. ), dose, twenty drops to a teaspoonful (1.2-4 C.c. ); an extract (EXTRACTUM QUASSI^E, U. S.), dose, one to three grains (0.06-0.19 Gm. ) ; and a fluid extract (FLUID- EXTRACTUM QUASSIA), dose, five to ten drops (0.3-0.6 C.c.). GENTIANA GENTIAN. U. S. The root of Gentiana lutea, or the yellow gentian of the Alps. This root occurs in the shops either in pieces of various sizes and shapes, but usually several inches in length, or else in transverse slices. The texture is spongy, the odor faint but peculiar, and the taste bitter. It contains gentisic acid, which was discovered by Leconte and is tasteless and physiologically inert. The active principle is probably the gentio- pikrin of Kromayer, a neutral, crystalline substance, of an intensely bitter taste. STOMACHICS. 623 THERAPEUTICS. Gentian is one of the most efficient of the simple bitters, and may be used whenever such a remedy is indicated. It is never given in substance, but in one of its preparations. These are the compound tincture (TINCTURA GENTIAN^E COMPOSITA ten per cent, U. S. ), which contains gentian, bitter orange peel, and cardamom, dose, one fluidrachm to half a fluidounce (4-15 C.c. ); the watery extract (EXTRACTUM GENTIANS, U. S. ), dose, two to four grains (0.13-0.26 Gm.); and the fluid extract (FUIDEXTRACTUM GENTIANS, U. S. ), dose, ten minims to half a fluidrachm (0.6-2 C.c.). The compound infusion, formerly official, was a valuable preparation, containing some alcohol, and much used in doses of one to two fluidounces (30-60 C.c.). CALUMBA COLUMBO. U. S. The root of Jateorhiza palmata, a climbing vine of Mozambique. It occurs in the shops in transverse disk-like slices, oval or circular in out- line, one or two inches in diameter, of a spongy texture, having a yellowish surface, a very bitter taste, and a slightly aromatic odor. It contains a great deal of starch, besides berberine, and, it is said, in lesser amount, columbin, a bitter neutral principle crystallizing in rhomboid prisms or needles. F. Roux 5 has found that columbin given to pigeons in doses of ten centigrammes produces death, preceded by failure of the appetite, marked signs of gastro-intestinal irritation, and jaundice. THERAPEUTICS. A bitter, slightly aromatic tonic, useful as a sto- machic in cases in which a simple bitter is indicated. It is not used in substance. Its preparations are a tincture (TiNCTURA CALUMB^E ten per cent. > U. S. ), dose, one to two fluidrachms (4-7 C.c.), and a fluid extract (FLUIDEXTRACTUM CALUMBA, U. S. ), dose, fifteen minims to half a fluidrachm (1-2 C.c.). CHIRATA, U. S. , the herb and root of Swertia chirata, a plant grow- ing in the northern part of India, is one of the best of the simple bitters, and is believed by some to exert a peculiar influence over the liver. Whenever a simple bitter is indicated, this drug may be employed, espe- cially if a cholagogue action be desired. The solid extract is an excellent preparation in doses of one to two grains (0.06-0.12 Gm. ); dose of the fluid extract (FLUIDEXTRACTUM CHIRATA, U. S. ), five to ten minims (0.3-0.6 C.c. ); of the tincture (TINCTURA CHIRAT^E ten per cent., U. S.), a fluidrachm (4 C.c.). BERBERIS, U. S. Barberry. The root and berries of the Berberis vulgaris of Europe have long been used abroad as a simple laxative tonic, and the U. S. Pharmacopoeia recognizes the rhizome and roots of B. Aquifolium and other species. These plants depend for their slight medical activity upon the presence of berberine (see Hydrastis) and other feeble alkaloids. They have been used in atonic dyspepsia, espe- cially when attended with hepatic torpor ; and also as alteratives in con- 624 LOCAL REMEDIES. stitutional syphilis. Dose of the fluid extract (FLUIDEXTRACTUM BER- BERIDIS, U. S. ), thirty minims (2 C.c. ). PRUNUS VIRGINIANA WILD CHERRY. U. S. Wild cherry bark is the product of Prunus (Cerasus) serotina or wild cherry tree, not of Prunus Virginiana or choke-cherry, whose name it bears. It occurs in pieces of various sizes, usually without epidermis. The color is a reddish cinnamon ; the taste slightly astringent, bitter, and peculiar, resembling that of peach-leaves. It contains tannic acid, bitter extractive, a nitrogenous, crystallizable, odorless glucoside (^Amygdalin), and an albuminous principle (^Emulsin). When amygdalin in watery solution is brought in contact with emulsin, it is decomposed, forming prussic and formic acids and a colorless, thin, volatile oil, which, when pure, has a peculiar, agreeable odor and a burning taste. According to Liebig and Wohler, 6 seventeen grains of amygdalin yield one of hydro- cyanic acid : therefore, if thirty-four grains of amygdalin be mixed with sixty-six grains of an emulsion of sweet almonds, a two per cent, (by weight) solution of hydrocyanic acid will be formed. PHYSIOLOGICAL ACTION. Amygdalin is physiologically inert, as much as sixty grains having been taken without result. Fifteen grains may cause death in the rabbit, but this is owing to its being converted into prussic acid by the emulsin contained in the green herbage in the stomach of the rabbit.* THERAPEUTICS. In wild cherry bark properly administered there are three active ingredients, tannic acid, bitter extractive, and prussic acid. The amount of prussic acid is too small to cause perceptible effects, so that wild cherry bark is simply a feeble astringent and tonic. It has been very largely used in phthisis, and has been supposed not only to act as a tonic and astringent, but also to exert a calmative influ- ence on the nervous system. The dose of the infusion (!NFUSUM PRUNI VIRGINIANS four per cent., U. S. ) is one to two wineglassfuls (60-118 C.c.). The syrup (SYRUPUS PRUNI VIRGINIANS fifteen per cent, U. S. ) is practically inert, but is often employed as a vehicle. The dose of the fluid extract (FLUIDEXTRACTUM PRUNI VIRGINIANS, U. S. ) is from one-half a fluidrachm to a drachm (2-4 C.c.). OREXIN. Phenyldihydrochinazoline Hydrochlorate , or Orexcz Hydrochlorate. This complex derivative of quinoline occurs as colorless, odorless crystals, with bitter pungent taste : freely soluble in hot water. Originally brought forward by F. Penzolt as a true stomachic it has been variously reported upon by clinicians. Ac- cording to the general reports, and especially to the experiments of Hofmann, it is practically nontoxic, two grains per pound weight not being sufficient to kill a rabbit, although after enormous doses free haemoglobin appears in the blood. Orexin hydrochlorate has, however, been entirely superseded by the orexin tannate, a yellowish, tasteless, odorless powder, insoluble in water but freely soluble in acid solutions, and consequently in the gastric juice. There seems to be little doubt but * See Husemann (Die Pflanzenstoffe). STOMACHICS. 625 that orexin tannate is a valuable gastric stimulant in all those cases in which a simple bitter is indicated, and that it is contra-indicated by gastric inflammation or hyper- acidity, and by gastric ulcer. It is stated, also, to be effective against the vomiting following the use of opium, chloroform, and other narcotics, and also in the vomiting of pregnancy. It is chemically incompatible with iron salts. Dose, five to twelve grains, one to two hours before meals. Owing to the insolubility of the salt it is much better to give it in powder than in tablets. AROMATICS. The aromatic oils are essentially local irritants, causing when taken into the mouth intense burning pain, and when confined upon the skin, rubefaction, blistering, and finally, if the contact be very prolonged, more destructive changes. Internally, taken in very large doses, they cause burning pain in the stomach, increased activity of the circulation, and a species of intoxication. In sufficiently large quantities they are irritant narcotic poisons. When administered in therapeutic doses they act almost exclusively upon the alimentary canal. As compared with that of the simple bitters, their influence is more powerful and more tran- sient. They do not permanently increase the digestive power, but sim- ply increase action for the time being. They are employed chiefly to increase the immediate stimulant effect of bitter tonics upon the secretory digestive glands ; as carminatives, to stimulate the intestines to contract upon and expel flatus ; to prevent the griping of purgatives ; to disguise the taste of medicines, and to render nauseating drugs acceptable to the stomach ; and to act as condiments and aid in the digestion of the food. It is probable that aromatics directly after their ingestion affect more powerfully the digestive glandular apparatus than do bitter tonics, since Gottlieb 7 has shown that such substances as mustard, which are local irritants to the stomach, cause a very marked increase in the secretion of the pancreatic fluids. Even when the gland had almost ceased its function, oil of mustard introduced into the stomach or duodenum caused active secretion in the pancreas. Quassia, taken as a type of the bitters, had no effect on the pancreatic activity. Injected into the circulation, most volatile oils lower the blood-press- ure by depressing the heart's action, and even in comparatively small doses may cause immediate diastolic arrest. In this respect oil of cloves is one of the most powerful. Their cardiac action is undoubtedly direct and upon the heart itself : other muscular structures would seem to be similarly affected, as H. Kobert 8 has found that the oil of mace directly lowers muscular excitability. When in concentrated form almost all of the volatile oils are direct paralyzants to nerve-tissues, and seem to act especially upon the sensory and peripheral nerve-endings ; hence most of them are local anaesthetics, and some are used for this purpose in practical medicine. Most of them also possess antiseptic properties. Some of the tonic drugs containing a volatile oil also have in them a bitter principle which modifies their action. Such drugs may be known 40 6 2 6 LOCAL REMEDIES. as aromatic bitters ; as bitters they are less powerful than such drugs as quassia, and are especially indicated when the stomach is delicate and easily nauseated. Inflammation of the stomach or bowels is the chief centra-indication to the use of aromatics. Unlike the simple bitters, they are often very useful in diarrhcea of nervous irritability or of relaxation, when no decided inflammation exists. CINNAMOMUM. The U. S. Pharmacopoeia recognizes the barks of undetermined species of the genus Cinnamon and the CINNAMOMUM SAIGONICUM, or Saigon Cinnamon, which comes from Cochin China ; it also recognizes Ceylon Cinnamon, the bark of the Cinnamomum zeylani- cum. Much of the cinnamon of the markets comes from China and is known as Cassia Bark, or Chinese Cinnamon. Of these barks the Ceylon is considered the finest and the Cassia the poorest in quality. They all contain tannic acid and a yellowish volatile oil (OLEUM CINNAMOMI, U. S. ) which, on account of its great fragrance and very pleasant taste, is largely used, in doses of from one to three drops (0.06-0. 1 8 C.c. ), as an adjuvant or to disguise the flavor of less agreeable drugs. Oil of cinnamon contains seventy-five to ninety per cent, of Cinnamic Aldehyde Cinnaldehydum, U. S. , which may also be prepared synthetically. It is a colorless, aromatic liquid, having the same medical properties as has the oil itself. Cinnamon water (AQUA CINNAMOMI oil 0.2 per cent., U. S. ) is used solely as a vehicle. The spirit of cinnamon (SPIRITUS CINNAMOMI oil ten per cent., U. S. ) is administered in doses of one-half to one fluidrachm (2-4 C.c.); the tincture (TiNCTURA CINNAMOMI Saigon Cinnamon twenty per cent., U. S. ) in doses of one to two fluidrachms (4-7 C.c.). PULVIS AROMATICUS. U. S. Aromatic Powder (cinnamon, ginger, cardamom, nutmegs) is an elegant carminative in doses of from ten to twenty grains (0.6-1.3 Gm. ). FLUIDEXTRACTUM AROMATICUM. U. S. Aromatic Fluid Extract is a concentrated tincture of aromatic powder, 15 minims (i C. c. ) of which represent 15 grains (i Gm.) of the powder. CARYOPHYLLUS. U. S. Cloves are the unexpanded flowers of Eu- genia aromatica, a tree growing in the Molucca Islands. OLEUM CARYO- PHYLLI, U. S. , is an exceedingly pungent, yellowish, volatile oil, be- coming dark by age, which, besides being used as a carminative and an aromatic, is often employed to benumb sensitive dentine, or even exposed pulp, in caries of the teeth. Dropped on a piece of cotton and placed in the cavity, it will frequently cure toothache. Oil of cloves is chiefly composed of an unsaturated phenol, EUGENOL, U. S. , which is a colorless or yellowish thin liquid, having the odor and taste of cloves, and becoming on exposure to the air dark and thick. It may be used for the same purposes as is the oil of cloves. Dose of oil STOMACHICS. 627 of cloves or of eugenol, one to four minims (0.06-0.24 C.c. ). Clove tea, two drachms to the pint, an infusion made with boiling water, is often used domestically in doses of a wineglassful or more for acute menstriial sup- pression and as a sudorific. MYRISTICA. U. S. Nutmeg is the kernel of the fruit of Myristica fragrans, a tree growing in the Molucca Islands. The nutmeg contains both a fixed and a volatile oil. Mace (U. S. P. 1890) is the arillus or outer imperfect supernumerary coating of the seed. :Both mace and nutmeg depend for their activity upon the volatile oil (OLEUM MYRIS- TIC^E, U. S. ) which, when injected intravenously into the lower animals, causes loss of coordination, tremors, profound coma, abolition of all re- flexes, and finally death from respiratory paralysis, its influence upon the circulation being comparatively feeble.* In man, one or two nutmegs will usually suffice to produce a dreamy, half-unconscious intoxication, and severe or even fatal poisoning has been caused by larger quantities. The symptoms of poisoning have been dizziness, stupor deepening into coma, muscular relaxation, dilated pupils, slow pulse and respiration, and suppression of urine, ending in death from respiratory paralysis, f Dose, of oil, ten to twenty drops (0.61.2 C.c.). In animals fatally poisoned fatty degeneration has been found (Wallace. ) PIMENTA. U. S. Pimenta, or Allspice, is the unripe berries of Pi- menta officinalis, a tree, native in the West Indies. Dose of the volatile oil (OLEUM PIMENT^E, U. S. ), two to five drops (0.12-0.3 C.c.). CARDAMOMUM. U. S. Cardamoms are the fruit of Elettaria repens, which grows in the East Indies. They consist of tough, seemingly fibrous, generally more or less triangular dry and tasteless capsules, con- taining a number of small, hard, very aromatic seeds. The colorless, highly aromatic, volatile oil is not official. Cardamom is a very grateful aromatic, much less stimulating and heating than most of the other drugs of its class. The dose of the tincture (TINCTURA CARDAMOMI twenty per cent., U. S.) is one fluidrachm (4 C.c.). The compound tincture (TiNC- TURA CARDAMOMI COMPOSITA two per cent., U. S.) is a very elegant addition to, or vehicle for, tonic medicines ; dose, one to two fluidrachms (4-7 C.c.) ZINGIBER. U. S. Ginger is the dried rhizome or root-stock of Zin- giber officinale, growing in the East and West Indjes. Green Ginger is the fresh rhizome. Black Ginger is the root-stock dried with the * Experiments of H. C. Wood ; also Cadeac and Meunier (Journ. Med. Vet., Lyons, 1890). t Fatal case, N. Y. Med. Record, Nov. 1886. Collection of Cases, George B. Wallace, C. M. R. V., 362. 628 LOCAL REMEDIES. epidermis on ; White or Jamaica Ginger is the same, deprived of its epidermis. The fresher ginger is the greater is its power, and by time and exposure it becomes completely inert. Its active principles are a soft, acrid, aromatic resin, and a yellow, volatile oil. Ginger is much used in domestic medicine as a stimulant carminative in colic; given in hot water, it is also used as a sudorific and stimulant in the pain due to suddenly suppressed menstruation. It is often added with advantage to other remedies in dyspepsia. The syrup (SYRUPUS ZINGIBERIS three per cent. , U. S. ) is used only as a cordial drink or vehicle, in doses of from half a fluidounce to a fluidounce (15-30 C.c. ). The tincture, often called Essence of Ginger (TINCTURA ZINGIBERIS twenty per cent., U. S. ) , is the most commonly employed preparation ; the dose is half a teaspoonful to a teaspoonful (2-4 C.c.). The dose of the fluid extract (FLUIDEXTRACTUM ZINGIBERIS, U. S.) is five to ten drops (0.3-0.6 C.c.). The oleoresin (OLEORESINA ZINGIBERIS, U. S.) is used as a stimulant addition to tonic pills ; the dose is from half a minim to two minims (0.03-0.12 C.c. ). PIPER. U. S. Black Pepper is the unripe fruit of Piper nigrum, a woody vine-like plant growing in the East Indies. White Pepper is the ripe berries stripped of their skin and dried. It is much less pungent than the black pepper. The active principles of black pepper are a soft, acrid resin, a pungent, fiery, volatile oil, and piperin. In 1819 Oersted discovered Piperin (PIPERINUM, U. S.), which crys- tallizes in colorless, glistening, four-sided, truncated prisms, of a neutral reaction, but capable of combining with acids to form salts. When pure it is tasteless ; but very commonly it has a burning taste, due to the presence of some of the volatile oil of pepper. The possession of very active antiperiodic properties has been asserted for piperin, and it was for a time employed in intermittent fever ; but it has fallen into complete disuse. The dose as an antiperiodic is four grains (0.26 Gm.), repeated once or twice during the interval between the paroxysms. Pepper is very largely used as a condiment ; but, as its taste is more hot than aromatic, it is rarely given internally in medicine except as an addition to simple bitters or to antiperiodics, generally in the form of the oleoresin (OLEORESINA PIPERIS, U.S.), the dose of which is one-half to one grain (0.03-0.06 Gm. ). In atonic dyspepsia the latter preparation is an excellent adjuvant to tonic pills. Schiffer is said (Fliess) to have used piperin successfully in a case of vaginismus, by injecting three-tenths of a grain (0.018 Gm. ) hypodermically near the vaginal entrance. In using piperin by hypodermic injections it is of the utmost importance to see that it is free from the oil of pepper. CAPSICUM. U. S. The U. S. Pharmacopoeia now recognizes only the small, less than an inch long, very fiery fruit of Capsicum fastigiatum, the African Pepper, or Chillies. The large, bright red, conical or ovate, STOMACHICS. 629 comparatively mild peppers of the market are from C. annuum ; they are sometimes known as West India peppers. Capsicum contains as its active principle an exceedingly acrid oleoresin.* Capsicum is a very powerful local irritant, its oleoresin when applied to the skin producing in a very few minutes intense pain and redness, and finally destroying the cuticle. In the alimentary canal it acts in a similar manner : thus, moderate doses produce merely a pleasant feeling of warmth in the stomach, while overdoses may cause gastro-intestinal inflammation, with severe pain, as well as vomiting and purging, followed after a time by strangury and other evidences of genito-urinary irritation. The chief use of Cayenne Pepper is as a condiment ; yet it is often added with advantage to tonic pills to increase their immediate action on the stomach. When there is habitual feeble digestion, with flatulence, its free use on food may do good. In adynamic diseases, especially as occur- ring among drunkards, capsicum is often very useful by stimulating the stomach up to the point of digesting food. Locally, either as the diluted tincture in a gargle or applied in powder or tincture by means of a swab, it is useful in severe tonsillitis, especially in that accompanying scarlet fever. The dose of capsicum is four to five grains (o. 26-0. 3 Gm. ) in pill ; of the very efficient oleoresin (OLEORESINA CAPSICI, U. S. ), from one- quarter to one-half a minim (0.0160.032 C.c. ) ; of the tincture (TiNC- TURA CAPSICI ten per cent., U. S. ), one-half to one fluidrachm (2-4 C.c. ) doses to drunkards; of the fluid extract (FLUIDEXTRACTUM CAPSICI, U. S. ), one-half to one minim (0.03-0.06 C.c.). OLEUM CAJUPUTI. U. S. The Oil of Cajuput is obtained from the leaves of Melaleuca leucadendron, a tree growing in the Molucca Islands. This volatile oil is of a green color, a peculiar fragrant odor, and a burn- ing, camphoraceous taste. It is not very irritating to the skin, but is exceedingly destructive to low forms of life, and consequently has been used as a parasiticide externally, and even internally against the Ascar- jdes. In intestinal pain and spasm and in serous diarrhoea it is efficient, especially in combination with chloroform, camphor, and opium. As a counter-irritant, it has been used in rheumatism ; as a stimulant to the skin, in psoriasis, acne rosacea, and pityriasis. Dose, from ten to fifteen drops (0.6-1 C.c. ). OLEUM SASSAFRAS. U. S. The Oil of Sassafras is largely used in the arts on account of its cheapness and pleasant flavor. It is capable of producing very marked narcotic-poisoning, 9 and is said to act upon the lower animals as a convulsant and narcotic. John Bartlett 10 asserts that it is capable of inducing uterine contractions, and reports cases of abor- tion caused by it. AURANTII AMARI CORTEX Bitter Orange Peel. U. S. The fluid extract (FLUIDEXTRACTUM AURANTII AMARI, U. S.) and the tinc- * The name of Capsicin has been applied by different observers to the oil, to the resin, and to their combination, but has no definite meaning. 6 3 o LOCAL REMEDIES. ture (TINCTURA AURANTII AMARI twenty per cent., U. S. ) may be given respectively in doses of twenty minims (1.2 C.c. ) and a fluidrachm (4 C.c. ). AURANTII DULCIS CORTEX Sweet Orange Peel. U. S. Of the syrup (SYRUPUS AURANTII five per cent., U. S. ) the dose is a dessertspoonful (7 C.c.), of the tincture (TINCTURA AURANTII DULCIS fifty per cent., U. S. ), a tablespoonful (15 C.c.). The orange peels are themselves scarcely medicinal, but are official as affording prepara- tions much used as vehicles. LIMONIS CORTEX, U. S. , or Lemon Peel (SPIRITUS LIMONIS five per cent., U. S. ), is also used for flavoring purposes. AURANTII FLORES. The flowers of the orange are official for the preparation of Orange Flower Water (AQUA AURANTII FLORUM, U. S. ), which is used as an elegant vehicle, free from medicinal properties. The fruits of the following umbelliferous plants Foeniculum capil- laceum, Carum carui, Coriandrum sativum, and Pimpinella anisum are official under the respective names of FCENICULUM (fennel), CARUM (Caraway), CORIANDRUM {Coriander), and ANISUM (Anise). They all depend for their virtues upon volatile oils which are official. The oil of anise of commerce is largely the product of a Chinese tree, the Illicium anisatum, or Star Anise, from whose five- to ten-rayed capsular fruit it is obtained by distillation. The AQUA FCENICULI (o. 2 per cent. ) and the SPIRITUS ANISI (ten per cent.) are official. All of these fruits and their preparations may be used as carminatives and stomachics. The herbal portions of the following mints are official : Salvia offi- cinalis, Mentha piperita, Mentha viridis, and Melissa officinalis. They are respectively known as Sage (SALVIA), Peppermint (MENTHA PIPERITA), Spearmint (MENTHA VIRIDIS), and Balm (MELISSA). The important U. S. preparations of them are as follows : AQUA MENTH^E PIPERITJE {Peppermint Wafer) and AQUA MENTHA VIRIDIS (Spearmint Water), both very frequently used as vehicles. SPIRITUS MENTHA VIRIDIS and SPIRITUS MENTH^E PIPERIT^E {Essence of Spearmint and Essence of Peppermint), used as carminatives, in doses of from ten to twenty drops (0.6-1.2 C.c. ). The oils of lavender,* peppermint, and spearmint are * Masoin and Bruylant have studied to some extent the physiological action of the oils of lavender, rosemary, marjoram, and aspic (Lavandula spica L.) (Bull. Acad. Roy. Med. de Bruxelles, 1879, 558; see also Schmidt's Jahrb., clxxx. 123, and Cadeac and Meunier, Compt.-Rend. Soc. Biolog., 1889, and Lyon Med., 1889). In frogs they caused generally paralysis, with loss of reflex activity, the muscles being intact, and the sensory nervous apparatus being affected before the motor. Upon the higher animals a similar effect was produced, except that oil of rosemary caused epileptiform convulsions. Oil of Peppermint ( M. piperita) has been studied by S. D. Markuson (Inaug. Dis., Halle, 1877; Schmidt's Jahrb., clxxx. 122), who finds that while very small doses in- crease, larger ones decrease the blood-pressure and lower the bodily temperature. Most of the volatile oils have germicidal properties, and the oil of peppermint has been highly praised as a practical dressing for burns, wounds, etc. (See The Medical Reporter of India, vi.) STOMACHICS. 631 also official, and may be used in doses of from three to ten drops as car- minatives. The oil of peppermint has been long used in China as a local application in neuralgia and subacute rheumatism, and is sometimes very effective in relieving pain. It should be applied to the part until the burning is no longer endurable, when it may be removed and petro- latum applied. (See also MENTHOL.) SPIRITUS LAVANDUL^E {Spirit of Lavender), a very elegant and agreeable stomachic and cordial, is made by dissolving oil of lavender flowers in alcohol. Dose, a fluidrachm to half a fluidounce (4-30 C.c. ). Sage contains tannin. Water of Rosemary has long been believed to have especial influence upon the skin, and in cases of acne a lotion composed of a pint of this water and an ounce of the flowers of sulphur has been often effective. AROMATIC BITTERS. ANTHEMIS. U. S. CHAMOMILE. Roman or true Chamomile, the dried flowers of Anthemis nobilis, a composite of Europe, contains a bluish or sometimes greenish volatile oil, a bitter principle, and a small amount of tannin. The infusion (one ounce to a pint) is a mild stomachic in doses of one to two wineglassfuls. MATRICARIA, U. S. , or German Chamomile, the flowers of Matricaria Chamomilla, is much less agreeable and effective. SERPENTARIA. U. S. Virginia snakeroot, the root of Aristolochia Serpentaria and of A. reticulata, small herbal plants of the United States, contains a volatile oil, a yellowish-green resin, and a bitter principle. It is an elegant stimulant tonic, especially useful as an adjuvant to more powerful bitters. The dose of the tincture (TINCTURA SERPENTARIA twenty per cent., U. S. ) is one to two fluidrachms (4-7 C.c.); of the fluid extract (FLUIDEXTRACTUM SERPENTARIA, U. S.), twenty drops (1.2 Gc). REFERENCES. STOMACHICS. 7. GOTTLIEB .... A. E. P. P., 1894, xxxiii. , - - 8. KOBBKT ..... AE. P. P, XV. . I V, 89 * 5 ; B'G T c'uiT-o 10. BARTLBTT .... Chi. M. J.. Dec. :88 5 . J ROUX ....... C.' R.' S. B., 1884, i. 33- BORISSOW .... A. E. P. P.. 1904. H. 3f>3- 6. LIEBIG and WOHLER . Ann. Chem. Pharm.. xxii. i. FAMILY II. EMETICS. EMETICS are those drugs which are employed in the practice of medi- cine for the purpose of producing emesis, or vomiting. Vomiting occurs under two provocations, or in two manners. Thus, a mental impression, or a disordered state of the blood, may influence the nerve-centres directly, and emesis, spoken of as centric, results ; or a peripheral irritation in the stomach itself, or in some other organ, as in the kidneys, may induce vomiting precisely similar in the method of its production to the more ordinary reflex movements ; such vomiting is called reflex or excentric. Emetics produce their results in both of these methods. Thus, tartar emetic has been believed to affect the centres directly, so as to cause centric vomiting, while copper sulphate has been believed to irri- tate the mucous membranes of the stomach, so as to produce reflex vomiting. Much doubt, however, has .been thrown upon the old views, and it is probable that most emetics have a double influence. Thus, the purging of veratria or of tartar emetic is almost certainly connected with its elimination, and is probably due to a direct action of the circu- lating poison upon the intestinal mucous epithelium, gland-cells, and peripheral nerves. It seems a priori almost a necessity that the vomit- ing caused by these poisons is produced in the same way as is the purging. D'Ornellas has found that when emetine is injected into the veins of animals the vomiting occurs simultaneously with the elimination of the alkaloid from the gastric mucous membrane, and asserts that Klei- mann and Simonowitsch have determined the same thing with antimony. Further, antimony seems to cause vomiting partly by acting upon the centres, partly by irritating the peripheral nerve. Irritant emetics are more prompt than those which chiefly affect the nerve-centres ; they always cause less nausea and general systemic disturbance than do the centric emetics. Another evident practical fact is, that while centric emetics will act in whatever way they are introduced into the system, the mechanical emetics must be exhibited by the stomach. Thus, apomorphine may be given by hypodermic injection, but mustard must be taken by the mouth. Nevertheless, it is probable that most of the so-called ' ' irritant emetics' ' act in part by being absorbed, since A Sacher l has found that even zinc sulphate will, when injected in proper dose into the blood, produce 632 EMETICS. 633 vomiting, and Brunton and West have demonstrated that a peptone of copper injected into a vein causes violent vomiting. A very curious property of emetics has been pointed out by E. Harnack,* who, as the result of an elaborate investigation, affirms as a law that all specific emetic substances destroy, even when in relatively small dose, the excitability of striated muscular fibre. Harnack seems to establish the general truth of this ; but that it is a universal law is scarcely probable, and the connection between the two properties is very obscure. According to H. Kobert,* antimony has an effect on muscle-fibre only when the contact is prolonged. In regard to the phenomena of vomiting, there are a few points to which it is necessary here to call attention. First of these is the fact that nausea always produces, or is accompanied by, muscular relaxation. Vomiting may take place, as from mustard, without much relaxation ; but when it is accompanied by much nausea the whole system is, as it were, unbent, the skin relaxed and bedewed with perspiration, the pulse soft and feeble, the muscular system limp and incapable of exertion, and the mental acts almost suspended. During violent vomiting the blood is driven to the head, so that the whole exterior of the cranium, and prob- ably the interior also, becomes very much congested. The abdominal circulation is greatly affected, and the blood is, as it were, squeezed out of the portal vein and its tributaries. The matters rejected consist of the contents of the stomach, and, in repeated vomiting, also those of the duodenum. The secretion from the gastric mucous membrane is very much enhanced, and without doubt is more or less modified. Bile in ejecta is to be recognized by the green color and the bitter taste, or more infallibly by testing with the proper reagents. The indications for the use of emetics are as follows : 1. To unload the Stomach. For this purpose they are employed in poisoning, or when the stomach is oppressed by indigestible substances or by its own acrid, perverted secretions. The symptoms induced by irritating materials in the stomach are various, and sometimes it requires a good deal of tact or experience to recognize their cause. Among them may be mentioned a feeling of weight or load in the stomach, gastric distress, or severe cramp or spasmodic pains, with or without some nausea and retching. In other cases no local manifestations of trouble may be present. Thus, convulsions in children are very fre- quently the result of gastric irritation, and are at once relieved by empty- ing the stomach. In adults, apoplectiform coma may offer a similar his- tory. Occasionally urticaria, or hives, and not rarely severe headache, have a similar origin, and require a similar treatment. 2. To affect the Abdominal Viscera and Circulation. In congestions of the portal circulation, especially such as follow a debauch, and in the condition of digestive derangement known as biliousness, emetics are often of service. In catarrhal jaundice they may effect much good by causing dislodgement of the mucus plugging the ducts. They have 634 LOCAL REMEDIES. been employed in cases of biliary calculi ; but the chances of forcing out the calculus by external violence are probably no greater than those of lethal rupture of the gall-bladder. 3. To dislodge Substances from the Respiratory Passages. For this purpose emetics are sometimes used when foreign bodies have found entrance into the larynx ; but it is chiefly in membranous croup that the present indication is met with. The emetics chosen for this purpose should be such as act with violence without producing much nausea or systemic disturbance : the mechanical emetics are therefore the best. 4. To produce Muscular Relaxation. The introduction of anaesthesia has rendered the use of emetics to meet this application almost obsolete. Occasionally, however, in asthmatic or other spasmodic affections of the respiratory organs, emetics are still employed. For this purpose the drugs causing much nausea are preferred. In adults, lobelia is the best ; in children, ipecacuanha. Nauseating rather than emetic doses should be employed. Contra-indications. The chief contra-indications to the use of emetics are the existence of congestion of the brain and of gastric inflammation. Advanced pregnancy, and hernia, while they do not positively centra- indicate the use of emetics, should cause great caution to be practised in their employment. ADMINISTRATION. Emetics should, as a general rule, be given in a full dose, so as to avoid unnecessary repetition, and should be adminis- .tered dissolved in water or in syrup. Their action should be assisted by frequent and copious draughts of tepid water, which also have the advantage of rendering the vomiting less painful. When for any reason protracted nausea is desired, the doses should be small and repeated at short intervals. Hyperemesis may advantageously be divided into two varieties : first, such as is due to overdoses of depressing centric emetics ; second, such as arises from irritation of the stomach, as by mechanical emetics. The treatment of the first of these consists in the enforcement of absolute quiet in the horizontal position, the free use of opium enemata, the application of counter-irritants to the epigastrium, and the use of alco- holic stimulants. The latter should be given in hot water, and should not be too much diluted. We have seen raw brandy arrest at once the most alarming centric emesis after the failure of other methods. Cocaine, creosote, chloroform, or chloroform and volatile oils are sometimes of value in this form of hyperemesis. When excessive vomiting is due to some irritant substance, the stomach should be thoroughly washed out by large draughts of warm mucilage, opium given by the rectum, a mustard plaster or blister, or, often better still, leeches applied to the epigas- trium, and no medicine at all be taken into the inflamed viscus. The swallowing of small pieces of ice is sometimes of service. If these remedies fail, the treatment of this form of hyperemesis soon resolves itself into that of gastritis. EMETICS. 635 CENTRIC EMETICS. IPECACUANHA. U. S. The U. S. Pharmacopoeia recognizes the Cephaelis Ipecacuanha, growing in Brazil, and the C. acuminata, growing in Colombia, plants whose roots respectively constitute the Rio, Brazilian, or Para ipecac - Tianha, and the Carthagena ipecacuanha. There is at present no sufficient reason for believing that these plants are specially distinct. (See U. S. Dispensatory, igth edition.) The true ipecacuanha plant has been culti- vated with success in the Straits Settlements, producing the so-called Johore ipecacuanha. The South American drug comes from wild plants exclusively. The ipecacuanha roots differ largely in the total percentage of the alkaloidal contents, hence the requirement of the U. S. Pharmacopoeia that they should contain at least two per cent, of aggregate alkaloids. It has been believed by various authorities that the Rio and Carthagena ipecac- uanhas because in the former emetine, in the latter cephaeline, predomi- nates are not interchangeable; but the reports of the large drug firms both in Europe and in this country indicate that the individual roots of either vary as much in the proportionate percentage of emetine and cephaeline as do Rio and Carthagena ipecacuanha, and that, therefore, these two ipecacuanhas may be considered as therapeutically identical. It is clear that apothecaries furnish to physicians the two varieties of ipecacuanha indiscriminately. Practical differences in their action have not been made out by clinicians ; and the belief of some experimentalists that when an emetic effect is desired Carthagena is best, and when an expectorant effect is wished Rio ipecac should be used, is not well founded.* Ipecacuanha occurs in pieces two or three lines in thickness, variously bent and con- torted, marked on their surface with numerous prominent rings, and com- posed of an outer, thick, active, hard, and horny cortex, and an inner, light, inert, woody centre. The root has very little odor, but the brown powder has a decided and peculiar smell, and in some persons excites sneezing, or even violent asthmatic dyspnoea. The taste is bitter, acrid, and nauseous. The alkaloid (emetine) found in 1817 by Pelletier in ipecacuanha is now known to be composed of three alkaloids, emetine, cephaeline and psychotrin. The emetine of the older physiological inves- tigators is this alkaloidal mixture. In the text of this book it is spoken of as crude or commercial emetine. Ipecacuanhic acid, with which the alkaloids are combined, according to Kimura, 27 is practically inert, although when brought in contact with the red blood-corpuscles outside of the body it dissolves out the haemoglobin. * According to the experiments of Carl Lowin emetine is only a feeble emetic, whilst <:ephaeline is a very powerful emetic. On the other hand, cephaeline does not act upon the lungs at all, so that the emetic influence of ipecacuanha is dependent upon the pres- ence of cephaeline, its expectorant influence upon the presence of emetine. 636 LOCAL REMEDIES. Local Action. Absorption and Elimination. Locally applied, ipe- cacuanha is a decided irritant, manifesting its action not only upon mu- cous membranes and upon denuded surfaces, but also causing, when applied by inunction, an eruption of small, discrete pustules, with a rather large areola, followed, it may be, by large pustulation and even severe ulceration. Both pure emetine and cephaeline were found by Lowin to be very irritant, and especially so to mucous membranes. Ipecacuanha rapidly yields its active principles to absorption. They are probably eliminated by the stomach, intestines and kidneys, but concerning this we have no definite knowledge.* PHYSIOLOGICAL ACTION. When given in small repeated doses to man, ipecacuanha produces malaise, with nausea, and perhaps an increase of the secretions of the salivary glands and of the mucous membranes of the bronchial tubes and of the stomach. In large amounts it causes vomiting, accompanied by only a moderate amount of nausea, but by a decided increase of the secretions mentioned above. The vomiting, even when very large amounts are taken into the stomach, is not apt to be severe, nor the prostration marked. The general physiological action of ipecacuanha is extremely feeble, although its alkaloids are certainly very active substances. The differ- ence is probably due to the fact that ipecacuanha is rejected from the stomach before it can be taken in sufficient dose to yield poisonous amounts of its alkaloids to absorption. According to D'Ornellas, 4 toxic doses of commercial emetine cause in the frog diminished sensibility, muscular feebleness deepening into abolition of voluntary movement, with at first increased and afterwards diminished activity, and finally death from failure of respiration; in the mammal, similar symptoms, with the addi- tion usually of severe vomiting. Nervous System. Respiration. Circulation. According to D'Or- nellas and Pecholier, commercial emetine exerts no influence upon the cerebrum, but acts powerfully upon the motor side of the spinal cord, in the frog killed with it both nerve and muscle retaining their suscepti- bility to feeble galvanic currents (D'Ornellas, Pecholier and Foulkrod. 5 ) It causes death by respiratory paralysis, which is probably of centric origin. The action of commercial emetine upon the circulation appears to be feeble, since Dyce Duckworth has shown that the fall of arterial pressure which the crude alkaloid produces does not occur until late in the poisoning. The fall is chiefly of cardiac origin, as it is prevented by previous section of the spinal cord (Foulkrod). Moreover, fatal immediate cardiac paralysis may be caused in the dog by injection of half a grain into the jugular vein. Further, Lowin w has found that pure emetine and pure cephaeline dimmish the rate and strength of the contraction of the isolated frog's heart, cephaeline being the feebler of the two alkaloids. Psychotrin had no distinct effect. Lowin also found that both cephaeline and emetine paralyze the heart in warm-blooded animals. * According to Maurel (Merck's Bericht, 1901) the lethal dose of emetine on the pigeon and rabbit is 0.15 gramme per kilo. Maurel also states that emetine acts upon the rabbit as a local anaesthetic. EMETICS. 637 Pulmonic and Digestive Organs. As emetine injected hypoder- mically causes vomiting, ipecacuanha must be looked upon as a centric emetic ; but the observation of D'Ornellas, that the emetine produces vomiting much more slowly when thrown into the veins than when given by the stomach, indicates that the local irritant action of the drug is a factor in the production of emesis. The great influence of the drug upon the abdominal viscera is further shown by the fact, attested by Pecholier, Dyce Duckworth, and D' Ornel- las, that in emetine-poisoning, although there is a distinct fall of tempera- ture in the mouth and on the surface of the body, in the intestines the temperature either remains stationary or, more commonly, rises. Again, the changes found after death from emetine are almost exclusively in the lungs and digestive organs. Pecholier, in his earlier experiments, found great paleness of the lungs, with intense hyperaemia of the stomach and the upper half of the intestines, but in some of his later experiments the lungs were profoundly influenced. Dyce Duckworth es- pecially noted intense hyperaemia of the lungs, which were in some places emphy- sematous, but in other portions collapsed and even affected with true consolidation. The lesions were much less marked in the intestines than in the lungs, which re- sembled very closely those taken from the bodies of animals killed by section of the vagi. The pulmonic lesions were found to be most intense in the rabbit ; the intestinal, in the dog, cat, and guinea-pig. Magendie first observed, years ago, the pulmonic lesions of emetine-poisoning, and D'Ornellas has likewise recorded them, but has also seen cases in which ischaemia of the pulmonary tissue was found after death. It is evident that the commercial alkaloids of ipecacuanha have a special influence upon the intestines and the lungs, but it has been a mystery why this influence should vary so in power, especially in regard to the lungs. Carl Lowin finds that the chemically pure alkaloid produces almost equal influence on the gastro-intestinal mucous membranes; but that, whilst cephaeline acts violently upon the lungs, after death from pure emetine no pulmonic changes are to be found. It would seem, therefore, that the different results obtained by earlier observers have depended upon the alkaloids they have used being really varying mixtures of the two alkaloids. THERAPEUTICS. Whenever it is desired to unload the stomach or to act by emesis upon disease, without inducing much prostration, ipecac- uanha is the best of the emetics. In narcotic poisoning it is less certain than the "mineral emetics," but, as it produces no irritation of the stomach, it can be given more freely than they can, and is constantly used as an adjuvant to them. It is especially useful in the diseases of children, never causing the serious depression which tartar emetic is so apt to produce. When, however, very violent emesis is desired, as in membranous croup, other emetics, such as zinc sulphate, are to be pre- ferred on account of the greater force of their action. In sick stomach of nervous origin, such as occurs in pregnancy, minute 638 LOCAL REMEDIES. doses of ipecacuanha have so often met with success that there can be no doubt of their value. One drop of the wine in a teaspoonful of water should be given every fifteen minutes. The use of ipecacuanha as an expectorant will be spoken of under that heading. One of the most important uses of ipecacuanha is in acute dysentery, all forms of which have been treated with it with asserted advantage. Its beneficial action is most obvious in bilious dysentery and in malignant dysentery, as is indicated by the fact that its use is most common in tropical climates. In sthenic inflammatory dysentery it seems to be less available, although even in this it has been strongly advocated. In a valuable clinical paper, A. A. Woodhull 6 brings forward strong evidence of the value of the remedy not only in dysentery, but also in choleriform diarrhoeas. It has likewise been used with great success in hepatic torpor and other forms of abdominal glandular derangement. It probably influences not only the intestinal glands, but also the liver, since Pe- cholier * affirms that in animals killed by it no hepatic glucose can be found. More- over, great advantage from its use may often be obtained in the condition known as biliousness. In bilious dysentery it will often produce large tarry discharges ; a change in the color of the stools sometimes follows its use in catarrhal jaundice. The mechanical effect of the vomiting induced by it in these cases, however, must not be lost sight of ; yet it does not seem to us sufficient to account for the results, especially as some observers state that the effects noted are produced even when little or no vomiting occurs. It has been proved by D'Ornellas and Pecholier that when emetine is introduced into the circulation or into the cellular tissue it escapes with the secretions of the stomach and bowels ; so that the changes which are pro- voked in these organs are evidently connected with the elimination of the drug. In 1890 Surgeon-Major Harris 8 used in dysentery the ipecacuanha root, de- prived of its emetine, with alleged excellent results. His paper has given rise to considerable discussion, and Surgeon-Captain Walsh, 9 as the result of his experi- ments, came to the contrary conclusion that the value of ipecacuanha in dysentery depends upon its emetine, and devised a method of giving emetine in combination with biniodide of mercury, affirming that in this combination the drug does not pro- duce vomiting. Other clinicians, however, have confirmed the statements of Sur- geon-Major Harris. When the ipecacuanha root has been de-emetinized it fails to produce vomiting, or causes only very slight vomiting ; and according to the clinical studies of Kanthack and Caddy, 10 it has all the curative effects of ipecac- uanha in dysentery, and does not cause depression. The freedom from alkaloid of this so-called de-emetinized ipecacuanha seems to us very doubtful.* As a h&mostatic, ipecacuanha has been recommended by Trousseau, and Pecholier " asserts that in hcemoptysis it is a specific, f It has been given with asserted advantage v& flooding after child-birth, and Carrigen 11 asserts that it possesses oxytocic powers. ADMINISTRATION. As an emetic, ipecacuanha is generally adminis- tered in powder, thirty grains (2 Gm. ) being given every fifteen or twenty minutes until the desired effect is produced. For a child a year * See especially A. A. Woodhull (Atlanta Med. and Surg.Journ., 1875). t Consult Pacific ^fed. and Surg.Journ., 1876. EMETICS. 639 old the emetic dose is five grains (0.3 Gm.). Its action should be aided and hastened by large draughts of lukewarm water. As a nauseant the dose is from two to five grains (0.130.3 Gm. ). In dysentery it is generally best to begin with a full emetic dose, or with ten grains repeated every half-hour until emesis is produced. Two or three hours after vomiting, fifteen drops of laudanum should be exhibited, followed in twenty minutes by five to ten grains of ipecacuanha in pill form ; this should be repeated every two or three hours, the amount of the opium being lessened, and that of the ipecacuanha increased, according to circumstances. The object is to have as much of the ipecacuanha re- tained as possible. Another plan is to give larger doses (twenty grains), repeated every two, four, or six hours, mustard being applied to the epigastrium and opium exhibited as before ; and it is said that after two or three doses tolerance is established and the drug retained. In India, enemata of ipecacuanha are often employed, either as a substitute for or an adjuvant to its use by the mouth. This treatment has recently been imitated by Chouppe " and others, and in our own practice found to be satisfactory. It undoubtedly often succeeds in dysentery and choleriform and chronic diarrhoeas, and the gastric symptoms are almost always avoided. In chronic cases the repetition of the enemata sometimes pro- duces so much local irritation as to forbid their continuance. We have been accustomed to give a scruple of the powder with starch and lauda- num, repeated every four hours. A decoction of the drug is to be pre- ferred, as probably causing less local irritation and being more thoroughly absorbed. To an adult, Chouppe gives daily two injections of a decoc- tion, each lavement representing two and a half drachms of the drug. As a counter-irritant, ipecacuanha is rarely used in this country ; but in England a liniment is employed composed of four parts of the powder to fourteen parts of olive oil. The preparations for internal use are : a syrup (SYRUPUS IPECACU- ANHA seven per cent., U. S. ), dose, as an expectorant, five to twenty minims (0.3-1.3 C.c. ); a wine (ViNUM IPECACUANHA ten per cent, U. S.), emetic dose, four fluidrachms to a fluidounce (15-30 C.c.); and a fluid extract (FLUIDEXTRACTUM IPECACUANHA, U. S. ), dose, as an emetic for an adult, thirty drops (2 C.c. ). TROCHISCI IPECACUANHA, and TROCHISCI MORPHINE ET IPECACUANHA, formerly official, were used in catarrh of the throat as a local application. Emetine has been used in doses of from one-twelfth to one-sixth of a grain (0.005-0.01 Gm. ), but it is very harsh and without advantage in its action. APOMORPHIN^E HYDROCHLORIDUM APOMORPHINE HYDRO- CHLORIDE. U. S. Apomorphine, discovered by Matthieson and Wright," occurs as a snow-white powder, which is permanent when dry, but when moist or in solution soon becomes green, and finally almost black. 640 LOCAL REMEDIES. General Effects. In man, apomorphine acts as a prompt emetic, the vomiting being accompanied by no symptoms of such nature as to be at all characteristic of the drug, unless it be excessive secretion from the salivary, nasal, and lachrymal glands. Very rarely great cardiac depres- sion has been produced, but there is reason to suspect that this has been due to decomposition products. PHYSIOLOGICAL ACTION. Local Action. The soluble salts of apo- morphine, when pure, are not irritant, and when used hypodermically should not cause pain. They are absorbed with great rapidity. Con- cerning their elimination we have no definite knowledge. In frogs, one to five milligrammes of apomorphine cause restlessness, followed by an increasing sluggishness and muscular weakness that may end in real or ap- parent death. In some instances there are violent convulsions, both clonic and tonic in character.* Sometimes recovery occurs after both respiration and cardiac action have apparently ceased. In dogs, one to two milligrammes cause vomiting, without any other decided symptoms ; after slightly larger amounts, the vomiting is severe, and accompanied by free salivation and muscular tremblings. After very large doses, vomiting does not occur, but a condition of intense restlessness, the animal jumping, running, howling, and champing constantly. The slightest noise or alarm throws the animal into violent excitement and terror ; with pupils dilated and ears drawn stiffly back, he endeavors to get out of the apartment, and even to climb the wall. After still larger amounts (four or five grains), to this excitement is soon added failing mus- cular strength, and the hind legs are dragged behind the animal in his movements. The respiration is exceedingly hurried, and convulsions are suddenly developed. The paresis and convulsions increase, so that the animal lies upon his back, kicking wildly into the air, and finally dies asphyxiated. Rabbits cannot vomit, but the general symptoms produced by the alkaloid in them and in cats are exactly parallel with those just described as occurring in the dog. Very small doses (ten milli- grammes, Harnack) suffice to kill the rabbit. On chickens and pigeons, according to C. David, 15 it acts very much as it does upon dogs ; the stage of excitement is very marked. After death no distinct lesions are to be found, unless, as Quehl 16 believes, there is habitually an excessive hyperaemia of the pons Varolii. To the therapeutist the chief interest in apomorphine is in connection with its power of producing vomiting ; but before taking this up we shall briefly review what is known in regard to its general actions. Nervous and Muscular Systems. The action of apomorphine upon the cerebrum seems to be that of a primary stimulant delirifacient and final paralyzant. The cause of the convulsions at present cannot be consid- ered as determined. f According to Reichert's experiments, both the sensory and motor nerves are first stimulated and afterwards paralyzed. In opposition to the experiments of Quehl, Harnack " found that apo- morphine directly affects the voluntary muscles, and as his experiments * G. Valentin (Arch.f. Exper. Path. u. Pharm., xi. 399). t The only one who has carefully studied them is Reichert, and his published account is self-contradictory. He reasons that the convulsions are chiefly spinal, and yet says that in mammals, after section of the spinal cord, except "in very exceptional cases," they are confined to the anterior part of the body. EMETICS. 641 have been confirmed by Reichert, there can be no doubt that apomor- phine is a muscle-poison. Circulation. The reports upon the action of this drug on the cir- culation are somewhat discordant. It appears to be proved that the therapeutic dose does not affect the blood-pressure, but, contrary to the statements of Seibert, 18 Max Quehl, and Bourgeois, 19 it has been shown by Harnack and by Reichert w that the toxic dose does lower the arterial pressure and is a direct paralyzant of the cut-out frog's heart. Reichert has shown that the mammalian heart is similarly affected by the drug, and the final fall of pressure must be at least in part of cardiac origin. Reichert states that preceding the fall of pressure there is a distinct rise, which is prevented by previous section of the cord, and is, therefore, probably due to stimulation of the vaso-motor centres. The pulse-rate is markedly increased by small and large doses of apomorphine, the maximum usually being reached about the time vomiting is fairly estab- lished ; subsequently, in poisoning, the pulse falls below normal. Reichert believes the rise to be due to stimulation of the accelerators, and the fall to the influence upon the heart-muscle. Respiration. Usually the respiration-rate is increased by decided or toxic doses. During the convulsive period of the poisoning the respi- rations become irregular and unequal, and they finally grow more and more shallow and infrequent, until death results from a paralysis of the respiratory centres. Both Harnack and Reichert have noted that in the rabbit previous section of the par vagum does not prevent, but rather increases, the respiratory acceleration ; Reichert affirms that in the cat and dog no increase of the respiration-rate occurs under the action of the drug if the pneumogastrics have been cut. Temperature. The action of apomorphine upon the temperature appears to be very trifling and inconstant. According to Ziolkowski," the bodily heat usually falls after large doses from o. i to 0.5 G. Moerz noticed in one man that the temperature rose during the vomiting o. 2 ; while Bourgeois affirms that in man the drug has no influence over the temperature, and Reichert has seen in animals a rise follow the hypo- dermic but not the intravenous injection of the alkaloid. Emesis. Gee 22 was the first to announce that apomorphine is a cer- tain and prompt emetic, producing but little nausea, and having the great advantage of acting in very small dose, a tenth of a grain being sufficient, when injected under the skin, to cause vomiting in ten minutes. The time required for action depends largely upon the amount of the drug exhibited. After very small doses twenty minutes may elapse ; and in Bourgeois's experiments 0.45 grain produced violent vomiting in less than two minutes. After these large doses the emesis usually recurs once or twice at intervals of a quarter to half an hour.* The vomiting seems to be of centric origin, as. Reichert has succeeded in pro- ducing it when the thoracic aorta was tied so as to prevent any of the poison from reaching the stomach. 642 LOCAL REMEDIES. THERAPEUTICS Apomorphine is a safe and reliable emetic, and may be used whenever it is desired simply to empty the stomach. Apo- morphine has a tendency in bronchitis to cause free secretion, and is especially useful in the suffocative catarrh of infants, when an emetic is re- quired to get rid of the bronchial exudation. Under these circumstances it is said not only to act efficiently as an emetic, but also to render the mucus more copious and fluid. In the ' ' drunk wards' ' of some of the Philadelphia hospitals for the relief of acute debauch apomorphine is pre- ferred because the subjects habitually go to sleep directly after the vom- iting ceases. Tull M has found it useful in acute chorea. Probably because it has morphine in its name there was at one time a rather wide-spread belief that apomorphine was not a suitable emetic in narcotic poisoning. In fact, however, narcotics influence the action of apomorphine only as they do that of every other emetic, and if apomor- phine has any narcotic influence it does not interfere with its emetic action. Apomorphine may, therefore, be used in any poisoning : hypo- dermically given, it is often especially useful as a reinforcement of a me- chanical emetic exhibited by the mouth. ADMINISTRATION. As an emetic, apomorphine has usually been ad- ministered hypodermically, in doses of one-tenth of a grain (0.006 Gm.), repeated every ten minutes until some effect is induced ; but it may be exhibited by the stomach in double the amount. In cases of severe poisoning, where time is of great moment, it may be well to give as much as one-fourth of a grain (0.016 Gm. ) at a single injection. In feeble persons, however, caution must always be exercised in using it, as one-fifteenth of a grain has caused death in seven minutes in an adult, fifty-four years old, suffering from chronic bronchitis with marked em- physema. 23 The expectorant dose is one-sixteenth of a grain (0.004 Gm. ). Care must be exercised in its use in children. Loeb 24 gave hypodermically 0.03 grain to an infant, thirteen months old, suffering from capillary bronchitis : the free vomiting which was induced left the infant much exhausted. In a very few cases apomorphine has failed to vomit, and even caused startling symptoms : so that care should be ex- ercised not to push the remedy too far. Carville affirms that three-tenths of a grain has caused a syncopal condition in an adult, and Prevost** details a case in which syncope and threatening collapse were apparently induced by a very small dose. In children especially must care be exer- cised, since, according to Harnack, the drug is very liable to produce collapse. Greenish preparations of apomorphine should not be used unless the dose be very small. Constantine Paul states that if glycerin be used as the sole menstruum the solution will keep three or four days. Carville M affirms that glucose acts well as a preservative, and it is also asserted that a few drops of muriatic acid will suffice. * For the doses required to vomit various animals, see Gaz. Med., 1874, 467. EMETICS. 643 MECHANICAL OR STIMULATING EMETICS. The only drugs of prac- tical value in this group are mustard flour and zinc sulphate ; copper sulphate being so irritant as to be dangerous, and alum and other drugs sometimes used too uncertain in their influence. Mustard flour is very prompt and even violent in its action, and is to be used when it is desired simply to evacuate the stomach rapidly. As it is generally to be had at once, it is especially useful in such emergencies as narcotic poisoning. Dose, a heaped tablespoonful in half a pint of water, repeated, if necessary, in ten minutes. Zinc sulphate is a very sure emetic, much used in narcotic poison- ing, especially with ipecacuanha or apomorphine. Dose, thirty grains ( 2 Gm. ) dissolved in about two ounces of water : it may be repeated in fifteen minutes, if necessary, REFERENCES. EMETICS. T. SACHER Thesis, Dorpat, 1893. 3. HARNACK . . . . A. E. P. P., iii. 44. 3. KOBERT A. E. P. P., XV. 36. 4. D'ORNELLAS . . Gaz. Med., 1873, 537. 5. FOULKROD . . . P. M. T., viii. 554. 6. WOODHULL . . . Atlanta Med. Surg. Journ., 1875- 7. PECHOLIER . . . Gaz. Med., 1862. 8. HARRIS L. L., 1890, ii. 9. WALSH Indian Med. Gaz., 1891. 10. KANTHACK and CADDY . Pract., 1893. 11. PECHOLIER . . . B. G. T., xcvii. 49. 12. CARRIGEN . . . . N. Y. M. J., 1878, 491. 13. CHOUPPE . . . . B. G. T., June, 1874. 14. MATTHIESON and WRIGHT . Proc. Royal Soc., xvii. 455. 15. DAVID . . . :6. QUEHL . . 17. HARNACK . 18. SEIBERT . . 19. BOURGEOIS 20. REICHERT . 31. ZlOLKOWSKI 22. GEE .... 23- 24. LOEB . . 25. PREVOST 26. CARVILLE 27. KlMURA . 28. LOWIN . 29. TULL . . . Gaz. Med., 1874, 465. In. Dis., Halle, 1872. A. E. P. P., ii. 291. L. M. R., i. 44. . De 1'Apotnorphine, Paris, 1872. P. M. T., x. no. In. Dis., Greifswald, 1872. . St. Bartholomew Hosp. Rep., v. 215. N. Y. M. R., 1877, 664. . S. Jb., civ. 272. . L. M. R., 1875, 183. . G. H. M. C., 1874, 408. . A. I. P., 1903, xi. A. I. P., 1902. N. Y. M. J., March 11,1905. FAMILY III. CATHARTICS. PURGATIVES, or cathartics, are those drugs which are employed in medicine to produce purgation, or catharsis. The question whether they act by increasing the intestinal secretions or the peristaltic movements has been much discussed. Thiry l experimented upon the subject of catharsis by drawing out a knuckle of intestine through a wound in the linea alba, cutting it free from the remainder of the gut without injuring its nerves or blood-vessels, sewing together the distal and proximal ends of the main portions of the intestines so as to reform a continu- ous tube, and then, after closing up one end of the knuckle, forcing the other into the wound so as to make an intestinal cul-de-sac which could be studied through a fistulous opening. In dogs which had recovered after this operation, Thiry found that large doses of magnesium sulphate, of senna, or of croton oil failed alike to increase the secretion of the separated piece of intestine, although they induced violent purging ; further, that neither concentrated solutions of Epsom salt nor infusion of senna, even though kept in the cul-de-sac for some time, were able to increase its secretion by exosmose. More recently, S. Radziejewski 2 has made an elaborate investigation of the subject. As the result of a number of very careful analyses, he asserts that there is nothing to be found in the stools produced by magnesium sulphate, calomel, castor oil, croton oil, senna, or gamboge to indi- cate that they are anything besides the ordinary contents of the upper and lower bowels. Radziejewski confirms the fact observed by C. Schmidt, that the stools of purgatives contain a great deal of soda, but denies that this proves that they are transudations, asserting that the alkaline salts are derived simply from the pan- creatic fluid. Radziejewski also corroborates the confirmation by Asp 3 of the dis- covery of Moreau,* that division of the intestinal nerves is followed by free serous exudation into the gut, but denies that purgatives act by paralyzing the vaso-motor nerves, because croton oil injected into a loop of intestine which had been sepa- rated by two ligatures from the remainder of the gut caused both vomiting and purging. As no emulsifying substance was contained in the intestine, he declares that no absorption could have occurred, and that consequently the general intes- tinal disturbance was simply due to increased peristaltic action, caused by the internal local irritation of the oil propagated along the intestines. The experiments of Thiry have also been repeated by Radziejewski with croton oil and with mag- nesium sulphate, as well as by Schiff 4 with aloes, jalap, and sodium sulphate. In all cases the results were the same as those already noted as obtained by Thiry. Carrying his investigations still further, Radziejewski, by forming intestinal fistulae at such positions as would enable him to study the rate of passage of the intestinal contents, found that after a dog is fed upon flesh the small intestine empties the partially digested food into the colon so rapidly and in such quantity as to consti- tute, so to speak, a normal diarrhoea, and that the long delay in the exit and the hardening of the faeces occur in the large intestine. The liquid which passed into * Comptes-Rendus, 1868, Ixvi. ; also Asp (Ludwig's Arbeiten, 1868). 644 CATHARTICS. 645 the ascending colon agreed in all its characteristics with the stools of purgation. Radziejewski also asserts that he has established by direct experimentation that the peristaltic movements of the small intestine are affected very decidedly by drastics, and to some degree by Epsom salt, and that in all cases the large intestine is still more intensely acted upon. Although these experiments are very interesting, it cannot be allowed that they prove what is affirmed of them, namely, that purga- tives cause no increase of intestinal secretion, but only of peristaltic action. So much violence to natural conditions is done in the experiments after the method of Thiry that they seem to have very little weight. The assertion of Radziejewski, that croton oil confined in a loop of intestine is not absorbed, is a pure assumption, and his experiment does not warrant the conclusions drawn from it. The most that can be claimed is that these various researches show that increased peristalsis, especially of the large bowel, plays a more important role in the production of diarrhoea. The fact that previous section of the par vagum prevents the action of purga- tives* is opposed to the German theory, since it is almost certain that division of the nerves of the neck does not arrest peristaltic movements. Further, Armand Moreau 5 has found that a solution of Epsom salt placed in a knuckle of intestine isolated by means of two ligatures does cause a serous exudation into it, and in repeating M. Thiry's 6 experiments he has obtained opposite results. His experi- ments indicate three possible sources of fallacy in the work of the previous investi- gators : first, if the Epsom salt be not kept in the intestine for a sufficient length of time (some hours), no transudation occurs ; second, in some cases the inner end of the isolated piece of intestine fails to adhere, so that the opening is not obliter- rated, and the matters injected into the arrested cul-de-sac really pass into the peritoneal cavity ; third, atrophy of the mucous membrane and glandular apparatus of the cul-de-sac often follows almost at once upon the operation, and of course necessitates a negative result in the subsequent experiments. Lauder Brunton, 7 in a communication to the Medical Society of London, states that he has repeated Moreau's experiments, and found that magnesium sulphate injected into the in- testine of a cat caused about two-thirds of a drachm of fluid to be secreted in four hours by each inch of the bowel operated on, although the proportion of sul- phate was only one grain to an inch. In further experiments by Brunton, 8 gam- boge, elaterium, and croton oil gave results similar to those of the Epsom salt. Vulpian 9 has also repeated the experiments of Moreau, and found that both mag- nesium sulphate and jalap provoke a "true intestinal catarrh," the vegetable cathartic at the same time increasing the peristaltic action, but the saline having no such effect. The experiments of Legros 10 and of M. Van Braam Houckgeest " show that salines do not increase the activity of the peristaltic movements, whilst those of Matthew Hay 12 are thought by him to prove that a saline purgative always excites more or less secretion from the alimentary canal, depending on the amount of the salt and the strength of its solution, and varying with the nature of the salt. To all this evidence may be added the experiments of Arthur Clopatt, in which various purgative dnigs thrown into the gut failed to increase the pressure in a manometer which had been introduced into a loop of the intestines tied at both ends, showing that they did not increase the intestinal contraction ; and also those of Hess.t made by introducing into the duodenum, through a gastric fistula, a disten- * See paper by H. C. Wood {American Journal of the Medical Sciences, 1870, Ix). t Hess also states that when, by the blowing up of the ball in the intestine, sodium sulphate, castor oil, calomel, senna leaves, croton oil, and colocynth were prevented from passing into the lower intestine, they failed to purge, although when introduced below the obstructing ball by a narrow tube running through it they at once caused diarrhoea. These experiments, if confirmed, would prove that the purgatives mentioned must come in direct contact with the lower part of the small intestine to produce liquid stools. 646 LOCAL REMEDIES. sible ball, which could be blown up by the long tube attached to it so as to fill the intestine, and noticing the rate at which the ball moved under the influence of a peristaltic movement. In these experiments it was found that hydragogues like senna affected very slightly the peristalsis, whilst drastics like croton oil had a very distinct influence. J. Bruce MacCallum 60 believes that the action of salines on peristalsis is due to an influence on the nervous system, and is preceded by absorp- tion, because he found that the intravenous injection of certain saline substances caused in the rabbit increased peristalsis in from one-tenth to one-fifteenth of the time that is. required for the action of the same saline when introduced into the intestines. Also, that only one-fifth of the intestinal dose is required intravenously to produce effect. The experimental evidence is very far from demonstrating that in- creased peristalsis is the cause of the watery stools produced by purga- tives. The evidence, both experimental and clinical, is indeed over- whelmingly in favor of increased secretion. The facts proved by clinical observations and by experiment that purgatives increase greatly the se- cretion in an isolated knuckle of intestine, that various purgatives act when taken into the blood, and that in these cases elimination by the bowels occurs ; that at least some purgatives (Headland 14 ), when given by the mouth, are absorbed, disappearing from the alimentary canal and reappearing when purgation occurs ; that the stools induced by overdoses of various drastics, as elaterium, are so enormous as to cause the pro- foundest depression, and even choleraic collapse, in a very few hours ; that the discharges caused by hydragogues contain a large percentage of soda, the alkali of the serum ; that the relief obtained in portal con- gestion by the depletion of salines is very marked are, when viewed together, incompatible with any other belief than that purgatives cause both increased secretion and increased peristalsis in the alimentary canal. The question of the action of drugs upon the flow of bile is a very important one, the evidence concerning which is best considered under two headings : first, the experimental ; second, the clinical. The experiments upon this subject which have attracted most attention are those of Scott, and of the Edinburgh committee, of which Bennett was chairman and Rutherford and Gamgee the workers. The method employed both by Scott and by the Edinburgh committee was to make biliary fistula? in dogs in the usual phys- iological manner, and, after recovery from the operation had taken place and the bile regularly escaped by the external orifice, to administer the drugs, especially calomel and podophyllin, and study the effects upon the excretion of bile. Of the accuracy of their experiments we do not think that there can be any reasonable doubt. They prove that in dogs with biliary fistulae mercury has no effect upon the flow of bile unless given in such quantities as to deteriorate the general health, when it diminishes the biliary secretion. The result does not, however, warrant the further conclusion that mercury does not increase the flow of bile in healthy dogs. The animals were in such an unnatural condition that, in spite of the daily ingestion of much more than the normal amount of food, they progressively ema- ciated, and finally died apparently of inanition : moreover, the innervation and probably also the blood-supply of the liver was very much interfered with. Under CATHARTICS. 647 these circumstances it is clearly conceivable that the mercurial or other purgative might in the uninjured dog affect the biliary secretion, and yet fail to do so in the experiment, hindered by some obscure yet sufficient cause. A. Rohrig 15 experi- mented by a method which simulated more closely the natural conditions, although even the results which he thus obtained do not seem to us conclusive. In curarized dogs in which life was maintained by artificial respiration, he placed a glass tube in the gall-duct so that the bile could escape only through it. Under these circum- stances, of course, after a time secretion ceased ; and Rohrig experimented not only on the effect of remedies upon the secretion while it was naturally going on, but also on their power of re-establishing it. He found that large doses of croton oil (eigh- teen drops) thrown into the duodenum caused an immediate very great increase, or a re-establishment, of the secretion. After the oil, the vegetable cathartics were most active, decreasing in power in the following order : colocynth, jalap and aloes, rhubarb and senna. Castor oil had very little influence, as had also the bitter salts. Calomel, even in large doses (twenty grains), very rarely re-established the secre- tion, but its power of increasing and maintaining it beyond the natural time for cessation was very marked. W. Rutherford w used the method of Rohrig with some improvements. The drug, mixed with bile to facilitate absorption, was injected directly into the duo- denum by means of a hypodermic syringe. The results obtained may be briefly summarized as follows : Croton Oil in enormous doses neither purged nor affected the biliary secre- tion. Podophyllin very greatly increased biliary secretion, especially when in such small doses that it did not purge severely. Aloes very greatly increased biliary secretion, the doses used not purging greatly. Rhubarb, Colchicum, Iridin, Colocynth, Jalap, Sodium Sulphate, Sodium Phosphate, and Rochelle Salt very greatly increased biliary secretion, at the same time purging. Senna, Taraxacum, Scammony, Gamboge, Castor Oil, Magnesium Sulphate, and Ammonium Chloride acted very feebly, if at all, upon the liver. Leptandrin, Sodium Chloride, and Potassium Bicarbonate had some, but not a powerful, effect on the liver. Ewmymin, Sanguinarine, and Ipecacuanha exerted a very powerful influence on the secretion of bile, and did not purge. Calomel had no effect on the biliary secretion, but when to it a minute propor- tion of corrosive sublimate was added the effect was very marked ; Corrosive Sublimate acted as a very powerful biliary stimulant. There is one objection to the experiments of Rutherford and Vignal entirely independent of the method employed, i.e., there were rarely more than two experi- ments with any one substance, and in several instances two experiments gave an- tagonistic results. It is very possible, indeed probable, that if a number of experi- ments had been made with each drug, the variation in results would have been much greater. Prevost and Binet, in their experiments with dogs, arrange the drugs as follows : GROUP I. Substances augmenting greatly the flow of bile : oil of turpentine and its derivatives, potassium chloride, sodium benzoate and salicylate, salol, euonymin, muscarine. GROUP II. Substances slightly and inconstantly increasing bile : sodium bi- carbonate and sulphate, sodium chloride, Carlsbad salts, propylamine, rhubarb, hydrastis. GROUP III. Substances lessening bile : potassium iodide, calomel, strychnine. GROUP IV. Substances without action upon the secretion of bile : sodium phosphate, lithium chloride, corrosive sublimate, arsenic, alcohol, ether, glycerin, quinine, caffeine, calumba, senna, pilocarpine, kairin. 648 LOCAL REMEDIES. Rosenberg found that in dogs sodium salicylate increased the quantity and diminished the consistency of the bile ; that turpentine had a slight stimulant power; whilst the Carlsbad salts seemed to increase rather than decrease the biliary flow. Neutral oils had a much greater power of stimulating biliary secretion than any other food or drugs, with the single exception of oxgall. Stadelmann, 67 in a series of apparently very careful experiments on dogs, found that water, whether hot or cold, had no influence upon the amount of the fluidity of the bile. Alkalies, including the sodium chloride, sulphate, bicarbonate, and phosphate, and many potash salts, artificial Carlsbad salts, Epsom salts, and many other alkaline salts, never caused any distinct increase indeed, in most of them there was appar- ently a lessening in the secretion of the liver. Purgatives, including gamboge, jalap, convolvulin, rhubarb, aloes, podophyllin, calomel, etc., were equally without distinct effect. Diarrhcea of itself had no influence on the amount of bile. Atropine very distinctly, pilocarpine, alcohol and olive oil less distinctly, lessened the flow of bile. Antifebrin, antipyrin, caffeine, santonin, and oil of turpentine, had a feeble cholagogic action. The only substances which were found to possess any certain or powerful influ- ence in increasing the flow of bile were the salicylates, bile itself, or bile salts. The interpretation of this more or less contradictory experimental evi- dence is difficult, and its application to practical medicine almost hopeless. It is apparent in the first place that an animal with a biliary fistula is not in the same position as a normal animal. Further, the records of the experiments show that the secretion of bile in dogs having biliary fistula varies so frequently, so suddenly, and without apparent cause, that there is always much doubt how far the biliary condition which fol- lows the administration of the drug is due to that drug or to some aiding cause. When it comes to the application of these experimental results to human medicine, it must be remembered that the canine diet and digestion are so different from the human that it is to be expected that medicines acting upon the digestive apparatus will influence dogs differently from man : thus, doses of elaterium that would kill a man can be given to some of the carnivora without causing the slightest purging. In view of these facts, the only fairly deducible conclusion, in regard to the experimental evidence that has been brought forward, is, that it must be received with the greatest reserve or be entirely laid aside when we desire to study the question as to the cholagogic action of remedies upon man. We know of but two experiments upon human beings, these having been on persons suffering from biliary fistula. In the one case of human biliary fistula, William Bain M reached the conclusion that Kissingen water, Carlsbad water, euonymin, sodium benzoate, and sodium sali- cylate increased both the amount of bile and of its solids, whilst podophyllin resin increased the elimination of solids without affecting the absolute quantity of the bile. In the second case, Pfaff and Balch w found that the biliary secretion varied extraordinarily and inexplicably ; that it was apparently not affected either by calomel or corrosive sublimate ; that salol increases the watery flow and the solids of the bile distinctly ; but that oxgall had a very remarkable effect, increasing the amount of the bile as well as the percentage of its solid contents, the biliary acids being especially thrown off in extraordinary quantity. CATHARTICS. 649 It may well be that the putting aside of the gall bladder, and the other conditions created by the biliary fistula, has a distinct influence upon the liver ; certainly thus far experimental evidence, both in the lower animals and in man, hardly coincides with clinical evidence as to the action of drugs upon the liver (see Hydrargyrum, p. 658), but this apparent dif- ference may rest upon the different conditions of the subjects, as already pointed out. In regard to the drastics, there can be little doubt that almost any irritant purgative will to a greater or less extent increase the escape of bile, probably both by increasing its flow into the duodenum and by sweeping it out of the small intestine before absorption can take place. There are, however, two actively purgative substances of which it is es- pecially asserted that they are cholagogues, namely, calomel and podo- phyllin. The discussion of the action of these will be found under their respective headings. Violent purgation, whether produced by drugs, poison, or disease, has a distinct influence in checking the secretion of urine. In the ex- periments of Hugo Heinrichsen, 17 various vegetable cathartics affected the renal secretion much less than did salines, a result probably due to their being less actively hydragogue in their intestinal action. Hein- richsen further found that whilst the vegetable cathartics do not increase the solids of the urine, the salines have such influence ; but in Matthew Hay's experiments the amount of the normal constituents of the urine was not found to be affected by the salt, and it is probable that the urinary solids are increased only by the weight of the eliminated saline. Various divisions of purgative medicines have been proposed by dif- ferent authors, but probably the most convenient arrangement is as follows : 1. Laxatives. Medicines which simply unload the bowels, and are not able to cause active purgation, even when given in very large doses. 2. Purges. Medicines which purge actively, but are not capable of acting as poisons, even in very large amount. 3. Hydragogues (including the Salines), which produce very large watery stools without much irritation. In overdoses, medicines of this class assume some of the characters of those of the next. 4. Drastics, which cause great irritation of the alimentary mucous membrane, and in overdoses are violent poisons. It must be borne in mind that this classification is somewhat artificial ; that the effects of the remedies depend much upon the doses in which they are administered, so that in sufficiently minute quantity a drastic may act as a laxative ; and that the dividing lines between the groups are not distinct. Enemata. When it is desired simply to unload the lower bowels, the object can often advantageously be attained by injecting various materials into the rectum, so as, by mechanical distention or by irritating the 650 LOCAL REMEDIES. mucous membrane, to stimulate the peristaltic action. The simplest, least irritant, and least active enema is one of cold water. In cases of habitual constipation, especially when complicated with piles, the injection of a pint of cold water at a fixed hour daily often acts most kindly. The ordinary ' ' opening injection' ' consists of a pint of water and a tablespoon- ful, each, of salt, molasses, and soft soap ; castor oil is often added to it, and, if it be desired to make it very active, a teaspoonful of oil of tur- pentine. Large Enemata. Except in individuals of extreme nervous irrita- bility, there is little difficulty in filling the large intestine with water, and sometimes the fluid can even be made to enter the small intestine. The greatest gentleness should always be practised, a forcing syringe never being used. The apparatus should consist of a rectal tube, and an ordi- nary india-rubber tube, four feet long, fitted to the rectal tube and to a funnel, india-rubber bag, or other receptacle. The patient should lie upon his back with the hips elevated, or in the knee-chest position, so that the pelvis may be much higher than the shoulder. The rectal tube having been introduced into the rectum, the end with the receptacle containing water is to be raised vertically. It is essential that the tube be fitted with a cock, or be pinched, so as to regulate the passage of the liquid. In this way from five to nine pints are readily injected. Unless it is especially desired to get the effect of cold or heat upon the intestine, the water in the receptacle should be about 100 F. Large enemata are especially valuable as affording a means of locally treating the intestines. Very frequently in dyspepsia, chronic constipa- tion, and other functional diseases of the digestive organs, the large in- testine habitually contains scybala, fecal matters, acrid secretion, or other irritant substances, whose removal two or three times a week by means of simple water or water impregnated with half a drachm of sodium bicarbonate to the quart brings great relief. In dysentery, chronic or acute, and in pseudo-membranous colitis or enteritis, by means of the large enemata, local application can be made to the colonic mucous membrane. In this way, in acute dysentery, water, antiseptics, germicides, bismuth subnitrate, and other appropriate remedies can be used. In chronic dys- entery, one drachm of silver nitrate dissolved in half a gallon of water is often of the greatest service. As originally recommended by Mosler, these injections are sometimes very useful against intestinal parasites. In this way especially may they be used against the oxyuris vermicularis , which often inhabits the whole of the large intestine. In bad cases of seat-worm, the large injection should always be employed. In obstinate cases of tape-worm, when the worm has been weakened, and partially or completely expelled from the small intestine under the influence of vermicides given by the mouth, filling the colon with a medicated solution often brings success. Some- times a saturated solution of salt suffices, or quassia may be employed. Mosler records as especially effective a tablespoonful of chlorine water CATHARTICS. 651 to every pint and a half of water. A. Rohrig 18 having found that in- testinal injections of water have a very great influence over the secretion of bile, Mosler has been led to try forced enemata in catarrhal and other jaundices, with asserted good results. HYPODERMIC PURGATION. Apocodeine is the only known substance which appears to have practical value as a purgative when given hypoder- mically. It seems to be moderately effective, producing soft but not numerous or very watery stools: it is probably not effective when the constipation is obstinate, and not sufficiently drastic or hydragogue in its action to be of value in cases of severe diseases of the brain when counter- irritation through the intestinal tract may be desired. From one-third to one grain of the hydrochlorate may be injected with proper antiseptic precaution. According to W. E. Dixon, 61 podophyllo-toxin given hypodermically purges actively, but produces severe local inflammation and sloughing at the point of in- jection. Apparently the first to notice that apocodeine had the power of increasing intestinal peristalsis was Guinard. After him, Toy 63 determined that when it was given by the mouth or hypodermically it acted as a laxative ; and Raviart 61 and Berlin in a number of cases found the injection of thirty minims (2 C.c.) of a one per cent, watery solution of apocodeine hydrochlorate produced soft stools without any other disturbances except some pain and diffused redness at the place of injec- tion. W. E. Dixon 61 determined by experiments upon the lower animals that apocodeine lessens blood-pressure by dilatation of the blood-vessels and increases intestinal peristaltic action. Heinze M has used the remedy in a large number of cases. He finds the dose of 2 c.c. of a one per cent, solution is usually insufficient, and that the strength of the injection may be increased to two or even three per cent. ; and in the latter dose is almost certainly effective, in some cases the effect continuing several days. No narcotic influence was perceptible, but in a number of cases there was distinct irritation at the place of injection. Fronmuller 19 says that one to three grains of Merck's aloin dissolved in hot water, administered hypodermically, act as an efficient purge ; R. Kohn * states that in his hands aloin of three different commercial varieties, hypodermically ad- ministered in ten times the dose employed by Fronmuller, failed to act. In 1881, as the result of an elaborate investigation, A. Hiller " reached the conclusion that whilst there are four purgatives, namely, aloin, cathartic acid, and the pure colo- cynthin and citrullin of Merck, which are capable of purging when given hypo- dermically, they are all too irritant for practical use ; a conclusion which was con- firmed by Kohlstock.** According to Meyer, the irritant action of Barbadoes aloin is largely due to the precipitation in the subcutaneous tissue of insoluble and ex- tremely irritating crystals of the drug, and may to a considerable extent be over- come by the use of formamide as a vehicle. Kohlstock affirms that aloin or ca- thartic acid acts much better when given by rectal injection than when admin- istered hypodermically.* * The following formulae are recommended by Kohlstock for rectal use : Acid, ca- thartic, e senna, gr. iii ; aq. dest. gr. vii ; natr. bicarb, ad react, alkalin., q.s. Colo- cynthin, gr. i ; alcohol, gr. xii ; glycerin, gr. xii. Citrullin, gr. ii ; alcohol, gr. xlix ; gly- cerin, gr. xlfcc. Aloin, gr. xv ; formamide, ^\\. For rectal use a solution of aloin in glycerin may be substituted. Kohlstock gives the full purgative dose by the rectum as aloin 15 grains ; cathartic acid, 6 grains ; colocynthin, 0.04 grain ; citrullin 0.02 grain. Some of these doses seem to us distinctly dangerous. 652 LOCAL REMEDIES. The indications to fulfil which cathartics are used are as follows : i. To unload the Bowels. It is not necessary, in a work like the present, to say anything about the evil results of retained fecal matter, but only to point out the methods of relief. Before this can be done to advantage, however, a summary of the causes of constipation is required. Constipation may be well divided into acute and chronic. Acute or temporary constipation is that which occurs under special, transient cir- cumstances, as in convalescence from acute disease, and in pregnancy. It is to be relieved by the use of laxative articles of diet, and, this not sufficing, by laxatives or purgative medicines. It should never be for- gotten that acute constipation is sometimes due to organic affections of the alimentary canal, such as enteritis or intussusception, or is caused by mechanical obstacles, such as a hard foreign body or an enormous gall- stone. It is evident that such cases are not simple constipation, that the treatment required is essentially different from that of the latter affection, and is various according to the lesion. For the diagnosis and treatment of these diseases the reader is referred to works on the practice of medicine. Chronic constipation may be due to sedentary habits of life ; to habitual overwork, especially of the nervous system ; to a de- ficiency of intestinal secretion and of peristalsis, apparently natural to the individual and without obvious cause ; to long-continued voluntary habit of restraining the desire to go to stool ; to lead or other forms of poisoning ; and to diseases of the nervous system producing a paralytic state of the intestinal muscular fibres. It is evident that in the treat- ment of these various forms of constipation due regard must be paid to the cause, which should always, if possible, be removed. There are also certain cardinal principles which apply to the treatment of all forms of chronic constipation. They are as follows : A voluntary effort at defecation is to be daily made at a fixed hour, whether the desire exists or not. Medicines are to be avoided as far as possible, a sustained effort being made to regulate the bowels by means of diet. In very many cases the daily use of enemata of cold water, with attention to diet, suffices to attain the desired result. If medicines become necessary, as small an amount as will suffice, and the mildest drugs, are to be used. Purgatives or laxatives are at best merely temporary devices, and if abused in costiveness increase the trouble. So far as can be, the attempt should be to produce a per- manent impression, an alteration of the intestinal glandular action or peristalsis. Thus, when atony of the muscular coat exists, strychnine, or, according to comparatively recent experiments and clinical observa- tions, Calabar bean, may be employed ; if the hepatic or other glands are habitually torpid, nitro-muriatic acid may be administered. When constipation is attended by low spirits and a coated tongue, it is almost always due to a deficiency of secretion, and may be looked CATHARTICS. 653 upon as a form of dyspepsia : in such cases nitro-muriatic acid is espe- cially valuable, but sometimes a mild mercurial course seems almost imperative. A second use of cathartics under the present indication is to remove offending materials, as indigestible or irritant food, foreign bodies, acrid discharges, etc. In many cases of indigestion with undue fermentation in the alimentary canal a brisk cathartic does great good by producing the expulsion of micro-organisms. The possible importance of this is shown by the experiments of Gilbert and Dominici, 23 who found that a single dose of a saline caused in a healthy man the expulsion of over four hundred and eleven billion organisms. 2. To deplete. On account of the large serous flow which they pro- duce, the hydragogue cathartics when freely exhibited cause a very decided general depletion. Local depletion by means of cathartics is called for in congestion of the portal circulation, as well as in dysentery and other acute intestinal inflammations. Under the first of these conditions may, we think, be included without violence cases of so-called torpidity of the liver, which will be discussed in the article upon calomel. In acute intestinal inflam- mations the salines are to be preferred when depletion is desired, as they produce large serous discharges and are not irritant. 3. To promote Absorption. By emptying the blood-vessels the ca- thartics favor the absorption of the exuded fluid in general dropsy. For this purpose the hydragogues, and especially elaterium, are the best purgatives. The production of catharsis is the surest method of relief in general dropsy, also in ascites ; in other forms of local effusion its effects are less marked. As, however, purgation is the most ex- hausting of all the plans employed for the cure of dropsy, due regard must always be had to the strength of the patient. It is frequently necessary actively to support or even to stimulate while it is being carried out. 4. To remilse. The long tract of the alimentary canal affords a great extent of surface upon which to practise revulsion in certain brain dis- eases, as in mania and rheumatic or gouty irritation of the cerebrum. In hyperczmia of the brain, purgatives do good by depleting as well as by acting as revulsives. The drastics should be preferred. 5. To eliminate. It cannot be doubted that the use of purgatives in such diseases as fevers and cholera, with the idea of eliminating some materies morbi, rests simply upon a crude, unproved, and probably false pathology. In rheumatic disease and in gout it is more prob- able that they do good in this way, although it is by no means certain that the advantage derived from their use is not simply due to deple- tion. In cases of retained renal secretion, the evidence is very decided that they do aid in expelling the products of retrograde metamor- phosis. 654 LOCAL REMEDIES. LAXATIVES. As has been already stated, constipation should always, when possi- ble, be overcome by laxative food. There are two qualities by virtue of which food is laxative. Chief of these is bulk. All aliment which con- tains a large amount of innutritious material affords a large residuum, which, by distending the intestine, stimulates peristalsis. Contrariwise, articles of diet which are highly nutritious and afford but little residuum are constipating. This holds good, more or less strictly, among the lower animals. Thus, the flesh-eating carnivora are habitually consti- pated, the grass-eating herbivora very generally lax. Owing to its containing so little of the innutritious portion of the grain, the finest white flour favors a costive habit, while the "cracked wheat," in which the whole grain is eaten, is laxative, as to a still greater degree is bran, which is com- posed almost wholly of the husk of the wheat, the least nutritious portion of it, and therefore leaves a large residuum after digestion. Cracked wheat is boiled into a sort of jelly-like mass, and eaten with cream and sugar, while bran is taken in the form of bran bread, bran crackers, or bran mush. Unbolted flour, containing the whole of the grain, is about equal to cracked wheat, and is often made into bread. Indian meal, in the form of cakes or of mush, is highly nutritious and somewhat laxative ; oatmeal is decidedly laxative, scarcely so much so as bran, but much more nutritious. When it agrees with the stomach, and is digested, it is prob- ably the best of all these laxative articles of food. As the oats produced in south- ern climates are very inferior, care should be taken to procure oatmeal manufac- tured from Northern grain. It should be thoroughly cooked, and is best eaten in the form of a thick porridge. In dyspepsia all of these articles sometimes disagree with the stomach and cannot be used. Some dietary articles seemingly possess dynamic laxative powers, i.e., they exert a direct action which is not mechanical, but is similar to, although far less active than, that of the true purgatives. They intensify the intestinal action. Chief among substances of this class are molasses (SYRUPUS Fuscus) and it scongener, brown sugar ; white sugar (SAC- CHARUM, U. S.) probably does not share these laxative powers ; sugar of milk (SACCHARUM LACTIS, U. S. ) is probably also nearly inert. Of course, great care is usually necessary in taking advantage of the laxa- tive virtue of molasses, on account of the danger of producing fermenta- tion and acidity in the primae viae. There are certain foods which combine the two methods of action spoken of. Chief among these are the fresh acidulous fruits such as apples, pears, etc. and the dried fruits. Of the latter, the fig (Ficus, U. S. ) is one of the most palatable, and, owing probably to the great number of small seeds which it contains, is the most efficient. Prunes, U. S. , are as agreeable as figs. To a limited extent the finest varieties of them may be eaten raw ; but they are especially to be recommended stewed. When it is necessary, a pinch of senna-leaves may be cooked with them, so as to increase their activity without affecting their flavor. Among constipating articles of diet, it is only necessary to call atten- tion to milk as one of the most decided of the class. CATHARTICS. 655 MANNA. U. S. An exudation of the European ash, Fraxinus Ornus, chiefly produced in Sicily and Calabria. The best quality, flake manna, occurs in unequal, rough, stalactite-like pieces with a crystalline or gran- ular fracture. Manna has a slight odor, a sweet, mawkish taste, and should contain from forty to eighty per cent, of the saccharine, active, crystalline principle, manmte, which differs from ordinary sugar in the relation between the amounts of hydrogen and oxygen, and is not readily convertible into grape sugar or its derivative, alcohol. It is a gentle laxative, in large doses sometimes causing flatulence and pain; rarely used by itself, it is often added to purgative infusions. The laxa- tive dose for an adult is half an ounce to two ounces ( 1 5-60 Gm. ) ; for a child, one to four drachms (4-15 Gm. ) in an aromatic infusion. FRANGULA. U. S. The bark of Rhamnus frangula, one of the buck- thorns of Europe, is considerably used abroad as a laxative. Its active principle is a glucoside, frangulin ; a fluid extract (FLUIDEXTRACTUM FRANGUL^E, U. S. ) is official, dose, ten to twenty minims (0.6-1.2 C.c. ). In this country it is employed very rarely, but the bark of Rhamnus Purshiana, or California buckthorn, is very largely used under the name of Cascara Sagrada (RHAMNUS PURSHIANA, U. S. ). It con- tains a glucoside, purshianin, closely allied to frangulin, and often acts most happily as a laxative in habitual constipation. Fifteen drops ( i C. c. ) of the fluid extract (FLUIDEXTRACTUM RHAMNI PURSHIAN^E, U. S.) may be given one or two hours after meals, or half a fluidrachm (2 C.c.) may be administered at bedtime, or of the aromatic fluid extract (FLUID- EXTRACTUM RHAMNI PURSHIANA AROMATICUM, U. S.), one to two fluidrachms. The solid extract (EXTRACTUM RHAMNI PURSHIANA, U. S. ) is effective in doses of two to five grains (0.13-0.3 Gm. ). FEL Bovis. U. S. The United States Pharmacopoeia recognizes crude Oxgall, and prepares from it by means of alcohol FEL Bovis PURIFI- CATUM {Purified Oxgall}, a yellowish-green, soft solid, having a peculiar odor, and a partly sweet and partly bitter taste. It is very soluble in water and in alcohol. When taken internally in large doses it is a feeble laxa- tive. There is much experimental evidence (see page 645) to show that oxgall has marked influence upon the secretion of bile, and the clinical evidence is strongly in favor of the belief that in that condition known as chronic biliousness, full doses of oxgall often act very favorably. We have also used it in catarrhal jaundice with apparent excellent results. Dose, five to twenty grains (0.33-1.3 Gm. ), best given in capsule. EUONYMUS, U. S., or Wahoo, the bark of Euonymus atropurpureus, was found by Noel Paton, 24 when given to dogs in small dose, to increase greatly the elimina- tion of urea and uric acid, and by Rutherford to be in large dose an active chola- gogue in dogs. In man its effects are often most happy in cases of habitual consti- pation and hepatic torpor. It acts very slowly and purges only moderately. The dose of the extract (FLUIDEXTRACTUM EUONVMI, U. S. ) is eight minims (0.5 C.c.); 656 LOCAL REMEDIES. of its extract (EXTRACTUM EUONYMI, U. S. ) the so-called euonymin (the best prep- aration), two to four grains (0.13-0.26 Gm.) : in cases of dyspepsia it may be repeated with good results two or three times a week. LEPTANDRA. U. S. The rhizome and roots of Veronica virginica, when given in a fresh state, are apparently cathartic, but in their officinal dried form are mild and less certain. They are believed by various practitioners to have special cholagogue properties, and in Rutherford's experiments upon dogs the impure resin acted feebly upon the liver. The U. S. Pharmacopoeia recognizes the fluid extract (FLUIDEXTRACTUM LEPTANDRUM). Dose, one-half to one fluidrachm. Leptandrin, an impure resinous substance used especially by the Eclectics, may be given in doses of from one to two grains (0.065 to 0.13 Gm.). TAMARINDUS. Tamarind. U. S. The preserved pulp of the fruit of Tama- rindus Indica, a large tree, native of the East and West Indies. In the market it occurs as adhesive masses composed of pulp, membranes, strings, and seeds, and having a sweet acidulous taste. It contains a good deal of citric acid, much less tartaric acid, and a little malic acid. It is rarely used at present, but is laxative in doses of half an ounce to an ounce or more, being eaten like preserves, and enters into the confection of senna. CASSIA FISTULA. U. S. Purging Cassia is the dark, sweetish, acidulous pulp of a hard, blackish, cylindrical pod produced by Cassia Fistula, a tree of Egypt and India. It may be used as a laxative in doses of half an ounce (15 Gm. ), but is apt to cause griping. It enters into the official confection of senna. MAGNESIA LIGHT MAGNESIA. U.S. MAGNESIA PONDEROSA HEAVY MAGNESIA. U.S. The heavy and the light magnesia differ only in their physical charac- ters, the particles being differently aggregated. Magnesium carbonate (MAGNESII CARBONAS, U.S.) is manufactured by precipitating a solu- tion of magnesium sulphate by one of sodium carbonate. If the two solutions be concentrated, the dense or heavy carbonate will fall ; on the other hand, if the solutions be dilute, the precipitate will be a light car- bonate. Heavy magnesia is obtained by calcining a heavy carbonate ; light magnesia, by using a light carbonate. All of these substances are of a milk-white color, and occur in powder ; the carbonates sometimes in very light cubical blocks. They are all practically insoluble in water, freely soluble in dilute acid, and in the presence of acids they all act as alkalies. THERAPEUTICS. Magnesia and its carbonate are antacid and laxa- tive. For their purgative powers they are probably dependent upon the presence of acids in the primae viae, and hence their effects vary. When taken repeatedly they are said at times to accumulate in the intestines, and should not be used as an habitual laxative. They are often given along with Epsom salt or senna, on account of their antacid properties. Their chief use is in acute acid dyspepsia, in sick headache, in diarrhoea with excessive acidity in children, in gout, in rheumatism, and in various cu- taneous affections, wherever, in a word, a laxative antacid is indicated. CATHARTICS. 657 Dose, one drachm to half an ounce (4-15 Gm. ); for a child a year old, from five to twenty-five grains (0.3-1.6 Gm.), according to the effect desired. SULPHUR. Sulphur is official in three forms : SULPHUR SUBLIMATUM, or Su&- limed Sulphur ; SULPHUR LOTUM, or Washed Sulphur ; and SULPHUR PR^CIPITATUM, or Precipitated Sulphiir. The first of these is made by subliming sulphur into cool chambers, and always contains some sul- phuric acid, generated during the process. When freed from the acid by washing with warm water and ammonia, it constitutes the washed sul- phur. The U. S. Pharmacopoeia directs the precipitated sulphur to be prepared by boiling lime and sulphur together, so as to form calcium sulphide, and precipitating this with hydrochloric acid. The sublimed and the washed sulphur occur as sulphur-yellow, crys- talline powders ; the precipitated as a whitish powder, whose particles are often coherent into friable lumps. For an account of the various allo- tropic forms of sulphur, and its chemical properties, the reader is referred to works on chemistry. It is insoluble in water, but soluble in alkaline solutions, alcohol, the fixed and volatile oils, chloroform, ether, etc. PHYSIOLOGICAL ACTION. When applied locally, sulphur is almost without influence. Taken internally, it is dissolved to some extent in the alkaline intestinal juices and absorbed. It has been detected in the milk, sweat, urine, and even in the breath. It would appear to suffer oxidation in the system ; at least its ingestion is followed by increase of the urinary sulphuric acid (Regensburger 25 ). When in sufficient quan- tity, sulphur acts as a mild laxative, producing soft, semi-liquid, feculent stools, accompanied generally by much offensive flatus of sulphuretted hydrogen. It is affirmed that in some instances the latter gas has been so freely generated and absorbed as to cause systemic poisoning. Cases have also been reported in which the flowers of sulphur acted as an irri- tant poison ; but this, without doubt, has been owing to their containing a large quantity of sulphuric acid. Its continued use has probably some effect upon nutrition ; the secretions generally are slightly increased, and some have affirmed that the temperature is somewhat elevated ; but the truth of this is certainly very doubtful. The results of clinical experi- ence indicate that it has an especial tendency to act upon the skin and mucous membranes. THERAPEUTICS. As an habitual laxative, sulphur has been used with asserted advantage in cases of hemorrhoids and of chronic rheuma- tism. In subjects of the latter disease it is affirmed that it exerts a bene- ficial alterative influence, especially in sciatica and in lumbago and other varieties of muscular rheumatism. It has also been employed as an alterative in various cutaneous affections ; and in the form of natural sulphur-waters, used externally and internally, there is much testimony as to its value in both rheumatic and skiri diseases. It is affirmed by 42 658 LOCAL REMEDIES. Doit z6 that the natural sulphur-waters are of very great value in the treatment of chronic syphilis, as they undoubtedly are in chronic gout and rheumatism. They may be substituted by the artificial sulphur- water described under the heading of EXPECTORANTS. The known germicidal properties of sulphur, and the compounds which it forms, indicate that it should have value as an intestinal germi- cide, and it has been found to be of very great service by the U. S. medi- cal officers in the Philippines in the treatment of the chronic amoeboid dysentery of that country. It has also been highly commended by Woro- schilsky 27 in typhoid fever. In every case from ten to fifteen grains may be given in capsules every three to four hours. Sulphur is very largely used as a parasiticide in cases of itch. Tilbury Fox recommends its application in the following manner. He says, " I have applied to all papules and vesicles the following ointment : sulphur, half a drachm ; ammonio-chloride of mercury, four grains ; creosote, four drops ; oil of chamomile, ten drops ; and an ounce of lard. This is rubbed in night and morning for three days, especially to the interdigits and wrists ; the same shirt is kept on till the third day, when it is changed and a warm bath given. The use of the parasiti- cide for two or three days should be followed by a good washing and the discon- tinuance of the remedy for a night. If the patient be not troubled with itching during the night, we may conclude that the acari are killed, and all we need to do is to guard against the hatching out of fresh acari by the light application of our parasiticide once a day to any ' pimply' or itchy place for a few days longer, taking care that the foul clothes are well heated or scalded. ' Not too strong and not too long' is my rule in the use of remedies for scabies. The occurrence of red, rough, erythematous patches is a sign that the remedy itself is creating disease." ADMINISTRATION. Dose, as an alterative, ten to twenty grains (0.6-1.2 Gm. ) three times a day ; as a laxative, one to three drachms (4-1 1 C. c. ) at bedtime. POTASSA SULPHURATA. Sulphurated Potassa occurs in liver-brown fragments, which form an orange-yellow solution in water. Its taste is acrid, alkaline, and very disagreeable. When moistened, it feebly emits the odor of hydrogen sulphide. Locally applied, the potassium sulphuret is a very decided irritant. Taken in large quantities, it is a violent corrosive poison, and is said to have produced fatal gastro-intestinal inflammation. In medicine it is chiefly employed externally. It has been used as a stimulating ointment (half a drachm to an ounce) in various skin affections, and is also used for the formation of sulphur baths, the strength of which should vary, according to the requirements of special cases, from two to six ounces of the drug in thirty gallons of water. They should be taken warm, the patient remaining in from twenty minutes to two hours, and are said to cause a general excitement, amounting in some susceptible persons to high fever. When employed strong, they sometimes occasion a papular eruption. They have been used in chronic rheumatism and in various scaly skin diseases. CALX SULPHURATA. U. S. Sulphurated Lime. Commercial Calcium Sul- phide. A mixture containing at least fifty per cent, of calcium sulphide with un- changed calcium sulphate. It has been strongly recommended by Sydney Ringer, CATHARTICS. 659 by Duhring and others, for the treatment of successive crops of boils,* and in scrofulous and other unhealthy sores and glandular enlargements in children. It probably affords a feeble and uncertain method of administration of sulphur. Of- cial dose, one grain. PURGES. OLEUM RICINI CASTOR OIL. U. S. A fixed, nearly odorless oil, of a nauseous taste, obtained from the seeds of Ricinus communis by expression. The seeds are slightly warmed before being put under pressure, so as to liquefy their con- tained oil ; and the crude oil obtained from them is boiled with a small amount of water, so as to coagulate its albuminous impurities. Castor oil is remarkable for being soluble not only in ether, but also in alcohol. The castor-oil seeds, or beans, as they are commonly called, contain an acrid, violently poisonous principle, Ricin.^ PHYSIOLOGICAL ACTION. Castor oil acts upon the human organism as a mild but decided purgative, producing copious fluid fecal discharges, and in overdoses sometimes vomiting, and always purging freely. The bulk of the castor oil is ricinolein, a glyceride of ricinoleic acid, which ap- pears to be the purgative principle, and to be absorbed ; at least Canvane \ affirms that in children castor oil sometimes purges when rubbed upon the skin of the abdomen, and when taken into the stomach it has been known to exude from the skin. Buchheim, 28 although he submitted the passages produced by the oil to careful chemical manipulation, failed to detect it or any derivatives. According to the experiment (quoted by Stille") of Hale upon himself, half an ounce of castor oil injected into a vein produces malaise, nausea, faintness, anxiety, and general dulness and depression, without purging. THERAPEUTICS. On account of the mildness of its action and a special property of soothing an irritated bowel, castor oil is constantly employed whenever it is desired simply to evacuate the intestinal canal ; not so much, however, in chronic constipation as when a temporary action is alone required. In various inflammatory or irritative affections of the * Furuncles appearing in successive crops are usually, perhaps always, due to local infection of the skin, and are to be treated by bringing about a condition of surgical cleanliness of the skin by the use of weak solutions of corrosive sublimate, hot water and soap, and by other methods similar to those used by surgeons for the disinfecting of their hands. t Three beans have caused death in the adult. The symptoms, which do not usually come on until from two to five hours, are severe abdominal pain, violent vomiting and purging, which after a time may become bloody, collapse, severe muscular cramps, cold sweating skin, contracted features, thirst, restlessness, and small rapid pulse. After death, intense redness and even abrasion of the stomach and of the small intestine are found. After the stomach and large intestine have been thoroughly washed out with warm water, the treatment of castor bean poisoning is that of toxic gastro-enteritis, namely, the use of opium, leeches, ice, demulcent drinks, counter-irritation, etc. See Robert and Stillmark (Arbeiten Pharmak. Inst. zu Dorpat, iii.). t See H. Meyer (Arch. f. Exper. Palhol. u. Pharm., 1890, xxviii.). \ Ward's case (London Med. Gaz., x. 377). 660 LOCAL REMEDIES. alimentary canal, castor oil is often of the greatest service. This is espe- cially seen in the acute diarrhoeas and even in the chronic enteritis of children, but also holds good in the diarrhoeas and dysenteries of adults. In chronic pseudo-membranous colitis we have seen very excellent results from the long-continued daily use of the oil. The application of the fresh leaves to the breasts, combined with the administration, three times a day, of a teaspoonful of a fluid extract of the leaves, is said to decidedly increase the secretion of milk. The dose of the oil is half an ounce to an ounce (15-30 C.c. ) for an adult ; for an infant a year old, one to two teaspoonfuls (4-7 C.c.). In dysentery it is sometimes advantageous to give the drug in small dose every three hours until a decided purgative operation is induced. The repulsive taste of castor oil will sometimes cause vomiting ; the oil should, therefore, be given in soft capsules, or in some way dis- guised, as in strongly aromatized water, or in emulsion. A mixture of equal parts of glycerin and castor oil, with two to four drops of the oil of cloves or cinnamon to the fluidounce, is readily taken by most persons ; especially if it be given in an ice-cold spoon, which chills it into a viscid mass. HYDRARGYRUM. U.S. The only preparations of mercury which are used as purgatives are calomel and blue mass. Of these the first is by far the more active, and indeed is the only one which can be relied upon to purge. The chief interest in the purgative action of mercurials centres in the question as to their influence upon the liver. The evidence at present derivable from experiments upon the lower animals has already been discussed, and the decision arrived at that it must be rejected.* When calomel is given to a healthy man in moderate purgative doses, green liquid stools are produced, which, after larger doses, are replaced by brown passages. The color of these passages has always been supposed by clinicians to be due to the presence of bile ; but re- cently it has been affirmed that the green tint is owing to a compound of the mercury itself. Although no chemical proof of the presence of the metal or its salt has, that we are aware of, been furnished, yet it can scarcely be doubted that mercury is present in the first passages produced by calomel. The question, evidently, is not, Is mercury ever present in the green stools ? but, Is it always present ? or, in other words, Is it an integrant portion of them ? The evidence is not so abundant upon this point as is desirable, yet seems sufficient to furnish a negative answer to the last question. Simon w and Golding Bird, 50 in careful analyses, both failed to detect the metal ; and, as the recognition of mercury is an exceedingly simple chemical problem, it seems impossible that these chemists could have overlooked the metal if it had been present. Simon's analysis was * For a very elaborate review of the clinical evidence, see Thomas R. Eraser's paper in the Edinb. Med. Jonrn., April, 1871. CATHARTICS. 661 performed upon the fifth stool after the administration of a large dose of calomel. The passage was fluid, perfectly green, had no fecal odor, exhibited a mild acid reaction, and showed under the microscope a great number of mucus-corpus- cles and epithelium-cells. Ether extracted from the solid residue (obtained by evaporation) a considerable amount of fat, which had an acid reaction, contained cholesterin, and was colored by biliverdin. All the other substances which were separated from the stool by water and alcohol were more or less colored by bile- pigment. Bilin, bilifellinic acid, and biliverdin were found in large quantity. The most satisfactory evidence is, however, that furnished by Miche"a, 31 who examined chemically the faeces under four different conditions. First, the spon- taneous dejections of six healthy individuals : no bile was detected. Secondly, green stools of three persons suffering from gastro-intestinal derangement : bile- pigment was found in one case only, and in that could not be detected after per- sistent vomiting had ceased. Thirdly, calomel having been given to eight healthy persons, five men and three women, bile was readily demonstrated in the green passages produced in all of the subjects. Fourthly, saline and resinous purgatives were given to five persons, but no bile could be detected in the liquid stools. To the evidence brought forward in favor of the proposition that calomel given to healthy men causes an increased escape of bile from the alimentary canal may be added the conclusive fact that in some persons, whose idiosyncrasies render them very susceptible to the action of calomel, it produces not merely purging, but also vomiting of bile, which is scarcely at all altered. From the facts which have just been passed in review, the conclusion seems inevitable that mercurial purgatives given to healthy persons cause the escape of large quantities of bile from the alimentary canal.* As is well known, when from any cause bile does not pass into the duodenum, the stools become very pale, of a peculiar potter's-clay, or even white, color. Very frequently under these circumstances, which may coexist either with diarrhoea or with constipation, mercurials will modify the color of the passages and alleviate or cure any symptoms present. In many cases the mercurials are, of course, powerless to effect the desired result ; but this depends upon the cause being organic, or of some other nature not to be overcome by a secretory stimulant. As mercurials in health increase the flow of bile from the intestine, and as they will sometimes re-establish it in disease when the secretion has altogether ceased or has been very materially diminished, the con- clusion seems inevitable that mercurials have the power of directly or indirectly increasing the secretion of bile. The only objection of any force to be urged against this deduction is founded upon the idea that the drug simply increases peristalsis in such a way as to cause the bile natu- rally in the duodenum to be swept out instead of being absorbed. The answer to this is embraced in the following facts : mercurials often restore the color of the passages when pale from arrested secretion, often without * J. Zawadzky (Vratch, 1887, abstracted, Bull. TMrap., 1887), as the result of his own researches, comes to the improbable conclusion that the presence of bile in the stools as the result of the use of calomel is due to the antiseptic property of the mercurial, the bilirubin being converted into biliverdin, which is prevented from undergoing decompo- sition. 662 LOCAL REMEDIES. producing diarrhoea; other even more active purgatives fail to induce the same bilious passages ; when diarrhcea exists with clayey stools, the change in the color of the passages caused by a mercurial may coincide with an unincreased, or even a lessened, amount of liquidity ; diarrhcea ordinarily does not cause bile to appear in the passages. THERAPEUTICS. A mercurial purge is especially indicated by the congeries of symptoms known as biliousness : a heavily coated tongue, bitter, disagreeable taste, severe headache, depression of spirits, loss of appetite, slight nausea, and light-colored passages. It should be borne in mind that one or several of these symptoms may be absent in any individual case. Of all single indications for the use of calomel, the occurrence of potter 1 s-clay-cohrcd passages is the most important ; and if such stools exist, and do not depend upon an organic cause, repeated small doses of the mercurial should be given, whether there be constipa- tion or diarrhcea. In bilious fever, i.e., malarial fever with congestion of the liver, a mercurial purge, or several mild mercurial purges, will often, by exciting the action of the hepatic gland, be of great service in preparing the way for or aiding in the action of quinine. In catarrhal jaundice, mercurials, on the whole, offer, we think, the most frequently successful mode of treat- ment. It is evident that in such cases calomel does good not merely by its cholagogue influence, but even to a greater extent by its antiphlogistic power, no doubt lessening the viscidity of the secretions and abating the inflammatory action in the hepatic ducts. In many instances it is well to exhibit the mercurial in purgative doses to start with ; but the main reli- ance is to be placed in the continuous exhibition of small doses of the drug until the gums are rendered slightly sore. Anything like profuse salivation is, of course, to be avoided. In dysentery of an acute sthenic type, calomel acts as an antiphlogistic and as an alterative, not only to the liver, but to all the intestinal glands. It is possible that it acts also as a bactericide, since N. P. Wassilieff S2 has found that although it has no effect in checking the action of the digestive ferments, it has a very pronounced influence in stopping putrefactive changes in food by killing the organisms which produce such changes. RHEUM RHUBARB. U.S. The root of Rheum officinale, Baillon, and other species of Rheum growing in China, Chinese Tartary, and Tartary. Rhubarb occurs in hard, irregularly cylindrical or roundish pieces, of a brownish-yellow color and peculiar bitter taste, and imparting to the teeth a sense of grittiness, due to the presence of great numbers of minute crystals of calcium oxalate. At one time rhubarb was cultivated to a considerable extent in Europe, but European Rhubarb is no longer found in our markets. Rhubarb contains, besides a peculiar tannic acid, chrysophanic acid, CATHARTICS. 663 emodin* and probably a third active substance, rhein, of Hesse. Rhein and rhabarbarin, of the older chemists, were complex bodies. PHYSIOLOGICAL ACTION. Rhubarb is somewhat stomachic, tonic, actively purgative, and, owing to its tannic acid, secondarily astringent, leaving a decided tendency to constipation after the primary purgation. Owing probably to its chrysophanic acid, it gives a yellowish color to the milk of nursing women and to the urine. Rhubarb urine is to be dis- tinguished from that of jaundice by its becoming purplish-red on the addition of an alkali. Rhubarb is asserted to affect chiefly the muscular coat of the bowels, and to purge by increasing peristalsis ; but we have never met with any proof of this common belief. THERAPEUTICS. Notwithstanding its astringent property, rhubarb is largely used as an habitual laxative, because it does not impair, but, on the contrary, seems to strengthen, the appetite and the digestion. It should not be used in a high sthenic state of the system, or when deple- tion is necessary, but is very valuable when it is desired simply to unload the bowels in a debilitated subject. It is much used in diarrhoea, with intestinal weakness or relaxation, to unload the bowels of acrid secretions. The aromatic syrup combined with an alkali is especially serviceable in the summer bowel-complaints of children when the stools are greenish and mucous. ADMINISTRATION. Rhubarb is seldom employed in powder, but, when used, may be given in pill, as a laxative in five grains, as a purgative in ten-grain doses. In chronic constipation, small pieces of the root are very often carried in the pocket and chewed by the person affected pro re nata. The U. S. Pharmacopoeia recognizes the follow- ing preparations of rhubarb: EXTRACTUM RHEI, dose, five to ten grains (0.3-0.6 Gm.); PILULE RHEI COMPOSITE (two grains of rhu- barb, one and a half grains of aloes), dose, two to four pills; PULVIS RHEI COMPOSITUS (rhubarb and magnesia), dose, half a drachm to a drachm (2-4 C.c. ); FLUIDEXTRACTUM RHEI, dose, twenty to thirty * Emodin. The nature of the active principles of many of the vegetable purgatives is still obscure. Several of them namely, rhubarb, senna, aloes, frangulin, and cascara sagrada are believed by some chemists to owe their properties to the presence of anthra- cene compounds. Such compounds are usually glucosides. Of these compounds at- tention has been recently especially drawn by Tschirch to emodin (trioxymethylantura- guinone), as being the real active principle of the class. The great difficulty is to tell how far a principle obtained by chemists from one of these drugs originally exists in the drug and how far it has been formed by the decomposition of some other principle. Thus, chemists of repute affirm that emodin is a decomposition product from frangulin ; whilst Tschirch believes that many of the drugs named owe their great activity to the presence in them of substances produced by the decomposition or change in emodin. Emodin has been used to some extent as a laxative in doses of one to two grains. In view of the fact that there is only two per cent, of aloe-emodin in Barbadoes aloes, about two per cent, of rhubarb-emodin in rhubarb, and in senna a still smaller percentage of emodin, it seems certain that emodin does not fully represent the various drugs. The experiments of Asher, upon which Tschirch based the theory that in the emodin group the irritation is caused by the local stimulation of the nerve-endings in the intestinal mucous membrane, with a consequently reflexly excited peristalsis, were not sufficient in number or thoroughness to establish the correctness of the theory. 664 LOCAL REMEDIES. minims (1.2-2 C.c. ) ; SYRUPUS RHEI, ten per cent, dose, for an infant, a fluidrachm (4 C.c.) ; SYRUPUS RHEI AROMATICUS, dose, for an infant, a fluidrachm (4 C.c.) ; TINCTURA RHEI, twenty percent., dose, one to two fluidrachms (4-7 C.c. ) ; TINCTURA RHEI AROMATICA, twenty per cent., dose, one-half to one fluidrachm (2-4 C.c.) ; MISTURA RHEI ET SOD^E one-and-one-half per cent., dose, one-half to one fluid ounce (15-30 C.c. ). The aromatic preparations are of pleasant taste and efficient, and are much used for children. ALOE ALOES. U. S. Aloes appears to have been first produced in the Island of Socotra, as far back as the time of Alexander the Great, 333 B. C. ; and the U. S. Pharmacopoeia of 1 890 recognized Socotrine and Barbadoes aloes, besides which a variety of aloes produced at the Cape of Good Hope, Cape aloes, largely occurred in commerce. At present, under the general name of Aloe, the Pharmacopoeia recognizes simply aloes, allowing the pharmacist to use any form of aloes which conforms to the standard given in the text of the Pharmacopoeia. Aloes is not now produced at Barbadoes, while the Socotrine aloes occurs in the American market only in small quantities, the mass of the commercial drug being produced in the Island of Curafoa. Aloes is obtained by cutting off the thick, succulent leaves of va- rious species of the genus aloe, allowing the juice to drain into skins, troughs, or other vessels, and afterwards inspissating either by exposure to the sun or by means of artificial heat. The aloes are blackish-brown or yellowish-brown, of a bitter, nauseous taste, often with a smooth fracture, and in the best varieties with garnetty edges; they yield their virtues to alcohol, imperfectly to water, and very imperfectly to alkaline solutions. T. and H. Smith M in 1850 discovered in Barbadoes aloes a crystalline principle, aloin, which was shortly afterwards found by Pereira to exist already crystallized in the sap of various species of aloe-plants, and was subsequently obtained by Groves* 4 from Socotrine aloes. Aloin crystallizes from its watery solution in sulphur-yellow granules, from a hot alcoholic solution in star-like groups of needles. It is neutral, odor- less, of a taste at first sweetish, afterwards intensely bitter ; is soluble with difficulty in cold water, freely in boiling water and in alcohol. There are three varieties of aloin, barbaloin, socaloin, and nataloin, obtained respectively from the Barbadoes, the Socotrine, and the Cape aloes. Aloinum, U. S. , is the aloin derived from Barbadoes aloes or from Soco- tra or Zanzibar aloes. The aloin of commerce is chiefly barbaloin, and is certainly an active cathartic in doses of half a grain to a grain. H. Meyer K finds that the Barbadoes and Curacoa aloin act both on man and on many lower animals as a purgative, whilst the Natal aloin fails ordinarily to affect man, although it is a certain cathartic in dogs and cats. The time required for the Barbadoes aloin to produce purgation was from eight to thirty hours, which Meyer believes to be due to the fact that its physiological action depends upon its CATHARTICS. 665 undergoing chemical change in the intestines. In order to facilitate this change he exhibited with it potassium carbonate and ferrous sulphate, and found that these salts markedly hastened the effect. He also found that Natal aloin, when given to per- sons who had been fed for six days an exclusively animal diet, acted as a cathartic.* In the lower animals Kohn ** found the hypodermic injections of aloin to cause gastro-enteritis with albuminous urine, and a peculiar inflammation of the kidneys ; o.i gramme of Merck's aloin for every kilogramme of bodily weight was a fatal dose for the dog. Aloin could be detected in the urine. ( Method of analysis given. ) Brandenburg S7 has experimentally shown that very large doses of aloin cause in the rabbit a fatal necrosis of the renal epithelium ; small doses produce a paren- chymatous nephritis. PHYSIOLOGICAL ACTION. Aloes is a stomachic, stimulant cathartic, remarkable for the slowness of its action. It has been supposed to influence chiefly, if not solely, the large intestine, and the clinical evi- dence is very strong that in overdoses it produces irritation of the rec- tum. The belief, formerly universal, that it is capable of producing hemorrhoids, and the statements that its habitual use in large doses causes tenesmus, a feeling of weight, heat, and uneasiness in the pelvis, and occasionally excitation of the sexual organs, are of very doubtful correctness. Aloin has been detected in the urine by J. Dietrich M and also by Meyer. THERAPEUTICS. Aloes, being a stimulating purgative, is chiefly used in the constipation of atonic subjects. In the constipation of plethora it should not be employed ; neither should it be administered when active abdominal or rectal inflammation exists. During pregnancy it is best avoided, and large purgative doses should never be given. Formerly it was taught that aloes should not be used in hemorrhoids ; but most, if not all, of the cases of this affection depend upon a condition of relaxa- tion of the rectal veins, and Fordyce Barker M insists upon the great value of aloes in piles, and states that Oppolzer was especially famous for his treatment of this affection, and that his prescriptions were, when piles are associated with constipation, aloes and quinine ; without con- stipation, aloes and sulphate of iron. For bleeding piles he used R Ferri sulphat. , 9i ; Ext. aloes aq. , 3} ; Ext. taraxaci, q. s. Ft. pil. no. 60. S. One morning and evening, and increase to three a day if necessary. When costiveness accompanies atonic amenorrhcea, aloes alone of all the laxatives should be exhibited ; and it is also of service in atonic menorrhagia. ADMINISTRATION. As aloes often contains sticks and other extrane- ous matters, the U. S. Pharmacopoeia directs that an ALOE PURIFICATA, or Purified Aloes, should be made by dissolving the crude drug in alcohol, straining, and evaporating. Of this the full purgative dose is ten to twenty grains (0.61.2 Gm. ). The official preparations of crude aloes have been almost entirely superseded by aloin. * Consult Chem. Gaz., 1851 ; Die Pflanzenstoffe, 1047 ; Trans. Brit. Pharm. Soc., 1872 ; Brit. Med.Journ., 1887, i. 747; Bull. Thfrap., xci. 259; Land. Med. Record, 1877, 459; and Edin. tfed. Journ., xx. 1002. 666 LOCAL REMEDIES. The tincture (TINCTURA ALOES ten per cent., U. S. ), dose, as a laxative, one to three teaspoonfuls; the tincture of aloes and myrrh, ELIXIR PROPRIETATIS (TINCTURA ALOES ET MYRRH.* aloes and myrrh, of each ten per cent., U. S. ), dose, as a laxative, one to two teaspoonfuls; EXTRACTUM ALOES, U. S., dose, t\vo grains; the pills ( PILULE ALOES, U. S. ), each two grains of aloes; the Pills of Aloes and Mastich (PILULE ALOES ET MASTICHES, U. S. ), the famous Lady Webster Dinner- Pill, each containing two grains of aloes; the Pills of Aloes and Myrrh ( PILULE ALOES ET MYRRHS, U. S. ), used in amenorrhcea, and containing two grains of each ingredient in every pill; the Pills of Aloes and Iron, formerly official, contained each one grain of aloes and one grain of dried ferrous sulphate. The Compound Laxative Pills ( PILULE LAXATIVE COMPOSITE U. S.), A. B. S. pill of the drug stores, aloin, grain one-fifth ; strychnine, belladonna extract, ipecacuanha, is a very efficient and popular combination in the treatment of chronic constipation, and has justly received recognition in the U. S. Pharmacopoeia. One or two pills may be given at a dose. Aloin is actively purgative in dose of half a grain (0.03 Gm. ); laxa- tive dose, one-fourth of a grain (0.016 Gm.). SENNA SENNA. U. S. Under the name of Senna various species of the genus Cassia have found their way into commerce, but at present the U. S. Pharmacopoeia recognizes only the leaflets of the Cassia acutifolia of Nubia and Upper Egypt {Alexandria Senna), and of the Cassia angustifolia of Southern India ( Tinnevelly Senna}. The senna-leaves vary from three-fourths of an inch to an inch and a half in length, and are to be distinguished by the inequality of their bases, the two sides of the lamina or leaf- blade joining the midrib at unequal heights and angles. Alexandria Senna is characterized by the presence of the shorter argel-leaves, with equal bases, by the ovate-pointed leaflets of Cassia acutifolia, and by the scattered mucronate-obovate leaflets of C. obovata. India Senna is distinguished by the oblong leaflets, from one to two inches in length, entire and perfect. Owing probably to the fact that it is largely culti- vated in the southern portion of the peninsula of Hindostan, especially near Tinnevelly, this senna at present constitutes the greater part of that which is sold in the drug-stores. Cathartic Acid, discovered by Dragen- dorff and Kubly, 40 is its chief active principle. According to Groves, four grains of the ammonium cathartate will purge actively, whilst R. Stockman 41 has shown that rabbits may be purged to death by a cathartate given by the mouth, although these salts have no effect upon the animal when injected into the blood or given subcutaneously. THERAPEUTICS. Senna is a very powerful, somewhat irritating hydragogue cathartic, acting, it is said, as readily upon swine, dogs, cats, and horses as upon man. When given alone, it is very apt to gripe severely, and is consequently more often used in combination. In obstinate fecal accumulation the Black Draught constitutes a most efficient and safe remedy. In small doses it is often used as a laxative. Its infusion injected into CATHARTICS. 667 the veins is said to cause both vomiting and purging, and the milk of nursing women taking it is affirmed to act as a cathartic. An aromatic should be administered with senna, to lessen its tendency to gripe. The leaves are not given in substance. The dose of the fluid extract (FLUID- EXTRACTUM SENN^E, U. S. ) is two fluidrachms to half a fluidounce (8-15 C.c. ) ; the confection (CoNFECTio SENN^E, U. S. , ten percent.) is a very complex but elegant preparation, used only as a laxative, in doses of one to two drachms (47 C.c.), especially in pregnancy ; it is not suited to dyspeptic cases, on account of its tendency to derange the digestion. INFUSUM SENN^E COMPOSITUM, six percent., U. S. {Black Draught}, contains manna and magnesium sulphate, an efficient hydra- gogue purge, causing very large watery discharges when given in dose of four fluidounces (120 C.c.) ; the dose of the syrup (SVRUPUS SENN^E twenty-five per cent., U. S. ) is one to four fluidrachms (4-15 C.c.) ; the PULVIS GLYCYRRHIZ.E COMPOSITUS, U. S., or Compound Licorice Powder, is an excellent, pleasant laxative in doses of thirty to sixty grains (2-4 Gm. ). SALINES. MAGNESII SULPHAS. U. S. Magnesium Sulphate. Epsom Salt ordi- narily occurs in small, acicular, slowly efflorescent crystals, containing about fifty-one per cent, of water of crystallization, soluble in their own weight of water at ordinary temperatures. The taste is bitter, saline, and nauseous. PHYSIOLOGICAL ACTION. Epsom salt is a most active hydragogue cathartic, producing very large watery discharges without causing any irritation of the intestines. The soluble magnesium salts injected into the blood are powerful poisons, causing death by failure of respiration, and also depressing the heart (J. H. Recke, 42 also M. Hay). These effects, are, however, never perceptible in the ordinary use of the mag- nesium sulphate, but recorded cases show that the drug is capable of acting as a violent general poison. Christison reports a boy, ten years old, killed by two ounces, without the induction of purgation. W. Sang ** reports as caused by four ounces of Epsom salt in a very concentrated solution, burning pain in the stomach and bowels, great dyspnoea, and collapse, with dilated pupils, muscular relaxation, and finally coma, end- ing in death, without purging or vomiting. In J. H. Neale's case the symptoms were violent enteritis, with most alarming heart depression, from which, however, the patient recovered. In the researches of Curci," it was found that the soluble magnesium salts first increase the blood- pressure and slow the pulse, and then lower the blood-pressure and quicken the pulse, causing finally cardiac paralysis. As the rise of the arterial pressure is prevented by previous destruction of the vaso-motor centres, it is probably the result of centric stimulation.* * The action of the saline purgatives upon the tissue-changes of the body has been laboriously investigated by a large number of chemists, with results which are so dis- 668 LOCAL REMEDIES. Epsom salt is very largely used when it is desired to deplete or to promote absorption through the bowels, as in dropsies ; or to relieve con- gestion of the bowels themselves, as in enteritis or colitis ; or when it is necessary to soften down fecal accumulation, as in obstinate constipation. The dose is half an ounce to an ounce (15-30 Gm.), properly diluted. M. Luton 45 affirms that ten centigrammes (1.53 gr. ) administered hypo- dermically usually provoke several watery stools ; but the practice seems to us a very doubtful one. The Pharmacopoeia now recognizes an Effervescent Magnesium Sul- phate (MAGNESII SULPHAS EFFERVESCENS) which represents fifty per cent, of the salt. This is intended to replace the formerly official Effer- vescent Magnesium Citrate, and offers a pleasant form of administering magnesium sulphate. LIQUOR MAGNESII CITRATIS. U. S. Solution of Magnesium Citrate is prepared by putting into a strong bottle a syrupy solution of magne- sium citrate containing an excess of citric acid, adding potassium bicar- bonate, and corking tightly. On account of its agreeable taste and effervescence, this preparation is much used as a purgative. It is similar to Epsom salt in its action, but is less efficient, more apt to gripe, and more irritating. It ought not to be used in inflammatory affections of the bowels. SODII SULPHAS. U. S. Sodium Sulphate, or Glauber 's Salt, occurs in six-sided, very efflorescent, striated prisms, which finally crumble into a white powder. It acts like Epsom salt, but is more powerful ; it is, however, little used on account of its extremely nauseous taste. It is the chief active principle of many natural purgative waters which are so useful in chronic gastric and other abdominal catarrhs with consti- pation. The combination of two ounces of sodium phosphate, one-half ounce of sodium sulphate, and one-half drachm of potassium iodide, taken in full laxative doses, well diluted, upon rising, is often very efficient in such cases as are benefited by Carlsbad waters. Dose of sodium sul- phate, one-quarter to one-half ounce (8-15 Gm. ). Soon PHOSPHAS. U. S. Sodium Phosphate occurs in colorless, trans- parent crystals, which effloresce and become opaque on exposure. It is a tribasic phosphate, one part of water acting as a base. It is soluble in 5.8 parts of cold water, and has a saline taste, closely resembling that cbrdant that it does not seem at present possible to come to any conclusion. The drift of the evidence, however, seems to us to show that the direct action upon tissue-change is very slight, and that it is incapable of producing a definite and fixed result amidst the varying and complicated daily causes which inevitably produce more or less disturbance and variation in the nitrogenous elimination. An elaborate research upon the subject has been published by London in the Zeilschr.f. Klin. Med., xiii. i. Most of the literature of the subject will be found in this article, the original work of which seems to lead to the conclusion just stated. CATHARTICS. 669 of common salt. In large doses it is a mild saline purgative, but as such is not at present very much employed. Sodium phosphate is a very useful remedy in chronic infantile diarrhoea with intestinal indigestion, especially as it occurs in bottle-fed subjects. It appears to have a specific action upon the liver and also upon the intestinal glands in general, so that it is often of great service where there are habitually chalky stools or white fluid motions, and in many cases of green stools. In chronic hepatic torpor and in catarrhal jaundice it is often used with great advan- tage, and it seems sometimes of value in litheemia. In 1888 Haig affirmed, as the result of his experiments, that sodium phosphate has very pronounced effect in increasing the excretions of uric acid. In a subse- quent paper, however, he stated that if the phosphate contain any sulphate, or if it be in the form of the acid phosphate, or meet with an acid in the stomach which should make it an acid phosphate, it has no power in increasing uric acid excretion; so that it seems to us that at present we cannot consider sodium phosphate as having distinct relations with uric acid excretion. Dose, twenty grains to half an ounce (15 Gm. ) ; laxative for infants, five to ten grains. Dose of SODII PHOSPHAS EFFERVESCENS, U. S. {Effervescent Sodium Phosphate}, twenty per cent, phosphate, two drachms to the ounce (8-32 Gm. ). Dose of SODII PHOSPHAS EXSICCATUS, U. S. {Exsiccated Sodium Phosphas}, fifteen grains to half an ounce. POTASSII ET SODII TARTRAS. U. S. Potassium and Sodium Tar- trate, or Rochelle Salt, is made by the addition of sodium carbonate to a solution of potassium bitartrate. It is soluble in two and a half parts of cold water, and has a slightly saline taste. It is a mild saline purgative, dedidedly less efficient, but much less offensive to the palate, than Epsom salt. Dose, from half an ounce to two ounces (15-60 Gm. ). F. Kleeberg* 5 finds that the intravenous injection of potassium sodium tartrate (thirty milligrammes per kilogramme) produces in the dog a marked fall of the blood-pressure ; after toxic doses, slowing of the heart and fatal diastolic arrest occur. In Kleeberg's experiments the neutral sodium tartrate (fifty milligrammes per kilogramme) caused a rise in the blood-pressure, so that the depressing in- fluence of the double salt is probably due to the potassium. PULVIS EFFERVESCENS COMPOSITUS. U. S. Seidlitz Powder is in two packets; the white paper contains about thirty-five grains of tartaric acid, the blue paper forty grains of sodium bicarbonate and two drachms of Rochelle salt. When they are taken, the powders are dissolved sepa- rately, the solutions added, and the whole drunk while effervescing. They are very acceptable to the stomach, refrigerant and laxative rather than purgative. Seidlitz powders are used almost exclusively to evacuate the bowels, and exhibited after blue mass to "carry off" mercurials, etc. They should be taken on an empty stomach, as before breakfast. One powder is the usual dose; but not rarely even two powders will fail to purge. 670 LOCAL REMEDIES. DRASTICS. As already stated, the drastics are those vegetable cathartics which are actively irritant. With perhaps one or two exceptions, in sufficient amount they are capable of causing fatal gastro-intestinal irritation. The line between the drastics and the stronger purgatives is, of course, placed more or less arbitrarily, since the various cathartics differ in action almost by insensible degrees. Thus, jalap, although included among the drastics in this work, might with perhaps even greater pro- priety be classed among the purgatives, since it is very little more active or irritant than is senna. Further, these remedies in combina- tion seem to lose, in a measure, their power of causing irritation, and to become useful purgatives. A fact, however, which makes the classi- fication here employed clinically useful, although it be not scientifically accurate, is that none of these remedies should be used when a purga- tive is desired to relieve gastro-intestinal inflammation or irritation ; and, on the other hand, when a revulsive action is wished for, as in some cases of brain disease, one of the drastics should always be selected. JALAPA JALAP. U. S. The tuber of Ipomcea Jalapa, a convolvulaceous vine growing in Mexico. Jalap comes into the market in two forms : one, that of the younger roots, which are sold undivided ; the other, that of the old roots, which are brought into the market in transverse or longitudinal slices and in pieces. The first variety consists of very hard, irregularly globular, brittle roots, about the size of a shut fist, or smaller, and often slashed with vertical incisions, made for the purpose of facilitating drying. The active principle of jalap is a resin, variously known as rhodeoretin or convolvulin, closely allied to the resin of scammony. PHYSIOLOGICAL ACTION. Upon dogs and horses jalap (Stilte 46 ) is said to act as a powerful hydragogue cathartic, and in overdoses as a gas- tro-intestinal irritant. Its active principles are absorbed, since Cadet de Gassicourt produced diarrhoea in dogs by the free application of jalap to the shaven skin, and J. Muller 47 found the resin in the blood of dogs to which he had given it. Still6, however, asserts that it does not impart its purgative properties to the milk of nursing women, and that in man it is not absorbed by the skin. In man jalap produces free hydragogue catharsis, often with nausea ; or, if in overdoses, violent vomiting and purging. THERAPEUTICS. Jalap is especially indicated when it is desirable to produce large watery stools. It is, however, very rarely used alone. A favorite combination with many practitioners is of it and calomel. In the form of the compound powder (PULVIS JALAP^E COMPOSITUS, U. S. , jalap, thirty -five parts, cream of tartar, sixty-five parts), jalap is very frequently used with great advantage in ascites and also in other forms CATHARTICS. 671 of general dropsy. It is believed when given in this way to exert some influence upon the renal functions : for very many cases the proportion of cream of tartar in the official compound powder is too small. ADMINISTRATION. The dose of powdered jalap is ten to twenty-five grains (0.6-1.6 Gm. ) ; of the extract, ten to twenty grains (0.61.3 Gm. ). The resin (RESINA JALAP^E, U. S. ), like the other purgative resins, is tasteless. Dose for adult, from two to four grains (0.13-0.26 Gm. ). COLOCYNTHIS COLOCYNTH. U. S. The fruit, deprived of its rind, of Citrullus Colocynthis, or bitter cucumber, a vine growing in South Africa, Japan, Syria, Egypt, Turkey, the islands of the Grecian Archipelago, etc. The fruit is a round gourd, from two to four inches in diameter, of a whitish or pale yellow color. It occurs in the market with or without its rind. The pulp is dry and mem- branous, whitish, and contains the active purgative glucoside colocynthin t first discovered by Herberger. Colocynth in large dose is an irritant hydragogue cathartic, capable of destroying life, and, according to Orfila and Schroff, acting upon the lower animals as upon man. Christison records the death of a woman twenty- four hours after taking a teaspoonful and a half of the powder. Roques chronicles a fatal result produced by less than a drachm of the powder in decoction, but, on the other hand, narrates a case in which three drachms failed to kill (Husemann 47 ), and W. A. Rolfe reports recovery after a quarter of an ounce of the powdered drug in which, although pregnancy existed, abortion was not produced. ADMINISTRATION. It should not be used in dropsy, and is employed almost solely in combination with other purgatives. The full purgative dose of the extract (EXTRACTUM COLOCYNTHIDIS, U. S. ) is three to five grains (0.2-0.3 Gm. ). The compound extract ( EXTRACTUM COLO- CYNTHIDIS COMPOSITUM, U. S. ) contains extract of colocynth, sixteen parts; purified aloes, fifty parts; resin of scammony, fourteen parts; carda- mom, six parts; soap, fourteen parts as laxative, one to three grains (0.06-0.2 Gm. ); as purgative, five to twenty grains (0.3-1.3 Gm.). SCAMMONIUM SCAMMONY. U. S. A resinous exudation from the root of Convolvulus Scammonia, a vine growing in Syria. It is said to be obtained by cutting off the root obliquely about two inches from the origin of the stems, and catching in shells the few drachms of milky juice which exude from each root. From these shells it is emptied into a vessel and allowed to concrete. Formerly scammonium was adulterated to a great extent with chalk, flour, ashes, sand, etc., constituting the Factitious Scammony of authors. Scammonin, the active resin of scammony, is believed to be identical with jalapin, originally separated by Mayer from male jalap, and closely allied to convolvulin of true jalap. The Pharmacopoeia requires that scammony shall contain seventy-five per cent, of this resin. Therapeu- tically scammony acts like jalap, but is somewhat more irritating. It 672 LOCAL REMEDIES. is almost solely used in combination with other cathartics, and on ac- count of its frequent adulteration should be given in the form of the resin (RESINA SCAMMONII, U. S. ). Dose, from two to five grains (0.13-0.3 Gm. ). The pure or Virgin Scammony is in irregular, rough, fissured masses, of various sizes, commonly solid, with a dull resinous fracture, and of a dark greenish color, inclining to black. The smell resembles that of old cheese. PILULE CATHARTICVE COMPOSITE. U. S. Compound Cathartic Pills contain each approximately: compound extract of colocynth, one and one-third grains; extract of jalap, one grain; calomel, one grain; gamboge, one-fourth grain. In the dose of two pills, they usually produce large watery stools without much pain, and, as they contain mercury, have some cholagogue influence. The mercury, however, makes them as an habitual laxative much inferior to the vegetable cathartic pill (PILULE CATHARTICS VEGETABILES, U. S. ), one or two of which will usually act kindly and efficiently. PODOPHYLLUM PODOPHYLLUM. U.S. The rhizome of Podophyllum peltatum, or May-apple, a perennial herb, growing in the Northern and Middle United States. Podophyllum occurs in simple or branched, cylindrical, brownish pieces, about the thickness of a goose-quill, smooth or wrinkled longitudinally, often obscurely marked with the scars of leaf-scales, and furnished with numerous rootlets or their remnants attached to the lower surface. The taste is bitterish, acrid, and nauseous. The rhizome contains the alkaloid berberine, but the purgative power resides chiefly in podophyllotoxin * of Podwyssotzki, 49 although it is probable that there are other purgative substances in the rhizome, especially an uncrystallizable resin, podophyl- loresin. Podophyllum is a rather slowly acting, but very thorough cathartic, whose large dose either in man or in most of the domestic animals pro- duces violent purging, with great pain, and often with vomiting ; the symptoms increasing, if the dose have been sufficient, to excessive hyper- catharsis, with bloody stools, great prostration, and death. It is said to act when given hypodermically. f A child four years old was killed by an unknown amount. The symptoms were repeated vomiting, slight purging, collapse, and finally coma, ending in epileptiform convulsions (T. G. Morton). An infant twenty-two months did recovered from four grains. 49 * Podophyllotoxin was believed by its discoverer to be composed of picropodophyllin in combination with podophyllinic acid. The latest chemical researches indicate, how- ever, that these substances are decomposition products. Podophyllotoxin appears to be a very irritant, active cathartic, and has been used in medicine in doses of one-fifteenth of a grain. According to J. Neuberger (Arch.f. Exper. Path. u. Pharm., 1890, xxviii.), it causes in the lower animals violent purging and severe nephritis, with fall of the arte- rial pressure and death from exhaustion. t See Amer. Med. Times, iv. ; also Med. Times and Gaz., March. 1863. CATHARTICS. 673 In therapeutic doses it is believed by very many practitioners to act especially upon the liver, and is much used in acute constipation and in so-called bilious attacks. As ten or more hours are usually required for its action, it should not be combined with quick cathartics. With calo- mel it acts very well. The only preparation that should be used is the resin (RESINA PODOPHYLLI, U. S. ), or podophyllin, the laxative dose of which is one-twelfth to one-sixth grain (0.005-0.01 Gm. ), the purgative dose, one-sixth to one-half grain (0.01-0.03 Gm. ). It is very advanta- geously combined with extract of belladonna as in the PILULE PODO- PHYLLI BELLADONNA ET CAPSICI, U. S. (Pills of Podophylhim, Bella- donna, and Capsicum), each of which contains about one-quarter grain of the resin of podophyllum. The fluid extract (FLUIDEXTRACTUM PODO- PHYLLI, U. S. ) is an inelegant preparation; dose, eight minims (0.5 Cc.). ELATERIUM. A substance deposited by the juice of the fruit of Ecballium ela- terium, or squirting cucumber, a native of Greece, but cultivated in England. In the interior of the ovate fruit is an elastic sac, which con- tains the seeds, and at ripening becomes so distended with juice that when the fruit falls off the vine, and the support is removed from the stem end, a rupture occurs at the latter position, and the liquid with the seeds is forcibly projected. The medicinal principle is said to be con- tained only in this inner juice. In order to avoid loss, the fruit is picked with a piece of the stalk adherent to it before ripening, and is opened by slicing. Elaterium occurs in light, friable, slightly incurved, greenish- gray cakes about a line thick. The taste is acrid and bitter, the fracture finely granular. Owing to the variability of commercial elaterium, the U. S. Pharmacopoeia now recognizes only the active principle, Elaterin (ELATERINUM, U. S. ), which was first separated in a pure state by Mor- ries. 51 It crystallizes in colorless, shining, rhombic, six-sided, odorless tables, of a very bitter sharp taste and neutral reaction. PHYSIOLOGICAL ACTION. Locally applied, elaterium is a very de- cided irritant, producing, according to Pereira, ulcerations in the fingers of those who handle the fruit and prepare the drug for market. When taken internally, it acts on man as a most powerful hydragogue cathartic. On the lower animals its action is much less certain. Viborg asserts that a horse was unaffected by a pound of elaterium fruit ; and H. C. Wood has given one and even two grains of a presumably active elaterium to a dog without producing very obvious results. If the dose be sufficiently large, all animals probably are, however, fatally affected by elaterium, perishing by progressive depression. Stille" M asserts that the death is not rarely preceded by violent vomiting and purging ; and even when these are absent during life, post-mortem examination reveals congestion and inflammation of the gastric and intestinal mucous membranes. In none of our own experiments, which have not been numerous, has any purging been present ; further, in K6hler*s M elaborate investigation, elaterium dissolved in alcohol was in- jected under the skin, the powdered elaterium was put into the rectum, and was given by the mouth after the gall-duct had been tied so as to prevent the flow of 43 674 LOCAL REMEDIES. bile into the intestine, and in neither case was there any purging, but prostration, apathy, disturbed respiration, salivation, and violent convulsions, ending in death. From these experiments Kohler draws the conclusion that elaterium exerts a general action upon the system, for which its introduction into the blood is all that is requi- site, and also a purgative influence, for which it is necessary that there be bile in the duodenum to dissolve the elaterium and cause it to act locally on the intestine. The objection to this conclusion is that it seems probable that elaterium does not purge dogs and rabbits, even when given by the mouth. Further, elaterium applied externally will cause purging in man (Stille'). So that the application to man of the conclusions arrived at by Kohler is incorrect. Kohler' s experiments proved that in animals elaterium is absorbed, even when given by the mouth, since he found it in the urine of poisoned dogs and rabbits. THERAPEUTICS. Elaterium is certainly the most efficient of all the hydragogue cathartics, producing in properly regulated doses the freest evacuations with comparatively little pain and irritation. It is the most efficient of all the medicines of the class in general dropsy or in ascites. As, however, its action is very exhausting, great care should be exercised not to give it in too large doses, and also to support the strength of the patient during the period of purgation, and afterwards, by alcoholic stimulants, easily digested nutritious food, and appropriate hygienic measures. In the latter stages of dropsy the injudicious use of elaterium may cause a fatal exhaustion. For the asserted power of elaterium in increasing the intestinal elimination of urea we have been unable to find authority. Clinical experience has, however, demonstrated the value of elaterium in tir&mia. In order to deplete, elaterium has been employed in various diseases ; but this use is not to be encouraged, and especially when there is any gastro- intestinal irritation or inflammation are the salines much preferable to elaterium. Elaterium is without doubt capable of destroying life, but we know of but one recorded death, that of a woman in whom two and two-fifths grains of the extract of elaterium and sixteen grains of rhubarb caused uncontrollable vomiting and purging, ending in a fatal gastro-enteritis.* Dose, one-sixth of a grain (o.oi Gm. ), combined with extract of hyoscyamus or of belladonna and an aromatic oil. Dose of the official elaterin, one-twentieth of a grain (0.003 Gm. ) ; of the trituration (TRIT- URATIO ELATERINI ten per cent., U. S. ), half a grain (0.03 Gm. ). Elaterium when injected hypodermically purges freely, but also produces an excessively severe local irritation, even fatal tetanus. f CAMBOGIA GAMBOGE. U.S. A gum resin, obtained in Siam by breaking off the leaves and young shoots of the tree known by botanists as Garcinia hanburii and catching in suitable vessels the juice as it drops. When the receptacles consist of hollow bamboos, the juice hardens into cylindrical casts, striated ex- ternally, and with a central cavity due to the loss of substance in drying. * See Beck's Medical Jurisprudence, I2th ed., ii. 719. t See Therap. Gaz., ii. 27. CATHARTICS. 675 This is the so-called pipe gamboge. Gamboge in sorts occurs in irregular masses. Gamboge is a hard, resinoid substance, of a brittle, often con- choidal fracture, of a deep reddish-orange color on exposed surfaces, more yellowish when freshly broken, affording a bright yellow powder, insoluble in water, with which it forms, however, an intensely yellow emulsion. It has little or no taste, but when chewed produces, after a time, an acrid sensation in the fauces. PHYSIOLOGICAL ACTION. Gamboge acts upon man as a violently irritant cathartic. On the lower animals it has a similar influence, but Schaur and Orfila state that when in large dose it often fails to purge, producing rapidly fatal gastro-enteritis, so intense as seemingly to par- alyze the bowels. According to Daraszkiewicz M and to Schaur, in order for gambogic acid to act as a purgative the presence of bile in the intes- tine is necessary. Schaur and Richter affirm that gamboge upon raw surfaces acts simply as an irritant : further, Gmelin and Tiedemann assert that they have found its principles in the urine ; it may therefore well be that solution by the alkaline fluids of the intestines is necessary for its purgative action. Lewis, Abeille, and Ferriar state that, when given in certain ways, gamboge acts as a decided diuretic. If this be true, ab- sorption of its active principle must occur. Schaur was not able, how- ever, to detect it in the urine of persons or of animals taking it. Even when he injected large quantities of it into the blood of dogs he failed to find it in the urine, although he did obtain a resinoid substance which he believes to be a derivative. Gamboge is so irritant that it is used in practical medicine only to give sharpness to purgative combinations. The full purgative dose would be from two to five grains (o. 13-0.3 Gm. ). OLEUM TIGLII CROTON OIL. U.S. The fixed oil obtained from the seeds of Croton Tiglium, a euphor- biaceous shrub of Hindostan and other portions of Southern Asia. This oil is quite viscid, varies in color from a pale yellow to a dark reddish brown, and has an acid reaction. Its taste is hot, acrid, and extremely persistent ; its odor faint, but peculiar. Croton oil consists chiefly of the glycerites of ordinary fatty acids, but contains also crotonoleic acid* which has been supposed to be its pure active principle, but is stated by Dunstan and Boole to be a mixture of inactive oily acids with a power- fully vesicating, resinous substance, croton-resin. THERAPEUTICS. Locally applied, croton oil is an intense irritant, producing upon the skin an eruption which is at first papular but in a very short time becomes pustular.* (See COUNTER-IRRITANTS.) Ad- ministered internally, croton oil produces in man and in most of the lower animals violent purging, with severe griping, and is capable of causing a fatal gastro-enteritis. Its action on the intestine is probably in part local * For a histological study of the eruption, see Wiener Med. Wochenschr., 1897, xlviL 1021. 676 LOCAL REMEDIES. and in part through absorption. In the experiments of Hertwig (quoted by Still6) and of Buchheim," purgation did not follow the injection of the oil into the veins of animals; but Conwell obtained a result contrary to this, and there is considerable testimony that its external use in man is sometimes followed by purging (Still6), and even by fatal results.* The experiments of Robert and of Hirschheydt x seem to prove that crotonoleic acid is both the purgative and vesicant active principle : it exists in the oil combined with glycerin. It is believed that the glycerite is slowly decomposed in the intestines, and that the acid which is thus set free acts progressively. Certainly, Hirschheydt found that pure crotonoleic acid, which has appeared in commerce, is not a practical purgative, ten milligrammes being very uncertain in their effects, whilst large doses are prone to produce excessive gastro- intestinal irritation. Injected into the blood, crotonoleic acid was found to be an exceedingly active depressant to the circulation. The amount of free crotonoleic acid in croton oil increases very markedly with age. On this account old croton oil, with an acid reaction, acts much more harshly than does the recent neutral or nearly neutral oil, and should be rejected for internal use. Croton oil is chiefly used in practical medicine in mania, apoplexy, or other diseases in which there is difficulty in administering a cathartic. It is also given in cases of very obstinate constipation when less active reme- dies have failed. It is the one cathartic employed when, as in some brain diseases, it is desired to revulse by the intestines. The dose is one drop, in emulsion, or by simply placing it upon the tongue. In over- doses, croton oil is a violent poison. TOXICOLOGY. Although in small amounts croton oil causes such severe symptoms, yet in larger quantities it has failed to produce as serious results as would be naturally expected. It is, however, very possible that in at least some of the recorded cases the oil was adul- terated. Cowan has reported a case (Husemann 57 ) of a child four years old who recovered in two days from a teaspoonful of croton oil taken on a full stomach ; Adams (Husemann) saw recovery in an adult after the ingestion of a drachm ; and the case is recorded of a woman M who took about an ounce, was vomited forty-five minutes afterwards with mustard, and finally recovered. The minimum fatal dose is not known, and prob- ably varies greatly. A child 59 aged thirteen months was killed by a quantity believed not to exceed three minims. Giacomini (Still6) reports a case in which twenty-four grains of the drug proved fatal in as many hours : although there were but four stools, the patient presented the symptoms of general collapse, preserving consciousness to the last. A little less than two drachms has caused vomiting and death without purging. 59 ! * See Schmidt's Jahrb., clxiv. ; also Robert's Arbeiten, 1890, iv. 45. t For other cases, see Med. Gaz., xliii. ; Edinb. Med. Journ., 1861 ; Lancet, 1870, i. ; Brit. Med. Journ., 1874, i. ; Ann. d'Hyg., 1871, i. ; also Robert's Arbeiten, 1890, iv. CATHARTICS. 677 The treatment of croton-oil poisoning is purely symptomatic. Opium should be given to lessen the purging, demulcent drinks to lessen the irri- tation. If collapse develops, cardiac stimulants should be administered hypodermically and bodily temperature maintained by the application of external heat. REFERENCES. CATHARTICS. 32 . 1. THIRY Sb. G. W., 1. 33. 2. RADZIEJEWSKI . . V. A. P. A., 1870, 37. 34. 3. ASP Ludwig's Arbeiten, 1868. 35. 4. SCHIFF Nuove Richerche sul 36. Potere Digerente, Mor- 37. . gagni, 1867. 38. 5. MOREAU A. G. M., 6 s., xvi. 234. 39. 6. THIRY Gaz. Med., 1871. 40. 7. BRUNTON .... Med. Press and Circular, Dec. 31, 1873. 41. 8. BRUNTON .... Pract., May, 1875. 4 2 - 9. VULPIAN Gaz. Md., 1873, 300. 43. 10. LEGROS Gaz. M6d., 1873. 44. 11. HOUCKGEEST . . A. G. P., 1872, 266. 45. 12. HAY J. A. P., xvi. ; xvii. 46. 13. CLOPATT . . . . S. Jb., 1896, ccli. 47. 14. HEADLAND . . . Action of Medicines, Lon- 48. don, 1867, 443. 15. ROHRIG Strieker's Med. Jahrbuch., 49. 1873. 5- 16. RUTHKRFORD . . Tr. R. S. Ed., xxix. 17. HEINRICHSEN . . S. Jb., ccii. 214. 51. 18. ROHRIG Exper. Untersuch. u. d. Physiol. der Gallenab- 52. sond., Vienna, 1873. 53. 19. FRONMULLER . . Med.-Chir. Centralb., 1879, 54. xiv. 20. KOHN S. Jb., cxciv. 246. 55. 21.. MILLER Z. K. M., 1881, iv. 56. 22. KOHLSTOCK . . . Charite Annalen, 1892, 57. xvii. 58. 23. GILBERT and DOMINICI . C. R. S. B., 1895, ii. 59. 24. PATON B. M. J., 1886, i. 60. 25. REGENSBURGER . C. M. W., 1877, 328. 61. 26. DOIT Gaz. des Hop., Oct. 24, 1885. 62. 27. WOROSCHILSKY . T. M., XV'i. 63. 28. BUCHHEIM . . . . V. A. P. A., xii. 64. 29. SIMON Animal Chemistry, Syden- 65. ham Soc. Trans, ii. 386. 66. 30. BIRD London Med. Gaz., 1845, 67. Soi. 68. 31. MICHEA L. L., 1849, i. 15. 69. WASSILIEFF . . . Z. P. C., 1882. SMITH, T. and H. . Chem. Gaz., 1851. GROVES Pharm. Journ., xvi. MEYER A. E. P. P., 1890, xxviii. KOHN S. Jb., cxciv. 246. BRANDENBURG . . In. Dis., Berlin, 1893. DIETRICH .... In. Dis., Dorpat, 1885. BARKER Amer. Pract., 1872. DRAGENDORFF and KUBLY . Vierteljahr. f Prakt. Pharm., xvi. STOCKMAN . . . . A. E. P. P., xix. 120. RECKE In. Dis., Gottingen, 1881. SANG L. L., 1891, ii. CURCI L. M. R., Oct. 1886. LUTON G. H. M. C., 1874, 455. STILLE Therapeutics, ii. MULLER In. Dis., Dorpat, 1885. HUSEMANN . . . Handbuch der Toxicolo- gie, 625. PODWYSSOTZKI . A. E. P. P., xiii. 40. Australasian Med. Gaz., ii. 237- MORRIES .... Reper. f. Pharm., xxxix. 134- STILL Therapeutics, ii. 459. KOHLER V. A. P. A., 1. 287. DARASZKIEWICZ . Meletemata de Resinarum, Dorpat, 1858. BUCHHEIM . . . . V. A. P. A., xii. i. HIRSCHHEYDT . . Robert's Arbeiten, 1890, iv. HUSEMANN . . . Toxicologie, ii. 443. B. M. S. J., 1868, i. 294. M. T. G., 1870, i. A. J. M. S., April, 1874. MACCALLUM . . . University of California, vol. i. DIXON B. M., 1902, ii. RAVIART S. M.,i895- TOY S. M., 1900. HEINZE P. N. W., 1903. KI.EEBERG .... Amer. Med., 1903, vi. STADELMANN . . B. K. W., xxxiii. BAIN B. M.J., 1898,1. PFAFF and BALCH . J. Ex. M., ii. FAMILY IV. DIURETICS. DIURETICS are medicines used for the purpose of increasing the flow of urine. Some of them act directly upon the secreting structure, but others only in some indirect way, as by increasing the blood supply to the kidney. It is notorious that diuretics often fail in practice when their action is most urgently needed. This result arises, in many cases, from the nature of the disease, and is not because diuretics are powerless or uncertain. Thus, in cardiac disease the congestion of the kidneys may be so great as to render secretion impossible ; and it is equally evident that when the secretory cells have been destroyed, as in advanced Bright' s disease, diuretics must be powerless. There are certain agencies whose influence upon the kidneys should never be lost sight of in exhibiting diuretics. Thus, cold, by checking the secretion of the skin, often acts as a most efficient remedy of the class. Again, mere vascular fulness tends to provoke excretion of water by the kidneys. E. Roux l found that the ingestion of large quantities of water greatly increased the flow of urine, but did not sensibly affect the elimination of urea or uric acid, although the elimination of the chlorides seemed to be augmented ; in Bocker' s 2 experiments, however, large draughts of water increased not only the amount but also the solids of the urine. The investigations of J. Meyer 3 explain these discrepancies and show how water may be of service in various diseases. Meyer found that when the tissues were full of the products of disintegration, the effect of water in increasing elimination was very marked, but that upon the wasting processes of the body the water exerted no influence. It would seem, therefore, that while we cannot by water produce tissue- disintegration, we can by it wash out the retained products of tissue- change ; and the great rarity of uninherited gout in America probably has some connection with the universal habit of drinking water very freely. Large draughts of simple water at regular intervals often act very favorably in acute Bright 1 s disease, greatly increasing the urinary flow and at the same time lessening the irritation of the kidneys. The origi- nal assertion of Porak and Bernheim, 4 that in violent irritation of the kidneys, in suppression of urine, in grave acute Bright' s disease, and in similar conditions great good could often be achieved by hypodermoclysis, is abundantly confirmed. This procedure consists in the injection deep into the cellular tissue of the buttocks of a thoroughly and very recently 678 DIURETICS. 679 sterilized normal salt solution ; * a half-pint to a pint of the liquid, at a temperature of about 100 F., may be slowly introduced without causing local irritation or giving much pain. A fountain syringe placed about three feet above the patient affords sufficient power to slowly force the liquid through a large hollow needle. In various inflammations or irrita- tions of the genito-urinary organs, as in gravel, whenever it is desired to make the secretion less irritating or less concentrated, the value of water as an adjuvant to medicinal diuretics should always be taken advan- tage of. That under various circumstances washing out of the blood, or, as Pierre Delbert 5 calls it, lavage of the blood, may be useful is shown by his experiments, in which it was found that the free intravenous injection of saline solution com- menced immediately after the hypodermic injection of a fatal dose of strychnine in the dog was able to prevent the development of the strychnine-poisoning, the excess of water in the blood evidently causing elimination to almost keep pace with ab- sorption. There is a very marked antagonism between the bowels, the skin, and the kidneys, so that great activity in the function of one of these emunctories lessens secretion in the others. When a diuretic action is desired, sweating and purging should be avoided. When a diuretic is exhibited, the patient should be kept cool, walking about, if able, or if it is necessary for him to remain in bed he should be covered lightly. Not rarely, a remedy which when administered cold and the patient kept cool afterwards will act as a diuretic, will when it is given hot and the patient kept warm act as a diaphoretic. The chief indications for the use of diuretics are as follows : 1. To maintain the action of the kidneys. It is hardly necessary here to discuss the necessity of excretion to the system. In various kidney diseases this indication is very urgent ; but as the lessened excretion too often depends upon a profound organic alteration of the renal secreting structure, it is evident that very frequently diuretics must fail when most needed. In the great majority of cases in which diu- retics are used to fulfil the present indication, only the mildest of the class should be employed. Whenever there is inflammation of the kidneys, even if it be chronic, irritating diuretics should be avoided. When lessened urinary excretion is purely functional in its origin, diuretics are often most serviceable. In fevers especially is it neces- sary to maintain the action of the kidneys ; for this purpose water should always be freely given during fever. The alkaline diuretics sometimes may be exhibited ; but the most generally serviceable of all remedies of the class in the febrile state is the sweet spirit of nitre. 2. To evacuate fluid. For this purpose hydragogue diuretics are employed in all forms of dropsy. * Normal salt solution is a 0.7 per cent, solution of common salt in distilled or pure water. For practical purposes it can be made by dissolving a teaspoonful of salt in a pint of water. 680 LOCAL REMEDIES. 3. To soothe and diminish irritation of the genito-urinary organs. The value of water in fulfilling this and the next indication has already been pointed out. By lessening the acidity of the urine and rendering soluble the uric acid which is present, the alkalies are equally important in carrying out the present and the following indication. 4. To alter the urinary secretion so as to prevent the deposition of calculons material. Notwithstanding it has been otherwise asserted, no practical measure has as yet been devised of dissolving a calculus when once formed. Even to alter the urine so as to prevent further deposition is probably impracticable, except in cases of uric acid or phosphatic diathesis. Diuretics are very naturally divisible into two sets, the hydragogue diuretics and the depurant diuretics. These classes, of course, grade more or less into each other, but they are sufficiently distinct for practical purposes. The drugs belonging to the first set simply increase the flow of water from the kidneys, and are therefore used chiefly for the relief of dropsy ; those of the second division exert a marked sedative action upon the system, and generally do not increase to any great extent the water of the urine, but modify the secretion in one way or another, and are mostly given to render the urine less irritant or for their sedative and eliminative action in acute disease. Under the heading of stimulant diuretics are considered certain sub- stances which do not of necessity increase the flow of urine, but whose active principles are eliminated by the kidneys, and by actual contact affect the mucous membrane of the genito-urinary organs. HYDRAGOGUE DIURETICS. SCILLA SQUILL. U. S. The bulb of Urginea maritima, a liliaceous plant growing in the south of Europe, especially on the shores of the Mediterranean. The bulb varies in size from that of a child's head to that of the fist. It is com- posed of numerous layers or scales, which separate when it is sliced for drying. As kept in the shops, squill is in horny flakes, of a white or red color, becoming leathery when wet, and having an acrid bitter taste. It yields to water and alcohol and also to vinegar. The nature of the active principle of squill has not been established. A number of glucosides have been described by chemists, and Merck has put upon the market three substances, scillin, scillipicrin, and scillitoxin* There is, however, no sufficient proof as to which, if any, of these sub- * Fronmiiller has reported (Memorabilien, 1879, xxiv. 250) a series of experiments made, upon persons suffering from various ailments, with the scillin, scillipicrin, and scillitoxin of Merck. He found that scillitoxin in doses of 0.45 grain acted as a rather uncertain diuretic, and frequently caused giddiness, headache, and loss of appetite ; scillin seemed to be devoid of diuretic properties ; while a gramme of a solution of scilli- picrin in water (one part in fifty) administered hypodermically usually caused a great flow of urine, without other evil symptoms than some smarting at the place of injection. DIURETICS. 681 stances represents the crude drug. Scillitin of the older writers and of Merck was a complex body. PHYSIOLOGICAL ACTION. In small doses squill acts upon man as a stimulating, slightly irritating, diuretic. In large doses it causes great abdominal pain, violent purging and vomiting, lessened or almost sup- pressed secretion of bloody albuminous urine, with slow pulse, ending, it may be, in collapse, convulsions, and death. Upon the lower animals squill acts very much as it does upon man, producing vomiting, violent purging, muscular weakness, dulness, stupor, disturbed respira- tion, muscular weakness deepening into paralysis, tremors disappearing in convul- sions, and finally death in the course of twelve or fifteen hours if the dose have been sufficient. In the experiments of Schroff 6 upon rabbits, scillitin of Merck differed from the alcoholic extract of squill in its effect upon the pulse and upon the pupil, and in the post-mortem appearances produced by it, the pericardial, sub- pleural, and pulmonary hemorrhages, and the gastric erosion produced by the scillitin, being wanting after death from the extract. C. Lupinski 7 found that scillitoxin is a powerful stimulant to the peripheral vagi in the frog, causing slowing of the pulse, and in certain doses diastolic cardiac arrest, and in the dog slowing of the heart. Large doses cause in the frog tetanic contractions of the heart. He also found that in the dog large doses finally paralyze the peripheral vagi and pro- duce a rapid pulse. The arterial pressure is increased, partly, it is affirmed, by the increased cardiac energy, and partly by a peripherally produced vaso-motor con- traction. It is certain that squill contains some substance which acts similarly to digitalis on the heart, and that this is to be found in the extract. Husemann affirms that the extract has no expectorant properties ; that it is a digitalis-like, cardiac stimulant, and acts as a diuretic solely by affecting the renal circulation. Squill is a stimulant to the kidneys, and in overdoses causes an irritation whose result is lessening of the secretion, scanty bloody urine, or absolute suppression of urine, according to the amount of the poison ingested. Its diuretic action has been noted in animals by Schroff and by Chiarenti (quoted by Stille), and there can be no doubt as to the power that squill has of increasing the watery portion of the urine. We know of no studies upon its action on the urinary solids. According to Stille, the external application of squill will pro- duce its characteristic effects on the system. It is a valuable remedy in dropsy when the condition of the system is atonic and when there is no disease of the kidney. It may even be used with advantage in serous cffitsion into the pleura or the pericardium dependent upon chronic inflammation of the membrane, especially in combination with calomel. A pill of one grain each of squill and digi- talis is very efficient in cardiac dropsy ; sometimes the addition of calomel is advantageous. The one centra-indication to the use of squill is the existence of Bright' s disease or of acute irritation of the kidney. TOXICOLOGY. According to Husemann, 8 twenty-four grains of squill have caused death. The treatment of the poisoning consists in the evac- uation of the stomach and bowels by ipecacuanha and castor oil, if nature 682 LOCAL REMEDIES. has not already fulfilled the indication ; the free use of opium ; the exhi- bition of large quantities of water, for its action on the kidneys ; and the usual measures for the relief of gastro-enteritis, if much tenderness be present. Early in the poisoning care should be exercised in the exhibi- tion of alcoholic stimulants, for fear of increasing the gastric irritation ; during the stage of collapse they may be imperatively demanded, and with their use should be combined that of dry heat applied externally, and of the other usual measures of relief during collapse. ADMINISTRATION. As a diuretic, squill should be given in solid form, one or two grains (0.06-0.12 Gm. ) every three hours, the dose being gradually increased until some nausea is felt. The preparations of squill are the tincture (TINCTURA SCILL^E ten per cent., U. S.), dose, ten to twenty minims (0.6-1.2 C.c. ) ; the vinegar (ACETUM SCILL^E ten per cent., U.S.), dose, ten to twenty minims (0.6-1.2 C.c.) ; the syrup (SYRUPUS SCILL.E, U.S.), dose, half to one flui- drachm (2-4 C.c.) ; and the fluid extract (FLUIDEXTRACTUM SCILL^E, U. S. ), dose, one to three minums (0.06-0.18 C.c.). SCOPARIUS BROOM. U. S. Scoparius is the dry tops of Cytisus Scoparius, or the common broom- plant of Europe, which is cultivated in this country and has in some places escaped from the gardens. It occurs as greenish twigs, with minute downy leaves, has a bitter nauseous taste, and, when bruised, a peculiar odor, and yields its virtues to hot water. Stenhouse discovered in scoparius a neutralized crystallizable principle, Scoparin, which prob- ably represents the purgative and diuretic influences of the drug, and also a liquid alkaloid, Sparteine. (See page 350). In overdoses, scoparius causes free purging, and even vomiting ; but as ordinarily administered it is an efficient hydragogue diuretic, which is much used in general dropsy, and is one of the most reliable remedies of its class. It is best given in decoction, half an ounce of the tops in a pint of water boiled down to half a pint ; of this an ounce may be given every three hours until some effect is produced ; or a fluid extract, which is not official, may be given in half-drachm doses. CALOMEL. Many years ago therapeutic writers, notably George B. Wood, asserted that the combination of digitalis, squill, and calomel yields in the treatment of dropsy, and especially of cardiac dropsy, diu- retic results much superior to either of the vegetable products alone ; but more recently E. Jendrassik 9 directed attention to the great practical value of calomel as a diuretic. The theory that mercury acts by increasing the amount of urea and thus provoking increased diuresis is hardly tenable.* * See Noel Paton (Brit. Med. Journ., 1886, ii.). DIURETICS. 683 The present experimental evidence in regard to the effect of mercury upon diuresis in the lower animals is contradictory. W. Cohnstein 10 affirms that the hypodermic injection of the mercurial produces very quick active diuresis in the rabbit, but Vejun-Tyrode and Nelson M failed to get a consistent diuretic action either in the dog, cat, or in the rabbit ; as they affirm that ' ' throughout all these experiments there were evidences of more or less severe renal irritation as shown by the presence of blood and casts and by diuresis, " it is probable that they employed the calomel in too large doses. According to Brasse and Wirth, 11 when mercury is given hypodermic- ally in large dose it soon appears in the urine, which is markedly in- creased in quantity ; if, as not rarely happens, the urine becomes albu- minous, excretion of mercury at once ceases, albumin and mercury never coexisting in the urine. Silva, 12 experimenting with defibrinated blood, finds that the addition of a mercuric salt causes the kidney vessels to dilate, the local blood-pressure to rise, and secretion to increase. More- over, it is certain that mercurials in excess cause desquamative nephritis ; so that it must be concluded that these preparations either stimulate or irritate the renal secretory structure proportionately to the amount present. According to Bieganski, the diuretic effect is most active after subcuta- neous injections and least so after inunctions. The destruction of renal secreting tissue by disease without doubt interferes with the diuretic action of mercurials, but the fact remains that in chronic parenchymatous nephritis with alarming decrease in the secre- tion of urine, calomel is one of the most effective diuretics known. In cardiac dropsy it is often very efficient in improving not only the dropsy itself but the condition of the digestive organs. In some cases of chronic cardiac disease the continued use of minute doses of the mercurial is very advantageous, but when it is desired powerfully to affect the kidneys large doses of the drug are required. Under these circumstances, we have found the administration of five grains of calomel every two hours until fifteen grains in all are taken to act most happily. It is sometimes, though rarely, necessary to use opium to check the purgative action of the calomel. When there is excessive debility some caution may be necessary in this use of mercurials, but we have seen life apparently saved for the time being by the removal of an acute suppression of wine in advanced Bright 's disease. XANTHIN COMPOUNDS. Xanthin, or Dioxypurin, yields the following compounds which are interesting therapeutically : First, Trimethylxanthin or Caffeine, which we have already fully considered. Second, three isomeric dimethylxanthins : i. Dimethylxanthin, Theobromine ; 2. Dimethylxanthin, Theophyllin (Theocin) ; 3. Dimethylxanthin, Paraxanthin. 684 LOCAL REMEDIES. Dimethyl.ranthin or Theobrominc has been chiefly used in the form of the sodium thcobromine salicylate, a white powder, soluble in less than half its weight of warm water, and containing about forty-nine per cent, of theobromine. It has been put upon the market as a proprietary remedy under the name of Diuretin, which, according to analysis, contains from thirty to forty per cent, of theobromine. Attention was first called to theobromine as a practical remedy, in 1890, by C. Gram 13 and Kouindig- Pomerantz. u PHYSIOLOGICAL ACTION. Theobromine is rapidly absorbed, and has been shown by the studies of Albanese, 83 Bondzynski and Gottlieb, 15 and of Kruger and Schmidt, 84 to be eliminated in part unchanged, and in part in the form of methylxanthin.* General Effects. The ordinary dose of theobromine causes no dis- tinct symptoms in man, and we know of no recorded cases of poisoning by it. According to I. M. Sabashnikoff 16 large doses produce in the lower animals a quickening of the respiration, which is followed after a toxic dose by intense dyspnoea, high temperature, free salivation, vomiting, diarrhoea, and excessive diuresis. The elevation of temperature, which sometimes amounts to 4 C. , is, according to Sabashnikoff, prevented by previous high section of the spinal cord. The detailed physiological action of the drug has not been worked out; according to Sabashnikoff there is increased irritability of the motor area of the cerebral cortex, and upon the striated muscles the drug acts as does caffeine. The toxic dose lowers the arterial pressure. (Cohnstein, 17 and Bock. ) Cohnstein found that the full therapeutic doses had no percepible influence upon the blood-pressure, and in Bock's researches the pressure was only elevated occasionally, the most marked phenomenon being great increase in the frequency of the pulse-rate, probably due to excitation of the accelerator mechanism of the heart, since the vagi was found to be thoroughly active. As the result of studies made upon the isolated heart of the mammal, Bock believes the fall of pressure is due to an action upon the cardiac muscles, which decreases its elasticity. He also believes that the rise of pressure, sometimes produced by the small doses, is the result of the increased pulse frequency. Kidney. In the oncometrical studies of Gottlieb and Magnus, 103 the increased diuresis was accompanied by an increase of the size of the kidney. In the chloralized animal these investigators found that the in- creased diuresis persisted, although the kidney was markedly below its normal size, evidence that the diuresis is the outcome of a direct action upon the secretive power of the kidney. THERAPEUTICS. Theobromine has been much used as a diuretic *The researches mentioned show that the exact form of elimination, as well as the per- centage of the various educts, varies in different species of animals, and very probably in different individuals under varying circumstances. In man, 3-methylxanthin seems to be the chief educt, though y-methylxanthin (Heteroxanthin) has been found ; whilst in rabbits 7-methylxanthin is especially produced. DIURETICS. 685 which is not irritant to the kidneys, and rarely causes disagreeable symp- toms. It has been given in acute and chronic nephritis with excellent results, and has been especially recommended in cardiac dropsy, with the statement that it increases the force and regulates the character of the cardiac beat when the heart is weak. (See Masius, also Pawinski. 18 ) In rare cases it acts unfavorably, causing headaches, irregularity of the pulse, vomiting, diarrhoea, and even according to W. Schmieden haematuria. From eighty to one hundred and twenty grains (68 Gm.) maybe admin- istered during the course of the day, in capsules or solution, or hypoder- mically. According to Demme, to a child six years old twenty to thirty grains (1.32 Gm. ) may be given in the twenty-four hours. AGURIN is a white, slightly bitter powder, freely soluble in water, which is said to consist of five parts of theobromine acetate and two parts of sodium acetate. It should always be prescribed in the form of the powder, its solution not being stable, but should be taken in dilute solution in doses of ten to fifteen grains, three or four times a day. In Mosauer's 98 experiments agurin seemed to be more irri- tant to the kidneys than theobromine. Concerning Paraxanthin we have not very much information, but, according to Dreser-Elberfeld, it acts in a manner similar to theocin, increasing the output of urinary solids as much as does that drug, but not having nearly as powerful an in- fluence in the excretion of water from the kidneys. Theophyllin or Theocin was first isolated from the tea-leaf by Kossel, but in such minute quantities as not to be a commercial product until the discovery by Traube that it could be produced by synthesis resulted in its being put upon the market under the name of Theocin. It is a crystalline substance, soluble in one hundred and seventy-nine parts of water at 18 C., in eighty-five parts at 37 C. It was first brought forward by Minkowski, 91 as a very active diuretic, and has been reported upon by a number of German clinicians. According to C. Doering, it is about as poisonous as caffeine, but Doering, 92 Thienger, 91 and Kramer, 94 all agree that it is much more active as a diuretic than is either caffeine or theobromine, in- creasing remarkably both the excretion of water and solid matters from the kidney. It has been tried both in cardiac and renal dropsies and is found to be very posi- tive in its influence. Not rarely theocin has produced disagreeable symptoms, the most common of which are those of gastric irritation ; in some cases severe vomit- ing, headache and general malaise have been reported ; and Schlesinger in two cases noted the occurrence of epileptiform convulsions after the taking of five doses of o. 2 gramme of theocin. The effect of theocin is also apt to be fugacious, the system apparently in a short time becoming accustomed to its use, so that it fails to cause diuresis.* Its maximum effect is commonly apparent the second or third day of its ingestion. In order to avoid gastric irritation, it is better to give in frequent small doses up to from 7.5 to 8 grains a day (0.5-1.2 Gm. ). SPIRITUS ;THERIS NITROSI. U. S. When given in a single large dose (a teaspoonful to a tablespoonful) and the patient afterwards kept cool, sweet spirit of nitre acts as a feeble diuretic, at the same time * Albanese 83 believes that the rapid diminution of diuresis after the administration of theocin is due to the deposit in the renal canaliculi of crystals of trimethylxanthin ; basing his belief upon microscopic studies, and upon the fact that he was enabled, by injecting large quantities of saline solution in the lower animals, to maintain the activity of the drug. 686 LOCAL REMEDIES. soothing the kidneys. It is often useful when there is slightly diminished renal excretion of functional origin, or when the kidneys suffer from slight congestion, as shown by aching in the loins. DIGITALIS, in its general relations, has already been sufficiently dis- cussed, and it remains only to speak of its employment as a diuretic. In the first place, it should be distinctly understood that it has no alterative effect whatever, either upon the nature of the secretion or upon the mucous membrane over which that secretion flows. In other words, when it has any effect it is purely a hydragogue diuretic, simply increasing the watery portion of the urine. That digitalis has direct diuretic properties cannot, we think, be doubted. Nor does it seem less certain that it varies greatly in their exercise, so that when given to persons in health it will sometimes produce free diuresis and will at other times fail to do so. Another point to be constantly borne in mind during its administration is the fact that, like all the other effects of digitalis, diuresis is very slowly induced, and is very persistent when produced by the ordinary cautious method of administration. The diuresis of digitalis is not simply a result of its action on the circula- tion, since it will sometimes appear before the circulation is sensibly affected. At the same time, it is very evident that in disease the good effect of digitalis upon the renal organs is often in large measure due to its action upon the heart. Thus, in dropsy from a dilated heart the renal gland-cells cannot secrete because they are not supplied with the proper kind and quantity of blood, their circulation, like that of the remainder of the body, being nearly stagnant. If under these circum- stances digitalis be exhibited, and the circulation becomes compara- tively free and active, the resultant diuresis is wrought out through a double mechanism, partly indirectly and partly directly produced by the drug. As a consequence of these facts, clinicians have long since practically determined that digitalis is especially valuable as a diu- retic in cardiac dropsy. Digitalis is also very useful in renal dropsy, both in the subacute and in the chronic form. Of course, like every- thing else, it frequently fails in these varieties of Bright' s disease, but certainly it should always be tried. In acute suppression of urine the external application of digitalis is often efficient. Flannels wrung out of the infusion, or containing an ounce of the tincture, may be applied to the abdomen and covered with oil-silk. Some practitioners prefer poul- tices made directly of the leaves. Lente 19 says that he has been accus- tomed to use, even in children, four ounces of the best English leaves, and with a quart of water ' ' make a poultice which extends all round the body, and from the thorax to the pelvis." The application should not be left on for more than from eight to ten hours, and only in desperate cases should very large amounts be employed, as the external use of a single ounce of the tincture has caused almost fatal collapse.* * Case of E. F. Fannell (Brit. Med. Journ., March, 1871). DIURETICS. 687 The dose of the powder of digitalis, as a diuretic, is three grains (0.2 Gm.) a day (in divided doses), increased by a grain every second or third day, until some sensible effects are manifested. The infusion or the tincture may be substituted for the powder, in corresponding dose. Digitalis, in the majority of cases, is best given in combination : in cardiac dropsy it is much more efficient if given with squill ; in renal diseases the potassium bitartrate may be exhibited simultaneously. Jaborandi, Strophanthus , and Caffeine are active, practical diuretics. (See respective articles.) SUGAR. In the last few years it has been affirmed by S. Meslach, Zavadsky, Germain-Se'e, and other clinicians that both glucose and the sugar of milk are active hydragogue diuretics, which may often advan- tageously be used in the treatment of cardiac dropsy, pleuritic effusions, etc., but are of little value when there is renal disease. The general testimony seems to be that the sugar of milk is the more active of the two. These sugars may be given in doses of from one to six ounces (30-180 Gm. ) a day, administered in concentrated syrup or in milk. How sugar under these circumstances acts as a diuretic, or whether it has any influence upon the nervous system and circulation, is at present doubtful. According to the experiments of Albertoni, all sugars injected into the veins cause a rise of the arterial pressure by a direct stimulation of the heart. He also found that the kidneys, as tested by Roy's oncometer, become congested or swollen. DEPURANT DIURETICS. POTASSIUM. On account of the physiological activity of potash as a base, it exerts great influence upon the physiological activity of its salts. These, for our present purposes, may be well divided into the vegetable salts, in- cluding the carbonates, and the mineral salts. The mineral salts of potash are all of them powerful local irritants, and most of them are capable of taking life when given in overdose. As therapeutic agents they have to be studied separately. The official vegetable salts of potash, with the exception of the bi-tartrate, act similarly upon the system, varying al- most solely in that some are more irritant than others. PHYSIOLOGICAL ACTION. Local Action. Caustic potash is a pow- erful escharotic, and many of its vegetable salts are more or less irritant. These salts are also powerful depressants probably of all of the higher tissues. Astalfoni % found that when locally applied to the brain cortex, to the spinal cord, to the peripheral nerves, or to the muscles, the potash salts produce a very pronounced lessening of irritability. When very weak solutions were employed this condition of depression was often preceded by one of excessive irritability, but when solutions of five per cent, were used, no such stage was observable. 688 LOCAL REMEDIES. The effects of the ordinary therapeutic doses of the potash salts upon the human system are not sufficiently obvious to be perceived by the clinical observer. Only when a single dose is overwhelmingly large, or when by long continued use there has been an accumulation of potash in the system, are there such obvious results as general muscular weak- ness, lowered temperature, depression of the circulation, dyscrasia, and, it may be, even excessive fluidity of the blood. With many of the pot- ash salts the local irritant influence upon the alimentary canal and the kidneys may overshadow the other phenomena of the poisoning. In the lower animals potash and its vegetable salts in toxic dose produce de- pression of the circulation, fall of temperature, lessening of both voluntary and reflex movements, and finally death from cardiac paralysis. Neuro-muscidar System. Podocaepow 20 believed that the action of potash salts in the frog is chiefly upon the muscles, but the experi- ments of Guttmann, of Ringer and Morshead, 21 and of Ringer and Mur- rell," have definitely proven that the brain, the spinal cord, the motor and sensory nerves, and the muscles are all attacked by potash. Ac- cording to Ringer and Murrell, the spinal cord and, next to it, the brain are the most sensitive to the action of the drug. Circulation. Our knowledge of the action of the small dose of pot- ash salts upon the circulation is very imperfect, but there is considerable testimony to show that such dose produces rise in the arterial pressure. If there be a rise of pressure produced by the minute doses of the chloride it would seem probable that it is due to an action upon the blood-vessel walls, since Boltazi 95 found it impossible by any dose of the potash salts to increase the work done by the frog's heart ; and in the experiments of Astalfoni, injection of minute doses of the potash through the blood-vessels of the kidney or of one exsected leg caused contraction of the arterioles. Traube 2S asserts as the result of his experi- ments that, injected into the blood in doses of two or three grains, the potassium nitrate produces a fall in the pulse and a rise in the arterial pressure. Aubert and Dehn have experimented with a number of the salts of potassium, and found that, with the exception of the permanganate, they all act upon the circulation in the manner just described. It remains at present writing, however, doubtful whether the rise of pressure just spoken of is a direct phenomenon caused by potash. No dose of a potash salt ever calls forth symptoms of circulatory stimulation from the human body. Further, Podocaepow and also Aubert and Dehn affirm that the rise following the potash injection in the animal usually lasts only three minutes, and that in no case is the maximum effect perceptible for more than ten minutes. Aubert and Dehn further assert that there is no cumulative action, the repetition of small doses of the drug at brief intervals leaving no residual effect, the pressure re- turning to the normal after each injection, just as though no previous injection had been given. The correctness of this statement remains doubtful, since Guttmann asserts that there is a gradual rise of pressure. Full doses of potassium greatly and progressively lower the arterial pressure, and this is the only influence of the potash salts upon the cir- culation which is clinically demonstrable. The fall of pressure is very largely due to the direct action of poison upon the heart, but there can DIURETICS. 689 be no doubt that the muscle-fibres of the blood-vessels are also de- pressed, so that the blood-pressure is reduced by the conjoint depression of the muscle-fibres of the heart and blood-vessels. This action is shown by Dogiel M to be a portion of the wide-spread general muscular influence of the poison, the heart muscle and the arterial muscle-fibres being sim- ply more sensitive to the influence of potash than are the skeletal and in- testinal muscles. The heart is usually arrested in diastole (Podocaepow and Guttmann), and as pointed out by Traube, its muscle may be unable to respond to electrical stimulation.* According to Aubert and Dehn," for a few seconds before complete suspen- sion of cardiac movements there are irregular, "stormy" convulsions, which run through the heart in a sort of peristalic manner with great rapidity, but have no effect in expelling the blood. The observations of Aubert and Dehn, that the effect of the potash is not per- manent unless it is continued a certain length of time, is in accord with that of Astalfoni, who found in using potash locally that functional irritability could be restored by washing out the part with a weak solution of sodium phosphate. Podo- caepow K and Guttmann have found that in fatal poisoning the contractility of the cardiac muscle may be in a measure preserved if the potash salt has been very slowly introduced into the circulation. The method by which the changes in the pulse are produced by the small dose of potash also remains uncertain. Traube affirms that if the vagi be cut after ex- hibition of the potash salt, the lessened pulse-rate instantly becomes rapid, and the already increased arterial pressure rises still further. The same observer also found that after section of the pneumogastrics small doses of the nitrate produced a fall in the pulse, with increased arterial pressure ; but on a repetition of the dose in the same animal no lessening of the pulse-frequency was perceptible, while each time the pressure rose. This seems to indicate that the cardiac action of the drug is independent of the inhibitory apparatus, which is confirmed by the experiments of Aubert and Dehn upon atropinized dogs. Section of the vagi, according to Guttmann, has no influence upon the action of the poison, and it seems to be established that the depres- sion of the cardiac muscle is by a direct action of the salt upon the muscle itself. Influence upon Nutrition. Outside of the body, potassium favors very greatly the oxidation of organic substances. Thus, when albumin or haematin is dissolved in water no change, or a very slow one, occurs, but if potash be added the organic principle is oxidized with extraordinary rapidity. There is now sufficient evidence to establish the original theory of Lehman, that this oxidizing influence is exerted by these salts in the living body. The fall of temperature produced by poisonous doses of potassium salts is probably due to excessive loss of heat caused by loss of * The poisonous influence of potash upon the heart was, we believe, first discovered by Black (Comptes-Rendtts, 1839), and has been confirmed by Bouchardat (Antiuaire de Therapeutique, 1844), by Grandeau ( Robin's Journal de I' Anatomic, 1864), by Rabuteau {U Union Medicate, 1871), and by others. 44 6 9 o LOCAL REMEDIES. tone in the blood-vessels. That there is under the influence of the alkali a great increase of nitrogenous elimination both in health and disease seems to be fairly proved. In an elaborate series of experiments upon himself, E. A. Parkes 27 found that liquor potassae (two fluidrachms) when taken fasting, produced in from thirty to ninety minutes an increased flow of slightly acid urine containing the whole of the alkali and organic matter, which differed in quality from that ordinarily found in urine, and was also larger in amount than normal. An organic acid, certainly neither uric nor hippuric, was believed to form a part of the solid matter by Parkes, who attributes the alteration of the urinary solids to the oxidizing influence of the potash. Taken after meals, the liquor potassae acted simply as an antacid, and had no perceptible effect upon the urine. Both potassium acetate and nitrate in Parkes' s experiments failed to act on the urine, probably because taken in too small doses, for it is a fair presumption that their oxidizing influence is less than that of potash itself. Certainly other experimenters have determined that they do influence the urinary excretion. Golding Bird M found that in a case carefully tested, under favor- able circumstances, three drachms of potassium acetate increased the solids of a dog's urine from four hundred and sixteen to seven hundred and eighty-two grains, or, deducting all the eliminated potash, to over six hundred grains. The increase of the uric acid was about thirty-two per cent. ; of the urea, about sixty per cent. ; of ex- tractives, including kreatine, kreatinine, etc. , about twenty per cent. ; or, speaking absolutely, the uric acid was increased eighty-five grains, the urea seventy-two grains, and the extractive thirty-six grains. Rabuteau w found that the daily in- gestion of seventy-five grains of potassium chloride caused an increase of twenty per cent, in the amount of urea discharged. Aug. Dehn M has also experimentally found that the potassium salts greatly increase the elimination of urea. The conclusion reached by experimental research made upon healthy men and animals namely, increased tissue-change as the result of potash ingestion is in close concord with those upon diseased organisms. In six observations upon subjects affected with what may be termed indifferent diseases, such as lead palsy, Parkes 31 found that the urea was increased, and also the sulphuric acid, by the use of drachm doses of liquor potassae. Austin Flint J2 has studied the effect of potassium nitrate upon a number of persons suffering from various diseases, and found that it very greatly increases the amount of solids in the urine. In rheumatism Parkes found that liquor potassae increased the elimination of sulphuric acid, but had no decided influence on the uric acid. He, however, used such small doses of the drug as not to get the effect obtained in the alkaline treatment of the disease, since he expressly states that the urine remained acid. Rheumatism, gout, and the uric acid diathesis certainly bear some relation with one another. It has long been customary to use potash salts in excess of uric acid in the urine, and the relief obtained has been believed to be due to the conver- sion of the acid into a urate. Basham M affirms, however, that as the result of a series of analyses he has found that in uric acid diathesis not only is there a great increase of the urea during the use of potash, but also that the uric acid, either free or combined, in the urine is greatly diminished. Basham, remembering that Schunck had proved that, under the oxidizing power of potash, uric acid outside of the body is converted into oxaluric acid, which in its turn is readily metamorphosed into oxalic acid and urea, carefully examined the urine of gouty patients taking the alkali, and found that not only was the urea increased, but that oxalic -acid also appeared as the uric acid decreased, and that the urine, on standing, deposited DIURETICS. 691 crystals of calcium oxalate, although none of these could be found in it when first voided. This research of Basham certainly seems to demonstrate that in uric acid diathesis the potassium salt increases the oxidation and the ultimate metamorphosis of tissue. Rabuteau, in his experiments with potassium chloride, found that the urine maintained its acidity, although potassium acetate, carbon- ate, or citrate produced alkalinity of the urine. A plausible explana- tion of this diversity is that the vegetable acid salts are oxidized into carbonates in the system, while mineral acids of necessity pass through unaltered. Thus, from the urine of a patient taking two hundred and seventy grains of the nitrate daily, Alfred S. Taylor 34 obtained 158.7 grains of the ingested salt per diem.* If, as there is much reason to believe, a vegetable acid when given alone passes through the system in great measure unchanged, while, as asserted by Munch, 35 and as seems to follow from the facts already brought forward, the same acid is found when combined with an alkali to be oxidized and converted into carbonic acid, there is in this strong corroboration of the belief that the potash salts increase oxidation in the system. Putting all the evidence together, it seems to us that the oxidation theory must be accepted as exceedingly plausible and probable, although not, perhaps, absolutely proved. When a potassium salt is given in large doses for a long time, it produces a condition of dyscrasia, with impoverishment and excessive fluidity of the blood. It is probable that there is some connection between these changes and the oxidizing power of the drug. POTASSII CARBONAS. U. S. Potash of commerce, obtained from wood-ashes and other sources, occurs in the form of fused, stony masses, variegated in color, and of a caustic, burning taste ; when purified so as to form pearlask, it becomes of a bluish-white color. When further purified so as to conform with the official tests, it occurs as a coarse, granular, whitish powder, very deliquescent, soluble in its weight of water, insoluble in alcohol. It is too irritant for use as an internal remedy. POTASSII BICARBONAS. U. S. Potassium Bicarbonate occurs in transparent, colorless crystals, not deliquescent, slightly alkaline to the taste and to test-paper. It dissolves in 3. 2 parts of water at 59 F. , but is insoluble in alcohol. This salt may be used as an antacid or to increase the liquidity of the bile, as in catarrhat jaundice, but it is so disagreeable to the taste that the acetate or citrate is much preferable when free con- tinuous medication of the general system is desired. Dose, as an antacid, fifteen to thirty grains (1-2 Gm. ), in dilute solution. * A portion of the potassium salts escapes through the intestines, as Kramer (Annales cTHygi&ne Publique et de Mid. Ltff., 1843, i.) has found the nitrate in the faeces of animals taking it ; and it is much more probable that the nitrate not accounted for in Taylor's investigation was eliminated by the intestines than that it was decomposed in the system. 692 LOCAL REMEDIES. LIQUOR POTASS^E. U. S. Solution of Potassa is a colorless, water-like liquid, of a strong, acrid, alkaline taste, and is made by boiling a solution of the potassium bicarbonate with lime. It contains only five and eight- tenths per cent, of the alkali, but is capable, in overdose, of acting as an irritant poison. Dose, ten to twenty minims (0.6-1.2 C.c.), well diluted. POTASSII CITRAS. U. S. Potassium Citrate is a whitish, granular, deliquescent salt, of neutral or very slightly acid reaction, freely soluble in water. It is the least offensive to the palate of all the potassium salts, except the tartrates. The Solution of Potassium Citrate ( LIQUOR POTAS- SII CITRATIS, U. S. ), has long been used as a diaphoretic in sthenic fevers. The dose is one-half to one fluidounce ( 1 5-30 C. c. ) every one or two hours. The so-called Effervescing Draught ! , which was formerly made by preparing two solutions, one consisting of lemon-juice and water, equal parts; the other of potassium bicarbonate, one drachm, water three ounces; an ounce of each of the solutions to be put together and drunk during effervescence, has been replaced by the POTASSII CITRAS EFFER- VESCENS, U. S. {Effervescent Potassium Citrate}, a powder which must be kept in well-stoppered bottles, which contains twenty per cent, of potassium citrate, and may be given in doses of sixty to one hundred and twenty grains (4-8 Gm.). This preparation is especially useful when in fever there is a tendency to sick stomach. POTASSII ACETAS. U. S. Potassium Acetate is a perfectly neutral white salt, of a decidedly saline taste, extremely deliquescent, and solu- ble in half its weight of water. It is made by dissolving the bicarbonate in acetic acid, and evaporating. It occurs sometimes as soft, fibrous masses, at other times it has a foliated structure. THERAPEUTICS. An important use of the vegetable salts of potas- sium is in acute inflammatory rJieumatism. Before the introduction of the salicylates the alkaline treatment was the best that was known for cases of thoroughly acute rheumatism : the medicine must be given freely, an ounce to an ounce and a half in the day, and be persisted in ; opium, of course, being at the same time employed in as large doses as are required to relieve the pain : after a few days, when the violence of the symptoms has abated and decided anaemia appears, the exhibition of the drug should be discontinued and potassium iodide, with tonics, be substituted. In cases subacute from the beginning a combination of the potassium iodide and acetate is sometimes very efficient, ten grains of the former and thirty of the latter being administered three or four times a day. The potash probably does good in rheumatism by lowering arterial action, by favoring oxidation and elimination of partially effete materials, and by neutralizing excessive acidity. DIURETICS. 693 As depurants, the potash salts are very useful in various diseases. Attention has been especially called by Golding Bird to their value in that class of cases spoken of as chronic biliorisness. In chronic malarial poisoning, in catarrhal jaundice, and in the jaundice of simple hepatic torpor they are often of use. In uric acid gravel and in uric acid cal- culus the vegetable salts are useful in checking the deposition of the uric acid, but have no influence upon calculi already formed. ADMINISTRATION. As usually exhibited, the potash salts are ex- ceedingly distasteful. There is no need of this whatever. The citrate may be given dissolved in lemon-juice, or, what is a still more pleasant method, a syrupy solution of the bicarbonate and the citrate may be made, of such a strength that every tablespoonful of it shall contain half a drachm of each salt. At the time of exhibition one or two tablespoon- fuls of this may be put in a little water, and to it be added a large table- spoonful of lemon-juice, the whole to be drunk while effervescing. If the patient takes in the course of the day six of the largest doses mentioned, the whole amounts to an ounce and a half of potassium citrate. When the remedy is used simply as a depurant, as in jaundice, such large doses are, of course, not proper ; a teaspoonful of the alkaline solution, with a corresponding amount of lemon-juice, taken three times a day, will gen- erally be sufficient. POTASSII BITARTRAS. U. S. Potassium Bitartrate occurs in white crystalline crusts or masses, which are commonly pulverized before being sold as Cream of Tartar. It usually contains calcium tartrate, and is only sparingly soluble in cold water. It is probably eliminated unchanged as a bitartrate, and certainly differs from its congeners in being an active hydragogue diuretic and cathartic. Half an ounce to an ounce (15-30 Gm. ) of it given at once will very generally cause watery purging. An ounce (30 Gm. ) of it in a pint of infusion of juniper-berries, taken, in divided doses, during the twenty-four hours, will very often act most happily in dropsy. In acute desquamative nephritis, cream of tartar is often very serviceable ; as, however, the avoidance of irritation of the kidneys is imperative in this disease, the infusion of juniper should not be used. POTASSII SULPHAS. U. S. Potassitim Sulphate occurs in small aggre- gated, transparent, very hard crystals, permanent in the air, usually short six-sided prisms, possessing a nauseous somewhat bitter taste. It is said to be, in doses of four or five drachms, ' ' a mild purgative, operating usually without heat or pain or other symptoms of irritation," and in doses of one or two drachms a laxative. It is, however, a powerful irri- tant, and we have never seen it administered. Mowbray states that the salt is used in France as a popular abortifacient, and that he has seen very alarming symptoms produced by four drachms of it. Two ounces have caused a fatal gastro-enteritis (Taylor). 694 LOCAL REMEDIES. POTASSII NITRAS. U. S. Potassium Nitrate, or Nitre, is ordinary saltpetre. Chili saltpetre has no physiological similitude with true salt- petre, being a sodium nitrate. Saltpetre occurs in more or less perfect, long, striated, semi-trans- parent, six-sided prisms, with dihedral summits ; of a sharp, saline, somewhat cooling taste ; containing no water of crystallization, but de- crepitating when thrown on the fire, from the evaporation of water me- chanically retained in the crevices of the crystals ; soluble in four or five times its weight of cold and in two-fifths of its weight of boiling water, sparingly soluble in proof spirit, insoluble in absolute alcohol. PHYSIOLOGICAL ACTION. Potassium nitrate is so violently irritant that the general effects of the potash in it upon the system are lost in the local symptoms caused by its overdose. If by very free dilution the local irritant influence of the nitre be overcome, the poison loses much of its virulence and extraordinary amounts can be taken without serious results. * The symptoms of poisoning by potassium nitrate are an intense burn- ing pain in the stomach, coming on in a few minutes after the ingestion of the poison, and soon followed by violent vomiting, and, it may be, free purging, with, after some hours, collapse, great muscular weakness, and not rarely local convulsive tremblings. The matters vomited, and even the stools, may be bloody (Husemann 36 ). Sometimes the ner- vous symptoms predominate, and the purging may be absent : col- lapse, with slight vomiting and with or without paralysis of the lower limbs, may alone exist. Suppression of urine has been noted in some cases.* After death, very grave lesions are found in the stomach and the intestines, such as intense redness and congestion, and effusion of blood into the submucous coat, and sometimes into the stomach itself. Even ulceration and corrosion of the mucous membrane have been ob- served. How far potassium nitrate acts upon the blood is at present uncertain ; Mairet and Combemale assert that it alters the red blood- corpuscles. Sometimes, however, death has occurred, in poisoning by saltpetre, with great suddenness. In the only cases of this character the record of which we have read the dose has been very large, and it is possible that the death has been the result of the paralyzing action of the potash upon the heart. Potassium nitrate is of no value as an internal remedy, having been superseded by the vegetable salts in acute rheumatism. Its local action is very similar to that of the chlorate. * In a case under the care of Wilks (Guy's Hasp. Rep., 3d series, 1863, ii. 173), a man suffering from renal dropsy took, between October 28 and December 26, 1862, one pound twelve ounces and six drachms of potassium nitrate, with benefit. As one ounce has caused death in three hours (Taylor, Medical Jurisprudence, 2d ed., i. 237), this patient received in fifty-nine days the equivalent of twenty-eight fatal doses. Again, according to Stille ( Therapeutics, ii.), Brocklesby habitually prescribed one ounce of the salt a day. and Martin-Solon even two ounces per diem. f Case, Pharmaceut. Journ., Feb. 1846, 356. DIURETICS. 695 In the treatment of poisoning by saltpetre, after the stomach and bowels have been emptied, the usual means for the relief of toxic gastro- enteritis should be resorted to. POTASSII CHLORAS. U. S. Potassium Chlorate occurs in white rhom- boidal plates of a pearly lustre and of an acerb taste, soluble in seventeen parts of water at 59 F. , and in two parts of boiling water. PHYSIOLOGICAL ACTION. Locally, this salt is a very active stimu- lant and irritant. As a poison it has frequently caused death.* The smallest fatal dose is not known, but half an ounce has killed. A drachm taken during a night has killed an infant a year old, and three drachms a child three to four years old. The symptoms may be acute or subacute. In the rapid cases there have been violent vomiting, profuse diarrhoea, excessive dyspnoea, great failure of the heart's action, and marked cya- nosis. In the subacute cases the gastro-intestinal symptoms have been severe, with generally vomiting of blackish-green matters and distinct swelling of the liver and the spleen. The urine is markedly lessened in quantity, albuminous, often of an opaque reddish-brown or blackish color, and showing under the microscope brownish or yellowish-brown tube-casts, frequently containing the detritus of blood-corpuscles. Haemoglobinuria has been noticed, f and methsemoglobin is a common constituent. The nervous symptoms have been severe delirium, coma, tonic and clonic cramps, and a peculiar stiffness of the extremities. Headache, loss of appetite, violent pains in the abdomen and other portions of the body, and marked abdominal tenderness have usually preceded the loss of consciousness. Not rarely there are minute ec- chymoses upon the surface of the body, and even more frequently there is a general jaundice. In some cases the patient has rallied and seemed to be on the road to recovery when the fatal relapse has oc- curred. After death the blood is usually chocolate-colored, the gastro-intes- tinal tract is inflamed, the liver and spleen are enlarged and filled with the brownish debris of red blood-corpuscles, the bone-marrow and the brain are often similarly colored, while the mucous membranes are usually swollen and ecchymosed. The kidneys are profoundly affected, their tubules full of brownish casts and their epithelial structure evincing a nephritis. The most characteristic and probably the most important of the lesions is the change in the blood, which was first noticed after death by F. Marchand." L. Riess 88 noted in a case during life that many of the red blood-corpuscles were decolorized, and others contained little granules of an elliptic shape. The changes in the blood are the result of the formation of a substance apparently identical with the * For collection of cases, see Chlorsaure A'ali, J. von Mering, Berlin, 1885. To Jacobi, of New York, belongs the credit of having first called attention to the dangerous action of this much-abused remedy (Amer. Med. Times, April, 1861, 245). t Trans. Internal. Congress, 1881, 1. 463. 696 LOCAL REMEDIES. methsemoglobin of Hoppe-Seyler and characterized by the appearance in its spectrum of a dark line in the red. Methaemoglobin is readily produced by mixing either sodium chlorate or potassium chlorate with blood: that it is produced in the body during life has been experimen- tally proved in cats, dogs, and rabbits by A. Falck, 89 by H. Lenhartz,* and by Cahn, 41 and is also shown in man by the wide-spread staining not only of the interior of the blood-vessels, but also of the walls of the whole lymphatic system, found after death from the chlorate. (Case, N. Hammer. 42 ) The physiological action of potassium chlorate is evidently not domi- nated by the base of the salt. S. J. Meltzer ** found that the injection of three to four minims of its five per cent, solution produced immediate violent convulsive disturbances, with coma, and that similar symptoms were caused by the sodium chlorate, and it is evident that both salts act directly upon the nerve-cells. The theory that potassium chlorate yields its oxygen in the system is absurdly untrue.* The potassium chlorate escapes unchanged with the saliva, urine, and probably all the secretions of the body. Isambert found it in the tears, the bile, the nasal mucus, and even in the milk of nursing women. Rabuteau took five grammes of the salt, and recovered from the urine 4.873 grammes. Isambert, in two experiments, recovered respectively ninety-five and ninety-nine per cent, of the ingested potassium chlorate from the urine. J. von Mering,* 3 out of fifteen grammes given to a dog, obtained 14.7 grammes ; out of five grammes which he took himself, he recovered 4.62 grammes ; and when he took but a single gramme he obtained from the urine of the next ten hours 0.91 gramme. From the saliva and urine of a case of mercurial stomatitis in which five grammes had been exhibited he recovered 4. 54 grammes. Indeed, Marchand, in experiments upon the lower animals, asserts that he has recovered all of the ingested chlorate from the secretions, and we must conclude that it practically all escapes from the body unchanged. F. von Mering believes that some of the potassium chlorate is reduced in the system, chiefly because he thinks that methae- moglobin is formed by a process of oxygenation. The exact nature of methaemo- globin is, however, not made out : according to C. A. Macmunn, 44 methaemoglobin is probably a mixture of haematin with soluble albumin, Hoppe-Seyler having shown that it is not a result of oxidation. Von Mering in one or two instances in the dog found a slight in- crease in the chlorides of the urine during the administration of the chlorate, and it is possible that a minute quantity of the chlorate does undergo deoxidation ; but it must be considered established that any such change, if it occurs at all, affects so small a portion of the drug as not to be worthy of consideration. The therapeutic dose of potassium chlorate produces no sensible effects in the system. Isambert found that, when taken by himself in doses of from two to five drachms, it caused salivation, free diuresis, increase of the appetite, and, when not well diluted, gastric irritation ; * For detailed discussion, see tenth edition. DIURETICS. 697 the urine continued strongly acid, and contained an excess of rosacic acid, uric acid, and the urates. THERAPEUTICS. Largely on account of the groundless belief that it favors oxidation of the blood, the profession has in the past used potassium chlorate in many forms of disease believed to be due to blood-poisoning. There is, however, no scientific or clinical reason for believing that the drug has any value whatsoever in these or other diseases, except through its local action, and without doubt its free use in diphtheria has often greatly aided in the production of a fatal result, its irritant action upon the kidneys making it a dangerous remedy in that disease. On the other hand, it is a very valuable local remedy, especially in diseases of the mucous membrane of the mouth. In the follicular or aphthous stoma- titis of children * it is almost a specific, its free elimination with the saliva causing it to be constantly present in the mouth, even when taken inter- mittently. Its local influence, however, is too feeble to be effective in such serious diseases as diphtheria. In ordinary sore throat or angina the combination of it with the fluid extract of sumach-berries is as a gargle most effective. In chronic dysentery and other diseases of the colon it may be applied by means of the large enemata. In hemorrhoids the injection, when the patient goes to bed, of half to one ounce of its saturated solution, com- bined with a few drops of laudanum to secure retention, is often of the utmost service. In stomatitis and allied diseases powders of potassium chlorate, ten to fifteen grains (0.6-1 Gm. ) each, should be put dry in the mouth every three to six hours, so as to secure the maximum of local action. LITHIUM. When one of the official salts of lithium is ingested ab- sorption begins almost immediately. The lithium has been detected in the urine by Clarence Good " ten minutes after the hypodermic injection. Excretion goes on, however, slowly, since the same chemist has found lithium in the urine twenty-three days after the injections had been stopped. The chief channel of escape is through the urine, but excre- tion occurs also from the salivary and gastro-intestinal glands. No cases of serious poisoning by a lithium salt have been recorded, but we have seen large, repeated doses produce pronounced malaise, with muscular weakness and some disorder of the digestion. According to P. Pergami 10 the exhibition of lithium carbonate distinctly increases the alkalinity of the blood. According to the studies of Binet, 45 the lithium salts produce in mam- mals pronounced feebleness, with nausea, diarrhoea, and other digestive disturbance, increasing dyspnoea, fall of temperature, and death, usually * Laborde (Bull. Theraf)., 1874, Ixxxvii.) and Tacke (Inaug. Diss., Bonn, 1878) have shown that sodium chlorate acts physiologically like the potassium salt ; and S. Ringer and H. Sainsbury (London Lancet, 1882, ii. 736) have found it equally efficient in stomatitis. 698 LOCAL REMEDIES. preceded by convulsions. Death is said to be due to a direct centric arrest of respiration, although a markedly depressing influence is exerted upon the heart, which is finally arrested in diastole. When life is main- tained by artificial respiration the peripheral nerves become entirely para- lyzed and the muscles affected, as is shown by peculiar fibrillary contrac- tions. In poisoned frogs, also, the excitability of the muscles is some- what diminished. Lithium salts were originally recommended by Ure and Garrod in the treatment of uric acid diathesis and of chronic gout ; theoretically because it was believed they had the power of dissolving uric acid and the urates. This has recently been denied (Clarence Good), nor has it ever been proven that these salts are distinctly depurative, increasing the elimi- nation of effete materials through the kidneys. That they have such action is, however, indicated by the results of their clinical use, and whilst they are not as valuable in gout as was originally claimed for them, as a minor remedy they are often serviceable in chronic cases in doses of from five to fifteen grains (0.3-1 Gm. ), given after meals. E. Duche 46 affirms that their prolonged local application is very useful in relieving gouty joints^ and that in gouty conjunctivitis frequent washing of the eye with a solution of lithium carbonate, i to 500, is effective.* The U. S. Pharmacopoeia recognizes Lithium Benzoate (LiTHii BENZOAS, U. S. ), a white powder, soluble in four parts of water; Lithium Carbonate ( LITHII CARBONAS, U. S. ), similar in appearance, but sparingly soluble in water, five to fifteen grains (0.3-1 Gm. ); Lithium Citrate (LiTHii CITRAS, U. S. ), a white deliquescent powder, soluble in two parts of water, ten to thirty grains (0.62 Gm. ) ; also the Effervescent Lithium Citrate (LiTHii CITRAS EFFERVESCENS, U. S. ), a white powder, each one hundred grains of which contains five grains of lithium citrate, with sodium bicarbonate and citric and tartaric acids to produce effervescence. When added to water it effervesces freely and affords the most pleasant means at our command of exhibiting an alkaline salt of lithium. The Lithium Bromide (LiTHii BROMIDUM, U. S. ) is used simply as a bromide. PIPERAZINUM. Piperazidine, or Diethylendiamine, occurs in small, glassy, lustrous tables, or, in the form of the hydrochlorate, in silky, lustrous, lanceolate crystals. It has been used as a solvent for uric acid, one part of which with one part of piperazine will dissolve in fifty parts of water. It has also been alleged that it will dissolve the albu- minous substances which form an important part of uric acid calculi. Undoubtedly, however, it will not dissolve an already formed calculus in * Mariinea.il 1 s Solution, Martineau affirms that he has obtained very remarkable results in the treatment of diabetes mellitus by the use of a solution of lithium carbonate and sodium arsenate. In gouty diabetes this arsenical solution of lithium may prove of service : from five to ten grains of lithium carbonate and one-thirtieth of a grain of sodium arsenate may be given three times a day. DIURETICS. 699 the human bladder, though it may sometimes be of service as a solvent in uric acid gravel. Piperazine is rapidly absorbed and eliminated through the kidneys, producing a reddish-brown urine. Concerning its general physiological action there is very little knowledge. The therapeutic dose produces in man ordinarily no symptoms, but we have seen muscular weakness and general depression follow the continuous exhibition of large doses. Whether it does or does not affect the general nutrition is unknown. Vogt asserts that it checks uric acid elimination. Ebstein and Sprague have found that it has no effect either upon the excretion of urea or of uric acid. It has been very largely used in gout, but has failed to sustain its first reputation, although in occasional cases it apparently exerts a markedly beneficial influence for a time. It causes too much pain to be used hypodermically ; fifteen to twenty grains (1-1.3 Gm. ) of it may be administered by the mouth, during the day, in a quart of plain or car- bonated water. It is too hygroscopic and too easily decomposed to be given in powder or in watery solution, but the solution of one part in twenty of alcohol and eighty of water is said to be fairly permanent. Van der Klip has found that in the lower animals, in sufficient dose, it produces vomiting, irregular breathing, general muscular weakness, and relaxation ; that it decreases the oxidizing power of oxyhaemoglobin and the coagulability of the blood ; and that it checks the action of peptonizing ferments. * LYCETOL. Dimethylpiperazine Tartrate. A white powder, readily soluble in water, with an acidulous rather pleasant taste. It has been brought forward as a substitute for piperazine, over which it is asserted that it has the advantage of being less apt to cause disturbances of digestion when given in large dose. It has been favorably reported upon in purulent cystitis as well as in various forms of uric acid diathesis. Dose, from fifteen to thirty grains (0.9-1. 9 Gm.) given daily in from one to two pints of water. HEXAMETHYLENAMINA. U. S. Urotropin. Formin. This substance occurs in rhomboidal, very soluble crystals, odorless, and of a sweet, bitterish taste. In the presence of acid it breaks up into formaldehyde and ammonia at the temperature of the human body. PHYSIOLOGICAL ACTION. Local Action. Absorption and Elimina- tion. Urotropin is distinctly irritant. It is absorbed with great rapid- ity, having been detected in the urine ten minutes after its ingestion, and is eliminated from the kidneys in great part unchanged, although, as first stated by Loebisch, 47 it is to some extent decomposed in the organism with the liberation of formaldehyde. * H. Hildebrandt (Berlin. Klin. Wochen., 1894) having found that piperazine, even in small quantities, checks the saccharifying influence of haemic and other hydrolytic ferments, although it has no destroying influence, tried the drug in diabetes produced in dogs by phloridzin with pronounced success ; so that the remedy is certainly worthy of trial in diabetes mellitus. 7 oo LOCAL REMEDIES. Casper 48 injected urotropin under the skin of a rabbit and found formaldehyde in the blood, and also was able in some cases to detect formaldehyde in the urine of persons taking urotropin, an observation which has been confirmed by Suter, 81 and by Citron. 51 In a number of cases, however, these chemists failed to detect formaldehyde in the urine after the ingestion of urotropin, and P. J. Cammidge 8 * could not get it at all ; so that it is evident that elimination of formaldehyde after the ingestion of urotropin is an inconstant phenomenon. It has been suggested that urotropin is decomposed by the acid juices of the stomach, but F. Suter 81 found that when he put formaldehyde into the stomach of the rabbit, or took formalde- hyde himself in safe dose, it was impossible to detect it in the urine ; so that any formaldehyde liberated by the urotropin in the stomach would in all probability either be distributed in the system or thrown off in some other form than formalde- hyde. It has been shown by Suter that when urotropin is mixed outside of the body with acid urine it undergoes decomposition, although this does not occur when the urine is alkaline. It is therefore probable that that portion of ingested uro- tropin which is decomposed suffers change in the kidney and upper urinary pas- sages ; a conclusion which is confirmed by an observation of Casper, that when the urine of a person who has taken urotropin is allowed to stand a continuous forma- tion of formaldehyde goes on in it for days. The bactericidal influence of urotropin in the urine is not altogether dependent upon its conversion into formaldehyde, since Cammidge 82 has shown that it has itself very marked bactericidal powers. General Effects. The ordinary therapeutic dose of urotropin pro- duces no general symptoms, and we know of no cases of poisoning by it. In the dog the daily dose of two hundred and eighty grains is said to cause no other disturbance than renal irritation (Nicolaier). The in- gestion of one hundred and twenty grains a day of it usually causes in man burning pain in the bladder and urethra, especially after urination, followed, if the dose be continued, by the appearance of albumin, red blood-corpuscles, and abundant renal epithelium in the urine. P. J. Cammidge has noted after the free exhibition of urotropin general formi- cation, especially intense at night, ending in a few days in a diffuse rash, suggesting that of measles. THERAPEUTICS. Urotropin was especially brought forward by Bar- det 49 and Laquers as a solvent for uric acid, but, according to the ex- periments of Arthur Nicolaier, 50 it is less active in this respect than is piperazine, and is of no practical value for the solution of renal calculi. On the other hand, it ranks with piperazine as useful in uric acid diathe- sis, and is especially valuable as an alterative diuretic in the treatment of Pyelitis, cystitis, and ammoniacal phosphaturia. In gonorrhoea it has failed to be of service. Our present experimental knowledge so strongly confirms the clinical experience of Citron that in order to get the good effects of urotropin in genito- urinary inflammations it is essential to maintain the acidity of the urine, that in most cases benzoic or boric acid should be exhibited at the DIURETICS. 701 same time as is urotropin.* Urotropin has been used as prophylactic against nephritis in scarlet-fever. Preisisch 10 * found 9 per cent, of kid- ney lesions with urotropin as against 13 per cent, without. Dose, fif- teen to twenty grains (1-1.3 Gm. ) three or four times a day, well diluted. QUINIC ACID. Acidum Quinicum. Chinic Acid. This is a white crystalline powder, soluble in water, which was originally suggested for use in the uric acid diathesis by Weiss, 88 who claimed that it markedly reduces the formation of uric acid. In the experiments of Ulrici, 87 however, quinic was found to have no distinct influence upon uric acid elimination, and Dolff is said to have reached similar con- clusions. Nevertheless, in gouty conditions quinic acid has been used to a consider- able extent, especially in combination with antilithic bases. Of these combinations the most important are as follows : PIPERAZIN^E QUINAS. Sidonal. A white powder, freely soluble in water, which has been employed in chronic gout and in other forms of uric acid diathesis. Richter w found that it was possible to prevent in pigeons the deposition of uric acid in the joints, which normally is produced by injecting potassium chromate, by a simultaneous use of sidonal. The dose of sidonal is seventy-five to one hundred grains (5-8 Gm. ) given in the course of the day, dissolved in a pint or more of water. UROTROPIN.*: QUINAS. Quinotropine. This is sold in two forms : Quino- tropine I., containing seventy-three percent, of quinic acid and twenty-seven per cent, of urotropine ; and Quinotropine II., containing eighty per cent, of quinic acid and twenty per cent, of urotropin. Both of these compounds are freely soluble in water, yielding with sugar a lemonade-like drink. Nicolaier and Hagenberg 90 were not able to observe any diminution in the excretion of uric acid in human subjects, produced by the administration of quinotropine. It is claimed for quinotro- pine that it yields formaldehyde, and is useful not only for the relief of t"he uric acid diathesis, but as a urinary antiseptic. Quinotropine I. is given in doses of from fifty-five to eighty-two grains (3.7-5.5 Gm.) per day; Quinotropine II., seventy- five to one hundred and twelve grains (5-7.5 Gm. ) per day ; dissolved in one to two pints of water. HELMITOL. This is a urotropine compound which is said by Paul Rosenthal 1(>l to give off formaldehyde in much larger amounts to the urine than does urotropine, and to be a valuable drug in the treatment of inflammations in the genito-urinary tract, when administered in doses of fifteen to twenty-three grains ( 1-1.5 Gm. ) three or four times a day. HETRALIN. This is said to contain sixty per cent, of hexamethylentetramin, and is soluble in one to four parts of hot water. It is highly recommended by Ledermann ^ in specific inflammations of the genitalia, administered in the daily dose of one and a half to two grammes in three to five portions. * The clinical experiments of Suter seem worthy of note. He found after fifteen grains of salol, boric acid, or benzoic acid were exhibited to a healthy subject at bed- time, the early morning urine made as good a medium for the growth of bacteria as ordinary urine ; but if forty-five grains of urotropin or of salol were given the urine passed was very inert towards bacteria ; one to two days being required for the growth of bacteria in the salol urine, four days in the urotropin urine, provided the urine was acid. Salol acted as well in the alkaline urine. 702 LOCAL REMEDIES. URASOL. Acetyl-methylene-disalicylic Acid. This substance, which was first made by S. Lewis Summers, is said to contain seventy-five per cent, of salicylic acid, sixteen per cent, of acetic acid, and eight per cent, of formaldehyde, and is alleged to be broken up in the system with the liberation of formaldehyde. It occurs as a yellowish-white powder, insoluble in water, and is asserted to be non- irritating, so that it may be given in capsules. It has been used as an antirheumatic and analgesic, but chiefly for germicidal influence on the genito-urinary tract, as in cystitis. Dose, ten to twenty grains (0.6-1.0 Gm. ). STRONTIUM. Although the contrary had been stated by Thomson in 1818, by Vul- pian in 1885, and by Gautier in 1886, the strontium salts were generally believed to be violently poisonous until in 1891 J. V. Laborde 52 pointed out that this reputation was due to the fact that the commercial strontium salts were contaminated with the violently poisonous barium salts, and further affirmed that the chemically pure strontium salts were innocuous unless in very large doses. Absorption and Elimination. Our present knowledge indicates that the soluble salts of strontium are precipitated by the alkalies and phosphates of the intestines, so that they are only partially absorbed; and that elimination is even more slow than absorption ; so that stron- tium has a tendency to accumulate in the liver, in the muscles, and espe- cially in the bones. Horatio C. Wood, Jr., 53 (confirmed by H. C. Wood and John P. Arnold 5 *) determined that when an official salt is administered by the mouth only a minute proportion of it can be obtained from the urine, whilst a great amount is readily obtainable from the faeces. It was further found that when it has been given hypodermically only a minute proportion of strontium escapes with the urine. The research of L. R. Mendel and H. C. Thacher 97 indicates, however, that more of the strontium is absorbed than would seem to be indicated by the results of the earlier investigators. These researches confirmed the results previously obtained, but showed further that when strontium is subcutaneously or intravenously given, a large portion of it can be obtained from the faeces, so that elimination must take place in the alimentary canal. These later results do not, however, disprove the theory that the strontium salts, given by the mouth, are chiefly precipitated in the alimentary canal and largely escape from the rectum. Wood and Arnold found that when a solution of strontium salicylate was added to the o. i per cent, solution of hydrochloric acid practically all of the salicylic acid is at once set free ; also, that when strontium salicylate is given to man the urine in an hour contains much of the acid, but only a trace of the base. As the o. i per cent, hydrochloric acid solution is considerably less acid than is normal gastric juice, and as alkalies and soluble phosphates ac- tively precipitate soluble strontium salts, it is altogether probable that the stron- tium found in the faeces after the administration of the drug by the mouth repre- sents not only, as believed by Mendel and Thacher, strontium which has been absorbed, but also even more largely strontium which has failed of absorption. It would appear that in most cases the strontium in a medicinal salt acts chiefly as a carrier, and there is reason for believing that the precipi- tated strontium is a feeble antiseptic, and that when in the alimentary DIURETICS. 703 canal it acts favorably upon the digestive glands and muscles, so that in the case of the official salts, strontium bromide, strontium iodide, and the non-official strontium salicylate, the base is useful as a carrier which yields the substance with which it is in combination to absorption and at the same time improves digestion. How far the clinical results which have been obtained from the use of the strontium lactate are due to the strontium and how far to the lactic acid is at present uncertain.* PHYSIOLOGICAL ACTION. So far as we are aware, there are no cases on record in which any distinct symptoms have been produced in man by the strontium salt unless the substance with which the strontium was combined was sufficiently active to make itself manifest. Binet affirms that the continuous use in the lower animals of excessive doses produces general feebleness with increasing dyspnoea, cyanosis, clonic convulsions, and death from asphyxia. When recovery occurs the motor power gradu- ally returns, with stiffness, ataxic movements, and not rarely with the assumption of bizarre positions. In an elaborate series of experiments by Horatio C. Wood and John P. Arnold it was found that the intra- venous injection of the strontium lactate or nitrate will produce in the lower animals a marked progressive lessening in the pulse-rate, with a notable increase in the arterial pressure ; the diastolic pauses becoming so long and the cardiac beats so powerful that in the dog the pulse-waves may extend over as much as eighty or ninety millimetres. If the dose has been repeated, or if it has been sufficiently large in the beginning, the pulse-waves after a time become very quick and the arterial pressure falls, although it may not reach the normal ; finally, after a toxic dose, both pulse-rate and pressure at last gradually fall to zero. It was found that section of the spinal cord high up does not prevent the rise of the arterial pressure produced by the strontium salt; and that, therefore, this rise must be due to an action exercised upon the heart itself or the blood-vessel walls. It was further demonstrated by Wood and Arnold that the strontium salts increase the cardiac energy in the isolated frog's heart and also cause contraction of the blood-vessels by a local action upon their walls ; and that, therefore, the circulatory phenomena spoken of are partly the outcome of cardiac stimulation and partly caused by contraction of the vessels, the final fall of the arterial pressure being due to the stimu- lation passing over into paralysis. As was pointed out some time ago by * That the effect of strontium is often subordinate to that of the substances with which it is combined is abundantly proved. Thus, in the experiments of Laborde a certain dose of strontium bromide caused localized anaesthesia with a rapid development of som- nolence deepening into stupor, with marked lessening of reflexes ; followed, if the dose had been large enough, by collapse, coma, and complete loss of reflex activity ; whilst a similar dose of strontium chloride produced no sensible effect. The presence of stron- tium phosphate in bone-ash is affirmed by some and denied by other chemists. Accord- ing to the experiments of Max Cremer, the feeding of strontium phosphate to young hounds has no influence in preventing the development of rickets (Munchen. Med. Wochen., 1892). 704 LOCAL REMEDIES. Lauder Brunton, strontium affects directly the muscles; and it was found by Wood and Arnold that the extremely minute dose of strontium at first markedly increases the height of the muscle-curve and widens out its base ; so that the drug primarily increases muscular power and pro- longs the contraction period ; later, there was muscular paralysis under the continuing influence of the poison. Experiments upon the frog's heart showed that the strontium salt has exactly this influence upon the heart, so that evidently strontium is a muscle-poison which first stimu- lates and afterwards paralyzes the muscle-fibres, acting both upon the muscles of the skeleton and upon those connected with circulation ; its stimulating effect upon the circulation being, therefore, the result of a wide-spread general influence of the drug upon the muscle-fibres both of voluntary and involuntary life. It is probable, though not proved, that the muscle-fibres in the intestines are also affected by the strontium salt. According to Binet, 55 in poisoning by strontium, the nerve-centres are more powerfully affected by the drug . than are the muscle-fibres them- selves, death occurring in the frog from centric respiratory paralysis ; the peripheral nerves and the muscles, although depressed, still retaining after death some functional power. STRONTII LACTAS. Strontium Lactate occurs as a white granular powder, or in crystalline nodules. It is odorless, of a slightly bitter saline taste, permanent in the air, and soluble in about four parts of water ; also soluble in alcohol. Accord- ing to Germain Se"e, Paul, Dujardin-Beaumetz, and other French clinicians, it is a valuable remedy in the treatment of chronic Bright 1 s disease, increasing the amount of urine, diminishing or arresting the excretion of albumin, and improving the gen- eral nutrition. In albuminuria due to pulmonary congestion the drug is said to be of service, and it is further affirmed that its influence for good is especially marked in desquamative nephritis and much less pronounced in interstitial nephritis. In many cases there is no increase in the flow of urine, and the good achieved seems to be due to an alterative influence upon the secreting structure of the kidney. In our own experience the strontium lactate has not yielded results such as are ascribed to it by the French observers. It is, however, a harmless remedy, whose use should not prevent the administration of other appropriate drugs. The usual dose is from twenty to thirty grains (1.3-2 Gm. ), given three times a day in solution ; but much larger amounts have been exhibited without producing apparent symptoms. ALTERATIVE DIURETICS. BUCHU BUCHU. U. S. The leaves of Barosma betulina and crenulata, natives of Southern Africa. These leaves are an inch or less in length, from three to five lines broad, of various forms, but always notched on the edges, and having a strong, rather rank, yet somewhat aromatic odor, and a warm, bitterish taste. They owe their virtues, which they yield to water and to alcohol, to a volatile oil and a bitter extractive. THERAPEUTICS. Buchu is a mild stimulant and alterative to the mucous membrane of the genito-urinary organs, useful in subacute and DIURETICS. 705 chronic cystitis, chronic pyelitis, and irritation of the bladder. Its oil is undoubtedly absorbed, and is eliminated by the kidneys, to whose secre- tion it imparts its odor. In irritated bladder, when the urine is highly acid, and when there is a constant desire to urinate, with but little relief from micturition, buchu, in combination with a vegetable salt of potash and the sweet spirit of nitre, often gives great relief. The dose of the fluid extract (FLUIDEXTRACTUM BUCHU, U. S. ) is a teaspoonful (4 C.c. ), well diluted, from four to six times a day. PAREIRA. U. S. Pareira Brava is the root of Chondodendron to- mentosum, a climbing plant of South America. There appear to be in the root one or more alkaloids.* Pareira Brava has been used with asserted advantage in cystitis, in irritable bladder, and in chronic gonor- rhoea, and appears to exert a stimulant action upon the mucous mem- brane of the whole genito-urinary apparatus. The doses of the infusion (one ounce to one pint) and of the fluid extract (FLUIDEXTRACTUM PAREIRA, U. S. ) are respectively a wineglassful (62 C.c.) and a tea- spoonful (4 C.c. ), four or six times a day. UVA URSI. U. S. Bearberry is the leaves of Arctostaphylos Uva Ursi, a low evergreen shrub, indigenous to northern maritime Europe, and also to our northern coasts as far south as New Jersey. They are from half an inch to an inch in length, wedge-shaped, thick, coriaceous, with a smooth, rounded margin. The odor is hay-like, the taste bitter- ish, astringent, and somewhat sweetish. Uva ursi contains gallic acid, besides arbutin, which occurs in long acicular colorless crystals, freely soluble in water, less so in alcohol and in ether, and is resolved by the action of sulphuric acid into glucose and hydrochinone. THERAPEUTICS. Uva ursi is capable of acting as a weak astringent, but has been long used in medicine for its influence upon the genito- urinary mucous membrane, and at present is employed only in chronic Pyelitis, cystitis, and other affections of the genito-urinary mucous mem- brane, when a slightly stimulant and an astringent action is desired. Hughes found that in doses of one grain arbutin is a powerful diuretic. It seems to be free from poisonous properties, as Jablonowski M took in forty-eight hours eighteen grammes of it without discomfort. It produces a discoloration of the urine varying from pale greenish to dark greenish brown, the color deepening upon standing. It has been proved by the researches of Von Mering, 57 of L. Lewin, 58 and of Steffen 5 ' that the discoloration of the urine is due to the breaking up of the arbutin in the body into glucose and hydrochinone. The change probably occurs in the kidneys, as arbutin is free from toxic properties, while Brieger has shown that hydrochinone is poisonous, producing in man giddiness, ringing in the ears, lessening in the force and frequency of the pulse, etc. The * See U. S. Dispensatory, isth ed., 1085. 45 7 o6 LOCAL REMEDIES. experiments of Lewin indicate that arbutin is the active principle of uva ursi, and Forster 60 has shown that hydrochinone * is a powerful dis- infectant and antiferment. It is stated that a one per cent, solution will arrest putrefaction and alcoholic fermentation, while one-half per cent, is sufficient to check butyric fermentation. Concerning the therapeutic value of arbutin there has been much discussion, but the fact that it has failed to come into general use indicates that it has little practical effect, and that H. Laurentz K1 was right in asserting that uva ursi is of value in genito-urinary diseases chiefly on account of its tannic acid and of the volatile oil which it contains. Whatever may be the value of arbutin, it is evident that the solid extract fully represents the drug, of which it is about four times the strength. It may be given in drachm (4 Gm. ) doses three or four times a day. The dose of the fluid extract (FLUIDEX- TRACTUM UV^E URSI, U. S. ) is two to four fluidrachms (7-15 C.c. ), three to four times a day. CHIMAPHILA. U. S. Pipsissewa is the dried leaves of Chimaphila umbellata, a little indigenous perennial, distinguished from its inert con- gener C. maculata by the uniform glossy green of its leaves. The latter are about an inch and a half long, wedge-shaped, notched, pointed, and coriaceous. They contain tannic acid, bitter extractive, and, according to Samuel Fairbank, a crystalline principle, Chimaphilin. Pipsissewa is nearly equivalent to uva ursi in its therapeutic value, though not so effec- tive. The dose of the fluid extract (FLUIDEXTRACTUM CHIMAPHILA, U. S. ) is a teaspoonful (4 C.c.) three or four times a day. TRITICUM. U.S. Couch-grass. The rhizome of Agropyrum repens, a common grass of Europe and the United States, is believed by many surgeons to have a sedative influence upon the genito-urinary organs, and has been considerably used in irritable bladder and cystitis. A decoction * According to the experiments of Brieger, hydrochinone produces in man giddiness, ringing in the ears, and lessening in the force and frequency of the pulse. In the experi- ments of P. J. Martin ( Therap. Gaz., 1887, 289), it caused in the frog violent convulsions, followed by paralysis and death through failure of the respiration, both convulsions and paralysis being the result of a direct influence upon the spinal cord. Small doses pro- duced in the mammal increase of the arterial pressure, which, if the dose were sufficient, was followed by a depression. When the vaso-motor system was paralyzed and the heart isolated from the central nervous system, the effect of hydrochinone on arterial pressure was scarcely perceptible : so that it is probable that it chiefly affects the vaso-motor sys- tem. The bodily temperature is lowered by large doses of hydrochinone. According to the experiments of Martin, this is mainly due to an increase of heat-dissipation, and is, therefore, probably the result of a vaso-motor paralysis. H. G. Beyer, after experimenting upon the frog and terrapin (Anter. Journ. Med. Sci., April, 1886), came to the conclusion that hydrochinone affects both the heart and the vessels as a paralyzant, lessening the rate of the heart and the amount of work done, and causing dilatation of the arterioles. Antaeff has found that if two per cent, of hydrochinone be added to fresh urine the latter will remain for many days without undergoing alkaline fermentation, but that if hydrochi- none be added to a solution of urea a rapid decomposition of the urea occurs, which Antaeff believes to be the result of a direct chemical action of hydrochinone or urea ( Lancet, April, 1887). DIURETICS. 707 of it may be taken ad libitum, or the fluid extract (FLUIDEXTRACTUM TRITICI, U. S. ) may be given in doses of two to three fluidrachms (8-12 C.c. ) in a tumblerful of water every three hours. JUNIPERUS. Juniper is the fruit of the common juniper, Juniperus communis, of Europe and this country. These berries are round, bluish bodies, about the size of a large pea, of a sweetish, terebinthinate, aro- matic taste. They owe their properties to a volatile oil (OLEUM JUNIP- ERI, U. S. ). They yield to boiling water and to alcohol. Juniper is gently stimulant and cordial to the stomach. Upon the kidneys the oil exerts a decided stimulant action, and when freely given is capable of irritating the renal organs above the secreting point, and of producing lessened secretion, strangury, and even suppression of urine. Juniper is largely used as an adjuvant to cream of tartar or the alkaline diuretics. On account of its stimulant local influence upon the alimentary canal, it renders the cream of tartar far more acceptable to the stomach, and at the same time aids its diuretic action. Sometimes juniper is employed for its stimulant action on the mucous membrane of the genito- urinary organs in chronic pyelitis and in chronic catarrh of the bladder. In the form of the compound spirit (SpiRixus JUNIPERI COMPOSITUS, U. S.), or its equivalent, gin, juniper is often useful in the subacute congestion of the kidneys frequently seen in old persons, and characterized by aching in the loins and lessened urinary secretion without more serious symptoms. Dose, two to four fluidrachms (715 C.c.). The infusion is made by macerating an ounce of the berries in a pint of boiling water for an hour, the whole to be taken in divided doses during twenty-four hours. The dose of the oil (OLEUM JUNIPERI, U. S. ) is from five to fifteen drops (0.3-1 C.c.) ; of the spirit (SPIRITUS JUNIPERI, U. S. ), from thirty to sixty minims (2-4 C.c.). OLEUM ERIGERONTIS. U. S. Erigeron Canadense, or Canada Flea- bane, contains a large proportion of a yellowish volatile oil of a rather pleasant odor and taste, which has properties resembling those of tur- pentine, but much less stimulating. It may be employed in affections of the genito-urinary organs and in passive hemorrhages. It is especially valuable in menorrhagia. According to Starke, 6 * it is very efficacious in gonorrhoea. The dose is five to twenty drops (0.3-1.2 C.c.) every two or three hours, and is best administered on sugar. OLEUM SANTALI, U. S. , is a pale yellowish, strongly aromatic vola- tile oil, of a pungent, spicy taste, from the distillation of the wood of Santalum album. It is insoluble in water, but readily soluble in alcohol. When pure, it is a local irritant and probably capable of affecting the general system, although its physiological action has not been properly investigated. S. Rosenberg w has noticed after doses of sixty drops a day irritation of the alimentary canal, burning in the urethra during 7 o8 LOCAL REMEDIES. urination, and an eruption of small red prominences upon the entire surface of the body, involving even the conjunctiva. Oil of sandal-wood is very efficient in chronic bronchitis and in the advanced stages of acute bronchitis, also in gonorrhoea after the first period of acute inflammation. From ten to twenty minims (0.6-1.2 C.c. ) of it may be given, in capsule or emulsion, three or four times a day. TEREBINTHINA TURPENTINE. U. S. Canada Turpentine (TEREBINTHINA CANADENSIS, U. S), or Canada Balsam, is the product of Abies balsamea, or Balm of Gilead, or Ameri- can Silver Fir, as it is variously named, a beautiful evergreen indigenous to the extreme Northern United States and to the British provinces. It is a thick and viscid but clear, yellowish liquid, which by age and ex- posure becomes converted into a hard, brittle, translucent, resinous mass. Canada Balsam is very rarely, if ever, used in medicine, but resembles turpentine in its action on the system : when fresh it contains about twenty per cent, of the volatile oil, which is its active ingredient. White Turpentine (TEREBINTHINA TURPENTINE, U. S. ) is the con- crete oleoresin obtained by incising Pinus palustris and other species of pine. The supply in the American market comes almost exclusively from North Carolina and other of our Southern States. It is rarely, if ever, itself used in medicine, but by distillation is separated into a vola- tile oil and a resin (Rositi), which is official under the name of RESINA. EMPLASTRUM RESINS, U. S. , Adhesive Plaster, or, in ordinary language, Sticking Plaster, is formed by adding rosin to lead plaster. CERATUM RESINS, U. S. , Resin Cerate, or Basilicon Ointment, contains rosin, yellow wax, and lard ; it is used as a mildly stimulating application to indolent burns, ulcers, etc. CERATUM RESIN^E COMPOSITUS, U. S., con- tains also turpentine (11.5 per cent. ) and linseed oil. OLEUM TEREBINTHINA OIL OF TURPENTINE. U.S. This is a yellowish, highly inflammable oil, of a strong peculiar odor and a hot biting taste, moderately soluble in alcohol, freely so in ether, very slightly so in water. By heating with muriatic acid it is converted into a red liquid and a white crystalline substance, which, from its re- semblance to camphor, has received the name of artificial camphor. Turpentine is remarkable for having the property of absorbing oxygen and converting it into ozone.* PHYSIOLOGICAL ACTION. Turpentine is a powerful irritant, causing in a very short time inflammation in any tissue with which it comes in contact. * For a study of the effect of the ozonizing turpentine oils, see Pal lop (Dorpat Thesis, 1889). DIURETICS. 709 When taken by a healthy person in moderate doses, it produces a sense of warmth in the stomach, soon followed by exhilaration, and, if the amount be sufficient, giddiness and even a species of intoxication. The pulse is increased in force and frequency. The turpentine escapes from the body through the lungs and kidneys, imparting its own odor to the breath and that of violets to the urine. Although several re- corded instances prove that turpentine is capable of producing death, cases of serious poisoning by it are rare, and a lethal result is exceed- ingly so. The symptoms noted in poisoning by it are most of them constant, but vomiting and purging are present in some cases and not in others. Unconsciousness is generally complete, and occasionally is accompanied by dilated pupils ; the urine is very much lessened in quantity, often bloody, not rarely suppressed ; the skin is sometimes dry, sometimes moist ; the pulse is feeble, rapid, and generally regular. The lethal dose must be very large, but it is not definitely known, since recovery from four ounces in an infant fourteen months old has been reported. In Maund's 65 case, death was supposed to have been produced in an intemperate woman by six ounces; and Philip Miall" has recorded an instance of death caused in an infant fourteen weeks old by turpentine, of which half an ounce was thought to have been taken. Our knowledge of the action of turpentine upon the circulation is very imperfect : the results which have been obtained by experimenters are so diverse as to indicate that different varieties of the oil affect the cir- culation differently, or else that the oil alters in its physiological influence when allowed to stand and absorb ozone. R. Kobert, 67 using the Euro- pean turpentine, found that in moderate doses it exerted a powerful stimulating influence upon the inhibitory reflex centre, and also elevated the blood-pressure by stimulating the vaso-motor centres. Very large doses appeared to paralyze both of the centres spoken of, causing de- cided fall in the arterial pressure. The respiration was first increased in frequency, but later very much diminished. The blood became very dark, and the heart was finally paralyzed. The vagi and depressor nerves did not appear to be affected, nor indeed did any of the peripheral nerves or the muscles. It is said that these results are in accord with those previously published by Azary in the Hungarian language, and Hoppe 68 concludes as the result of his own experiments, presumably made with European oil of turpentine, that the vaso-motor nerves are very early influenced by the drug. On the other hand, in a series of experiments made in the laboratory of the University of Pennsylvania by H. A. Hare 69 with American oil of turpentine, it was found impossible to raise the arterial pressure for more than two or three minutes, and then no more than ten millimetres of mercury. Large doses produced a pro- nounced fall of arterial pressure, with great cardiac depression, to which, indeed, Hare attributes the fall of the blood-pressure. Doses which had no effect on the blood-pressure increased the frequency of the pulse for yio LOCAL REMEDIES. a length of time. The increase of the pulse-rate was evidently due to an action upon the heart itself, for it occurred when the turpentine was applied directly to the heart of the frog as well as in the dog after section of the accelerator nerves and the vagi. When large doses were ad- ministered the pulse became slow, probably, as Hare believes, as the result of stimulation of the pneumogastric nerves, since section of these nerves was followed by the normal rise in pulse-frequency. Le"on Crucis 70 has made some experiments which indicate that when turpentine is given in toxic doses to rabbits it increases the coagulability of the blood and gives rise to numerous minute hepatic and pulmonic thrombi. F. Fleischmann 7l found that two drops produced paralysis in the frog, first of voluntary and afterwards of reflex activity ; in the cat and in the rabbit, toxic doses abolished reflex activity, but caused violent lethal convulsions. The preservation of voluntary movement in the frog after the loss of reflex activity, which has been confirmed by Hare, indicates that toxic doses of turpentine paralyze the sensory nervous system, either in the cord or in the peripheral nerves. The irritant action of turpentine upon the kidneys and genito-urinary tract is very decided. When moderate doses (ten drops every three hours) of turpentine are taken, there are usually no renal symptoms produced, except a slight increase of the urine. Somewhat larger amounts, when exhibited, are apt to give rise to aching in the loins and to frequent micturition, with perhaps urethral pain accompanying the act. If still larger quantities are ingested, these symptoms are intensi- fied, and at the same time the secretion of urine is diminished. After very large repeated doses of the drug, the aching in the loins is very great, often with spasmodic pain in the ureters ; a constant desire to pass water struggles with the inability to micturate, caused by the urethral spasm ; the urine is very scanty, albuminous, and even bloody ; priapism may be present, and an intolerable irritation may affect all the pelvic organs. THERAPEUTICS. Externally the oil of turpentine is very much em- ployed as a powerful counter-irritant. It is useful more especially when it is desired to act upon a large extent of surface. When a very in- tense permanent local impression is required, a blister is to be preferred. Thus, in pleurisy a blister may be used, in bronchitis turpentine stupes. In preparing the latter the turpentine should first be warmed by setting the vessel containing it in hot water, then a piece of flannel, just previ- ously saturated with hot water and wrung out as dry as possible, should be dipped in the turpentine and again wrung out. It is then ready for application, and may be left on from fifteen minutes to half an hour, according to the sensitiveness of the skin. Another local use of the oil of turpentine is as an addition to ene- mata. From a teaspoonful to a tablespoonful of it mixed with double its amount of olive oil renders opening enemata much more active, espe- cially in causing the expulsion of flatus. Turpentine enemata contain- DIURETICS. 711 ing much of the oil in a small bulk are also constantly used with good effect in arousing the system from stupor arising from narcotic poison or similar causes. In ulcer ation of the bowels turpentine taken by the stomach is often very efficient, probably acting locally in the intestine, and in old gastric ulcers good results are sometimes derived from its use. In a single large dose (half to one fluidounce, with an equal amount of castor oil) it is an efficient vermifuge. It may also be used as a stimulant in low fevers, particularly when the tongue is dry and red. In typhoid or enteric fever it without doubt acts as a local stimulant to the ulcerated bowel, besides influencing the general condition of the system. There are two conditions or stages in the diseases named in which it is especially useful, indeed, is of incalculable service. About the end of the second week the tongue sometimes becomes very dry, red, chapped, perhaps coated in the centre with a brownish fur, and at the same time marked meteorism develops. Ten drops (0.6 C.c. ) of turpentine every two hours during the day and every three hours during the night will in the majority of cases remove the bad symptoms noted. That the action of the oil is largely a local one is shown not only by the arguments of the introducer of the practice, George B. Wood, but also by the value of the same treatment when diarrhoea persists after the acute stage of the fever has passed. When convalescence is protracted, when there is a constant tendency to the recurrence of diarrhoea, when, in other words, the ulcers of Peyer's patches are slow to heal, turpentine acts almost as a specific. These clinical results have received scientific confirmation in the work of Theo. Omelchenko, 72 who finds that the bacillus of typhoid fever will not develop in air containing diluted vapor of turpentine, and dies when the atmosphere is saturated with the vapor. Thymol appears to be even more active than is turpentine. In typhoid bronchitis and pneumonia, especially as intercurrent in typhus fever and similar diseases, turpentine applied externally and taken internally is often very useful. The same may be said of the low forms of piierperal fever. In this disease the abdomen should be kept covered with fomentations of the oil and of warm water alternately, the counter- irritant being used as constantly as a proper regard for the skin of the patient will allow. Internally it should be given in very large doses (ten to fifteen minims every two hours). In hemorrhages from the stomach, bowels, or lungs turpentine has acquired celebrity, but it is hardly so much used as formerly. It is in the ataxic cases that it is useful. We have very rarely employed it, as the oil of erigcron has seemed even more efficacious, and is much more pleasant to the patient. In purpnra hamorrhagica turpentine has been highly praised. Oil of turpentine is never employed to increase the flow of urine for the purpose of affecting serous effusions. As a diuretic, it is used solely for its local influence upon the organs. Excessive diuresis sometimes is 712 LOCAL REMEDIES. apparently dependent upon a relaxed condition of the kidneys, and under these circumstances oil of turpentine may be of service. Chronic pye- litis, chronic cystitis, and gleet may be benefited by its use. In giving turpentine in these cases, it should always be borne in mind that, with the exception of cantharides, it is the most actively stimulating of all the diuretics, and must be employed only when such a remedy is called for. In those comparatively rare cases of urinary incontinence which are dependent upon debility of the bladder, turpentine is some- times of great service. When the same symptom is spasmodic, the remedy, of course, is harmful. In absolutely passive htzniaturia, in im- potence, in certain conditions of spermatorrhoea, and in amenorrhcea, when great local debility exists, turpentine may be tried with fair hopes of its being useful. ADMINISTRATION. The dose of turpentine is ten to fifteen drops (0.6-0.9 C.c. ) in emulsion, given from four to six times a day. EMUL- SUM OLEI TEREBINTHIN.E, U. S. , contains fifteen per cent, of oil of turpentine and is flavored with oil of bitter almonds. Dose, one drachm ( 4 C.c.). It has been asserted that oil of turpentine is a powerful bactericide; but the experiments of Koch and of Christmas- Dirckinck-Holmfeld" appear to show that its general antiseptic properties are feeble. COPAIBA COPAIBA. U.S. The oleoresin of Copaiba Langsdorffii and of other species of Co- paiba, large trees growing in Brazil. Copaiba is a yellowish liquid, of varying viscidity according to age, of a strong, terebinthinate, peculiar odor, and a bitter, burning, disagreeable taste. It mixes uniformly with absolute alcohol and volatile and fatty oils, and is readily dissolved by ether. It contains a volatile oil, a small quantity of soft, viscid resin, about fifty per cent, of a hard, acid resin, and a peculiar crystallizable acid, copaivic acid, which, according to Bernatzik, is unimportant, the activity of the drug depending upon the oleoresin. PHYSIOLOGICAL ACTION. The local action of copaiba is that of an active stimulant or a mild irritant. When taken internally, it yields its active principle to absorption and elimination through the kidneys. The elimination takes place slowly, as Bernatzik 7i found the oil in the urine as much as four days after its ingestion. Upon the general system copaiba has little influence ; eighteen grammes of its volatile oil, taken in three doses during twelve hours, caused only a slight elevation of the pulse-rate and of the temperature, with later vomiting and purging, and still later burning in the urethra and strangury (Bernatzik). In susceptible persons the evidences of the local action of the drug are more marked, it causing decided symptoms of gastro-intestinal irritation, accompanied by marked fever and irrita- tion of the urinary organs, such as strangury, and even almost complete suppression. In Bernatzik' s trials fifteen grammes of the resin, taken DIURETICS. 713 within five hours, produced violent purging and vomiting, with much abdominal pain. The discovery in 1841 by G. O. Rey, that the addition of nitric acid to the urine of persons taking copaiba will produce a precipitate re- sembling that of albumin, has led to much discussion. To obtain this precipitate the copaiba must be freely given. As shown by Bernatzik, the precipitate probably consists of the oxidized oil united to some urinary principles. The copaiba-red of Quincke is a substance found in the urine of persons taking the oil of copaiba ; it is an acid, whose salts have the property of reducing the oxide of copper and of polarizing to the left, and may be a source of error in the diagnosis of diabetes. When a pure copaiba resin is used, although the copaiba-red cannot be detected in the urine, the urine still responds to Trommer's test for sugar. As a stimulant to the genito-urinary mucous membrane, copaiba is distinctly more active than buchu, but less irritating than the oil of tur- pentine. It may be used in chronic pyelitis and cystitis, but is chiefly em- ployed in advanced stages of gonorrhoea; if administered during the height of the inflammation in these diseases, it is liable to aggravate the symptoms. It is also capable of affecting other mucous membranes than that of the genito-urinary tract, so that it may sometimes be given with advantage in old indolent ulcers of the stomach, in chronic diarrhoea and dysentery, in advanced bronchitis, and especially when in chronic bron- chitis there is very free muco-purulent expectoration. As a local appli- cation it is sometimes very advantageous in chronic chilblains and other diseases of the skin. In doses of forty-five grains (3 Gm.) a day the resin is said to be actively hydragogue and effective in dropsies which are not dependent upon renal disease. Dose of copaiba, half to one fluidrachm (2-4 C.c.), in capsules ; of the oil (OLEUM COPAIBA, U. S. ), which is isomeric with oil of turpentine, eight to fifteen minims (0.5-1 C.c. ), in capsules. MASS A COPAIBA, U. S. , is an entirely ineligible preparation. CUBEBA CUBEB. U. S. The unripe fruit of Piper cubeba, a climbing plant of Java and other portions of the East Indies. These berries are blackish-veined, about the size of a small pea, and have attached to them a short stalk three or four lines long. Their odor is aromatic and peculiar ; their taste warm, camphoraceous, and peculiar. They contain cubebic acid, cu- bebin, volatile oil, and resin, and are fully represented by the official oleo- resin. Bernatzik 75 has found that cubebin is inert, which is in accord with the statement of Heffter, 76 that cubebin passes through the ali- mentary canal without absorption, so that it is possible to recover from the faeces almost the whole amount ingested. Cubeb is a local stimulant which has very little effect upon the gen- eral system. In large doses it produces a gastric and genito-urinary irri- tation proportionate in severity to the amount taken. Like copaiba, it 7 i4 LOCAL REMEDIES. occasionally causes an urticaria, which is probably due to the gastric irritation. It yields to absorption and elimination its active principles, which can be detected in the urine by the addition of nitric acid, when a precipitate resembling that of albumin occurs. In Bernatzik's experiments ten grammes of magnesium cubebate caused slight acceleration of the pulse and gastric uneasiness, with increased elimination of uric acid. Half an ounce of the oil, taken in thirty-six hours, produced very decided gastric irritation, with the appearance in the urine of the oxidized oil in the form of a resin, and a very great decrease in the elimination of uric acid. After fifty grammes of the powdered cubeb the gastro-mtestinal irritation was most pronounced and the nitric acid precipitate in the urine very abundant. Cubeb is used to relieve precisely the same conditions as copaiba. In many cases the best results are to be obtained by the combined employment of the two remedies. It has received much praise as an internal remedy in chronic hemorrhoids. It is useful as a local stimulant in the relaxation of the larynx frequently seen in public speakers following slight colds and overuse of the voice, chewing the berries often bringing relief to the throat and tone to the voice. The powdered drug may be used as a snuff in coryza. In this disease, as in all others, cubeb should not be employed in the earlier stages before secretion has been established, but later in the affection when the discharge is profuse. The dose of the powdered cubeb is from half to three drachms (2-11 Gm.); of the volatile oil (OLEUM CuBEByE, U. S. ), fifteen drops (i C.c. ), given in capsules and gradually increased to half a drachm, unless some effect is previously produced upon the urinary organs ; of the fluid ex- tract (EXTRACTUM CUBEB^E FLUIDUM, U. S. ), ten to forty minims (0.6-2.5 C.c. ). The best preparation is the oleoresin (OLEORESINA CUBEB/E, U. S. ), dose, ten to fifteen minims (0.6-1 C.c.), in capsules. MATICO. U. S. Matico, the dried tops of the Piper angustifolium of Peru, contains a volatile oil, resin, and, it is said, a bitter principle, maticin. It is a softish mass which is largely employed as a styptic, and probably acts chiefly mechanically, coagulating the blood in its inter- stices, adhering to the wound, and thus arresting the hemorrhage. It has also been employed in internal hemorrhages and in gonorrhcea. In these affections it probably acts similarly to oil of turpentine, although much less of a stimulant and much more feeble. The fluid extract (FLUIDEXTRACTUM MATICO, U. S.) and the tincture (TINCTURA MATICO ten per cent. , U. S. ) may be respectively given in doses of forty-five minims (3 C.c.) and two fluidrachms (7 C.c.). CANTHARIS. Cantharides is considered elsewhere in detail (see EPISPASTICS), and it is only necessary here to say a few words in regard to its use in diseases of the genito-urinary tract. The active principle of Spanish flies is certainly eliminated by the kidneys, and acts therefore locally upon these organs, as well as upon those over which their secre- DIURETICS. 715 tion flows. The influence exerted by this means is simply one of intense irritation, cantharides being an irritant to these organs in any dose suffi- ciently large to have an effect. Indeed, of all the official drugs can- tharides is the most actively irritant to the kidneys and their subordinate organs. Consequently it is employed only when an intensely stimulant action is desired, as in obstinate gleet, in which affection it is often com- bined very advantageously with the tincture of ferric chloride. In pyelitis and cystitis it is very rarely indicated, but may be cautiously used in very chronic cases. The tincture of cantharides is the only preparation used in- ternally. Dose, one to five minims. Cantharides has been strongly recom- mended by Beven. M Other clinicians give the full dose in ataxic hamaturia. KAVA. The root of Piper methysticum is used in the Sandwich Islands as the basis of an intoxicating liquor known as kava-kava, kawa, or ava. It contains a crystalline principle analogous to piperin, which its discoverer, Gobley, called meihysticin, besides an acrid resin, kavin, and a volatile oil. L. Lewin " finds that when the kava resin is injected into the frog it produces a very pronounced loss of sensation at the point of injection, due to a paralysis of the peripheral endings of the sensory nerves, and that after the absorption of the remedy there is loss of voluntary motion and reflex activity, which is chiefly of spinal origin. In experiments made upon the warm-blooded animals he obtained similar phenomena, namely, local anaesthesia at the point of injection, followed, after absorption, by general paralysis, due to a direct depression of the motor side of the spinal cord, the motor nerves and the muscles remaining intact. According to Dario Baldi, 78 the active principle of kava produces in the dog a very short period of excitement of the sensory nerves, followed by a complete paralysis, at a time when the whole motor system still responds to stimuli. In small doses kava is said to act as a stimulant tonic, but when taken in large amounts to produce an intoxication which differs from that caused by alcohol in being silent, drowsy, and without emotional exaltation. The great loss of -muscu- lar power which is said to follow kava debauch in those unaccustomed to the use of the drug shows that its influence upon the spinal centres in man is the same as in other mammals. According to Baldi, Randolph, and Lewin, the resin of kava is a local anaesthetic of extraordinary persistency of action, but it appears to be too irritant for practical use. A decoction of the root is used in Oceanica very largely in the treatment ok gonorrhoea, and its value has been strongly affirmed by Sanne". 79 The dose of the root itself, given in decoction, is half a drachm three or four times a day : of a fluid extract, half a fluidrachm (2 C.c. ). YOHIMBINE. This alkaloid is obtained from the bark of Corynanthe yohimbi, a rubiaceous tree, growing in the southern Cameroons district in Africa. It was originally investigated by Oberwarth and Loewy, 101 who found it was in animals and also in man a very active excitant to the sexual organs and func- tions. On the other hand, Kravkoff, as the result of experiments upon the lower animals and upon man, concluded that it has no aphrodisiac effect ; and frequently produces nausea, salivation, irritability, and other disagreeable results. It has been used, however, by numerous clinicians in neurasthenic impotence, with reports which are generally favorable to its influence. (For literature see Merck's Report, 1901, 1902. ) It is said to be of no value when impotence depends upon organic nerve trouble, and to be harmful when it is caused by chronic inflammatory disease of the sexual organs or of the prostate gland. Dose, 0.005 gramme of the hydro- chlorate, either in tablet or solution, three or four times a day. It has also been employed in a one per cent, solution three times a day, hypodermically. LOCAL REMEDIES. REFERENCES. DIURETICS. 1. Roux A de P., 1874,578. 2. BOCKER Brit. For. Med.-Chir. Rev., 1854, xiv. 3. MI-IYER H. S. Jb., 1881, 345. 4. POKAK and EKRNHEIM Nouv. Arch. d'Obst. et Gyn., 1893, viii. 5. DELBERT . . . . C. R. S. B., 1896, iii. 6. SCHROHF .... \Vb. G. A. W., 1864, 424. 7. LUPINSKI . . . . H. S. Jb., 1883, 123. 8. HUSKMANN . . . Toxicologie, i. 413. 9. JENDRASSIK . . . D. A. K. M., 1886, xxxviii. 10. COHNSTKIN . . . A. E. P. P., 1892, XXX. 11. BRASSE and WIRTH . C. R. S. B., 1887. 12. SILVA C. K. M., 1888, ix. 13. GRAM Th. M., 1890, iv. 14. KOUINDIG-POMKRANTZ . B. G. T., 1890. 15. BONDZYNSKI and GOTTLIEB . A. E. P. P., xxxvi. 16. SABASHNIKOKF In. Dis., St. Petersburg, 1892. 17. COHNSTEIN . . . In. Dis., Berlin, 1892. 18. PAWINSKI .... Vrach, 1893. 19. LENTE Psychol. and Med.-Leg. Journ., 1875. 20. PODOCAEPOW . . V. A. P. A., 1866, xxv. 460. 21. RINGER and MORSHEAD . J. A. P., xii. 82. 22. RINGER and MURRELL . J. P., i. 88. 23. TRAUBE Gesammelte Beitrage, i. 386. 24. ALBERT and DEHN . A. G. P., 1874, 122. 25. PoDOCAtPow . . V. A. P. A., xxiii. 26. DOGIEI C. M. \V., 1892. 27. PARKES Brit. For. Med.-Chir. Rev., 1853, xi. 258. 2.v. BIRD On Urinary Deposits, 1859, 356. 29. RABUTEAU .... L'Union Med., 1871, 389. 30. DKHN A. G. P., xiii. 368. 31. PARKES Brit. For. Med.-Chir. Rev., 1854, xiv. 32. FLINT Arner. Med. Monthly, Oct. 1860. 33. EASHAM Pract., 1870, v. 34. TAYLOR Guy H. R., 1863, 177. 35. MUNCH Arch. d.Vereins. f. gemein. Arbeiten, 1863, 370. 36. HUSEMANN . . . Journ. f. Pharmacodynam., 1859, ii. 178. 37. MARCHAND . . . V. A. P. A., 1879, Ixxvii.; A. E. P. P., xxiii. 38. RIESS B. K. W., 1882. 39. FAI.CK A. G. P., 1889. 40. LENHARTZ . . . Beitr. Path. Anat. etc., Festschrift. 1887. CAHN A. E. P. P., 1887, xxiv. . HAMMKK VON ME RING Prag. Med. Wochensch., 1888, xiii. Chlorsaure Kali, Berlin MACMUNN .... Spectroscope in Medicine, 1881, 100. BINET R. M. S. R., 1892, viii. DUCHE Bull. d. 1. Soc. Med. de 1'Yonne, 1884-86, 25-27. LOEBISCH . . . . W. K. W., 1897. CASPER D. M, W., 1897. BARDET Les Nouv. Rem., 1894. 87. 90. 9>- 92. 93- 94- 95- 96. 97- 98. 99- 100. 101. 1O2. 103. 104. NICOLAIKR . . . Z. K. M., 1899, xxxviii. CITRON Monats. d. Harn. u. Sex. Appar., 1898. LABORDE . . . . C. R. S. B., 1890, ii. ; 1891, iii. WOOD, JR. . . . A. J. P., 1898, i. 83. WOOD and ARNOLD . Phila. Monthly Med. Journ., April, 1899. BINET R. M. S. R., 1892, viii. JABLONOWSKI . . In. Dis., Dorpat, 1858. VON MERINO . . A. G. P., 1877, xiv. 276. LEWIN V. A. P. A., 1883, xcii. STKFFEN .... I'ntersuchungen, Wiirz- burg, 1883. FORSTER .... Acrztl. Intelligenzbl., 1881. LAURENTZ . . . Jn. Dis., Dorpat, 1886. STARKE L. M. R., 1876, 267. ROSENBERG . . Th. M., 1887, 219. VEJUN-TVRODE and NELSON . J. M. R., 1903. x. MAUND Annuaire de Therap., 1846. MIALL L. L., March, 1869. KOBERT . . . . C. M. W., 1877, 129. HOPPE Journ. i. Pharmacodyn., i. 105. HARE M. News, Nov. 19, 1887. CRUCIS Thesis, Paris, 1874 FLEISCHMANN . S. Jb., clxxx. 125. B. G. T., 1891. Fon. M., Oct. i, 1887. Prager Vierteljahrs., 1868, c. 239. Prager Vierteljahrs., 1864, Ixxxi. 9. Atti dell, XI. Cong. Med. Internazionale, 1894, iii. Piper Mtthysticum, Berlin, 1886. BALDI S. Jb., ccxxxix. SANNE J. de Th., 1886. LEDERMANN . . D. C., 1903, xii. . C. B. S. A., 1901, xxxi. . L. L., Jan., 1901. . A. E. P. P., xxxv. KR()GER and SCHMIDT . A. E. P. P., xiv. BEVEN B. M. J., 1898, Nos. 1968, 1977. . International Contribu- tions Festschrift, A. Jacobi, New V'ork. . A. E. P. P., 1901, xlvi. . B. K. W., 1899. . D. M. W., 1900. NICOLAIER and HAGENBERG . M. R., 1900. MINKOWSKI . . T. G., 1902. DOERING . . . . M. M. W., 1903. THIENGER . . . M. M. W., 1903. KRAMER . . . . M. M. W., 1903. BOLTAZI . . . . A. I. B., xxvi. ASTALFONI . . . A. I. P., 1903, xi. MENDEL and THACHER . A. J. P., 1904, xl. MOSAUER .... W. M. W., 1903. GOOD C. M. R. V., 1903. PERGAMI . . . . A. I. B., xxxiv. ROSENTHAL . . Ther. Geg., 1902, iv. OBERWARTH and LOEWY . V. A. P. A., cliii. ; B. K. W., 1900, No. 42. GOTTLIEB and MAGNUS . 1900-01, xiv. 223. PREISISCH . . . Ther. Geg. 1905, xlvi, 211. OMELCHENKO HOLMFKI.D BERNATZIK . . BERNATZIK . . HEFFTER . . . LEWIN . Sl'TKR . . CAMMIDGE ALBANESE 86. MELTZER ULRICI . WEISS . RlCHTER FAMILY V. DIAPHORETICS. DIAPHORETICS are those medicines which are employed to increase the action of the skin. It is scarcely in place here to discuss the results of suppression of the functional activity of the skin or the importance of the surface-elimination to the system. It does seem well, however, to call attention to the fact that the perspiratory glands have a double func- tion to perform, that of elimination, already alluded to, and that of keeping down the temperature of the body during exposure to heat. When a man enters a Turkish bath the temperature of which is perhaps 1 60 F. , or when he works in the sun on a very hot day, there is, if he be used to such exposure, little or no rise in the temperature of the body, because the surface-glands secrete sweat so actively as to expose a great amount for evaporation, and by the conversion of so much water into vapor such an amount of heat is absorbed i.e., converted from heat into repulsive force that the body is cooled. The reason that even a moderate degree of heat in a moist atmosphere is intolerable is because evaporation cannot take place. From what has already been stated, it is obvious that the use of dry external heat, or rather exposure to a hot atmosphere, is a powerful means of producing perspiration. It may be applied either in the form of the Turkish bath, in which the air of the hot chamber is very dry, or in the Russian or vapor-bath* in which the atmosphere is surcharged with hot vapor. Neither of these baths has any other physiological property than that of a sweat-producer. Hot-water baths offer another very successful method of inducing profuse perspiration. The patient should be placed in a bath of about 100 F., and remain there from fifteen to twenty minutes, during which time, by the repeated addition of very hot water, the temperature should be raised to 110 F., or to such point as the patient can endure. Warmed blankets having been plentifully provided, the sick man should be lifted from the bath into them, be closely wrapped up, and so left for * For home use there are in the market various " Cabinet Baths," so called, which afford a cheap and efficient means of giving vapor-baths. The term Turkish bath is here applied to the bath used in this country under that name. This bath appears not to be a copy of the Oriental bath, but merely a derivative from it. Writers affirm that in the East the sudarium, or sweating-chamber, rarely has a temperature of more than 98 F. : in London we have been in a Turkish bath at 200 F. ; from 140 to 160 F. is a common temperature in American baths. ?I 8 LOCAL REMEDIES. three or four hours before being transferred to the usual bed. According to A. Steffen, 1 after this use of the bath the body has been proved to undergo loss of weight continuously for one or two days. The popular belief that after a sweat there is a greater liability than usual to take cold appears to us to be well founded : care must, there- fore, be exercised to avoid exposure after the hot bath of any kind. The liability to take cold may, however, be overcome by the use of the cold douche or plunge-bath. The possibilities of the hot-water bath as a therapeutic measure are probably much greater than is ordinarily recognized. In severe burns, in nervous shock, and in various skin diseases continuous immersion would probably often be found of the greatest service. According to Baelz,* the baths which are habitually taken by the entire native population of Japan are at a very high temperature (109 to 114 F. ), and the immer- sion continuous during the whole evening. The mouth temperature rises to 104 or 105 F. , whilst the pulse becomes very full and increased in frequency, with marked evidences of relaxation of the arteries. When there is a high grade of atheroma, the softening of the arteries after an hour's bath is very pronounced. Baelz believes that there is no increase in the elimination of nitrogenous matter, and that the Japanese custom is extremely useful, because, the winter being cold and the houses not heated, the people lose bodily heat during the day, and for two pennies in the evening acquire a supply of heat which lasts through the night. Profuse sweating is always more or less exhausting, but is not nearly so much so as purging, and therefore may be practised in dropsical patients too feeble to allow of the use of purgatives. The hot baths are not, however, altogether free from danger or objection. Sometimes in the Turkish and Russian baths the patient fails to sweat freely, and a feeling of distress, a bounding, rapid pulse, and perhaps severe headache develop themselves : under these circumstances the bodily temperature rises, and a fever develops, which may go on to the production of -a true ' ' thermic fever, ' ' and perhaps terminate in sudden death. This is an exceedingly rare result, and one that can never occur if the patient is removed from the hot chamber so soon as any unpleasant symptoms are manifested. Sudden death has been recorded once from ' ' sunstroke' ' in a patient while taking the ' ' Turkish bath, ' ' also once from ' ' conges- tion of the lungs. ' ' The use of hot baths of any kind is, of course, contra- indicated by the existence of fever ; but, according to Steffen, the hot- water baths are pre-eminently contra-indicated by the existence of congestion or oedema of the lungs, or of a tendency towards these disorders, since under such circumstances the bath greatly increases the disease, or precipitates a perhaps fatal attack. Our own experience corroborates these state- ments. We have seen, under the conditions mentioned, the most fright- ful dyspnoea result from the use of the hot-water bath. If disturbance of the respiration comes on during the bath, the patient should immedi- DIAPHORETICS. 719 ately be taken out, and, if the symptoms be urgent, cold water should be freely dashed over the head, neck, and chest. Severe cardiac disease is also a centra-indication both to the Turkish and Russian or vapor-bath. Precisely as water may act as a diuretic by increasing the fluidity and amount of blood, so may it also act as a diaphoretic, provided that it is directed to the skin by being itself given warm and aided by the use of external heat ; hence the importance of hot drinks when it is desired to produce free sweating. The colliquative so-called " night- sweats " of phthisis are undoubtedly largely due to a paralytic weakening of the blood-vessels of the skin. In similar manner aconite, veratrum viride, tartar emetic, and other substances which profoundly affect the vaso-motor system produce a free sweating which resembles that often seen in col- lapse from other than drug causes. Diaphoretics are employed in the practice of medicine to fulfil the following indications : First. To arrest forming diseases of not very severe type, probably by causing a flow of blood to the surface, and thereby relieving slight internal congestions, and possibly by eliminating principles which have been retained in the blood instead of being excreted as they ought to have been. In general cold, in muscular rheumatism, in suppressed men- struation, and other results of exposure to cold and of checked perspira- tion, the diaphoretics afford the most efficient means at our command for restoring the normal functions. Second. To favor absorption. In dropsy the diaphoretics are of very great value, often aiding diuretics and purgatives in effecting a cure, and sometimes, when these fail, or when circumstances forbid their use, rescuing the patient from impending death. None of the medicinal diaphoretics except jaborandi is of sufficient power to be relied upon in dropsy. The Turkish, the Russian, and the hot-water bath are capa- ble of producing sufficient sweating to cause absorption of dropsical fluid, but must be vigorously employed. Third. To aid in the subsidence of diseases which naturally pass off with a sweat. The chief use of diaphoretics for this purpose is in miasmatic fevers, especially in the remittent form of the affection, when the sweating stage fails to develop itself thoroughly and the paroxysms run into one another. Even in the single paroxysm of intermittent fever, by hastening the closing stage, diaphoretics will often shorten the paroxysm. Fourth. To eliminate noxious materials from the blood. The old humoral idea that the groundwork of such diseases as fevers is a dis- tinct matcrics morbi which can be eliminated from the blood has no sufficient demonstration to be accepted, and, although diaphoretics do good in fevers, yet it cannot be granted that it is in this manner. The very great power of increased diaphoresis in cooling the body through surface-evaporation has already been dwelt upon, and much of the good effected by diaphoretics in diseases of high temperature probably has its origin in this power. 720 LOCAL REMEDIES. Modern science seems clearly to point out that diaphoretics may aid in separating from the blood retained secretions, and may to some extent replace the action of the kidneys when these organs are disabled by disease. In 1851 Schottin* discovered urea in the sweat of patients suffering from the collapse of cholera. Not only has the discovery of Schottin been confirmed by the researches of G. O. Rees, 5 of Fiedler, 6 of Hirschsprung, 7 of Kaup and Jiirgensen, 9 of Leube, 9 and of G. Deininger, 10 but it has also been abundantly proved that the skin excretes urea freely during the advanced stages of Bright' s disease, and also during the partial urinary suppression of scarlatinal desquamative nephritis. The urea in renal disease may even form a distinct crystalline powder on the skin, but it is most abundant about the mouths of the sweat-glands. We believe Landerer was the first to announce that urea is present in the sweat of healthy persons ; and, although excellent chemists have been unable to detect it, its presence at times can no longer be denied, since it has been found not only by Landerer, but also by Funke 11 in 1858, by Meissner, 12 and by Leube ; Fourcroy (quoted by Rees) has also found it in the sweat of horses. By a series of elaborate experiments, Leube has rendered it probable, if he has not actually proved, that in health there is such a relation between the skin and the kidneys that when the former is very active the latter excrete less than the normal amount of urea. When to the facts already cited are added the observation of Grie- singer, that in diabetes the perspiration contains sugar, and the well- known circumstances that in rheumatism the sweat contains lactic acid, and in jaundice biliary products, the value of diaphoretics as a means of getting rid of retained excretions becomes manifest. For this reason, in Bright 1 s disease, especially of the acute form, they are of the greatest value, acting beneficially in three different ways, by drawing the blood to the surface, and thereby relieving any internal congestions of the kidneys or other organs that may exist ; by promoting the absorption of dropsical effusions ; and by eliminating retained secretions. PILOCARPUS. U.S. JABORANDI. This drug, which has long been employed by the natives of South America, received its first notice, under the various names of Jaborandi, Jaguarandy ', and Jamguarandi, from T. J. H. Langgaard in his Dic- cionario de Mededna domestica, Rio Janeiro, 1865. It attracted no attention, however, until 1874, when it was brought to Paris by Cou- tinho. The leaves * alone are official ; of them there are in commerce two varieties : the Rio Janeiro Jaborandi, which is believed to be the product of Pilocarpus selloanus, and the Pernambuco Jaborandi, the product of P. Jaborandi. The two varieties agree in that the leaves are oval, oblong, and entire, four to six inches long and one and a half to two inches wide, with a bitter taste and a hay-like odor : they differ in that the Rio Janeiro leaves have a tendency to become obovate * Under the name of Jaborandi various drugs other than the product of Pilocarpus are sold in Brazil. As the Pilocarpus pinnatus has been found to be active when grown in France, it is probable that the Jaborandi plant might be successfully cultivated in our Southern States. Frerichs (Berlin. Klin. Wochenschrift, 1875) found the wood inert. DIAPHORETICS. 721 in shape and are not prominently veined upon the upper surface, whilst in the Pernambuco leaves the upper venation is very pronounced. Each variety contains the alkaloid pilocarpine, discovered by Byarson,* but the Pernambuco leaves are said to be much the richer. PHYSIOLOGICAL ACTION. Local Action. Absorption and Elimina- tion. Jaborandi is practically free from irritant properties, and yields its active principle rapidly in the alimentary canal. After hypodermic in- jection of pilocarpine the symptoms may set in in five minutes. It is probable that the alkaloid escapes from both the skin and kidneys. General Effects. When an infusion of from sixty to ninety grains of Jaborandi is given to an adult, in about ten minutes the face and neck become deeply flushed, and free perspiration and salivation commence. The sweating begins on the face ; both it and the salivation are exces- sively profuse, and last from three to five hours. There is not rarely nausea, and sometimes vomiting. The pulse is usually more or less quickened, .as is also frequently the respiration. After the sweating has ceased, the patient is left more or less exhausted. The nasal and lachrymal secretions are also very generally increased under the action of the drug, and Gubler has noted diarrhoea, which in the experiments of Ringer and others has not been present. There is sometimes con- traction of the pupils, and even disturbance of vision. These effects of the drug are in the adult fairly constant ; but subjects have been occa- sionally found who were not susceptible to the action of the remedy, and, very curiously, in Ringer's experiments children were found to be very insusceptible, although doses of sixty grains were employed. Schwann, Moral, and other observers have noticed in the lower animals that very violent gastric and intestinal movements are produced by the drug. Secretion. The sweat produced by Jaborandi is often enormous in quantity (nine to fifteen ounces by estimation). It is stated to be at first acid, then neutral, and finally clearly alkaline. Vulpian IS denies that even the first sweat has other than alkaline reaction, and believes, with Luchsinger and Trumpy, that there has been a mistaken observation, due to the fact that the secretion of the sebiferous glands is acid. In the analyses of Robin the chlorides were found in excess, the carbonates and phosphates in very minute amount, and the urea in more than five times its normal proportion, the amount eliminated in the sweating being esti- * Concerning the alkaloids of Jaborandi and their derivatives there is much confusion and imperfection in our knowledge. Three alkaloids have been thought to exist in Jaborandi leaves, namely, pilocarpine and its derivatives, jaborine and pilocarpidine. According to its discoverers, Harnack and Meyer (A. E. P. P., xii.), jaborine acts upon the heart, pupil, intestines, and salivary glands in a manner almost identical with that of atropine, so that its occasional presence in commercial pilocarpine gives rise to vagaries of physiological and therapeutic action. Jowett, however, has been unable to isolate jaborine, and there is much doubt as to its being a constant constituent of Jaborandi. (See Marshall, B. M., 1900, ii.). Further, according to Marshall, jaborine sold by Merck is a mixture of pilocarpine and a fourth alkaloid, isofiilocarpine. Pilocarpidine, according to Harnack (A.E.P.P., xx.), causes in excessive dose violent sweating, salivation, also vomiting and purging, with great disturbances of circulation. 46 722 LOCAL REMEDIES. mated at from ten to fifteen grains. Hardy and Ball " believed that in their experiments the average amount of urea eliminated by the skin was seventeen grains. Jaborandi appears to have an extraordinary influence upon secreting glands, not only in the skin but almost throughout the whole body. The nasal mucus is often greatly increased. The assertion of Pilicier, 15 that in a dog with a gastric fistula the gastric juices were greatly in- creased by the drug, is in conformity with the free vomiting of large quantities of glairy secretion which it causes in man. Morat 16 has noted a temporary increase of the sugar in the blood, an evidence that the glycogenic function of the liver is stimulated. The suprarenal cap- sules appear to share the action of the drug, since Auguste Pettit " has noticed that in animals poisoned by jaborandi there is marked conges- tion and swelling of these bodies. On account of the antagonism be- tween the skin and the kidneys the diaphoretic dose of pilocarpine may cause a decrease in the urinary flow, but the assertion of Gubler that the alkaloid administered in very small repeated doses has a marked diuretic influence has received clinical confirmation.* According to Gottlieb, 18 pilocarpine causes an increase of both the watery and solid con- stituents of the pancreatic secretion. There appears to be some relation between the flow of saliva and that of perspiration produced by jaborandi : if the one is very profuse the other is often, but not always, correspondingly scanty. Sometimes the salivation almost replaces the sweating (Fereol 19 ) ; very frequently it commences before the sweating, and often it is more persistent. During it the mouth is warm, and there is often a feeling of tenseness about the maxillary glands. The saliva contains an abundance of salts and of ptyalin, as well as a small excess of urea. Pilicier, it is true, states that the proportion of albuminous compounds, and especially of potassium sulphocyanide, is much diminished, but in Robin's analyses the proportion was even beyond the normal, and Ch. Bougarel has by careful experimentation shown that the power of jaborandi -saliva in con- verting starch into sugar is equal to that of the normal secretion. Ac- cording to J. N. Langley, in the frog the mouth and skin, after the exhibition of jaborandi, become covered with a viscid secretion ; in the dog, the rabbit, and the cat there is profuse salivation. * Much interest attaches to the effect of jaborandi upon urea-elimination, but it can- not be considered as determined, except that in various diseases the combined renal and dermal elimination is greatly increased by the drug. Hardy and Ball state that in health urea-elimination from the kidneys is diminished by the drug, while Tyson and Bruen have found it increased both in health and in disease. The experiments have, however, been too few, and especially the conditions of their performance too lax, for much im- portance to be attached to them. As the result of experiments upon the lower animals, J. Horbaczewski ( Therap. Gaz., 1893) believes that there is a distinct relation between the elimination of uric acid and the number of leucocytes in the blood, and that pilocarpine in proper dose increases the size of the spleen and increases also the number of leucocytes in the blood and the quantity of uric acid eliminated. DIAPHORETICS. 723 The action of pilocarpine in increasing secretion is direct and upon the glands themselves. The salivary glands are affected equally before and after section of all of the salivary nerves (Langley 20 and Carville," confirmed by Schwann M ) ; also when the drug is injected directly into the gland and prevented from entering the general circulation (Langley). According to the elaborate experiments of Langley upon cats poisoned with pilocarpine, stimulation of the chorda tympani or of the sympathetic nerve causes respectively some increase or lessening of the secretion, but this increase or lessening is not nearly equal to that which occurs in the normal animal, and is due to the action of the nerves upon the circula- tion, and not to any influence on their secretory fibres. Very large doses of the drug injected into the gland immediately arrest the accretion, and doses of less size given in the same way, while increasing secretion, para- lyze both chorda tympani and sympathetic nerve, so that stimulation of them has no effect. It is probable from the last fact that jaborandi has an action upon the secretory gland- cells. Although the evidence just deduced indicates that an influence is exerted by jaborandi upon the gland-cells, the fact that atropine arrests the jaborandi salivary secretion prevents us from considering it entirely settled that the drug does so act upon the salivary gland-cells rather than upon the peripheral nerve-endings, since there is reason for believing that atropine acts upon the nerve-endings. Fuchsinger (confirmed by Nawrocki) has found that section of the nerves of the cat's leg did not prevent the paws from sweating when jaborandi was exhibited. This demon- strates that the action of the drug is peripheral, not centric. Five or six days after the section, when the peripheral nerve-endings had undergone degeneration, Fuchsinger found that jaborandi was unable to excite sweating. This, however, can hardly be considered to prove absolutely, as Fuchsinger ra asserts, that the drug acts upon the peripheral nerve-endings and not directly upon the glandular cells themselves, since it is probable that these glandular cells shared the anatomical changes of the nerve-endings. Jaborandi appears to stimulate the nutrition of the hair, and Pren- tiss, 24 of Washington, has reported several cases in which the continued internal use of pilocarpine caused the hair to become exceedingly coarse and to change its color from light to dark. H. Rasori 25 has noticed a tuberculated eruption apparently produced by jaborandi. M. Grocco ** has found that pilocarpine hypodermically injected or locally applied sen- sibly affects hysterical anaesthesia. Temperature. Robin affirms that before and during the early stages of the sweating from jaborandi the temperature rises i to 2 F. , but afterwards falls as much below the normal point and remains depressed for one or two days. This primary rise of temperature has been noted by other observers/ 11 but is frequently absent altogether or very trifling, f * See Ringer {Lancet, 1873, i. 157), Greene (Phila. Med. Times, vi. 56), Scotti (Ber- lin. Klin. Wochens., 1877, 141), Pilicier (Med. Centralbl., 1876,429), and Weber (Ibid., 770). Pilicier noted that the rise occurred in the axilla, but not in the rectum : this would indicate that it is a local phenomenon, the result of a heating of the surface, not of the interior, of the body. | Consult Riegel (Berlin. Klin. Wochens., 1875, 86), Bardenhewer (Ibid., 1877, 8), and Auschmann (Ibid., 353). 7 2 4 LOCAL REMEDIES. The subsequent fall of temperature, which is a constant phenomenon, probably depends in great part, or altogether, upon the loss of heat during the sweating. Nutrition. The interesting question whether the excessive secretion of solids from the skin and urine produced by pilocarpine is accompanied by any increase of waste products in the body, or is only due to an in- creased activity of the glands in clearing out waste products already pro- duced, cannot at this time be answered. According to Otto Frank and Fritz Voit, 46 the first dose of the alkaloid causes in the curarized dog increased elimination of carbonic acid, but a second dose, given when the carbonic acid elimination has returned to the norm, has no such effect ; it is therefore probable that the drug has no direct influence upon nutrition. Circulation. The action of jaborandi upon the circulation has been studied by Langley, 27 E. Ley den, M Kahler and Sayka, 29 and Harnack and Meyer. 80 The phenomena noted by these observers are in most respects in accord, but Kahler and Sayka using the extract of jaborandi, and E. Leyden commercial pilocarpine, have found the pulse either as a constant or occasional phenomenon at first increased in its rate, while Harnack 31 has never seen this with chemically pure pilocarpine. It has been shown, however, by E. T. Reichert 32 that the result reached by Harnack was not due to the purity of the alkaloid, but to his not having used sufficiently minute doses. According to Reichert' s experiments, the minute dose increases, the large dose decreases, the pulse-rate, there being a broad line between the two effects in which the pulse is normal. Immediately after the injection of the alkaloid into the jugular vein the arterial pressure falls, but in a few moments the characteristic phenomena of a slow pulse with increased arterial pressure come on. This slowing of the pulse is not prevented by previous section of the pneumogastric, but is at once set aside by an injection of atropine (Langley, Leyden, Harnack and Meyer), as is also the diastolic arrest of the heart which pilo- carpine produces in the frog. Harnack and Meyer therefore believe that in both the frog and the mammal the chief cardiac influence of the alka- loid is exerted upon the intra-cardiac inhibitory ganglia ; but Ringer M finds that jaborandi and atropine act antagonistically upon the ventricles separated from the auricles, and, as the ventricles contain no inhibitory ganglia, some other explanation of the antagonism must be found.* The rise of the arterial pressure is stated by Harnack and Meyer to be pre- vented by the use of curare and artificial respiration, and to be, there- fore, a secondary, not a direct, result of the drug's action : it is probably due to the convulsive muscular contractions produced by the drug. In the latter stage of the poisoning the arterial pressure falls. As in the * Ringer's explanation seems at present the most probable. It is, that pilocarpine paralyzes the heart by combining with the molecules of the excito-motor apparatus and of the muscular tissue, and that atropine displaces the pilocarpine and thereby substi- tutes its own action. DIAPHORETICS. 725 experiments of Harnack and Meyer asphyxia in this stage did not cause rise of pressure, although the heart appeared still to retain its force, the vaso-motor system is probably paralyzed, a conclusion confirmed by the later experiments of Reichert. The pulse still continues slow, although, according to Harnack, the vagi are completely paralyzed. Respiration. According to the experiments of Morat and Doyon," pilocarpine produces a distinct slowness of the respiration, and as a respiratory poison is the antagonist to atropine.* Sexual Organs. Jaborandi does not appear to have any power over the sexual organs, except the pregnant womb. Cases of abortion during its use have been reported by Masmann (quoted by Larvand K ) and by Schanta, 36 but in the hands of other observers the drug has appeared to have little, if any, abortifacient influence, and Hyernaux and Chanteril have found it powerless in the lower animals (quoted by Larvand). When, however, the pregnant female is at her full term, the drug may affect the uterine contractions, as Larvand and others have noted an increase of the pains, or even a precipitation of labor, both in women and in the lower animals. Nevertheless, the oxytocic powers of jaborandi are very feeble.f Motor System. In man, muscular tremblings have been observed during the action of jaborandi, but it is doubtful whether they are due to a direct action of the remedy. In the frog, as first noticed by Mur- rell, 37 small doses (three milligrammes of pilocarpine) produce violent convulsions with heightened reflex activity, while larger amounts cause complete palsy. According to Harnack and Meyer, the convulsions are due to spinal stimulation, and the paralysis partly to overwhelming of the spinal centres and partly to paralysis of the muscles, the motor nerves themselves not being affected. The action of the drug upon the mus- culo-nervous system is entirely subservient to its other effects. Eye. When applied to the eye, pilocarpine produces contraction of the pupil, tension of the accommodative apparatus, and an approxima- tion of the near and far points of distinct vision. \ Tweedy also states that there is impairment of vision, due to benumbing of the retina. According to P. Albertoni, the myosis is followed by a moderate but persistent mydriasis, and is not prevented by previous section of the oculo-motor nerve or of the upper cervical sympathetic ganglion. It is certainly the result of a peripheral influence. Galezowski, who uses a solution of one part of a pilocarpine salt in fifty parts of water, affirms that it answers as well as a solution of eserine in diseases of the eye, and has the great advantage of not producing irritation. * H. Dreser (Arch.f. Exper. Path. . Pharm., 1892, xxx.) has experimentally found that pilocarpine markedly increases the oxygen in the air of the swimming bladder of the carp. t See British Medical Journal, 1879, ii. 509 ; alsoWu-H. Med. Bliitt., 1879, ii. 1178, 1207. j See John Tweedy (Lancet, 1875, i. 159), C. Scotti (Berl. Klin. Wochens., 1877, 143). and Galezowski ( Med. Times and Gaz., 1877, ii. 358). 726 LOCAL REMEDIES. THERAPEUTICS. Jaborandi is by far the most reliable and powerful remedy of its class, and is always selected when it is desired to produce a very active sweating, as in jircemia or in dropsy. Both in acute and chronic Bright' s disease it is of very great value, either as an aid to or as a succedaneum for the vapor-baths. The sweating should be repeated at regular intervals, varying from one a day to one a week, according to the nature of the case. Not only is jaborandi valuable for the removal of distinctly excremen- titious material from the blood, but it is often of the greatest service in arresting the development of a forming disease, probably by eliminating peccant matters. Thus, in the onset of an attack of influenza, in the be- ginning of a bilious fever, and in subacute and muscular rheumatism it may often be used with great advantage. On the other hand, when in a fever it is desired not to produce a single excessive sweating, but simply to maintain moisture of the skin, jaborandi will hardly serve the purpose of the practitioner, and in typhoid or other asthenic fevers more or less danger of exhaustion attends its use. In doses of from one-twelfth to one-fifteenth of a grain (0.005-0.004 Gm. ), given every two to four hours, pilocarpine usually causes a decided increase in the secretion of urine, and is a valuable remedy in the treat- ment of cardiac and of renal dropsies. In rare cases albuminuria and even strangury * have followed this use of the drug, so that some caution would seem to be necessary in its employment in the early stages of acute nephritis. Nevertheless, we have seen it apparently successful in acute suppression of urine. In the treatment of pseudo-membranous laryngitis and in diphtheria pilocarpine was at one time extensively used, under the belief that by in- creasing the secretion beneath the membranes it would loosen them ; it has, however, failed to establish its value for this purpose. Ringer S8 has re- ported several cases of unilateral sweating cured by the use of full doses of pilocarpine given hypodermically. It has been used with asserted suc- cess in alopecia. Cheron affirms that, when given in doses of one-twelfth of a grain hypodermically, pilocarpine is very effective as a galactagogue, but Ch. Cornevin w found that in cows, at least, pilocarpine has no influ- ence upon the quantity of milk secreted, though it increases the produc- tion of lactose. Locally applied (half-ounce of the leaves) in the form of a poultice, jaborandi may sometimes produce local sweating only, but we have seen very marked and extraordinarily prolonged general sweating so caused. The Use of Pilocar'pine in Diseases of the Eye.^ The instillation of a one per cent, solution of pilocarpine hydrochlorate into the eye is fol- lowed by exactly the same results as those which have been described in * See Purjesz (Deutsch. Arch.f. Klin. Med., xvii. 533) ; also Stumpf (Deutsch. Arch., xvi.). t This section was written by Professor George E. de Schweinitz. DIAPHORETICS. 727 connection with eserine. Pilocarpine fulfils all the therapeutic indications of eserine. It is not, however, as active, and therefore the strength of the solution used must be greater. It has the advantage of being less irritating and less liable to cause iritis. ADMINISTRATION. The fluid extract of jaborandi (FLUIDEXTRACTUM PILOCARPI, U. S. ) may be given in doses of half a drachm to a drachm (2-4 C.c. ), but is inferior to the alkaloid in being more uncertain and more liable to nauseate. Dose of the nitrate or hydrochlorate (PiLOCAR- PINE HYDROCHLORAS, U. S., PILOCARPINE NITRAS, U. S. ), from one-eighth to one-third of a grain (0.0080.02 Gm. ). In larger doses it is capable of producing so severe sweating as to end in collapse. Even pilocarpine, however, is apt to cause vomiting, and we have found that when it is desirable to produce an excessive sweating for the purpose of breaking up a forming disease, much better results may be obtained by conforming to the following procedure than by giving pilo- carpine unaided: let the patient, prepared for bed, take one dessert- spoonful of a mixture containing, to the dessertspoonful, one-twelfth of a grain of pilocarpine hydrochlorate, five grains of antipyrin, and one to three minims of tincture of aconite-root ; soak the feet fifteen minutes in a hot mustard bath ; on getting into bed take a teaspoonful of the pilo- carpine mixture, with a tumbler of very hot lemonade or whiskey punch ; repeating every twenty minutes the pilocarpine mixture until free perspiration sets in. Antagonism, with Atropine. In 1875 Langley * called attention to the antagonism existing between jaborandi and belladonna. When the heart has been slowed or arrested by jaborandi, atropine will bring the rate of pulsation almost to normal ; the reverse of this also occurs, pro- vided the amount of atropine previously applied has not been too great (Langley). Upon the sweat-glands the two drugs have also antagonistic powers, one being able to annul the action of the other (Fuchsinger). The same is true in regard to the salivary secretion (Langley). This antagonism between atropine and jaborandi is affirmed by H. Larvand to extend to the intestines and pupil. In belladonna-poisoning the alka- loid has been used with no advantage in very small dose, 41 but in a case in which nine-tenths of a grain of atropine had been taken, nine grains of pilocarpine are said to have been injected hypodermically in between one and two hours with success (Purjesz"). L. Juhasz" reports a case in which it was estimated that about one and a half grains of atropine were taken, followed in half an hour by vomiting ; four and a half grains of pilocarpine were injected in about seven hours, with a favorable result. Hofferts u reports a case in which seven and a half grains of extract of "belladonna were ingested, and nearly two grains of pilocarpine given, with recovery.* * For other cases of like import, see I^ancet, 1890, ii. ; also Therap. Gaz., 1887 728 LOCAL REMEDIES. SPIRITUS ^THERIS NITROSI SPIRIT OF NITROUS ETHER. U. S. Sweet spirit of nitre is an alcoholic solution of ethyl nitrite. It is soluble in all proportions in water and alcohol, and has a neutral reaction, is a volatile, inflammable liquid, of a pale yellow color inclining slightly to green, having a fragrant, ethereal odor, free from pungency, and a sharp, burning taste. It has the specific gravity 0.836 100.842, and contains 4.3 per cent, of its peculiar ether. It should not be long kept, as it becomes acid by age. Sweet spirit of nitre when taken freely in the form of fumes may cause symptoms of nitrous acid poisoning. Thus, as produced by its inhalation, D. R. Brown 45 noted very pronounced cyanosis of the face and hands, mental confusion, headache, cold extremities, excessive muscular weakness, very rapid, feeble pulse, a slow, regular respiration which on the least exertion became hurried and accompanied by a pain- ful sense of oppression in the chest and by cardiac distress. When the spirit is taken by the mouth, the alcohol in it asserts its physiological powers. Thus, in a child three years old, killed in twelve hours by four ounces of the spirit, the symptoms closely resembled those of alcoholic poisoning, with the addition of vomiting and purging.* The therapeutic dose of nitre is somewhat calmative, and has some in- fluence, though not a very great one, in increasing the secretions of the skin and kidneys. It is a very popular remedy, especially useful in the case of children suffering from adynamic fevers with such nervous symp- toms as starting, jerking, mental excitement, etc. If the patient be kept on his feet and cool instead of being warmly covered in bed, the single large dose of the spirit of nitrous ether acts as a mild diuretic. When a diaphoretic action is required, small doses should be exhibited at short intervals. Thus, for a child one year old a teaspoonful may be put in five ounces of water and a tablespoonful be given every half to one hour. The adult dose is one to two fluidrachms (4-7 C.c. ). Spirit of Mindererus ( LIQUOR AMMONII ACETATIS. U. S. Solution of Ammonium Acetate} is a colorless, odorless liquid, prepared by satu- rating dilute acetic acid with ammonium carbonate. It was formerly used to a considerable extent in the treatment of adynamic fevers as a mild stimulant and diaphoretic, but has very properly fallen into disuse except as a vehicle for more powerful remedies. The dose usually given is one to two tablespoonfuls (7.5-15 C.c.), but two ounces (60 C.c.) of it may be exhibited at one time. Before the introduction of jaborandi, probably the most useful and most efficient known diaphoretic was Dover's Powder (PuLVis IPECACU- ANHAS ET OPII, U. S. ), which contains one grain of opium, one grain * Case, Lancet, 1878, ii. Christison reports a case of a woman whose death was attributed to sweet spirit of nitre. DIAPHORETICS. 729 of ipecacuanha, and eight grains of sugar of milk. When, as in some cases of acute rheumatism, it is desired at the same time to allay pain and increase the action of the skin, Dover's powder may be exhibited in doses of from three to five grains (o. 2-0. 3 Gm. ) every two, three, or four hours, pro re nata, in capsules or pill. Given in a single large dose, ten grains (0.7 Gm.), especially when aided by proper measures and other diaphoretics, it is efficient in producing a free perspiration, and may thus be used in forming acute colds, etc. In the intense suffering which some- times results from sudden suppression of menstruation, Dover's powder, by relieving pain and aiding in the production of diaphoresis, often acts most favorably. REFERENCES. DIAPHORETICS. 23 1. STEFFEN . . . . Jahrb.f. Kinderheilk., 1871, 24. iii. 25. 2. BAELZ Verhandl. d. Congress, f. innere Med., 1893. 26. 3. B. M. J., Oct. 1878. 27. 4. SCHOTTIN .... Arch. f. Physiol. Heilk., 2 8. 1851, xi. 29. 5. REES Encyclopaedia of Anat., iv. 841- 30. 6. FIEDLER In. Dis., Leipsic, 1854. 3I . 7. HIRSCHSPRUNG . Gaz. des H6p., 1865. 32. 8. KAUP and JURGENSEN . D. A. K. M., 1869, 33. vi. 54- 34- 9. LEUBE D. A. K. M., 1869, vii. 3. 35. 10. DEININGER . . . D. A. K. M., 1869, vii. 587. 36. n. FUNKE U. N. M. T., vi. 37. 12. MEISSNER .... In Dis., Leipsic, 1859. 38. 13. VULPIAN Lecons sur Subst. Tox- 39. iques, Paris, 1881, 87. 40. 14. HARDY and BALL . J. de Th., 1874. . 41. 15. PILICIER Med. Centralb., 1876, 430. 42. 16. MORAT Lyon M., July, 1882. 17. PETTIT C. R. S. B., 1896, iii. 43. 18. GOTTLIEB . . . . A. E. P. P., 1894, xxxiii. 261. 19. FEREOL J. de Th., Jan. 1875. 44. 20. LANGLEY .... J. P., 1878, 339. 21. CARVILLE . . . . J. de Th., 1875. 45. 22. SCHWANN .... Med. Centralb., 1875, 440. 46. FUCHSINGER . . . A. G. P., xv. 482. PRENTISS . . . . P. M. T., xi. 610. RASORI Trans. Internal. Med. Cong., 1881, iii. 146. GROCCO L. M. R., 1882, 137. LANGLEY . . . . J. A. P., x. 188. LEYDEN . . . . B. K. W., 1877, 406. KAHLER and SAYKA . Med. Centralb., 1876, 541- HARNACK and MEYER . A. E. P. P., xii. HARNACK .... A. E. P. P., xx. REICHERT . . . . U. M. M., 1893. RINGER Pract., xxvi. 12. MORAT and DOYON . C. R. S. B., 1892, iv. LARVAND .... La Pilocarpine, 1883. SCHANTA . . . . W. M. W., 1878, No. 18. MURRELL . . . . P. J. and Tr., vi. 228. RINGER Pract., xvii. 401. CORNEVIN . . . . C. R. S. B., 1891, iii. LANGLEY . . . . B. M. J., Feb. 1875. L. L., 1876, i. 346. PURJESZ Pest. Med.-Chir. Presse, 1880. JUHASZ Klin. Monatsbl. f. Augen- heilk., xx. 86. HOFFERTS .... Wien. Med. Presse, 1883, xxiv. 1412. BROWN P. J. Tr., March, 1857. VOIT Z. B., 1902-03, xliv. FAMILY VI. EXPECTORANTS. UNDER the present heading we propose to discuss not only true ex- pectorants, that is, those medicines which have the power of influencing diseased conditions of the respiratory mucous membranes, but also vari- ous substances and even various procedures which are employed for the relief of pulmonic conditions. Cough. When from disease or from other causes obnoxious materials, be they secretions or foreign matters, accumulate in the bronchial tubes, cough is necessary for their expulsion, so that in a large proportion of cases no treatment of cough is desirable. On the other hand, there are cases in which, owing to excessive irritability of the pulmonic mucous membrane, the amount of cough is out of all proportion to the amount of material to be expelled. Under these circumstances the symptom is not only annoying, but also, by irritating the mucous membrane of the lungs and by exhausting the patient, directly harmful. In another set of cases, owing to muscular weakness and to lack of irritability of the mucous membrane, the cough is not sufficient for the expelling of the secretions, which gradually accumulate in the lungs, fill up the bronchial tubes, and finally, it may be, cause death by a process comparable to that of drowning. It is plain that the medical practitioner must study in each individual case the relations between the cough and the amount of work required ; so that if the cough be excessive it may be allayed, if it be insufficient it may be stimulated. For the purpose of allaying cough, soothing vapors or liquids may be applied to the respiratory mucous membrane by inhala- tions, but in the majority of cases internal anodynes are necessary. In some instances the cough is maintained by an excessive irritability in the upper throat and air-passages, so that demulcents such as liquorice are very useful, or relief may be obtained by sipping a mixture composed of glycerin and whiskey, each one part, with two to four parts of water. The anodyne substances which are employed for the relief of cough are hydrocyanic acid, belladonna, hyoscyamus, chloroform, the bro- mides, and heroine. The action of hydrocyanic acid is too brief for the remedy to be of practical value. Belladonna, unless locally applied by means of atomization, is very uncertain in its action and of entirely sec- ondary importance ; superior to it is hyoscyamus, although even full doses of this remedy often are ineffective. Chloroform, in doses of ten to fifteen minims, sometimes acts most happily, but must be given at very EXPECTORANTS. 73 i short intervals on account of the fugaciousness of its influence, and is more useful in combination than alone. The bromides in full doses are often effective, and may well be combined with chloroform ; in some cases they are too depressant. Much more certain in its influence than any remedy yet mentioned is opium ; its tendency to check secretion forbids its use, however, in a very large proportion of cases, notably in those in which there is persistent dryness of the bronchial mucous mem- brane, whether this dryness represents the first stage of an acute bronchi- tis or whether the case be one of a continuing subacute bronchial irritation so frequent in neurotic individuals. Moreover, the usefulness of opiates is further limited by their tendency to derange digestion, and in chronic cases by the danger of forming the opium habit. Under these circum- stances the diacetic ester of morphine (heroine) is very valuable. We know of no method of increasing the irritability of the pul- monic mucous membrane when impaired. In such cases, if the loss of irritability be, as it usually is, dependent on general atony, strychnine and cocaine may be administered in full doses, and are sometimes very serviceable. In an acute case, with failure to expel the secretion, as in the suffocative catarrh of infants, life may sometimes be saved by me- chanical treatment. Stimulating emetics are often of the greatest service in freeing the bronchial tubes of secretion. On various occasions we have resuscitated young children after they had become completely coma- tose and lost the ability of swallowing from asphyxia due to suffocative catarrh, by the following procedure, which was suggested to us by the well-known reflex spasmodic contraction of the respiratory muscles pro- duced by a dash of cold water on the chest : Provide three tubs, one empty, one containing ice-water, and one with water at about 115 F. Hold the naked body of the child over the empty tub, and dash over the upper thorax a ladleful of the hot water, followed immediately by one of the cold water. So soon as the color of the skin has begun to change under the respira- tory gaspings, and some evidences of consciousness appear, dip the body of the child momentarily in the hot water, when the scream produced by the pain will usually fill the lungs with air. In this procedure the hot water is used alternately with the cold water to prevent chilling of the body as well as to increase the shock. To allay Spasm. When a spasm affects the laryngeal muscles acutely it may often be put an end to by an emetic dose of ipecacu- anha or, in a very robust subject, of lobelia ; but in some cases, espe- cially in so-called laryngismus stridulus, the exhibition of an anaesthetic may be necessary for the saving of life. In such cases chloroform should be selected on account of the locally irritating influence of ether. Amyl nitrite in alarming cases often acts most happily. For the prevention of the recurrence of these spasms the various anodynes mentioned above may be employed. The most generally successful is the bromide, which in spasmodic croup should be given repeatedly in full doses. Local appli- cations of belladonna the smoking of belladonna cigarettes are often very useful. 73 2 LOCAL REMEDIES. In extreme cases of asthmatic bronchial spasm relaxation may be ob- tained by the exhibition, in robust cases, of lobelia in full doses, by smoking belladonna or stramonium cigarettes or pipes,* by the inhala- tion of amyl nitrite or chloroform, or by hypodermic injections of mor- phine or of heroine hydrochlorate. Local applications may be made to the lungs in the form of vapor or of fine spray obtained by the so-called pulverization of water. Atomization consists in breaking up by a mechanical contrivance watery solutions of a medicinal substance into a fine spray. At one time it was believed that in this way the finest ramifications of the bronchial tubes could be reached, but the method has gradually passed out of use except for cases in which the disease is in the fauces, larynx, or trachea. In using atomization it must be remembered that it is only a means of making a local application to a certain part, so that the rules governing the choice of drugs to be employed are precisely those affecting local applications to other than the respiratory mucous membrane. By atomization warm water may be applied as a diluent and as a soothing application, its soothing properties being capable of increase by the addition of cocaine, opiates, or other narcotic remedies. By atomi- zation stimulant substances, such as ammonium chloride, also benzoates, carbolates, or other antiseptics, may be brought in contact with a dis- eased mucous membrane. When there is excessive secretion, as in bron- chorrhoea, or hemorrhage, as in haemoptysis, the practitioner may use in the atomizer such astringents and haemostatics as tannic acid, one to twenty grains to the fluidounce ; alum, from five grains to the fluidounce to a saturated solution ; iron, Monsel's solution, five to fifteen drops to the fluidounce. In all cases in which strong local applications are being made to the lungs the occurrence of severe cough is an indication that the application is causing much irritation. TRUE EXPECTORANTS. From a therapeutic point of view acute bronchitis is divisible into three stages : first, that of extreme dryness of the mucous membrane and tightness of cough ; second, that in which secretion is about to be established ; third, the final stage, in which expectoration is free. In an * There are upon the markets numerous proprietary mixtures for the relief of asthma by smoking ; most if not all of them consist of powdered belladonna or stramo- nium, mixed with potassium nitrate and sometimes other substances. Clinical expe- rience has shown that the efficiency of these powders is increased by the presence of arsenic, which probably acts by stimulating the bronchial mucous membrane to secrete freely. The following formula, taken from an old Pharmacopoeia of the Philadelphia Hospital, we have found to yield a very efficacious paper. CHARTA ARSENICALIS COMPOSITA (Compound Arsenical Paper). R Belladonnae fol., gr. xcvi ; Hyoscyami fol., Stramonii fol., aa gr. xlviii ; Extr. opii, gr. iv; Tabaci, gr. Ixxx ; Aquae, Oj ; M., ft. sol. et add. Potas. nit., gr. clx ; Potas. arsenit., gr. cccxx. Satu- rate bibulous paper and dry for use. Roll the paper into cigarettes, one of which is to be smoked two to six times a day until relief is afforded or some giddiness is produced. EXPECTORANTS. 733 exacerbation of chronic bronchitis either one of these stages may be rep- resented, but in a continuing course of the chronic bronchitis there is usually a condition of the mucous membrane which requires the use of such expectorants as are employed only in the most advanced stages of an acute bronchitis, i.e. , of a stimulating expectorant. In accordance with the division just made of the stages of a bron- chitis, expectorants may be arranged in three groups : first, sedative ex- pectorants ; second, expectorants which are suitable for the second stage of bronchitis, which may be termed simply, expectorants ; third, stim- ulating expectorants. Of course, it must be understood that the division which has been made is arbitrary, and that very frequently there are conditions in which expectorants of one group may well be combined in one prescription with those of another group. Thus, ipecacuanha and ammonium chlo- ride are often very serviceable in union. EXPECTORANTS OF THE FIRST GROUP. The sedative expectorants among which we have choice in the first stages of a bronchitis are lobelia, tartar emetic, ipecacuanha, potassium citrate, and apomorphine. Of these substances Lobelia is to be employed only in asthmatic cases in which there is distinct tendency to spasm of the bronchial tubes. The tincture (TiNCTURA LOBELIA, U. S. ) may be given in doses of fifteen to twenty drops (1-1.2 C.c. ) every three hours, or when a spasm amounts to a violent asthma, one fluidrachm (3.7 C.c.) may be exhibited every two hours until vomiting is produced. When large doses of lobelia are given the patient must be closely watched, as sometimes an alarming de- pression is produced. Tartar Emetic is similar in its expectorant influence to ipecacuanha, but much more powerful and much less safe. It should never be used in adynamic cases or with young children. Dose, as an expectorant, one- twelfth to one-sixth of a grain (0.005-0.01 Gm.), repeated according to circumstances. ipecacuanha is very largely used in the early stages of acute bron- chitis, and is the safest of the nauseating expectorants. The dose of the syrup is from thirty drops to a teaspoonful (1.8-3.7 C.c.) every two to four hours, according to the exigencies of the case. Potassium Citrate, when given in large doses, has a very notable effect in increasing bronchial secretion during the dry stage of a bronchitis, and especially lends itself under these circumstances to combination with ipecacuanha, or in very robust cases with tartar emetic ; one ounce (30 Gm. ) of it should be given in the twenty-four hours. For many patients its taste is well concealed by lemon-juice. Apomorphine Hydrochlorate is a valuable sedative expectorant, useful in exactly the class of cases in which ipecacuanha is commonly given. 734 LOCAL REMEDIES. The expectorant dose is one-twelfth of a grain (0.005 Gm.), repeated every two or three hours. EXPECTORANTS OF THE SECOND GROUP. AMMONII CHLORIDUM AMMONIUM CHLORIDE. U. S. Ammonium Chloride occurs in large concavo-convex plates, white, translucent, tough and fibrous, free from odor, but having a sharp, saline taste, and soluble in three parts of cold and one part of boiling water. THERAPEUTICS. Ammonium chloride is a powerful irritant, concern- ing whose poisonous properties there is great diversity of statements. Oesterlen affirms that he has seen two ounces of the salt taken by man without the production of more serious results than violent gastro-intes- tinal pain and diarrhoea, whilst older observers state that two drachms of the salt are sufficient to cause death in a dog. According to Arnold, thirty grains will kill a rabbit in ten minutes ; but Rabuteau found that one drachm injected intravenously produced in the dog only vomiting, muscular weakness, temporary paralysis of the hind legs, and general prostration, lasting four or five hours. After absorption it shares the general physiological activity of the ammoniacal salts. When given for a length of time in very large doses it affects the general nutrition. We have seen extreme prostration and a typhoid condition apparently produced by the taking of half an ounce per diem for some days, whilst great prostration, with an eruption of bloody blebs, haematuria, and hemorrhages from the mucous membranes, has been reported by Isham as caused by the continuous use of the drug. These symptoms are concordant with the statements of Sundelin, that the blood suffers especially and loses its plasticity under the action of the drug. In an elaborate series of analyses, F. W. Bocker 1 determined that its long use is accompanied by a decided decrease in the solids of the blood, an observation confirmed by Arnold. Both Bocker and Rabu- teau 2 found that in healthy man it notably increases the urea and other solids of the urine except uric acid, so that when taken in large amount and continuously it evidently has a positive influence on the chemical movements of the organism. According to Rabuteau, ammonium chloride is freely secreted by the salivary glands, but chiefly escapes from the kidneys, almost all the salt taken being recoverable from the urine. Although there is sufficient reason for believing that ammonium chloride especially affects the respiratory mucous membrane, the state- ment of Bocker, that it hastens very greatly the nutritive changes and the exfoliation of the epithelium in all mucous membranes, is in accord with clinical experience as to its value in various gastro-intestinal condi- tions. In Germany more than in this country it has been extensively used in the treatment of chronic gastric and intestinal catarrhs. The statement of W. Stewart, 8 made in 1870, that it is an effective remedy EXPECTORANTS. 7 / O*J in chronic torpor of the liver and chronic hepatitis, has been sustained by subsequent clinical experience, and it has become a standard remedy in these affections and in catarrhal jaundice. As an expectorant ammo- nium chloride is useful in an aczitc bronchitis when free secretion has just been established. In chronic bronchitis it should be administered from time to time when the secretion is not very free. Ammonium chloride was at one time frequently given in intermittent fever, but has failed to sustain itself. Another old use was for relieving pain in neuralgia, especially of the ovarian variety. Thirty grains of it were administered in combination with two to five drops of tincture of aconite root, repeated in half an hour if necessary. In our hands this treatment has not given satisfaction. The expectorant dose of ammo- nium chloride is five to ten grains (0.3-0.6 Gm. ) every three hours, in at least two ounces of water. The dose in hepatic diseases is twenty to thirty grains (1.3-2 Gm. ) in four or five ounces of water, three or four times a day, administered when the stomach is empty. EXPECTORANTS OF THE THIRD GROUP. GRINDELIA. U.S. This is the leaves and flowering tops of Grindelia robusta and of Grindelia squarrosa, plants inhabiting the extreme western portions of North America. In commerce the whole herb, including the stems, roots, and floral heads, is sold. The taste is warmish, peculiar, and very persistent.* The presence of a crystalline alkaloid in grindelia has been asserted by several investigators, but at present it seems probable that its activity depends upon a turpentine-like volatile oil. PHYSIOLOGICAL ACTION. The toxic powers of grindelia are said to be so feeble that three drachms of the fluid extract are required to kill a rabbit. Concerning its physiological action we have little definite knowledge ; according to Buffington, it produces narcosis with dilated pupils by a cerebral influence, but acts more powerfully in paralyzing the nerves of sensation and the sensory side of the cord, and finally attacks both the motor cord and nerves. Dobroklowski asserts that it acts upon the motor nerves and the muscles. Buffington affirms that it causes in warm-blooded animals a slowing of the action of the heart by stimu- lating the inhibitory apparatus, and an elevation of the blood-pressure by stimulating the vaso-motor centres. Dobroklowski states that the large but non-toxic doses increase the pulse-rate as well as the arte- rial tension ; also that these phenomena not being affected either by isolation of the heart from the nervous system, by the previous use of atropine, or by division of the spinal cord, they must be caused by a direct influence upon the heart or the peripheral vessels. Do- broklowski further affirms that in toxic dose the drug depresses the * See Centralbl.f. Med. Wissens., 1885, xxiii. ; Amer. Journ. Med. Set., Jan. 18, 1886; Land. Med. Rec., March, 1886. 736 LOCAL REMEDIES. pulse-rate and the arterial tension, and finally arrests the heart in diastole. THERAPEUTICS. Grindelia has not been employed for its effect upon the circulation, and in the doses used in medicine it appears to exert no distinct influence upon the heart or arteries. It has been largely used, often with alleged excellent results, in asthma, and in bronchitis associ- ated with a tendency to bronchial spasm. It is probable that in these cases it not only has a relaxing influence, but also stimulates the mucous membrane, and even in chronic bronchitis, especially of the aged, it is said to do good. It has been employed in w hooping -cough. Its active principles are probably excreted by the kidneys ; hence after large doses there are sometimes evidences of renal irritation, and in chronic catarrh of the bladder good has been effected by its stimulant influence upon the mucous membranes of the viscus. It has also been employed as a local application, with alleged good results, in vaginitis. The dose of the fluid extract (FLUIDEXTRACTUM GRINDELI^E, U. S. ) is from twenty to sixty minims (1.23.7 C.c. ). The fumes of burning grindelia are sometimes inhaled with alleged relief in asthma. The plant should be steeped in a solution of nitre, dried, and burnt upon a plate, or may be smoked in cigarettes or in a pipe. BALSAMUM PERUVIANUM, U. S. , Balsam of Peru, is obtained from Toluifera Pereirae, a tree of Central America. This balsam is a viscid, honey-like, fragrant, brownish fluid, of a warm, bitterish taste, which has been shown by Brautigam and Nowack 4 to be practically devoid of anti- septic properties. According to Fre"my, it contains not benzoic, but cin- namic acid. It has been used in chronic catarrhs of the respiratory and the genito-urinary systems, in doses of half a fluidrachm (2 C.c.). BALSAMUM TOLUTANUM, U. S. , Balsam of Tolu, is obtained from Toluifera Balsamum, a tree very closely allied to that which yields the balsam of Peru. Balsam of Tolu is at first a thick, viscid fluid, but by time it is converted into a hard, translucent, resinous solid. Its odor is highly fragrant and its taste vanilla-like. It contains cinnamic acid and a volatile oil, and its medical properties are the same as those of the balsam of Peru. On account, however, of its grateful taste, it is preferred to the latter, and is very much used to flavor medicines, especially cough-mix- tures. In large doses, twenty to thirty grains (1.32 Gm. ) every three hours, it may be of some value in chronic bronchitis, but as generally used its preparations are simply agreeable vehicles. The dose of the tincture (TINCTURA TOLUTANA twenty per cent. , U. S. ) is one-half to one fluidrachm (2-4 C.c.); of the much more frequently used syrup (SYRUPUS TOLUTANUS, U. S. ), half a fluidounce (15 C.c.). ALLIUM, or English Garlic, the clove of Allium sativum, con- tains a volatile oil which in small doses is a stimulant to digestion, and EXPECTORANTS. 737 is also used as a stimulating expectorant in the advanced stages of obsti- nate bronchitis, and in the acute bronchitis of infants, when the powers of the system begin to flag. The oil of garlic is further believed to have the ability to stimulate the expulsive function of the small bronchial tubes, and is certainly a powerful rubefacient and a decided nervous stimulant. For these reasons, garlic poultices are a favorite application in the acute suffocative catarrh of infants, and are not rarely applied to the spine, legs, and feet in general infantile convulsions. They are made by simply re- ducing the garlic to a pulp by pounding. When a continuous applica- tion is desirable to the delicate skin of an infant, as in catarrh, it is generally necessary to reduce their strength with flaxseed meal. The dose of the syrup (SYRUPUS ALLII, U. S. 1890) for a child a year old is one fluidrachm (4 C.c.). SCILLA, U. S., or Squill, is one of the most used of the stimulating expectorants, coming especially into play in the advanced stages of ordinary bronchitis. The syrup (SYRUPUS SCILL^E, U. S. ) is the favor- ite expectorant preparation. As it contains acetic acid, it is incompati- ble with ammonium carbonate. Compound Syrup of Squill, or Coxe's Hive Syrup ( SYRUPUS SCILL^E COMPOSITUS, U. S.), contains one grain of tartar emetic to the ounce, and is therefore sedative to the circulation, although stimulant to the bronchial mucous membrane. It is not suit- able for young children, although it has been much used in spasmodic croup. The dose of the simple syrup is one-half to one fluidrachm (24 C.c. ) ; of the compound, twenty to forty drops ( i. 2 2.5 C.c. ), according to age, repeated every twenty minutes until it operates. Pix LIQUIDA. U. S. Tar is a black semi-liquid substance, of peculiar odor and taste, obtained by the destructive distillation of various species of pine. The tar used in this country is almost exclusively the product of the Pinus palustris of North Carolina and other of the Southern States. In composition it is very complex, containing pyroligneous acid, creosote, empyreumatic oil, and a number of more or less peculiar principles. When distilled, it yields an oily liquid, known as oil of tar, and a solid, black residue, pitch. It is freely soluble in alcohol, ether, and the fixed and volatile oils, and also to a slight extent in water. The physiological action of tar resembles that of creosote. According to Taylor, the oil of tar has produced death in man. To cause death, tar itself would have to be ingested in enormous quantity, since a sailor (according to Still) recovered after taking between a pint and a quart of it. It is used internally solely in the advanced stages of obstinate acute bronchitis, or in chronic bronchitis. Locally, it is much employed in chronic diseases of the skin, as a stimulant application in the form of the official ointment (UxcuENTUM PICIS LIQUIDS, U. S., equal parts). In many cases this is too severe, and the strength must be reduced. Hebra states that if it be applied too freely enough of the tar may be ab- 47 738 LOCAL REMEDIES. sorbed to darken the color of the faeces and the urine, and even to cause gastric irritation and black vomit. For internal administration the best preparation is the Syrup of Tar (SYRUPUS PICIS LIQUIDS 7.5 per cent., U. S.) Dose, one to two fluidrachms (3.7-7 C.c. ). TEREBENUM. U. S. Terebene is a clear, colorless liquid, insoluble in water, isomeric with turpentine, and of a peculiar odor, somewhat resembling that of freshly sawed pine wood. It is prepared by the action of sulphuric acid upon oil of turpentine. Terebene, one of the most effective of the stimulant expectorants, was first recommended by William Murrell. 5 It is very useful not only in chronic bronchitis, but also in the acute disease after the earlier stages have passed by. As an expectorant it is nearly equivalent to the oil of eucalyp- tus, but is more stimulating. It has also been employed with asserted good results in dyspepsia, especially in the flatulent intestinal variety, and may be used in chronic or subacute inflammations of the genito-urinary tract. Its action upon the general system has not been investigated, but proba- bly resembles that of oil of turpentine. From twenty to forty minims (1.2-2.5 C.c.) of it may be given to the adult in the course of twenty- four hours. It lends itself well to use by inhalations, either by atomiza- tion of water containing it or by vaporization from hot water. The vapor should be as concentrated as can be borne without exciting cough. OLEUM SANTALI, U. S., Oil of Sandal Wood, is a pale yellowish, strongly pungent, aromatic, and spicy volatile oil, obtained from the wood of the Santalum album. It is a stimulant or irritant to the various mu- cous membranes, and while its general action upon the system is not known, it is a very valuable remedy in chronic bronchitis and in the ad- vanced stages of acute bronchitis, and also in the advanced stages of gon- orrhcea. It seems to be more stimulating than is the oil of eucalyptus. From ten to twenty drops ( i . 2-2. 5 C.c.) may be given every three or four hours in capsules, emulsions, or on sugar. Among the most valuable of the stimulant expectorants are the oil of eucalyptus and creosote. ( See pages 550 and 565. ) TERPIN HYDRATE. TERPINI HYDRAS. U.S. This substance, which occurs in colorless, nearly odorless prisms, of a slightly aromatic and some- what bitter taste, nearly insoluble in water, soluble in alcohol, is used in practical medicine as a stimulant expectorant, resembling in its action other members of the turpentine group, and especially useful in chronic bronchitis and in the advanced stages of acute bronchitis when the secre- tion is unusually free. In our experience it is better borne by the stomach than is terebene, and is, in its action upon the lungs, scarcely distinguish- able from that agent. It has also been used in chronic cystitis, and in gonorrhoea. It may be given in doses of from three to six grains (0.2-0.4 Gm. ) four to six times a day, in capsules. EXPECTORANTS. 739 SAPONINE. This glucoside is very widely spread throughout the veg- etable kingdom, Robert T giving a list of one hundred and forty plants which contain principles of the saponine class. According to the same authority, chemically pure saponine is physiologically inert, but saponine of com- merce is a very active poison, and all of the plants containing it in con- siderable amount are capable of producing symptoms similar to those caused by commercial saponine. The symptoms caused by poisoning with saponine plants are violent vomiting and purging, the result of an intense gastro-irritation ; convulsions ; renal irritation ; alterations in the blood itself, these plants being, in fact, actively toxic to all forms of protoplasm. Of the drugs containing saponine, two are recognized by the U. S. Pharmacopoeia, and, to some extent, used in practical medicine. SENEGA. U. S. The root of the indigenous Polygala senega containing saponine (the polygalic acid of the older chemists) and a second active principle, senegin is used to a considerable extent in the United States as a stimulating expectorant in the very advanced stages of acute bronchitis, and in chronic bronchitis with free expectoration. It is really of little value, and causes in full dose much gastro-intestinal irritation. Dose of the fluid extract (FLUIDEXTRACTUM SENEGA, U. S. ), ten to fifteen drops (0.6-1 C.c. ); of the syrup (SYRUPUS SENEGA, U. S. ), one fluidrachm (3.7 C.c.). QUILLAJA. U. S. Soap-bark, the inner bark of the Chilean tree, is probably the most actively poisonous of all the saponine-containing drugs. On account of its detergent properties, it is very largely used in the arts for cleansing silk and other fabrics. It is also employed as an emulsi- fying agent by the apothecaries, but its active physiological properties forbid such use of it. Robert recommends it as a cheap substitute for senega, given to the adult as a stimulating expectorant, a tablespoonful of a two and a half per cent, decoction. There are a number of expectorants of very small value, but requiring notice on account of their being in use. Ammoniac (AMMONIACUM), an irritant gum- resin, was formerly used to a considerable extent in chronic bronchitis in doses of from twenty to thirty grains (1.3-2 Gm.); of the emulsion (EMULSUM AMMONIACI four per cent.), one to two tablespoonfuls may be given. The EMPLASTRUM AMMONIACI CUM HYDRARGYRO, containing sulphur, has been employed as a local alterative and discutient in scrofulous swellings. Horehound (MARRUBIUM, U. S. ) contains a volatile oil and a bitter principle, marrubiin ; also tannin. It is used domestically to a considerable extent in catarrhs of the upper respiratory tract. Dose of the powder, thirty grains to one drachm (2-4 Gm. ). Bloodroot (SAN- GUINARIA, U. S. ) is in overdoses an emetocathartic and narcotic poison. It con- tains sanguinarine and other alkaloids, and has been used in chronic bronchitis, but has no practical value. Dose of the fluid extract (FLUIDEXTRACTUM SANGUINARY, U. S. ), two minims (o.i C.c.). Sanguinarine is a violent poison, causing in mam- mals vomiting, purging, collapse, convulsions, loss of reflex activity, cardiac 740 LOCAL REMEDIES. depression, and finally death from asphyxia. (For details see eleventh edition of this treatise. ) SULPHURETTED HYDROGEN. In 1886 Bergeon 6 proposed a method of treating phthisis by filling the large intestine with sulphuretted hydrogen diluted with pure carbonic acid gas. After an extraordinary but very brief popularity the method has fallen into such complete desuetude that it is only necessary here to refer to the tenth edition of this treatise for details. Sulphuretted hydrogen is, however, a valuable remedy in the treatment of purulent pulmonic catarrhs, whether of tubercular or other origin. When, under any circumstances, a bronchial catarrh is accompanied by very free expectoration the remedy may be useful in relieving the mucous membrane. We have also found it of service in chronic gout, when administered persistently for months. The method of administration employed by Bergeon was barbarous and absurd. The sulphuretted hydrogen may be given by the mouth in the form of a natural sulphur- water or, better, by means of water saturated with sulphuretted hydrogen and car- bonic acid gas. The dose of the saturated solution is two to four ounces (60-118 C.c. ), three or four times a day. In some cases it produces digestive disturbance, and its use has to be abandoned. That the gas is absorbed and eliminated by the lungs is proved by the very perceptible odor upon the breath. Many of the sulphur springs of Europe have inhaling chambers, and experience has shown that the sulphurous vapors are of value. REFERENCES. EXPECTORANTS. 4 . BRAUTIGAM and NOWACK . C. K. M., 1889, 1. BOCKER Beitr. z. Heilk., ii. 170. xxiv. 2. RABUTEAU . . . . L'Union M6d., 1871, xii. 5. MURRELL B. M. J., Dec. 1885. 329. 6. BKRGEON C. R. A. S., July, 1885. 3. STEWART Chloride of Ammonium, 7. ROBERT Chem. Centralblatt, 1893, Rangoon, 1870. . i. FAMILY VII. EMMENAGOGUES. EMMENAGOGUES are medicines which are employed to promote the menstrual flux. In the great majority of cases amenorrhoea is due to some local pelvic disease or general constitutional condition, the removal of which relieves the symptom. There are a few substances which appear to act directly as stimulants to the uterine mucous membrane, although they are notoriously uncertain in their effectiveness. When amenorrhoea is a symptom of chlorosis or due to other forms of anaemia, full doses of iron should be given. With iron may be com- bined the gum-resin myrrh, as in the compound mixture of iron (Mis- TURA FERRI COMPOSITA, U. S. Griffith's Mixture}. Dose, from one to two fluidrachms (4-7 C.c. ), three times a day. When atonic amenor- rhoea exists with constipation, aloes should be given along with the other emmenagogues. Ordinarily it should be administered in repeated doses (three times a day) of such size as will produce daily one or two soft, semi-liquid stools. At the menstrual period advantage may sometimes be derived from the administration of a full purgative dose. POTASSIUM PERMANGANATE, originally recommended by Sydney Ringer as an emmenagogue, has been very highly commended by For- dyce Barker and other physicians.* According to Barker, the perman- ganate is not to be employed when menstruation has been arrested by grave constitutional or local disease, or suddenly by cold, moral shock, or acute disease. Abortifacient properties have been attributed to it, and cases are reported in which abortion has followed its administra- tion, f Therapeutic doses of the permanganate must be entirely decomposed in a very short time after they reach the stomach, so that any action which the drug exerts upon the general system is due to the manganese oxide ; indeed, the ordinary black manganese oxide has been affirmed by various practitioners to be as active an emmenagogue as is the per- manganate. We have employed these agents to a limited extent in func- tional amenorrhoea, sometimes with, sometimes without, success. The only difference which we have been able to perceive in their action is that the permanganate is the more irritant to the stomach. The dose of either preparation may be set down as one to two grains (0.06-0. 13 Gm. ), always administered after meals, in order to avoid, as far as possible, * See Therap. Gaz., ii. and iii. t J. L. Watkins (Therap. Gaz., ii.), and S. B. Sperry (Ibid., iii.). 741 742 LOCAL REMEDIES. gastric irritation. Cases of severe gastritis produced by the permanganate have been reported. 1 CANTHARIDES is a very decided uterine stimulant, and is much used in emmenagogue mixtures. From two to five minims (o. 13-0. 3 C.c. ) of the tincture may be given three times a day ; if no unpleasant symp- toms arise, the dose may cautiously be increased to six minims, the production of strangury being, of course, sedulously avoided. GUAIAC, as an emmenagogue, is much less stimulating than can- tharides, and is believed by some to be especially useful in rheumatic dysmenorrhcea. In this affection, full doses of the ammoniated tincture should be given. The following formula, adapted from that of Dewees, known as Dewees' s Emmenagogue Mixture, is probably the most effec- tive combination ever made in atonic amenorrhoea. The proportion of the various ingredients should be varied to suit the exigencies of indi- vidual cases. R Tincturae ferri chloridi, f 3 iii ; Tincturae cantharidis, f^i ; Tincturae aloes, 555; Tincturae guaiaci ammoniatae, f^iss; Syrupi, q. s. ad f,^vi. S. Table- spoonful three times a day. SABINA. U. S. Savine. The dried tops of Juniperus sabina, a juniper, native of the south of Europe and the Levant, contain a turpen- tine-like volatile oil. This oil is a powerful irritant. When taken in sufficient dose, it produces severe abdominal pain ; incessant vomiting and bloody purging ; diminution or even suppression of the urine, which is often albuminous and bloody ; disordered respiration ; symptoms of disturbed innervation, such as unconsciousness, stertorous breathing, and convulsions or convulsive tremblings ; the scene closing by death in collapse. In pregnant females, abortion, accompanied by violent flood- ing, almost always occurs before the fatal issue. After death, signs of gastro- intestinal inflammation are generally present, but in some in- stances these are wanting, and in one case reported by Letheby * pul- monary apoplexy and congestion of the brain were the chief lesions. In rare cases of menorrhagia dependent upon uterine relaxation, the oil of savine is useful in doses of from five to ten drops (0.3-0.6 C.c.).. It owes its importance to the frequency of its domestic use as an aborti- facient, a use which is accompanied by the gravest danger to life and has often ended in death. The dose of the volatile oil (OLEUM SABIN^E, U. S. ) is from three to five minims (0.2-0.3 C.c.); of the fluid extract (FLUIDEXTRACTUM SABIN^E, U. S. ), ten to twenty minims (0.6-1.2 C.c. ). RUE. The leaves of Ruta graveolens, or common garden rue, contain a volatile oil whose properties are similar to those of oil of savine. It has been used in Europe for the production of criminal abortion, but seems to be less employed than is the oil of savine, and to be less dangerous, EMMENAGOGUES. 743 as we have met with no records of death from it except that of a man weakened by dysentery.* According to M. Helie, taken internally, in large doses, it causes violent gastric pains, excessive and sometimes bloody vomiting, profuse salivation and swelling of the tongue, great prostration, confusion of mind, and convulsive twitchings, with, in preg- nant women, abortion. TANACETUM. The common tansy of the gardens, Tanacetum vul- gare, in the form of decoction, or of its volatile oil, is sometimes used as a stimulant emmenagogue or for the purpose of producing abortion, but is a very unsafe remedy. When taken in sufficient amount it causes abdominal pain, vomiting, loss of consciousness, and violent epileptiform convulsions.! The minimum fatal dose of the oil of tansy is not known, but in two cases 3 a teaspoonful of the oil pro- duced violent epileptiform convulsions, and the same aanount is said to have caused death. Recovery is stated to have occurred after one and a half fluidrachms ;* also after three fluidrachms. 5 The action of the oil upon the lower animals has been studied by Guillery.' In frogs the most important effects which it was found to produce were paralysis of the peripheral endings of the motor nerves, with early appearance of post-mortem rigidity ; and paralysis of the vaso-motor centre of the medulla and of the inhibitory cardiac apparatus, with at last paralysis of the heart itself. In warm-blooded animals the oil produced symp- toms precisely similar to those which it causes in man. After section of the spinal cord the convulsions did not occur in the hind legs : they are therefore of cerebral origin. The arterial pressure was not affected until death was at hand : so that it is evident that the drug has little action upon the heart. OLEUM HEDEOM.E. U. S. Under the name of oil of pennyroyal, in the United States, the oil of the Hedeoma pulegioides is used as a stimu- lating emmenagogue in domestic practice, but has very little power. Two fluidrachms taken by a young woman produced vertigo, faintness, muscular weakness, frequent feeble pulse, cold skin, and cold extremities (C. A. Bryce 7 ). Dose, from two to ten minims (o. 12-0.6 C.c. ). In Europe the oil of Mentha pulegium is known as oil of pennyroyal. APIOL. Apiol is a peculiar non-nitrogenous, yellowish, oily liquid, which is obtained from the root of the Apium petroselinum, or common parsley. According to its discoverers, Joret and Homolle, 8 one gramme * Case of G. F. Cooper ( Med. Examiner, N. S., ix. 720). f For references to fatal cases, most of which have occurred in the United States, see U. S. Dispensatory, also Guillery (loc. cit.). Guillery believes that the symptoms caused by the oil and by tansy tea are different. In a case of poisoning by the leaves, however, reported in the Nashville Med. and Surg. Journ., 1879, xxiii., the symptoms were those alleged to be characteristic of oil-poisoning ; and the oil probably is the only active principle of the drug. 744 LOCAL REMEDIES. of it will produce in man a cerebral excitation very similar to that in- duced by coffee, without other symptoms. In doses of from two to four grammes it causes a species of intoxication, with vertigo, ringing in the ears, and severe frontal headache, a group of symptoms very similar to those seen in cinchonization. Apiol has been used to a considerable extent as an antiperiodic, but it is certainly of very inferior rank. It was originally recommended in anienorrhaca by Joret and Homolle, who exhibited three or four grains twice a day for a week preceding the time in which the return of men- struation was due. Whenever any symptoms of the menstrual molimen appear, fifteen grains of it should be administered in the course of three or four hours. It is always given in capsules, each of which, as imported from France, usually contains one-quarter of a gramme (3.9 grains). VIBURNUM OPULUS. U. S. Cramp-root. VIBURNUM PRUNIFO- LIUM. U. S. Black Haw. These remedies are believed by various practitioners to be of value in the treatment of dysmenorrhcea and menor- rhagia, and ovarian irritation. FLUIDEXTRACTUM VIBURNI OPULI, U S., or FLUIDEXTRACTUM VIBURNI PRUNIFOLII, U. S. , maybe given in doses of one to four fluidrachms (4-16 C.c. ) three to four times a day. The solid extract is sometimes employed, but is not an eligible prepara- tion and is not official. REFERENCES. EMMENAGOGUES. 4 ' L. M. R., 1882, 48. 5- Med. Bull., 1888, x. 1. T. G., 1887, iii. 6. GUILLERY . . . . B. A. R. B., 1878, xii. 2. LETHHBY L. L.. 1845. 7. BRYCE Southern Clinic, vi. 323. 3. Cincinnati Lancet and 8. JORET and HOMOI.I.E . Journ. de Pharmacie, Clinic, 1881. 3 s ., xxviii. 219. FAMILY VIIL OXYTOCICS. OXYTOCICS are those remedies which are employed during or directly after parturition, to increase the uterine action. Of the few drugs which have claims for position in the present class, quinine has already been fully considered ; it apparently differs entirely from the other known oxytocics in not producing continuous tetanic spasms of the uterus, and is therefore the safest stimulant to parturition at our command. The peculiar dangers which beset the use in labor of drugs which cause uter- ine tetanus will be fully discussed in the article upon ergot. ERGOTA ERGOT. U.S. Ergot is a blackish body, one to two inches in length, irregularly cylindrical, grooved along one side, and very generally curved ; it is composed of very thick walled microscopic cells, containing oil-drops but no starch. As was first demonstrated by Tulasne, 1 ergot is the sclero- tium of the Claviceps (C. purpurea, Tulasne) which infests the grain of Secale cereale, or rye. Among the lowest of vegetable organisms, and distinguished from all other plants by the absence of chlorophyll, are the fungi. There are in most cases two distinct states or stages in the life of a fungus : in the first of these, the vegetating period, it exists as a mycelium, a usually filamentous mass or flocculus, whose sole function is to grow and increase ; in the second stage the thai/us, or ordinary fungus or mushroom, is formed, and to it is assigned the function of developing repro- ductive bodies, after whose maturation it perishes. Between these stages there is in some fungi an intermediate one, in which the plant exists as a sclerotium. The genus Claviceps comprises a number of parasitic fungi, which develop in the pistils of the various species of Graminea?. The first appearance of the ergot is in the flower of the rye, at the base of whose pistil there arises a minute flocculent mass of mycelial filaments. These filaments, continually growing and invading all parts of the tissue of the pistil, at last form of it an irregular whitish body, at the base of which after a time appears a dark-colored body, the sclerotium, which continues to grow, lifting up the diseased and withering mass formed out of the original pistil, and finally developing into a perfect ergot. If a fresh, living ergot be placed in a damp, warm place, after a time little cracks will appear in its surface, and through these cracks little round bodies will project, and finally be raised up on stalks and constitute perfect thalli, minute fungi, which finally produce spores. Ergot is an exceedingly complex substance, containing nearly thirty- five per cent, of an inert fixed oil. 745 746 LOCAL REMEDIES. A large number of substances have been isolated and claimed to be the active principles of ergot. It is probable that the drug owes its activity to a number of ingredients rather than to any one substance. The most important of the prin- ciples as yet discovered is the resinous body sphacelotoxin, isolated by Jacobi," which seems to be identical with Robert's sphacelinic acid. According to Jacobi sphacelo- toxin enters into various combinations with other constituents of ergot, two of which he has isolated and shown to be physiologically active ; namely, chrysotoxin and secalintoxin. Robert 3 has found a tetanizing alkaloid cornutine which is also a powerful stimulant to the uterus. The term ergotin has been applied to a variety of substances, and to-day is most commonly understood to refer to Bonjean's ergotin, which is practically a watery extract of the drug. PHYSIOLOGICAL ACTION. Local Action. Absorption and Elimina- tion. The preparations of ergot have a very feeble local action, but their irritant properties are sufficient to interfere with their hypodermic use, and sometimes to make them disturb the stomach. They yield their active principles readily to absorption, but concerning the fate of these bodies in the organism we have no knowledge. General Effects. Even the largest therapeutic doses (an ounce of the fluid extract) produce in man no perceptible symptom save some nausea. In a number of cases death has resulted from abortion caused by large doses of ergot,* but we know of but two instances of serious poisoning in a non-pregnant person, f In the first case gastric irritation, thirst, diarrhoea, burning pain in the feet, and convulsions are said to have preceded death. In the second case (G. S. Oldright 4 ), two hours after taking the drug (amount not stated) there were developed tingling in the fingers and feet, cramps in the legs, arms, and chest, with dizziness and weakness ; the pupils were dilated, the pulse was very small, and a feeling of coldness was complained of. These symptoms were relieved by the administration of stimulants and the use of external heat ; after a time they recurred with greater violence ; finally, under the . reinstitution of the measures previously employed, the face became intensely congested and purplish red, pain in the head was felt, the patient seemed much excited, and convulsions were feared, but did not occur ; there was some diarrhoea, with dark gray stools. According to Diez (quoted by Stille"), the principal effects of poison- ous doses of ergot are in the lower animals profuse salivation, vomiting, dilatation of the pupils, hurried breathing, frequent pulse, cries, trem- bling, staggering, paraplegia, in some cases diarrhoea and urgent thirst, convulsions, and death. Among the lower animals chickens are most susceptible to the action of ergot. * For cases, see Neubert (Journ. fiir Pharmacodynamik, 1860, ii. 483); also, same case Richter (Caspar's Vierteljahrschrifl, xx. 177); Tardieu (Ann. d'Hyg., 1855, i. ; Toledo Med. and Snrg. Journ., July, 1878). t Davidson reports a case with fluid blood, jaundice, and universal hemorrhages, attributed with doubtful correctness to poisoning by ergot (London Lancet, 1882, ii. 526). OXYTOCICS. 747 In these it produces besides, ataxia and general weakness, a cyanosis of the comb and wattle which become, if the dose has been sufficient, finally gangrenous and fall off. So marked is this effect that it has been used as a method of determining the comparative activity of different specimens of the drug. It is asserted that in pigs the tips of the ears become gangrenous. The mortification is due to obstruc- tion of the arteries by a transparent hyaline mass following a local vascular spasm. An examination of the above summary of the toxic effects of ergot on the lower animals shows that the symptoms are mainly paralytic, and that the only ones which are in any sense characteristic are the anaes- thesia and the coldness of the surface. As this coldness of the surface has been noted in various women in whom the drug has caused fatal abortion, it is probably characteristic of the poisoning. Nervous System. The action of ergot upon the general nervous sys- tem is extremely feeble, but is not well understood : as both Wright and Kohler have found that the voluntary muscles are not affected by the drug, the motor symptoms of the poisoning would appear to be of nervous origin.* The statement of Eugene Haudelin, 7 that the peripheral nerves are not affected, has been confirmed by the experiments of Kohler, so far as concerns the motor nerves and the watery extract of the drug. According to Robert cornutine acts as a convulsant but sphacelotoxin is a motor depressant. A specimen containing excessive amounts of cornutine may therefore cause spasms but ordinarily from preparations of ergot itself, as shown by S. A.|Wright 5 the paralysis is much more marked than the spasms; in some cases the special senses seemed to be destroyed, and coldness of the surface was a very prominent symptom. He found that the intravenous injection of a strong infu- sion caused immediate dilatation of the pupils, great increase in the rate of the car- diac pulsations, paralysis, and convulsions and death in a few minutes : when the dose was not sufficient to kill at once, great anaesthesia and coldness of the skin and also paralysis of the special senses were developed. InKersch's 6 experiments intrave- nous injections of the poison caused marked coldness of the surface and also great muscular rigidity. Upon rabbits, according to Wright, ergot acts very feebly. Enormous doses of ergot are required to produce toxic symptoms in animals, since in one of Wright's experiments an amount equivalent to two drachms for every pound weight of the dog failed to kill. Circulation. According to the observations of Parola, Gibbon, Arnal, Hardy, Beatty (quoted by Still6), and Bailly and Se, 8 very large doses of ergot reduce the pulse-rate in man, but only under the rarest circumstances below sixty. Eberty found that in the frog the drug still lessened the rate of the cardiac beats after destruction of the medulla, but that in the atropinized mammal ergot was powerless to alter the cardiac rhythm. By toxic doses the rapidity of the heart's action is increased, and, according to Boreischa, galvanization of the parvagum has at this time little or no effect upon the pulse. It may be that ergot first stimu- * In 1884 T. Korkorin, in a St. Petersburg thesis, affirmed that pronounced and char- acteristic pathological alterations can be found in the spinal cord of animals slowly killed with ergot. The correctness of this, however, seems to be more than doubtful. See paper by A. Grunfeld (Archiv f. Psych, u. Nerven., 1889-90, xxi). 748 LOCAL REMEDIES. lates and then paralyzes the peripheral pneumogastric, but before any conclusion can be considered established further investigation is imperative. In 1870 Charles L. Holmes 9 found that ergot injected into the jugular vein of a dog caused a sudden immediate fall of the blood-pressure, fol- lowed in a short time by a marked rise above the normal. This fact has been confirmed by Kohler and Eberty, 10 by H. C. Wood, 11 by Robert and by Jacobi. Plumier, 39 however, asserts that the rise is insignificant, and in the experiments of Sollman and Brown 40 if was either absent en- tirely or else very slight. The most probable explanation of the results obtained in the last two investigations is found in the ease with which ergot undergoes spontaneous decomposition. Houghton examined some two hundred specimens of ergot, many ot wnich he found to be quite inert. The primary fall of pressure is probably due to the depressant action of an excessive amount of the drug, which reaches the heart in concen- trated form when thrown into the vein, directly upon the cardiac muscle. Plumier has shown that ergot thrown into the isolated mammalian heart produces at first almost complete extinction of cardiac action, followed by a prompt return to, or even slightly beyond, the normal. The rise in pressure, which is to be regarded as the characteristic effect of ergot upon the circulation, is due to a constriction of the blood- vessels. Holmes, Wernich, 1 "' Vogt, 15 Kersch, Schuller 37 and Boldt 38 assert that they have seen invariably diminution in the caliber of the arteries under the influence of ergot.* According to Wood, Hemmeter and Kobert the rise in pressure does not occur after section of the spinal cord. It appears therefore to be an established fact that ergot causes con- traction of the blood-vessels and consequent rise of the arterial pressure by stimulating the vaso-motor centre in the medulla. There is however some evidence that it also exerts some direct stimulant influence on the vessel-walls. The evidence which has been brought forward in favor of the direct stimulant action of ergot upon the blood-vessel fibres consists of the statements of Holmes, Wernich, 12 and J. H. Peton," that after the nerves going to certain blood-vessels have been cut, these vessels can be seen to contract when ergot is injected into the animal. The observations of Holmes, Wernich, and Peton are, however, in dis- tinct contradiction to the very elaborate experiments of Paul Vogt, 15 in which the dilated vessels in the ear of the rabbit whose cervical ganglion had been extirpated could not be made to contract by ergot. Moreover, any observations made with the eye as to the contractions or dilatations of the blood-vessels are of doubtful value. Greater importance should be attached to the experiments of Ringer and Sains- bury, made upon tortoises according to the method of Gaskell (see DIGITALIS, page 300). In these the addition of ergotin greatly slowed the rate of flow through * Patrick Nicol and J. Mossop (Brit, and For. Medico-Odr. Kei 1 ., 1872, 1.) have noted with the ophthalmoscope the contraction of the retinal vessels after the exhibition of ergot in man. OXYTOCICS. 749 the arterioles, but in these experiments it was found that the addition of ergotin to the saline solution used had no distinct effect until there was ten per cent, of the extract in solution. Ten per cent, of ergotin is enough very seriously to influence the viscidity of the saline solution, and it is probable that the slowing effect of the ergotin was the result of altered physical conditions. They have however received some confirmation in the investigations of Plumier who found that perfusion through the pulmonary vessels separated from the central nervous system produced a slight constriction of these vessels, and of Jacobi, who found that the rate of flow through the vessels of the leg was diminished when per- fused with chrysotoxin. As has been shown by Haudelin, Boreischa, 16 Brown- Sequard, 17 and others, the toxic dose of ergot produces immediately or after a time a fall of the arterial pressure. The assertion of Brown-Se'quard, that this fall of arterial pressure is due, at least in part, to a vaso-motor paralysis, is corroborated by the experiments of Boreischa, who found that when the vessels were paralyzed by section of the spinal cord high up, the fall of pressure produced by the toxic dose of ergot was proportionately not nearly so great as in a normal animal. The fall of pressure however is brought about also through cardiac failure for Hemmeter" has demon- strated that the isolated heart is slowed and weakened by large doses of ergot and Eberty 42 found that the heart is arrested in diastole and non- irritable. Bodily Temperature. The coldness of the surface in ergotic poison- ing seems to depend upon a general fall of temperature. Hemmeter has noticed that this fall of temperature commonly amounts to, and often exceeds, 5 C. in the lower animals and 2 F. in the human being. The cause of it has not been made out. Hemmeter states that in several ex- periments he has found pronounced reduction of urea elimination in dogs under the influence of ergot, and believes it possible, though not proved, that the fall of temperature is due to diminished general metabolism ; it may, however, be only a secondary phenomenon due to the action of the drug upon the circulation. Action on the Intestines. The muscle-fibres in the coats of the blood- vessels are certainly not the only non-striated muscles influenced by ergot. According to Wertheimer and Magnin, 18 ergot produces active movements in the coats of the stomach, and Wright found very active intestinal peristalsis at the post-mortem examinations of poisoned ani- mals ; further, both Wernich and Haudelin bear witness to the violent intestinal peristalsis produced in the lower animals by toxic doses of ergot. Uterus. Upon the uterus of parturient women or of the parturient lower mammal ergot exerts a very pronounced and fixed influence, in- creasing the length and force of the pains, and, if it be given in sufficient dose, causing after a time violent tetanic cramp of the whole organ. The action of ergot in producing contraction in the impregnated but not parturient womb is by no means so constant. Clinical experience shows that in pregnant women it often fails to originate uterine contrac- 750 LOCAL REMEDIES. tions. Upon animals Wright found it to fail in all of a number of trials, as did also Bonjean in a single experiment. On the other hand, Diez,* Oslere,* and Percy and Laurent* found it to cause abortion in guinea- pigs, sows, rabbits, cows, and cats ; and Bodin 19 has reported an epi- demic of abortion occurring among cows near Trois Croix, which he attributed to feeding upon ergotized grasses. Our present knowledge indicates very strongly that the uterine con- tractions produced by ergot are of centric origin. It is true that some years ago Boreischa asserted that he had succeeded in producing violent uterine movements with ergot after division of the nerve connections of the organ, but the result reached by Wernich namely, that no ver- micular movements are produced in the unimpregnated womb after pre- vious section of the spinal cord has received confirmation from John C. Hemmeter. In repeated experiments, having found that the injection of ergotin produced contractions in the exposed uterus of a narcotized rabbit, he destroyed the spinal cord with a hot wire, and determined that ergot was no longer able to cause uterine contractions : that the failure of the ergot in these cases was not due to paralysis of the uterus by shock was then demonstrated by injecting ammonia into the veins, when violent uterine contractions occurred. SUMMARY. Ergot can scarcely be considered to be a poison, but when taken in enormous amounts it is capable of causing vomiting, rapid breathing, -weakness, growing paralysis, urgent thirst, peripheral and cerebral pains, dilated pupils, great feebleness of the circulation, convulsions, and death, the most characteristic symptom being the great fall of bodily temperature. The method by which these symp- toms are produced has not yet been determined. Therapeutic doses of ergot increase blood-pressure by stimulating the vaso-motor centre in the medulla, but have no distinct influence upon the heart or the walls of the arterioles. Toxic doses depress the pressure by cardiac paral- ysis, and probably also by paralysis of the blood-vessels. Ergot, in full therapeutic doses, so acts upon the centres in the lower spinal cord which preside over the uterine muscles as to produce in the parturient womb violent uterine contractions, a.nd finally uterine tetanus. THERAPEUTICS. Owing to the power that ergot possesses of intensi- fying labor-pains, it has long been used in uterine inertia during partu- rition. Indeed, it was for this purpose that the drug was first employed in medicine, and thereby acquired the name of pulvis parturiens. The literature of the subject is immense, and all imaginable opinions as to the effects of the drug when given in labor, and as to the advisability of its employment, have been advanced ; but, without discussing these, we shall here simply point out the clearly established rules for its use and the clinically determined dangers and advantages of its employment. If * Quoted by Still6 ( Therapeutics, ad ed., ii. 585). OXYTOCICS. 75i ergot be given in very small doses during labor, the natural pains are simply intensified ; but if the dose be large enough to have a decided effect, their character is altered : they become not only more severe but much more prolonged than normal, and finally the intervals of relaxation appear to be completely abolished and the intermittent expulsive efforts are changed into one violent, continuous strain. It is evident that, if the resistance be sufficiently great, this may endanger the safety both of the mother and of the child. The dangers to the mother are twofold : there is a possibility of the uterus rupturing itself by its efforts ; and, when the head comes down upon the perineum, if the soft parts be rigid there is a very strong probability that they will be lacerated. The danger of uterine rupture is, we think, a remote one ; for although several alleged cases have been recorded, yet in very few is the accident clearly trace- able to the asserted cause.* The fatal character of the accident is such, however, that the possibility of its occurrence should always prevent the reckless use of the drug. The improper use of ergot is far more serious in its effects upon the child than upon the mother. During a violent uterine contraction the passage of the blood from the placenta to the child must be interfered with, or, in other words, the respiration of the foetus is temporarily stopped, so that its life depends upon the aeration of the blood during the intervals. If the latter be very much shortened, the life of the child is greatly im- perilled ; and if they be abolished, it must be destroyed, unless delivery occurs in a very few moments. These considerations are, we think, suf- ficient, without further discussion, to show the imperativeness of the rule never to give ergot in uterine inertia when there is much resistance, either in the bony or in the soft parts of the mother. In primiparae such resist- ance is always to be looked for, and its degree often difficult to judge of beforehand ; and in such women ergot should not be used for the pur- poses of expulsion. Even under the most favorable circumstances when the woman has previously borne children, when the bony pelvis is capacious, and the soft parts are relaxed and dilatable its use should be entered upon with caution ; and if the accoucheur be skilful in the application of instruments, cases must be rare in which the latter are not preferable to the ecbolic. In women of lax fibre, with roomy pelves, ergot may be used in uterine inertia if instruments are not at hand, or if they are objected to, or if the obstetrician is timid in their application. At the close of parturition, ergot is very commonly employed to prevent post-partum hemorrhage ; and in this case there is no objection to its use, and the remedy is invaluable. But, as it requires from fifteen to twenty minutes for its action when given by the mouth, ergot exhib- ited in this way cannot be relied upon to arrest flooding when it has already set in. To prevent the occurrence of the latter, it is an excel- * See Stilte ( Therapeutics, 2d ed., ii. 591). 752 LOCAL REMEDIES. lent rule to give a full dose of the ecbolic when the child's head is well down upon the perineum and beginning to emerge at the vulva. After labor, if a tendency to bleeding is manifested, ergot may be administered hypodermically. For the induction of premature labor, ergot has been and still is to some extent used ; but it is uncertain in its action, and offers no advan- tages over instrumental methods. The success of ergot in arresting hemorrhage after labor soon led to its use in uterine hemorrhages in other than parturient or pregnant women ; and the next step beyond this was its employment in other hemorrhages. In all forms of hemorrhage in which no direct local application can be made, ergot is to-day probably the most generally used remedy. It is thus employed in menorrhagia, haemoptysis, hemorrhage from the giims, epistaxis, etc. Even mpurpura h&morrhagica, the hypodermic injection has been highly praised.* The value of ergot as a styptic in an internal hemorrhage is generally attributed to its power of contracting blood-ves- sels. It must be remembered however that any substance which leads to a general vaso-constriction increases the force of the circulation. The in- creased pressure tends to dislodge any clot which may be formed at the bleeding point. Therefore those drugs which narrow the lumen of the vessels must incline to continue rather than check internal hemorrhages. In colliquative night-sweats due to relaxation of the blood-vessels, ergot is a most efficient remedy. Allied to its use in hemorrhage is the employment of ergot in enlarge- ment of the spleen from various causes. Da Costa * was the first to sug- gest hypodermic injections of the drug for this purpose, and he asserts that he has even cured leukezmia. Led by the probably erroneous belief that ergot acts upon the muscle- fibres in the walls of the blood-vessels, Langenbeck 21 injected the drug into the immediate vicinity of the diseased blood-vessels for the cure of aneurism, with asserted extraordinary success. The practice has been followed by various surgeons, not only in diseases of the arteries but also for the relief of varicose veins. A great deal of local swelling and hard- ness is induced, involving the blood-vessels themselves, and the good which has been achieved is probably simply the result of the local inflam- mation, the ergot acting as an irritant and having no specific action. Very many years ago F. E. Barlan-Fontayral 22 proposed the use of ergot in chronic dysentery and diarrhoea, on account of its power of causing contraction of the capillaries ; and Massolaz, in an epidemic of chronic diarrhoea among the French troops serving in the East, found that the suggestion was well timed. Although Barlan-Fontayral after- wards published a book f upon the subject, it attracted little or no atten- * Cases, Brit. Med. Journ. , 1874, ii.; Phila. Med. Times, v. \Le Seigle ergote et V Application de V Ergotine d la Cure de la Dyssenterie et de la Diarrhee chroniqttes, Montpellier, 1858. OXYTOCICS. 753 tion. In 1871 A. Luton, 28 of Rheims, stated, as something new, that he had used ergot with remarkable success in a violent and protracted epidemic of dysentery. Successful cases of chronic diarrhcea are also reported by other observers, 2 * so that trials of the remedy should be made in all obstinate cases. Another employment of ergot for the purpose of restraining exces- sive secretion is in galactorrh&a, in which affection it has been used with success by Le Gendre, 25 who was led to employ it by an observation of Poyet and Commarmond, 26 that wet-nurses fed upon ergotized bread lost their milk. The action of ergot upon the blood-vessels suggests its employment in those cases in which there is local or general dilatation of the vessels. We have used it in pulmonic congestion with apparent good results, and it has been highly lauded in the first stages of pneumonia by N. S. Davis, 21 by Sunol, 28 and later by other clinicians. It has been especially noted by J. E. Kelly, 29 as giving immediate relief when injected hypo- dermically in low forms of pulmonary hyper&mia, such as occur in typhoid fevers. Ergot has also been recommended by O. Rosenbach, as a means of raising blood-pressure in cases of cardiac disease where there is thought to be insufficient peripheral resistance ; and Hemme- ter believes that the dicrotic pulse is due to a very low degree of pressure in the arterial system, and is an indication, especially in chronic cardiac disease, for the use of ergot. Rosenbach recommends the drug strongly in aortic insufficiency with cardiac dilatation. Ergot would seem to be indicated as a vaso-motor stimulant in surgical shock, but is much less prompt in its influence than atropine. As originally suggested by Brown- Se'quard, it is still much used for the relief of chronic cerebral and spinal congestion. When there is a rupture of the vessels, as in apoplexy, by increasing the blood-pressure it tends to do harm rather than good. It is largely used for the relief of congestive headaches, and has been em- ployed in epilepsy, in which disease, according to Hemmeter, it greatly increases the efficiency of the bromides. Dehenne M states that he has obtained most remarkable effects in the relief of diabetes by subcutaneous injections of ergotin. The general clinical experience, however, seems to be that whilst occasionally ergot does great good in diabetes, it usually fails to accomplish anything. When successful, it rapidly diminishes the glycosuria, thirst, and polyuria. In diabetes insipidus, though it often fails, ergot is perhaps the most generally useful remedy that we have. In 1872 Hildebrandt 31 announced that in nine cases of fibroid tumors of the uterus he had used with the utmost advantage hypodermic injec- tions of ergotin, and this practice has been followed very widely on this continent. It is scarcely to be doubted that cures are sometimes effected ; but probably in the majority of cases * the drug simply lessens * See Amer. Jonrn. Med. Sci., July, 1873 ; Amer. Practitioner, May, 1873, May, 1874, August, 1874; Clinic, April, 1873; Lancet, May, 1873; Chicago Med. Journ., 1874; and especially Byford's Address ( Trans. Amer. Med: Assoc., 1875). 48 754 LOCAL REMEDIES. the uterine congestion, and does good precisely as it does in chronic or sub- acute metritis and in subinvohition and hypertrophy of the uterus (Mead- ows* 2 ) ; it may be that sometimes it strangles the growth by causing uterine contractions. If the latter be the case, a cure, as is suggested by Goodell, 33 is to be expected from the remedy only in mural and sub- mucoid tumors. An objection to the method of Hildebrandt is the great pain and local inflammation which often result ; and Goodell proposes as a substitute the use of enemata or suppositories containing the drug. TOXICOLOGY. Enough has already been said in regard to the acute poisoning by ergot, except it be to state that, when abortion is threat- ened from its ingestion, in the maintenance of perfect quiet and in the free exhibition of opium are to be found all the measures of relief at our command. Since the days of Galen there have swept over larger or smaller dis- tricts of Europe epidemics of diseases which have been attributed to ergot. In many parts of Europe rye bread forms the great staple article of food of the lower classes. It always contains a small quantity of ergot, but not enough to have any deleterious effect upon the health. When the summer is wet and cold, the rye becomes very extensively ergotized, so that the fungus constitutes a large proportion of the mate- rials entering into the bread. It is under these circumstances that there occur epidemics of ergotism or chronic ergotic poisoning. It is not always the rye that causes these frightful losses of life, as Heusinger 14 has traced one epidemic to diseased oats. Before going further, it seems proper to state that Trousseau and Pidoux assert that these epidemics are not dependent upon any specific action of ergot, but are either epi- demics of blood diseases or simply the results of improper and insufficient food, the outcomes of poverty, wretchedness, and famine. It seems to us indisputable that some of the various epidemics which have been re- corded were of this character, but certainly it is no less indisputable that others were not. Moreover, numerous scattered cases are on record in which a few persons or a family have been affected with ergotism unmis- takably traceable to the use of bread largely composed of the fungus.* The scope of the present treatise is such as to forbid our entering into an elaborate discussion of the epidemics of ergotism, especially as the subject has no practical bearing so far as the American profession is con- cerned, since the absence of deep poverty is so complete in our country that no one would feed on largely ergotized bread ; and, in fact, no case of ergotism has as yet been recorded as occurring in the United States, f * For an account of a modern epidemic, see Deutsch. Arch.f. Klin. Med., xxxiii. 246. t Any one especially interested in the subject will find the literature very well repre- sented in the references of Stille's work on Therapeutics, Duboue's Recherches sur les Proprttlts Therapeutiques du Seigle Ergote, Paris, 1873, and Husemann's Handbuch der Toxicologie. OXYTOCICS. 755 There are two varieties of ergotism, the gangrenous and the spas- modic. In some epidemics the cases have been of mixed type. Gangrenous ergotism has been especially observed in France, and is believed to be the same as the Ignis Safer or the Ignis Sancti Antonii of the Middle Ages, an affection which in 922 killed forty thousand persons in Southwestern France, and in 1128-29 fourteen thousand in Paris alone. It generally commences with itching and formications in the feet, severe pain in the back, contractions in the muscles, nausea, giddiness, apathy, with abortion in pregnant women, in suckling women drying of the milk, and in maidens amenorrhcea. After some time deep, heavy, aching pains in the limbs, an intense feeling of coldness, with real coldness of the surface, profound apathy, and a sense of utter weariness develop them- selves. Then a dark red spot appears on the nose or on one of the extremities ; all sensation is lost in the affected part ; the skin, perhaps over a large surface, assumes a livid red hue, and in the foci of local changes bullae filled with serum appear. The adynamic symptoms, in severe cases, deepen as the gangrene spreads, until finally death puts an end to the scene. Very generally the appetite and digestion are preserved to the last, and not rarely there is an almost ferocious hunger. The gangrene is generally dry, the parts withering and mummifying ; but sometimes it is moist, and pyaemic symptoms may even be developed. Of course a very large number of cases do not terminate in death ; but the part immediately affected is generally lost. In these cases the toes most generally are the portion destroyed, but it may be any one or all of the extremities ; and the nose, lips, ears, and even the buttocks sometimes bear the brunt of the disorder. Spasmodic ergotism may in the lightest cases be manifested only by itching, formications, numbness, or complete anaesthesia of the fingers and toes or of the buttocks, and by gastro-intestinal irritation, as shown by colic, vomiting, diarrhoea, or constipation, and withal a ravenous hunger. In more severe cases these mani- festations are intensified, and spasmodic symptoms appear, violent and painful tonic contractions affecting especially the flexors of the extremities, interrupted at times by intervals of quiet, but gradually growing into severe general tetanic parox- ysms, with opisthotonos and emprosthotonos. In the intervals there are very gen- erally muscular tremblings, and as the case progresses there are developed cerebral manifestations, such as disturbances of vision, photophobia, chromopsia, hemiopia, and periodic amblyopia and amaurosis, giddiness, cataleptic and epileptic parox- ysms with or without loss of consciousness, delirium, and idiocy. Gastro-intestinal symptoms are always very marked, but with them are a characteristic ravenous hunger and a longing for sour food and drink. The skin is earthy or yellowish in tint, and is often spotted with boils or pustules or semi-grangenous vesicles. Death is apparently caused by exhaustion ; and in those that recover, various local paralyses, habitual spasms, amaurosis, mental aberrations, or even idiocy often remain through life. In a few cases the symptoms are still more violent, and the spinal and cerebral disturbances soon lead to death. The primary changes in ergotism are in the blood-vessels. Ergotic gangrene can readily be produced in the comb and tongue of chickens, and Von Recklinghausen asserts that the essential lesion in these cases is hyaline thrombi in the arterioles and capillaries; whilst Griinfeid 35 has found the walls of the vessels thickened, structurally changed, and their lumen occupied by thrombi which in some places are full of blood-cor- puscles and in other parts undergoing hyaline degeneration. ADMINISTRATION. Ergot should not be administered in substance. 756 LOCAL REMEDIES. The wine (ViNUM ERGOTS twenty per cent., U. S. ) is very feeble; ecbolic dose, half to two fluidounces (15-60 C.c. ). The fluid extract (FLUIDEXTRACTUM ERGOTS, U. S. ) is a very efficient preparation; ecbolic dose, one to two fluidrachms (4-7 C.c.), repeated in twenty min- utes, if necessary ; in nervous diseases much larger doses are required: thus in congestion of the spinal cord we usually begin with half an ounce, and increase it to an ounce three times a day.* Extract of ergot (Ex- TRACTUM ERGOTS, U. S. ) is preferable to the fluid extract when time is not important, as being less apt to cause nausea. When administered by the mouth, it should be given in capsules containing from five to seven grains (o. 3-0. 46 Gm. ) Its strength is five times that of the fluid ex- tract ; when used hypodermically, five grains should be dissolved in five minims of glycerin, fifteen minims of boiled water, and one-fourth of a minim of carbolic acid, and filtered : the danger of causing severe local trouble is lessened by plunging the nozzle of the syringe deeply into the muscular tissues. JBonjean's ergotin, so-called, is a refined watery extract, practically the official extract. Wiggers 1 s ergotin, which contains everything in ergot insoluble in water, should not be employed therapeutically. (See Kohler 56 . ) The attempt to assay preparations of ergot by their action upon the comb of the cock is of doubtful utility; it is at present uncertain whether the action of ergot upon the uterus and upon blood-vessels is due to one or to several more or less antagonistic substances. HYDRASTIS. U. S. The rhizome and roots of Hydrastis Canadensis, an indigenous per- ennial, commonly known as Golden Seal. Hydrastis contains the alka- loid berberine, to which it owes its yellow color, and probably also two other alkaloids, canadine^ and xanthopuccine, besides its characteristic alkaloid, hydrastine.\ The latter occurs in brilliant four-sided prisms, inodorous and almost tasteless, but having a very bitter and somewhat acrid taste when in the form of a salt. Pure hydrastine and its salts can be obtained in the shops, but the hydrastzw of commerce is an impure body containing berberine, hydrastm*?, and probably other more or less active alkaloids besides resin. PHYSIOLOGICAL ACTION. There appear to be no cases on record of * It would appear that sometimes, owing to idiosyncrasies, even small amounts of ergot cause much disturbance. Thus, R. B. Faulkner reports (New York Med. Journ., June 14, 1884) a case in which a fluidrachm of the fluid extract caused great sleepiness, swelling and redness of the feet, and violent prickling of the extremities, probably as the outcome of gastric irritation. t According to the experiments of Bunge, 1 canadine in toxic doses produces a brief stage of psychical and motor excitability, followed by general paralysis and depression, with death from respiratory paralysis, and has little direct action upon the blood-pressure. The rate of pulsation in the isolated frog's heart is lessened, but the work done is not decreased by the moderate dose ; larger doses paralyze the muscle of the heart. The voluntary muscles are not affected by the alkaloid, nor is the uterus, although diarrhoea with violent intestinal peristalsis is produced. J For an article on the chemical and physiological activities of a number of deriva- tives from hydrastine by Falck, see Virchow's Archiv, 1895, cxlii. OXYTOCICS. 757 serious poisoning from any of the alkaloids of hydrastis, and in the only case of poisoning by the crude drug, nine grammes of the fluid ex- tract produced vomiting, giddiness, headache, dyspnoea ; a slow, weak, irregular pulse, mydriasis, and hallucinations of sight (Friedeberg ! ). As hydrastis is chiefly used in the form of its alkaloids, we shall consider these principles separately. The alkaloid hydrastine is so dominant in its action, that to it is chiefly due the influence of the crude drug. Berberine is an inactive alkaloid, Buchner having taken twenty grains with very little effect. In doses of from two to five grains (o. 1-0.3 Gm. ) it is a simple bitter, and as such may be given in pill or alcohol. Toxic doses of berberine cause in the lower animals diarrhoea, rapid loss ot flesh, tremors, diminished respirator)' action, progressive paralysis, lessening of the pulse-rate, depression of the arterial pressure, partial anaesthesia, albuminous or bloody urine, and in some cases final convulsions. (Falck and Guenste ; s Mosse and Tautz. 4 ) After death hemorrhagic nephritis may be found. Both Schurinow and Curci 5 agree that berberine causes the arterial pressure to fall rapidly from vaso-motor paralysis ; the peripheral vagus is paralyzed. (Schurinow, Marfori, 6 denied by Curci. ) According to Curci, the heart-muscle is directly affected. Schurinow and Mosse aud Tautz are in accord in asserting that the nerve-trunks are especially implicated in the poisoning, but Curci believes that the motor and sen- sory disorders are due to an action upon the spinal cord ; probably both the cord and the nerve-trunks are affected. Hydrastine causes, in animals, increased, followed after a time by lessened, respiratory movements, salivation, vomiting, excessive peri- stalsis, muscular tremblings, weakness and rigidity, loss of voluntary movement, rise of bodily temperature (Bunge) (often followed by a fall), feeble, rapid pulse, clonk: and tetanic convulsions, increased reflex activity, and death from cramp-asphyxia or general paralysis, or exhaustion with respiratory failure. Hydrastine is probably eliminated through the kid- neys. (See Phillips and Pembrey. 7 ) In a research upon the effect on the lower animals of the long-continued use of hydrastine and hydrastinine, J. De Vos 8 found that these alkaloids have no cumulative action, but that gradually the animals seem to become accustomed to their use. Neither of them in any way disturbed the gastric or intestinal digestion. Albuminuria never occurred, nor was there apparent disturbance of assimilation. Nervous System. So far as is known, hydrastine has little or no action upon the cerebral hemispheres, but is a very powerful stimulant to the motor side of the spinal cord. Death may occur during the period of violent convulsions with heightened reflex activity ; but if the animal survives, there follows a general paralysis, which, as the alkaloid is a marked depressant to the motor nerve-trunks, is probably of peripheral origin. According to Cerna, 9 when voluntary movements and the reflexes are first 758 LOCAL REMEDIES. depressed in the frog, the reflexes can be restored by section of the cord, so that the palsy is probably due to stimulation of Setschenow's centre; later it is irremediable. Late in a protracted poisoning, and after death, the motor nerves are depressed or altogether paralyzed (Falck, Cerna), and Bunge ' has found that the local appli- cation of a solution of the alkaloid to a nerve kills it. According to Falck, hydras- tine placed in the eye has no effect upon the sensitiveness of the conjunctiva, but both Slavatinski (quoted by Bunge) and Mays affirm that late in the poisoning there is general loss of sensibility. Mays further states that when brought in con- tact with a nerve-trunk, hydrastine paralyzes its sensory fibres, although tying an artery does not prevent the development of anaesthesia in general poisoning by the alkaloid. If these experiments be correct, the alkaloid acts both upon the sensory cord and sensory nerve ; this action, however, is entirely subordinate to its influence upon the motor tract. Muscles. Upon the muscles the alkaloid has some influence, since both Falck and Bunge have found that its not too dilute solution directly applied to a muscle destroys its contractile power, a conclusion which is confirmed by Cerna, who further states that preceding the depression there is a stage of excitation in which the muscular contraction under stimuli is more complete and prolonged than normal. Respiration. When death takes place during a convulsion, it prob- ably is due to cramp-asphyxia ; but when it occurs during the paralytic stage, it is from paralytic-asphyxia (probably, in part at least, of centric origin), the heart-beat continuing after death (Serdzeff "). Circulation. The characteristic primary effect of a full dose of hydras- tine upon the circulation is a rise of the arterial pressure with slowing of the pulse-rate, this condition being followed after a time, if the dose has been toxic, by a fall of the arterial pressure. The rise of the arterial pressure is probably due in part to a direct action upon the heart itself and in part the result of contraction of the blood-vessels, caused probably by an action upon their muscle-fibres. Marfori believes that the vaso- motor centres are also stimulated, but at present this is only a probability. The fall of the arterial pressure is in part of cardiac origin, there being in the later stages of the poisoning a depression of the heart muscle, which ends in diastolic arrest with loss of muscular irritability. When hydrastine in sufficient dose is injected directly into the circulation there is an immediate fall of pressure, followed by a marked and long-continuing rise unless the original dose has been excessively large, when the pressure falls progressively until death. (See the observations of Bartholow, 12 of Fellner, 10 of Falck, of Serdzeff (quoted by Bunge), of Marfori, and of Pellacani.) The primary fall of pressure does not occur after subcutaneous injections (Falck), and is due to direct action of the concentrated drug upon the heart. That the rise of pressure is partly of cardiac origin is proven by the following facts : Marfori, also Phillips and Pembrey, 43 have noted that when hydrastine is applied to the isolated frog's heart it produces slowing of the rate with increased amplitude and power of the cardiac beat, and Serdzeff has proven an actual increase in the work of the isolated heart. Further, the rise of the arterial pressure is not prevented in the mammal by previ- ous section of the splanchnic nerve or of the spinal cord high up (Fellner). Again, Cerna found that the slow pulse of hydrastine-poisoning occurs after section of the OXYTOCICS. 759 pneumogastric nerve ; also, that the vagi nerves retain their power up to the fatal issue ; the slow pulse, therefore, is not of inhibitory origin. That the vessels are contracted is indicated by the oncometrical experiments made by Marfori upon the dog's kidney, in which the contraction of that organ was found to be a constant phenomenon of the early stages of hydrastine-poisoning. It is probable that both voluntary and involuntary muscle-fibres show the primary stimulating influence and the later depressing power of hy- drastine, and that the action of the drug upon the circulation is the same as that upon the uterus and the voluntary muscles, only that the voluntary muscle-fibres are less susceptible to its action than are those of involuntary life. Abdominal Action. It is probable that hydrastine influences both the glands and muscular fibres of the alimentary canal. According to Cerna, it markedly increases the secretion of saliva and of bile, also the intestinal peristalsis. Uterus. As long ago as 1883 Schatz called attention to the prac- tical value of hydrastis in all forms of hemorrhage from the womb, assert- ing that, though the drug acts well in cases of uterine fibroids or myoma, it is also efficacious in various cases of menorrhagia, dysmenorrhoea, etc. These results have been confirmed by numerous gynaecologists. It is, of course, not possible from these clinical results to determine whether the good is obtained by an action of the drug upon the uterine mucous mem- brane or blood-vessels or by provoking contractions of the uterine walls. As the result, however, of experiments upon the lower animals, both Fellner and Slavatinski affirm that hydrastine has a distinct ecbolic action, causing uterine contractions in the non-pregnant uterus and abortion in pregnant rabbits. Slavatinski reports a case of premature labor produced by hypodermic injections of two or three grammes repeated daily. It would seem, therefore, that hydrastine is an ecbolic, and that it arrests uterine hemorrhage in part, if not altogether, by provoking muscular contractions. Eyes. Hydrastine locally applied to the eye causes at first contrac- tion and afterwards dilatation of the pupil (Cerna). Absorption and Elimination. Hydrastine appears to be absorbed from the alimentary canal somewhat slowly ; at least it is stated by Bunge that ten times as much of it is required to kill an animal when given by the mouth as when injected hypodermically. Marfori states that it is apt to have a cumulative action when given for a length of time. It escapes unchanged through the kidneys, and has also been found by Hirschhausen in the faeces. SUMMARY. By primarily stimulating the spinal motor cord hy- drastine causes tetanic convulsions, -with heightened reflexes, folio-wed, if the dose have been large enough, by loss of reflex activity, and motor paralysis, -which are probably in part due to depression of the motor centres, and are certainly, at least in part, the outcome of depression of the motor nerves and also of the muscles themselves. According to Cerna, the first loss of reflex activity is due to stimulation of Setsche- 760 LOCAL REMEDIES. now's centre, and the final muscular depression is preceded by excita- tion of the muscle-fibres. Death may occur in a convulsion from cramp- asphyxia, or [later from simultaneous paralysis of the respiratory centre and of the peripheral apparatus. The arterial pressure is first elevated and secondarily depressed : the first rise of pressure is proba- bly due to the stimulation of the heart-muscle, increasing 1 the output of force, and of both the vaso-motor centres and the muscle-fibres in the arteriole coats, causing contraction of the blood-vessels : the fall of pressure is the result of a direct paralytic action exerted upon the muscle-fibres in the heart and in the arterioles. Hydrastine notably increases intestinal peristalsis, and probably uterine contractions. It would seem to be a universal muscle-poison, -which acts upon both striated and non-striated muscle-fibres in heart, arterioles, intestines, uterus, and generally throughout the body ; its first stimulant action being folio-wed by marked depression. THERAPEUTICS. When locally applied, the preparations of hydrastis have a very remarkable effect upon the mucous membranes. They have been used with asserted excellent results in chronic gastro-intestinal ca- tarrhs, especially those due to alcoholic excesses : as Rutherford 13 found in his experiments upon the lower animals that the hydrastin of com- merce caused a marked increase in the biliary secretion, it is probable that in these catarrhs spoken of the good result is, at least in part, due to a specific influence upon the liver and, it may be, other abdominal glands. Nevertheless, it would seem certain that hydrastis has a pecu- liar action upon mucous membranes. In the second stages of gonor- rhoea, after the acute inflammation has been subdued, injections of hydras- tin, or the fluid extract, suspended in mucilage, are often of service. Five grains of the commercial impure hydrastin, or ten to twenty minims of the fluid extract, may be used to the ounce of fluid. It is also asserted by various specialists that in otorrhcea, nasal, vaginal, and other mucous catarrhs the remedy is locally of great value. In dyspepsia it has been used as a stomachic stimulant, and has received especial praise in the vomiting of pregnancy. At present it is not known to which of the various ingredients of commercial hydrastin these local effects are chiefly due, so that either the hydrastin or a preparation of hydrastis is prefera- ble to the pure alkaloid. These preparations are a tincture (TiNCTURA HYDRASTIS twenty per cent., U. S. ), the dose of which is from one to two fluidrachms (4-7 C.c. ); a fluid extract (FLUIDEXTRACTUM HY- DRASTIS, U. S. ), dose, from one-half to one fluidrachm (2-4 C.c.); and a glycerite (GLYCERITUM HYDRASTIS, U. S. ), dose, from one-half to one fluidrachm (2-4 C.c.). The dose of commercial hydrastin is five to ten grains. For internal or general medication, as contrasted with the local use of hydrastis, the alkaloid or its salts is much preferable to the cruder preparation. As anti-hemorrhagic or ecbolic, the alkaloid hydrastine (HYDRASTINA, U. S. ) may be used in doses of from one-sixth to one- half grain (0.01-0.03 Gm.). OXYTOCICS. 761 HYDRASTININ^E HYDROCHLORAS HYDRASTININE HYDRO- CHLORATE. U. S. Hydrastinine is an artificial alkaloid first produced by Martin Freund by the oxidation of hydrastine. The hydrochlorate is a light yellow crystalline powder, somewhat deliquescent, odorless, having a bitter saline taste, soluble in o. 3 part of water and in three parts of alcohol. PHYSIOLOGICAL ACTION. For our knowledge of the physiological action of hydrastinine we are chiefly indebted to Pius Marfori, P. J. Archangelsky, and Kuno von Bunge. 1 No cases of poisoning by the drug in man have been reported, but in frogs the alkaloid is said to produce complete paralysis with death from failure of respiration, the heart being finally arrested in systole ; whilst in mammals it causes hy- peraesthesia, general tremors, rapid pulse, and dyspnoea, followed by paresis, which is said primarily to affect the front legs and to pass into general paralysis with dilated pupils, lowered temperature, and death from failure of respiration. According to Bunge, intestinal peristalsis is markedly increased by hydrastinine. Nervous System. Our present knowledge of the action of hydras- tinine upon the cerebrum is derived from experiments upon the lower animals, in which it has been found by W. Kiselew" that the excitability of the motor cerebral cortex progressively decreases with progressively increasing doses of hydrastinine, although it never entirely disappears ; and that the white substance of the brain is affected similarly to but less powerfully than the gray matter. Kiselew has also confirmed the previ- ous observation of Tarchanoff, that the alkaloid arrests or greatly dimin- ishes the convulsive attacks in epileptic guinea-pigs. It is further worthy of remark that Kiselew, in a few cases of human epilepsy, obtained very favorable results from the administration of o.oi to 0.03 gramme of hydrastinine four times a day. So far as the lower motor apparatus is concerned, the chief symptoms produced by hydrastinine are paralysis with loss of reflex activity, and also lessening of the general sensibility. It seems at present doubtful whether there is or is not an early stage of nervous excitement, since Archangelsky affirms that there is increase of susceptibility to touch and to pain in the frog after small doses, whilst Marfori states that there is no increase of the reflex activity at any time. If there be any stage of excitement, it cannot be well pronounced. It is affirmed that hydras- tinine is the natural antagonist of strychnine, and Marfori asserts that the paralysis is of purely central origin. This, however, seems to be in- correct, for not only, as Archangelsky found, is the excitability of the voluntary muscle lessened by the toxic dose of the alkaloid, but Bunge has shown that both the peripheral nerves and the muscle-fibres were paralyzed by a local application of the hydrastinine solution. In the advanced poisoning the respiratory centre seems to show the depressing influence of the alkaloid, and hence respiratory failure ; but here again, according to Archangelsky, especially when the dose has not been too large, there is a period of primary centric stimulation. 762 LOCAL REMEDIES. Circulation. The elaborate studies of Bunge show that hydras- tinine has no influence upon the blood itself, but all observers are in accord in stating that the blood-pressure is increased by the large dose of the alkaloid. The increase appears to be in part of cardiac and in part of vascular origin. Thus, both Marfori and Bunge, in experi- ments made with the Williams apparatus, found that the systolic impulse of the isolated frog's heart becomes abnormally strong under the influ- ence of the drug, and that the amount of the heart's work is distinctly increased. A second cause of the rise of the arterial pressure is asserted to be contraction of the vessels, which, according to Marfori, may be- come so great as entirely to arrest the renal secretion. As the result of elaborate experiments made with section of the splanchnics and of the spinal cord, Archangelsky reaches the conclusion that the contraction of the vessels is chiefly of peripheral origin,* although there is at the same time some stimulation of the vaso-motor centres in the medulla, a conclusion concordant with Marfori' s results. When the amount of the hydrastinine has not been too large, the elevated arterial pressure gradually returns to the normal (Bunge) ; but after a fatal dose of the alkaloid a pro- nounced fall of pressure finally comes on, apparently as the result of the paralysis of progressive asphyxia, since artificial respiration will bring back the pressure to the normal (Marfori): further, it is asserted by various observers that the heart is finally arrested in systole, so that it would seem that hydrastinine differs from hydrastine in not being a cardiac paralyzant in any dose. Pupils. Archangelsky has noted that one to two drops of the ten per cent, solution of a salt of hydrastinine in the eye will produce a dila- tation of the pupil, which reaches its maximum in two to three hours, and remains twelve to fifteen hours. Uterus. The effect of hydrastinine upon the uterus was studied in pregnant and puerperal dogs, cats, and rats by Archangelsky, who found that it produced rhythmic contractions, independent of any vaso- motor influences, apparently by stimulation of the uterine walls. On the other hand, Bunge, having failed in two experiments to provoke abortion or uterine contractions in pregnant animals by large or even fatal doses of the alkaloid, affirms that it is not an ecbolic. Nevertheless, Faber, 15 as the result of a number of trials, states that hydrastinine given hypodermically during human labor very notably increases the force and length of the uterine contractions, causing a spasm which affects all portions of the uterus, and which is similar in character to that provoked by ergot. In some of the cases there was uterine tetanus, lasting as long as fifteen minutes. Faber also asserts that distinct contractions can be produced in the unimpregnated womb. * The assertion of Bunge, that because in heavily chloralized animals hydrastinine fails to elevate the pressure, therefore it acts chiefly upon the vaso-motor centre, is a non stqttitur, as chloral acts upon the whole circulatory apparatus. Moreover, Bunge's own experiments show that the alkaloid lessens the size of the spleen by contracting the blood-vessels. OXYTOCICS. 763 Absorption. Bunge has found that hydrastinine is readily absorbed and eliminated unchanged, chiefly with the urine, but also to some extent with the saliva, bile, and intestinal secretions. It did not appear to increase the amount of bile secreted. SUMMARY. Hydrastinine in sufficient dose appears to be a pow- erful depressant to the -whole motor tract, commencing- in the motor area of the cerebral cortex and ending in the muscle, motor brain, motor cord, motor nerve, and muscle being all more or less affected. "Whether this depression be or be not everywhere preceded by a brief stage of excitement is at present somewhat uncertain, but it is ex- tremely probable that there is a primary stimulation, at least, of the muscles. It is a stimulant to the circulation; the heart under its in- fluence acts more slowly, but more powerfully, and is in fatal poison- ing finally arrested in systole, -whilst the blood-vessels undergo powerful contractions until late in the poisoning; the vascular con- tractions are probably the result of stimulation both of the vaso- motor centres and of the muscle in the -walls of the arterioles. The final fall of arterial pressure is asserted to be the result of the as- phyxia, and not produced directly by the drug. Although it is denied by some, hydrastinine appears to be a powerful oxytocic, and it is probable that its action upon the heart, the arterioles, the uterus, the intestines, and the skeletal muscles is the outcome of a wide-spread general muscular stimulation. THERAPEUTICS. Hydrastinine is used in medicine chiefly for those complaints for which it was originally recommended by Falck, namely, menorrhagia, metrorrhagia, congestive dysmenorrhcea, and even endo- metritis. The testimony in favor of its arresting uterine hemorrhage in all forms is, on the whole, very consistent, and is abundant, but it is also believed by many gynaecologists to have some alterative influence upon the mucous membrane of the uterus. It is affirmed by some gynae- cologists, but denied by others, that it is an active oxytocic, and exerts its influence upon impregnated and unimpregnated wombs largely by causing muscular contractions. It will be seen that the range of its useful- ness in gyneecology is entirely similar to that of hydrastine ; it has, how- ever, acquired popular favor more rapidly and decidedly than the natural alkaloid. It may possibly be more effective as an ecbolic, but its supe- riority probably lies in chief part in its being distinctly less toxic and pro- ducing cardiac stimulation rather than cardiac depression. When an immediate impression is desired, the sulphate should be given hypoder- mically. When a prolonged continuous action is required, it may be administered by the mouth. The results obtained by Kiselew demand a fair trial of it in epilepsy. Hydrastinine has some value as a subsidiary cardiac tonic; it does not belong in the same class as digitalis, but its tonic influence is often decidedly helped by its cardiac action. Dose, three-quarters of a grain to a grain and a half (0.05-0. i Gm. ). GOSSYPII CORTEX. U. S. The root of the ordinary cotton-plant, the Gos- sypium herbaceum, is said to be used by the negroes in various portions of the 764 LOCAL REMEDIES. South as an abortifacient, and Bouchelle, as long ago as 1841, affirmed that it has medical properties similar to those of ergot. It has not, however, come into gen- eral use, and our knowledge of its properties is very scanty and uncertain. In the experiments of I. C. Martin 1 enormous doses produced heaviness and stupor in both frogs and mammals, but did not cause abortion in pregnant guinea-pigs or rabbits : On the contrary, Mohr 2 produced abortion in a cat with three doses of 20 C.c. each of the fluid extract. H. I. Garrigues 3 has found cotton-root a service- able agent in arresting hemorrhage and ameliorating the other symptoms of uterine polypoid and fibroid tumors, and even of uterine cancer. He insists that the com- mercial fluid extract is inert and the decoction must be freshly prepared. The oxytocic dose of a decoction (four ounces in a quart of water boiled to a pint) is stated to be a wineglassful, to be repeated every thirty minutes as necessary. The remedy has also been employed in amenorrhcca and in dysinenorrhcea, in which diseases from three to five grains of a solid aqueous extract have been given three times a day. The fluid extract may be used in doses of a fluidrachm (3.7 C.c.). Absorbent Cotton (GOSSYPIUM PURIFICATUM, U. S. ) is ordinary cotton wool deprived of impurities and fatty matters. It is used mechanically, and as an absorbent. ERGOT. 1. TULASNE .... Ann. des Sciences Nat., Botan., 1853, 35., xx. 2. JACOBI A. E. P. P., 1897, xxxix. 85- 3. ROBERT A. E. P. P., 1884, xviii. 316. 4. OLDRIGHT .... Canada Med. Journ., 1870, 404. 5. WRIGHT Ed. M. S. J., Oct. 1839, lii. 6. KERSCH Betz's Memorabilien, xviii. 7. HAUDELIN . . . . S. Jb., civ. 8. BAILLY and SEE . B. G. T., Ixxviii. 435. 9. HOLMES A. de P., 1870. iii. 10. KOHLER and EBERTY . V. A. P. A., Ix. 384. n. WOOD P. M. T., 1874, iv. 518. 12. WERNICH . . . . V. A. P. A., 1872, Ivi. 510. 13. PETON De 1'Action de 1'Ergot, Paris, 1878. 14. RINGER and SAINSBURV . B. M. J., Jan. 1884. 15. VOGT B. K. W., 1869, No. 12. 16. BOREISCHA . . . Arb. Pharmak. Lab. Mos- kau, i. 55. 17. BROWN-SEQUARD . A. de P., 1870, iii. 434. 18. WERTHEIMER and MAGNIN . A. de P., 1892, 5 s., iv. 92. 19. BODIN Journ. des Connaissances Med., 1842. 20. DA COSTA . . . . A. J. M. S., Jan. 1875. 21. LANGENBECK . . B. K. W., 1869, vi. 22. BAR LAN- FONTA YR AL . Journ. des Sci. Med.- pratiques de Montpellier, vi., vii. 23. LUTON G. H. M. C., Oct. 1871. 24. S. Jb., Dec. 1871; Lancet, 1876, ii. 409. 25. LE GENDRE . . . B. G. T., Ixxvii. 282. 26. POYET and COMMARMOND . Ann. de la Soc. de Med. de Saint-Etienne et de la Loire, 1863. 27. DAVIS J. A. M. A., 1884. 28. SUNOL L. M. R., 1884. 29. KELLY 30. DEHENNE . . . 31. HlLDEBRANDT . 32. MEADOWS . . . 33. GOODELL . . . 34. HEUSINGER . . 35. GRUNFELD. . . 36. KOHLER . . . . 37. SCHULLER . . . 38. BOLDT .... 39. PLUMIER ... 40. SOLLMANN and 41. HEMMETER . 42. EBERTY . . . . Med. Register, 1887. . Munich Med., xlv. 86. . B. K. W., June 17, 1872. . Pract., i. 166. . Proc. Med. Soc. of Penn- sylvania, 1873. . Journ. fur Pharmakod., i. 405- . In. Dis., Dorpat, 1892. . V. A. P. A., Ix. . B. K. W., 1874, 304- . S. Jb., March, 1872. . J. de P. P., 1905, vii. 13. BROWN . J. A. M. A., 1905, xlv. 229. . M. News, 1891, Ivii. . In. Dis. Halle, 1873. HYDRASTIS. BUNGE In. Dis., Dorpat, 1893. FRIEDEBERG . . S. Jb., Bd. 278. FALCK and GUENSTE . V. A. P. A., 1890, cxix. MOSSE and TAUTZ . Z. K. M., xliii. CURCI L. M. R.,Oct. ii, 1886. MARFORI . . . . A. E. P. P., xxvii. PHILLIPS and PF.MBREY . J. P., 1897, xxi. DE Vos Presse M. B., 1895, xlvii. o. FELLNER . . . i. SERDZEFF . . . 2. BARTHOLOW . . 3. RUTHERFORD . 4. KISELEW . . . ;. FABF.R . . Wien. Med. Jahrb., 1885. . In. Dis., Moscow, 1890. . Lloyd's Drugs and Med of North America. . B. M. J., 1879, i.,ii. . S. Jb., ccxxxviii. . Th. M., 1892, vii. GOSSYPII CORTEX. 1. MARTIN . . 2. MOHR . . 3. GARRIGUES . A. J. M. S., Jan. 1882. . Ther. Geg. 1905, vii. 360. . Quart. Bull. Clin. Soc..N. Y., Jan. 1887. FAMILY IX. IRRITANTS AND COUNTER- IRRITANTS. IRRITANTS. In the treatment of diseases of the skin various irritating substances are used for the purpose of stimulating the nutritive activity of the diseased part. The most important of these drugs are noticed at this place. Under the name of Sapo the U. S. Pharmacopcea recognizes ordinary white castile soap, a combination made between olive oil and soda, and consisting chiefly of a mixture of sodium, oleate and palmitate. This soap is entirely free from irritant properties, and is used externally as a detergent and sometimes internally in combination with laxatives to ren- der their action milder and perhaps more effective. SAPO MOLLIS, U. S. , formerly known officially as Sapo Viridis, Soft soap, or Green soap, is made by the action of caustic potash upon linseed oil ; more potash being used than is necessary for the neutralization of the fatty acids, so that the resulting combination is not only strongly deter- gent but also irritant, and even mildly caustic. Formerly, when vege- table oils contained much chlorophyll, this soap had a distinct greenish color, but as now prepared it is a brownish or yellowish semifluid mass, which yields a nearly clear solution with five times its weight of hot water. It is used chiefly in the treatment of eczema. It destroys fatty matter rapidly, softens down exudation, and markedly affects the nutrition of the skin. CHRYSAROBINUM. U. S. Chrysarobin. Under the name of Goa Powder, Araroba or Chrysaroba, certain powders varying from fine to coarse and from light yellow to dark chocolate, have long been used in Brazil and the East Indies. Formerly supposed to be the product of certain lichens, they are now known to be obtained from irregular inter- spaces in the wood of the Andira Araroba, a large Brazilian tree. Goa powder depends for its activity upon chrysarobin. The percentage of chrysarobin in the goa powder varies so much that the crude drug is not recognized in the U. S. Pharmacopcea. Chrysarobin * is an odorless, tasteless powder, when first obtained of a pale orange color, but darkening on exposure. It is very slightly soluble in cold water or alcohol, but is freely soluble in alkaline solutions and in hot fats ; formerly supposed to be identical with chrysophanic "Chrysarobin must not be confounded with anthrarobin, a distinct substance pro- duced by Liebermann from alizarin (Ber. d. Chent. Ges., 1888), which Weyl (Arch. f. d. Ges. Phys., 1888, xliii.) has proved to be free from poisonous properties. 765 766 LOCAL REMEDIES. acid, chrysarobin is now known to be a distinct neutral principle. When taken internally in doses of from six to eight grains, it produces in about four hours repeated vomiting, sometimes followed by purging (I. A. Thompson 7 ), and it has been shown by Weyl to be an active irritant poison. Chrysarobin is never used internally, but as a local application in various skin diseases when there is a tendency to excess of dry exudation, being especially effective in psoriasis. COUNTER-IRRITANTS. Almost from time immemorial physicians have believed that morbid processes in deep-seated or superficial organs could be modified by irrita- tions artificially induced in distant parts. To the drugs used for producing these remedial irritations the name of revulsants, or counter-irritants, has been given, the process being called revulsion, or counter-irritation. The question as to the manner in which a counter-irritant acts is essentially distinct from the question whether it does or does not act. However crude and uncertain our theories may be, clinical experience has demonstrated the value of counter-irritants in various internal condi- tions. It is proved beyond cavil that internal morbid processes may at times be relieved by creating external irritations. Our present explanations of the way in which counter-irritants act are certainly not satisfactory. There are abundant physiological proofs demonstrating the connection between distant organs having no appar- ent anatomical connection ; such is the relation between the mammary glands and the uterus ; such are the phenomena of so-called metastasis seen in mumps, gout, and other constitutional disorders, in which the development of a new irritation is accompanied by the disappearance of one already existing. Familiar examples, also, may be found in the paraplegias sometimes produced by irritation of a renal calculus, in the headache of gastric irritation, in the shoulder-pain of diseased liver, and in the amaurosis or epileptiform attacks sometimes caused by a decayed tooth. In the well-known experiment of Brown-Sequard it was found that if one sciatic nerve of the guinea-pig be cut epileptic attacks may be produced by gently rubbing the back of the ear upon the same side. One commonly offered explanation of counter-irritation is that there is only a certain amount of blood and of nervous energy in the body, and that if the blood or the nervous energy be drawn to one part there must be less in another part. Surely, however, the amount of blood drawn to the skin by a mustard plaster is too small sensibly to affect the general mass in the body. It is more probable that the phenomena of counter-irritation are the result of reflex disturbances of the vaso-motor nerves which influence the size of the blood-vessels, or of the trophic nerves which directly affect nutrition. It is of great practical importance to know where the counter-irritant should be placed to affect most powerfully any given internal organ. COUNTER-IRRITANTS. 767 We have no thoroughly scientific experimental knowledge as to this matter, but it has been clinically demonstrated that the general law for deep-seated parts is that the revulsant should be put directly over the part. When a superficial action is desired, other directions are needed. We are indebted to Anstie for pointing out what appears to be a law, or at least a good working rule for practice, namely, that when a superficial part supplied by the anterior branches of a spinal nerve is to be affected, the counter-irritant should be placed over the posterior roots of the nerve. Not only can obstinate neuralgia often be relieved by this reflex action, but also the inflammatory changes so often coincident with intercostal neuralgia. The law seems also to apply to cervical nerves, since the proper position for the blister in trigeminal neuralgia is back of the ear or on the nape of the neck.* For the purposes of study, counter-irritants are conveniently arranged under two heads : first, those which do not provoke decided alteration of the dermal structure, but simply cause an irritation which soon passes away ; these are the Rubefacients : second, counter-irritants which pro- duce severe structural alterations ; in this class belong the hot iron, the issue, the seton, and other destructive appliances, and also the epispastics, vesicatories, or more colloquially blisters, which are used to produce that peculiar inflammation of the cuticle with an outpouring of serum commonly known as the blister. In choosing between a rubefacient and a blister, the physician is guided by the character of the disease present in the subject. A rube- facient causes a wide-spread, intense but temporary, irritation and con- gestion of the part, an irritation which for the moment produces a strong influence, but leaves no permanent impression upon the nutritive acts of the diseased organ. A rubefacient is to be employed when the disease is functional, when there is only a nervous disturbance or a congestion to be dealt with ; whereas the blister is useful when inflammation has produced permanent change. Very frequently in inflammatory condi- tions, however, rubefacients are useful to relieve accompanying con- gestion. Thus, in a pneumonia the rubefacient may have no effect upon the focus of the disease, but may be very serviceable in checking a wide-spread collateral congestion. To the careful use of rubefacients there are scarcely any contra- indications ; some caution is, however, necessary in their application. A severe internal irritation may so successfully counter-irritate against the external counter-irritation that the latter has for the time being no ap- parent effect, and yet really exerts a disorganizing influence. Thus, a mustard plaster, under the circumstances named, may at the time of its application produce no pain or redness, and yet twenty-four hours after- * The statement of A. Dumontpallier (Gaz. Hebdomadaire, November, 1879), that the best results of counter-irritation are obtained by applying the counter-irritant upon the opposite side of the body, so as to be exactly symmetrical with the diseased part, has never to our knowledge been confirmed. 7 68 LOCAL REMEDIES. wards disorganizing inflammation may set in at the seat of the applica- tion. When there is severe internal irritation the counter-irritant should always be removed when it has been applied long enough to endanger violent local effects, even though it has exerted no sensible influence. There is one use of rubefacients which is not that of counter-irritation, but which is often of practical importance. An irritation of the sensitive nerve in the normal animal produces an immediate vaso-motor spasm, and in certain conditions of the body irritation of the mucous membrane or of the skin is of great service in stimulating respiration or circulation. In a true exhaustion rubefacients are of very little value, for the only possible source of absolute increase of power to the system is in food ; and in exhaustion those stimulants should be employed which increase the power of assimilating food. For this reason, external irritants are useful as stimulants in conditions of depression rather than of exhaustion. Especially are they valuable when there is wide-spread loss of functional activity in the vaso-motor system. Such conditions of depression, with vaso-motor weakness, exist in acute collapse from any cause, in shock following injuries, in the first stage of pernicious malarial fever, and in other cases when the powers of the system are seemingly overwhelmed by some depressing agency. Blisters are especially useful in inflammations of serous membranes, such as pleuriti s and peritonitis ; are very strongly recommended by some practitioners in parenchymatous inflammations, such as pneumonia ; and may be of service in persistent forms of nervous irritation, such as the maniacal delirium of fevers, when dependent upon the irritant action of a blood-poison, and not upon exhaustion. The amount of serum which is poured out from a blister is sometimes quite large, and vesicants have even been employed to relieve dropsy. In general dropsy their use is simply unjustifiable ; but in local dropsies, as, for example, serous effusion into the pleural sac or into the pericardium, dependent upon local inflam- mation, they often do good, not only by affecting favorably the disease- process, but also by hastening the removal of the effusion. In some chronic affections, long-continued severe counter-irritation is required : in such cases a blister may be "kept open" by the use of stimulating ointments, such as the mezereon ointment. In chronic in- flammation of the joints, repeated blistering is very often of service. When the inflammatory action is rheumatic, in our experience better results are obtained by repeated blistering than by keeping a blister sore by means of irritants. In neuritis, whether rheumatic or other- wise, blisters are often of service : they should be applied as a long narrow strip along the course of the nerve. In obstinate local neural- gia, very mild blistering over the seat of pain, or in accordance with Anstie's law, is sometimes advantageous. The contra-indications to the use of blisters are high arterial and febrile excitement and a decided want of vital power. In the former case, the irritating influence which they exert upon the general system COUNTER-IRRITANTS. 769 may increase the constitutional disturbance to such an extent as to do more injury than any local benefit derived from them can do good. When the vitality is very low, blisters may give rise to sloughing ulcers, which, refusing to heal, may waste very seriously the already exhausted system. Hence, in all acute diseases of such type that the nutritive forces are exceedingly depressed, blisters must be avoided, or be used only with great caution. For the same reason, great care must be exercised in their employment in the very young or the very aged. Very rarely indeed is a blister called for in the case of a young infant, and if it be employed at all, it should be allowed to remain in con- tact with the skin only long enough to produce slight pain or redness, and the complete vesication should be obtained by the after-use of a poultice. The hot iron or other destructive counter-irritant is to be used only in cases of continuing chronic disease with structural lesion. At present, neither the moxa nor the issue is ever employed in civilized countries ; the seton with extreme rareness. The actual cautery, however, affords a valuable method of treating chronic neuritis, chronic meningitis, cere- bral or spinal, and various forms of chronic arthritis. EPISPASTICS. There are various substances which are capable of producing vesica- tion, but the only one in ordinary use is cantharides. .In cases of emer- gency ammonia is sometimes employed. (See page 281.) CANTHARIS CANTHARIDES. U.S. The dried bodies of the Cantharis vesicatoria, a beetle inhabiting Southern Europe. Spanish flies are from half an inch to nearly an inch in length and two to three lines in breadth, and have a large heart- shaped head and brilliant metallic-green elytra, or wing-cases. Their odor during life is very strong and fetid, but is almost entirely lost in drying ; their taste is urinous, very burning, and acrid. When ground, Spanish flies afford a grayish-brown powder, full of minute greenish spangles, the remains of the feet, head, and wing-cases. The active principle of cantharides is Cantharidin, which occurs in white crystalline scales, is inodorous, tasteless, insoluble in water, nearly so in cold alcohol ; soluble in ether, benzole, the oils, and very freely so in chloro- form. Notwithstanding the insolubility of pure cantharidin, Spanish flies yield their virtues to alcohol and to water. Local Action. Absorption and Elimination. Cantharides is very irritating, and, when applied to the skin, causes at first redness, with burning, then free vesication and severe pain, and, if the contact be longer maintained, deep inflammation and sloughing. Upon the mucous membranes it produces a no less intense effect. The cantharidin is rapidly absorbed, and is eliminated unchanged by the kidneys. General Action. The first symptom produced by the small dose of 49 770 LOCAL REMEDIES. cantharides is burning in the genito-urinary passages. After the ingestion of ten minims of the tincture the irritation may amount to complete stran- gury. The toxic dose produces in a very few minutes burning in the pharynx and oesophagus and a sense of stricture in the throat. The pain soon spreads to the stomach, and vomiting comes on. The symp- toms rapidly increase in severity ; the abdominal pain becomes very severe, and in the majority of cases purging takes place. The matters rejected by the stomach are first mucous (with, if the drug have been taken in powder, little greenish specks through them), then bilious, and finally bloody. The stools are mucous, then fibrinous, bloody, becoming often very scanty, but excessively numerous, and in their passage accom- panied by great tenesmus. Probably in most cases, early in the poi- soning severe salivation is developed, and is frequently accompanied by great swelling of the salivary glands. Sometimes death occurs in a very short time, from collapse produced by the intense gastro-intestinal inflam- mation ; but more generally it is postponed for some hours, and a new train of symptoms arises. Aching pains in the back and very frequent micturition indicate the commencing urino-genital irritation. These symptoms increase in intensity until there is a constant, irresistible desire to urinate, with violent tenesmus of the bladder, and yet an inability to pass more than a few drops of urine, which is albuminous, and not rarely bloody. In some cases there is a violent erotic excitement, an unquench- able lust, accompanied in man by numerous seminal emissions ; * violent priapism, swelling and heat of the organs, and even severe inflammation of the parts may indicate the intensity of the local action of the poison ; some- times gangrene ultimately occurs. Consciousness and general power are often long preserved when the local symptoms and agony are intense, but, if the dose have been large enough, sooner or later collapse comes on, with the usual accompaniments, and the prostration deepens into complete powerlessness, stupor, coma, and finally death. In some cases violent hydrophobic delirium and severe tetanic convulsions are said to have occurred (Tardieu). Paraplegia has 'been noticed in several cases by Palle 1 : l it was probably reflex in its origin, and due to the intense irritation of the genito-urinary organs. In animals, cantharides produces very much the same symptoms as it does in man. In dogs, according to the experiments of Orfila and of Beaupoil, the symptoms of gastro-intestinal inflammation are more prominent than those of irritation of the genito-urinary tract. It has been asserted that the lack of erotic excitement in these cases shows that the medicine acts differently upon man and upon animals. As already stated, however, erotic delirium is very often absent in fatal poison- ing in man, while Schroff states that ten drops of the tincture of cantharides will frequently produce great sexual excitement in man, and the whole drift of the evi- dence is that libidinous desires are much more apt to be caused by amounts ot Spanish flies but slightly toxic than by fatal doses. Indeed, the irritation caused by the latter would seem to be too intense, the general perturbation too great, for * Cases, Journ. de Pharm. ei de CJiimie, June, 1871. COUNTER-IRRITANTS. 771 erotism to be induced. There appear to be the same differences in the effects of dif- ferent doses of the drug upon animals. Fatal doses very generally do not excite sexual desire ; but Schubarth (quoted by Stille') found that small doses do cause evident salaciousness and irritation of the genital organs, while, according to Huse- mann, 2 the peasants of Northern Germany habitually give cantharides to cows when backward in coming into heat at the proper season. According to Cautieri, 3 toxic doses of cantharides rapidly lessen blood- pressure and the force of the cardiac pulsations, but markedly increase the pulse-rate. Cautieri found in animals killed with cantharides marked hyperaemia of the brain and spinal cord, and nephritis : Galippe 4 noted inflammation of the alimentary canal, kidneys, and bladder. THERAPEUTICS. Cantharides is employed internally only for the purpose of influencing the genito- urinary organs.* When cantharides is freely used externally as a vesicant there is always some danger of the absorption of a sufficient amount of the active principle for strangury to be induced. The blister should therefore not be left on longer than is absolutely necessary, and in susceptible persons care has to be exercised in its use : whenever active irritation of the kidneys exists, cantharidal blisters should not be applied, f TOXICOLOGY. The minimum fatal dose of cantharides is not certainly determined, and probably varies very much. According to Stille, twenty-four grains of the powder, taken in two doses, have caused fatal abortion, and an ounce of the tincture has destroyed life after the lapse of a fortnight. After death, intense injection, swelling, patches of exudation, loss of epithelium, and other results of inflammation are found along the whole tract of the alimentary canal ; intense hyperaemia of the kidneys, with contraction and congestion of the bladder, also usually exists. According to the experiments of Aufrecht, 5 all the forms of nephritis may be produced by cantharidin, but it is probable that in most cases of poisoning the first change is exudation of the white blood- corpuscles, rapidly followed by a desquamative nephritis, with profound alteration in the glomerules (see Ida Eliaschoff 6 ). There is no known antidote to cantharides, and the treatment of the poisoning must be conducted upon general principles. The stomach should be washed out repeatedly and freely by large draughts of warm water, aided by the stomach-pump or tube, or by a stimulating emetic if the stomach-pump be not at hand. Large quantities of mucilaginous or albuminous drinks should be taken ; and all oily substances should be avoided, as favoring the solution, and consequently the absorption, of the poison. Opium should be freely exhibited, especially by the rectum, to allay pain and relieve the strangury. For the latter purpose warm sitz- * See DIURETICS and EMMENAGOGUES. f In 1891 Liebreich advocated the use of cantharidin salts in lupus, phthisis, and other forms of tubercular disease. His theory of their action was, however, very im- probable, and the method has so entirely failed in practice that it is not necessary here to do more than refer the curious reader to the tenth edition of this treatise for informa- tion concerning it. 772 LOCAL REMEDIES. baths or general baths should be employed. In some cases leeches to the epigastrium are advisable. When the suffering is very intense, the cautious use of anaesthetics is not only justifiable, but imperative. ADMINISTRATION.- For blistering, the Cantharides Cerate (CERATUM CANTHARIDIS, U. S. ) is best spread upon sticking-plaster in such a way as to leave a margin about an inch in width, which shall adhere to the skin and hold the plaster in its place. In order for a blister to " draw" thoroughly, it usually has to be left on some eight hours ; but in most cases the same result can be achieved with less suffering by allowing the blister to remain only five or six hours, or until decided redness and slight vesication have been induced, and then applying a flaxseed poul- tice. In certain localities vesication requires a much longer application than that just spoken of ; thus, upon the shaved scalp a blister will rarely act efficiently in less than twelve hours, and often not in that time. In maniacs, in the delirious sick, in children, and in other unruly patients it is often necessary to put on a blister in such a way that the sick person has no control over it. For this purpose the Cantharidal Collodion (CoLLODiuM CANTHARIDATUM sixty per cent., U. S. ) * may be used. It is ordinary collodion impregnated with cantharidin, and on evaporation leaves an adhesive blistering film : two or three coats of it should be applied by means of a camel' s-hair brush. When there is any especial danger to be feared from absorption of the active principle, the use of the poultice, after a brief application of the blister as de- scribed above, should always be practised. The tincture (TiNCTURA CANTHARIDIS ten per cent. , U. S. ) is used internally in doses of one to two drops (0.06-0.12 C.c. ). R UBEFA CIENTS. SINAPIS ALBA WHITE MUSTARD. U. S. SINAPIS NIGRA BLACK MUSTARD. U. S. The seeds of Brassica alba and Brassica nigra respectively, Euro- pean crucifers, cultivated in the temperate regions of the world. These seeds are minute, globular bodies, yellowish within : they are to be dis- tinguished one from the other by the smaller size, external brown color, and more fiery taste of the black mustard, and the light yellowish exte- rior of the white mustard. Black Mustard yields on distillation a volatile oil, which does not pre-exist in the seeds, but is formed by the decomposition of sinigrin or potassium myronate in the presence of emulsin. OLEUM SINAPIS VO- LATILE, U. S., is a colorless or yellowish fluid, of an intensely pungent, or corrosive, odor and taste. A momentary contact with it suffices to redden and blister the skin, and mucous membranes are said to be rap- idly destroyed by its vapors. WJiite Mustard contains sinalbin, which in the presence of water and * For a case of poisoning by cantharidal collodion, see Phila. Med. Times, iv. 312. COUNTER-IRRITANTS. 773 emulsin forms acrinyl sitlphocyanate, an oily, non- volatile, very acrid sub- stance, upon which the activity of white mustard depends. THERAPEUTICS. Mustard affords a most excellent material for the practice of mild revulsion. One advantage it possesses is the ease with which it can be controlled, all grades of action, from the mildest impres- sion up to severe blistering, being at the will of the practitioner. It should be remembered, however, that the blister produced by it discharges but little, and is exceedingly sore and painful, as well as very slow and diffi- cult of healing : so that, as an epispastic, mustard is in every way infe- rior to cantharides, and should not be employed. The black mustard is much stronger than the white, and must usually be diluted at least one- half (by the addition of flour or of flaxseed meal). The white variety may sometimes be employed pure, but generally it also should be reduced in strength. In many cases it is desirable to maintain for hours a mild, equable counter-irritant impression, and this may be done by adding from one to three teaspoonfuls of mustard, more or less, to a poultice of flaxseed. A mustard poultice (half-and-half black mustard, three parts to one of white mustard and flour) may generally be left on from twenty minutes to half an hour without danger of blistering. Weaker preparations may be used longer. A mustard plaster may be prepared like an ordinary poultice ; but a very con- venient method is to take a newspaper folded to a little larger than the desired size, and tear open the front piece so that it can be folded back like a flap, leaving one edge attached ; next, to spread upon the thick portion the mustard, leaving the edges free, and then to close the flap upon it and fold the edges back to the desired shape : when done with, this plaster can be thrown away, and no rags are lost. The mustard draws well through the single layer of newspaper covering it, but is, we think, less apt to leave troublesome after-soreness than when employed in the usual manner. CHARTA SINAPIS, U. S. , or Mustard Paper, consists of black mustard mixed with solution of gutta-percha and spread upon stiff paper four inches square. It is not so good as the domestic plaster, because not so easily regulated as to power and size. CAPSICUM and the stronger spices afford excellent materials for rube- faction. Cayenne pepper is nearly as strong as mustard, but is much less pleasant to handle, on account of the readiness with which it is dif- fused, and is much less frequently employed. Spice-plasters are useful when it is desired to make a steady, continuous mild impression, as in certain abdominal complaints. Spice-plasters may be made by the apothecary by means of the following recipe. Take of powdered ginger, 3 " ; powdered cloves and cinnamon, each, g i ; Cayenne pepper, 3 ii ; tincture of ginger, f 3 ss ; honey, q. s. ; mix the powders, add the tinc- ture, and sufficient honey to make of proper consistence for a stiff cataplasm. The 774 LOCAL REMEDIES. domestic spice-plasters are much more elegant and cleanly than those made on the above plan. They are to be prepared as follows. Take equal parts of ground ginger, cloves, cinnamon, and allspice, and one-fourth part of Cayenne pepper, and thor- oughly mix them ; then put the resulting dry powder into a previously prepared flannel bag of the desired size, distribute the powder equably through the latter, and quilt it in, i.e., run lines of stitching across the bag, so as to confine the pow- der in little compartments : when using, moisten thoroughly with common whiskey or with alcohol. A plan which has seemed to us still more pleasant is to put two ounces of unground ginger, an ounce of unground cloves, cinnamon, and chillies, or African peppers, in a pint bottle, and pour the whiskey upon them. After this has stood awhile, the liquor is to be put upon a piece of flannel of the proper size, and the latter is to be laid upon the part and covered with a larger piece of oiled silk, or else a piece of spongiopilin may be employed. If the strength of the prep- aration is too great, it can readily be reduced by dilution ; if it is too little, it can as readily be increased by adding more of the spices, especially of the peppers. In many cases, when the tenderness is very great, the weight of the spice-plaster is objected to. Under these circumstances the substitute here proposed is especially valuable. OIL OF TURPENTINE is a very powerful rubefacient, capable, if ap- plied to the skin for too long a time, of destroying the epidermis. It produces, when properly used, simply an intense diffused redness. The most frequent mode of application is in the form of stupes, which should be made by dipping a piece of flannel, previously wrung out with warm water, into a cup of turpentine which has been warmed by setting it in hot water, and then wringing out all excess of the turpentine and applying. These stupes may be left on from ten to thirty minutes, ac- cording to the severity of the impression desired and the susceptibility of the patient's skin. On some persons the least contact of turpentine, or even of its vapors, produces a most painful furuncular eruption. Where this idiosyncrasy exists, of course the remedy should never be used. The official liniment (LINIMENTUM TEREBINTHIN^E, U. S. , Kentish Ointment) has been used as a stimulant application to burns and old ulcers, but has passed out of vogue. AMMONIA is a most efficient rubefacient, which in its general relations has been sufficiently discussed elsewhere. When great haste is required, it may be employed as an epispastic by applying a piece of common lint saturated with the stronger water of ammonia, and covering it with some impervious coating. Great care must be practised lest the am- monia act as an escharotic, since a too prolonged application may pro- duce a deep slough. To raise a blister requires from five to ten minutes. On account of its cheapness and efficiency, ammonia is very largely used in extemporaneous liniments. In prescribing, it must always be borne in mind that there are two waters of ammonia, AQUA AMMONITE FOR- TIOR, U. S. , with a specific gravity of o. 90, containing twenty-eight per cent, by weight of the gas, and AQUA AMMONITE, U. S. , with a specific gravity of 0.960, containing ten per cent, by weight of the gas. The rubefacient action of ammonia is less permanent than that of turpentine. COUNTER-IRRITANTS. 775 The liniment (LINIMENTUM AMMONITE, U. S. ) is composed of three hundred and fifty parts of ammonia water, fifty parts of alcohol, and. six hundred parts of cotton-seed oil. Burgundy Pitch was formerly official. It is a concrete juice ob- tained by wounding the Abies excelsa, or Norway spruce, lofty forest trees of Middle and Northern Europe, melting the product of the exudation with hot water, and straining. It is hard, opaque, brittle, of a feeble terebinthinate odor and taste, and contains resin and a minute amount of volatile oil. It is a mild rubefacient, which, in the form of plaster, may be kept applied for a long time in chronic bronchitis and in rheumatic affections of the trunkal muscles. The plaster contains fifteen per cent, of wax. The Wanning Plaster contains one part of cantharides cerate to twelve parts of Burgundy pitch, and is a very decided counter- irritant whose prolonged use will sometimes blister. CARBONEI DISULPHIDUM. U. S. Carbon Disulphide. Carbon Bi- sulphide. A clear, colorless, highly refractive, very volatile liquid, of a strong, disagreeable odor and a sharp aromatic taste. It is very much used in the arts as a solvent, and is an active poison, half an ounce of it having produced death, preceded by coma, with collapse and abolition of reflexes. It has not been used as an internal remedy, but has been employed as a counter-irritant and local anaesthetic for the relief of focal, facial, and other neuralgias. A small dossil of cotton, saturated with the drug, should be placed on the part and covered with wax paper ; or better, a wide-mouthed bottle containing the disulphide and cotton may be inverted upon the part for a few minutes. Even the counter-irritant use of carbon disulphide is not to be encouraged. REFERENCES. COUNTER-IRRITANTS. 3 . CAUTIERI S. Jb., clxv. 237. 1. PALLE Journ. de Pharm. et de 4. GALIPPE G. H. M. C.. 1874, 439. Chim., June, 1871. 5. AUFRECHT . . . . C. M. W., 1882, xx. 850 2. HUSEMANN .... Handb. der Toxicologie, 6. EUASCHOFF . . . V. A. P. A., xciv. 323. 1862, 264. 7. THOMPSON .... Brit. Med. Jour., 1887. FAMILY X. ESCHAROTICS. ESCHAROTICS are drugs which are used to destroy diseased or sound tissue. Many of them exert a purely chemical influence, while others seem to destroy life by directly affecting the vitality of the part, and are said to act dynamically. Those which act chemically do so in sev- eral ways : some, like bromine, probably produce an intense corrosive oxidation, while others, like sulphuric acid, abstract the water. Escharotics are used for various purposes. Formerly they were employed to open abscesses ; but in the very few cases in which the knife is not allowable, aspiration usually affords a superior and safer method. They are constantly applied to destroy unsound, harmful tissues and growths. Thus, they are used to remove the specific tissue of a chancre, or to kill a malignant or semi-malignant tumor. Another purpose which they fulfil is the destruction of poisoned wounds. In these cases they may in some instances destroy the poison itself, but at other times they simply prevent the absorption of the toxic agent by putting an end to the life-actions of the tissue containing it. It is hardly necessary to mention all the various cases in which caustics are employed to overcome the effects of poisoned wounds. Hydrophobia is a perfectly uncontrollable disease ; but the thorough destruction of the wounded tissue at any time before the manifestation of the symptoms will probably prevent its occurrence, as it certainly will if performed early. In malignant pustule, life depends upon the free early use of escharotics. Escharotics are employed to produce ulcerations which shall be the bases of issues ; also, by destroying the exuberant granula- tions or the indolent surfaces of ulcers, to remove at the same time dis- eased tissue, afford protection to the parts below by forming an imper- meable surface, and exert such alterative action upon the part as shall modify for good the life-processes. It is evident that the choice of the caustic should depend upon the object to be attained. When large tumors are to be killed, or when it is all-important completely to destroy a poisoned wound, a powerful deep-reaching escharotic must be employed ; but when the surface of an ulcer is to be filmed over, a caustic which acts superficially and forms a dense albuminous coating, as does silver nitrate, is to be chosen. An observation of N. A. Randolph and S. G. Dixon ' indicates that the pain produced by a caustic may be almost nullified by the use of 776 ESCHAROTICS. 777 cocaine. They find that the saturated solution of cocaine in nitric acid acts as powerfully as nitric acid, although much more slowly, and that the only sensation experienced during the production of even a deep eschar is a slight prickling. All of the more powerful of the escharotics, when taken internally in sufficient amount, act as violent corrosive poisons, producing agonizing pain in the oesophagus and hypogastrium, violent bloody vomiting, often purging of similar character, and finally collapse, deepening into death, which is sometimes preceded by convulsions. When the dose is not so large, the patient may rally from the immediate effects of the poison, to succumb finally to the local lesions produced, or to struggle through a protracted convalescence to health, perhaps only to die years afterwards from organic stricture, caused by the ulcerations of the oesophagus or other of the digestive tubes. The first indication in poisoning by one of these substances is to neutralize or chemically antidote the poison : with the alkalies, dilute acid, generally convenient in the form of vinegar; with the acids, alkalies, usually at hand in the shape of whitewash or of soap ; with other poisons, specific antidotes. Opium should always be freely given, and the symptoms during and after the first poisoning be treated as they arise. POTASSII HYDROXIDUM. U. S. Caustic Potash occurs in grayish, semi-translucent sticks, about three inches long and as thick as a large goose-quill, very deliquescent, and extremely soluble in both water and alcohol. When it is placed upon the skin it soon melts, and, as it does so, gives rise to a pain which increases until it becomes very intense, and continues until the power of the alkali is so diminished that it can no longer reach through the tissue it has killed to the sound flesh below. Under the action of the escharotic the skin becomes of a dirty ashen- gray, and finally a slough is formed, with inflammation of the surround- ing parts, and ulceration and detachment of the dead tissue in from six to ten days. The potash appears to act chiefly by abstracting the water, and, to some extent, by combining with the fatty and other portions of the tissues. Its slough being perfectly permeable, and its power being but slowly expended by its own action, potash is one of the most thor- ough of the escharotics : it is, therefore, to be preferred when a very deep and decided influence is required, as after the bite of -\ rabid dog. It is somewhat uncontrollable in its action, and requires care in its use. The best method of application is as follows. Take a piece of thick adhesive plaster, and cut a hole in it of such size that, when the piece is warmed and properly placed upon the skin, the part to be acted upon will be exposed while all around it will be protected. Then apply the plaster, and grease the outer surface of it, without allowing any of the oil to come in contact with the exposed central skin. Then lay the caustic potash upon the latter, and, when the action is believed to have extended deep enough, .wash the part with dilute vinegar. 77 8 LOCAL REMEDIES. POTASSA CUM CALCE, 1890. Vienna Paste, a grayish- white powder, composed of equal amounts of caustic potash and caustic /. e. , unslaked lime. It is not so active as caustic potash, but is less apt to spread and diffuse itself. It is to be mixed with sufficient alcohol to form a paste, and then applied like caustic potash. Piedagnel 2 affirms that this caustic may be rendered nearly or entirely painless by mixing one part of morphine hydrochlorate with three parts of the powder, and then by the addition of chloroform forming a paste that may be spread upon lead plaster and so applied. In five minutes the skin under the application becomes of a dead-white color, and at the end of fifteen minutes is brown and carbonized. If the application be persisted in, the thickness of the eschar will become finally about equal to that of the layer of the paste employed. Cocaine would probably be more efficient in preventing pain than the morphine. ARSENI TRIOXIDUM. U. S. As a caustic, arsenic is energetic and powerful, but somewhat slow, and causes intense pain, with violent inflam- mation of the neighboring parts. It is stated to affect more rapidly mor- bid than normal structures, and is especially used for the destruction of malignant growths. It appears to act chiefly upon the vitality of the part, acting, when sufficiently diluted, as a powerful irritant, and when in a concentrated form producing an irritation so intense that life cannot endure it. Hence, probably, the reason of its affecting more rapidly morbid growths, which have a lower vitality than sound tissues. The great objection to the employment of arsenic is the possibility of its absorption in sufficient amount to cause constitutional symptoms : even death has resulted from its external use. Since absorption takes place much more rapidly in a healthy than in an intensely inflamed or a dead tissue, whenever arsenic is employed as a caustic it should be used so freely as to kill the tissues rapidly, and under no circumstances should it be applied to a fresh wound. Used in any way, arsenic is a hazardous caustic, and it ought to be employed only with the knowledge and distinct remembrance of this fact. Cancer, and perhaps some forms of semi-malignant ulceration, such as lupus, appear to be the only dis- eases which justify its use. There is no reason for believing that any of the almost innumerable substances which have been proposed as a basis for arsenous pastes pos- sess peculiar advantages : the only needful direction is to mix the caustic with from eight to ten times its bulk of inert material of such a nature as to make either an ointment or a paste, and to allow this to remain on the part for from eighteen to twenty-four hours. ZINCI CHLORIDUM. U. S. Zinc Chloride occurs in broken fragments of a grayish-white color, translucent and waxy in appearance, of an acrid corrosive, or, when diluted, acrid astringent, metallic taste. It is ex- tremely deliquescent, fusible, volatilizable at a high temperature, and very soluble in both water and alcohol. Zinc chloride is a very powerful ESCHAROTICS. 779 caustic, producing, when applied in a concentrated form, intense pain lasting from six to eight hours, and a whitish eschar, which usually sep- arates in from six to twelve days. Its penetrating powers are a little less, and its action more readily controlled, than is that of potash ; its absorption does not endanger life, as is the case with arsenous acid ; and it leaves a slough which is free from odor. Canquoiri s Paste is made by mixing zinc chloride with flour and water. The strength varies according to the purpose, the weakest paste containing only one part of the caustic in six parts ; the strongest, one part in three. When used, ten or fifteen drops of water are added to the paste, which is applied in layers, successive applications being re- quired when a large tumor is to be destroyed. Anhydrous calcium sul- phate has been especially commended by A. Ure, as forming a drier paste with the escharotic and limiting its action more definitely to the site of application than any other substance. Concentrated alcoholic or watery solutions of zinc chloride are often used as caustics in cases of chancres and other small specific ttlcers, and are reputed to be efficient. They should be applied by means of little pledgets of lint. As the action of the chloride upon the skin is slow and very painful, whenever the cuticle over the part to be destroyed is sound it should be removed by means of blisters. By some surgeons the escharotic is introduced directly into the tumor to be destroyed. The official solution (LIQUOR ZINCI CHLORIDI, U. S. ) has been used as a disinfectant, but is of very little value. HYDRARGYRI CHLORIDUM CORROSIVUM. U. S. Corrosive Sublimate is an escharotic of moderate power, which shares the dangers of arsenic, since death has followed its external use. In saturated solution it is much used as a caustic in chancres, but is scarcely equal to the solution of mer- curic nitrate. In these cases it should be applied by means of a camel' s- hair brush. The late George B. Wood recommended very highly that in onychia maligna a powder composed of equal parts of corrosive subli- mate and zinc sulphate intimately mixed should be sprinkled thickly over the diseased surface, and a pledget of lint thoroughly wet with laudanum laid thereon. There is severe pain for half an hour to an hour ; but the dressings are not to be removed until eight or ten hours have elapsed. When the slough which is thus formed separates, a healthy granulating surface is left. LIQUOR HYDRARGYRI NITRATIS. U. S. Solution of Mercuric Nitrate is a nearly colorless, highly corrosive, acid liquid, having a specific gravity of 2.086, and made by dissolving mercury, or its red oxide, in a large excess of nitric acid. Its application to a space not bigger than a half-crown has produced very serious poisoning.* It is rarely used, except for the purpose of destroying specific or cancerous ulcers. * Case, I^ancet, January 3, 1874. 780 LOCAL REMEDIES. It is especially useful in chancres, to which it should be applied with a glass rod. In obstinate acne, an indolent tubercle may be destroyed by a minute drop without producing a scar. It has been largely employed by gynaecologists in ulcerations of the cervix uteri. Its action is very prompt and is moderately deep; the pain is severe, but transient. ACIDUM NITRICUM. U. S. Nitric Acid is a powerful caustic, which is never employed to destroy large tumors, but is a favorite application to chancres, to syphilitic, phagedenic, and other unhealthy ulcers, and to condylomata and other small dermal growths. A drop or two may be applied by means of a glass rod or a wood splinter, and when the action has gone far enough, neutralized with soapsuds. CHROMII TRIOXIDUM. U. S. Chromium trioxide, commonly known as Chromic Acid, occurs in anhydrous acicular crystals, of a deep red color, and an acid, metallic, corrosive taste. They are very deli- quescent, melting down, when exposed to the air, into a deep red solution. Chromic acid is a very active oxidizer, and when mixed with organic matter rapidly alters it, and if in slight excess will dissolve almost any form of tissue. It is used to destroy condylomata and other dermal growths, and is best applied by means of a glass rod, the liquid formed by the spontaneous deliquescence of the crystals being used. Chromic acid is sometimes prescribed, dissolved in or made into a paste with glyc- erin, but it is stated that in mixing the two great care must be taken to add the liquid slowly drop by drop, as otherwise there is danger of an explosion. In the German army, painting the soles of the feet and the skin between the toes with a five per cent, solution of chromic acid is said to have had a very great influence in increasing the marching powers of the troops, by arresting excessive sweating and hardening the skin. Chromic acid is a violent corrosive poison, a single drop of the saturated solution having caused very severe symptoms.* The nature of the poison may often be recognized by the reddish-brown, or more rarely greenish, discoloration of the skin of the lips and of the mucous membrane of the mouth and gullet, but this discoloration may be absent. In a number of cases death has resulted from the too free external use of the acid, f ACIDUM TRICHLORACETICUM. U.S. Trichloracetic Acid occurs in deliquescent crystals. It has been used to a considerable extent for the destruction of papilloma and other growths ; a single crystal placed on a growth produces immediately a white, dry, adherent mass, which falls off in a few days. The pain is said to be not at all severe, and may be entirely prevented by the use of cocaine. * Case, Brit. Med. Journ., 1889, i. t For experiments as to its effects on animals, see A. E. P. P., vi. ; also Strieker's Jahrb., 1877, 139. For cases of poisoning, see Ibid.; S. J., 1884, cci. 129; U. M. M., ii.; M. M. W., 1903, i. 691 ; D. A. K. U., Ixxv. ESCHAROTICS. 781 BROMUM. U. S. Bromine is a dark red liquid which has a very power- ful, disagreeable, chlorine-like odor, and at ordinary temperatures emits exceedingly acrid, pungent fumes. It is sparingly soluble in water, more soluble in alcohol, and still more so in ether. When brought into contact with organic matter, it oxidizes and completely destroys it with great rapidity. On account of this property and of its liquid form, bromine is one of the most severe, thorough, and rapid of all the caus- tics. It has not been much employed to destroy morbid growths, but has been found very efficient in hospital gangrene. After most of the slough has been cut away, the caustic should be applied pretty freely to the living tissue by means of a glass rod. When taken internally, bromine acts as a very powerful corrosive poison.* Zinc Sulphate, Copper Sulphate, and Burnt Alum are feeble escha- rotics, never used except to destroy exuberant granulations in ulcer. PYROGALLOL. U. S. Pyrogallic Acid. This triatomic phenol may be prepared synthethically, but is usually obtained, in accordance with the directions in the U. S. Pharmacopoeia, as the result of the igneous decomposition of gallic acid. In concentrated form it is a powerful caus- tic, and as such, and also in the form of dilute ointment or solution, five to forty grains to the ounce, has been considerably used in the treatment of lupus, psoriasis, and allied affections of the skin. It is a violent poison, and in various cases death has followed its too free external use. Half an ounce of it, taken internally, has produced death in four days. The symptoms which follow its external use have been malaise, vomiting, diarrhoea, headache, pallid and cyanosed lips, collapse, a peculiar greenish hue of the skin, rapid pulse and respiration, albuminous urine, becoming dark brown or black from the presence of methaemoglobin, icterus, insomnia, restlessness with diminished reflexes, and death pre- ceded by delirium, convulsions, and coma. In pregnant women abortion without death of the mother has occurred as the result of the external use of the ten per cent, ointment of the pyrogallol, in psoriasis ( Busch 1 ). When the poison has been due to the internal use, violent burning pains, black vomit, and other evidences of its irritation to the gastro-intestinal tract are usually present. As noted by Personne, 4 these symptoms re- semble those of phosphorus-poisoning, and wide-spread fatty degenera- tion and other post-mortem lesions similar to those caused by phos- phorus are found after death. REFERENCES. 2. PIKDAGNEL .... Journ. dc Pharm. et de ESCHAROTICS. Chim., 3 s., xxxiii. i RANDOLPH and DIXON . M. News, Jan. 4, 3. BUSCH W. K. W., 1901. j885. 4- PKRSONNK . . . . C. R. A. S.. 1869. * For cases, see Schmidts Jahrb., ccxxi. ; also Vierteljahr. f. Getichtl. Med., 1889. FAMILY XL DEMULCENTS. THESE are bland substances, which form more or less gummy or mucilaginous solutions in water, capable of exerting a calming or sooth- ing influence upon inflamed surfaces. Their action is probably purely mechanical, their adhesiveness causing the water they are in to remain long upon the part ; they are, as it were, vehicles for water, the de- mulcent par excellence. It has been affirmed not only that demulcents soothe surfaces to which they are immediately applied, but also that taken internally they relieve irritation in distant organs. There is, however, no reason for supposing that such of them as escape digestion are absorbed or yield to absorption any principles in sufficient quantity to exert an in- fluence upon the general system. The relief which undoubtedly follows their use in certain affections of parts which they can reach only through the circulation is probably due to the large quantities of water with which they are administered, lessening the concentration, and hence the acridity, of the urine and other secretions. Clinically, demulcents are useful as local applications in all forms of acutely inflamed surfaces, and they are taken internally in acute inflam- matory conditions of the alimentary canal. In slight bronchial irritation they are often of service, especially when allowed to dissolve slowly in the mouth : used in this manner, they not only exert an influence upon the mucous membrane of the mouth, but very probably find their way also into the respiratory passages. ACACIA GUM ARABIC. U.S. A gummy exudation from Acacia Senegal, a small tree growing in Northern Africa, Senegambia, Guinea, etc. , the Cape Colony, and Aus- tralia. Gum arabic occurs in roundish or irregular pieces, more or less transparent, hard, brittle, varying in color from white or yellowish white to red, or even deep orange brown. It consists of a peculiar, feebly acid, amorphous principle, Arabin, united with about three per cent, of lime, potash, and magnesia. In the plant, arabin, like other gums, appears to be formed by a retrograde metamorphosis of cellulose. On account of its solubility in water and pleasant taste, gum arabic is often used as a demulcent in irritation of the fauces and in angina. It is sometimes em- ployed as an addition to drinking-water in fevers, and is believed to have slight nutritious properties. Its chief use, however, is in Pharmacy, in the making of emulsions, pills, etc. The mucilage (MuciLAGO U. S. ) is used in various doses as a vehicle. 782 DEMULCENTS. 783 TRAGACANTHA. U. S. Tragacanth is the concrete juice of Astraga- lus gummifer, and of other species of Astragalus, a small shrub of Asia Minor. Tragacanth occurs in large, whitish, horny, waved flakes, or sometimes in filamentous pieces. It is odorless and nearly tasteless. In- troduced into water it does not dissolve, but swells up into a soft paste. One hundred parts of it contain, according to Guerin, 53.3 parts of ara- bin, 33. i parts of bassorin, and 2. 5 parts of inorganic ash. Bassorin is a gummy principle, at once distinguished from arabin by its not dis- solving in water, but simply swelling up into a pasty mass. Tragacanth is used only in the manufacture of troches and in suspending heavy pow- ders, for which purpose the difficulty of its solution and the extreme viscidity of its mucilage especially fit it. Its mucilage (MuciLAGO TRAGACANTH^E, U. S. ) is used in varying dose as a vehicle. ULMUS. U. S. Slippery Elm is the inner bark of Ulmus f ulva, a large indigenous tree. The bark is of a yellowish-white or tan color, fibrous, yet when dry somewhat brittle, and occurs in long, flat strips or pieces one or two lines thick. It is pleasantly mucilaginous when chewed. It contains a large quantity of a peculiar mucilage, which it yields freely to water. Its infusion is sometimes taken in large quantities in inflamma- tions of the intestines, as a demulcent laxative ; but its chief use is as an external application. When ground into powder, slippery elm makes an excellent soothing poultice. The mucilage (MUCILAGO ULMI, U. S. ) is used in varying dose as a vehicle. CHONDRUS. U. S. Irish Moss, or Carrageen. The fronds of Chon- drus crispus, and of Gigartina mamillosa, sea-weed growing on the coast of Ireland, and also on the northern coast of the United States, where it is now gathered in large quantities. The fronds are purplish red, but, as kept in the shops, bleached by washing in fresh water, whitish and translucent, cartilaginous, slender, much branched, swelling up but not dissolving in water, and having a slightly saline taste. Their virtue depends chiefly upon a starch- or gum-like principle, Carrageenin, which is distinguished from starch by not turning blue with iodine, and from gum by not precipitating from its watery solution on the addition of alcohol. Chondrus also contains a notable proportion of a vegetable albumin. Carrageen, being demulcent and nutritious, is employed as an article of diet in those cases requiring food of such character, and may be used instead of arrow-root. It is to be prepared by first soaking for ten minutes in cold water, and then boiling from half an ounce to an ounce of it (according to the desired consistency) in a pint and a half of water down to a pint, sweetening and flavoring to taste. Milk may be substi- tuted for water. 784 LOCAL REMEDIES. GLYCYRRHIZA. U. S. Licorice Root is the root of Glycyrrhiza glabra and glandulifera, native herbs of Southern Europe. It occurs in long, cylindrical pieces, from a few lines to more than an inch in diam- eter, brownish externally and yellowish within. Its fracture is fibrous, its taste sweet and mucilaginous, its odor none. Its active principle is Glycyrrhizin. This is a sweet, neutral substance, differing from the sugars in not being converted by nitric acid into oxalic acid, and by its inability to undergo the vinous fermentation. Licorice root is very largely used as a demulcent in pectoral complaints, and, on account of its pleasant taste, as a means of disguising or of flavoring medicines. In the form of glycyrrhizin it is said to conceal almost entirely the bitter taste of quinine and similar substances. It is used almost exclusively in the form of the extract (ExTRACTUM GLYCYRRHIZA, U. S. ), known as Licorice. The MISTURA GLYCYRRHIZ^E COMPOSITA, U. S. , or Brown Mixture, contains paregoric, antimonial wine, and sweet spirit of nitre, and is much used as a domestic remedy in colds and the early stages of mild bronchitis. The dose for an adult is half a fluidounce to a fluidounce (15-30 C.c. ) every three hours ; for a child three years old, a teaspoon- ful (3.7 C.c. ). The pure extract (EXTRACTUM GLYCYRRHIZA PURUM, U. S. ) and the fluid extract (FLUIDEXTRACTUM GLYCYRRHIZA, U. S.) are excellent preparations. GLYCYRRHIZINUM AMMONIATUM, U. S., is an elegant demulcent preparation which, however, is incompatible with acid or alkaline solutions : its dose is from five to ten grains (0.3-0.6 Gm). The compound licorice powder (PULVIS GLYCYRRHIZA COM- POSITUS, U. S. ) contains senna and washed sulphur. It is an elegant laxative, acting usually mildly and without the production of pain, in doses of one to two teaspoonfuls (4-8 Gm. ). ELIXIR ADJUVANS, U. S. Adjuvant Elixir contains twelve parts of fluid extract of licorice to eighty- eight of Elixir Aromaticum. It affords an excellent aromatic and slightly demulcent vehicle for extemporaneous prescriptions. LINUM, U. S. , or Flax-seed, is the seed of Linum usitatissimum, or common flax, and contains large quantities of mucilage and of oil ; its infusion, Flax-seed tea, is much used internally. It is often made with boiling water ; but the application of too much heat causes the extraction of the oil, and renders the preparation less palatable. The addition of lemon and sugar makes it more palatable. It may be drunk ad libitum in pectoral catarrhs, in enteritis and dysentery, and in irritation of the kidneys or the urinary passages. AMYLUM. U. S. Starch. Obtained from Indian corn, a white, inodorous, tasteless powder, composed of microscopic granules, is phys- iologically inert except as a food. It is often used as a dusting powder in irritant conditions of the skin ; as a soothing demulcent in the preparation of opiates and other rectal injections, and pharmaceutically for the purpose of thickening or gelatinizing ointments, and the making of paste for use DEMULCENTS. 785 in skin diseases. GLYCERITUM AMYLI, U. S. Glycerite of starch is a translucent jelly, containing ten per cent, of starch, eighty per cent, of glycerin, ten per cent, of water, affording a useful vehicle. MEDULLA SASSAFRAS, or Sassafras Pith, yields a delicate mucilage much used in eye diseases (MUCILAGO SASSAFRAS MEDULLA, U. S). ALTHAEA. U. S. The roots of Althaea officinalis yield a bland muci- lage ; their decoction is sometimes given in gastric irritation, and their syrup SYRUPUS AL.THJEJE, U. S. 1890) is used as a vehicle. CETRARIA. Iceland Moss is the fronds of a lichen, Cetraria islandica, growing on rocks in Iceland and in most of the northern portions of the world. It is said to be abundant in the mountains of New England. The foliaceous, dry, shining, lobed, and laciniated fronds are about four inches long, of various intermixed colors, gray, brown, and red, and of a mucilaginous, bitter taste. Iceland moss contains a peculiar lichen starch and a bitter principle. It yields to cold water its bitterness ; to boiling water all of its virtues. Cetrarin, or Cetraric Acid, is the bitter principle, which may be obtained as a snow-white mass of interlaced acicu- lar crystals. It unites with alkalies to form salts. With it in the lichen is asso- ciated in small quantities lichenstearic acid. Robert has found that cetrarin has no effect upon the arterial pressure ; also that in toxic dose it produces violent con- vulsions in the cat and in the dog, whilst in small dose it distinctly increases the activity of the motor area of the brain and spinal cord. Robert ' also asserts that in healthy men cetrarin increases the number of the red and, in a still greater degree, of the white corpuscles ; and believes that in chlorosis and an&mia, espe- cially when there is constipation, cetrarin will prove a valuable remedy. Lichenin, or Lichen Starch, the mucilaginous, nutritive principle of Iceland moss, differs from ordinary starch in not being deposited in granules within the cells, but in layers or irregular masses between the cells, or indeed forming the walls of the cells (De Bary*) . In cold water it swells up without dissolving ; in hot water it dissolves, and on cooling condenses into a jelly. With iodine it strikes a yellow, green, or sometimes rather faint blue, color. It is found in very many lichens ; also in many species of sea-weed, notably in the so-called Corsican moss. Iceland moss has enjoyed some reputation as a demulcent in pectoral com- plaints. From its bitter principle, it is somewhat tonic, and its lichenin is probably about equal to ordinary starch as a nutrient. When prepared as an article of diet, in the form of jelly, the bitter taste should be removed by soaking for some hours in a very weak, cold alkaline solution, and afterwards for a little while in cold water. HORDEUM. The decorticated seeds of the common barley constitute the pearl barley of commerce. They contain starch and mucilage, and the decoction was formerly official. Barley water is used as a nutritious, demulcent drink in fevers and inflammatory conditions, especially when the gastric mucous membrane is involved. The U. S. Pharmacopoeia of 1870 directed that it should be prepared as follows: "Take of barley two troyounces ; water a sufficient quantity. Having washed away the extraneous matters which adhere to the barley, boil it with half a pint of water for a short time and throw away the resulting liquid. Then, having poured on it four pints of boiling water, boil down to two pints, and strain." REFERENCES. DEMULCENTS. a. DE BARY Hofmeister's Handb. d. ,. ROBERT Verhand.d. Internal. Med. Physiol. Botan.. ii. 55- Cong., Berlin, 1890. 50 FAMILY XII. EMOLLIENTS. TRUE emollients are perfectly bland, fatty substances, which, when applied to the skin, soften it and render it more pliable. The action of these remedies is largely mechanical, and they probably soften the derm in precisely the same way as they affect a raw hide or a piece of leather. They are therefore especially useful when the skin has a tendency to crack or to chap. Whenever surfaces become sore by attrition, or, in other words, chafe, emollients are also useful mechanically. They often afford relief in simple inflammations of the skin under such circum- stances that their action cannot be explained as purely mechanical : indeed, they seem to exert a dynamic influence upon the nutrition of the parts concerned. It may be that they shut out or interfere with the de- velopment of pathogenetic germs, or, in other words, that they are mechanical antiseptics. Be these things as they may, clinical experience has demonstrated that fatty matters are of very great value in the treat- ment of superficial inflammations. The blandest fat, when it becomes rancid, is very irritating, and will do more harm than good, so that the strictest attention must be paid to the condition of the fatty material employed. Any perfectly bland oily substance may be used as an emol- lient. There does not appear to be any marked difference in the power of true fats in penetrating the skin, excepting in so far that a hard fat does not readily melt at the temperature of the body, and therefore does not yield itself to absorption so readily as does a soft one. SEVUM, U. S. Suet. Mutton Suet. The fat obtained from the abdomen of the ordinary sheep is a white, solid, bland fat, not melting below 45 C. (113 F.), and is therefore a hard fat, which is used chiefly for the purpose of render- ing more firm various ointments. ADEPS, U. S. Lard. This is a soft fat, melting at about 38 C. (100 F. ). Ordinary lard of the market contains salt, from which it must be freed by washing before it is used for medical purposes. ADEPS BENZOINATUS, U. S. , is lard impregnated with two per cent, of benzoin, which acts as a preservative and has no delete- rious influence whatever upon the skin or the mucous membranes. Spermaceti (CETACEUM, U. S. ) is employed to give consistence to oint- ments, as is also wax (CERA ALBA, or White Wax, and CERA FLAVA, or Yellow Wax, U. S. ). Cold Cream (UNGUENTUM AQU^E ROSJE, U. S. ), containing oil of sweet almonds, spermaceti, white wax, and rose water, is one of the most elegant of the official emollients. 786 EMOLLIENTS. 787 OLEUM AMYGDALAE EXPRESSUM. U. S. Oil of Sweet Almond, ob- tained from ordinary sweet almonds, Amygdala Dulcis, is a pale, straw- colored or colorless, almost inodorous oil, having a mild, nutty flavor. The oil of sweet almond is one of the most delicate of the fixed oils, and may be used for making elegant emollient applications for the skin. OLEUM THEOBROMATIS. U. S. Cacao Butter. A whitish, solid, very bland vegetable fat, which melts at or about 30 C. (86 F. ), and consequently lends itself to the formation of suppositories, which are firm outside the body, but when placed inside the body melt freely. OLEUM LINI, U. S. , or Linseed Oil, is a yellowish oily liquid, with a peculiar odor and a bland taste. When exposed to the air it thickens and acquires a strong odor and taste. It is the least elegant of these oils, and is not often used in medicine, except when in fecal accumula- tions or other conditions large rectal injections of oil are required, when it is preferred on account of its cheapness. OLEUM OLIV^E, U. S. , or Olive Oil, is expressed from the fruit of the European olive ; has a pale yellow or light greenish-yellow color, and a pleasant odor and taste. It is the ordinary salad oil of the table, and may be used wherever a very bland oil is desired. It has, however, no superiority for ordinary purposes over the OLEUM GOSSYPII SEMINIS, U. S. , or Cotton-seed Oil, which is expressed from the seeds of the ordi- nary cotton-plant ; indeed, a very large proportion of the olive oil of commerce is cotton-seed oil ; it is credibly affirmed that more cotton- seed oil is exported from New Orleans to the Mediterranean cities than olive oil is exported from those ports, much of the cotton-seed oil coming back with olive oil labels. There seems to be no sufficient reason for believing that olive oil differs from cotton-seed oil in its physiological or therapeutic properties. These oils are sometimes used internally with advantage, for nutritive purposes, and are also very mildly laxative. The assertion, originally made by Kennedy, that large doses of olive oil are very useful against biliary calculi, has received strong clinical con- firmation. S. Rosenberg 1 found that in dogs with biliary fistulae olive oil not only increased the amount of bile, but also rendered the bile much more liquid. Since fats are absorbed chiefly, if not entirely, through the thoracic duct, it would appear that the oil must pass through the pulmonary circulation before reaching the liver. This is confirmed by the experiments of Chauffard, who could not find in the bile-duct or gall-bladder any trace of oil which he had injected into the stomach of the dog. If olive oil has the asserted remedial influence, it probably acts reflexly through the nervous system, through a mechanism provided by nature for the purpose of aiding in the digestion of fats when in excess. The dose of the oil should be not less than from five to seven ounces (150-215 C.c. ) taken in four to eight portions in not longer than three hours. It may be given in aromatized emulsion, with a little brandy or whiskey if desired. The U. S. Pharmacopoeia recognizes two fatty acids, namely, ACIDUM 788 LOCAL REMEDIES. OLEICUM, U. S. Oleic Acid is a yellowish or brownish oily liquid, having peculiar oil-like odor and taste, which is used in medicine solely for the preparation of the oleates. In the making of an ordinary ointment with a metallic basis an oleate is formed, and various practitioners prefer the chemically pure oleate as more certain and definite in its action. In our own experience, however, these preparations have not seemed to have any practical superiority over the older ointments. The second fatty acid, Stearic Acid (AciDUM STEARICUM, U. S. ), is a hard, white, glossy solid, odorless and tasteless, melting at 69.2 C. (156.6 F. ) It is used in the form of stearates. ADEPS LAN^E. U. S. Wool fat is obtained from the wool of sheep, which is said to contain, on an average, forty-five per cent, of it. It appears to be practically the same as the natural oil of the hair in man and other animals.* ADEPS LAN^E HYDROSUS, U. S. , or Lanolin, con- tains about thirty per cent, of water, and is the form of the unguent ordi- narily employed. It was first recommended by Oscar Liebreich as a basis for ointments or preparations to be applied to the surface of the skin. It is entirely free from irritant properties, has the power of taking up a large amount of water without losing its unctuousness and does not easily become rancid; it has been asserted that it is absorbed through the skin much more readily than are other fats. In the experiments of Patschkowsky, 2 half an hour after inunction with lanolin and potassium iodide the iodine was recognized from the urine, while official potassium iodide ointment yielded negative results. This has been confirmed by Kaspar, 3 but Ritter and Pfeiffer obtained contrary results, and in a con- siderable series of experiments were unable to perceive that lanolin had any superiority over other fats in promoting absorption. The facts, moreover, that lanolin is largely the secretion of sebaceous follicles, con- tains an abundance of cholesterin, and is in the nature of a waste product which is intended, not for absorption, but for the keeping soft of the skin and its appendages, indicate very strongly that it will yield itself, and medicinal substances with which it may be impregnated, less readily to absorption than do other fats. As a basis of ointments used to medicate the skin it is most effective, but when absorption is desired it is probably inferior as a vehicle to ordinary fats. GLYCERINUM GLYCERIN. U. S. This is a thick, syrupy liquid, colorless, free from odor, and of a sweet taste. Chemically speaking, it is propenyl alcohol. It is always set free during the process of saponification, and formerly was a by- product in the manufacture of soaps. At present it is made by the direct decomposition of fats by superheated steam. Under certain circumstances, not well understood, glycerin forms hard, brilliant crystals. In its usual liquid form it mixes in all propor- * See Virchow's Archiv, 1890, cxxi. EMOLLIENTS. 789 tions with water and alcohol, and itself dissolves iodine, bromine, the alkalies, tannic and other vegetable acids, a large number of neutral salts, salicin, and other organic principles. It throws, however, most alkaloidal salts out of their watery solution. Glycerin does not evaporate upon exposure, but is very hygroscopic, and absorbs water from the air. When pure, it is incapable of becoming rancid or of fermenting spontaneously. The acrid glycerin owes its irri- tant properties to impurities, especially to oxalic and formic acids; cheap grades of glycerin are frequently contaminated with arsenic. PHYSIOLOGICAL ACTION. When large doses of glycerin (in the dog eight or more parts per thousand by weight) are injected subcutaneously, death is produced in a period varying, according to the dose, from one hour to several days. The symptoms are loss of muscular strength, lethargy, bloody urine, vomiting, dryness of the mucous membrane, with marked thirst, fall of temperature, gradual extinction of both respiration and circulation, and finally convulsions and coma (Dujardin-Beaumetz and Audije"*). The convulsions occur earlier and are more severe when large doses are employed, and are then said to be tetanic, and to be accompanied by a decided rise of temperature. The fall of temperature is, even in the milder cases, present only late in the poisoning, and is sometimes, if not always, preceded by a rise. After death intense conges- tion, with more or less softening of the tissue, is found in the lungs, kid- neys, and intestines. So far as we know, the largest amounts of glycerin taken by the stomach in man have produced no other symptoms than those of mild gastro-intestinal irritation ; but Schellenberg 5 has reported a long series of cases in which serious, and in one instance fatal, poison- ing followed the injection of glycerin containing iodoform, for coxitis and other diseases. The conclusion of Schellenberg, that the manifesta- tions were due to the glycerin, is confirmed by the fact that they were those seen in the lower animals poisoned by injections of glycerin, namely, loss of muscular strength, elevation of temperature, rapid pulse, albuminous bloody urine with tube-casts, and in the fatal case the lesion of acute parenchymatous nephritis. Catillon * asserts that glycerin administered in small continuous doses exerts a decided effect upon nutritioYi, but the general drift of the present evidence is to show that glycerin has no distinct effect upon tissue-changes. In Catillon' s experiments, eight grains given daily to guinea-pigs caused a very marked gain in weight, with a lessened excretion of urea. In man an ounce daily also produced a decided diminution in the elimination of urea, which was not increased by increasing the doses of glycerin. The appetite in many cases was, after a little time, much improved, and then the increased ingestion of food pro- duced an increased elimination of urea. The fact that an increase of food was per- mitted in these experiments shows, however, that the conditions of experimentation were not rigid enough to allow much weight to be attached to the result ; and the relation of glycerin to the elimination of urea has been investigated by L. Lewin, 7 by N. Tschirwinsky, 8 and by I. Munk,' with somewhat contradictory results. Of these experiments the most extensive are those of Munk, who seems to have used 790 LOCAL REMEDIES. all proper precautions, and who found that glycerin has no effect upon the elimina- tion of urea or upon the general bodily nutrition. The results reached by Lewin correspond with those of Munk. Tschirwinsky omitted fatty materials from the food, and found that while at first the elimination of urea was diminished, it after- wards, under the use of very large doses of glycerin, was increased. Glycerin is absorbed from the alimentary canal, and when freely ad- ministered is in part eliminated and in part burnt up in the system. Both Ustimowitsch 10 and P16sz " found a substance in the urine which they believe to be a derivative product of glycerin, while Catillon proved that it is not eliminated by the skin or, even when it purges, by the intestines. Catillon and Lewin recovered from the urine only a small proportion of that ingested, Tschir- winsky only 8.7 per cent., while Ludwig Arnschink 12 found that not more than thirty per cent, escapes from the body. Since a large proportion of ingested glycerin is oxidized in the body, it would appear that it is capable of replacing to some extent true fatty carbohydrates for the production of heat or energy, and, therefore, has food value. According to the calculations of Arnschink, two hun- dred and nineteen parts of it are equivalent to about one hundred parts of fat. This view is corroborated by the work of Scheremetjewsky, who found in rabbits that the intravenous injection of glycerin was followed by an immediate increase of the consumption of oxygen, and of the giving up of carbonic acid. The work of Scheremetjewsky has given rise to considerable contro- versy, but the latest experiments, those of I. Munk, seem to lead to the conclusion that glycerin is capable of taking the place of the bodily fat.* According to Fuchsinger, IS the bloody urine produced by poisonous doses of glycerin contains an abundance of the coloring- matter of the blood, but no free corpuscles. Very interesting in connection with the use of glycerin in diabetes is the assertion of Fuchsinger, 1 * that in rab- bits slightly poisoned with glycerin no sugar appears in the urine after the ' ' diabetic puncture. ' ' The experiments of Eckhard 15 gave, however, a contrary result, and Catillon affirms that given in very large continuous doses glycerin increases the amount of sugar in the blood. THERAPEUTICS. Locally applied, glycerin is usually unirritating, and it is much employed as an emollient. The chief disadvantage that attends its use is its stickiness ; on the other hand, its non-volatility and its hygroscopic properties give a persistency to its action which is often very advantageous. It enters largely into the composition of popular emollient ointments, or "creams," as they are called, and is often used itself for chapped hands, excoriations, and similar troubles. It is also employed by dermatologists to some extent in chronic eczema ; in seborrhcea, whether affecting the hairy scalp or other parts, it is as- serted to be especially useful, softening the masses of secretion, and, used in conjunction with such remedies as borax, zinc, and lead acetate, diminishing the amount of secretion. When there is a want of seba- ceous secretion, it is said also to act efficiently ; in scabies, pruritus, * For discussion, see Archivf. d. Ges. Phys., 1889-90, xlvi. EMOLLIENTS. 791 and even psoriasis, glycerin is used, diluted with water, as a vehicle for more active remedies. Upon the mucous membranes glycerin acts very much as it does upon the skin, and diluted with water is very useful in coryza, and even, by enemata, in dysentery ; in croup or laryngitis it may with advantage be applied freely by means of a large camel' s-hair brush to the orifice of the larynx, so as to run into the latter. In laxative doses it is asserted to be very effective in hemorrhoids. It also forms an excellent basis for mouth-washes ; or a paste may be made with it and borax, or similar substance, for use in ulcerations of the same cavity. The list of diseases in which this remedy is employed might be very much lengthened ; but the examples already given are sufficient to indi- cate the range of its application as an emollient and as a vehicle. There are certain persons upon whose skin and mucous membranes even the purest glycerin seems to act as an irritant. This influence is most intense when the glycerin is nearly or entirely free from water. It is, however, discernible even when the remedy is much diluted, and often inhibits its use. The existence of this idiosyncrasy to glycerin can be determined only by trial. When administered internally in doses of one or two ounces, glycerin acts as a gentle but very uncertain laxative. It was proposed many years ago as a substitute for cod-liver oil in cachectic diseases, but has failed to come into use. It has also been highly commended in diabetes* but is of no service. It is valuable as a harmless substance which has the power of disguising nauseous medicines. In this way it may be em- ployed with castor oil, in emulsions of turpentine, in solutions of iron, and in various mixtures. It seems, as it were, to envelop the medicinal substances and prevent their acting on the palate. Plasma or Glycerite of Starch (GLYCERITUM AMYLI, U.S.) is often used as a protective; Glycerite of Yolk of Egg (GLYCERITUM VITELLI, U. S., 1890) is no longer official in making emulsions. BENZOSULPHINIDUM. U. S. GLUSIDUM. Br. SACCHARIN.f Saccharin is a substance discovered by Fahlberg in 1879. Chemi- cally it is an imide derived from the toluene of coal-tar. It occurs as a white powder composed of irregular crystals, very slightly soluble in water, readily soluble in glycerin, alcohol, and ether. Its watery solu- tion has a distinctly acid reaction, and it forms salts. Its most remarkable property is its sweet taste, which is said to be three hundred times more intense than is that of sugar, so that if one grain of it be dissolved and neutralized in about ten pints of water its presence can still be recognized. Taken internally, saccharin is rapidly absorbed; it is eliminated unchanged * For literature and discussion of point, see Ztemssen's Encyclopedia, xvi. f The present is probably as good as any other place in this treatise to notice a sub- stance whose use in practical medicine depends upon its lack of medicinal properties. On account of its being a proprietary or patented drug it is not recognized by the U. S. Pharmacopoeia. 792 LOCAL REMEDIES. chiefly through the kidneys, Bruylants 16 having recovered about eighty per cent, of it from the urine. It has been found by Bruylants in the milk of a nursing woman, and by Hedley abundantly in the saliva. Its influence upon man and animals is very slight ; Mosso and Aducco administered seventy-five grains to a man without sensible effect, and found that frogs will live for months in a solution rendered neutral with soda ; also, that six hundred grains given to a dog during ten days caused no change in the daily renal excretion of water, urea, hippuric acid, sulphuric acid, or phosphoric acid, and no alteration of the weight or of the general health. On the other hand, it appears to have a feeble influence upon various fermentations. Its solution has antiseptic prop- erties, and in Plugge's numerous experiments it checked the action of ptyalin, pepsin, trypsin, and other allied ferments. Sawitzki, indeed, alleges that it depresses proteid metabolism. | In Bruylants' s trials it failed to check artificial gastric digestion, probably on account of the acidity of the solution, but as little as one per cent, is enough distinctly to lessen the activity of pancreatin solutions. The general innocuousness of saccharin is, in accord with our own experience, asserted by Salkowski," by Bruylants, by Dreschfeld, 18 by Levenstein, 19 and by other clinicians. Mixed with sodium bicarbonate, two parts to three, saccharin becomes soluble. Its chief value in practical medicine is as a substitute for sugar in diabetes, obesity, and other diseases in which sugar is contra-indicated, but the observation of James Little, 20 that when freely given it is of great antiseptic value in the treatment of ammoniacal urine, from cystic, phosphatic, or other diseases producing retention or fermentation, is probably correct. It may be used freely as an article of diet, in the form of a solution in glycerin ; for medical purposes it is sometimes adminis- tered in compressed pills : dose, five grains (0.3 Gm. ). PETROLATUM. The solid basis of petroleum is paraffin, and after the distillation of the more volatile portions of the petroleum there are left mixtures sold as vaseline, cosmoline, etc., whose consistency varies in proportion to the amount of the liquid hydrocarbon left in them. Such substances are PARAFFINUM, U. S. , a solid, colorless mass; PETROLA- TUM, U. S., popularly called vaseline, a yellowish to whitish amber oint- ment-like mass; PETROLATUM ALBUM, U. S. , a white unctuous mass; PETROLATUM LIQUIDUM, U. S. , a colorless or yellowish liquid. All the cosmolines are insoluble in water, do not become rancid, are free from irritating properties, and act mechanically on the skin like fats. They are used as local emollient applications to the skin and mucous mem- branes and as a basis for ointments. When taken internally in the dose of a drachm to an ounce they exert no influence upon the system, but act locally upon the mucous membrane of the alimentary canal, allaying irri- tation and provoking soft fecal discharges. * See Sajous's Annual, 1891. EMOLLIENTS. 793 KAOLIN. U. S. Porcelain Clay. Fuller' s Earth. A white pow- dery clay, unctuous when moist, a hydrated aluminum silicate. It is largely used in the arts for the purpose of clarifying and decolorizing oils and other fluids. It is a non-irritant, inert substance, which is well fitted for thickening ointment or paste. It enters into the official Cataplasma Kaolini, U. S. Cataplasm of kaolin, a thick, paste-like substance con- taining in round numbers fifty-two per cent, of kaolin, 4.5 per cent, of boric acid, one-tenth of one per cent, of thymol, and one-twentieth of one per cent, of methyl-salicylate and oil of peppermint each, held to- gether with glycerin. A vast amount of nonsensical rubbish has been written and believed of the virtues of this paste. It possesses however no virtues that do not belong to the flaxseed poultice and is probably even less efficient. POULTICES. Poultices are moist, soft, scarcely adhesive, perfectly bland plasters, used to a very great extent to combat superficial inflam- mation. Poultices are much more powerful agents than are the true fatty emollients, and are correspondingly more capable of being abused : the results of such abuse will be spoken of directly. A poultice may, of course, be stimulating and irritant if made of such a substance as mus- tard ; but the ordinary emollient or true poultice is prepared out of some bland material which is totally free from action upon the skin, and de- pends for its remedial power solely upon the warmth and the water which it contains. Water, when pure and of a temperature approximating that of the body, is a sedative, checking all action, possibly by a direct in- fluence, but probably by the merely mechanical acts of dilution of the pabulum and of separation of the germinal granules. It is also a relax- ant, rendering all tissues soaked in it soft and yielding. Poultices are sometimes applied in the early stages of phlegmonous and other superficial inflammations, for the purpose of checking the morbid action. Their influence is in such case simply one of sedation, and they are certainly not so efficient as the cold-water dressing. They are, however, especially useful in the advanced stages of inflammation, when suppuration has already commenced or is about to set in. Clini- cal experience has demonstrated that they then favor the formation of pus. Further, the poultice in the latter stages of a superficial phleg- mon not only hastens the formation of pus in the inflammatory focus, but lessens irritation in the outlying parts by its sedative action, and so softens the tissues as to aid in the passage outward and the discharge of the inflammatory products. When poulticing is too long persisted in, the part becomes pale or white, swollen, relaxed, and has a sodden look ; the granulations of the ulcer or abscess are large, pale, and very flabby, and all the vital actions are below the normal point. It is pos- sible that even death of a part might be brought about by continuous poulticing. Be this as it may, after the discharge of pus, whenever the parts put on the aspect just spoken of, the poultice should be re- moved and stimulating applications substituted. 794 LOCAL REMEDIES. Any material which is in itself physiologically inert, and will long retain water, may be used as the basis of the poultice. Flaxseed meal is cheap, and is probably the most used of any substance. Ground slip- pery elm makes a very elegant mucilaginous poultice. Ordinary Indian- meal mush is often used. The bread and milk poultice is non-irritating, but is prone to undergo putrefaction. The poultice is rarely aseptic, and is often a carrier of germs. This in a measure may be prevented by boiling the poultice just before putting it on ; but even with this pre- caution, when applied to an infected wound, poultices, by retaining and stimulating the growth of germs, often increase the inflammation. For this reason other methods of applying warmth and water have largely replaced the old-fashioned poultice. Spongiopiline, or absorbent cotton, or similar material, which is readily rendered aseptic, and is incapable of undergoing fermentation, when saturated with heat and water affords an application which is practically a poultice, and which may be rendered germicidal by the addition of minute quantities of corrosive sublimate or similar substances, as called for by the exigencies of the case. Poultices are frequently used in the treatment of deep-seated inflam- mations. Under these circumstances, according to the dictates of ex- perience, they should be applied very hot, and be frequently renewed ; very often, too, a small amount of mustard or of some similar stimulating material is added to them with advantage. As a result, these poultices act as gentle but deep-reaching counter-irritants, which in all likelihood affect not merely the blood-vessels ot the skin, but also those of the subdermal tissue. When it is borne in mind that in all these cases the poultice is applied to a very large surface, it will readily be perceived that this counter-irritation is a powerful one. Thus, in pleurisy or in pneumonia the whole anterior or posterior surface of the chest is covered, or perhaps the whole chest is enveloped, by the jacket-poultice. In peritonitis the poultice should be as large as the abdomen of the patient. In either of these cases the amount of blood drawn to the surface must be considerable. It is probable that the water of the poultice in some cases actually soaks through and exerts its direct sedative influence upon the affected tissue. The value of poultices in lung diseases is much greater in children, whose chest-walls are very thin, than in adults ; and it is not illogical to believe that the difference may be dependent upon the inequality of the chest-walls. The jacket-poultice should be made of thin flannel formed into a sort of double bag, so cut and shaped as to fit the individual, and secured in front with safety-pins and over the shoulders with tapes, or it may be fastened directly to an undershirt, a piece of oiled silk always being placed directly outside of the jacket. The jacket should be divided into two parts by a horizontal line of stitching, and be filled from one end. In order to prevent sagging of the contents, it is well, after filling, to take a stitch here and there, in the manner of quilting. The effect of a jacket- poultice may be imperfectly attained by covering the patient with wool batting and oiled silk outside of this, in fever patients the moisture from the surface and the heat of the body serving to form a kind of fomentation. EMOLLIENTS. 795 The value of the jacket-poultice in disease is, however, greatly lessened by the fact that it enormously increases the heat-retention of the body, and has, therefore, in many cases a very serious influence in heightening a fever temperature whose reduction is urgently indicated. Whenever, in a pneumonia, the temperature is high, the application of cold water by means of compresses, or absorbent cotton, is preferable to the use of the jacket-poultice. In cases of peritonitis the sensations of the patient are often a practical guide to the choice of the dressing. If the pain is aggravated by external warmth, the cold-water dressing is preferable ; whilst, if the cold-water dressing is steadily obnoxious to the patient, the best results may usually be achieved by the use of hot water. EMOLLIENTS. REFERENCES. 12. ARNSCHINK 1. ROSENBERG . . . S. Jb., 1890. 2. PATSCHKOWSKY . Pharm. Zeit., 1885. 3. KASPAR D. M. W., Dec. 1885. 4. DUJARDIN-BEAUMETZ and AUDIJ . B. G. T., xci. 62. 5. SCHELLENBERG . A. K. C., 1894, xllX. 6. CATILLON . . . . B. G. T., xcii. 130; A. de P.. 1877- 7. LEWIN Z. B., xv. 8. TSCHIRWINSKY . Z. B., xv. 9. MUNK ..... V. A. P. A., Ixxvi. 130. 10. USTIMOWITSCH . A. G. P., xiii. 453. 11. PL6sz A. G. P., xvi. 153. 13. FUCHSINGER . 14. FUCHSINGER . 15. ECKHARD . . 16. BRUYUANTS . 17. SALKOWSKI . 18. DRESCHFELD 19. LEVENSTEIN 20. LITTLE . . . . Sitzungsb. Gesellsch. Mor- phol. Physiol., Miinchen, 1886, ii.; Z. B., xxiii. 4I3- . A. G. P., xi. 502. . A. G. P., xii. 501; C. M. W., 1877. . C. M. W.. 1876, 273. . B. A. R. B., 1888. . V. A. P. A., cv. 46. . Birmingham Med. Journ.. 1886, 409. . Journ. Soc. of Chem.. 1886. . Trans. Royal Acad. of Med., Ireland, 1888, vi. FAMILY XIIL PROTECTIVES. IN the present class are included those materials used by the physi- cian as protective applications to the skin. Adhesive plaster (EMPLASTRUM ADH^ESIVUM, U. S. ) is used for me- chanical purposes. It, however, irritates the skin somewhat, and con- sequently is rarely employed where protection is the only object. Under the latter circumstances, the lead plaster (EMPLASTRUM PLUMBI, U. S. ) or the soap plaster (EMPLASTRUM SAPONIS, U. S. ) is preferable. These substances are free from irritant properties, but are only slightly adhesive, and are scarcely used except to protect the skin from pressure or friction, as when bed-sores are threatened. They should be spread upon very soft kid. It is important that they be not so thick or hard as to lose their pliability. If they are stiff, by their movements during the motions of the body they may do much harm. Isinglass Plaster is readily applied when simply dampened, and is much used domestically under the name of court plaster. Collodion (COLLODIUM), U. S. ) is a solution of pyrox- ylin in alcohol and ether, pyroxylin (PYROXYLINUM, U. S. ) being soluble gun-cotton, chiefly made up of the tri- and tetra-nitro-cellulose ; upon evaporation collodion leaves on the skin an adherent protecting film. Physiologically, gun-cotton is inert. Collodion is a colorless, slightly opalescent liquid, of a syrupy consistence, and smelling strongly of ether. By long standing it deposits a layer of fibrous matter, and becomes more transparent. This layer should be reincorporated, by agitation, before the collodion is used. When it is applied to the skin, and the menstrua are allowed to evaporate, collodion forms an impervious, colorless, transparent, flexible, and strongly contractile film, which ad- heres very closely, and cannot readily be removed. The contractility of the film may in a great measure be destroyed by the addition to the col- lodion of certain substances, as in flexible collodion ( COLLODIUM FLEX- ILE, U. S. ), which contains five per cent, of Canada turpentine and three per cent, of castor oil, and on evaporation leaves a film which does not contract. A collodion may be rendered actively medical by the addition of some principle soluble in its menstruum, as in cantharidal collodion. As a substitute for collodion the non-official solution of gutta-percha in chloroform ( LIQUOR GUTTA-PERCHA) is sometimes employed. 796 DIVISION II. EXTRANEOUS REMEDIES. THESE are drugs which are employed not to act directly upon the human system or upon any of its tissues, but upon some extraneous material or entity either in the cavities of the body or upon its exterior. Thus, an antacid neutralizes acid in the stomach, or an anthelmintic kills the tapeworm in the intestines, or a disinfectant destroys poisonous emanations in the exterior world and thereby wards off disease. FAMILY I. ANTACIDS. ANTACIDS are, strictly speaking, substances which are capable of neutralizing acid. The class, as here defined, contains those remedies which in medicine are used for the purpose of neutralizing an excess of acidity in the primae viae. They are almost solely employed in forms of dyspepsia. Without doubt, cardialgia, gastric uneasiness, heartburn, and the rising of sour water in the mouth are often the result of too much acid in the stomach, perhaps secreted by a perverted glandular action, but more probably in the great majority of cases formed by fer- mentative changes in the partially digested food. As excessive acidity of the stomach causes gastric uneasiness and derangement, so will a similar condition of the intestinal canal cause pain and spasm and func- tional disturbance in the bowels. This is seen most frequently in infants, and is very often associated with a diarrhoea in which the passages have a green color, similar to that of spinach, and hence are sometimes spoken of as "spinach-stools." In diarrhoea of this character, as well as in colic, antacids are often of service by neutralizing the acid in the intes- tinal canal. Clinical experience has demonstrated that dyspepsia is often perma- nently relieved by the use of alkalies when they are given steadily day after day, about twenty minutes after eating, for a long time. Accord- ing to Thomas K. Chambers, 1 this is dependent upon an effect pointed out by Claude Bernard, the augmentation of the acid gastric juice, and so of the normal peptic powers of the stomach. The same authority further says, ' ' The test of benefit being derived from an alkali is the dose not requiring to be increased as the patient goes on taking it, but, 797 79 8 EXTRANEOUS REMEDIES. on the contrary, being diminished gradually, while relief from the recur- rence of heartburn continues still to be experienced." Sick headache is sometimes dependent upon gastric irritation pro- duced by an excess of acid in the stomach. This true sick headache is generally to be distinguished from migraine by the early occurrence of the stomach symptoms, either as heartburn, nausea, vomiting, or simple gastric distress, and by the fact that the pain comes on with an attack of blindness or of dizziness, and is not limited to any one spot, as the supra- orbital or other neuralgic foci, but is felt all across the brows. In this form of cephalalgia antacids often afford prompt relief. Various substances which have already been discussed in this work are excellent antacids, most of them uniting this to other medicinal prop- erties. Thus, when a stimulating antacid is desired, as is very often the case in sick headache, half a drachm of the aromatic spirit of harts- horn may be taken, well diluted with water. Again, when a laxative antacid is needed, a teaspoonful to a tablespoonful of magnesia may be exhibited. Potassa and its carbonates have already been dwelt upon with sufficient detail. They may be used as antacids ; but, as they exert other powerful influences upon the system, they are, we think, not so generally useful as the soda preparations. SODIUM. Pure soda is an escharotic, and most of its salts are irritant. It is absorbed and eliminated freely.* Soda being the only alkali of the blood, even very large doses of it have very little influence upon man or mammalia, but it is probable that it acts much more powerfully on cold-blooded animals. Grandeau 3 found that one hundred and seven grains of sodium carbonate in- jected into the vein of a dog produced only very slight symptoms, and that thirty- five grains of the nitrate similarly administered to a rabbit caused only some con- vulsive movements. According to Guttmann, 4 however, the sodium salts thrown directly into the blood in very large amounts will slowly cause death, the agony being very prolonged, and, when the chloride is used, convulsions being developed. Both Podocaepow and Guttmann assert that even the largest doses do not sensibly affect the heart or the temperature ; and the latter observer further declares that they are without influence upon the nerve-centres, the peripheral nerves, or the muscles. But if this be the case, it is difficult to perceive how they can cause death ; and the earlier experiments of Podocaepow indicate that they do exert a very feeble action upon the peripheral nerves or the muscles. Curci 5 also finds that the sodium salts increase the blood-pressure after the destruction of the oblongata, and believes that they influence the peripheral vaso-motor nerves. H. G. Beyer, 8 as the result of experiments made upon terrapins, comes to the conclusion that sodium salts excite first the ganglia of the vaso-dilator nerves and afterwards those of the vaso-motor nerves. * As Rabuteau 2 found that in dogs with gastric fistula both the quantity and the acidity of the gastric juice are decidedly increased by the use of salt meat, it would appear probable that the local action of common salt upon the stomach is that of a stimulant. ANTACIDS. 799 Although Mayet ' affirms that sodium chloride increases the elasticity of the red blood- corpuscles, the immediate influence of the sodium salts upon the blood * is probably very slight, since, according to Podocaepow, 8 one part dissolved in twelve parts of blood does not affect either the physical characters of the red corpuscles or the intensity of the ozone reaction. Podocaepow and Schonlein 9 both affirm that they cause in the frog spinal con- vulsions, but in Ringer and H. Sainsbury's 10 experiments the influence of the sodium salts upon the frog was found to be so slight that they could hardly be made to kill. It seems established, however, that they will produce cataracts in the frog.f Most observers state that the sodium salts are capable of arresting the frog's heart in diastole, either when it is in position or after it is removed from the body ; and Laffout" states that there Is a primary period of cardiac stimulation, which is in accordance with the observation of T. VV. Mills l ' 2 upon fishes. There is, however, much difference of statement by different observers in regard to the action of these salts upon the frog's heart. J Nutrition. A certain amount of soda is a necessary food for the higher animals, yet it is very doubtful whether an habitual excess has decided effect upon the nutrition, the general drift of the present evi- dence being to show that when in excess the sodium salts neither increase nor yet decrease the elimination of urea or other products of tissue- waste. In the experiments of Munch 1$ the continuous exhibition of large doses of com- mon salt to man apparently produced at first a slight diminution of excretion and a corresponding gain of the body in weight ; but after a time the excretion increased and the weight of the body decreased. The variations in excretion affected chiefly the urine, but sometimes the perspiration and faeces were also influenced. The urine was rendered alkaline, but its solid ingredients were scarcely at all affected. The conclusion of Damourette and Hyades, 1 * that salt increases the elimination of urea and uric acid, is not warranted by their own experiments ; and in the re- searches of I. Mayer, 15 of A. Ott, 18 of C. Clar," and of L. Klemptner, 18 neither the sodium citrate, acetate, phosphate, or sulphate increased nitrogenous elimination, whilst in those of Dalebe and Carberet" the alkaline sodium salts reduced the output of urea. THERAPEUTICS. The fact that soda, in moderate amount, has no de- pressing action, and indeed very little, if any, influence upon the general * Kowalewsky records in the Centralbl.f. Med. Wissen., 1887, the results of an elab- orate study of the effects of adding, either in solid form or in concentrated solution, salts of potassium, sodium, lithium, and ammonium to the blood. As it is not possible at present to connect this influence with the effects of therapeutic doses of the drug inside of the body, we content ourselves with referring to the paper. t For a discussion of this, and literature on the subject, see Limbourg (Arch./. Exper^. Path. u. Pharm., 1888, xxiv.). For a series of papers on the antagonistic actions of sodhim, potassium, and calcium salts on the frog, by Sydney Ringer, see Journal of Physiology, 1890, 1894, 1895. | See Podocaepow (Virchow's Archiv, xxxiii. 507), Schonlein (Arch. f. d. Ges. Physio!., xviii. 26), Laffout (Compt.-Rend. Soc. Biol., 1880, 282), Ringer and Sainsbury (Lancet, 1882, ii. 736), Ringer (Brit. Med. Journ., 1884). Limbourg (Arch. f. Exper. Path. u. Pharm., 1888, xxiv.). 8oo EXTRANEOUS REMEDIES. system, renders it preferable to potash in cases of acidity of the primae viae. It is par excellence the alkali for acid dyspepsia. On the other hand, the circumstance clearly established by Roberts, 19 that it is less powerful as a solvent of uric acid than is its sister alkali, together with the property, believed to belong in a much greater degree to potash, of pre- venting the formation of uric acid, makes soda of very inferior value in uric acid gravel or uric acid diathesis. When in any case it is desirable simply to render the urine alkaline, and at the same time to avoid de- pressing the system generally, soda would, on theoretical grounds at least, seem preferable. It appears to be well proved, clinically, that the alkaline sodium salts given one to two hours before meals in full doses are of decided value in the treatment of chronic hepatic torpor, of catarrhal jaundice, and especially of gall-stones or other affections associated with excessive viscidity of the biliary secretions. As the result, however, of an elaborate series of experiments made upon dogs with biliary fistula, J. Glass * concludes that the alkalies given by the mouth do not increase the alkalescence or amount of the bile. The caution necessary in apply- ing such experiments to human medicine has been spoken of in an earlier chapter. Moreover, it was apparently proved by the experiments of S. W. Lewaschen that the sodium carbonate, sulphate, or phosphate, given to dogs with biliary fistula, increases very markedly the liquidity of the bile by diminishing the percentage of solids. The sodium salicylate acted similarly to, but much more powerfully than, the other salts. E. Dufourt, experimenting with the sodium bicarbonate upon dogs, found that there was a very constant and pronounced increase both of the glycogen and of the sugar of the liver. A possible therapeutic use of sodium carbonate is suggested by the experiments of W. H. Howell, 80 who found that in the lower animals in- travenous or rectal injections of solutions of sodium carbonate increase markedly in animals suffering from shock the amplitude of the heart- beat, and cause a rise of arterial pressure. Dalebe and Carteret Sl affirm that in diabetes, especially of the azoturic form, sodium carbonate is a very valuable remedy. Although so harmless, the sodium salts when in great excess are de- cidedly irritant, and it has been shown by Stokvis 21 and Levi '" that it is possible with the sodium chloride to produce albuminuria, tube-casts, and organic renal changes. The following are the antacid preparations of soda ; the pure bicar- bonate should usually be selected, as being the least irritant. Soon HYDROXIDUM. U. S. Caustic Soda occurs in grayish-white fragments, which deliquesce on exposure and subsequently absorb car- bonic acid. It is an active escharotic. The five per cent, solution of soda (LIQUOR SODII HYDROXIDI, U. S. ) has a specific gravity of 1.056, and is too acrid for practical use. ANTACIDS. 801 SODII CARBONAS MONOHYDRAS. U. S. Sodium Carbonate occurs in strongly alkaline, colorless crystals, which rapidly effloresce on ex- posure to the air, and fall into a white powder. It is very soluble in water; by heat its water of crystallization is driven off, and the Dried Carbonate is left. Commercial Sodium Bicarbonate (Soon BICARBONAS VENALIS) is a white, opaque powder, containing variable amounts of soda not fully saturated with carbonic acid. Pure Sodium Bicarbonate (Soon BICARBONAS, U. S. ) should always be selected for internal use. The antacid dose of these preparations is ten to twenty grains (0.6- 1.2 Gm. ). Sodium Nitrate (Soon NITRAS, U. S.) and Sodium Acetate (Soon ACETAS, U. S. ) are never used in medicine. CALX CALCIUM. When calcium carbonate (marble, limestone) has its carbonic acid driven off by heat, certain white or grayish- white masses are left, consti- tuting the unslaked lime of commerce (CALX Lime, U. S. ). When to this lime is added about half its weight of water, there is formed a white powder, calcium hydrate, or slaked lime. Unslaked lime is an active escharotic ; slaked lime is an irritant, or, when in concentrated form, a feeble escharotic. Lime is never used in substance in medicine, but in the form of a watery solution. When in such dilute form it acts as a detergent and sedative, especially to mucous membranes. Its official insoluble prepara- tions are free from irritant properties and are mild astringents. Neither the soluble nor insoluble preparations of lime are absorbed to any large extent, the lime escaping, if given in considerable dose, in great part with the faeces in the form of some insoluble salt. Minute quantities of it probably circulate in the blood in combination with proteids. When a soluble salt of calcium is given intravenously, an insoluble form of lime is probably rapidly deposited in the tissue. Excretion of lime chiefly takes place through the urine, or perhaps more largely through the large intestine. PHYSIOLOGICAL ACTION. Probably owing to the difficulty of their absorption, even the soluble preparations of lime have not been found in practical medicine to have any general effect upon the body. Carl Franke, indeed, states that the intravenous injection of large amounts of soluble lime salts has no effect upon rabbits. The soluble salts of lime are evidently not without physiological activity, and have close relation with the general bodily well-being. W. H. Howell and E. Cooke" have proved that the inorganic salts of the blood, milk, gastric juice, etc., are able to keep the isolated frog's heart beating with force and regularity for many hours without other food, and, according to the experiments of Ringer, among these salts those of lime are especially important. Further, it seems to be demonstrated that small doses of soluble calcium salts increase the energy of the 802 EXTRANEOUS REMEDIES. heart's action, as the experiments of Ringer " have been confirmed by Mickwitz and also by Binet. Langendorff and Hueck S2 believe that their own and previous experiments justify the conclusion that the presence of calcium in the nourishing liquid is absolutely essential for the continuance of the cardiac action, not only in cold but also in warm-blooded animals. Binet K states that though the cardiac ar- rest usually takes place in systole in calcium-salt poisoning, yet if the salt have come directly in contact with the heart in concentrated form there is paralytic ar- rest (diastolic). Further, according to Ringer 36 and to H. G. Beyer," the volun- tary and involuntary muscles of the frog are stimulated by small amounts of cal- cium ; and, according to Franke, 38 they are paralyzed by large amounts of the drug. Stefani w states that calcium chloride when applied locally in minute amount increases the functional activity of the motor nerve-trunks, but when in large amount produces rapid paralysis ; whilst Binet has demonstrated that the toxic dose of the calcium salt directly paralyzes the cerebral cortex and the motor centres of the spinal cord. It is certain that the calcium salts are essential to all the higher tis- sues. It is probable that under ordinary circumstances a sufficiency of these salts is furnished to the system by the food, and that no gain is to be achieved by their further administration. This is, however, only a probability, not a definitely demonstrated fact ; it may be that the soluble haloid salts have more practical value than is at present believed. LIQUOR CALCII OXIDI. U. S. Solution of Lime. Lime-water \s a colorless liquid, having the sp. gr. 1.0015, an d containing about 0.15 per cent, of lime. It has an alkaline taste, and is nearly destitute of irritant properties. On exposure to the air it absorbs carbonic acid and deposits calcium carbonate. Twenty minims of syrup of lime (SYRUPUS CALCIS, U. S. ) equal a fluidounce of lime-water. THERAPEUTICS. Lime-water is used exclusively as a local remedy. In vomiting, from almost any cause except acute gastritis, equal parts of lime-water and milk afford an elegant, simple, and much-used remedy. If the vomiting be severe, all other food should be inhibited, and one or two tablespoonfuls of the mixture given every half- hour, the quantity, as well as the proportion of milk, being increased as the stomach is able to bear it. As lime-water when put in milk prevents the formation of dense coagula, it is often added with advantage to that fluid when used as food for infants, or for adults with weak digestion. As an alkaline astringent, the syrup is often useful in diarrhoea in doses of one to two fluidrachms (4-7 C.c. ), well diluted. Externally, lime-water has been used as a wash in various skin dis- eases, especially in tinea capitis : it is also applied to ulcers, and is said to have a very marked influence in lessening the amount of discharge. When mixed with an equal bulk of linseed or olive oil (LINIMENTUM CALCIS, U. S. ), lime-water forms a thick, soapy liquid (Carron Oil, so called from the name of the iron-works at which its reputation was first made), which is much used in recent burns. Lime-water has the power of dissolving mucus and also false mem- brane, and has therefore been introduced as a local remedy in pseudo- ANTACIDS. 803 membranous croup and in diphtheria. It is sometimes used by causing the patient to inhale the vapors of slaking lime, but a better method is to pulverize lime-water by means of an atomizer and direct the spray upon the back of the fauces while the patient is respiring deeply. The application should be made every two or three hours. CALCIUM CARBONATE. Chalk is the native, friable calcium carbonate, a milk-white, soft solid, of an insipid, earthy taste, insoluble in water, wholly soluble, with effervescence, in dilute muriatic acid. CRETA PR^EPARATA. U. S. Prepared Chalk is chalk freed from impurities by pulverization, leviga- tion, and elutriation ; a white, perfectly smooth powder. CALCII CAR- BONAS PR^ECIPITATUS. U. S. Precipitated Calcium Carbonate is a white powder, free from grittiness, which is made by precipitating calcium chloride with sodium carbonate. Dose of either preparation, twenty grains to a drachm (1.3-4 Gm. ). THERAPEUTICS. Calcium carbonate in its different forms is used in- ternally as an antacid and a very mild astringent. As none of the salt? which it forms are purgative, it, with the other preparations of lime, is the best antacid when diarrhoea is present. The crude chalk should never be used, but the other preparations are probably of equal value. Some practitioners assert, however, that the oyster-shell is more acceptable to delicate stomachs, on account of the animal matter which it contains ; and, under the name of Castilloes Powder, a mixture of salep, tragacanth, sago, of each three parts, prepared oyster-shell one part, and cochineal sufficient to color it, has been much used in obstinate summer diarrhoeas. A drachm of this is boiled in a pint of milk, and the decoction taken as food ad libitum. Chalk Mixture (MISTURA CRET^E, U.S.) contains thirty grains of chalk to the ounce ; dose, one to two tablespoonfuls (15-30 Gm. ). It is often combined with laudanum or paregoric and tincture of kino or catechu. Externally, prepared chalk and precipitated calcium carbonate are used as desiccants and protective applications to idcers and chronic burns, also in excessive sweating of the feet, and in intertrigo and other affec- tions of the skin. CALCII SULPHAS EXSICCATUS. U. S. Dried calcium sulphate, cr plaster of Paris, is never used in medicine save for mechanical purposes in the making of plaster bandages, splints, etc. CALCII CHLORIDUM. U. S Calcium Chloride is locally a violent irri- tant, but it is strongly recommended by S6e in the treatment of gastric catarrh and fermentative dyspepsia. The results of experimental studies as to the action of calcium chloride upon the heart suggest the probability that when hypodermoclysis is indicated in conditions involving also car- 804 EXTRANEOUS REMEDIES. diac failure, the addition of chloride of calcium to the normal saline so- lution might be of great service. J. Bruce MacCallum (confirmed by Ott) has found that calcium chloride very markedly inhibits peristalsis in the rabbit, and suggests its use in nervous diarrhoea. Dose, fifteen to seventy -grains a day (1-5 Gm). CALCIUM IODIDUM. Calcium iodide, containing eighty per cent, of iodine, has been strongly recommended by Germain Se as superior to the ordinary iodides and less apt to derange digestion. REFERENCES. ANTACIDS. 1. CHAMBERS . . . . The Indigestions, Am. ed., 1870, 67. 2. RABUTEAU .... L'Union Med., 1871, xii. 186. 3. GRANDEAU . . . J. de I'A. P., 1864. 4. GUTTMANN . . . V. A. P. A., XXXV. 5. CURCI L. M. R., Oct. 15, 1886. 6. BEYER M. News, Sept. 4, 1886. 7. MAYET C. R. S. B., 1897, ios., iv. 8. PODOCAEPOW . . V. A. P. A., xxxiii. 507. 9. SCHONLEIN . . . A. G. P., xviii. 10. RINGER and SAINSBURY . L. L., 1882, ii. 736. 11. LAFFOUT . . . . C. R. S. B., 1880, 282. 12. MILLS Canada Med. Surg. Journ., March. 1886. 13. MUNCH Arch. d. Vereins f. Gemein. Arbeit., 1863, vi. 369. 14. DAMOURETTE and HYADES . J. de Th., 1880, 440. 15. MAYER Z. K. M., 1881, 82. 16. OTT H. S. Jb., 1883, 220. 17. CI.AR C. M W.. 1888, xxiv. 18. KLKMPTNER . . . Thesis, Dorpat, 1889. 19. ROBERTS .... Urinary and Renal Dis- eases, Am. ed., 1866, 240. 20. GLASS A. E. P. P., 1892, xxx. 31. STOKVIS A. E. P. P., xxi. 22. LEVI Centralbl. f. Allg. Path. u. Path. Anal., 1895, vi. 23. HOVVELL and COOKE . J. P., 1893, xiv. 24. RINGER J. P.,v., vii. 25. BINET R. M. S. R., 1892. 26. RINGER N. Y. M. R., xxxi. 27. BEYER M. News, Sept. 1886. 28. FRANKE Thesis, Wiirzburg, 1889. 29. STEFANI A. I. B., 1894, xxii. 30. HOWBLL Contrib. Med. Research, Vaughan. 31. DALEBE and CARTERET . B. G. T., Nov. 1901. 32. LANGENDORFF and HUHCK . A. G. P., 1903, xcvi. 33. OTT Ott's Contributions to Physiology, part 16, 1905. FAMILY II. ANTHELMINTICS. THESE are medicines which kill or cause the expulsion of intestinal worms. They are sometimes divided into vermicides, those which kill, and vermifuges, those which expel ; but there is little or no practical use in the division. It is of much greater importance to establish the rela- tions between these drugs and the different species of entozoa, since clinical experience has demonstrated that an anthelmintic very efficient against one form of intestinal worm may be not injurious to another species. Therapeutically considered, the entozoa may be divided into the Tapeworms (T&m&}, the Round-worms (Lumt>rzct\ and the Seat- worms {Ascarides}. The last of these differ from the others in that they are to be attacked solely by enemata. It is obvious that the value of an anthelmintic depends not only upon its power of poisoning the articulate, but also upon its harmlessness as regards the patient. Thus, it is the eminent combination of these quali- ties that renders the infusion of quassia so valuable in cases of seat-worms, while carbolic acid, though very efficient, should never be used against the same parasite, since it has greatly imperilled, if it has not destroyed, the life of the patient when so employed. There are certain general rules which govern the administration of anthelmintics, and which should not be lost sight of. They may be summed up as follows : Let the alimentary canal be as empty as possible, so that the drug may act with the greatest force upon the enemy. For this reason, anthelmintics are best administered early in the morning ; and in ob- stinate cases the patient should be required to fast until dinner-time. If the drug be not itself a purgative, from four to eight hours after its ad- ministration a brisk cathartic should be given ; or a purgative dose of calomel may be combined with it, as the bilious purging induced by the latter drug seems to be especially obnoxious to the entozoa. SPIGELIA PINKROOT. U.S. The root of Spigelia Marilandica, an herbaceous perennial, growing in the Southern and Southwestern United States. It consists of a knotty head, with numerous fine, crooked, branching rootlets. The odor is faint and peculiar ; the taste sweetish and slightly bitter. W. L. Dudley 805 806 EXTRANEOUS REMEDIES. separated from it an alkaloid, spigeline, which, according to Boorsma, 1 is actively poisonous. PHYSIOLOGICAL ACTION. Full therapeutic doses of spigelia produce in man no symptoms, but, according to Hodge Thompson (quoted by Eberle), Eberle, 2 and Spalsberg, s an overdose causes acceleration of the pulse, dilatation of the pupils, heat and dryness of the skin, flushing and a swollen appearance of the face, with, in Eberle' s cases, talkative de- lirium. Two fatal cases * of poisoning by it are said to have been re- corded. According to H. A. Hare,* toxic doses slow the pulse and depress the heart, the respiratory centre, and the motor spinal cord. In Hare's experiments toxic doses of spigelia caused in the dog hurried re- spiratory movements, retching, wide dilatation of the pupil, internal strabismus, marked exophthalmia, muscular weakness and loss of coordination, and at last sleep, passing into coma and death from failure of respiration ; in the frog exoph- thalmia, excessive muscular weakness, loss of reflex activity, and slowing of the heart, with at first increase of power of the systolic contractions but afterwards arrest in a condition of semi-diastole. THERAPEUTICS. Spigelia is a most efficient remedy in cases of the round-worm, and is, when given within the bounds of moderation, entirely safe. It appears to narcotize the worm, and requires the use of a brisk cathartic. The fluid extract (FLUIDEXTRACTUM SPIGELIA, U. S. ) is efficient in doses of two fluidrachms (7 C.c. ). A better preparation is the Fluid Extract of Spigelia and Senna (XTRACTUM SPIGELIA ET SENN^E FLUIDUM, U. S. 1870), which is much liked by children on account of its agreeable taste. The dose for an adult is one-half a fluid- ounce (15 C.c. ); for a child two years old, one-half to one fluidrachm (2-4 C.c. ), repeated every four hours until it purges. AZEDARACH, the bark of the root of Melia Azedarach, or Pride of China, is used in the South as a remedy for the round-worm. It is said to possess poisonous properties similar to those of spigelia, yet it is affirmed that animals and children eat its fruit with impunity. It is usu- ally given in decoction (two ounces to one and a half pints, boiled to a pint), the dose being for a child a tablespoonful (15 C.c) every two or three hours until the bowels are affected. CHENOPODIUM, or Wormseed, is the fruit of Chenopodium anthel- minticum, or Jerusalem Oak, a rank, odorous plant, growing about waste places in the suburbs of towns in the United States. It consists of minute, globular, light brown seeds about the size of a pin's head, of a nauseous odor and a pungent taste, due to the volatile oil which * These cases appear to have been indefinitely copied, and are of doubtful authen- ticity. ANTHELMINTICS. 807 they contain in large quantity. Wormseed Oil (OLEUM CHENOPODII, U. S. ) is of a light yellow color, becoming darker and less fluid by age, of a peculiar powerful odor and a hot burning taste.* It has been used in hysteria, but is now employed only as an anthelmintic against the lum- bricus, and more rarely the tapeworm. It is very efficient, and ten drops (0.6 C.c. ) of it on sugar may be given to a child three years old, before breakfast, dinner, and supper, for two days, followed by a brisk purge. Cusso, U. S., Kousso, Brayera, is the female inflorescence of Ha- genia abyssinica, a tree of Abyssinia. It occurs in compressed greenish- yellow clusters, of a fragrant balsamic odor, and a taste which in a little while becomes acrid and disagreeable. The crystalline resin Kosin, discovered by Pavesi, is believed by Bedall 5 to be the active principle of kousso. Leichsenring affirms it to be Kosotoxin, an amor- phous, yellowish-white substance, which, according to Handmann, is an active paralyzant to all muscles, including the heart, and also of the motor nerv e-endings. Brayera is a most efficient remedy against the tapeworm, and even in large doses causes no greater inconvenience to the patient than some nausea, abdominal pain, and looseness of the bowels. It is generally not necessary to administer any purgative with it, and the worm is discharged dead with the last watery passages. A half-ounce of the powdered flow- ers is given suspended in water in the morning, with the usual precau- tions as to diet. The best preparation is the yellowish-brown, impure, amorphous kosin of commerce, which may be given in doses of seven to fifteen grains (0.51 Gm. ) repeated every half-hour until four doses have been taken, a full dose of castor oil being administered one hour later. Care should be exercised in giving bray era to pregnant women, as it is stated that it has produced abortion. SANTONICA SANTONICA. U.S. Levant Wormseed consists of the unexpanded flowers and peduncles of Artemisia pauciflora, a composite of Northern Middle Europe and Asia. It consists of pale, greenish-brown, smooth heads of four or five tubular flowers of a very strong aromatic odor when rubbed, and a bitter, disagreeable taste. It contains volatile oil, resinous matter, and a crys- talline principle, Santonin (SANTONINUM, U. S. ), or Santoninic Acid, which occurs in colorless, pearly, four-sided, orthorhombic, very insoluble * In the Maryland Med. Journ., iv. 20, T. R. Brown reports a case in which death was attributed to the taking of an ounce or more of wormseed oil in divided doses. The patient was found in bed unconscious, with vomited matters over his surroundings, after some hours became sensible, relapsed an hour or two later into heavy sleep, was again roused, and while playing cards became aphasic, deaf to conversation, acutely sensitive to other sounds, and finally died of hemiplegic apoplexy. It is plain that the worm- seed was not the direct immediate cause of all these symptoms or of the fatal result. 8oS EXTRANEOUS REMEDIES. tables. It has a neutral reaction, but unites with alkalies to form salts, and hence is freely soluble in alkaline solutions. PHYSIOLOGICAL ACTION. Absorption and Elimination. Santonin is only feebly irritant. It is absorbed readily, probably as a sodium santo- ninate, and by its elimination produces a very pronounced reddish discol- oration of the urine, which is characteristic of the poisoning. According to the researches of Jaffe, 85 santonin is eliminated as a new substance santogcnin, and also as a derivative of santogenin B-oxy santonin. The color of the urine is a very marked yellow, which has at first an orange tint, but after very large doses becomes saffron-like, or sometimes even a purplish red, which has given origin to the idea that blood was present in it. According to Manns,' the addition of an alkali to the yellow urine causes it to become red. The exact form in which santonin is thrown off is not established, but probably it undergoes oxidation in the system. Kletzinsky asserts that the drug receives in the system six atoms of oxygen.* General Effects. The first and most characteristic symptom produced by large doses of santonin, xanthopsia, or yellow vision, is probably due to a direct action of the poison upon the retina. Xanthopsia was first noticed by Calloud. Usually it consists of a very deep yellow tint imparted to the landscape and to every object looked at, an effect perhaps most comparable to that of looking through yellow glass ; sometimes this yellow is replaced by green ; and Heydloff states that he has seen patients in whom the tint was red, and others in whom it was blue. As was first pointed out by Knies," the period of yellow vision is usually preceded by one of violet vision, and during the stage of yellow vision there is a lessening or complete destruction of the sensibility towards the violet end of the spectrum. Two theories have been ad- vanced as to the cause of the yellow vision ; first, that it is simply due to staining of the humors of the eye, but Rose 7 was unable to find any dyestuff in any portion of the body except in the medulla of the kidney ; and Filehne, 34 in a very large series of studies upon human beings and lower animals was unable to find any staining either of the humors or of the retina itself. Moreover, the theory of staining does not satisfactorily account for the violet vision which precedes the yellow, nor for the later failure of the power of recognizing violet. The second theory, that the disturbance of vision is due to the action of the drug upon the retinal elements themselves, would seem to be strengthened by the statement of Filehne that changes in the visual purple can be demonstrated in animals fatally poisoned with santonin. The accuracy of this statement is, however, denied by Knies, who af- firms that santonin has no influence upon the visual purple or the function of the rods of the retina, so that the matter would seem to be still sub judice. In poisoning by santonin great pallor of surface, with a blue color around the eyes or involving the whole countenance, has been gen- * Chrysophanic acid produces a discoloration of the urine similar to that caused by santonin. According to Hoppe-Seyler, the cause of the coloration can readily be distin- guished by adding caustic soda to the urine, and then shaking up with amylic alcohol, when, if the coloration proceeds from santonin, the urine is decolorized, while, if it be due to chrysophanic acid, the alcohol takes up only traces of the coloring matter. ANTHELMINTICS. 809 erally an early symptom ; vomiting has not rarely been present, and sometimes has been accompanied by colicky pains. Besides these mani- festations, giddiness, mental apathy or stupor, great coldness of the surface, profuse sweating, trembling, mydriasis, and finally loss of con- sciousness, with convulsions, often violent and accompanied by opis- thotonos and emprosthotonos, and failure of respiration, are the usual phenomena of santonin-poisoning. The circulation seems to be very little affected.* According to Frohner, moderate doses of santonin produce in domestic animals polyuria, sometimes strangury, and very commonly so pronounced sexual excite- ment as to suggest that the drug may have value as an aphrodisiac. The toxic dose causes in dogs and other domestic animals accelerated breathing, slowing of the pulse, universal trembling, cramps, free salivation, unconsciousness, convul- sions, dilated pupils, and death, f. After death the lesions are not absolutely con- stant, but hyperaemia of the nerve-centres and congestion of the lungs and heart are nearly always present. Santonin must have a powerful action upon the nervous system, but we have no detailed knowledge as to its general physiological action. Santonin often increases the flow of urine, and, according to Farquharson,* it also increases slightly the elimination of urea. THERAPEUTICS. Santonin was introduced into therapeutic use in 1830 almost simultaneously by Alms and by Kahler, and is one of the most reliable remedies that we have in the treatment of the lumbricoid or round-worm. Von Schroder 9 believes that he has proved by direct experiment that santonin is feebly toxic to the round-worm ; but in this he is in opposition to the general clinical experience and the almost universal belief of helminthologists that santonin acts directly upon the intestinal parasite. It certainly is a very efficient remedy, but it should either be combined with or followed in about two or three hours by a brisk cathartic. The combination of calomel and santonin has been much commended. As long ago as 1862 Guepin and Martin 10 recommended santonin in amaurosis, asserting it to be especially useful in those cases in which there had been choroiditis and iritis. These statements have been con- firmed by D. Dyce Brown," as well as by Ogston. G. Frank Lydston affirms that santonin is a valuable remedy in epilepsy. D. H. Bergey " asserts that santonin has especial relations with the uterus, and, -if given in full dose at the time of the molimen, is an efficient remedy in acute suppression of the menses. TOXICOLOGY. There was at one time a tendency in the profession to attribute the toxic symptoms caused by santonin medicinally given to * Case, Arch, fur Exper. Path, und Pharm., vi. 302. t See experiments of Manns (Das Santonin, Marburg, 1851), of Rose {Virchow's Archiv, 1859, xvi.), of T. Krauss (Inaug. Diss., Tubingen, 1869), and of Frohner (Monats- hefte f. Thierheilk., 1893, iv.). 8io EXTRANEOUS REMEDIES. contaminating strychnine. The incorrectness of this has been demon- strated by Krauss and others. The following cases are instructive: A child five years old was killed in half an hour by an unknown quantity," and one six or seven years old is said to have been destroyed by six grains of the acid, after suffering from haematuria: 14 * four grains produced very serious symptoms in a child four years old. 15 In Grimm's 16 case, a rather feeble child five years old took two one-grain doses of santonin, and was seized with convulsive tremblings, which increased in severity until they became severe convulsions, accompanied by uncon- sciousness, trismus, pallor of the face, cold sweats, dilated pupils, and rapid pulse and respiration. Thirteen or fourteen hours after the ingestion of the poison, while the patient lay on her back, quiet, unconscious, with moderately dilated pupils and a slow, feeble pulse, death occurred suddenly. Nine-tenths of a grain of santonin are said to have caused complete unconsciousness in a child five years old." Six grains of santonin caused in a child five years old epileptiform convulsions and death in thirty-five minutes (W. J. Kilner 18 ). One grain and a half produced in a child three and a half years old symptoms of the utmost severity, not reaching their maximum until two days after the ingestion of the poison : 19 for other cases, see C. Bevill. 20 In one case complete blindness persisted for nearly a week. It is a curious fact that some of the text-books advise the use of santonin in doses larger than those which have produced serious or even fatal poisoning. Very alarming symptoms have been occasioned by two one-grain doses exhibited within three hours in a child eight years old (Grimm) ; in a child two and a half years old, four grains apparently came very near causing death (Berg 21 ) ; and in the fatal case noted on page 792, only two grains were taken by a child five years old. The reason large doses have been so often given with impunity is the great insolubility of the crystals of the drug. The treatment of poison- ing by santonin, after evacuation of the stomach and bowels, must at present be entirely tentative. One case appears to have been saved by artificial respiration ; but Binz 22 has found amyl nitrite, morphine, and artificial respiration alike useless in animals : chloral given before the poison appeared to be of service. ADMINISTRATION. Santonin is best administered in troches (Tno- CHISCI SANTONINI, U. S. ) each one-half a grain, so that the slow solu- tion of the santonin in the intestine shall produce the greatest possible effect upon the worm with the least absorption of the remedy. The dose for an adult is two to four grains (0.13-0.26 Gm. ) ; for a child two years old, one-quarter to one-half a grain (0.016-0.03 Gm.). For young infants, santonin is hardly a safe remedy in any efficient dose. When a dose of any size is given, it should not be repeated in less than eight hours, and the last dose should be accompanied by a purgative amount of calomel. The soluble sodium santoninate is much more dangerous and less efficient than santonin : the object is to get as much of the remedy as * This is probably a mistaken observation, the urine being only blood-colored, and not containing blood (see page 806). ANTHELMINTICS. 811 possible in contact with the worm, and, as in order to do this a slow, not a rapid, absorption is necessary, the insolubility of santonin is an advantage. ASPIDIUM. U. S. Filix Mas, or Male Fern, is^the rhizome of Dryop- teris filix mas, or male fern of Europe. Under the name of Aspidium * the present U. S. Pharmacopoeia recognizes both it and the rhizome of the indigenous D. marginale. The rhizome, when perfect, is from six to twelve inches long, and covered with large, brown, imbricated scales. Its taste is bitter and astringent. Aspidium contains an amorphous acid, filicic, ^ which, according to the ex- periments of E. Poulsson,* 3 is a very active substance, causing, in the frog, at first excitement and then paralysis of the central nervous system, and finally paralyzing the heart and exerting a marked influence upon the muscles : producing in warm- blooded animals violent diarrhoea, with a general paralysis due to depression of the spinal-centres, and finally cardiac palsy. Robert, 2 * however, as the result of his experiments, believes that the vermifuge principles of male fern do not depend solely or even chiefly upon filicic acid, but upon the ethereal oil. The official oleoresin (OLEORESINA ASPIDII, U. S. ) thoroughly rep- resents the crude drug. It is a dark, thick liquid, of a bitter, nauseous, slightly acrid taste. In overdose it is a violent poison, producing ex- cessive vomiting and purging, with general weakness, tremors, cramps in the extremities, increased reflexes, amaurosis, and finally, in some cases, violent tetanic convulsions, with opisthotonos, stupor deepening into coma, and collapse. Icterus is sometimes apparent. Disturbance of the special senses is a not infrequent symptom in aspidium-poisoning. Deafness without loss of vision has been noted (case of Grant 26 ). More commonly amblyopia or complete amaurosis occurs. One or both eyes may be affected, and total blindness, with gray atrophy, may remain as a permanent condition (Katayama and Okamoto ; 27 also Bayer 18 ). Experiments upon dogs indicate that the primary influence of the drug is on the ganglion-cells of the retina. The icterus of aspidium poison has been attributed to the inflammation of the duodenum, but Grawitz, conceiving that it might be of haemic origin, found on ex- amination of the blood of patients that immediately after the taking of large doses of the extract of male fern there was a marked lessening in the number of the red blood-corpuscles. Grawitz, therefore, came to the conclusion that the extract is powerfully destructive to the red blood-disks, and that the icterus was haemic in its etiology. C. Georgiewsky has found that in rabbits fatally poisoned with male * It is probable that many species of the genus Aspidium are active. Poulsson (Arch, f. Exper. Path. u. Pharm., 1895, xxxv.) separated from the rhizome of Aspidium spinulo- sum two acids closely allied to filicic acid, a yellow and a white polystichic acid ; and both he and Valter Laur6n have found these extracts of the plant to be active taeniacides. t Aspidin of R. Boehm (Archivf. Exper. Path. u. Pharm., 1896, xxxviii.) is distinct from filicic acid, and although poisonous both to frogs and to higher animals, appears not to be an active taeniacide. 8i2 EXTRANEOUS REMEDIES. fern no destruction of the red blood-corpuscles occurs if death takes place within twenty-four hours ; but that if the symptoms be protracted over several days there is a very distinct lessening in the amount of haemoglobin in the blood ; and that after death the characteristic change of the poisoning is a pronounced wide-spread deposit of ferrous pigments in the liver, the spleen, the marrow of the bones, and sometimes in the kidney^. In these later researches, the theory of Grawitz that the poison acts specially upon the liver-cells was not confirmed. After fatal poisoning in the lower animals by aspidium, besides the granular pigmentation just spoken of, hemorrhagic gastro-enteritis and cystitis, with violent parenchymatous nephritis, maybe found (Frohner w ). The fatal result is partially due to violent irritation of the gastro-intes- tinal tract of the kidneys ; but Ouirll is probably correct in his belief that it is also largely the outcome of the influence of the poison upon the nerve-centres, to which factor should also be added its action upon the circulation. The minimum fatal dose of the oleoresin is hardly known, but eight grammes of the extract have caused death in a child about three years old ; six drachms of the oleoresin have several times proved fatal in the adult:* in Paltauf's 25 case the fatal result is said to have been due to four and a half grammes. THERAPEUTICS. Male fern is employed almost exclusively against the tapeworm. In its administration it is necessary to regard strictly the general rules applying with greater or less force to all anthelmintics, but which are especially imperative when a drug is employed against the tapeworm. The patient should live upon milk and a little bread for one day, and the following morning take a full dose one half to one flui- drachm (2-4 C.c. ) of the oleoresin, fasting, and repeating it in two or three hours. At noon the patient may eat freely, and in the evening a brisk cathartic should be given. PEPO. U. S. Pumpkin Seed. The seeds of the ordinary pump- kin are a most valuable remedy in cases of tapeworm, perhaps even more efficient than the male fern, and perfectly harmless. Two ounces (62 Gm. ) of the seeds may be beaten up with sugar into an electuary, or with water into an emulsion, and be taken fasting in the morning, the patient having dieted the previous day. Some hours after their adminis- tration a brisk purge should be given. I. G. Wolff asserts that the active principle is a resin, which he has found efficient in doses of fifteen grains (i Gm. ). TURPENTINE, in doses of half a fluidounce, has been used in cases both of tapeworm and of round-worm. It is efficient, but is liable to produce unpleasant effects, and should be employed only when other remedies have been used without success or are not to be had. It * TTierap. Monatsch., 1889, iii. ; Munchen. Med. Wochen., 1890, xxxvii. ; Lancet, 1882; Deutsch. Med. Wochen., 1891, xvii. ANTHELMINTICS. 813 should be given in combination with twice its bulk of castor oil, or sometimes in smaller doses as an aid to other vermifuges. GRANATUM. U. S. Pomegranate Rind. The bark of the pome- granate root is efficient, though very unpalatable, against the tapeworm. The decoction of the fresh root (two ounces to one pint) is to be pre- ferred; a pint of it to be taken in three doses, an hour apart, before breakfast. The dose of the fluid extract (FLUIDEXTRACTUM GRANATI, U. S. ) is thirty minims (2 C.c. ). As originally stated by C. Tanret," pomegranate bark contains four alkaloids; the most important are pdle- tierine (pumcine) and iso-pelletierine (iso-punicine), which Dujardin- Beaumetz has shown to be active t&niacides. In the higher animals these alkaloids paralyze the peripheral motor nerves, having a curare- like action, without affecting sensation or muscular contractility. G. Coronedi " agrees with the statement that the paralysis is peripheral, but believes that the muscles themselves are affected. The efficiency of pelle- tierine as an anthelmintic has been confirmed by various clinicians. A mixture of the tannates of the four alkaloids is recognized by the U. S. Pharmacopoeia as PELLETIERIN^E TANNAS, U. S. , and may be used in doses of four grains (0.3 Gm. ) as a tceniacide. Dujardin-Beaumetz also has employed it successfully in Meniere' s disease, and states that hypo- dermic injections of six grains produce in man severe vertigo and mus- cular weakness, with great retinal congestion. We have seen five grains cause in the adult pronounced muscular weakness amounting almost to general paralysis, and a number of cases have been reported in which it has produced in infants symptoms so severe as to discourage its employ- ment in patients of that class.* Galezowski S2 has used pelletierine in paralysis of the third and sixth pairs of nerves with asserted good results. THYMOL, U. S. , has been used by Neuma Campi f for the destruction of tapeworm ; he gives half an ounce of castor oil in the evening, in the morning two drachms (7 Gm. ) of thymol divided into twelve doses, one to be taken every quarter of an hour, and twenty minutes after the last dose of thymol another dose of castor oil. Thymol is a specific against hook-worms the Ankylostoma {Uncinaria) duodenale and the A. (U.) Americana. After starvation for twenty-four hours, a thirty-grain dose may be given and repeated in twenty-four hours, followed by a brisk purge, as suggested by F. M. Sandwith. 38 Giddiness, fall of temperature from one to two degrees C. , slowness of the pulse and respiration, stag- gering, and even collapse are liable to occur; a cure is almost invariably effected by such doses, but probably smaller amounts would suffice. K AM ALA. Kamala. The glands and hairs from the capsules of Mallotus philippinensis are used against the tapeworm. It is an * See Bull, de Therap., Ixxviii., Ixxix., Ixxx., cxi., July, 1886; also University Med. Magazine, \. 639. t II Raccoglitore Medico, abstracted in Buffalo Med. Journ., Oct. 1886. 8i 4 EXTRANEOUS REMEDIES. orange-red, very inflammable, granular powder, mixing with water with some difficulty, and containing traces of a volatile oil and coloring resinoids, to one of which Anderson has given the name of Rottlerin. Kamala is actively purgative, indeed drastic, and may cause nausea and vomiting. A tincture of it may be used. Dose of the powder, one to two drachms (4-8 Gm. ) in syrup, given in the morning, and repeated in ten hours if it does not purge. ACIDUM PICRUM. Picric or carbazotic acid, on account of its corrosive char- acter, is used internally exclusively in the form of the ammonium picrate, which, according to Erb,* 7 is rapidly absorbed and eliminated in the urine, and produces, in doses of fifteen grains, yellowness of the conjunctiva, skin and urine, often accompanied by gastric disturbances. Von Beck K reports urticaria and measles- like eruptions produced by the long use of the drug ; and Achard and Clerc s9 have seen violent general erythematous swelling of the limbs produced by the local appli- cation of the solution of picric acid. According to Binz,* picric acid acts similarly to but much less powerfully than does quinine upon infusoria. W. Erb found that a single dose of eight grains will produce in the rabbit falling temperature, weakness, diarrhoea, collapse ending in death, sometimes preceded by convulsions. The blood of animals slowly killed by the picrate was a dirty-brown color, with distinct nuclei in the red blood-disks and floating free in the serum. The alterations in the red blood-corpuscles occurred during life, and could be produced by mixing ammonium picrate with blood out- side of the body. Ammonium picrate has been commended as an antiperiodic, but is of no value; nor does it seem useful as an anthelmintic or in trichiniasis. (See Erb.) Hammond 41 declares that the salts of picric are specific in exophthalmic goitre. According to Erb, the ammonia salt, nine to twelve grains a day, may be given with safety. REFERENCES. ANTHELMINTICS. 21. BERG Wiirtemberg Med. Corres- pondenzbl., 1862. i. BOORSMA .... P. J. Tr., 1898. 22 BINZ A. E. P. P., vi. 300. 2 - EBERLE Mat * na . Medlca and 23. POULSSON .... A. E. P. P., 1891, xxix. fherap , i. KOBERT Th. M., 1893. 3. SPALSBERG . . . fc M S. J 1885. 25 PALTAUF s Jb ^^, HARE M News, March 12, 1887. 26 GRANT S. Jb., ccxlix. 5- BEDALL SydSoc. Year-Book, 1868, 27 . YANAMATSU and OKAMOTO . Viertelj. f. Gericht. Med. u. Off. 6 - MANNS ^ Santonin, Marburg, San ^ ^ viij Supp , 28. BAYER Prag. Med. Wochens.. 7- ROSE V. A. P. A., xvi. 233; xvni. l888 xjj 15; xix. 522; xx. 245; ^ FROHNER . . . . Monats. Prakt. Thier- heilk., 1890. 8. FARQUHARSON . . . B. M. J., 1872. TANRET . . B. G. T., xcviii. 316. 9. VON SCHRODER . A. E. P. P., xix. 304. CORONEDI .... La Sperimentale, 1892. 10. GUEPIN and MARTIN . Ann. de Therap., ^ GALEZOVVSKI . . B . M. J., Nov. 28, 1885. 33. SANDWITH .... Anchylostomiasis. 1894. ji. BROWN ... . Brit, and For. Med.-Chir. ^ FlLEHNE . A . G . P., 1900, Ixxx. 35- JAFFE P. J. Tr., 1897. lix. 12 ' BERGEY Amer - Therap., July, 1892. ^ KNIES A of Op IgOQj xxix P. J. Tr., vin. 996- 37. ERB Die Pikrinsaiire, Wiirz- 14. B. G. T., Ixxiv. 362. burg I865 38. VON BECK. . . . Charite-Annalen, 1892, 16. GRIMM Schweizer Zeitsch. f. Med.- ^jj Chir., u. Geb., 1852, 493- 39 . ACHARD and CLERC . G. H. M. C., 1900, xlvii. S. Jb., cci. 128. 4<) BlNZ V. A. P. A., xlvi. 130. 18. KILNER St. Thomas's Hos P .Rep.,x. 4 , HAMMOND . . . . N. Y. M. J., Jan. 1890. 20. BEVILL T. G., iii. 428. FAMILY III. DIGESTANTS. IN this family are associated a few remedies which are used to aid the alimentary canal in dissolving the various articles of food. PEPSIN. As is well known, there is secreted by the gastric glands a peculiar albuminous body, which has the power not only of coagulating albumin, but also, with the aid of acidulated water, of redissolving it. To this principle the name of pepsin has long been given. A discussion of its nature and properties would be more in place in a work on physiology than in one on therapeutics. The U. S. Pharmacopoeia now recognizes a stronger and weaker pepsin. PEPSINUM, U. S. , or Pepsin, is required by the Pharmacopoeia to be able to digest three thousand times its weight of freshly coagulated egg albumin. The U. S. Pharmacopoeia of 1890 recognized a Saccharated Pepsin containing ninety per cent, of sugar of milk. The dried stomach of calves has been used from time immemorial for the pur- pose of coagulating milk, by housewives, with whom it is customary to place the dried viscus in wine, and to call the liquid thus formed, as well as the prepared stomach, rennet. It is stated by James Gray l that rennet-wine should be of such strength that one teaspoonful of it will coagulate a pint of milk. Rennet is said to have been long employed in England as a domestic remedy in dyspepsia. 2 In South America the inner coat of the gizzard of the ostrich is stated to be put to a similar use (E. S. Wayne 8 ), and in our own country the dried gizzards of chickens and turkeys are no less famous among medically inclined housewives. Various processes have been suggested for the preparation of the drug, but none of them yields a pure proximate principle, if indeed pep- sin have really such nature and be not an albuminous body of varying constitution. Whatever form of pepsin be used, if good effects are to be obtained from it it must be given with acid, unless indeed there be reason to be- lieve that this constituent of the gastric juice is not wanting. Alcohol destroys the digesting power of pepsin, and therefore wines are inferior preparations of it. The reactions of pepsin with organic and inorganic matters are very complex, and not well understood : consequently we think the physician should eschew all elixirs or compound preparations 815 8i6 EXTRANEOUS REMEDIES. of the drug, using only the powdered pepsin or a glycerole of pepsin, or a freshly prepared digestive solution of water and muriatic acid, or glyce- rin, water, and muriatic acid. If other remedies are to be given it is no great hardship to write a second prescription for them. THERAPEUTICS. It is a question of some importance to decide how far pepsin is valuable and reliable as a medicine. It is evident that any influence for good which it possesses is dependent upon its solvent power, and that this, therefore, is a measure of its value. Only a small portion of commercial pepsin approximates in power the official stand- ard. Moreover, the pepsin in life must soon pass out of the stomach. One of two conclusions seems to be inevitable : either the doses of pepsin habitually used are preposterously small or else pepsin acts upon the stomach itself in some way as a stimulant. Clinically, pepsin has been used with asserted advantage in the /oss of digestive power in adults, whether primary or occurring in the course of other affections. Proba- bly four-fifths of the drug which has been given has been inert, either originally or from the method of its administration ; and in the great majority of cases the good that has been achieved has been due, not to the pepsin, but to the regulation of the diet and habits of the patient and to the drugs which have been exhibited along with the animal fer- ment. The value of pepsin has been overestimated, and it has been given to adults in ridiculously small doses : at least half a drachm (2 Gm.) of the ordinary commercial article, or of the Saccharated Pepsin, U. S. , should be exhibited at a dose. The testimony as to the usefulness of pepsin in diseases of young children is very strong. To such it is generally given in doses proportionately much larger than those usually exhibited to adults. The use of small doses of pepsin in children is therefore much more rational than in adults ; and our own experience is in close accord with what seems to us the dictates of common sense : in the chronic indigestion and consequent diarrhoea of young children it may be tried with great hope of benefit. To a baby six months old five grains (0.3 Gm.) of the saccharated pepsin may be given in a little acidulated water after each feeding. Pepsin (U.S.) given in doses of ten to fifteen grains (0.71 Gm. ) to the adult probably has some digestive value. PANCREATIN, U. S., has been extensively used in dyspepsia as a digestant in lieu of pepsin. For action it requires the presence of an alkali, and in the acid gastric juice would not only not act, but would itself in all probability be digested and destroyed as a ferment ; * and it is of no value except for the preparation of predigested foods. EXTRACTUM MALTI. Malt is the seeds of the ordinary barley caused to enter the incipient stage of germination by artificial means and dried. It is prepared by soak- ing the grains in water and leaving them in heaps in a room of moderate DIGEST ANTS. 817 temperature, and by occasional turning preventing the heat given off during the process of germination from accumulating ; then finally killing the germ with heat. The color varies from pale amber to black, according to the degree of the heat used in drying. There is formed during germi- nation a peculiar ferment, diastase, one part of which is able to convert about two thousand parts of starch into dextrin and glucose. The Ex- TRACTUM MALTI of the U. S. Pharmacopoeia is made by rapidly evapo- rating an infusion of malt to the consistency of a thick, honey -like liquid at a temperature not above 130 F. It should contain practically all the diastase of the malt. The odor of the extract of malt is slight and pecu- liar, the taste sweet, and the reaction to paper distinctly acid. It dis- solves freely in water, and is precipitated by alcohol, tannic acid, mercuric chloride, and various other metallic salts. Commercial malt extracts vary greatly : some of them are practically preparations of glucose, others are of the nature of strong or weak beers. True extract of malt contains no alcohol at all. Extract of malt has been much used in cases of disease with failing nutrition, and especially when the power of digesting substances is feeble. When it contains largely either glucose or alcohol it affords food -material to the system ; but the important ques- tion for the therapeutist is, How far is it possible in disease to aid in the digestion of starchy substances in the stomach and intestines by the use of diastase ? R. H. Chittenden and G. W. Cummins have made a series of investigations in order to determine the conditions which are necessary for the amylolytic action of diastase. They find that it acts better in a neutral than in an alkaline solution ; that proteid matters when present in the alkaline solution prevent the retarding influence of an alkaline carbonate ; that neutral peptone exerts a direct stimulant effect on the amylolytic action, but that the greatest amylolytic action is observed in the presence of proteid matter partially saturated with acid, although a larger percentage of acid-proteids may cause complete destruction of the ferment. These results seem to prove that diastase, when taken into the stomach, must sooner or later be completely destroyed by the gastric juice, and that in order for it to have any distinct effect upon digestion it must be given at the beginning of the meal. In cancer of the stomach and other diseases in which the gastric juices lack acidity, the action of diastase upon starch must be more pronounced ; but unfortunately the failure of the starch-digestion is usually associated with gastric hyper- acidity. PAPAIN. The Carica Papaya is an herbaceous tree universally cultivated in tropical countries for its fruit, the papaw, the juice of which yields a peculiar ferment, to which the name of Papain was given by Wurtz, but which is now generally known by the name originated by Pekolt, Papayotin. This substance is a ferment, which has the power of dis- solving fibrin, muscular fibres, tissues, etc. 52 8l8 EXTRANEOUS REMEDIES. According to \Vurtz, one part of papain in alkaline solution at a temperature of 40 C. is capable of dissolving one hundred and seventy-five parts of moist fibrin, which it converts into a peptone. VVurtz affirms that it makes no differ- ence whether the solvent solution be alkaline or acid, but Brunton, Wyatt, and Martin state that as little as one-half per cent, of hydrochloric acid arrests the digestion. Albrecht, however, reaffirms that hydrochloric acid hastens the action of papain, and states that the official preparation in use in the Paris hospitals is an acid one. Further, in an elaborate series of experiments, August Hirschler 5 reaches the result that digestion goes on most rapidly in acid solutions, that it is very feeble in alkaline solutions, and ceases entirely when the alkalinity becomes excessive. It is stated that in order to convert fibrin entirely into pure peptone, so that nitric acid will produce no precipitate, the proportion of the ferment must be at least three per cent., and the digestion must continue for forty-eight hours. Papain first coagulates milk, then precipitates it, and finally digests it into a thin fluid. Taken into the stomach, papain has no action upon the living tissues, but one grain of it injected directly into the blood is sufficient to cause death in a very short time in rabbits or in dogs. Its action on albuminoids is said to resemble that of trypsin rather than that of pepsin. (See Martin. 6 ) Papain has been used in medicine as a substitute for pepsin, in doses of five to ten grains (0.3-0.6 Gm. ). It has also been very highly recom- mended for the purpose of destroying organic tissues of low type, as in diphtheria (A. Jacobi 7 ), in the thickening of chronic eczema, in warts, and in pyogenic membranes surrounding old sinuses or abscesses. It is not caustic, but simply dissolves the diseased tissues, and is said to cause no pain. 8 It should be applied, one part each of papain, glycerin, and water. In our laboratory experiments commercial papain of the most esteemed brands has failed to exert any solvent power over albuminous substances, and it is probably a remedy of little value. REFERENCES. DIGESTANTS 5- HlRSCHI - ER Ungar. Arch. f. Me.L, 1893, i. 1. GRAY Ed. M. J., Jan. 1853. 6. MARTIN B. M. J., July 25, 1885. 2. M. T. G., April, 1857. 7. JACOBI T. G., ii. 3. WAYNE Amer. Journ. Pharm., 1868. 8. Birmingham Med. Rev., 4. N. Y. M. R., xl. 398. May. 1886. FAMILY IV. ABSORBENTS. THIS class contains remedies which are used for the purpose of absorbing acrid and deleterious materials, such as offensive discharges on the exterior of the body, and acrid secretions, or the irritant products of the partial decomposition of food, in the alimentary canal. For the first purpose very fine dry earth and plaster of Paris are used to some extent in practice ; but, as their employment is purely within the prov- ince of the surgeon, we shall say no more about them here. CHARCOAL. Charcoal is official in the U. S. Pharmacopoeia in two forms : CARBO LIGNI. Charcoal prepared from wood. CARBO ANIMALIS. Animal Charcoal, prepared from bone. Charcoal for medicinal purposes should be made out of a light, porous wood : that prepared from the young shoots of the willow or of the pop- lar is almost exclusively employed. It is a black, brittle substance, and should have more or less lustre. It has a very remarkable power of ab- sorbing many times its own bulk of gases, and, when exposed to the air, increases rapidly in weight. It should therefore, when intended for medicinal purposes, be powdered as soon as it is burnt, and put in small, completely filled, closely sealed bottles. Animal charcoal, or bone-black, formed as it is by the partial burning of bones, contains a large percentage of calcium phosphate and carbon- ate. Purified Animal Charcoal (CARBO ANIMALIS PURIFICATUS, U. S. ) is prepared by removing the lime salts by dilute muriatic acid. THERAPEUTICS. Internally, charcoal is employed as an absorbent in fermentative intestinal dyspepsia, cardialgia, and similar disorders. As moist charcoal is not an absorbent, it is evident that it is of very little value ; its habitual employment is generally combined with that of laxa- tives for fear of accumulation in the alimentary canal. Dose of charcoal from one to two drachms (4-8 Gm. ). Except in a mechanical way, it is perfectly innocuous in any dose. 819 FAMILY V. DISINFECTANTS. DISINFECTANTS are agents which are used for the purpose of pre- venting the growth of bacteria. This may be accomplished in two ways, either by killing the germs (germicides) or by rendering the media un- favorable for the growth of the micro-organisms (antiseptics). All chemical germicides become, however, when in dilute solution, antiseptic, so that the natural division of these agents, as given above, does not serve well as a basis of a classification for systematic study. Disinfectants may be conveniently divided into forces, and material chemical groups as follows : I. Forces ; heat and cold. II. Metallic salts, including certain salts of mercury, silver, copper, zinc, and iron. III. Halogens, including chlorine and the hypochlorites, iodine, bromine, and their various compounds. IV. Oxidizing disinfectants, including especially hydrogen dioxide and potassium permanganate. V. Carbon compounds, including carbolic acid, cresylic acid, creosote, salicylic acid, benzoic acid, thymol, menthol, alcohol, formaldehyde, the volatile oils and allied drugs. VI. Acids and alkalies, including especially sulphurous acid, boric acid, hydrofluoric acid, and their salts. I. COLD AND HEAT. Cold. The effect of low temperature in preventing the growth of micro-organisms is well known and daily taken advantage of by the housewife in the preservation of foodstuffs. Very few bacteria will multi- ply at a temperature lower than 40 F. On the other hand, cold cannot be considered as a germicidal agent, for it has been shown that even the extraordinarily low temperature of liquid air does not destroy the vitality of the typhoid bacillus and other test organisms. Heat. As a germicide fire is absolutely efficient, but destructive. The lower degrees of heat have been used without moisture (dry heat), and with moisture (moist heat). Moist heat is much more efficient than is dry heat. According to Sternberg, while most micro-organisms are destroyed in the presence of moisture by a temperature of 62 C. (143 F. ), certain of the more resistant species of bacteria will withstand a heat considerably higher than this ; but all bacteria free from spores are destroyed by the heat of boiling 820 DISINFECTANTS. 821 water in one to two minutes. On the other hand, some spores are able to with- stand boiling water for several hours. To destroy with certainty all forms of life requires, according to Steinberg, 5 an exposure to moist heat of a temperature of 115 C. (239 F. ) for half an hour. This temperature can of course be produced only under pressure. The most satisfactory manner of using this method of ster- ilization is by means of the autoclave, an apparatus so arranged as to prevent the escape of the steam until the pressure within the autoclave has reached nine to ten pounds, at which time the temperature will approximate 115 C. Dry heat is much inferior in its germicidal effect to moist heat. Wolf 1 found that dry air at 140 C. was scarcely more destructive than its watery vapor at 100; Koch, that five minutes' exposure to steam was equal to an hour or an hour and a half with the dried air. The results reached 'by Koch and Wolffhiigel* are in accord with other evidence, and may be considered correct. They are as follows : 1. A temperature of 100 C. (212 F.), dry heat, maintained for one hour and a half, will destroy bacteria which do not contain spores. 2. Spores of mould-fungi require for their destruction in hot dry air a tem- perature of from 110 to 115 C. (23o-239 F.) maintained for one hour and a half. 3. Bacillus-spores require for their destruction in hot air a temperature of 140 C. (284 F. ) maintained for three hours. 4. In dry air the heat penetrates objects so slowly that packages, such as pillows or small bundles of clothing, are not disinfected after an exposure of from three to four hours to a temperature of 140 C. (284 F. ). 5. Exposure to a temperature of 140 C. ( 284 F. ) in dry air for a period of three hours injures most objects requiring disinfection (clothing, bedding, etc.) to a greater or less degree. George H. Roh 3 found that rolls of blankets exposed in a chamber heated to 280 F. for three hours were very slightly affected in their interior. This is in strict accord with the teaching of Parsons and Klein,* of the London Local Governing Board, and of other observers. Dry heat is so inferior to moist heat that it is at present never em- ployed as a germicide. Quarantine and other health stations are or ought to be supplied with apparatus for exposing infected articles to the prolonged action of hot steam in chambers, etc. For ordinary household purpose, however, the physician is forced to rely upon boiling, which, when maintained for thirty minutes, may be considered as practically efficient. II. METALLIC SALTS. . HYDRARGYRUM CHLORIDUM CORROSIVUM. The bichloride of mer- cury has long been recognized as one of the most powerful germicides known. In 1870 John Dougall announced that corrosive sublimate, i part in 6500, would kill spermatozoa, and i part in 6000 infusoria ; the later researches of Koch, Jalan de la CroSx, and Sternberg have confirmed this result, and shown that corrosive sublimate is one of the most powerful of known germicides. Micrococci and bacilli in active growth without spores are killed by solutions of i in 20,000, while solutions 822 EXTRANEOUS REMEDIES. of i in 1000 will rapidly destroy the spores of B. anthracis and B. subtilis. Results contrary to these have, it is true, been obtained by Klein, of London, who asserts that a one per cent, solution of the mercuric chloride is no more a germicide than is vinegar ; but the evidence to the contrary is so strong that it seems almost a cer- tainty that there was some error in Klein's experiment. According to the detailed experiment of Koch, the spores of B. anthracis are absolutely incapable of germi- nating in a proteid solution if as little as i part of corrosive sublimate in 300,000 be present. Sternberg has confirmed the experiments of Koch. It must be remembered that corrosive sublimate is so readily decomposed by ammonia and other substances usually present in a mass of filth that it is not availa- able for disinfectant purposes on a large scale ; even when the amount of organic matter is small, the usefulness of corrosive sublimate is often destroyed by its chemical instability : thus, it should not be employed for the destruction of germs in fecal discharges. A standard solution of i part in 1000 may be used for bedding, which can be soaked in it, for washing the floors and walls of infected apartments, and for disinfecting the hands of surgeons and gynaecologists. After the corrosive sublimate has done its work it should be removed by free washing with pure water. Even in the cases just spoken of corrosive sublimate is often inferior to formaldehyde. For various surgical purposes the sublimate may be used in strengths varying from 1:2000 to i: 10,000. It is well to add to the solutions of corrosive sublimate an equal quantity of ammonium chloride or else a small proportion of tartaric or hydrochloric acid, as these substances lessen the liability to precipitation. HYDRARGYRUM IODIDUM RUBRUM. U. S. The biniodide of mer- cury, although not nearly so widely employed as the bichloride, seems to be even more active as a germicide. According to the experiments of Burgess, 1 a i : 5000 solution of the biniodide is equivalent in strength to a i : 2000 solution of the bichloride. Sternberg has found that a i : 20,000 solution of the biniodide is equivalent to i : 15,000 solution of the bichloride of mercury. The probable reason why the mercuric iodide has not come into use as a germicide is the fact that it is almost insoluble in water. It may be readily dissolved, however, by the addition of potassium iodide or lithium iodide to the solution. Rosenberger and England " suggest the double lithium mercuric iodide, which is freely soluble in water, is not pre- cipitated by the fixed alkalies, and according to their experiments is actively germicidal. ARGENTI NITRAS. U. S. The salts of silver rank next to the salts of mercury as the most powerful germicides we possess. According to Miquel, silver nitrate prevents the growth of atmospheric germs when present in the proportion of i part to 12,500. According to Boer, a i : 4000 solution destroys typhoid bacillus in two hours, but it required a i : 2500 solution to kill the diphtheria bacillus in the same time. Behring found that a i : 10,000 solution is capable of destroying the anthrax spores in forty-eight hours. DISINFECTANTS. 823 Unfortunately, the silver nitrate is an extremely unstable salt, being decomposed by the alkalies, the mineral acids, albumin, and even decom- posing in the air on exposure. Various other less active metallic salts have been used in the past as disinfectants but are of very little practical value, and have been superseded by the numerous active modern germicides. Many of these salts act chiefly by the capability which they have of taking sulphur away from sul- phuretted gases, and thereby lessening odor; so that they are rather deodorants than disinfectants. The most used of these disinfectants are the zinc sulphate, zinc chloride, and lead nitrate, the latter forming the basis of the so-called Ledoyeri s Disinfectant Solution. They should, 'all of them, be totally disregarded. Old iron, and the impure ferrous sul- phate {Copperas), have to some extent resisted modern innovation, and have been believed to have the power of oxidizing organic matter and of attacking disease germs, which makes them of value. Of the two, cop- peras is certainly the more efficacious; but in an official study Dr. A. J. McLaughlin * has shown that it has no dominant influence over putre- factive changes unless present to the extent of five per cent. that its saturated solution does not affect pathogenetic organisms, and that the same solution mixed with half its bulk of faeces fails to disinfect the mass after three days. III. HALOGENS. CHLORUM CHLORINE. When chlorine is brought into contact with organic substances and moisture, it unites with the hydrogen of the water and liberates nascent oxygen, which rapidly oxidizes and destroys the organic compound. When chlorine comes in contact with sulphuretted hydrogen, it removes its hydrogen and thereby destroys it. On account of its destructive action on organic matter, its being extremely obnoxious to animal life, and its comparative expensiveness, chlorine gas is at present never used to disin- fect rooms, ships' holds, or similar places. Inspired in sufficient amount, chlorine gas produces, both in man and in the lower animals, narcotism, and finally death from paralysis of the respiratory centre.* The germi- cidal influence of chlorine is very great. Fisher and Proskauer found that dried anthrax spores mantained their integrity for one hour when exposed to the action of a dry chlorine atmosphere containing 44.7 parts of chlorine in 100 ; but when the air and the spores were moist, one hour's exposure to an atmosphere containing four per cent, of chlorine produced complete disinfection. If the exposure were continued for three hours, one per cent, of chlo- rine was an efficient germicide : and if the spores were exposed for twenty-four hours, the effective proportion of chlorine could be still further reduced. In Sternberg's ' experiments, six hours' exposure of vaccine lymph dried upon ivory points to an atmosphere containing i part of chlorine in 200 was sufficient to destroy the infec- tive property of the lymph, while the bacteria of putrid urine were destroyed after * Consult Arch.f. Exper. Path. u. P/iarm., xiii. 824 EXTRANEOUS REMEDIES. six hours' exposure to an atmosphere containing i part of chlorine in 400. Klein * also found that after the compartment of a stable in which pigs had died of swine- plague had been thoroughly fumigated for six hours with chlorine, healthy animals could be placed therein with safety. The result of all our knowledge upon the subject of the disinfectant properties of chlorine, iodine, and bromine has been summed up by George H. Roh6 3 as follows: 1. Chlorine is an efficient disinfectant when present in the proportion of i part in 100, provided the air and the objects to be disinfected are in a moist state and the exposure continues for upwards of an hour. 2. Chlorine, when used in sufficient concentration to act as a trustworthy disin- fectant, injures colored fabrics and wearing apparel. 3. Bromine is an efficient disinfectant in the proportion of i part in 500, pro- vided the air be in a moist state and the exposure continues for upwards of three hours. 4. Iodine, in solution, is an efficient disinfectant in the proportion of i part in 500, the exposure continuing for two hours. 5. The use of chlorine, and in a greater degree of bromine, requires consider- able experience in management : when carelessly handled these elements may cause inconvenient or even dangerous symptoms in persons using them ; hence they are not suitable as disinfectants for popular use. For purposes of practical disinfection chlorine is usually obtained from the decomposition of one of the hypochlorites. CALX CHLORINATA. U.S. Chlorinated Lime. Bleaching-powder is a grayish-white substance occurring in powder or friable lumps, having a hot, acrid, astringent taste, and an odor resembling that of chlorine. It is made by the action of chlorine upon calcium hydrate, or slaked lime, and should contain at least thirty per cent, of chlorine. It probably varies in its chemical constitution, but, according to the most recent views, is chiefly composed of the calcium hypochlorite and chloride. When exposed to the air it slowly evolves hypochlorous acid, which, being an unstable compound, undergoes spontaneous decomposition, and finally sets free fourteen-fifteenths of its chlorine. When an acid is added to chlorinated lime, the chlorine gas is rapidly evolved. If a specimen of bleaching-powder be very moist, it generally contains an over-proportion of the deliquescent calcium chloride, is correspondingly unable to liberate chlorine, and is therefore of inferior value. The experiments of J. R. Duggan 4 indicate that the hypochlorites are among the very best of our practical germicides. He found that o. 25 of one per cent. ( i part to 400) of chlorine as hypochlorite is an effective germicide even when allowed to act for only two minutes ; while 0.06 of one per cent. (6 parts to 10,000) will kill the spores of B. anthracis and B. subtilis in two hours. Bleaching-powder usually contains from twenty-five to forty per cent, of available chlorine. For most purposes, a solution made with i part DISINFECTANTS. 825 of this preparation to 100 parts of water is strong enough, for it will con- tain from 0.25 to 0.40 of one per cent, of chlorine as hypochlorite. As is stated above, the smaller of these quantities is sufficient to destroy spores almost instantly. There are very few purposes to which disinfectants are applied that are not fulfilled by this solution of i to 100 of bleaching- powder. It is not dangerously poisonous, is said not to injure the fibre of clothing, bedding, etc. , and is very cheap, since it is worth only about five cents per pound. For the destruction of disease-germs in urine, fecal discharges, sputum, etc. , a saturated solution of bleaching -powder appears to be in all respects the best disinfectant known : for the purification of cesspools, sewers, or similar receptacles, or of masses of infected filth, chlo- rinated lime stands at the head of known germicides. * LIQUOR SODE CHLORINATE. U. S. Solution of Chlorinated Soda, Labarraque' s Solution, is made by triturating chlorinated lime with a * There are not many affairs in life in which the public have been so superabundantly fleeced as in the matter of disinfection. A most extraordinary part of this swindling is the ease with which distinguished members of the medical profession have given certifi- cates of efficiency and value to comparatively inert and extraordinarily expensive pro- prietary compounds. Oddly enough, the cat that has drawn the chestnuts out of the fire for avaricious manufacturers has not even had the sense to smell the odor of its own paws when burning ! There is no proprietary disinfectant whose value corresponds with its selling price. The following table was compiled some years since by A. W. Harlan, of Chicago. The cost represents the same germicidal power. Name. Full Cost. Corrosive sublimate $o.oo^j Chlorine OI A Copper sulphate oi>& Mercury biniodide 02^ Mineral acids 03$ Bromine 08 Ammonia gas 13$ Chloroform 14! Chromic acid 15 Potassium chlorate i6| Silver iodide 20 Picric acid 2o| Iodine 2if Silver nitrate 22^ Potassium permanganate y>\ Carbolic acid 34f Benzoic acid 5 Salicylic acid 69 Osmic acid 4-62i 9 Thymic acid 4-8 Anhydrous prussic acid .... n.oo Dr. H. C. Wood, Jr., has compiled for the present edition (i2th) the following table on the basis of one cent's worth of corrosive sublimate. In comparing these tables it should be remembered that the constitution of some of these proprietary disinfectants has entirely changed. Name. Full Cost. Corrosive sublimate $o.oo$j Little's sol. phenyl 13.00 Fifty per cent, chlor. zinc, Squibb's 35.00 Feuchtwanger's disinfectant . . 35.00 Ph6nol sodique (Hance Bros. & White) 51.00 Platt's chlorides 66.00 Girondin 80.00 Williamson's sanitary fluid . . . 80.00 Bromo-chloralum 80.00 Blackman's disinfectant .... 96.00 Squibb's solution impure carbolic acid 112.50 Burchardt's disinfectant .... 182.50 Ph6nol sodique, French .... 255.00 Listerine 495-oo Name. Full Cost. Mercury bichloride fo.oi Chlorinated lime o.oj Cresol 0.06 Bacillol 0.24 Lysol 0.23 Name. Full Cost. Creolin $0.50 Platt's chlorides 3.19 Sanitas 11.72 Listerine . . 62 81 826 EXTRANEOUS REMEDIES. solution of sodium carbonate. It is a greenish-yellow liquid, having a slight odor of chlorine and a sharp saline taste. It contains, among other substances, sodium hypochlorite, and possesses the therapeutic and disinfectant properties of the chlorinated compound. Owing to its liquid form, its comparative freedom from odor, and its depositing sodium chloride on evaporation, it is the most elegant of all the chlorine prepa- rations for use in the sick-room. Properly diluted, Labarraque's solution may be employed for all the therapeutic purposes for which chlorine water is used. The dose is half a fluidrachm to two fluidrachms (2-7 C.c. ) in half a tumblerful of water. According to Duggan, a two per cent, solution of sodium hypochlorite, representing six per cent, of available chlorine, will kill the anthrax spores in thirty minutes. Sternberg found that it required seven per cent, of a commercial Labarraque's solution to kill the anthrax spores in two hours. It must be remembered that the commercial preparations of both chlor- inated lime and chlorinated soda vary enormously in strength. The Committee on Disinfection of the American Public Health Association, 1885, found that commercial specimens of Liqitor Sod 2. KUSSNER 3. BLUM . . 4. HENRY . 5. SOLLY . . 6. BUCHOLZ 7. FISCHER . . M. T. G., 1878, 716. . D. M. W., 1891, xvii. . M. News, Sept. 18, 1887. . Centralb. f. d. ges.Therap. Feb. 1892. . A. E. P. P., 1874, iv. . D. M. W., 1898, xxiv. SALOL. 1. SAHLI Science Med., April 14, 1886. 2. KUMAGAWA . . . V. A. P. A., 1888, cxiii. 3. LESNIK A. E. P. P., 1888, xxiv. CREOSOTE. 1. FREUDENTHAL . N. Y. M. R., April, 1892. 2. ZAWADZKI . . . . S. Jb., 1896, ccxlix. 3. SAILLET B. G. T., cxxiii. 4. IMBERT Nouveau Mont. M6d., 1892, i. 5. CATILLON .... Bull. Mem. Soc. Therap., 1892. 6. HARE U. M. M., i. 7. HOLSCHER and SEIFERT . B. K. W., 1892, xxix. 8. BRISSONET . . . T. G., 1893. 9. Internal. Klin. Rundschau, Feb., 1890. 10. BUCHOLZ .... A. E. P. P., 1874, iv. i. KUPRIANOW GUAIACOL. . . . Centralb. f. Bakter., 18 2. LINOSSIER and LANNOIS . E.G. T., 1894. Ixiii. 3. ESCHLE S. Jb., 1896, ccl. 4. GUINARD . . . . B. G. T., 1893. 5. HESSE D. M. W., 1898. 6. HATCH M. News, 1903, Ixxxiii. CRESOL. I. SCHWYZER 2. FRIES 3. MAASS 4. VONDERGOLDZ . 5. BURGESS .... 6. VAN ERMENGEN 7. PFREUGER . . . 8. DELPLANQUE . 9. FRXNKEL . . . 10. FAUST II. TOLLENS . N. Y. Med. Monatschrift, 1904, vi. 427. . M. M. W., 1904, No. 16. . D. A. K. M., 1894, lii. 446. . N. Y. M. R., 1892, xlii. 367. . L. L., 1900, i. 1797. . B. A. R. B., 1889, iii. 60. . A. Pharm., 1890, 701. . Thesis, Paris, 1888. . Zeitsch. f. Hyg., 1889. . Jahrsb. Gesells. Nat. Heilk., Dresden, 1895-98. . A. E. P. P., lii, 220. NAPHTOL. i. SURVEYOR and HARLEY . B. M. J., 1895, ii. a. SAHLI Th. M., 1887. 3. WEEKS N. Y. M. R., 1889, xxxvi. "3- MENTHOL. 1. PELLACANI . . . A. E. P. P., xvii. 376. 2. GOLDSCHKIDER . A. G. P., l886. 3. RUSSELL N. Y. M. R., Nov. 1885. 4. lOTEYKO C. R. S. B., 1903, Iv. 5. BISHOP Kansas City Med. Exam., 1892. THYMOL. J. BXLZ L. M. R., 1878. RESORCIN. 1. SCHOMACKER . . Thesis, Dorpat, 1886. 2. COHN In. Dis., Berlin, 1882. 3. ANDEER Ueber das Resorcin, Wurz- burg, 1880; C. M. W., 1881. 4. PLATT A. J. M. S., 1883, i. 5. MURRELL . . . . M. T. G., 1881, ii. 6. LOEFFLER .... Thesis, Wiirzburg, 1889. 7. DUJARDIN-BEAUMETZ . B. G. T., ci. 113. FORMALDEHYDE. 1. Mosso and PAOLETTI . A. I. B., 1895, xxiv. 2. TRILLAT .... La Formaldehyde, Paris, 1896. 3. KLUBER M. M. W., 1900, ii. 4. ZORN M. M. W., 1900, ii. 5. TUNNICLIFFE and ROSENHEIM . Cb. P., 1901, xv. 2. 6. FOULKRTON . . . L. L., 1899, ii. 7. SLATER and RIDKAL . Dis. and Preserv. of Food, 1903, 309. 8. RAVENEL and GILLILAND . U. P. M. B., April, 1903- 9. KOCH A. J. P., 1902, vi. 10. VAN ERMENGEN and SUGG . A. Pharm., 1895, i- 11. HORTON M. News, August, 1896. 12. HERZOG Cb. B., xxxiv. 1903. 13. ORTH B. K. W., 1896, xxxiii. 14- B. M. J., 1903, i. 15- B. M. J., 1902, ii. 16. BRICKDALE . . . L. L., 1903, i. 17. PARK N. Y. M. J., Ixxvii. 18. BARROWS . . . . N. Y. M. J., Ixxvii. 19. HONAN N. Y. M. T., 1903. BENZOIN. 1. SELIGSOHN . . 2. URE 3. MEISSNER and 4. GRUBE . 5. GARROD 6. KELLER 7. VIRCHOW . 8. ASHHURST . 9. DOUGALL . 10. SALKOWSKI 11. BUCHOLZ . 12. FLECK . 13. SENATOR . . 14- 15. LEWANDOSKY . Chem. Centralb., 1861. . M. C. Tr., 1841, xxix. 30. SHEPARD . Untersuch. iiber das Entstehen der Hip- pursaure, Hanover, 1866. . Cb. C., 1876, 777. . L. L., Nov. 1844. . Ann. der Chem. u. Pharm., 1842, xliii. . Z. P. C., vi. . P. M. J., Feb. 24, 1900. . M. T. G., 1872, i. . B. K. W., 1875, 297. . A. E. P. P., iv. . Benzoesaiire, etc., Munich, 1875- . Allg. Wien. Med. Zeitung, 1876, xxiii. P. M. T., iv. . Z. K. M., 1903, xl. DISINFECTANTS. 877 REFERENCES. Continued. CINNAMIC ACID. 1. LANDHRER . . . . M. M. W., xxxv. a. ROBINSON .... M. A., 1902. SULPHUROUS ACID. i. PFEIFFER .... Sajous's Annual, 1891. FLUORIDES. 1. TAPPEINER . . . A. E. P. P., xxvii. 2. TISCHER and BEDDIES . A. R., 1898. 3. BINZ V. C. M., 1891, ii. 4. GORL M. M. W., 1899. BORIC ACID. 1. DUJARDIN .... Union M6d. du Nord-Est, Nov. 1891. 2. DUMAS and SCHNATZLES . Pharm. Journ., April, 1874. 3. BUCHOLZ . . . . A. E. P. P., iv. 4. WALB C. K. M., 1882, iii. 529. 5. STERNBHRG . . . A. J. M. S., Ixxxiv. 321. 6. ANDREWS .... Chicago Med. Exam., 1889, Iviii. 7. CHITTENDEN and GIES . A. J. P., i. 39. 8. STRAUB S. Jb., 280. 9. WELCH N. Y. M. R., 1888, xxxiv. 10. MODODEWKOW . . St. L. C. R., 1881. 11. HOGNER S. Jb., 202. 12. ROSENTHAL . . . Allg. Wien. Med. Ztg., Jan. 1884. 13. GREENS B. M. S. J., ciii. 209. 14. FOLSOM B. M. S. J., Feb. 18, 1886. 15. MAASS Th. M., 1903, iii. 16. GRUBKR H. S. Jb., 1879. 17. PLAUT Thesis, Wiirzburg, 1889. 18. FERE Semaine M6d., 1894, xiv. 19. HARRINGTON . . A. J. M. S., cxxviii. 418. PRACTICAL DISINFECTION. 1. ABBOTT Tr. I. C. C., 1893. 2. WOOD, JR U. P. M. B., 1905. APPENDIX. Pound, Ounce, Drachm, Scruple, Grain, APOTHECARIES' WEIGHT-APOTHECARIES' MEASURE. FORMERLY OFFICIAL IN THE UNITED STATES PHARHACOPCEIA. 12 Ounces. 8 Drachms. 3 Scruples. 20 Grains. 1 Grain. Gallon, Pint, Fluidounce, Fluidrachm. Minim, "I 8 Pints. 16 Fluidounces. 8 Fluidrachuis. 60 Minims. 1 Minim. WEIGHTS AND MEASURES OF THE METRICAL OR FRENCH SYSTEM. NOW OFFICIAL IN THE UNITED STATES PHARMACOPEIA. MEASURES OF LENGTH. One Myriametre = 10,000 Metres. One Kilometre = 1,000 Metres. One Hectometre = 100 Metres. One Decametre = 10 Metres. One METRE = the ten-millionth part of a quarter of the meridian of the earth. One Decimetre = the tenth part of one Metre or 0.1 Metre. One Centimetre = the hunredth part of one Metre, or 0.01 Metre; written Cm. One Millimetre = the thousandth part of one Metre, or 0.001 Metre; written Mm. WEIGHTS. One Myriagramme = 10,000 Grammes. One Kilogramme = 1,000 Grammes. One Hectogramme = 100 Grammes. One Decagramme = 10 Grammes. One GRAMME = the weight of a cubic Centimetre of Water at 4 C. ; written Gm. One Decigramme = the tenth part of one gramme, or 0.1 Gramme. One Centigramme = the hundredth part of one Gramme, or 0.01 Gramme. One Milligramme = the thousandth part of one Gramme, or 0.001 Gramme. MEASURES OF CAPACITY. One Myrialitre =10 cubic Metres, or the measure of 10 Milliers of Water. One Kilolitre = 1 cubic Metre, or the measure of 1 Millier of Water. One Hectolitre =100 cubic Decimetres, or the measure of 1 Quintal of Water. One Decalitre = 10 cubic Decimetres, or the measure of 1 Myriagramme of Water. One LITRE = 1 cubic Decimetre, or the measure of 1 Kilogramme of Water. One Decilitre = 100 cubic Centimetres, or the measure of 1 Hectogramme of Water. One Centilitre = 10 cubic centimetres, or the measure of 1 Decagramme of Water. One Millitre = 1 cubic Centimetre, or the measure of 1 Gramme of Water. 879 88o APPENDIX. RELATION OF APOTHECARIES' WEIGHTS AND MEASURES TO EACH OTHER. One Pound One Ounce One Drachm One Scruple One Grain One Gallon One Pint One Fluidounce One Fluidrachm One Minim In diftilled water at the temperature of 60. 0.7900031 Pint = 1 .0533376 Fluidonnces = 1.0533376 Fluidrachms = 10.1265427 Pounds 1.2668178 Pounds 0.9493633 Ounce 0.9493633 Drachm 6067.22.S 505.6019 63.2002 21.0667 1.0533 5S328.8862 7291.1107 455.6944 56.9618 0.9493 Minims. Minims. Minims. Minims. Minims. Grains. Grains. Grains. Grains. Grain. RELATION OF APOTHECARIES' OR WINE MEASURE TO CUBIC MEASURE. One Gallon One Pint One Fluidounce = 231. Cubic Inches. = 28.875 Cubic Inches. = 1.80468 Cubic Inches. One Fluidrachm One Minim 0.22558 Cubic Inch. 0.00375 Cubic Inch. RELATION OF APOTHECARIES' WEIGHTS TO METRICAL WEIGHTS. Fraction of a grain in Drachmt, Ounctt, and Povndt in Milligramme*. Grain. Milligrammes. Grain* in equivalent metrical weight*. equivalent metrical weight*. Drachms. Grammes. A "" 1.012 1.079 Grains. 1 Centigrammes. 6.479 1 2 _ 3.887 7.775 - 1.295 2 Decigrammes. 1.295 I _ Decagramme*. 1.166 A M 1.349 I _ 1.943 4 tm 1.555 A 1.619 4 2.591 5 m 1.943 40 1 799 5 _ 3.239 6 2.332 l *" 'I UP 3.887 7 B 2.721 A = 2.159 7 4.535 Ounces. A A A - 2.591 2.699 3.239 4.049 8 9 10 12 15 _ 5.183 5.831 6.479 7.775 9.798 ) 4 5 - 3.1103 6.2206 9.3309 Hectogrammes. 1.2441 1.5551 JL _ 4.319 Grammes. A _ MM 16 AA - .036 OQFL 6 7 ~; 2.1772 A - 6.479 XV 24 zy* .555 8 2.4882 _ 8.098 25 .619 9 2.7992 10 3.1103 - 10.798 30 40 = .943 2.591 11 - 3.4213 B 12.958 Pounds. - 16.197 50 60 _ 3^887 1 2 3.7324 7.4648 21.597 Kilogrammes. 32.395 3 - 1.1197 APPENDIX ttl RELATION OF METRICAL WEIGHTS TO APOTHECARIES' WEIGH*. .154 - .M3 J17 .771 .92C .1254 .1>43 .17S .7717 1.2347 L 1.M3 3jM< 4.S3* - - ' 12JU7 i I I I A A i U H 3 44 ' r| 11 14 gr. XT. 31- Si. 5oT. fti 3ri|. ( ft xrrL 882 APPENDIX. TABLE OF THE PROPORTION BY MEASURE OF ALCOHOL (SP. 0.825) CONTAINED IN ONE HUNDRED PARTS OF DIFFERENT WINES, ETC.* Lisa (mean) 25.41 Raisin wine (mean).... 25.12 Marsala [Sicily ma- deira] (mean)... 25.09 strongest (J.) 21.10 weakest (J.) 19.90 Port, strongest 25.83 mean 22.96 weakest 19.00 strongest (C.) 20.49 mean (C.) 18.68 weakest (C.) 16.80 strongest (J.) 23.20 weakest (J.) 20.70 White port (C.) 17.22 Madeira, strongest 24.42 mean 22.27 weakest 19.24 strongest (C.) 20.35 strongest (J.) 19.70 weakest (J.) 19.00 Sercial madeira 21.40 Ditto (C.) 18.50 Sherry, strongest 19.81 mean 19.17 weakest 18.25 strongest (C.) 19.31 mean (C.) 18.47 weakest (C.) 16.96 Amontillado (C.).. 15.18 strongest (J.) 24.70 weakest (J.) 15.40 Teneriffe ... .. 19.79 Teneriffe (C.) 16.61 Colares 19.75 Lachryma Christi 19.70 White Constantia 19.75 Red Constantia 18.92 Lisbon 18.94 Ditto (C.) 19.09 Bucellas 18.49 Red madeira (mean)... 20.35 Cape muscat 18.25 Cape madeira (mean).. 20.51 Grape wine 18.11 Calcavella (mean) 18.65 Vidonia 19.25 Alba flora 17.26 Zante 17.05 Malaga 17.26 White Hermitage 17.43 Roussillon (mean) 18.13 Claret (strongest) 17.11 mean 15.10 weakest 12.91 ditto (F.) 14.73 vin-ordinaire (C.). 10.42 Chateau- Latour, 1825 (C.) first-growth, 1811 (C.) strongest (J.) weakest (J.) 9.38 9.32 11.10 9.10 Malmsey madeira 16.40 Ditto (C.) 15.60 Lunel Ditto (F.) Shiraz Ditto (C.) Syracuse Sauterne Burgundy (mean) strongest (J.) weakest (J.) Hock (mean) strongest (J.) weakest (J.) Nice Barsac Tont Champagne (mean) Ditto (F.) Ditto, strongest (J.).... weakest (J.) Red hermitage Vin de Grave (mean)... Frontignac (Rives Altes)..... Ditto (C.) ... C6ter6tie Tokay Rudesheimer, first quality (C.) inferior (C.) Hambacher, first quality (C.) Catawba (Stearns) GR. 15.52 18.10 15.52 15.56 15.28 14.22 14.57 13.20 10.10 12.08 13.00 9.50 14.63 13.86 13.30 12.61 12.20 14.80 14.10 12.32 13.37 12.79 12.29 12.32 10.14 8.35 8.88 8 to 11 Cider, highest average. 9.87 lowest average 5.21 Perry, average of four samples 7.26 Mead 7.32 Ale (Burton) 8.88 Ale (Edinburgh) ... 6.20 Ale (Dorchester) 5.56 Brown stout 6.80 London porter 4.20 London small beer 1.28 Brandy 53.39 Rum 53.68 Gin 51.60 Scotch whisky 54.32 Irish whisky 53.90 * The analyses whose results are given in this table were mostly made by Mr. Brande. When no mark is attached, the quotation is upon his authority. When the mark (F.) is added, the analysis was made by Julia-Fontenelle ; (C.), by Professor Christison ; (J.), by Dr. H. Bence Jones. APPENDIX. 883 1, M. corrugator supercil. ; 2, M. com" pressor nasi et pyramidal, nasi ; 3, M- orbicular, palpebr. ; 4, M. levator lab- sup, alaeque nasi ; 5, M. levator lab. sup- ropr. ; 6, M. zygomatic. minor ; 7, M. ilatat.narium ant. et post.: 8, M. zygo- matic. major; 9, M. orbicularis oris; 10, Ram. comm. pro Mm. triangular, et levator menti ; 11, M. levator menti; 1'2, M.quadratus menti; 13, M.triangu- laris menti; 14, Ram. subcutan. colli N. facial. ; 15, Ram. cervical, pro Pla- tysmat.; 16, M. stern o-hyoideus ; 17, M. omo-hyoideus ; 18, M. sterno-tbyroi- deus; 19, M. sterno-hyoideus ; 20, M. frontalis : 21, Mm. attrahens et attol- lens auriculae ; 22, Mm. retrahens et attoll. auriculae ; 23, M. occipitalis ; 24, Nerv. facialis; 25, Ram. auricular, post. prof. N. facialis; 26, M. stylo-hyoi- deus; 27, M. digastricus; 28, Ram. buc- cales, N. facialis; 29, M. splenius capi- tis ; 30, Ram. subcutan. maxill. infer.; 31, Ram.ext. N. accessorii Willisii; 32, M. sterno-cleido-mastoideus ; 33, M. cucullaris ; 34, M. sterno-cleido-mas- toideus ; 35, M. levator anguli scap- ulae ; 36, N. thoracic, post. (Mm. rhom- boidei) ; 37, N. phremcus ; 38, M. omo- hyoid ; 39, N. thoracic, lateral. (M. serrat. magn.) ; 40, N. axillaris; 41, Ram. plex. brachialis (N. musculo- cutan., pars N. mediani) ; 42, N. tho- racic, ant. (M. pectorales). M. rectus ab- dominis. (Nervi intercos- tal es abdomi- nales.) M. serratus Mag- nus. M.latissimus dorsi. M. obliquus ab- dominis exter- nus. (Nervi intercos- tales abdomi- nales.) M. trans versus ab- dominis. $84 APPENDIX. N cruralis X. obturatorius. M.sartorius M. adductor lorigus Kami N. cruralis pro M. quadrici- pite. M. cruralis Kami N. cruralis pro M. vasto in- terno.... M. tensor vaginae femoris. (Kami N. glutaei superioris.) M. tensor vagina: femoris. (Kami N. cruralis.) M. rectus femoris. M. vastus externus. M. vastus externus. M. peroneus longus. M. tibialis anticus ... M. extensor hallucis longus Kami N. peronei prof, pro M extensore digitorum brevi Mm. interossei pedis dorsales. < -' N. peroneus. M. gastrocnemius externus. M. solcus. M. extensor digitorum longus, M. ]>eronous brevis. M. solcus. .... M. flexor hallucis longus. ..M. extensor digitorum brevis. M. abductor digiti minimi pedis. APPENDIX. 88=; Kami inferiores N. glutati inferioris pro M. glutseo maximo N. ischiadicus M. biceps (caput longum) M. biceps (caput breve) N. tibialis N. peroneus M. gastrocnemius externus M. soleus. M. gastrocnemius interims M. soleus M. flexor digitorum longus N. tibialis. M. abductor hallucis M. adductor magnus. ....M. semitendinosus. ...M. semimembranosus. M. gastrocnemius, 886 APPENDIX. N. Museulo-cutaneus. M. biceps. N. musculo- Caput in- N. Media- ; N. ulnaris. Kami N. mediant cutaneus. ternus M. nus. M. brachialis pro M. pronatore tricipitis. internus. radii terete. Ranli Nervi mediani pro M. pro natore radii terete M. palmaris longus.. M. ulnaris internus. M. flexor digitorum sublimis (digitt. II et III.) N. ulnaris M. flexor digitorum sublimis (digitt. indicia et minim) Kami volar. prof. Nervi ulnaris- M. palmaris brevis M. abductor digiti minimi M. flexor digitiminimi M. opponens digiti minimi Mm. lumbricales II, III et iv| .M. radialis internus. M. flexor digitorum profundus. M. flexor digitorum sublimia. M. flexor pollicis longus. N. medianus. M. abductor pollicis brevie. M. opponens pollicis. M. flexor pollicis brevifl. M. adductor pollicis. M. lumbricalis I. APPENDIX. 887 Caput externus M. tricipitis N. radialis M. brachialis internus M. supinator longus M. radialis externus longus M. radialis externus brevis M. supinator longus M. radialis externus us longus M. radialis externus brevflf M. extensor digitorum communist M. extensor indicis proprius M. extensor indicis proprius et M. abductor pollicis longus M. abductor pollicis longus M. extensor pollicis brevis M. flexor pollicis longus M. interosseus dorsalis I M. interosseus dorsalis II M. interosseus dorsalis III M. ulnaris externus. M. extensor digiti minimi pro- prius. M. extensor indicis proprius. M. extensor pollicis longus. M. abductor digiti minimi. M. interosseus dorsalis IV. INDEX OF DISEASES. Abscess . alcohol, to support system by its food value also as heart stimulant, 306. bismuth oxyiodogallate , glycerin solution injected into cold abscesses, 426. boric acid, a feeble antiseptic, 869. formaldehyde, employed in tuberculous cases, 859. hydrogen dioxide, as a disinfectant and cleansing agent, 829. iodoform, in tuberculous forms, 513. menthol, a saturated alcoholic solution painted on superficial abscesses, 852. naphtol, solution for injection into abscesses, 851. potassium permanganate, as a cleansing disinfectant when fetid discharges, 827. tannic acid, when excessive secretion, 404. Acidity of Stomach : ammonia, stimulant, promptly acting, too irritating to be used in inflamma- tory conditions 282. magnesia, antacid and gently laxative, 654. soda, the most generally serviceable antacid, 800. Acne: arsenic, valuable alterative, especially in chronic cases, 474. calcium sulphide, credited with peculiar alterative action, 631. ichthyol, supposed to possess the power of penetrating the skin and exercising a local alterative action, 527. iodine, powerfully antiseptic but of doubtful value, 504. oil of cajuput, stimulant and parasiticide, 629. phosphorus, used internally in cases with poor nutrition, 461. solution of mercuric nitrate, caustic, used to destroy pustules, 780. Aconite Poisoning : alcohol, a rapidly acting cardiac stimulant, 306. digitalis, a powerful stimulant to the heart, but slowly acting, 327. Actinom ycosis : potassium iodide, only drug likely to be of service internally, 506. Addison's Disease : suprarenal capsule, supplies lacking secretions, use must be continued indefi- nitely, 542. After Pains : antipyrine, 608. Ague: See MALARIA. Alcoholism : apomorphine, emetic and sedative, 640. capsicum, for alcoholic gastritis, 629. gold and sodium chloride, supposed to exercise a specific effect on central ner- vous system in alcoholic habit, 497. strychnine, valuable in chronic alcoholism, 222. treatment of acute alcoholism, 310. Alopecia : arsenic, in atrophic variety, 474. pilocarpine, 726. 889 890 INDEX OF DISEASES. Amaurosis : See BLINDNESS. Ambl yopia : strychnine, especially useful in tobacco or alcoholic cases, 221. Amenorrhoea : aloes, cathartic, tends to increase pelvic congestion, enters into several em- menagogue combinations, 665. apiol, to be given for a week previous to expected menses, 744 cantharides, stimulating to uterine mucous membranes, 742. clave tea, useful where menses suppressed by "cold", 627. cotton root, stimulant to uterus, 764. Dewees's emmenagogue mixture, a valuable routine combination, 742. diaphoretics, of service in acute suppressions, 719. emmenagogues, their limitations and uses, 741. ginger, may be given in form of infusion, 628. Griffith's mixture (mistura ferri composita), employed in anaemic cases, 449, 741 guaiac, an ingredient of Dewees's mixture, 449, 741. iron, useful in anaemic cases, 741. myrrh, an ingredient of Griffith's mixture, 741. oil of pennyroyal, feeble, 743. oxalic acid, active but somewhat dangerous, 398. pills of aloes and myrrh, 666. potassium permanganate, not very valuable, but sometimes of service, 741. saccharated ferrous carbonate, a useful form of administering iron, 449. santonin, has been recommended in acute menstrual suppression, 809. sumbul, useful in cases associated with nervous symptoms, 80. turpentine, when there is much relaxation, 710. Ammonia Poisoning : treatment, 282. Ammoniacal Urine : See CYSTITIS. Anaemia : See CHLOROSIS and PERNICIOUS ANAEMIA. Anaesthesia, Accidents in : ammonia, rapidly acting heart stimulant, 281. artificial respiration, a most important factor, 115. cardiac massage, may be tried in desperate cases, 115. treatment of, 113. Aneurism : digitalis, useful where heart is very feeble, but must be employed with great caution on account of danger of rupture, 326. ergot, recommended to be injected in the immediate vicinity, 752. gelatin, promotes coagulation of the blood, 533. potassium iodide, largely employed, but there is no explanation of the manner in which it benefits, 506. Angina : See SORE THROAT. Angina Pectoris: amyl nitrite, very prompt and efficacious, to be used during the attack, 258. erythrol tetranitrate , acts like nitroglycerin but more lasting, 262. mtroglycerin, similar in its action to amyl nitrite, more persistent, 261. Anorexia : bitters, stimulate the flow of gastric juice, also probably increase appetite through their bitter taste, 621. orexine, a synthetic bitter, highly lauded, 625. quinine, acts as a bitter, but also has effect on metabolism, 572. INDEX OF DISEASES. 891 Anthrax : phenol, to be injected into the ulcer, 838. Aortic Lesions : See ENDOCARDITIS. Aphthous Stomatitis : See STOMATITIS. Apoplexy : croton oil, useful as a purgative where patient cannot swallow; also acts as revulsant, 676. emetics, not useful in true apoplexy, but in those forms of coma resembling apoplexy. 633. nitro-glycerin, useful to advert threatened apoplexy by dilating the blood- vessels. 262. Arsenic Poisoning : dialyzed iron, less useful than the freshly precipitated hydrate, but may be of service in emergency, 451. ferric hydrate, may be prepared extemporaneously by adding any alkali to a solution of ferric sulphate or chloride, 448. Jerri hydroxidum cum magnesii oxido, chemical antidote, 448. treatment, 480. Ascites : See DROPSY. Asthenopia : strychnine, acts almost specifically, 222. Asthma : Symptomatic Treatment: amyl nitrite, very prompt and powerful, used by inhalation during attack, 258. anesthetics, sometimes useful during attack, 82. atropine, may be given hypodermically in large doses, probably less useful than the burning belladonna, 180. belladonna, useful, especially to be burned and vapors inhaled, 180. chloral, occasionally but not generally useful, 152. chloralformamid, recommended in asthma depending upon cardiac disease, 165. ether, sometimes of service, 91. ethyl nitrite, probably of less value than amyl nitrite, may be employed in similar cases, 260. grindelia, useful as an expectorant, may be added to a burning powder, 736. heroin, especially useful in secondary asthma, acts by lessening irritability of respiratory centers, 145. lobelia, may be used as an expectorant, also in emetic doses during parox- ysms, 263, 733. nitroglycerin, maybe used hypodermically in the place of amyl nitrite, 261. stramonium, acts like belladonna, used especially for making cigarettes or burning powders, 185. Constitutional Treatment: antipyrine, lessens irritability of nervous system, 608. arsenic, may be used either locally or internally, 474. aspidosperma, acts upon respiratory center, 278. atropine, may be used as a preventative of spasmodic asthma, 180. hyoscine, similar to atropine in its effect, more sedative, 189. potassium iodide, one of the most valuable drugs known between the par- oxysms, 506. spartein, may be employed in asthma depending upon cardiac lesions, 350. suprarenal capsules, recommended to be used internally, 543. thymus gland, has been recommended, but of doubtful utility, 543. 892 INDEX OF DISEASES. Atheroma : digitalis, useful in heart failure, must be employed with caution, 326. nitre/glycerin, used to reduce tension in arteries, 261. sodium nitrite, similar in its effect to nitroglycerin, but more persistent, 261. Atropine Poisoning: pilocarpine, physiological antagonist to atropine, 727. treatment of, 184. B Biliousness : emetics, mechanically relieve portal congestions, 633. ipecacuanha, has a special action on the liver, 638. mercury, in the form of calomel or blue-mass, the most generally valuable remedy in acute cases, 662. nitro-hydrochloric acid, of service especially in chronic cases, 456. oxgall, is the most powerful stimulant to hepatic secretion known, 653. podophyllum, sometimes called "vegetable mercury" on account of its effect on the liver, 673. potassium acetate and citrate, of service in chronic biliousness, 693. taraxacum, of doubtful value, 530. Bites: See HYDROPHOBIA; also SNAKE-BITES. Black-water Fever: methylene-blue, is destructive to malarial parasite, but not irritant to the kidney, 581. Bladder, Irritable: See CYSTITIS. Bladder, Tuberculosis of: guaiacol, dissolved in olive oil and injected into bladder, 846. Blindness : santonin, 809. strychnine, especially useful in toxic cases as alcohol or tobacco, 221. Boils: calcium sulphide, useful where successive crops of boils, 659. infiltration anesthesia, to open boils, 120. kaolin, as substitute for flaxseed poultice, 793. menthol, saturated alcoholic solution painted over area will sometimes abort, 852. phosphorus, as general tonic and alterative, 461. Bone Diseases: carbolic acid, injected deeply, 838. iodine, internally in scrofulous cases, 503. phosphorus, has a stimulant action on growth of bone, 467. Brain Softening: phosphorus, sometimes of benefit, 461. Bright'* Disease: antipyrine, 609. apocynum, to eliminate dropsical effusions, 334. caffeine, to evacuate dropsy, to be used only very cautiously if at all in acute cases, 348. calomel, one of the most powerful diuretics known, 683. diaphoretics, aid in the excretion of waste products through the skin, 717. digitalis, in acute suppression may be applied externally with benefit, 684. diuretics, 679. gattic acid, to diminish excessive secretion in chronic interstitial nephritis, 406. hypodermoclysis, in acute irritation of kidneys or suppression, 679. INDEX OF DISEASES. 893 pilocarpine, may be used to produce sweating, also to stimulate kidney in acute suppression, 7 2 6. potassium bitartrate, of value in acute nephritis, 693. strontium lactate, claimed to diminish the amount of albumin, but of doubtful value, 704. strophanthus, more stimulant to kidneys than digitalis. 338 tannalbin, in cases where large amounts of albumin, 405. theobromine, may be employed in both acute and chronic cases when secretion is insufficient, 685. theocin, a synthetic alkaloid of value in dropsical cases, 685 thyroid extract 538 tincture of ferric chloride, much employed in chronic cases, 449. water, in acute irritations large draughts of water often valuable, 678. Bronchitis, Acute: ammonium chloride, somewhat stimulant, use after secretion is established, 735- antimony, to be employed only in robust or sthenic patients, 364 apomorphine hydrochloride , encourages the establishment of secretion, 642. Brown mixture, demulcent for mild cases, 784. codeine, as a cough sedative, 142. demulcents, 782. eucalyptus, used when there is free secretion, 584. garlic, sometimes useful in feeble infants, 737. heroine, a very valuable cough sedative, 145. ipecacuanha, increases expectoration, use in early stages, 731. lobelia, of service when there is tendency to asthmatic spasms, 263. oil of sandal-wood, in the latter stages, 708, 738. opium, cough sedative, avoid where expectoration is profuse, 134. potassium citrate, increases secretion, especially serviceable in early stages, 733- senega, 739. sulpnuretted hydrogen, useful where free expectoration, 740. tar, used only in advanced stages, 737. terebene, stimulating expectorant, use in later stages, 738. terpin hydrate, of service after secretion has been established, 738. turpentine stupes, act by counter-irritation, 710. Bronchitis, Chronic : ammoniac, 739. ammonium chloride, employed where expectoration is not profuse, 735. arsenic, may be used either internally or in form of cigarettes, 474, 730. asafetida, of service in the aged, 76. aspidosperma, to relieve dyspnoea, 278. balsam of Tolu, 736. benzoic acid, a valuable remedy, 863. Burgundy pitch, externally as a counterirritant, 775. cimtcifuga, 79. compound tincture of benzoin, may be used either internally but especially by inhalation, 863. copaiba, in cases with free muco-purulent expectoration, 713. creosote, one of the most active stimulating expectorants, 845. creosote carbonate, supposed to be less irritating to the stomach than creosote, 845- ethyl nitrite, in asthmatic cases, 260. eucalyptus, an active stimulant expectorant, 584. formaldehyde, inhalations of, 860. garlic, 737. grindelia, relaxes spasm of bronchial muscles and stimulates mucous mem- branes, 736. naphthalin, when free expectoration, 850. oil of sandal-wood, a useful stimulant expectorant, 708, 738. oil of turpentine, 709. opium, to quiet cough when not too free expectoration, 134. physostigma, when there is weakness of bronchial muscles, 237. 894 INDEX OF DISEASES. Bronchitis, Chronic Continued: respiratory stimulants, often of great service in aged or feeble patients, 277. sanguinaria, no use, 739. senega, of little value, 739. squill, 737. strychnine, as a stimulant in the feeble to aid expulsion of secretion, 221, sulphuretted hydrogen, an unpleasant but active remedy especially where purulent expectoration, 740. tar, a useful remedy best employed in form of syrup. 737. terebene, an active stimulating expectorant, 738. terpin hydrate, a very useful drug in cases of mild type, 738. theocol, 847. Bronchorrhoea : expectorants, 732. gallic acid, an internal astringent, 406. Bruises : arnica, 373. camphor, 288. ichthyol, 528. solution of lead subacetate, sedative and astringent embrocation, 422. vinegar, a useful external application, 397. Buboes : chloral, in solution forms a stimulant and antiseptic wash, 152. phenol, deep injections of, 838. Bubonic Plague: serum treatment, useful as prophylactic as well as curative, 550 Burns : boric acid, as a mildly antiseptic dressing, 869. Carron oil, a soothing local application, 802. chalk, offers a desiccant protective dusting powder, 803. creosote, recommended when there is excessive granulation, 844. hot baths, to combat the collapse, 718. ichthyol, 528. iodoform, analgesic, desiccant, and antiseptic, 511. Kentish ointment, stimulating, used but rarely, 774. lead carbonate, in the form of ointment is a sedative astringent, use with care, 422 phenol, anesthetic and germicidal, 837. resin cerate, to stimulate healing process in old burns, 708. treatment of, (note) 511. turpentine liniment, as a stimulant to old ulcers, 774. Bursze, Inflamed : phenol, deeply injected, 838. C Cachexia : cod-liver oil, appears to have specific influence on nutrition, 517. glycerin, 791. Calculi : anesthetics, to alleviate pain and produce relaxation during passage of stone, 82. atr opine, to relieve spasm, 180, benzoic acid, in uric acid calculi, supposed to check elimination of uric acid. 863. piperazine, will not dissolve calculi, 698 potassium acetate, to check the further deposition of uric acid, 693. Cancer : arsenic, as a caustic in inoperable cases, 778. chloral, locally anaesthetic and antiseptic, 152. cocaine, to relieve pain, apply locally, 207. escharotics, only to be used in inoperable cases, 776. INDEX OF DISEASES. 895 formaldehyde, deodorant and germicidal, 860. iodoform, lessens pain and absorbs discharge, 511. solution of mercuric nitrate, as a caustic, 779. streptococcus toxin, generally fails but may be tried, 545. Cancer of Stomach : bismuth subnitrate, to relieve pain and vomiting, 424. chloretone, local anaesthetic, 162. diastase, to digest food when gastric secretions fail, 817. malt, 817. Carbolic Acid Poisoning : treatment, 840. Carbuncle : menthol, paint saturated alcoholic solution over surface, 852. Cardiac Disease, Chronic : See HEART DISEASE. Cardiac Dropsy : See DROPSY. Cardialgia : antacids, correct hyperacidity, 797. charcoal, to absorb gases, 819. Cataract : phosphorus, 461. Catarrh of Air Passages : balsam of Peru, in chronic cases, 736. benzole acid, to be given internally in subacute and chronic cases, 863. camphoric acid, applied locally, 288. compound tincture of benzoin, may be given by mouth or put into hot water and vapors inhaled, 863. ftaxseed, may be used freely in the form of a decoction, 784. guaiacol, as a stimulant in chronic cases, 846. horehound, feeble, 739. hydrastin, applied locally, 760. thymol iodide, dusted on the mucous membranes, 515. Catarrh of Bladder: See CYSTITIS. Catarrh, Suffocative : apomorphine, useful in emetic doses to get rid of bronchial exudation, 642. expectorants, 634. garlic, applied in the form of a poultice, 737. Catarrhal Jaundice : See JAUNDICE. Cerebral Congestion : cathartics, 653. ergot, 753. Cerebral Excitement: cathartics, act by revulsion, 653. potassium bromide, useful when condition is not inflammatory, 245. Cerebral Scleroses: gold and sodium chloride, 498. Cerebral Softening: See BRAIN SOFTENING. Chancres and Chancroids : black wash, as a local application, 496. Canquoin's paste, contains zinc chloride, 779. 896 INDEX OF DISEASES. Chancres and Chancroids Continued: corrosive sublimate, less useful than solution of mercuric nitrate but actively germicidal and somewhat caustic, 779. eschar otics, 776. hydrogen dioxide, cleansing and germicidal, 829. ichthargan, actively germicidal, 440. nitric acid, should be applied with a glass rod, 454, 778. red mercuric oxide, may be used in powder form, 496. resorcin, apply as dusting powder, 855. solution of mercuric nitrate, actively caustic, 780. sulphuric acid, actively caustic, 453. yellow mercuric oxide, 496. yellow wash, 496. zinc chloride, caustic and disinfectant, 779. Chapped Hands, Lips, or Nipples: benzoic acid, stimulant and antiseptic, especially useful in the form of ben- zoin, 863. glycerin, 790. tannic acid, to harden tender nipples, 404. Chilblains : copaiba, 713. creosote, 844. Child-birth : See LABOR. Chloral Poisoning : treatment of, 152. Chlorosis : bone marrow, 531. cacodylic acid, doubtful if it is of value, 482. cetrarin, 785. copper sulphate, an old remedy, recently revived in cases with amenorrhcea, 428. iron, the general facts as to the value and use of iron in anemia are discussed on p. 447 and the individual preparations on the four following pages. lecithin, probably of some value but less beneficial than iron, 552. Cholelithiasis : See BILIARY CALCULI. Cholera Asiatica : acetozone, an active intestinal antiseptic, 830. ammonia, for the collapse, 281. antitoxin, especially for immunization, 550. camphor, to lessen the diarrhoea, 287. chloral, 152. sulphuric acid, of value as a prophylactic, 453. Cholera Infantum : antipyrine, 607. bismuth subnitrate, one of the most useful remedies known, 424. Castillon's powder, a means of exhibiting lime, 803. cold bath, frequently of value, 37. creosote, of service on account of local anesthetic as well as antiseptic action, 844- resorcin, antiseptic, 855. rhubarb, purgative and astringent, 663. sodium phosphate, useful to clean out bowel and encourage flow of bile, 669. sulphuric acid, actively astringent, 453. Chordee : camphor, 288. sulphonal, 157. INDEX OF DISEASES. 897 Chorea : antipyrine, has some effect as motor sedative, 607. apomorphine, has been recommended in acute cases, 642. arsenic, one of the most generally useful remedies, give Fowler's solution in increasing doses, 474. cacodylic acid, an arsenical preparation, 482. Calabar bean, 236. chloral, to temporarily control convulsions when violent, 151. cimicifuga, give in conjunction with iron, 78. conium, 272. euquinine, used like quinine, 579. exalgine, 617. quinine, efficacious when patient can take large enough quantities, stimulates spinal inhibitory center, 572. sodium bromide, 248. strychnine, if any value it is as general tonic, 220. sulphonal, 157. zinc oxide, 427. Choroldltis : santonin, 809. Chronic Intestinal Atony : Calabar bean, a stimulant to non-striated muscle fibre, 230. Chyluria : methylene-blue , 581. Cicatrices : thiosinamine, claimed to have the power of absorbing scar tissue, 530. Cirrhosis of the Liver: apocynum, to evacuate effusion, 334. nitro-hydrochloric acid, in early stages exercises a directly beneficial action on liver, 456. Cocaine-poisoning : treatment of, 208. Cocainism : treatment of, 209. Cold, a General : alcohol, as a preventive, 304. Brown mixture, 784. diaphoretics, most efficacious treatment, 719. See also BRONCHITIS and CORYZA Colic : antacids, in conditions with hyperacidity, 797. asafetida, in flatulent colic, a useful stimulant to peristalsis, 76. belladonna, useful in spasmodic colic, 180. cajuput, 629 chloroform, anodyne and carminative, frequently very useful, 99. ether, mildly carminative, 91. ginger, actively carminative, useful in flatulent colic, 628. opium, to allay irritation, 134. Colica Pictonum : alum, chemical antidote to lead, also claimed to act specifically, 410. belladonna, probably most useful drug in this condition, 180. chloroform, 99. See also LEAD-POISONING. Colitis: castor oil, purgative and sedative to inflamed mucous membrane, 660. copper sulphate, occasionally useful, applied locally, 428. forced enemata, best treatment; various drugs, as silver nitrate or potassium chlorate, may be thus locally applied, 650 57 898 INDEX OF DISEASES. Colitis Continued : magnesium sulphate, benefits by cleaning out the cause, 668. silver nitrate, probably the most generally useful local application, 436. Collapse : ammonia, prompt but temporary stimulant, give hypodermically, 281. atropine, of great service in the collapse of low fevers, 181. caffeine, sodium and caffeine benzoate for hypodermic use, 348. counter-irritants, 768. digitalis, powerfxil but slow, may be given hypodermically, 326. ergot, slow in its effect, 753. heat, 30. hot baths, only efficient method of maintaining body temperature, 718. sodium carbonate, 798. strychnine, one of the most generally useful remedies, 222. suprarenal extract, very quick but fugacious, may be given intravenously, but a dangerous remedy, 542. Warburg's tincture, 579. Colliquative Sweats: See NIGHT-SWEATS. Coma : emetics, 633. Comedo : arsenic, 474. Condylomata : chromic acid, caustic, 780. nitric acid, actively caustic, 780. phenol, mildly caustic, 837. Congestion of Brain : See CEREBRAL CONGESTION. Congestion of Lungs : atr opine, 181. ergot, 753. Congestion of Spinal Cord: ergot, 753. Conium -poisoning : treatment of, 273. Conjunctivitis : alum, in the form of alum curd, astringent, 410. atropine, rests the eye and has an anodyne alterative effect, 181. betanaphtol, applied locally dissolved in olive oil, 851. boric acid, one of the best local applications, soothing and antiseptic, 869. citrine ointment, in chronic cases, 496. cocaine, lessens pain and overcomes congestion, a very useful treatment, 207. copper sulphate, used in the granular type, 429. ichthargan, may be topically applied in one per cent, solution, 440. largin, a modern silver preparation recommended in the form of gelatin tablets locally, 439. lithium, in gouty cases, 698 protargol, recommended especially in gonorrhceal cases, 441. silver nitrate, a standard and useful treatment, an active germicide and astrin- gent, 435. suprarenal extract, powerfully antagonizes the congestion, 542. yellow mercuric oxide, in chronic cases, 496. Constipation : aloes, in atonic cases, especially when accompanied with amenorrhrea, 665. asafetida, as stimulant to the intestinal muscles, especially useful in the aged, 76. INDEX OF DISEASES. 899 belladonna, prevents griping and increases laxative effects of cathartics, 180. black draught, a very valuable remedy in fecal impaction, 666. blue mass, used where hepatic torpor, 662. bran, 654. calomel, most valuable drug in biliousness, not to be used habitually, 662. cascara sagrada, especially useful in chronic constipation, 655. castor oil, useful only in acute cases, 659. cathartics, 652. compound cathartic pills, in acute constipation, 672. compound infusion of senna, same as black draught, 666. cracked wheat, 654. croton oil, probably most powerful purgative known used to revulse or when patients refuse to swallow, 675. diet, 654. enemata, 650. Epsom salt, a prompt and efficient saline, 667. euonymus, 655. Indian meal, 654. magnesia, antacid laxative, 657. manna, 655. molasses, 654. oatmeal, 654. physostigma, stimulant to intestinal muscles, useful in atonic cases, 273. pills of aloes and asafctida, 666. podophyllum, supposed to act upon the liver, hence the name "vegetable mer- cury," 673. rhttbarb, used in debilitated cases, 663. Seidlitz powder, an elegant form of saline, 669. senna, a very efficient laxative when soft passages desired, 666. solution of magnesium citrate, non-irritating, especially useful in inflamma- tory conditions, 668. strychnine, when intestinal atony, 222. sugar, 654. sulphur, 657. tamarind, 656. taraxacum, 504. treatment of, 652. unbolted flour, 654. vegetable cathartic pills, 670. wahoo, in chronic cases with hepatic torpor, 655. Convulsions : amyl nitrite, the remedy when convulsions must be controlled immediately, quick and powerful but fugacious, 258. anesthetics, when prompt action desired; chloroform the most efficacious, 82. asafetida, in hysterical cases, 76. camphor, of little value except in hysteria, 288. chloral, useful in all types of convulsions if severe enough to threaten life, IS 1 . !S2- emetics, when convulsions of gastric origin, 633. garlic, 737. musk, 74. potassium bromide, a useful remedy when a persistent action desired, 246. See also EPILEPSY, TETANUS, etc. Copper-poisoning : treatment of, 430. veratrum viride, 345. Corneal Ulcer : atr -opine, rests the eye by paralyzing accommodation, 183. dionine, increases the lymphatic circulation in the eye, 144. largin, germicidal, 439. physostigmine, to limit the spread of ulcers, 237. Corpulence : See OBESITY. 900 INDEX OF DISEASES. Cory za : air? pine, give internally in acute stage; it checks excessive secretion, 181. oismuth subnitrate, locally applied, soothing and protective, 425. cocaine, contracts the engorged vessels. 206. cubebs, as a snuff in not too acute conditions, 714. glycerin, locally, 791. ichthyol, a ten per cent, ointment locally, 528. salipyrin, 615. validol, apply locally, 75. Cough : air opine, when cough is of spasmodic character, 180. codeine, acts on respiratory center, 142. dionine, 1 43 . gelsemium, 267. heroine, one of most generally useful cough sedatives known, 145. opium, to be avoided when expectoration is profuse, 134. prussic acid, of little value, 391. treatment of, 730. Croup : compound syrup of squill, not suitable for children, 737. emetics, to evacuate membrane or mucus, 634. expectorants, 731. glycerin, 791. ipecacuanha, emetic and expectorant, 637. lime-water, apply locally by means of an atomizer, 803. squill, nauseating expectorant, 737. sulphonal, 157. yellow mercuric subsulphate, a dangerous remedy, 496. Cystitis : arbutin, alterative diuretic, 706. benzoic acid, valuable urinary antiseptic, especially useful when ammoniacal urine, 863. betol, antiseptic, 852. boric acid, antiseptic, may be given by mouth or used to wash out bladder, 868. buchu, acts as sedative to inflamed mucous membrane, 705. camphoric acid, 288. cantharides, stimulating, use only in chronic cases, 715. copaiba, in chronic cases, 713. flaxseed, infusion, sedative to mucous membrane, useful in acute cases, 784. grindelia, 736. guaiacol, urinary antiseptic, 846. helmitol, supposed to liberate formaldehyde, 701. hexamethylenamine, one of the best urinary disinfectants, supposed to lib- erate formaldehyde in the bladder, 699. hippurate of lime andlithia, (note) 86 1. iodine, 504. juniper, in chronic cases, 707. lycetol, especially in lithemic patients, 699. methylene-blue, mildly antiseptic, 581. pareira, 705. resorcin, a three per cent solution employed to irrigate the bladder, 855. salicylic acid, rarely used to-day, 594. silver citrate, as local application to bladder, 438. terebene, stimulant alterative diuretic, 738. terpin hydrate, 738. triticum, sedative to cystic mucous membrane, 706. turpentine, in chronic cases, 712. urasol, supposed to act as antiseptic, 702. urotropin, proprietary preparation of hexamethylenamine, 699. uva nrsi, a valuable sedative alterative diuretic, 705. INDEX OF DISEASES. 901 D Debility . See NEURASTHENIA. Delirium of Low Fevers: blisters, when condition is not due to exhaustion, 768. chloral, in early stages, 1 50. valerian, 75. Delirium Tremens : chloral, to produce sleep, powerful but depressant, i 50. chloretone, 164. digitalis, to maintain circulation, large doses well borne, 327. hops, 77. hyoscine hydrobromide, a useful hypnotic, especially in combination with morphine, 189. monobromated camphor, of little value, 79, 251. opium, serviceable, but not to be used too lavishly, 133. paraldehyde, a useful somnifacient, 161. potassium bromide, as a general nerve sedative, not to produce sleep, 245. valerian, too feeble, 75. veratrum, capable of harm, 369. Dermal Growths : chromic acid, caustic, 780. nitric acid, caustic, 780. Dermatitis : vinegar, a soothing astringent lotion, 397. Diabetes Insipidus : antipyrine, 609. ergot, probably the most generally useful remedy known, 753. exalgine, 617. oil of turpentine, 711. opium, may be used in combination with gallic acid, 134. Diabetes Mellitus : antipyrine, 609. arsenical solution of lithium, in gouty cases, (note) 698. ergot, may do good, usually fails. 753 eucalyptus, 584. glycerin, as a sweetening agent instead of sugar, 791. hydrogen dioxide, probably of no service, 829. jambul, in some cases may greatly reduce sugar, usually no effect, 529. lecithin, recommended to improve nutrition, 552 opium, the most valuable drug in this condition, use in large doses, 134. piperazine, recommended on scientific grounds, (note) 699. saccharin, extraordinarily sweet, used as substitute for sugar, 792. sodium carbonate, 800. thymol, 851, 853 Diarrhoea : antacids, in cases with "spinach-stools", 795. antipyrine, 609. argentol, as an astringent antiseptic, 438. aromatics, in diarrhoeas of relaxation, 626. astringents, 402. att -opine, in colliquative diarrhoeas, 181. bismuth and ammonium citrate, differs essentially from other salts of bismuth, useful only in serous types, 426. bismuth subgallate, 426. bismuth subnitrate, perhaps the most generally useful remedy we have in diarrhoeas of an inflammatory character, acts as a sedative, protective antiseptic and astringent, 424 9 02 INDEX OF DISEASES. Diarrhoea Continued : bismuth subsalicylate , acts about like the subnitrate, 426. calcium carbonate, in summer diarrhoeas when intestines are acid, 803. calcium chloride, asserted to inhibit peristalsis, suggested in nervous types, 804. camphor, in serous forms of diarrhoea, 287. Castillon's powder, 803. castor oil, useful to cleanse bowel in inflammatory diarrhoea, is sedative, 660. cocaine, 207. cold baths, in summer diarrhoeas often very useful, 37. copaiba, in chronic cases, 713. copper sulphate, used in chronic ulcerative types, but is of little value, 429. creosote, intestinal antiseptic, 844. cresol, antiseptic, 849. ergot, in chronic serous diarrhoeas restores tone to relaxed vessels, a valuable remedy, 752. ferrous sulphate, astringent, employed in chronic cases, 449. gambir, a powerful astringent in relaxing diarrhoeas, 407. geranium, contains tannin, especially used in children, 409. hcematoxylon, efficient astringent with pleasant taste, 408. hamamelis, 408. Hope's camphor mixture, a valuable combination in serous diarrhoeas, 455. ipecacuanha, in chronic cases, 639. jambul, 529. kino, actively astringent, 529. lead acetate, employed in serous diarrhoeas combined with opium, 422. lime-waler, especially when acidity of intestines, 802. magnesia, in cases with intestinal acidity, 656. naphtol, a valuable intestinal antiseptic, 85. nitric acid, 454. nitro-hydrochloric acid, in chronic cases with hepatic torpor, 456. nitrous acid, preferred in Hope's camphor mixture to nitric acid, 455. oil of cajaput, 629. opium, lessens both peristalsis and secretion, to be used in serous, not in mucous, diarrhoeas, 134. pepsin, 8 1 6. phenol, as an intestinal antiseptic, 837. rhatany, 408. rhubarb, cathartic and astringent; of service in summer complaint, 663. sodium phosphate, useful in chronic diarrhoea of infants, 669. strychnine, in atonic cases, 222. sulphuric acid, an active astringent, 453. syrup of lime, 806. tannalbin, possesses the astringent properties of tannin without deleterious effects upon the stomach, 405. tannic acid, in serous types to check excessive secretion, 404. tannoform, claimed to combine antiseptic influence of formaldehyde to as- tringency of tannin, 405. tannopine, 405. zinc oxide, in chronic catarrhal varieties, 427. zinc sulphate, in chronic diarrhoea with ulcerations, 427. Digitalis-poisoning : treatment of, 330. Dilatation of Heart : convallaria, 350. digitalis, 323. Dilatation of Stomach : beta-naphtol, to check fermentation, 851. Diphtheria : antitoxin, specific, use early and freely, 545. benzoic acid, locally as antiseptic, 863. boric acid, 869. cold, ice bag over the throat, 31; to reduce fever, 37. INDEX OF DISEASES. 903 colloidal silver, used by inunction, of doubtful value, 439. creosote, apply locally as antiseptic, 844. hydrochloric acid, to destroy membrane, 454. hydrogen dioxide, one of the most useful germicides, apply with swab, 829. faborandi, 726. lime-water, to dissolve the membrane, 803. mercury, after antitoxin probably the most valuable internal remedy; calomel may be dusted on diseased surface, 489. Monsel's solution, apply locally, astringent, 449. papain, to dissolve membrane, 818. phenol, germicidal, may be used in form of lozenge, 837. potassium chlorate, dangerous internally on account of irritant effect on kid- neys, may be applied locally, 697. resorcin, antiseptic and feebly caustic, 855. salicylic acid, of no value, 594. streptococcus antitoxin, may be used for mixed infections, 548. tincture of ferric chloride, value doubtful, 450. Dislocation : anesthetics, 82. Diuresis, Excessive : turpentine, 711. Dropsy : apocynum, diuretic and cardiac stimulant, 334. blisters, in local dropsies, 768. caffeine, actively diuretic, 348. calomel, a powerful diuretic if used in large doses, 683. cathartics, 653. convallaria, is diuretic and sometimes cathartic, 350. copaiba, 713. diaphoretics, 719. digitalis, increases urinary secretion by stimulating the circulation, 320, 686. diuretics, 668. elaterin, hydragogue cathartic, especially useful in renal dropsies, 674. hot baths, 718. jaborandi, eliminates the fluid through the skin, 726. jalap, hydragogue cathartic, use in the form of compound jalap powder, 671. magnesium sulphate, eliminates fluid through the bowels, 668. potassium bitartrate, non-irritant diuretic, 693. scoparius, diuretic but irritant to kidneys, 682. squill, powerful diuretic, avoid in acute Bright's disease, 681. strophanthus, cardiac stimulant, has more action on kidneys than digitalis, 337- sugar, 687. theobromine, useful in either cardiac or nephritic dropsy, 685. theocin, diuretic, 685. veratrine, 372. Dysentery : calomel, internally in fractional doses every hour, antiphlogistic and purgative, 662. castor oil, purgative, also soothing to inflamed mucous membrane, 660. cathartics, 653. cocaine, in the form of suppositories when irritability of rectum, 207. cold, ice suppositories or injections of ice-water of great value, 38. copaiba, in chronic cases, 713. creosote, 844. enemata, a very important part of the treatment of dysentery is the applica- tion of various drugs to the inflamed area by means of the high enema, 650. ergot, useful in chronic cases, 752. flaxseed, to be used freely in form of decoction, 784. forced enemata, 650. glycerin, applied locally by means of enema, 791. 904 INDEX OF DISEASES. Dysentery Continued : iodine, 504. iodoform, in the form of suppositories as local anodyne, 513. ipecacuanha, except the purgatives ipecac in large doses the most valuable drug which can be given by mouth, 638. naphtol, 851. nitrous acid, in chronic dysentery of hot climates, 455. opium, acts as antiphlogistic and analgesic (134), may be given by rectum (140). potassium chlorate, useful for rectal injections in chronic cases, 697. potassium permanganate, wash out colon with one to two thousand solution, 827. silver nitrate, by rectal injection in chronic cases, 435. sulphur, seems to act as intestinal antiseptic, highly recommended, 658. Dysmenorrhoea : amyl nitrite, in spasmodic type, 259. antipyrine, to relieve pain, 608. air opine, in spasmodic type, 180. black haw, 744. camphor, in nervous cases, 287. cotton-root, has stimulant action of the uterus, 764. guaiac, stimulant to uterine mucous membrane, 742. nydrastinine hydrochlorate, stimulant to uterus, 763. thermal, to relieve pain, 618. viburnum, 744. Dyspepsia : alcohol, often relieves, but danger of habit, 307. antacids, curative as well as alleviating, 797. asafetida, in atonic cases, 76. barberry, 623. calcium chloride, recommended in fermentative cases, 803. charcoal, as an absorbent in fermentative dyspepsia, 819. enemata, 650. euonymus, as a laxative, 656. finger, must not be used when there is inflammation, 628. ydrastis, 760. hydrochloric acid, as a digestant where insufficient gastric secretion, 454. magnesia, of value in acid dyspepsia, 656. naphtol, antiseptic, useful where much fermentation, 851. nitric acid, to replace the hydrochloric acid of stomach, 455. pancreatin, cannot have any effect as digestant, 816. pepper, may be used in atonic types, 628. pepsin, used where gastric secretion fails, usually of little benefit, 816. physostigma, in intestinal dyspepsia, 237. silver nitrate, valuable astringent in true gastritis, especially when ulcer pres- ent, 436. soda, corrects hyperacidity, encourages gastric secretion, 800. strychnine, when associated with atony, 222. taraxacum, 530. terebenc, in flatulent intestinal dyspepsia, 738. Dyspnoea : aspidosperma, active respiratory stimulant, 278. oxycamphor, respiratory sedative and cardiac stimulant, 291. physostigma, when dependent on bronchitis, 236. Eclampsia : See also PUERPERAL CONVULSIONS. Eczema : ancesthesin, to relieve itching, used as ointment, 118. arsenic, internally, beneficial in chronic cases, 473. betanaphtol, oily solution, locally applied, 851. INDEX OF DISEASES. 905 bismuth subgallate, as a dusting powder, 426. cacodylic acid, an arsenical preparation, 482. camphor-menthol, (note) 852. glycerin, useful emollient, 790. ichlhargan, 440. ichthyol, a very useful external application, 527. menthol, to relieve itching, 852. papain, to destroy thickened skin, 818. resorcin, a valuable local application in chronic cases, 855. soft soap, 765. suprarenal capsule, to blanch reddened areas in chronic cases, 542. tannoform, 406. zinc oxide ointment, a useful astringent application, 428. Effusion, Pericardia! : potassium iodide, aids the absorption of fluids, 506. squill, eliminates fluid through kidneys, 68 1. Effusion, Pleura! : antipyrine, 609. iodoform, as a substitute for iodides, 510. potassium iodide, 506. squill, 68 1. sugar, diuretic, 687. Emesis : See VOMITING. Emphysema : aspidosperma, 278. Empy ema : creosote, locally as disinfectant, 844. iodine, inject after cleaning out cavity, 504. iodoform, in tuberculous cases glycerin solution locally applied, 513. Endocarditis : aconite, when cardiac excitement or excessive hypertrophy, 382. camphor, as a stimulant where immediate danger of heart failure, 287. convallaria, much disagreement as to its value, 350. digitalis, the most reliable stimulant and heart tonic in all cases where com- pensation is lost, 323, 326. ichthargan, has been injected intravenously in septic cases, doubtful if it be a method of value, 440. mercury, 489. sparteine, occasionally of service as heart stimulant, 353. suprarenal extract, value very doubtful, 543. See also HEART DISEASE. Endometritis : hydrastininc hydrochlorate , 763. thyroid extract, 537. Enteric Fever: See TYPHOID FEVER. Enteritis : ammonium chloride, 734. bismuth, the insoluble salts of bismuth (subnitrate, subcarbonate, subgallate, subsalicylate) are our most efficient remedies in enteritis, 424. castor oil, useful to cleanse the bowel, also sedative to inflamed mucosa, 660. cathartics, benefit by getting rid of irritating substance, use in beginning of treatment, 653. chlorine, recommended as an intestinal antiseptic, 820. copper sulphate, 428. demulcents, soothe the inflammation, use in acute cases, 782. enemata, 650. 906 INDEX OF DISEASES. Enteritis Continued : flaxsced, used as demulcent in the form of a decoction, 784. hydrastis, beneficial especially in chronic cases, 760 magnesium sulphate, a non-irritating cathartic, 668. naphtalin, as an intestinal disinfectant, 850. opium, should be used for antiphlogistic effects, not to check the diarrhoea, 134- physostigma, in chronic cases, 237. resorcin, 855. silver nitrate, 436. slippery elm, demulcent. 783. tannalbin, a non-irritant astringent, 405. See also DIARRHCEA. Enuresis : See INCONTINENCE OP URINE. Ephemeral Fever: aconite, 383. Epidid ymitLs : silver nitrate, painted over the scrotum, 435. Epilepsy : acetanilid, 612. ammonium bromide, especially useful in combination with strontium bromide, 248. amyl nitrite, in cases with a distinct aura, or in status epilepticus, 248. anaesthetics, rarely needed except in status epilepticus, 82. antipyrine, efficacious in some cases, may be tried in any, 603. borax, probably of no value, 869. bromahn, 251. bromipin, administered either hypodermically or by inunction, 251. calcium bromide, less disturbing to digestion than other bromides, 249. camphor, 288. chloretone, recommended especially in petit mal, 162. ergot, increases effect of bromides, 753. gold bromide, 250. hydrastinine hydrochlorate, theoretically is strongly indicated, 761, 763. hydrobromic acid, too irritant to be used alone but may be combined with alkaline bromide, 250. lithium bromide, claimed to do good in cases in which potassium salt has failed, 249. physostigma, 237. pituitary body, no good, 543. potassium bromide, the standard remedy in epilepsy, 246. santonin, 807. silver nitrate, useless, 436. sodium bromide, about equivalent to the potassium bromide, 248. strontium bromide, slow but persistent in its action, 249. sulphonal, 157. zinc bromide, by some believed of service, but doubtful if of value, 428. zinc oxide, 427. Episcleritis : physostigmine, 237 Epistaxis : cocaine, acts by constricting blood-vessels, 207. ergot, of little if any value, 752. gelatin, may be employed with advantage both locally and internally, 533. suprarenal extract, a very powerful local constrictor of blood-vessels, 542. tannic acid, acts by coagulating blood and contracting vessels, 404. Epithelioma : resorcin, as a caustic, 855. INDEX OF DISEASES. 907 Erysipelas : antipyrine, to reduce the temperature, 607. alropine, as a circulatory stimulant, 181. benzoic acid, as an antiseptic, 863. boric acid, saturated solution applied locally, 869. creosote, used in the form of an ointment, 844. ferrous sulphate, as an astringent lotion, 449. ichthyol, 527. iodine, beneficial results from local application but must not be used too freely 53- phenol, deep injections, 838. streptococcus antitoxin, has not fulfilled expectations, but may be tried, 548. tincture of ferric chloride, specific action from internal use, 450. Excoriations : glycerin, soothing and softening, 790. Exophthalmic Goitre: picric acid, 814. sparteine, to relieve the cardiac symptoms, 353. splenic extract, well worth trying, 544. strophanthus, to control the heart action, 337. thymus gland, has not proved of service, 543. Fatty Heart: See HEART DISEASE. Faucitis : See SORE THROAT. Favus : naphthol, in the form of a soap, 851. Fecal Accumulation : black draught, a very efficient remedy, 666. Epsom salt, 668. linseed oil, by rectal injection, 787. senna, 666. Feet, Sweating of : See HYPERIDROSIS. Feet, Tender: tannic acid, 404. Felon : carbolic acid, injected deeply, 838. silver nitrate, to abort, paint finger with solution of, 435. Fever : acetanilid, probably less depressant than antipyrin, 613. acetofyrin, coal tar antipyretic, 610. aconite, useful febrifuge in mild fevers, 383. alcohol, acts as accessory food and cardiac stimulant, 305. ammonia, 281 antipyretics, less serviceable than cold bath in severe fever, 586. antipyrine, to lessen fever, 607. apirin, especially in rheumatic fever, 598. cardiac depressants, increase heat elimination, 359. chloral, as a sedative, 1 50. cold, most rational mode of reducing temperature, 37 methods of applying, 39. diaphoretics, useful to break up some kinds of fever, 719. digitalis, to maintain circulation, 327. diuretics, water especially useful in febrile conditions, 677. eupyrine, antipyretic, 608. 908 INDEX OF DISEASES. Fever-r- Continued : exalgine, 617. gelsetnium, as arterial sedative in sthenic fevers, 266. hydrogen dioxide, probably no value. jaborandi, efficacious sudorific, 726. lemon- juice, as refrigerant drink, 396. neutral mixture, as diaphoretic, 692. nitric acid, 455. oil of turpentine, 711. opium, to support the system, 134. phenacctin, probably safest of coal-tar antipyretics, 615. phcnocoll hydrochloride, 616. potassium citrate, 692. quinine, useful in conjunction with cold bath, 570. salicylic acid, not generally useful as antipyretic, 593. salipyrin, as antipyretic especially in rheumatic fever, 617. saloquinine, 580. solution of potassium citrate, 692. sweet spirit of nitre, in adynamic fevers of children, 728. thermal, coal tar antipyretic, 6r8. See also TYPHOID FEVER, SCARLET FEVER, etc, Fibroid Tumors of Uterus : See UTERUS, FIBROID TUMORS OF. Fissure of Anus: atr opine, to relieve accompanying spasm, 180. benzoic acid, antiseptic and healing, 863. cocaine, as a local anaesthetic, 207. Fistula : creosote, 844. Flatulence : dramatics, to stimulate intestinal peristalsis, 625. asafetida, enemata in flatulent constipation, 76. Hoffmann s anodyne, carminative, 77. physostigma, a stimulant to intestinal muscle, 237. See also COLIC. Fractures : calcium phosphate, in ununited fractures, 520. sulphonal, to relieve muscular spasm, 157. thyroid extract, has sometimes proved useful in delayed union, 540. Frost-Bites : ichthyol, 528. Furuncles : See BOILS. O Galactorrhoea : antipyrine, 609. belladonna, either internally or applied locally to breasts, 181. ergot, 753. Oall-Stones : See BILIARY CALCULI. Gangrene : carbolic acid, 837. nitric acid, 454. Gangrene of the Lungs: phenol, 837. INDEX OF DISEASES. 909 Gastralgia : ancesthesin, a local anaesthetic, 118. arsenic, in neuralgic types, 474. bismuth, especially in feeble patients, 424. hydrocyanic acid, a useful remedy, probably acts on sensory nerves, 392. manganese dioxide, 451. orthoform, useful in cases of gastric ulcer, 1 18. phenol, of value on account of local anaesthetic action as well as antiseptic, 837. validol, a compound of menthol and valeric acid, 75. Gastric Crisis: See LOCOMOTOR ATAXIA. Gastric Ulcer: copaiba, as a stimulant in chronic and indolent ulcers, 713. ichthargan, a combination of silver and ichthyol, 440. orthoform, to lessen pain through local anaesthetic effect, 118. resorcin, a not generally useful remedy, 855. silver nitrate, the standard remedy, sedative, astringent, and antiseptic, 436. Gastric Uneasiness: antacids, 797. Gastritis : ammonium chloride, in chronic cases, 734. bismuth, all its insoluble salts act similarly; they are sedative, astringent, protective, and antiseptic, 424. calcium chloride, 803. demulcents, in acute inflammations may be freely employed, 782. hydrastis, useful especially in chronic cases, 760. ichthargan, 442. phenol, antiseptic and anaesthetic, 837. silver nitrate, useful sedative astringent, 436. See also DYSPEPSIA. Gingivitis : argyrpl, germicidal, 441. tannin, astringent, 404. Glands, Enlarged : ammonium iodide, may be used both internally and externally, 507. cod-liver oil, to improve nutrition in scrofula, 517. ichthyol, applied externally, 528. iodine, used externally in indolent hypertrophy, 504. iodoform, either by mouth (510) or glycerin solution injected into tuberculous glands, 513. mercurial ointment, in enlarged indurated glands, 493. mercurial plaster, 493. naphtol, alcoholic solution to be injected directly into glands, 851. phenol, deeply injected, 838. sulphurated hme, 659. thiosinamine, especially in cases with fibrous tissue, 530. Glaucoma : dionine, used locally increases the flow of lymph in the eye, 143. physostigmine, relieves ocular tension by contracting the pupil, 237. salicylic acid, useful especially in rheumatic cases, 594. Gleet : cantharides, a powerful stimulant to the urethral mucous membrane, 715. tincture of ferric chloride, in combination with cantharides, 450. turpentine, a stimulant alterative diuretic, 712. Glycosuria : See DIABETES MELLITUS. 9 io INDEX OF DISEASES. Goitre : iodine, useful in true goitre, 503. thyroid extract, only in simple goitre, not in exophthalmic, 538. Goitre, Exophthalmic: See EXOPHTHALMIC GOITRE. Gonorrhoea : acetozone, locally as antiseptic, 830. albargin, a silver preparation, 438. antimony, internally as a circulatory depressant and diaphoretic, 364. argonin, a silver preparation, 440. argyrol, claimed to be a non-irritant and active silver preparation, 439. benzoic acid, internally as urinary antiseptic, 863. betol, given internally, 850. bismuth, used locally in later stages, 713. copaiba, in the beginning stages employed internally, 425 hydraslin, locally in the later stages, 758. hydrogen dioxide, 829. ichthargan, active silver preparation, 440. kava, 715. largin, recommended especially in gonorrhoea in women, 439. matico, 714. methylene-blue, of doubtful value, 581. oil of erigeron, 707. oil of sandal-wood, used internally in the advanced stages, 708. pareira, in chronic gonorrhoea as alterative diuretic, 705 potassium bromide, to allay sexual excitement, 246. protargol, an organic silver preparation, 441. quinine, applied locally, 575. resorcin, 853. silver citrate, claimed to be non-irritant and actively germicidal, 438. silver nitrate, especially useful in chronic cases, 435. silver sulphocarbolale, 439. tariar emetic, as a diaphoretic, 364. terpin hydrate, used internally, 738. urotropin, given by mouth as urinary antiseptic, 700. zinc acetate, 428. Gonorrhoeal Cystitis : betol, 852. Gonorrhoea! Rheumatism : salicylic acid, 594. Gout : cathartics, 653. colchicum, most useful in typical gout (podagra), 653. ether, in the collapse of retrocedent gout, 91. ichthyol, as an external application, 528. lithium, supposed to be depurant and to increase solubility of urates, 698. magnesia, antacid and laxative, 656. piperazine, occasionally useful in chronic cases, 699. potassium iodide, of some service in irregular or chronic gout, 506. salicylates, used in combination with colchicum, 594 sidonal, used in chronic cases, 701. sulphur, 658. sulphuretted hydrogen, in chronic cases, 738. treatment of, 24. Gout, Retrocedent: ether, 91. Granular Conjunctivitis : See CONJUNCTIVITIS. INDEX OF DISEASES. 911 Granulations, Exuberant : burnt alum, caustic and astringent, 781. copper sulphate, antiseptic astringent and mildly caustic, 781. silver nitrate, caustic and powerfully germicidal, 435. zinc sulphate, 781. Gravel : benzoic acid, probably lessens uric acid excretion, 863. potassium acetate, renders urine alkaline, also lessens formation of uric acid, 6 93- soda, less valuable than potash salts, 800. water, 679. Graves 's Disease : See EXOPHTHALMIC GOITRE. Grippe : See INFLUENZA. (iummata : See SYPHILIS. Gums, Retraction of: iodine, applied locally by means of camel's-hair brush, 504. H Htematemesis : gelatin, increases the coagulability of blood, especially useful in subacute cases, 533. MonseVs solution, one of the most trustworthy styptics in acute cases, 449. suprarenal extract acts by constricting vessels at bleeding point, 542. tannic acid, 404. vinegar, useful especially in emergencies is quite efficient, 397. Hcematuria : cantharides, in atonic haematuria, 715. gallic acid, perhaps the most generally useful remedy, 406. gelatin, believed by some to be irritant to kidneys, is probably beneficial, 533. turpentine, in passive hemorrhage, 712. See also BLACK-WATER FEVER. Haemophilia : gelatin, 533. Haemoptysis : alum, used by atomization, 410. atomization, as a means of applying remedies locally to lungs, 732. cotarnine, 410. ergot, commonly used, but doubtful if of service, 752. gallic acid, given internally, 406. gelatin, probably most useful drug known (except opiates); increases coag- ulability of blood, 535. ipecacuanha, claimed to be specific, 638. lead acetate, doubtful if of service, 422. MonseVs solution, applied by atomization, 449. oil of turpentine, 711. opium, some form of opium or morphine should always be given, 134. Hay Fever : ammonium valeratc, 75. antitoxin, 549. cocaine, applied locally, relieves congestion and is anesthetic, 207. quinine, locally applied, probably not much value, 575. resorcin, 885. suprarenal extract, probably the most useful remedy known for local applica- tion, 542. 912 INDEX OF DISEASES. Headache : ammonia, when due to sick stomach, 282. ammonium valerate, 75. antacids, in gastric headaches to correct hyperacidity, 798. antipyrine, promptly acting coal-tar analgesic, 609. caffeine, especially useful in conjunction with coal tars, 347. camphor, in nervous types, 287. emetics, 631. ergot, in congestive headaches, 753 ether, in hysterical or nervous cases. 91. magnesia, antacid laxative in cases with gastric disturbances, 656. phcnacetin, one of the most valuable of the coal tars, 615. strychnine, when associated with optic atrophy, 221. See also MIGRAINE and NEURALGIA. Heartburn : See CARDIALGIA. Heart Disease: adonidin, a heart stimulant, 355. apocynum, acts on the heart like digitalis but is more diuretic, 334. caffeine, useful as a temporary stimulant. 348. convallaria, employed especially when dropsy, 350 digitalis, the most useful drug known in all forms of prolonged heart failure, is both stimulant and tonic to heart muscle, 322. Hoffmann's anodyne, to relieve heart pains in valvular lesions, 77. mercury, as an antiphlogistic in acute endocarditis, 489. spartcine, 353. strophanthus. very similar to digitalis, but more prompt and less powerful, 337. strychnine, especially valuable where muscular weakness or degeneration, 222. suprarenal extract, of doubtful utility, 542 veratrum, to allay overaction in excessive hypertrophy, 369. See also ENDOCARDITIS, ANGINA PECTORIS. Heart Failure : alcohol, promptly acting, not very powerful, 304. ammonia, must be given hypodermically to have an effect, 281. amyl nitrite, 258. caffeine, useful in cases not too acute, 348 camphor, hypodermic-ally in olive oil, a very powerful resuscitant, 287. digitalis, 323. nitroglycerin, an overestimated remedy, 262. strophanthus, 337. suprarenal extract, a dangerous drug, 542. Heart, Palpitation of: convallaria, 350. sparteine, 353. Hemicrania : See MIGRAINE. Hem iplegia : electricity, after symptoms of irritation have passed off, to exercise muscles, 56. massage, to maintain nutrition of muscles, 5. strychnine, avoid during early stages, later useful as general tonic, 220. Hemorrhage from the Bowels : oil of erigeron, highly recommended, 707. oil of turpentine, 712. suprarenal extract, acts locally by constricting vessels, 542. tannic acid, best given in form of crude galenical rather than pure tannin, 404. Hemorrhages : alum, precipitates albumin of blood, forming hard coagulum, 410. astringents, 402. cocaine, applied locally powerfully constricts vessels, 207 cotarnine, highly praised in both internal and local bl INDEX OF DISEASES. 913 Is, 207. , --- - . bleeding, 410. creosote, useful only to check capillary oozing, 844. ergot, widely used but probably no good, 752. gelatin, hastens the clotting of blood, useful either locally or internally, 533. ipecacuanha, 638. lead acetate, 422. matico, in external hemorrhages, acts mechanically, 714. Monsel's solution, a powerful styptic and astringent when locally applied, 449. oil of erigeron, 705. oil of turpentine, 709. sulphuric acid, 453. suprarenal extract, locally applied, a very useful drug, contracts blood- vessels, 542. tannic acid, for local application, 404. Hemorrhoids : aloes, as a laxative, 665. ancBSthesin, in form of suppositories, to diminish pain, 118. cocaine, local anaesthetic and constrictor of blood-vessels, 207 cubebs, used internally in chronic types, 714. enemata, 650. glycerin, used as laxative, 791. hamamelis, mildly astringent, 410. infiltration anesthesia, for operative purposes, 121. iodoform, in suppositories a very useful anodyne, 513. potassium chlorate, saturated solution injected into the rectum a useful treat- ment, 697, stramonium, in the form of an ointment, anodyne, 185. sulphur, as a laxative, 657. tannic acid, useful astringent in form of ointment, 404. tobacco, 268. Hepatic Congestion and Torpor : ammonium chloride, a useful remedy in chronic cases, 735. calomel, probably most generally serviceable remedy in acute cases, 662. cathartics, 653. chlorine, 826. emetics, 633. eiwnymus, used in chronic cases, 655. ipecacuanha, frequently of service, 638. lemon- juice, employed in habitual hepatic torpor, 396. nitric acid, 455. nitro-hydrochloric acid, one of the best remedies in chronic cases, 456. potassium salts, act as depurants by increasing oxidation, 693. soda, in chronic cases, 800. sodium phosphate, of value in chronic cases with constipation, 669. taraxacum, of doubtful value, used in cases with dyspepsia, 530. Hepatitis : ammonium chloride, in chronic cases. 735. mercury, as antiphlogistic rather than purgative, 489. nitro-hydrochloric acid, in chronic cases, may be used internally or in form of bath, 458. Hernia : ancesthesia, 82. Herpes : naphtol, in the form of a soap, 851. Hiccough : atropine, 180. chloral, acts by depression of motor centres, 152. ether, acts locally on stomach, also on nervous centres, 91. 58 9H INDEX OF DISEASES. H iccough Continued : musk, claimed to be almost a specific, 74. sulphonal, 157. High Arterial Tension : antimony, powerful depressant used only in very robust patients, 364. nitroglycerin, employed especially in habitual conditions, 262. veratrum, used in more or less acute arterial excitement, 369. Hospital Gangrene : bromine, a very active caustic and germicidal agent, 781. nitric acid, actively caustic, 454. H vdrocele : iodine, inject directly into sac, 504. phenol, deep injections of, 838. Hydrocephalus : potassium iodide, 506. Hydrophobia : caustic potash, applied to bite as a prophylactic, 777. eschar otics, 776. Hyperacidity : See ACIDITY OF STOMACH. Hyperemesis : See VOMITING. Hyperidrosis : arsenic, internally in neurotic cases, 474. chalk, applied locally as a desiccant, 803. tannic acid, used in form of wash, 404. tannoform, astringent and antiseptic dusting powder, 406. See also NIGHT-SWEATS. Hyperpyrexia : See FEVER. Hypertrophy of Heart: aconite, 382. veratrum viride, 369. Hypertrophy of Uterus: ergot, 754. Hypochondriasis : alcohol, 307. cypripediitm, 79. Hysteria : anesthetics, to check convulsions, 82. antipyrine, in convulsive cases, 607. antispasmodics, 73. asafetida, a useful nerve sedative, 76. camphor, useful as a nerve sedative and anticonvulsant, 288. cocaine, as a stimulant and stomachic, 207. conium, 272. creosote, to check hysterical vomiting, 844. electricity, to cure local anaesthesias, 58. ether, given internally, 91. gold and sodium chloride, 497. monobromated camphor, especially where sexual excitement, 79, 251. musk, 74. oil of wormseed, 807. potassium bromide, one of the most widely used of all remedies, 245. sodium bromide, 248. INDEX OF DISEASES. 915 sparteinc, 353. sumbul, especially in cases with uterine disturbances, 80. valerian, a mildly acting but widely useful drug, 75. validol, a combination of valeric acid and menthol, 75. valyl, a synthetic preparation of valeric acid, 75. Hysterical Paralysis : electricity, 54. I Ichthyosis : naphtol, 851. Idiocy : thyroid extract, valuable probably only in myxcedematous subjects, 537. Ileus : See INTESTINAL OBSTRUCTION. Impotence : turpentine, 712. yohimbinc, useful only in neurasthenic cases, not in organic, 715. Incontinence of Urine : antipyrine, in spasmodic cases, 606. atropine, when due to irritability of bladder, 180. chloral, in spasmodic cases, 152. quinine, in large doses frequently useful, 572. strychnine, when due to nervous relaxation, 222. turpentine, in atonic forms, 712. Indigestion : See DYSPEPSIA. Infantile Colic: See COLIC. Infantile Convulsions: See CONVULSIONS. Infantile Diarrhoea: See CHOLERA INFANTUM. Infantile Paralysis: electricity, not to be used until inflammatory symptoms have passed off, 56. massage, 5. Inflammations : belladonna, locally applied as anodyne, 182. blisters, useful in serous and other internal inflammations, 768. carbolic acid, deep injections in deep-seated inflammations of chronic type, 838. cold, in acute stage, 30. lead acetate, sedative astringent embrocation, especially in acute conditions, 422. mercury, especially valuable in serous inflammations, may be used internally or externally, 488. opium, seems to exercise a specific antiphlogistic effect, 134. silver nitrate, applied locally to inflamed mucous membranes, 435. solution of lead subacetate, 422. stramonium, used for same purposes as belladonna, 185. tartar emetic, to quiet arterial excitement in sthenic inflammations, 364. Influenza : aconite, to encourage sweating, 383. betanaphtol, 849. eupyrin, for relief of pains, 608. pilocarpine, used to produce sweat will sometimes abort, 726. salipyrin, to allay pain and fever, 617. 916 INDEX OF DISEASES. Insanity : chloretone, used as a somnifacient, uncertain, 162, hyoscine hydrobromide, acts as hypnotic and in some cases seems to have curative effect, 189. hyoscyamus, is similar but inferior to hyoscine, 186 paraldehyde , one of the most valuable somnifacients, 161. spleen extract, 544. veronal, as a hypnotic, 164. See also MANIA. Insomnia : See SLEEPLESSNESS. Intermittent Fever: See MALARIA. Intertrigo : clialk, protective tind desiccant, 803. ichthyol, 527. Intestinal Atony : physostigma, the most useful stimulant to unstriped muscle fibre known, 237 strychnine, 222. Intestinal Catarrh : ammonium chloride, in chronic cases. 734. Calabar bean, 237. cathartics, to cleanse the bowel from irritant substance, 650. forced enemata, 650. hydrastis, in chronic cases, especially if of alcoholic origin, 760. naphtalin, as an antiseptic, 850. salol, intestinal antiseptic, 847. tannalbin, 405. See also ENTERITIS. Intestinal Indigestion : betanaphtol, to check fermentation, 851. physostigma, 237. salol, 847. Intestinal Obstruction : atropine, when due to intestinal spasm, 180. opium, in spasmodic or irritative types, 134. Iritis and Irido-cyclitis : atropine. to rest eye and prevent adhesions, best mydriatic for this purpose 183. dionine, increases the flow of lymph in eye, 144. mercury, in cases with marked lymphatic exudation. 489. salicylic acid, especially but not exclusively useful in rheumatic persons, 594. santonin, in amaurosis following iritis, 809. thiosinamine, probably of very little value, 530 Irritable Bladder: See BLADDER, IRRITABLE Irritable Heart: digitalis, 325. Itch: See SCABIES. Ivy-Poisoning: See RHUS-TOXICODENDRON POISONING. INDEX OF DISEASES. 91; J Jaundice : ammonium chloride, in chronic torpor of the liver and catarrhal jaundice, 735. emetics, to relieve portal congestion, 633. forced enemala, 650 ipecacuanha, 638. lemon juice, in catarrhal jaundice, 396. mercury, probably the most generally serviceable drug in catarrhal jaundice and acute biliousness, 662. nitro-hydrochloric acid, especially valuable in cases depending on chronic hepatic torpor, 456. oxgall, most powerful stimulant to hepatic secretion known, 655. potassium bicarbonate, 691. potassium salts, depurant and alkaline; useful in chronic hepatic torpor and catarrhal jaundice, 693. sodium phosphate, in chronic cases with constipation, 669. sodium salts, alkalies of value, 800. Joints, Inflammation of : blisters, in chronic cases, 768. cautery, 769 cod-liver oil, in tuberculous joint diseases, 517. ichthyol, especially in gouty or rheumatic forms, 528. iodine, externally as alterative and counter-irritant, 504. iodoform, injected into the joint directly, in tuberculous arthritis, 513. lithium, in gouty or rheumatic patients, 698. massage, when traumatic in origin, 5. mercurial plaster, 493. K Keloid : ichthyol, locally applied, 527. thiosinamine, may be used either internally or injected locally, 530. thyroid extract, recommended highly for internal use, 538. Keratitis : atr opine, to lessen liability to iritis, 183. dionine, increases lymph flow in eye, 144. iodipin, 508. physostigmine, to reduce vascularization, 237. salicylic acid, especially, but not exclusively, useful in rheumatic cases, 594. Kidneys, Congestion of: flaxseed, sedative, useful in acute conditions, 784. gin, use in chronic conditions, avoid in acute, 707. sweet spirit of nitre, feebly diuretic, 686. L Labor: anaesthetics, to allay the suffering, 8 1 . chloral, to lessen pain and overcome rigidity of os, 152. ergot, to increase uterine contractions, used only in latter stages, 750. Laryngismus stridulus : antipyrine, 608. atr opine, 180. chloral, 152. expectorants, 731. Laryngitis : camphor-menthol, dissolved in liquid petrolatum and used as spray, (note) 852. cocaine, applied locally as palliative, 207. gelsemium, internally in spasmodic types, 267. glycerin, 791. 9i8 INDEX OF DISEASES. Laryngitis Continued : heroine, used as local anaesthetic in laryngeal tuberculosis, 145 ichthargan, a solution in glycerin as a spray, 440. mercury, administered internally as antiphlogistic, 489. naphtol, 851. orthoform, a valuable local anaesthetic in tuberculous laryngitis, 118. pilocarpine, 728. silver nitrate, two per cent solution applied locally, 435 suprarenal capsule, 541. Lead Poisoning: alum, recommended in colica pictonum, 410 atropine, most valuable remedy for lead colic known, 180. electricity, for local palsies in chronic cases, 56. potassium iodide, to increase elimination of lead in chronic poisoning, 506. strychnine, of value in plumbic poliomyelitis. 220, 222. sulphuric acid, chemical antidote, 453. treatment of acute, 412. treatment of chronic, 418. Lepra : ammonium iodide, 507. ichthyol, 527. thiosinamine , 530. Leucorrhoea : aluminum sulphate, astringent and antiseptic, but irritant, 411. bismuth subnitrate. sedative astringent, 425. creosote, disinfectant, 844 ferric ammonium sulphate, actively astringent, 451. iodine, tincture of. locally applied, 504, potassium permanganate, disinfectant and deodorant, 827. resorcin, 855 tannic acid, astringent, 404 Leukaemia : bone-marrow, probably not of value, 531. cacodylic acid, of no more value than official forms of arsenic, 482. cold douche, over splenic area, 32. ergot, injected hypodermically. 752. spleen extract, 531. Lichen : arsenic, 473. Lipoma : ichthyol, 528. Lithaemia : See URIC ACID DIATHESIS. Liver Diseases : See HEPATIC. Local Anaesthesia: eletricity, in form of electrical brush, 58. Local Paralysis : massage, 5. Locomotor Ataxia : acetanilid, for relief of pain, 614. anlipyrine, for painful crises, 608 aspirin, as analgesic, 598. glycero-phosphat.es, as nerve tonic, 519. hyoscine, as analgesic, 189. rheumatine, 579. silver nitrate, used to affect conditions in cord, but of doubtful service, 436. INDEX OF DISEASES. 919 Lumbagc: cod-liver oil, in chronic cases with cachexia, 490. ichthyol, applied locally, 527. potassium iodide, in subacute types, 506. salicylates, the standard remedy, 592. sulphur, 657. Lumbrici : See ROUND- WORMS. Lupus : aristol, as a dusting powder, 515. arsenic, used internally, 778. arsenic iodide, as an external application, 482. cantharidin, (note) 771. guaiacol, actively germicidal, 846. ichthyol, 527. phosphorus, internally as a tonic alterative, 461. pyrogallol, an ointment used as a caustic, 781. red mercuric iodide. 496. thiosinamine, 530. thyroid extract, 537. Lymphadenitis : ichthyol, applied externally in form of ointment, 528. sulphurated lime, used internally, 647. See also SCROFULOSIS. L\ mphoma : arsenic, 473. M Malaria : ammonia, as a heart stimulant in malarial collapse, 281. ammonium chloride, not of much service, 735. amyl nitrite, will abruptly end a chill; perhaps useful in pernicious type, 258. apiol, not of much value. 744. aristochin, an almost tasteless ester of quinine, 579. arsenic, useful especially in chronic or irregular malarias; also in convalescence from acute ague, 472. chloroform, may be used to abort a chill, 99. cinchonine. similar to but less powerful than quinine. 578. counter-irritants, in the collapse of pernicious malaria, 768. diaphoretics, to shorten duration of paroxysm, 719 eucalyptus, frequently of service when quinine contraindicated, 584. euquinine, a tasteless substitute for quinine, 579. gefsemium, 266. methylene-blue, a very powerful antiperiodic, especially valuable where haematuria, 581. piperin, 628. potassium salts, in hepatic disturbances, 693. quinine, the standard remedy, best given immediately before paroxysm, 572. saloquinine, 580. Warburg's tincture, probably the most effectual combination known against the more severe types of the disease, 579. Malarial Neuralgia: arsenic, as an adjunct to cinchona alkaloids, 473 electricity, probably of little value, 57. quinine, large doses required to produce an effect, 574. Malignant Pustule: escharotics, 776. Mania : atropine, when disease dependent on exhaustion, as puerperal mania, 181. cathartics, as revulsants, 653. 920 INDEX OF DISEASES. Mania Continued : chloral, for its somnifacient effect, 150. conium, to lessen the motor excitement, 272. croton oil, as a revulsant, 674. gelsemium , 267. hyoscine hydrobr ornate, seems to have some curative effect as Well as general sedative action, 189. Mania a Potu : See DELIRIUM TREMENS Mastitis : belladonna plaster, 182. Masturbation : heroine, claimed to be a sexual sedative, 145. potassium bromide, the most generally serviceable sexual sedative known, 246. Melancholia : alcohol, will often relieve symptoms, but great danger of habit, 307. cocaine, of very little service, 207. thyroid extract, may be tried, but not likely to be successful, 537. Membranous Croup : See CROUP. Meniere's Disease : pelletierine, 813. Meningitis : cautery, the most active form of counter-irritation, 769. cold, ice bag to the head, 31. electricity, contraindicated in the acute stages, 56. Menorrhagia : aloes, when constipation; acts as laxative and tends to pelvic hyperaemia, 665. calcium phosphate, when associated with anaemia, 520. cotarnine, 410 creosote, applied locally, 844. digitalis, claimed to act as a stimulant to uterine muscles, 328. ergot, perhaps the most generally efficient remedy known, 752 gelatin, increases coagulability of blood, may be used both internally and locally, 533 hydrastinine hydrochlorate, probably acts by causing contraction of womb, 763. mammary glands, extract of, 53 1 . oil of erigeron, 707. savine, useful only in conditions of relaxation, 742. suprarenal extract, given internally, probably causes uterine contraction, 543. thyroid extract, 537. viburnum. 744. Menstruation, Suppression of : See AMENORRHCEA. Mercurial Ptyalism : See PTYALISM. Metritis : bismuth oxyiodogallate , employed in form of suppositories, 426. creosote, as a disinfectant, especially in puerperal cases, 844. ergot, in chronic cases, 754. Metrorrhagia : ergot, acts by stimulating uterine muscle, 752. felatin, increases coagulation of blood, 533. ydrastinine hydrochlorate, 763. INDEX OF DISEASES. 921 Migraine : acetopyrin, coal-tar analgesic, 610. amyl nitrite, in cases with spasm of capillary blood-vessels, 258. antipyrine, during paroxysm, to relieve headache, 608 caffeine, sometimes promptly relieves headache, at others fails, 347. cannabis indica, used as curative between paroxysms, 195. cocaine, 207 electricity, of little service, 57. gold bromide, 250. salipyrin, used to relieve headache, 617. thermal, analgesic of coal-tar series, 618. validol, 75. Mitral Disease : See HEART DISEASE. Morphine-Poisoning : See OPIUM-POISONING. Morphoea : arsenic, 474. Multiple Sclerosis : acetanilid, 614. Muscarine Poisoning : atropine, counteracts effects of poison on inhibitory and secretory nerves, 182. digitalis, as heart stimulant, 327. Muscular Rheumatism : aconite, to produce sweating, especially in conjunction with pilocarpine, 383. diaphoretics, 719. Dover's powder, encourages sweating and relieves pain, 729. ichthyol, applied locally, 528. massage, 5. pilocarpine, to produce sweating, 726. potassium iodide, in subacute or chronic cases, 505. sulphur, 657. Myelitis : electricity, avoid during inflammatory stage, later useful to restore muscular tone, 56. phosphorus, as a reconstructive tonic for nerve centres, 617. silver nitrate, value questionable. 436. Myocarditis : See HEART DISEASE. Myopathy : thyroid extract, 538. Myxcedema : thyroid extract, is a specific, 537. N Narcotic Poisoning : See POISONING. Nasal Catarrh : See RHINITIS. Nausea : See SICK STOMACH. Nephritis : See BRIGHT'S DISEASE. 922 INDEX OF DISEASES. Nervous Exhaustion : See NEURASTHENIA. Nervous Vomiting : See VOMITING. Nervousness : asafetida, in cases of hysterical type, 76. camphor, a very useful sedative, 287. potassium bromide, the most reliable sedative except in hysterical cases, 245. valerian, useful in milder forms of hysteria, 75. Neuralgia : aconite, applied locally, 383. alcohol, grave danger of formation of habit, 307. ammonium chloride, formerly used in ovarian neuralgia, not generally effica- cious. 735 antipyrine, one of the best analgesics, 608. arsenic, especially but not exclusively useful in malarial cases, 474. aspirin, of service in nervous a? well as rheumatic types, 598. blisters, 768. butyl chloral- hydrate. 166 caffeine, very markedly increases the analgesic power of other antineuralgics, especially the coal-tar products, 347. cannabis indica, used both as an anodyne and as a curative, 195. carbon disulphide, employed locally as a counter-irritant. 775. chloroform, in the form of a liniment, 99. cod-liver oil, 518. croton chloral. 166. electricity, not useful when organic lesion or toxic cause. 57. ether, internally sometimes of service, 91. gelsemium, used especially as a curative agent in recurring neuralgias, 267. gold and sodium chloride, 497. Jiydrocyanic acid, in neuralgia of the stomach, 392. iodoform. when syphilitic origin, 510. methylene-blue, not so useful as other aniline derivatives, 578. oil of peppermint, applied locally over painful area, counter-irritant and anaes- thetic, 631. phosphorus, when due to nervous exhaustion, 461. potassium bromide, very frequently of service, especially in combination with caffeine, 245. potassium iodide, in rheumatic or syphilitic cases, 506. pyrosal, combination of antipyrin and salicylic acid, 618. quinine, especially in periodic types, even if not malarial, 574. saloquinine, 580. thermal, 618. veratrine, used externally in form of ointment, but is a dangerous remedy, 372. See also HEADACHE. Neuralgia, Intermittent : See MALARIAL NEURALGIA. Neuralgia, Rheumatic : See RHEUMATIC NEURALGIA. Neurasthenia : bromipin, a preparation of bromide, 251. bromolein, 251. cocaine, as a nerve stimulant and tonic, 207. digitalis, when circulation is feeble, 327. euquinine, as general tonic, 579. glycero-phosphates, supposed to represent phosphorus in easily assimilable form, but of unproved value, 519. gold and sodium chloride, used as nerve alterative, value doubtful, 497. hops, mildly sedative, useful in nervous unrest, 77. hypophosphites, 521. INDEX OF DISEASES. 923 paraldehyde, as a hypnotic, 161. phosphorus, increases reconstructive metabolism of nerve centres, frequently of great service, 460. rest-cure, 17. sparteine, to relieve cardiac palpitation, 353. strychnine, especially useful in chronic cases, 222. treatment of, 16. validol, a nerve sedative of valerian group, 75. valyl, 75. Warburg's tincture, in acute nervous exhaustion, 579. Neuritis : acetopyrin, to lessen pain, 608. aconite, rarely of value, may be used locally, 383. atropine, in cases with local muscular spasm, 180. blisters, the most generally useful form of counter-irritation, repeat frequently as necessary, 768. cautery, often valuable in chronic cases, 769. electricity, use galvanic current, but not during active inflammatory stage, 57. methylene-blue, to relieve pain, 581. rheumatine, a combination of salicylic acid and quinine, 579. salicylates, in rheumatic cases, 594. saloquinine, combination of quinic and salicylic acids, 580. Night-Pains, Syphilitic : iodoform, 510. Night-Sweats : agaric, a very frequently useful remedy, 409. alum, to be employed externally, 410. atropine, the most generally serviceable remedy known, 181. camphoric acid, 288. dionine, especially useful in phthisis, as it is also cough sedative, 143. ergot, in cases with passive relaxation of blood-vessels, 752. gallic acid, 406. sulphonal, 157. sulphuric acid, one of the best remedies, 453. Nipples, Sore: benzoic acid, best applied in form of compound tincture of benzoin, antiseptic and protective, 863. tannic acid, for purpose of hardening, 404. Nocturnal Emissions : See SPERMATORRHOSA. Nocturnal Enuresis : See INCONTINENCE OF URINE. N ymphomania : heroine, recommended as sexual sedative, 145. hyoscine hydrobromate , has especial action on sexual centres, 189. potassium bromide, in conjunction with hyoscine most efficacious remedy, 246. O Obesity : saccharin, as a sweetening agent free from objections to sugar, 792. treatment of, 20. thyroid extract, will reduce weight temporarily more certainly than any other drug, 537. Obstruction of Bowels: See INTESTINAL OBSTRUCTION. (Edema of the Lungs : strophanthus, 337. See also DROPSY. 9 2 4 INDEX OF DISEASES. (Esophagus, Stricture of: anaesthetics, when spasmodic origin, 82. Onychia Maligna : corrosive sublimate, powerfully germicidal, mildly caustic, 779. lead nitrate, to be- powdered on inflamed area, 423. Ophthalmia : iodine, used in scrofulous cases, 504. salicylic acid, in sympathetic ophthalmia, 594. silver acetate, in ophthalmia neonatorum, 438. Opium- Habit : cocaine, 207. treatment of, 135. Opium-Poisoning : atropine, as respiratory stimulant, 181. caffeine, respiratory and cerebral excitant, 347. potassium permanganate, as chemical antidote, 827. treatment of, 135. Osmidrosis : tannic acid, 404. Osteomalacia : calcium phosphate, 520. phosphorus, 461. Osteoporosis : phosphorus, 461. Otitis : betanaphtol, as an antiseptic, 851. resorcin, in chronic cases, 855. Otorrhcea : creosote, as a disinfectant in fetid types, 844. hydrastin, acts directly on mucous membrane, 760. potassium permanganate, oxidizing disinfectant, 827. Ovarian Irritation : gold and sodium chloride, in conditions of lowered nervous power, 497. viburnum, 744. Ovarian Neuralgia: ammonium chloride, of doubtful service, 735. gelsemium, acts beneficially in some unknown manner, 267. gold and sodium chloride, 49 7 . Over-Secretion : astringents, when due to relaxed condition, 402. tannic acid, 404. Oxalic Acid Diathesis : nitric acid, 455. nitro-hydrochloric acid, a specific in neurasthenic oxaluria, 455. Oxalic- Acid Poisoning: treatment of, 398. Oxyuris Vermicularis : See SEAT-WORMS. Ozsena : iodine, an alterative stimulant, 504. potassium permanganate, disinfectant, 827. INDEX OF DISEASES. 925 Pain: acetanilid, when pain of nervous origin, 614. aconite, locally applied in neuralgia arid similar conditions, 383. anaesthetics, of service in severe medical as well as surgical conditions, 8r. antipyrine, in various nervous pains whether functional or organic, 608. atropine, as local anodyne, 180. cannabis indica, frequently of service although not very powerful, 195. chloral, of little use as analgesic, 152. chloroform, externally as counter-irritant, 99. Dover's powder, 729. electricity, useful in neuralgic, not in organic pains, 57. exalgine, 617. iodofornt, as a local anaesthetic, 510. methylene-bhte, similar to, generally less useful than other aniline derivatives, 581. oil of peppermint, locally anaesthetic and counter-irritant. 622. opium, the most generally efficient drug, but danger of habit, 135. phenacetin, useful in nervous pains, especially in combination with caffeine, 615- Palpitation of Heart : See HEART, PALPITATION OF. Papilloma : resorcin, 855. Paralysis : electricity, not to be used during inflammatory stages, 56. strychnine, useful only when depressant poison is cause, 222. veratrine, applied as counter-imtant over the spine, 372. Paralysis Agitans: conium, 272. hyoscine.. a useful palliative, 189. Paraplegia, Myelitic : phosphorus, may be of service, 461 . silver nitrate, probably of no value, 436 Parturition : See LABOR. Pemphigus : arsenic, 473. Pericardial Effusions: See EFFUSION, PERICARDIAL. Pericarditis : mercury, when exudate is fibrinous 489. potassium iodide, in cases with serous effusion, 506. Peritonitis : blisters, 768. cold, applied to abdomen, 31. iodoform, in tuberculous peritonitis, 513. mercury, in sthenic forms of puerperal peritonitis or where fibrinous exudate, 489. opium, very useful for its antiphlogistic action as well as checking intestinal peristalsis, 134 poultices, a useful means of applying heat, 792, 793. veratrum, acts almost specifically, its tendency to vomit must be controlled by opium, 369 926 INDEX OF DISEASES. Pernicious Anaemia : bone-marrow, may be tried, 53 1 . iron, of very little service, 447. Pernicious Fever i See MALARIA. Pertussis : See WHOOPING-COUGH. Petit Mai : amyl nitrite, as a diagnostic agent, 259. chloretone, 162. potassium bromide, less generally of service than in true epilepsy, 246. Phagedaena : nitric acid, as a caustic, 780. Phantom Tumor: Calabar bean, acts by stimulating intestinal muscles, 231. Pharyngitis : suprarenal extract, to overcome congestion, 542. Phenol-Poisoning : treatment, 840. Phlegmons : ichthargan, applied in form of ointment, 440. phenol, deep injections of value, 838. Phosphatic Gravel : bcnzoic acid, 863. Phosphaturia : benzoic acid, to prevent precipitation of phosphates from urinary fermentation, 863. glycero-phosphoric acid, when daily elimination of phosphorus is excessive, 519. urotropin, as a urinary antiseptic, 700. Phosphorus-Poisoning : treatment of, 466. Phthisis : alcohol, of value as an accessory food and stimulant to digestion, 307. ammonium iodide, as a resolvent in incipient cases, 507. antipyrine, to control the fever, 607. arsenic, in fibroid or slowly progressing types. 474. calcium phosphate, 520. camphoric acid, to check the night-sweats, 288. cannabis indica, as a euthanasiac, 195. canlharidin, (note) 771. cocaine, as a local application in irritated throat conditions, 207. codeine, to check the cough, 142. cod-liver oil, of service on account of food value and perhaps through some specific action, 517. creosote, acts as a stimulant expectorant, 843 creosote carbonate, asserted to be less injurious to the stomach than creosote, 845- formaldehyde, has been employed by inhalation with doubtful benefit, 850. gallic acid, to lessen the night-sweats, 406. guaiacol, as a stimulant expectorant, 846. neroine, perhaps the most generally useful cough sedative known, 145. hyppphosphites, 520. iodine, applied externally as a counter-irritant, 503. prunus virginiana, used for cough, but very feeble, 622. sulphuretted hydrogen, an active but unpleasant expectorant. theocol, 845. tuberculin, its precise value as a curative agent is uncertain, 544. INDEX OF DISEASES. 927 Piles : See HEMORRHOIDS. Pityriasis : oil of cajnput, 629. res or tin, 855. Pleurisy : atropine, as a circulatory stimulant in conditions of collapse, 181. blisters, their counter-irritant effect often of service, 768. cold, applied over chest, 3 1 . gelsemium, 266. iodine, applied externally in chronic cases with serous effusion, 504. mercury, beneficial in cases with fibrinous exudate, 489. potassium iodide, when serous effusion is present, 477. poultices, the whole chest may be covered, 794. salicylic acid, recommended as diuretic in pleural effusion, 594. Pleuritic Effusion : See EFFUSION, PLEURAL. Pneumonia : aconite, in the early stages as a cardiac sedative not so good as veratrum, .383. alcohol, as a cardiac stimulant, 305. ammonia, used as an expectorant with doubtful advantage, 282. antipyrine, to lessen fever, 607. arsenic, in chronic or fibrous pneumonia, 474. atropine, as a circulatory stimulant, 181. blisters, 766. camphor, used hypodermically is a very useful cardiac stimulant in emer- gencies, 287. cold, 31, 37. cold-water compresses, preferable to hot applications when temperature is high, 795. digitalis, as heart stimulant, especially valuable in later stages, 327. ergot, used in the early stages, 7 53 . gelsemium, 266. guaiacol, used as antipyretic, but is dangerous, 846. mercury, 489. musk, as a nervous stimulant in adynamic forms, 74. naphtol, oily solution dropped into trachea, 851. oil of turpentine, as a counter-irritant application. 711. phosphorus, for the nerve exhaustion in adynamic cases, 462. poultices, 794. respiratory stimulants, 277. tartar emetic, to reduce circulatory excitement, 364. theocol, 847. veratrum viride, useful in early stages to diminish the congested area, 369. Poisoning : alcohol, as cardiac stimulant, 306. ammonia, hypodermically. as circulatory stimulant, 281. apomorphine, as emetic, 642. atropine, as a respiratory and circulatory stimulant, 181. heat, to combat collapse, 30. ipecacuanha, as an emetic, 637. mustard, a prompt and efficient but unpleasant emetic, 643. physiological salt solution, useful to maintain circulation and increase elimi- nation, 209, 679. strychnine, probably most powerful respiratory stimulant known, 222. zinc sulphate, the most generally useful emetic in poisoning, 643. Poisonous Fungi : atropine, the physiological antagonist of muscarine, 182. Poliomyelitis, Acute : See INFANTILE PARALYSIS. 928 INDEX OF DISEASES. Polyuria : exalgine, 615. See also DIABETES IXSIPIDUS. Post-partum Hemorrhage : ergot, acts by causing uterine contractions, most valuable remedy known, 751. ipecacuanha, supposed to affect coagulability of blood, 638. Pregnancy : calcium phosphate, as a prophylactic against foetal rickets, 520. cerium oxalate, for vomiting, 427. confection of senna, useful as a laxative, 667. ipecacuanha, for the relief of vomiting, 637. Prolapse of Rectum : strychnine, 222. Prurigo : hydrocyanic acid, a local anaesthetic used to allay itching, 394. naphtol, used in form of soap as antiseptic, 851 . Pruritus : anoesthesin, used in form of ointment, 118. brucine, 227. glycerin, when there is lack of sebaceous secretions, 790. hydrocyanic acid, 394. menthol, a useful local anaesthetic, 852. tobacco, 268. validol, combination of menthol and valerian, 75. Pseudo-membranous Croup : See CROUP. Psoriasis : ammonium iodide, used locally in form of an ointment, 507. aristol, 515. arsenic, employed internally, 473. chrysarobin, one of the most efficacious remedies known for this disease, 766. glycerin, emollient, is excellent vehicle for more powerful drugs, 791. iodine, of secondary value, 504. oil of cajuput, stimulant and parasiticide, 629. phosphorus, used internally, 461. pyrogallol, dangerous if used too freely, 781. resorcin, 855. thyroid extract, claimed to have a peculiar alterative effect on skin, 537. Psorophthalmia : citrine ointment, 496. Ptyalism : air opine, the most valuable internal remedy known, 181. tannic acid, used in solution as mouth wash, 404. Puerperal Convulsions : amyl nitrite, if used immediately after labor may cause post-partum hemor- rhage, 259. anesthetics, 82. camphor, of little value, 288. chloral, one of the most powerful anticonvulsants known, 151. nitroglycerin, 261. See also ECLAMPSIA. Puerperal Eclampsia: See ECLAMPSIA. Puerperal Fever: digitalis, as a circulatory stimulant, 328. nuclein, claimed to prevent the growth of septic bacteria, 531. INDEX OF DISEASES. 929 oil of turpentine, may be used both internally and externally, 711. streptococcus antitoxin, results have not proved encouraging, 548. See also SEPTICAEMIA. Puerperal Mania : atr opine, 181. splenic extract, 544. Puerperal Peritonitis : mercury, 489. Purpura Haemorrhagica : ergot, probably not of much value, 752. gelatin, acts by increasing coagulability of blood, 533. oil of turpentine, 711. Pysemia : alcohol, as a circulatory and general stimulant, 305. quinine, not probable that it exercises any direct action on pyogenic organ- isms, 571. tincture of ferric chloride, 450. Pyelitis : buchu, a mild stimulant to the urinary mucous membranes, 705. cantharides, actively stimulating, to be used only in chronic cases, 715. copaiba, 713. juniper, diuretic and stimulating, used in chronic cases, 707. methylene-blue, doubtful if of value, 581. salicylic acid, acts as urinary antiseptic, 594. turpentine, 712. iirotropin, urinary antiseptic, especially useful in lithaemic patients, 700. uva ursi, mildly astringent and diuretic, 705. Pyogenic Membranes: papain, 818. Pyrexia : See FEVER. Pyrosis : bismiith, antiseptic and sedative, 424. manganese dioxide, 451. silver oxide, feebly astringent, 438. Q Quinsy : salicylates, 594. R Rachitis : See RICKETS. . Remittent Fever: arsenic, used only when quinine not available, 472. diaphoretics, when paroxysms are close together, 719. quinine, must be used in full dose, 5 7.3 . Warburg's tincture, a very powerful combination containing quinine, 579. Renal Calculi: atropine, to lessen spasm during attacks of colic, 180. piperazine, to prevent deposition of uric acid, 689. Retention of Urine: strychnine, when due to atony of bladder, 222. Retina, Detachment of: dionine, 144. 59 930 INDEX OF DISEASES. Retinitis : iodipin, 508. Retraction of Gums: iodine, to be applied locally with camel's-hair brush, 504. Rheumatic Neuralgia : aconite, applied locally, 383. potassium iodide, in subacute or chronic cases, 506. salicylates, the most generally serviceable remedy, 594. Rheumatism : aconite, used to produce sweat, 383. ammonium iodide, especially in chronic forms, 507. avnyl salicylate, 599. arsenic, in chronic cases; may be alternated with iodides, 474. aspirin, a form of exhibiting salicylic acid much less likely to disturb diges- tion, 598. Burgundy pitch, as a mildly counter-irritant plaster, 775. carbolic acid injections, 838. cathartics, 653. chloroform, externally as counter-irritant, 99. cod-liver oil, useful in chronic types especially when poor nutrition, 518. colchicum, in those cases approaching the gouty type, 528. diaphoretics, to prevent muscular rheumatism following exposure, 719. Donovan's solution, used only in chronic cases, 507. Dover's powder, as a sudorific, 729. electricity, 52. glycosal, a salicylic preparation for external use, 599. gold and sodium chloride, may perhaps be of some service in chronic cases, 498. guaiac, 529. heat, local application may relieve joint, but has no beneficial effect on general condition, 29. ichthyol, mildly counter-irritant and alterative, 528. iodine, used externally in chronic cases, 510. iodoform, internally in chronic cases as analgesic, 510. jaborandi, to produce sweating, 726. magnesia, antacid and laxative, 656. massage, 5. meso/an, a salicylic acid preparation absorbed readily through the skin, 599. mfthylene-blue, as an analgesic, 581. oil of cajuput, 629. oil of gaultheria, an active form of salicylate, 598. oil of peppermint, externally, 631. phenocoll hydrochloride , 616. phenosol, 618. potassium acetate, is antacid and increases oxidation, especially valuable in acute cases, 692. potassium iodide, a very valuable remedy in chronic cases, 505. pyramidon, in acute cases to relieve pain, 618. pyrosal, 618. quinine, 572. rheumatine, combination of salicylic acid and quinine, 579. salicin, inferior to salicylates, 599. salicylates, the standard remedies in all forms of rheumatism, 594. salipyrin, as an analgesic, 617. salol, not very powerful but often of service in chronic cases, 847. salophen, acts much like salol, 600. sulphur, as a laxative, also as alterative in chronic cases, 657. sulphurated potassa, 658. urasol, a salicylic acid combination, 702. xanthoxylum, 530. Rheumatism, Inflammatory : antipyrine, to relieve excessive fever, 607. benzoic acid, asserted to be equal to salicylic acid, 863. INDEX OF DISEASES. 931 cimicifuga, an old remedy rarely employed to-day, 80. Dover's powder, valuable on account of diaphoretic effect, 729. lemon-juice, 396. oil of gaultheria, 597. phenocoll hydrochloride, 616. potassium acetate, 692. potassium nitrate, inferior to vegetable salts, 694. potassium salts, one of most valuable treatments; encourages oxidation and corrects systemic hyperacidity, 692. quinine, in very large doses, efficacious but dangerous, 572. salicylic acid, relieves pain and hyperpyrexia and probably has direct curative effect on morbid metabolism, 594. salipyrin, as antipyretic, 617. veratrine, dangerous and not effective, 372. Rheumatoid Arthritis: arsenic, probably the most frequently useful remedy known, 474. potassium iodide, 506. salicylic acid, but rarely of service, 594. Rhinitis : camphor-menthol, applied locally dissolved in liquid petrolatum, 852. hydrastin, an excellent local remedy especially in chronic catarrhs, 700. ichthargan, actively germicidal, may be used in spray, 440. suprarenal extract, constricts the engorged blood-vessels, 542. See also CATTARRH. Rhus-Toxicodendron Poisoning : lobelia, 264. Rickets : calcium phosphate, when there is a deficiency of lime salts in nutriment, 520. cod-liver oil, a valuable remedy especially in poorly nourished subjects, 518. phosphorus, stimulates the growth of bone, 461. Rigidity of Os Uteri : belladonna, applied locally, 180. Round- Worms : anthelmintics, 805. azedarach, used but comparatively little, 806. chenopodium, a useful remedy, 807. oil of cajuput, 629. oil of turpentine, 812. santonin, one of the most active drugs against this parasite, 809. spigelia, safe and efficient, 806. Salivation : See PTYALISM. Sarcoma : streptococcus toxin, results have been generally disappointing, 545. Scabies : glycerin, as an emollient vehicle, 790. rcsorcin, somewhat antiseptic, 855. sulphur, the most frequently employed remedy, 658. Scarlet Fever: aconite, as a febrifuge in the early stages, 383. alcohol, as a circulating stimulant for threatened collapse, 305. ammonia, rapidly acting cardiac stimulant, 281. antipyrine, to reduce hyperpyrexia, 607. atropine, has no specific action, as formerly believed, but is valuable as a stim- ulant, 181, 183. 932 INDEX OF DISEASES. Scarlet Fever Continued: capsicum, as a local application for the accompanying sore throat, 629. cold, to reduce fever, 37. hydrogen dioxide, used as antiseptic application to the throat, 829. streptococcus antitoxin, for secondary infections, especially of throat, 548. urotropin, probably of use as preventive of nephritis, 701. Sciatica : acetopyrin, as an analgesic, 610. electricity, galvanic current often of great service after acute inflammation is gone, 57. guaiac, 529. potassium iodide, of value in subacute rheumatic cases, 506. salicylatcs, the most useful remedy in rheumatic cases, 594. saloquinine, analgesic and antirheumatic, 580. sulphur, used in small doses as alterative, 657. Scleritis : iodipin, 508. physostigmine, 237. Scleroderma : hiosinamine, 530. Scrofulosis : alcohol, as an accessory food, 307. ammonium iodide, used both internally and externally as a resolvent, 569. calcium phosphate, 520. calx sulphurata, internal remedy for scrofulous glands, 659. cod-liver oil, to improve nutritive condition, 517. gold and sodium chloride, 498. gold oxide, 498. ichthalbin, a derivative of ichthyol suitable for internal use, 528. iodine, used internally for glandular enlargements., especially when no sup- puration, 505. phosphoric acid, largely used but of little value, 519. sarsaparilla, 529. syrup of ferrous iodide, combines alterative action of iodine with tonic effect of iron, 450. Scurvy : lemon-juice, a specific; the only remedy of value, 396. vinegar, may be substituted for lemon juice, but much inferior, 397. Seat- Worms : forced enemata, 650. naphtalin, given by injection, 850. quassia, probably the most generally useful remedy; use in enema, 622. vinegar, 397. Seborrhoea : arsenic, internally when of neurotic origin, 474. glycerin, externally to soften the skin, 790. resorcin, stimulant and antiseptic, 855. Seminal Emissions : See SPERMATORRHCEA Septicaemia : antitoxin, has not given brilliant results, 548. cold, to reduce fever, 37. colloidal silver, its value is problematical, 439. formaldehyde, intravenous injections of no service, 860. ichthargan, used hypodermically, but no positive evidence of value, 440. quinine, perhaps useful as antipyretic, has no specific action, 369. Serous Diarrhoea : See DIARRHOEA. INDEX OF DISEASES. 933 Sexual Excitement: camphor, a feeble sedative, 288. hops, frequently employed but of little use, 77. hyoscine hydrobromate, one of the most reliable sedatives known for this con- dition, 189. monobromated camphor, 79, 251. potassium bromide, a very valuable remedy, 246. See also NYMPHOMANIA. Shock : See COLLAPSE. Sick Headache: antacids, to correct acidity of stomach, 798. aromatic spirit of ammonia, the most generally useful antacid, 796 magnesia, laxative and antacid, 656. Sick Stomach : creosote, local anaesthetic and antiseptic, 844. ipecacuanha, as a gastric stimulant in atonic nausea, 637. Silver-Nitrate Poisoning : treatment of, 437. Singultus : See HICCOUGH. Sinking-Spells : See SYNCOPE. Skin Diseases: ammoniated mercury, 496. arsenic, used internally in chronic conditions, 473. cataplasm of kaolin, 793. chalk, as a protective and desiccant, 803. chrysarobin, an excellent stimulating application, especially in psoriasis, 766. citrine ointment, 496. cod-liver oil, used internally to improve nutrition, 518. Donovan's solution,used internally as an alterative, 507. gold iodide, 498. 'ichthyol, a local remedy of wide applicability, 527. iodine, occasionally used as an antiseptic, 504. magnesia, as a laxative antacid, 656. naphtol, as an antiseptic soap, 851. nitro-hydrochloric ac^d, for its stomachic effect, 456. oil of cajuput, stimulating and parasiticide, 629. ointment of zinc oxide, 428. oxide of mercury, 496. phosphorus, internally in various chronic conditions, 461. sulphur, used both internally and externally, 657. sulphurated potassa, 658. tar, 737. thyroid extract, especially in psoriasis and keloid, 537. vinegar, as a sedative astringent in acute inflammations, 397. zinc oxide, a widely useful astringent, 427. Sleeplessness : amylene hydrate, 163. bromipin, a preparation of bromides, 251. bromolein, 251. cannabis indica, 195. chloral, the most powerful hypnotic known in nervous insomnia, 150. chloralformamid, less powerful but less depressant than chloral, 165. chloralase, uncertain in its effects, 165. chloretone, feeble but safe, 162. dormiol, of moderate power in insomnia of nervous origin, 163. 934 INDEX OF DISEASES. Sleeplessness Continued. hedonal, sometimes of use in cases of not great severity nor associated with pain, 163. hyoscide hydrobromide, especially serviceable in insomnia of insanity or de- lirium, 189. hypnone, 164. isopral, 164. lactic acid, feeble and uncertain, 457. methylal, 163. opium, chiefly of value in insomnia due to pain, 133. paraldehyde, a safe and powerful remedy in sleeplessness not associated with pain, 161. potassium bromide, comparatively feeble as direct somnifacient, but useful in cases where wakefulness is caused by stimuli from without, 245. sulphonal, a slowly acting but fairly powerful remedy, 156. trional, less likely to cause chronic poisoning than sulphonal, 160. urethan, a safe and moderately active remedy in nervous insomnia, 163. veronal, 164, Smallpox : ichthyol, employed locally to prevent pitting, 527. opium, to sustain system by blunting sensibilities, 134. thiosinamine , to cure the scars after smallpox, 530. Snake- Poisoning : alcohol, of value as circulatory stimulant, but is not a specific as sometimes believed, 306. ammonia, a useful heart stimulant, inject hypodermically, 281. antitoxin, acts specifically in bites from certain varieties of snakes, 550. potassium permanganate, as a local antidote; should be injected into wound, 827. Sore Nipples : See NIPPLES, SORE. Sore Throat: acacia, dissolved in the mouth is very soothing in acute inflammations, 782. alum, as an astringent, not fitted for gargle, 410. atr opine, 181. carbolic acid, in ulcerated or diphtheritic sore throat as an antiseptic, 837. chlorine water, as a disinfectant gargle in violent infections, 826. cocaine, applied locally as vasoconstrictor and anaesthetic, 207. creosote, locally as antiseptic, 844. gum arabic, a demulcent, used in high-grade irritations, 782. mercury, internally as antiphlogistic, 489. phenol injections, 838. potassium chlorate, a very valuable astringent in not too acute inflammations, 697. salicylates, specifics in tonsillitis and rheumatic angina, 594. silver nitrate, sedative astringent and germicidal, 435. sumach berries, make an excellent astringent gargle, 409. tannic acid, applied by swab or as a gargle, 404. Spasms : aconite, not generally useful, 383. amyl nitrite, a very powerful and rapidly acting but fugacious relaxant, 259. anaesthetics, in severe hysterical or spinal convulsions, 81. asafetida, when due to hysteria, 76. atr opine, in local spasms especially of involuntary muscles, 180. chloral, in all forms of violent generalized convulsions a valuable remedy, 152. ether, 91. hyoscine, in asthma, whooping-cough, and similar disorders, 189. lobelia, in spasms of the bronchial muscles, 264. oil of cajuput, recommended in intestinal spasms, 629. opium, especially in cerebral or painful spasms, 133. INDEX OF DISEASES. 935 potassium bromide, one of the most valuable remedies in spinal and epileptic convulsion, 246. sulphonal, a feeble anticonvulsant, 137, Spermatorrhoea : antipyrine, 608. chloral, useful in spasmodic types, 152. digitalis, asserted to be actively anaphrodisiac, 328. kyoscine hydrobromide, one of the most valuable remedies known, 189. monobromated camphor, 251. potassium bromide, a very useful sexual sedative, 240. sulphonal, 157. turpentine, in cases with marked atony, 712. Spinal Congestion : ergot, 753. Spinal Depression : strychnine, 220. Spinal Scleroses : gold and sodium chloride, beneficial results have been claimed for it, 498. silver nitrate, an old remedy of doubtful value, 436. Spleen, Enlargement of: cold, douche said to be of service in post-malarial or even leukaemic spleens, 32. ergot, contracts vessels, useful in cases of chronic congestion, 752. potassium bromide, in post-malarial spleens, 246. Spongy Gums : tannic acid, 404. Sprains : arnica, as a stimulant application, 373. camphor, as a counter-irritant, 288. dilute acetic acid, a sedative, astringent lotion, 397. heat, locally applied of great service after acute inflammation has subsided, 29. ichthyol, 528. lead water, a frequently employed sedative embrocation, 422. massage, to be used after acute stage has subsided, 5. vinegar, 397. Status Epilepticus: amyl nitrite, 258. Stomatitis : boric acid, a large crystal of borax allowed to dissolve in the mouth is an excel- lent treatment, 869. phenol, the ulcers to be touched with a concentrated solution in glycerin, 837. potassium chlorate, employed both as a mouth wash and taken internally, 697. sodium chlorate, (note) 695. Strangury : ftaxseed, popularly used in form of a decoction, 784. opium, best administered per rectum, 140. Stricture : anaesthetics, in spasmodic stricture of oesophagus, 86. belladonna, in spasmodic stricture of either urethra or bowels, 180. thiosinamine , asserted to be useful in true urethral stricture, 530. Strychnine-Poisoning : amyl nitrite, use by inhalation or hypodermically to produce immediate re- laxation, 259. chloral, a very useful spinal depressant, 151. physiological salt solution, to aid in elimination of poison, 679. physostigma, a remedy of only secondary power, 237. potassium bromide, a valuable physiological antagonist, 246. treatment of, 225. 936 INDEX OF DISEASES. Subinvolution of Uterus: ergot, 754. Suffocative Catarrh: apomorphine hydrochlorate, as an emetic to evacuate exudate, 642. garlic, used externally in form of poultices, 737. treatment of asphyxia in, 729. Sulphonal-Poisoning : treatment of, 158. Summer Complaint: See CHOLERA INFANTUM Sunburn : dilute acetic acid, a valuable sedative astringent, 397. vinegar, 397. Suppressed Menstruation : See AMENORRHCEA. Suppression of Urine : calomel, one of the most powerful diuretics known in parenchymatous nephritis, 683. digitalis, in acute suppression a poultice of the leaves may be applied over loins, 686. jaborandi, given in small doses sometimes of service, 726. water, when suppression dependent on acute irritation of kidneys, 678. Sweating, Excessive : See HYPERIDROSIS. Syncope : alcohol, a rapidly acting cardiac stimulant, 304. ammonia, irritant action of vapors on mucous membrane of nose acts reflexly as stimulant, 281. amyl nitrite, a dangerous remedy, as the slightest overdose is depressant, 258. digitalis, give hypodermically in large doses, 326. ether, 91. Synovitis : carbolic acid, injections, 838. heat, applied locally especially in chronic cases, 29. Syphilis : ammonium iodide, used either internally or externally as a resolvent, 507. aristol, as a dusting powder for ulcers, 515. berberis, 624. calcium phosphate, recommended in syphilitic periostitis, also in gumma, 520. cod-liver oil, in the cachexia of tertiary stage, 518. gold and sodium chloride, in sclerosis of nervous system, 498. gold iodide, 498. guaiac, a remedy of secondary importance, may be used as adjunct, 529. ichthaWin, 528. iodipin, has same effect as iodides, but acts more slowly and persistently, 508. iodoform, used internally especially when "night-pains, '510. iodol, 514. mercury, especially useful in early stages, but a specific in all forms, 489. nitric acid, 455. nitro-hydrochloric acid, to improve digestion, 456. oxide of gold, 498. potassium iodide, a specific, employed most frequently in tertiary stage, 506. red mercuric iodide, a valuable form of mercurial, 496. sarsaparilla, perhaps of service as adjunct, 528. sulphur, natural sulphur-waters, recommended in chronic syphilis, 658. thiosinamine, as a local application in syphilitic skin lesions, 530. yellow mcrcurous iodide, a very efficient mercurial, 495. INDEX OF DISEASES. 937 T Tabes Mesenterica : cod-liver oil, increases general nutrition, 517. Tapeworm : anthelmintics, 805. aspidium, one of the best remedies against tapeworm, but is poisonous, 812. chloroform, probably of little value, 99. cusso, efficient and harmless, 807. ether, of only secondary value, 91. forced enemata, 650. kamala, 813. oil of wormseed, rarely used, 807. pepo, the safest and one of the most powerful taenicides, 812. pomegranate, efficient, but poisonous in overdose, 813. thymol, 8 1 1 . turpentine, 812. Tetanus : amyl nitrite, to allay spasm which threatens immediate death, although power- ful too fugacious for constant use, 259. antipyrine, 608. antitoxin, is of service in more chronic cases, 547. cannabis indica, 195. chloral, one of the most generally serviceable remedies known, 151. phenol, hypodermic injections have been asserted to act very favorably, 837. physostigma, useful as adjunct, too feeble to be relied upon, 236. potassium bromide, probably the best single remedy, must be used in large doses, 246. urethane, 163. Tic Douloureux: croton chloral, 1 66. gelsemium, 267. Tinea Capitis : acctozone, as a local germicide, 830. lime-water, valuable as a sedative application, 802. resorcin, stimulant and parasiticide, 855. Toadstool-Poisoning : atropine, 182. Tonsillitis : capsicum, applied locally with a swab, 629. gnaiac, used internally, 529. ichthargan, as a local germicidal astringent, 440. See also SORE THROAT. Toothache : oil of cloves, saturated pledget of cotton placed in cavity, 626. Torticollis : atropine, injected deeply into muscle, 180. hyoscine, usually fails, 189. Trachoma : ichthargan, 440. Trichiniasis : picric acid, 814. Trismus Nascentium : Calabar bean, 236. chloral, 151. physostigma, 236. 938 INDEX OF DISEASES. Tuberculosis : arsenic, as a reconstructive alterative especially in chronic cases, 474. arsenic iodide, as a local application in external tuberculosis, 482. cacodylic acid, a mode of exhibiting arsenic, 482. camphoric acid, for the relief of night sweats, 288. cantharidin, (note) 771. cinnamic acid, in pulmonary tuberculosis probably useful as a stimulating ex- pectorant, 864. cod-liver oil, one of the most valuable drugs known to improve nutrition, 517. colloidal silver, 439. fuaiacol, as a stimulant expectorant, 846. eroine, to allay cough in phthisis, 145. iodoform, as a local application especially in joint tuberculosis, 512. lecithin, asserted to exercise a beneficial effect on nutrition, 552. nucleins, 531. pyramidon, to reduce excessive fever, 618. tannoform, as an antiseptic astringent in diarrhoea, 405. See also PHTHISIS. Tympanites : aromatic s, 625. asafetida, especially valuable in debilitated subjects, 75. escharotics, 776. physostigma, a direct stimulant to intestinal muscle fibres, 237 Typhoid Fever: For methods of controlling temperature see under FEVER. For treatment of hemorrhage see under HEMORRHAGE FROM THE BOWELS. acetozone, as an intestinal antiseptic, 830. alcohol, an essential part of the treatment; aids digestion, acts as food, and stimulates circulation, 307. beta-naphtol, lessens intestinal fermentation by its antiseptic effects, 851. caffeine, 347. camphor, hypodermically in threatening collapse, a powerful heart stimulant, 287. cold, best means of combating hyperpyrexja, 37. creosote, as intestinal antiseptic, 844. digitalis, claimed to act as antipyretic as well as cardiac stimulant, 328. guaiacol, as an antipyretic is dangerous, 846. hydrochloric acid, of little benefit, 454. jaborandi, 726. musk, in conditions with low muttering delirium a very valuable remedy, 74. naphtalin, 850. oil of turpentine, best remedy for tympanites, acts as an intestinal antiseptic and carminative, 711. salol, probably most effective intestinal antiseptic, 845. sulphur, 656. suprarenal extract, to check hemorrhage from bowels, 542. thymol, of little value, 853. Typhus Fever: alcohol, useful as an accessory food as well as circulatory stimulant, 305. antipyrine, to reduce excessive pyrexia, 607. ati -opine, as a circulatory stimulant, 181. chloral, as a cerebral sedative in delirious cases, 150. chlorine water, 826. cold, to control fever, 37. U Ulcer of Cornea: See CORNEAL ULCER. liberation of the Bowels : copper sulphate, 429. oil of turpentine, 711. INDEX OF DISEASES. 939 Ulcers : acetozone, 830. alum, astringent, used when excessive secretions, 411. aluminum sulphate, 411. black wash, in syphilitic ulcers, 496. Canquoin's paste, as a caustic in syphilitic growths, 779. chalk, as a desiccant and protective, 803. chloral, anaesthetic and antiseptic, 152. chloretone, somewhat antiseptic and locally anaesthetic, 162. chlorine water, a stimulant disinfectant application, 826. cold douclie, as a stimulant to sluggish ulcers, 31. copaiba, in chronic ulcers of the stomach, 711. copper sulphate, in \ndolent ulcers especially of mucous membranes, 429. creosote, as a disinfectant in foul ulcers, 844. eschar otics, to destroy exuberant granulations, 776. ichthargan, a silver germicidal preparation, 440. ichthyol, 527. iodoform, a desiccant, alterative, and antiseptic, 511. lead plaster, as a protective in superficial ulcers, 421. lime-water, 803. mezereon, 529. nitric acid, actively caustic, 780. phenol, an active germicide, 837. potassium permanganate, antiseptic and cleansing, used where much suppu- ration, 827. red mercuric oxide. resin cerate, a stimulant application, 708. silver nitrate, mildly stimulant and actively germicidal, used especially to destroy exuberant granulations, 435. solution of mercuric nitrate, as a caustic, 779. sulphuric acid, a dilute solution stimulant and astringent, 452. tannic acid, to lessen excessive secretion on old ulcers, 404. tannoform, supposed to be both antiseptic and astringent, 406. thyroid extract, 538. yellow wash, in syphilitic ulcers, 496. zinc oxide, used as desiccant and astringent dusting powder, 427. zinc sulphate, 781. Uncinariasis : thymol, 813. Unilateral Sweating: jaborandi, 726. Uraemia : chloral, to control convulsions, 151. elaterin, a hydragogue purgative believed to eliminate urea through the bowels, 674. jaborandi, as a diaphoretic, 726. nitroglycerin, used to overcome spasms, 261. opium, used as anticonvulsant and diaphoretic, but dangerous on account of effect on secretion of urine, 135. quebracho, to combat dyspnoea, 278. Urethral Fever: aconite, 383. potassium bromide, lessens irritability of genital system, 246. Urethral Spasm : belladonna, 180. Urethritis : acetanilid, a suspension may be used locally, 614. copper sulphate, 429. silver nitrate, actively astringent and germicidal, 435. terebene, used internally in later stages, 738. See also GONORRHOEA. 940 INDEX OF DISEASES. Uric Acid Calculus and Gravel : bcnzoic acid, one of the most generally useful remedies known, 863. piper azine, useful in gravel, 699. potassium salts, of service as prophylactic, 693. quinic acid, claimed to greatly lessen output of uric acid, 701. quinotr opine, 701. sidonal, a combination of piperazine and quinic acid, 701. soda, inferior to potash, 800. Uric Acid Diathesis: benzoic acid, a useful remedy, 863. lithium, much employed but of uncertain value, 698. lycetol, 699. potassium salts, increase oxidative processes of body, frequently of much ser- vice, 693. sodium, 800. sodium phosphate, as a laxative, 669. treatment of, 24. Urticaria : arsenic, in chronic forms, 473. cimicifuga, acts almost specifically in neurotic cases, 78. emetics, when due to gastric irritation, 633. ichthyol, as a local application, 527. menthol, as a local application to lessen itching, 852. Uterine Inertia: ergot, to be used very cautiously on account of danger of uterine spasm, 750. quinine, in full dose sometimes of service, 568. Uterus, Cancer of : chloral, as a local anaesthetic and antiseptic, 152. cotton root, to arrest the hemorrhage, 764. iodoform, applied locally to allay pain, 513. Uterus, Fibroid Tumors of : cotton-root, to allay hemorrhage or other symptoms, 764. ergotin, has been administered hypodermically, 753. mammary gland, 53 1 . Uterus, Subinvolution of: ergot, 754- Uveitis : dionine, increases lymphatic circulation in eye, 144. salicylic acid, 594. Vaginismus : piper in, 628. Vaginitis : acetanilid, used locally in a suspension, stimulant antiseptic, 614. bismuth oxyiodogallate , used in suppository, antiseptic and sedative, 426. erindelia, 736. hydrastin, influences mucous membrane directly, 760. ichthargan, a germicidal silver preparation, 440. Valvular Heart Disease : See ENDOCARDITIS. Varicose Veins : ergot, used locally, but probably of little value, 752. hamamelis, feebly astringent, 408. Venereal Ulcers : See CHANCRES AND CHANCROIDS. INDEX OF DISEASES. 941 Venereal Warts : nitric acid, 454. Veratrum- Viride Poisoning : alcohol, as a heart stimulant, 306. treatment of, 369. Vesical Tenesmus : ancesthesin, 118. Vomiting : aconite, locally stimulant and anaesthetic, especially valuable in pregnancy, 383. ancesthesin, acts as a local anaesthetic, 118. bismuth subnitrate, sedative, astringent, and antiseptic, 424. cerium oxalate, believed to have a specific action especially in vomiting of pregnancy, 427. chloretone, 162. cocaine, paralyzes the sensory nerves of stomach, 207 creosote, antiseptic and local anaesthetic, 844. hydrastin, stomachic, 760. ipecacuanha, in atonic conditions especially in pregnancy, 637. lime water, to render milk more easily digested, 802. opium, one of the best remedies we have, benumbs vomiting centre; may be given per rectum, 134, 140. orexin, stimulant to gastric mucosa, especially recommended after anaesthesia and in pregnancy, 625. phenol, antiseptic and locally anaesthetic, often of great service in gastritis, 837. potassium bromide, in reflex vomiting from uterine disturbances, .246. prussic acid, local anaesthetic, 391. treatment of, 634. valyl, in hysterical conditions, 77. W Warts: nitric acid, one of the most generally useful caustics, 454. pa fain, supposed to dissolve them by a process similar to digestion, 8r8. White Swelling : See JOINTS, INFLAMMATION OF. Whooping-Cough : antipyrine, of some value as antispasmodic, 607. aristochin, a synthetic quinine derivative, 579. arsenic, 476. asafetida, antispasmodic and expectorant, 76. atropine, a valuable remedy on account of antispasmodic action, 180 bromoform, doubtful if it possesses any virtue not found in bromides, 250. camphor, its use has largely passed out of vogue, 288. chloral, useful temporarily to check spasms, 152. conium, an unreliable remedy, 272. euquinine, probably less efficient than quinine, 579. gelsemium, 267. grindelia, as an expectorant, 736. heroine, as a cough sedative, 145 hyoscine, for its antispasmodic effect, 185. quinine, seems to act specifically, perhaps exercises antiseptic effect, 575. thermal, acts like phenacetin, 618. thyme, 853. Winter Cough : See BRONCHITIS. Worms : See ROUND-WORMS and TAPEWORMS. 942 INDEX OF DISEASES. Wounds : acetanilid, as antiseptic dusting powder, of secondary value, 614. alcohol, actively antiseptic and sedative, especially used as a dressing, 309. aristol, a useful desiccant and antiseptic dusting powder, 515. bismuth subgallate, as a dusting powder, 427. boric acid, feebly antiseptic, 869. chloretone, locally anaesthetic and somewhat antiseptic, 162. escharotics, in poisoned wounds, as bites, or when seriously infected, 776. formaldehyde, powerfully disinfectant but too irritant for ordinary uses, of service when severe infection, 859. hydrogen dioxide, cleansing on account of its oxidizant action, also antiseptic. iodoform, desiccant, anaesthetic and slightly antiseptic, 511. orthoform, useful in painful wounds, local anaesthetic, and somewhat antiseptic, 118. phenol, actively bactericidal, 837. potassium permanganate, oxidizant and disinfectant, 827. protargol, a germicidal silver preparation, 441. quinine, (note) 575. Y Yellow Fever: antipyrine, to control hyperpyrexia, 607. GENERAL INDEX. Abies balsamea, 708 excelsa, 775 A. B. S. pill, 666 Absolute acetic acid, 397 alcohol, 289 Absorbent cotton, 764 Absorbents, 819 Acacia, 782 catechu, 407 Senegal, 782 A. C. E. mixture, (note) 106 Aceta, 61 Acetanilid, 610 Acetanilidum, 610 Acetic acid, 397 ether, 79 poisoning, 397 Acetonchloroform, 162 Acetone, 397 Acetonum, (note) 397 Acetophenone, 164 Acetopyrin, 610 Acetozone, 830 Acetphenetidin, 614 Acetphenetidinum, 614 Acetum, 396 opii, 141 scillae, 682 Acetyl-methylene-disali- cylic acid, 702 Acetylparamidophenyl, 599 Acetyl-salicylic acid, 598 Acetyl-salicyl-phenetidin, ' 618 Acid potassium pxalate, 398 Acids and alkalies, 864 Acidum aceticum, 397 aceticum dilutum, 397 aceticum glaciale, 397 benzoicum, 861 boricum, 866 camphoricum, 288 carbolicum crudum,83i cinnamicum, 864 citricum, 395 gal lieu m, 406 hydriodicum dilutum, 508 hydrobromicum dilu- tum, 249 hydrochloricum, 454 hydrochloricum dilu- tum, 454 Acidum hydrocyanicum, 385 hydrocyanicum dilu- tum, 385, 393 hypophosphorosum , 520 lacticum, 457 nitricum, 454, 780 nitricum dilutum, 455 nitro-hydrochloricum, 455 nitrp-hydrochloricum dilutum, 455 nitrosum, 455 oleicum, 787 oxalicum, 397 phosphoricum, 518 phosphoricum dilutum, 5i8 picrum, 814 quinicum, 701 salicylicum, 587 stearicum, 788 sulphuricum, 453 sulphuricum aromati- cum, 454 sulphuricum dilutum, 454 sulphurosum, 864 tannicum, 402 tartaricum, 394 trichloraceticum, 780 Aconine, 374, (note) 380 Aconite, 373 poisoning by, 383 Aconitine, 374, 385 Aconitum, 373 anthora, (note) 374 cammarum, (note) 373 ferox, (note) 373 fischeri, (note) 374 japonicum, (note) 374 lycoctonum, (note) 374 napellus, 373 neomontanum, (note) 373 , pamculatum, (note) 37.3 tauncum, (note) 373 variabile, (note) 373 Acrinyl sulphocyanate, 773 Actol, 438 Adeps, 786 benzoinatus, 786, 863 lanae, 788 Adeps lanae hydrosus, 788 Adhesive plaster, 421, 708, 796 Adjuvant elixir, 784 Adonidin, 354 Adonis vernalis, 354 Adrenalin, 539 Adrenals, 538 yEther, 87 aceticus, 79 ^Ethylis chloridum, 100 carbamas, 163 ^thyl-sulphonic acid, 155 African arrow-poison, 312 pepper, 628 Agaric, 409 acid, 409 Agaricin, 409 Agaricinic acid, 409 Age in relation to dose, 66 Agropyrin repens, 706 Airol, 426 Albargin, 438 Alcohol, 289 absolutum, 289 dilutum, 289 poisoning, 310 Alexandria senna, 666 Alimentation, rectal, 14 Allis inhaler, in Allium, 736 sativum, 736 Allspice, 627 Allyl-sulphocarbamide, 529 sulpho-urea, 529 A*loe, 664 purificata, 665 Aloes, 664 Barbadoes, 664 Cape, 664 Socotrine, 664 Aloin, 664 Aloinum, 664 Alpha-eucaine, 117 Alterative diuretics, 704 Alteratives, 459 Althaea, 785 officinalis, 785 Alum, 410 curd, 411 dried, 410 poisoning, 410 Alumen, 410 exsiccatum, 410 943 944 GENERAL INDEX. Aluminii hydroxidum, 411 sulphas, 411 Aluminum hydrate, 411 hydroxide, 411 sulphate, 411 Alypin, 118 American silver fir, 706, 708 Amido-camphor, (note) 283 Ammonia, 279, 774 alum, 410 poisoning, 282 water, 282 Ammoniac, 739 emulsion, 739 plaster with mercury, Ammoniacum, 739 Ammoniated mercury, 496 tincture of guaiac, 529 tincture of valerian, 75 Ammonii benzoas, 864 bromidum, 247 carbonas, 282 chlpridum, 734 iodidum, 507 nitras, 283 salicylas, 596 valeras, 75 Ammonium acetate, solu- tion of, 728 benzoate, 864 bromide, 247 carbonate, 282 cathartate, 666 chloride, 734 ichthyo-sulphate, 527 iodide, 507 nitrate, 283 picrate, 814 sal icy late, 596 valerate, 75 valerianate, 75 Amorphous aconitine, 374 aspidospermine, 277 Ampere, 45 Amygdala amara, 394 Amygdalin, 624 Amylene chloral, 163 hydrate, 163 Amyl nitrite, 252 Amylis nitris, 252 salicylas, 599 Amylum, 784 Anaesthesia, practical, 103 accidents in, 112 after-effects of, 116 local, 117 Anaesthesin, 118 Anesthetics, 81 Anarcotine, 142 Anclira araroba, 766 Animal charcoal, 819 drugs, 530 Anise, 630 Anisum, 630 Annidaline, 514 Antacids, 797 Anthelmintics, 805 Anthem is, 631 nobilis, 631 Anthracene, (note) 663 Anthrarobin, (note) 766 Antidiphtheric serum, 545 Antifebrin, 610 Antimonial ointment, 366 wine, 366 Antimonii et potassii tar- tras, 360 oxidum, 360 sulphidum, 360 purificatum, 360 Antimonium sulphuratum, 360 Antimony, 360 and potassium tartrate, 360 oxide, 360 poisoning by, 304 sulphide, 360 Antinosine, 515 Antiperiodics, 555 Antipyretics, 586 Antipyrin, 600 aceto-salicylate, 617 salicyl-acetate, 618 salicylate, 617 Antipyrina, 600 Antipyrylurea, 617 Antiseptics, 820 Antispasmodics, 73 Antitoxins, 544 Antitussin, 865 Antivenin, 550 Apiol, 743 Apium petroselinum, 743 Apocodeine, 651 Apocynein, 333 Apocynin, 333 Apocynum, 333 cannabinum, 333 Apomorphinae hydrochlo- ras, 639 Apomorphine, 639 hydrochlorate, 639, 734 Apothecaries' measure, 879 weights, 879 Apparatus for artificial res- piration, 114 Appendix, 879 Aqua ammoniaa, 282, 774 ammoniac fortior, 282, 774 .. aurantu florum, 630 camphorae, 288 chloroformi, 100 cinnamomi, 626 creosoti, 845 foeniculi, 630 hamamelis, 408 hydrogenii dioxidi, 828 menthae piperitae, 630 menthae viridis, 630 Aqua rosce, 409 Aquae, 61 Arabin, 782 Araroba, 766 Arbutin, 705 Arctostaphylos uva ursi, 7t>5 Argel-leaves, 666 Argenti acetas, 438 casein, 439 citricum 438 cyanidum, 394, 438 lactas, 438 nitras, 431, 822 nitras dilutus, 438 nitras fusus, 431 oxidum, 438 sulphophenas, 439 Argentol, 438 Argentum, 431 solubile, 439 Argol, 395 Argonin, 439 Argyria, 432 Argyrol, 438 Aristochin, 579 Aristol, 514 Aristolochia reticulata, 631 serpentaria, 631 Arnica, 372 montana, 372 root, 372 Arnicine, 372 Aromatic bitters, 631 fluid extract, 626 fluid extract of cascara sagrada, 655 powder, 626 spirit of ammonia, 282 spirit of hartshorn, 282, 798 sulp phuric acid, 454 syrup of rhubarb, 664 tincture of rhubarb, 664 Aromatics, 625 Arrow-poison, 334 Arrow-root porridge, 1 2 Arseni iodidum, 482 Arsenic, 468 antidotes, 480 as a caustic, 778 -eating, 472 iodide, 482 poisoning, acute, 474 chronic, 478 post-mortem imbibi- tion, 481 trioxide, 468 Arsenical paper, com- pound, 732 solution of lithium, 698 Arsenii trioxidum, 468 Arsenous acid, 468 Art of prescribing medi- cines, 67 Artemisia pauciflora, 807 GENERAL INDEX. 945 Artificial camphor, 708 respiration, 114 respiration, apparatus for, (note) 114 Artificially digested foods, 13 Asafetida, 75 Asafoetida, 75 Asagraea officinalis, 370 Aspic, oil of, (note) 630 Aspjdin, (note) 811 Aspidium, 8n spinulosum, (note) Sn Aspidosamine, 277 Aspidosperma, 277 quebracho-bianco, 277 Aspidospermatine, 277 Aspidospermine, 277 Aspirin, 598 Astragalus gummifer, 783 Astringents, 401 Atomization, 65, 732 Atoxyl, 483 Atropa belladonna, 168 Atropina, 168 Atropinae sulphas, 184 Atropine, 168 poisoning by, 183 sulphate, 184 Aurantii amari cortex, 629 dulcis cortex, 630 flores, 630 Auri et sodii chloridum, 497 Ava, 715 Azedarach, 806 Baked flour porridge, 12 Balm, 630 of Gilead, 708 Balsam of Peru, 736 of Tolu, 736 Balsamum peruvianum, 736 tolutanum, 736 traumaticum, 863 Banks oil, 515 Bantingism, 22 Barbadoes aloes, 664 Barbaloin, 664 Barberry, 623 Barley, 785 water, 785 Barosma betulina, 704 cernata, 704 Basilicon ointment, 708 Bassorin, 783 Bearberry, 705 Beef essence, 9 tea, 9 Belladonna, 168 leaf, 168 plaster, 184 Belladonna poisoning, 183 root, 1 68 Belladonnas folia, 168 radix, 168 Benzaconine, 374, (note) 380 Benzaldehyde, 394 Benzaldehydum, 394 Benzine, (note) 106 Benzojc acid, 86 1 Benzoin, 861 Benzoinated lard, 786, 863 Benzoinum, 86 1 Benzosulphinidum, 791 Benzoyl-acetyl-peroxide, 830 Benzoyl-tropein, 117 Benzozone, 830 Berberine, 623, 756 Berberis, 623 vulgaris, 623 Bertoni's ether, (note) 252 Beta-eucaine, 117 Beta-naphtol, 850 Beta-naphtol-ether salicyl- ate, 852 Beta-oxysantonin, 808 Betol, 852 Bichloride of mercury, 821 Bile, 655 effects of drugs on, 646 Biniodide of mercury, 822 Bismuth, 423 and ammonium citrate, 425 citrate, 425 oxyiodide, 427 oxyiodpgallate, 426 poisoning, 424 salicylate, 427 subcarbonate, 423 subgallate, 426 subnitrate, 423 subsalicylate, 426 tetraiodophenolphtha- lein, 515 Bismuthi citras, 425 et ammonii citras, 425 subcarbonas, 423 subgallas, 426 subnitras, 423 subsalicylas, 426 BismuthutTii 423 Bisulphites, 865 Bitter almonds, 394 cucumber, 671 orange peel, 629 Bitters, 622 Black draught, 667 drink, (note) 338 drop, 141 ginger, 627 haw, 744 manganese oxide, 741 mustard, 772 oak bark, 408 60 1 Black pepper, 628 snakeroot, 78 wash, 496 Blackmail's disinfectant, (note) 825 Bleaching powder, 823 Blisters, 766 Bloodroot, 739 Blue galls, 406 mass, 493, 660 ointment, 492 pills, 493 stone, 429 Boletus, 409 laricis, 409 Boneblack, 819 Bone-marrow, 531 Bonjean's ergotin, 756 Boracic acid, 866 Borax, 866 Boric acid, 866 Borneo camphor, (note) 76 Bornylamin, (note) 283 Boroglycerin, 869 Bougies, 65 Bran, 654 Brandy, 289 Brassica alba, 772 nigra, 772 i Brayera, 807 ; Bread-and-milk poultice, 794 Bromal hydrate, 251 Bromalin, 251 Bromated camphor, 79, 251 Bromethylformin, 251 Bromides, comparative power of, 250 Bromine, 781 as a disinfectant, 824 Bromipin, 251 Bromism, 241 Bromocoll, 251 Bromoform, 250 Bromoformum, 250 Bromolein, 250 Bromum, 781 Broom plant, 350 Broth, chicken, 9 Brown mixture, 784 stock, 10 sugar, 654 Brown-Sequard's elixir, . 53i Brucine, 212, 227 nitrate, 227 sulphate, 227 Bubonic plague serum, 549 Buchu, 704 Buckthorn, 655 Burgundy pitch, 775 pitch plaster, 775 Burnt alum, 781 Butyl-chloral hydrate, 165 946 GENERAL INDEX. Cabinet baths, (note) 717 Cacao butter, 787 Cacodylic acid, 482 Caffeina, 338 citrata, 339 citrata effervescens, 339 Caffeine, 338 poisoning, 348 Caffeol, (note) 340 Caffeone, (note) 339 Cajuput, 629 Calabar bean, 229 Calabarine, 229 Calabarinum puruni,(note) 231 Calamine, 428 Calcii bromidum, 249 Calcii carbonas praecipi- tatus, 803 chloridum, 803 hypophosphis, 521 iodidum, 804 phosphas pnecipitatus, 520 sulphas exsiccatus, 803 Calcium, 801 bromide, 249 carbonate, 803 chloride, 803 hypophosphite, 521 iodide, 804 lactophosphate, 520 phosphate, 519 precipitated, 520 sulphate, 803 sulphide, 658 California buckthorn, 655 Calomel, 493, 660, 682 Caloric, 28 Calumba, 623 Calx, 801 chlorinata, 824 sulphurata, 658 Cambogia, 674 Campherol, (note) 283 Camphor, 283 artificial, 708 bromated, 79 cymol, (note) 283 liniment, 288 -menthol, (note) 852 mixture, Hope's, 455 mqnobromated, 251 poisoning, 288 water, 288 Camphora, 283 monobromata, 79 Camphorated tincture of opium, 141 Camphoric acid, 288 Canada balsam, 708 fleabane, 707 turpentine, 708 Canadian hemp, 333 Canadine, 756 Cannabene, 192 tannate, 195 Cannabin, 191 Cannabinol, 192 Cannabinon, 191 Cannabis indica, 191 Canquoin's paste, 779 Cantharjdal collodion, 772 Cantharides, 714, 742, 769 cerate, 772 poisoning, 771 Cantharidin, 769 salts, (note) 771 Cantharis, 714, 769 vesicatoria, 769 Cape aloes. 664 Capsicin, (note) 629 Capsicum, 628, 773 annuum, 629 fastigiatum, 628 Capsules, 69 Caraway, 630 Carbamic ether, 163 Carbazotic acid. 814 Carbo, 819 animalis, 819 purificatus, 819 ligni, 819 Carbolic acid, 831 poisoning, 838 Carbon bisulphide, 775 compounds, 831 Carbonei disulphidum, 775 Cardamom, 627 Cardamomum, 627 Cardiac depressants, 359 massage, 115 stimulants, 279 Cardiants, 279 Carica papaya, 817 Carminatives, 625 Carolina jessamine, 264 Carrageen, 783 Carrageenin, 783 Carron oil, 802 Carum, 630 carui, 630 Caryophyllus, 626 Cascara sagrada, 655 Cassia acutifolia, 666 angustifolia, 666 bark, 626 fistula, 656 obovata, 666 Castile soap, 765 Castillon's powder, 803 Castor oil, 659 oil beans, 659 Cataplasm of kaolin, 793 Cataplasma kaolini, 793 Catechu, 407 Cathartic acid, 666 Cathartics, 644 Caustic potash, 777 soda, 800 Cayenne pepper, 628 Centric emetics, 635 local anaesthesia, 121 Cephaeline, 635 Cephaelis acuminata, 635 ipecacuanha, 635 Cera alba, 786 flava, 786 Cerasus serotina, 624 Cerata, 62 Cerates, 62 Ceratum cantharidis, 772 resinae, 708 compositus, 708 Cerebritis, saturnine, 414 Cerii oxalas, 426 Cerium oxalate, 426 Cetaceum, 786 Cetraria, 785 islandica, 785 Cetraric acid, 785 Cetrarin, 785 Cevadine, 366 Ceylon cinnamon, 626 Chalk, 803 mixture, 803 Chamomile, 631 Champagne, 309 Charcoal, 819 Charta arsenicalis compos- ita, (note) 732 sinapis, 773 Chartae, 62 Chemical current, 47 Chenopodium, 806 anthelminticum, 806 Chicken broth, 9 Children, comparative dose for, 65 Chili saltpetre, 694 Chillies, 628 Chimaphila, 706 umbellata, 706 Chimaphilin, 706 Chinese cinnamon, 626 Chinic acid, 701 Chirata, 623 Chloral, 146 hydrate, 146 intravenous injections of, 152 poisoning, 152 poisoning, chronic, 153 Chloralamid, 164 Chloralformamid, 164 Chloralformamidum, 164 Chloralose, 165 Chloralum hydratum, 146 Chloretone, 162 Chloric ether, 449 Chlorinated lime, 824 Chlorine, 823 water, 826 Chloroform, 92 liniment, 100 water, 100 GENERAL INDEX. 947 Chloroformum, 92 Chlorum, 823 Chocolate porridge, 12 Cholera antitoxin, 548 Choline, 551 Chondodendron tomento- sum, 705 Chondrus, 783 crispus, 783 Chromic acid, 780 Chromii trioxidum, 780 Chromium trioxide, 780 Chronic antimony-poison- ing, 3 6 5 arsenic-poisoning, 478 chloral-poisoning, 153 digitalis-poisoning, lead-poisoning, 412 sulphonal-poisoning, 157 Chrysaroba, 765 Chrysarobin, 765 Chrysarobinum, 765 Chrysophanic acid, 662 Chrysotoxin, 746 Churrus, 191 Cigarettes, arsenical, (note) 732 Cimicifuga, 78 racemosa, 78 Cimicifugin, 78 Cinchona, 555 flava, 555 pallida, 555 rubra, 555 Cinchonamine, 578 Cinchonidinae sulphas, 57.8 Cinchonidine, 578 bromohydrate, 578 sulphate, 578 Cinchoninae sulphas, 577 Cinchonine, 577 sulphate, 577 Cinnaldehydum, 626 Cinnamic acid, 864 aldehyde, 626 Cinnamomum, 626 saigonicum, 626 zeylanicum, 626 Cinnamon, 626 water, 626 Citrated caffeine, 339 Citric acid, 395, (note) 453 Citrine ointment, 496 Citrullus colocynthis, 671 Clarke's Rule for Doses, (note) 66 Classification, 70 Claviceps purpurea, 745 Clear stock, 10 Clove tea, 627 Cloves, 626 Coca, 195 Cocainae hydrochloridum, 207 Cocaine, 196 habit, 209 hydrochloride, 207 poisoning, 207 Cocainismus, 209 Coca-tannic acid, 196 Codeina, 141 Codeinae phosphas, 141 sulphas, 141 Codeine, 141 phosphate, 141 sulphate, 141 Cod-liver oil, 577 Coffee, 338, (note) 339 Cohnheim's salt frog, 150 Colchiceine, (note) 521 Colchici cormus, 521 semen, 521 Colchicina, 527 Colchicine, 521, 527 Colchicum, 521 autumnale, 521 poisoning, 526 root, 521 seed, 521 Cold, 30 as a diuretic, 678 as an antiseptic, 820 as a tonic, 32 bath, 36 cream, 409, 786 in pyrexia, 32 local use of, 30 physiological action of, 32 Colica pictonum, 413 Collargol, 439 Collodion, 796 Collodium, 796 cantharidatum, 772 flexile, 796 stypticum, 405 Colloidal silver, 439 Colocynth, 671 Colocynth in, 671 Colocynthis, 671 Columbian spirits, 311 Columbin, 623 Columbo, 623 Commercial calcium sul- phide, 658 sodium bicarbonate, 801 zinc oxide, 427 Compound arsenical paper, (note) 732 cathartic pills, 672 decoction of sarsapa- rilla, 528 extract of colocynth, 671 fluid extract of sarsa- parilla, 529 infusion of gentian, 623 Compound infusion of sen- na, 667 jalap powder, 670 licorice powder, 667, 784 mixture of iron, 448 mixture of licorice, 784 pills of rhubarb, 663 powder of jalap, 680 powder of rhubarb, 663 solution of chlorine, 826 solution of cresol, 848 solution of iodine, 506 spirit of ether, 76 spirit of juniper, 707 syrup of hypophos- phites, 528 syrup of sarsaparilla, 528 syrup of squill, 737 tincture of benzoin, 863 tincture of cardamom, 627 tincture of cinchona, 555 tincture of gambir, 407 tincture of gentian, 623 Confectio rosae, 409 sennae, 667 Confection of rose, 409 of senna, 667 Confectiones, 62 Confections, 62 Conine, 269 hydrobromate, 273 Conium, 269 maculatum, 269 poisoning, 269, 273 Consomme", 10 Continuous current, 46 Convallamarin, 349 Convallaria, 349 maialis, 349 Convallarin, 349 Convolvulin, 670, 671 Convolvulus scammonia, 671 Copaiba, 712 langsdorffii, 712 -red, 713 Copaivic acid, 712 Copper, 428 arsenite, 479 poisoning, 429 sulphate, 428, 781 Copperas, 823 Coriander, 630 Coriandrum, 630 sativum, 630 Cornutine, 746 Corrosive mercuric chlo- ride, 494 sublimate, 494 as a caustic, 779 as a disinfectant, 821 948 GENERAL INDEX. Corsican moss, 785 Corynanthe yohimbi, 715 Cosmoline, 792 Cotarnine gauze, 410 hydrochlorate, 409 Cotton-root, 764 -seed oil, 787 Couch-grass, 706 Counter-irritants, 766 Court-plaster, 796 Coxe's hive syrup, 737 Cracked wheat, 654 Cramp-root, 744 Cream of tartar, 693 Creasote, 842 Creolin, 849 Creosotal, 845 Creosote, 842 carbonate, 845 water, 845 Creosotum, 842 carbonicum, 845 Cresalol, 849 Cresol, 848 salicylate, 849 Cresylic acid, 848 Cresylol, 848 Creta, 803 prseparata, 803 Croton-chloral, 165 oil, 675 tiglium, 675 Crotonoleic acid, 675 Croton-resin, 675 Crude camphor, 283 Cryptopine, 142 Crystallized digitalin, 312 Cubeb, 713 Cubeba, 713 Cubebic acid, 713 Cubebin, 713 Cupri sulphas, 428, 874 Cuprum, 428 Cusso, 807 Cyanogen gas, 394 Cynips galte tinctorise, 406 Cypripedin, 79 Cypripedium, 79 parviflorum, 79 pubescens, 79 Cytisine, 372 Cytisus laburnum, 372 scoparius, 350, 682 Dandelion, 530 Daphne mezereum, 529 Daphnin, 529 Datura stramonium, 185 Daturine, 185 Decocta, 60 Decoction of kava, 715 sarsaparilla, com- pound, 528 Decoctions, 60 Delirifacients, 168 Demulcents, 782 Deodorized opium, 140 tincture of opium, 141 Depresso-motors, 229 Depurant diuretics, 687 Dermatol, 426 Dewees's emmenagogue mixture, 742 Diaethylsulfondimethylme- than, 155 Diagnosis, use of electricity in, 52 Dialyzed iron, 450 Diaphoretics, 717 Diastase, 817 Diet, 22 Diethylendiamine, 698 Di-fluor-diphenyl, 865 Digestants, 815 Digested foods, 13 Digitalein, 312 Digitalin, 312, 332 crystallized, 312 German, 312 of Kiliani, 312 Digitalinum crystallatum, 312 Gallicum, 312 Germanicum, 312 verum, 312 Digitalis, 312 as a diuretic, 686 eriostachys, (note) 312 ferruginea, (note) 312 fontanesii, (note) 312 gigantea, (note) 312 glandulosa, (note) 312 nervosa, (note) 312 poisoning by, 328 purpurea, 312 Digitin, 312 Digitonin, 312 Digitoxin, 312, 332 Dihydroxyl-qumine, (note) 56i Diiodoparaphenolsul- phonic acid, 515 Di-isobutyl-ortho-cre-sol- iodide, 515 Dilute acetic acid, 397 alcohol, 289 hydriodic acid, 508 hydrobromic acid, 249 hydrochloric acid, 454 hydrocyanic acid, 385, .393 nitric acid, 455 nitro-muriatic acid, 455 phosphoric acid, 518 prussic acid, 393 silver nitrate, 438 solution of lead subace- tate, 422 sulphuric acid, 454 Dimethylamidophenyl-di- methylpyrazolon, 617 Dimethylarsenic acid, 482 Dimethylpiperazine tar- trate, 699 Dimethylxanthine, 683 Dinner-pill, 666 Dionine, 142 Dioxypurin, 683 Diphtheria antitoxin, 545 Disinfectants, 820 proprietary, (note) 825 Di-steary 1-glycerophos- phate of cholin, 550 Distilled oils, 61 Disulphones, 155 Dithymol-diiodide, 514 Diuretics, 678 Diuretin, 684 Donovan's solution, 507 Dormiol, 163 Doses, rules for, 65 Dover's powder, 140, 728 Drastics, 670 Dried alum, 410 blood, 445 calcium sulphate, 803 ferrous sulphate, 449 sodium carbonate, 801 suprarenals, 543 thyroid body, 538 Dry heat as a germicide, 820 Dryobalanops camphora, (note) 76 Dryopteros filix mas, 811 marginale, 811 Ductless glands, 534 Dunbar's hay-fever anti- toxin, 549 Duotal, 846 Ebstein method, 23 Ecballium elaterium, 673 Effervescent titrated caf- feine, 339 lithium citrate, 698 magnesium citrate, '668 magnesium sulphate, 668 sodium phosphate, 669 Effervescing draught, 692 Eggnog, ii, 310 Elaterin, 673 Elaterinum, 673 Elaterium, 673 Electric brush, 52 Electricity, 41 therapeutic application of, 52 use of, as a tonic, 58 Elettaria repens, 627 Elixir adjuvans, 784 GENERAL INDEX. Elixir of phosphorus, 468 of testicles, 531 of valerianate of am- monium, 75 phosphori, 468 proprietatis, 666 Emetics, 632 Emetine, 635, 639 Emmenagogues, 741 Emodin, 663 Emollients, 786 Emplastra, 62 Emplastrum ammoniaci cum hydrargyro, 739 adhaesivum, 796 belladonnas, 184 hydrargyri, 493, 496 plumbi, 421, 796 resinae, 421, 708 saponis, 421, 796 Empyreumatic oils, 61 Emulsin, 624, 772 Emulsion of ammoniac, 739 of asafetida, 76 of chloroform, 100 of cod-liver oil, 518 of cod-liver oil with hypophosphites, 518 of oil of turpentine, 712 Emulsions, 61 Emulsum ammoniaci, 739 asafcetidae, 76 chloroform!, 100 olei morrhuae, 518 . cum hypophos- phitum, 518 terebinthinae, 712 Encephalopathia saturnina, 414 Endermic administration, 65 Enemata, 649 high, 650 nutritive, 14 English garlic, 733 Eosote, 847 Epinephrin, 540 Epispastics, 769 Epsom salt, 667 Ergot, 745 Ergota, 745 Ergotin, 746, '756 Ergotism, 755 Erigeron, 707 canadense, 707 Erythrol tetranitrate, 262 Erythroxyline, 195 Ery thro xy Ion coca, 195 Escharotics, 776 Eserine, 229 Essence of beef, 9 of ginger, 628 of peppermint, 630 of spearmint, 630 Essential salt of lemons, 398 Ether, 87 Bertoni's, (note) 252 pneumonia, (note) 108 Ethereal oil, 61, 76 Ethyl bromide, 100 carbamate, 163 chloride, 100 ester of p-amidoben- zoic acid, 118 nitrite, 260, 728 oxide, 87 Ethylacetamidopheno 1 , (note) 611 Ethylene bromide, 101 Eucaine, 117 Eucalypsinthe, (note) 582 Eucalyptol, 582 Eucalyptus, 582 globulus, 582 gum, 582 Eudoxine, 515 Eugenia aromaticus, 626 jambolana, 529 Eugenol, 860 Euonymin, 656 Euonymus, 655 atropurpureus, 655 Eupyrin, 610 Equmine, 559 European rhubarb, 662 Europhen, 515 Exalgine, 616 Excito-motors, 212 Expectorants, 729 of the first group, 733 of the second group, 734 of the third group, 735 Expressed oil of almonds, 787 Extract of aconite, 385 of aloes, 666 of belladonna leaves, alcoholic, 184 of bone-marrow, 531 of Calabar bean, 238 of cannabis indica, 195 of cascara sagrada, 655 of chirata, 623 of cimicifuga, 79 of colchicum root, 527 of colocynth, 671 of conium, 273 of dandelion, 530 of digitalis, 330 of ergot, 756 of euonymus, 656 of gentian, 622 of glycyrrhiza, 784 of heematoxylon, 408 of hemp, 195 of hyoscyamus, 186 of Indian cannabis, 195 of krameria, 408 of licorice, 784 of logwood, 408 Extract of malt, 816 of nux vomica, 212 of opium, 140 of physostigma, 238 of quassia, 622 of rhatany, 408 of rhubarb, 663 of spleen, 531 of stramonium seed, 185 of sumbul, 80 of syzygium jambola- num, (note) 398 of taraxacum, 530 of uva ursi, 706 of wahoo, 656 Extracta, 61 Extracts, fluid, 62 solid, 61 Extractum aloes, 666 belladonnae foliorum, 184 cannabis indicae, 195 cimicifugae, 79 colchici cormus, 527 colocynthidis, 671 colocynthidis composi- tum, 671 conii, 273 digitalis, 330 ergotae, 756 euonymus, 656 gentianae, 623 glycyrrhizae, 784 purum, 784 haematoxyli, 408 hyoscyami, 186 krameriae, 408 lactucarii fluidum, 84 malti, 816 nucis vomicae, 2 1 2 opii, 140 pnysostigmatis, 238 quassiae, 622 rhamni purshianae, 655 rhei, 663 spigeliae et sennae flui- dum, 806 stramonii, 185 sumbul, 80 taraxaci, 530 Extraneous remedies, 797 Factitious scammony, 671 Fagus sylvatica, 842 Farad ic current, 47 Faradization, general, 59 Feeding by the rectum, 14 of the sick, 6 Fel bovis, 655 purificatum, 655 Fell's apparatus, (note) 114 Fennel, 630 950 GENERAL INDEX. Fennel water, 630 Ferratin, 445 Ferri carbonas saccharatus, 448 chloridum, 450 citras, 451 et ammonii citras, 451 et ammonii sulphas, 45i et ammonii tartras, 451 et potassii tartras, 451 et quininae citras, 451 et quininae citras solu- bilis, 451 et strychninae citras, 451 hydroxidum, 448 hydroxidum cum mag- nesii oxido, 448 hypophosphis, 451, 521 iodidum saccharatum, 450 lactas, 451 phosphas solubilis, 451 pulvis, 448 pyrpphosphas solu- bilis, 451 sulphas, 449 sulphas exsiccatus, 449 sulphas granulatas, 449 Ferric ammonium sulphate, 45i chloride, 450 citrate, 451 hydrate, 448 hydrate with magnesia, 448 hypophosphite, 521 phosphate, soluble, 451 pyrophosphate, solu- ble, 451 subsulphate, solution of, 449 sulphate, solution of, 449 Ferrous carbonate, saccha- rated, 448 iodide, saccharated, 45o lactate, 451 sulphate, 449, 823 sulphate, dried, 449 Ferrum, 443 dialyzatum, 450 reductum, 448 Ferula foetida, 75 sumbul, 80 Ficus, 654 Figs, 654 Filicic acid, 811 Filix mas, 811 Fire, 820 Flake manna, 655 Flaxseed, 784 poultice, 794 Flaxseed tea (infusion), 784 Fleabane, 707 Fleming's tincture of aco- nite, 385 Flexible collodion, 796 Fluidextract of aconite, 385 of apocynum, 334 of belladonna root, 184 of bitter orange peel, 629 of black haw, 744 of buchu, 705 of calumba, 623 of cannabis indica, 195 of capsicum, 629 of cascara sagrada, 655 of chimaphila, 706 of chirata, 623 of cimicifuga, 79 of cinchona, 555 of coca, 207 of colchicum seeds, 527. of conium, 273 of convallaria, 350 of couch-grass, 706 of cramp-root, 744 of cubeb, 714 of dandelion, 530 of digitalis, 330 of ergot, 756 of eucalyptus, 582 of euonymus, 655 of frangula, 655 of gelsemium, 267 of gentian, 623 of geranium 409 of ginger, 628 of glycyrrhiza, 784 of grindelia, 736 of hamamelis, 408 of hemp, 195 of hydrastis, 760 of hyoscyamns, 186 of Indian cannabis, 195 of ipecacuanha, 639 of jaborandi, 727 of kava, 715 of krameria, 408 of lactucarium, 80 of leptandra, 656 of licorice, 784 of lobelia, 264 of lupulin, 78 of matico, 714 of mezereon, 529 of nux vomica, 212 of oak bark, 409 of pareira brava, 705 of pilocarpus, 727 of pomegranate, 813 of podophyllum, 673 of quassia, 622 of rhamnus purshiana, 655 of rhatany, 408 Fluidextract of rhubarb, 663 of rhus glabra, 409 of rose, 409 of sanguinaria, 739 of sarsaparilla, 529 of savine, 742 of scopola, 187 of senega, 739 of senna, 667 of serpentaria, 631 of spigelia, 806 of spigelia and senna, 806 of squill, 682 of stillingia, 530 of stramonium, 185 of sumach, 409 of sumbul, 80 of taraxacum, 530 of uva ursi, 706 of valerian, 75 of veratrum, 370 of wild cherry, 624 of xanthoxylum, 530 Fluidextracta, 62 Fluidextracts, 62 Fluidextractum aconiti, 385 apocyni, 334 aromaticum, 626 aurantii amari, 629 belladonnas radicis, 184 berberidis, 624 buchu, 705 calumbae, 623 cannabis indicae, 195 capsici, 629 chimaphilae, 706 chiratae, 623 cjmicifugae, 79 cinchonae, 555 cocae, 207 colchici seminis, 527 conii, 273 convallariae, 350 cubebae, 714 cypripedii, 79 digitalis, 330 ergotae, 756 eucalypti, 582 euonymi, 655 frangulae, 655 gelsemii,*267 gentianae, 623 geraniae, 409 glycyrrhizae, 784 granati, 813 grindeliae, 736 hamamelidis foliorum, 408 hydrastis, 760 hyoscyami, 186 ipecacuanhae, 639 krameriae, 408 lactucarii, 80 leptandrae, 656 lobelia;, 264 GENERAL INDEX. Fluidextractum lupulini, 78 matico, 714 mezerei, 531 nucis vomicae, 212 pareirae, 705 pilocarpi, 727 podophylli, 673 pruni Virginianae, 624 quassiae, 622 quercus, 409 rhamni purshianae, 655 aromaticum, 655 rhei, 663 rhois glabrae, 409 rosae, 409 sabinae, 742 sanguinariae, 739 sarsaparillae, 529 compositum, 529 scillae, 682 scopolae, 187 senegae, 739 sennas, 667 serpentariae, 631 spigeliae, 806 stilhngiae, 530 stramonii, 185 sumbul, 80 taraxaci, 530 tritici, 707 uva ursi, 706 valerianse, 75 veratri, 370 viburni opuli, 744 viburni prunifolii, 746 xanthoxyli, 53 zingibens, 628 Fluorides, 865 Fluoroform, 866 Fluoroformol, 866 Fluorol, 865 Fceniculum, 630 capillaceum, 630 Foods, artificially digested, 13 composition of, 23 Forced artificial respira- tion, 114 enemata, 639 insufflation, 114 Formaldehyde, 855 Formalin, 856 Formin, 699 Formol, 855 Formyl, 855 bromide, 250 Fowler's solution, 482 Foxglove, 312 Frangula, 655 Frangulin, 655 Fraxmus ornus, 655 French digitalin, 312 Fresh juices, 61 Fuller's earth, 793 Fumigations, mercurial, 492 Furfur-alcohol, (note) 340 Fused silver nitrate, 431 Gaduin, 516 Gadus morrhua, 515 Galla, 406 Gallic acid, 406 Gallo-tannic acid, 402 Galls, 406 Galvanic current, 47 Galvanization of the spinal cord, 58 of the sympathetic, 58 Gambir, 407 Gamboge, 674 in sorts, 675 Gangrenous ergotism, 755 Garcinia hanburii, 674 Garden rue, 742 Garlic, 736 Gaulthena, 597 Gelatin, 532 tannate, 405 Gelatinum, 532 glycerinatum, 534 Gelatose silver, 438 Gelsemin, (note) 265 Gelsemine, 264 Gelseminic acid, 264 Gelseminin, (note) 265 Gelsemium, 264 sempervirens, 264 General faradization, 59 Gentian, 622 Gentiana, 622 lutea, 622 Gentiopikrin, 622 Gentisic acid, 622 Geosote, 847 Geranium, 409 maculatum, 409 German chamomile, 631 digitalin, 312 Germicides, 820 Gigartina mamillosa, 783 Gin, 707 Ginger, 627 Glacial acetic acid, 397 Glandulae suprarenales, 538 siccae, 543 thyroideae, 534 siccae, 538 Glauber salt, 668 Glonoin trinitrate, 262 Glucose, 687 Glusidum, 791 Glycerin, 788 Glycerinated gelatin, 534 Glycerinum, 788 Glycerita, 61 Glycerite of boroglycerin, 869 of hydrastis, 760 Glycerite of starch, 785, 791 of tannin, 405 of yolk of egg, 791 Glycentes, 61 Glyceritum acidi tannici, 405 amyli, 785 boroglycerini, 869 hydrastis, 760 phenolis, 841 Glycero-phosphoric acid, 519 Glyceryl nitrate, 261 Glyco-formalin, 858 Glycosal, 599 Glycyrrhiza, 784 glabra, 784 glandulifera, 784 Glycyrrhizin, 784 Glycyrrhizinum ammonia- turn, 784 Goa powder, 766 Gold and sodium bromide, 250 chloride, 497 iodide, 498 oxide, 498 Golden seal, 756 Gossypii cortex, 764 Gossypium herbaceum, 764 purificatum, 764 Goulard's extract, 422 Granatum, 813 Gray powder, 493 Green galls, 406 ginger, 627 soap, 765 Griffith's mixture, 448, 741 Grindelia, 735 robusta, 735 squarrosa, 735 Ground slippery elm, 794 Guaiac, 742 resin, 529 Guaiaci resina, 529 Guaiacol, 845 carbonate, 846 Guaiacolis carbonas, 846 Guaiaconic acid, 502 Guarana, 330 Tiuaranine, (note) 339 }um arabic, 782 jun-cotton, 796 iunjah, 191 iutta-percha, 796 H rtaematin, 407 Haematogen, 445 [-laematoporphyrin, 157 hlaematoxylin, 407 Hasmatoxylon, 407 campechianum, 407 laemoglobin, 445 952 GENERAL INDEX. Hagenia abyssinica, 807 Halogen disinfectants, 823 Hamamelidis cortex, 408 folia, 408 Hamamelin, 408 Hamamelis, 408 Virginica, 408 Hashish, 191 Hay-fever antitoxin, 549 Heat as a disinfectant, 820 Heavy magnesia, 656 oil of wine, 76 Hedeoma pulegioides, 743 Hedonal, 163 Helmitol, 701 Hemp, 191 Heroine, 144 Heteroxanthin, 684 Hetol, 864 Hetralin, 701 Hexamethylenamina, 699 Hexamethylenetetramine, 699 High enemata, 650 Hippurate of lime and lithia, (note) 861 Hippuric acid, 861 Hive syrup, Coxe's, 737 Hoffmann's anodyne, 76 Holly tea (note) 338 Homatropinae hydrobro- midum, 190 Homatropine, 190 hydrobromide, 190 Honey of rose, 409 Honeys, 61 Hop poultice, 78 Hope's camphor mixture, 455 Hops, 77 Hordeum, 785 Horehound, 739 Hot baths, 30, 717 Humulus, 77 lupulus, 77 Hundred-leaved rose, 409 Huxham's tincture, 555 Hydragogue diuretics, 6So Hydragogues, 653 Hydrargyri chlondum cor- rosivum, 493, 779, 821 chloridum mite, 493 iodidum flavum, 495 rubrum, 495, 822 oxidum flavum, 496 rubrum, 496 Hydrargyrum, 483, 659 ammoniatum, 496 cum creta, 493 Hydrastin, 756 Hydrastina, 760 Hydrastine, 756, 760 Hydrastininse hydrochlo- ras, 761 Hydrastinine hydrochlo- rate, 761 Hydrastis, 756 canadensis, 756 Hydrated oxide of iron, 448 Hydrobrpmic acid, 249 Hydrochinone, 705, 854 Hydrochloric acid, 454 poisoning, 452 Hydrocyanic acid, 385 poisoning by, 392 Hydrofluoric acid, 865 Hydrogen dioxide, solu- tion of, 828 peroxide, solution of, 828 Hydroquinone, 854 Hydroxybenzene, 831 Hyoscinae hydrobromidum, 187 Hyoscine, 185, 187 hydrobromide, 187 Hyoscyaminae sulphas, 186 Hyoscyamine sulphate, 186 Hyoscyamus, 185 niger, 138, 185 Hyperemesis, 634 Hypnone, 164 Hypochlorites, 824 Hypodermic injections, 64 purgation, 651 Hypodermoclysis, (note) 209, 678 Hypophosphites, 521 Hypophosphorous acid, 520 Hypophysis, 543 Hypoquebrachine, 377 Ice-poultice, 31 Iceland moss, 785 Ichthalbin, 528 Ichthargan, 440 Ichthyodin, 528 Ichthyol, 527 albuminate, 528 Idiosyncrasies, 66 Igasuric acid, 212 Ignis sacer, 755 sancti Antonii, 755 Ilex cassine, (note) 338 Paraguaiensis, (note) 338 Illicmm amsatum, 630 Impure haemoglobin, 445 Incompatibilities, 69 Index of diseases, 889 India senna, 666 Indian cannabis, 191 hemp, 191 meal, 654, 794 Indications for drugs, 62 Induced current, 47 In6e poison, 334 Infiltration-anaesthesia, 119 Infusa, 61 Infusion of chamomile, 631 of cloves, 627 of coffee, (note) 318 of digitalis, 330 of gentian, compound, , 6 . 2 3. or jumper, 707 of pareira brava, 705 of senna, compound, 667 of wild cherry, 624 Infusions, 61 Infusum digitalis, 330 pruni virginianae, 624 sennae compositum, 667 Injections, 65 subcutaneous, 64 Insoluble gold prepara- tions, 498 Intravenous injections of chloral, 152 salt solution in poi- soning, (note) 209 Inunctions, mercurial, 491 lodic acid, (note) 512 Iodine, 498 as a disinfectant, 824 ointment, 504 lodipin, 508 lodism, 500 lodoform, 508 ointment, 513 poisoning, 513 lodoformogen, 515 lodoformum, 508 lodol, 514 lodolum, 514 lodothyrin, 535 lodum, 498 Ipecacuanha, 635 as a diaphoretic, 728 as an expectorant, 733 Ipecacuanhic acid, 635 Ipomcea jalapa, 670 Irish moss, 783 Iron, 443 and ammonium cit- rate, 451 and ammonium tar- trate, 451 and potassium tartrate, 45i and quinine citrate, 451 and strychnine citrate, 451 by hydrogen, 448 citrate, 451 Quevenne's, 448 tartrates, 451 Irritants, 765 and counter-irritants, 765 Isacomtme, 374 GENERAL INDEX. 953 Isarol, 528 Isinglass plaster, 796 Iso -butyl nitrite, (note) 244 Isopelletierine, 813 Isophysostigmine, 229 Isopilocarpine, (note) 721 Isopral, 163 Isopunicine, 813 Itrol, 438 Jaborandi, 720 Jaborine, (note) 721 Jacket-poultice, 794 Jaguarandy, 720 Jalap, 670 Jalapa, 670 Jalapin, 671 Jamaica ginger, 628 Jambul, 529 Jamestown weed, 185 amguarandi, 720 apaconitine, (note) 374 jateorhiza palmata, 623 "erusalem oak, 806 ervine, 366 iiices, 6t Julienne soup, 10 Juniper, 707 Juniperus, 707 communis, 707 sabina, 742 Kaiserling's solution, 859 Kamala, 813 Kaolin, 793 Kava, 715 Kava-kava, 715 Kava resin, 715 Kavin, 715 Kawa, 715 Kentish ointment, 774 Kiliani's digitalin, 312 Kinic acid, 555 Kino, 407 Kino-tannic acid, 402 Kinovic acid, 555 Kola nut, (note) 338 Kombe" poison, 334 Kosin, 807 Kosotoxin, 807 Koumys, n Kousso, 807 Krameria, 408 ixina. 408 triandra, 408 Kumys, n Kuzazu, (note) 374 Labarraque's solution, 825 Lactic acid, (note) 394, 457 Lactophosphate of lime, 520 Lactuca virosa, 80 Lactucarium, 80 Lactucin, 80 Lady Webster pills, 666 Lanolin, 788 Lard, 786 Large enemata, 650 Largin, 438 Laudanine, 142 Laudanum, 141 Laurus camphora, 283 Lavage of the blood, (note) 209, 679 Lavandula spica, (note) 630 Lavender, oil of, 630 Laxatives, 654 Lead, 411 acetate, 421 carbonate, 422 chrpmate, (note) 412 colic, 413 nitrate, 423, 823 oleomargarate, 421 oxide, 421 plaster, 421, 796 poisoning, 410 water, 422 Lecithin, 551 Ledoyen's disinfectant so- lution, 423, 823 Lemon-juice, 396 Lemon-peel, 630 Lemons, essential salt of, 398 Leptandra, 656 Leptandrin, 656 Levant wormseed, 807 Lichen starch, 785 Lichenin, 785 Lichenstearic acid, 785 Licorice, 784 root, 784 Liebig's beef tea, 9 Light magnesia, 656 Lily of the valley, 349 Lime, 801, lactophosphate, 520 liniment, 802 stone, 801 unslaked, 801 water, 802 Limonis cortex, 630 Liniment of ammonia, 775 of belladonna, 184 of camphor, 288 of chloroform, 100 of lime, 802 of soap, 288 of turpentine, 774 Linimenta, 62 Liniments, 62 Linimentum ammoniac, 775 belladonnae, 184 Linimentum calcis, 802 camphorae, 288 chloroformi, loo saponis, 288 terebinthinae, 774 Linseed oil, 787 Linum, 784 usitatissimum, 784 Liquid cosmoline, 792 meat foods, 7 petrolatum, 792 Liquor acidi arsenosi, 482 ammonii acetatis, 728 arseni et hydrargyri iodidi, 507 calcii oxidi, 802 chlori compositus, 826 cresolis compositus, 848 ferri chloridi, 450 fern subsulphatis, 449 ferri tersulphatis, 449 formaldehydi, 856 gutta-percnae, 796 hydrargyri nitratis, 779 iodi compositus, 504 magnesii citratis, 668 pancreaticus, 13 plumbi subacetatis, 421 plumbi subacetatis di- lutus, 422 potassae, 692 potassii arsenitis, 482 potassii citratis, 692 sodae chlorinatae, 825 sodii arsenatis, 482 sodii hydroxidi, 800 zinci chloridi, 779 Liquores, 61 Lisbon diet-drink, 528 Listerine, 874 Litharge, 421 Lithiasis, 24 Lithii benzoas, 698 bromidum, 249, 698 carbonas, 698 citras, 698 citras effervescens, 698 Lithium, 697 arsenical solution of, 698 benzoate, 698 bromide, 249 carbonate, 698 citrate, 698 mercuric iodide, 822 Lobelia, 262, 733 inflata, 262 Lobeline, 262 Local anaesthesia, 117 applications, 65 cold, 30 heat, 28 remedies, 621 Logwood, 407 Lozenges, 62 954 Lozenges of ipecacuanha, 63? of ipecacuanha and morphine, 639 Lugol's solution, 504 Lump asafetida, 75 Lunar caustic, 431 Lupulin, 77 Lupulinum, 77 Lycetol, 699 Lycoctonine, (note) 374 Lysol, 848 M Mace, 627 Macis, 627 Macrotin, 78 Magnesia, 656, 798 ponderosa, 656 Magnesii carbonas, 656 sulphas, 667 sulphas effervescens, 668 Magnesium carbonate, 656 citrate, 668 sulphate, 667 Magnetism, 59 Male fern, 81 1 Malic acid, 409 Mallotus philippinensis, 813 Malt, 816 Mammary glands, 531 Manganese, 451 dioxide, 451, 741 sulphate, 451 Mangani dioxidum prae- cipitatum, 451 sulphas, 451 Manna, 655 Mannite, 655 Marble, 801 Marjoram, oil of, (note) 630 Marrubiin, 739 Marrubium, 739 Martineau's solution, (note) 698 Mass of copaiba, 713 of mercury, 493 Massa copaibae, 713 hydrargyri, 493 Massage, 2 of the heart, 115 Mat, (note) 338 in leaf, (note) 338 in powder, (note) 338 Materia medica, 60 Maticin, 714 Matico, 714, Matricaria, 631 chamomilla, 631 Matzoon, 12 May-apple, 672 Meadow saffron, 521 Measures of the metrical system, 880 GENERAL INDEX. Meat-juice, 8 Mechanical emetics, 643 Meconic acid, 125 Meconine, 125 Medulla sassafras, 785 Mel rosae, 409 Melaleuca leucadendron, 629 Melia azedarach, 806 Melissa, 630 officinalis, 630 Mellita, 61 Mentha piperita, 630 pulegium, 743 viridis, 630 Menthol, 852 Mercurial cachexia, 487 fumigations, 492 inunctions, 491 ointment, 492 pills, 493 plaster, 493 poisoning, local, 487 ptyalism, 484 purgatives, 660 Mercuric nitrate, solution of, 765 oxide, 496 Mercury, 483, 682 ammoniated, 496 bichloride, 494, 821 biniodide, 822 hypodermic use of, 492 with chalk, 493 Mesotan, 599 Meta-arsemc-anilid, 483 Metacresol, 848 Metallic salts as disinfect- ants, 821 Methaemoglobin, 256 Methenyl chloride, 92 Methyl alcohol, 311 bromide, 102 propyl-carbinol-ure- thane, 163 pyrocatechin, 845 salicylas, 597 salicylate, 597 Methylacetanilid, 617 Methylal, 163 Methylene bichloride, 102 blue, 580 Methylic alcohol, 311 amblyopia, 311 Methylthioninse hydro- chloridum, 580 Methylxanthine, 683 Methysticin, 715 Metric system, 880 Mezereon, 529 ointment, 529 Mezereum, 529 Mild mercurous chloride, 493 Milk diet, 26 Milk foods, 10 of asafetida, 76 punch, ii, 310 toast, pancreatized, 14 Mineral acids, 452 astringents, 410 tonics, 443 Minor hypnotics, 162 Mistura cretae, 803 ferri composita, 448, 74i glycyrrhizae compos- ita, 784 potassii citratis, 692 rhei et sodae, 664 Misturae, 61 Mixed anaesthetics, (note) 106 Mixture of asafetida, 76 of potassium citrate, 680 of rhubarb and soda, 664 Mixtures, 61 Moist heat as a germicide, 820 Molasses, 654 Monobromated camphor, 79. 2 5i Monomethyl ether, 845 Monosalicylic-glycerin ester, 599 Monsel's solution, 450 Morphina, 141 Morphinae acetas, 141 hydrochloras, 141 sulphas, 141 Morphine, 125, 141 acetate, 141 benzyl-ester hydro- chloride, 142 derivatives, 142 diacetic ester, 144 hydrochlorate, 141 sulphate, 141 Moschus, 73 moschiferus, 73 Motor points, 51, 883 Mucilage of gum arabic, 782 of sassafras pith, 785 of slippery elm bark, 783 of tragacanth, 783 Mucilages, 61 Mucilagines, 61 Mucilago acaciae, 782 sassafras medullae, 785 tragacanthae, 783 ulmi, 783 Mulled wine, 309 Muriate of morphine, 141 Muriatic acid, 454 Muscarine, antidote for, 182 Musk, 73 Musk-root, 80 Mustard, 772 GENERAL INDEX. 955 Mustard as an emetic, 643 flour, 633 paper, 773 plaster, 773 poultice, 759 Mutton suet, 786 Myristica, 627 fragrans, 627 Myrrh, 741 Myxcedema, 535 N Napelline, 374 Naphtalenum, 849 Naphtalin, 849 Naphthalol, 852 Naphtol, 850 Narceine, 142 Narcotine, 142 Nataloin, 664 Nativelle's digitalin, 312 Neodermin, 865 Nervines, 73 Neural anaesthesia, 122 Neurine, 551 Neutral mixture, 692 Ngai camphor, (note) 283 Nicotine, 267 Nirvanin, 119 Nitre, 694 Nitric acid, 454 as a caustic, 780 oxide, 82 poison, 452 Nitrite-oxyhsemoglobin, 256 Nitrogen monoxide, 82 Nitroglycerin, 261 Nitro-hydrochloric acid, 455 poison, 452 Nitrous acid, 455 oxide, 82 Normal salt solution, (note) 679 Norway spruce, 761 Nosophen, 515 Nucleic acid, 531 Nucleins, 530 Nutgall, 406 Nutmeg, 627 Nutriants, 401 Nutritive enemata, 14 Nux vomica, 212 Oatmeal, 654 porridge, 12 Ohm, 45 Ohm's law, 42 Oil of absinthe, 860 of allspice, 627 of anise, 630 Oil of aspic, (note) 630 of bitter almonds, 394 of cajuput, 629 of camphor, 288 of caraway, 630 of chenopodium, 807 of cinnamon, 626, 860 of cloves, 626, 860 of copaiba, 713 of coriander, 630 of cotton seed, 787 of cubeb, 714 of erigeron, 707 of eucalyptus, 582 of fennel, 630 of gaultheria, 597 of geranium, 860 of hedeoma, 746 of juniper, 707 of lavender, 630 of mace, 627 of marjoram, (note) 630 of mentha pulegium, 743 of mustard, 772 of myristica, 627 of nutmeg, 627 of pennyroyal, 743 of peppermint, 630 camphor, 852 of phosphorus, 468 of pimenta, 627 of rose, 409 of rosemary, (note) 630 of rue, 742 of sandal-wood, 707, 738, 860 of sassafras, 629 of savine, 742 of spearmint, 630 of sweet almonds, 787 of sweet birch, 597 of tansy, 743 of tar, 737 of theobroma, 787 of thyme, 852, 860 of turpentine, 708, 774 of valerian, 74 of vitriol, 453 of wine, heavy, 81 of wintergreen, 597 of wormseed, 807 of zedoary, 860 Oils, 61 Ointment of ammoniated mercury, 496 of ammonium iodide, 507 of antimony, 366 of belladonna, 184 of fluor-pseudocumol, 865 of galls, 407 of iodine, 504 Ointment of iodoform, 513 of lead carbonate, 422 of mercuric nitrate, 496 of mercury, 492 of mezereon, 529 of nutgall, 407 of nutmeg, 627 of potassium iodide, , 5 7 ^ of red mercuric ox- ide, 496 of rose-water, 409 of stramonium, 185 of tannic acid, 405 of tar, 737 of veratrine, 372 of white precipitate, 496 of yellow mercuric oxide, 496 of zinc oxide, 428 Ointments, 62 Olea destillata, 61 Oleata, 61 Oleate of mercury, 493 Oleates, 61, 788 Oleatum hydrargyri, 493, 496 Oleic acid, 788 Oleoresin of capsicum, 629 of cubeb, 714 of fern, 8n of ginger, 628 of lupulin, 77 of pepper, 628 Oleoresina aspidii, 8ir capsici, 629 cubebae, 714 lupulinae, 77 piperis, 628 zingiberis, 628 Oleoresinae, 61 Oleoresins, 61 Oleum aethereum, 76 amygdalae expressum, 787 betulae volatile, 597 cajuputi, 629 camphorae, 80 caryophylli, 626 chenopodii, 807 cinnamomi, 626 copaibae, 713 cubebae, 714 erigerontis, 707 eucalypti, 582 gaultneriae, 597 gossypii seminis, 787 nedeomae, 743 juniperi, 707 lini, 787 morrhuae, 515 myristicae, 627 ohvae, 787 phosphoratum, 468 pimentae, 627 956 GENERAL INDEX. Oleum ricini, 659 sabinae, 742 santali, 707, 738 sassafras, 629 sinapis volatile, 772 terebinthinae, 708 theobromatis, 787 tiglii, 675 Olive oil, 787 Onaye poison, 334 Opii pulvis, 140 Opinanine, 125 Opium, 125 alkaloids, 142 deodoratum, 140 deodorized, 140 poisoning by, 126, 135 smoking, 139 Orange-flower water, 630 flowers, 630 peel, 629 Orexae hydrochloras, 624 Orexin, 624 tannate, 624 Orthocresol, 848 Orthocresotic acid, (note) 589 Orthoform, 118 Orthoguaiacol-sulphonic acid, 847 Oxalic acid, 397 poisoning, 398 Oxgall, 655 Oxide of gold, 498 of zinc, 428 Oxidizing disinfectants, 826 Oxycamphor, 289 Oxycannabin, 191 Oxydicolchicine, 521 Oxysparteine, (note) 350 Oxytocics, 745 Pahouius poison, 334 Pale catechu, 407 cinchona, 555 rose, 409 Pancreatin, 816 Pancreatized foods, 14 Papain, 817 Papaver somniferum, 125 Papaverine, 142 Papaw, 817 Papayotin, 817 Papers, 62 Paracetamidophenol , (note) 611 Paracresol, 848 Paracresotic acid, (note) 589 Paraffin, 792 Paraffinum, 792 Paraform, 858 Paraform aldehyde, 857 Paraguay tea, (note) 338 Paraldehyde, 160 Paraldehydum, 160 Paramidophenol, (note) 611, 614 Paramorphine, 125 Paraphenetidin-vanillin- ethyl-carbonate, 610 Paraxanthin, 685 Paregoric, 141 Pareira, 705 brava, 705 Parillin, 528 Parillinic acid, 528 Parsley, 743 Paullinia campana, 339 Pearl barley, 785 Pearlash, 691 Pelletierinae tannas, 813 Pelletierine, 813 Pennyroyal, 743 Pental, 102 Pepo, 812 Pepper, 628 Peppermint, 630 water, 630 Pepsin, 815 Pepsinum, 815 Peptonized beef tea, 14 gruel, 14 milk, 14 milk toast, 14 oysters, 14 Pernambuco jaborandi, 720 Peronine, 142 Peroxide of hydrogen, 828 Pertussin, 853 Pest serum, 549 Petrolatum, 792 album, 792 liquidum, 792 Petroselinum sativum, 743 Pharmacodynamics, 60 Pharmacology, 60 Pharmacopoeia, 60 Pharmacy, 60 Phellandrene, 582 Phenacetin, 614 Phenazonum, 600 Phenic acid, 831 Phenocoll hydrochloride, 616 Phenol, 831 liquefactum, 831 poisoning, 838 sodique, 874 Phenosol, 618 Phenyl sal icy late, 847 Phenylacetamide, 610 Phenyldihydrochinazoline hydrochlorate, 624 Phenyl-dimethyl-pyrazo- lone, 600 Phenylic alcohol, 831 Phenylis salicylas, 847 Phosphorated oil, 468 Phosphoric acid, 518 Phosphorus, 459 antidote to, 466 necrosis, 468 poisoning, 461 sesquisulphide, (note) 468 Physostigma, 229 poisoning, 238 venenosum, 229 Physostigminae salicylas, 238 sulphas, 238 Physostigmine, 229 sal icy late, 238 sulphate, 238 Picraconitine, 374 Picrsena excelsa, 622 Picric acid, 814 Picropodophyllin, (note) 672 Pill of aloes, 666 of aloes and asafetida, 164 of aloes and iron, 666 of aloes and mastic, 666 of aloes and myrrh, 666 of asafetida, 76 of opium, 140 of phosphorus, 468 of podophyllum, capsi- cum, and belladonna, 673 of rhubarb, com- pound, 663 Pills, 62 Pilocarpidine, (note) 721 Pilocarpinae hydrochloras, 727 Pilocarpine, 721 hydrochlorate, 727 Pilocarpus, 720 jaborandi, 720 pinnatus, (note) 720 selloanus, 720 Pilulae, 62 aloes, 666 aloes et asafcetidae, 666 aloes et ferri, 666 aloes et mastiches, 666 aloes et myrrhae, 666 asafoetidae, 76 catharticae compositae, 672 catharticae vegetabiles, 672 taxativas compositae, 666 opii, 140 GENERAL INDEX. 957 Pilulae phosphpri, 468 podophylli, capsici et belladonnas, 673 rhei composite, 663 Pimenta, 627 officinalis, 627 Pimpinella anisum, 630 Pinkroot, 805 Pinus palustris, 708, 737 Pipe gamboge, 675 Piper, 628 angustifolium, 714 cubeba, 713 methysticum, 715 nigrum, 628 Piperazidine, 698 Piperazinae quinas, 701 Piperazine, 698 hydrochlorate, 698 Piperazinum, 698 Piperin, 628 Piperinum, 628 Pipsissewa, 706 Pitch, 737 Pjtuitary body, 543 Pix burgundica, 775 liquida, 737 Plasma of starch, 791 Plaster of ammoniac with mercury, 739 of belladonna, 184 of mercury, 496 Plasters, 62 Platt's chlorides, 874 Plumbi acetas, 421 carbonas, 422 nitras, 423 oxidum, 421 Plumbism, 412 Plumbum, 411 Podophyllin, 673 Podophyllinic acid, (note) 672 Podophylloresin, 672 Podophyllotoxin, 651, 672 Podophyllum, 672 peltatum, 672 Polygala senega, 739 Polygalic acid, 739 Polymerized formalde- hyde, (note) 858 Polystichic acid, (note) Sii Pomegranate rind, 813 Poppy, 125 Porcelain clay, 793 Porphyroxine, 142 Potash, 691 Potassa cum calce, 778 sulphurata, 658 Potassii acetas, 692 bicarbonas, 691 bitartras, 693 bromidum, 239 carbonas, 691 chloras, 695 Potassii citras, 692 cyanidum, 393 et sodii tartras, 669 hydroxidum, 777 hypophosphis, 521 iqdidum, 505 nitras, 694 permanganas, 826 sulphas, 693 Potassium, 687 acetate, 692 alum, 410 and sodium tartrate, 669 bicarbonate, 691 bi tartrate, 693 bromide, 239 carbonate, 691 chlorate, 695 poisoning by, 695 citrate, 692, 733 cyanide, 393 hypophosphite, 521 iodide, 505 myronate, 772 nitrate, 694 poisoning by, 694 nitrite, 260 oxalate, 398 permanganate, 741, 826 sulphate. 693 Poudre de succession, (note) 411 Poultices, 793 Powder of ipecac and opium, 140 Powdered opium, 140 Powders, 62 Practical anaesthesia, 103 disinfection, 869 local anaesthesia, 1 19 Precipitated calcium car- bonate, 803 calcium phosphate, 520 sulphur, 657 zinc carbonate, 428 Predigested foods, 13 Preparations of drugs, 60 Prepared chalk, 803 Prescribing, art of, 67 Prickly pear, 530 Pride of China, 806 Primary current, 46 Propenyl alcohol, 788 Proprietary disinfectants, (note) 825 Propylamin, 516 Protargol, 440 Protect) ves, 796 Protiodide of mercury, 495 Prunes, 654 Prunus serotina, 624 virginiana, 624 Prussic acid, 385 poisoning, 392 Pseudaconitine, (note) 374 Pseudocannabinol, 192 Pseudojervine, 366 Psychotrin, 635 Pterocarpus marsupium, 407 Ptyalism, 484 Pulveres, 62 Pulvis aromaticus, 626 effervescens composi- tus, 669 glycyrrhiza composi- tus, 667, 784 ipecacuanhas et opii, 140, 728 jalapae compositus, 670 parturiens, 751 rhei compositus, 663 Pumpkin seed, 812 Punicine, 813 Purgative enemas, 650 Purgatives, 644 hypodermic use of, 651 Purges, 659 Purging agaric, 409 cassia, 656 Purified aloes, 665 animal charcoal, 819 oxgall, 655 Purshianin, 655 Pyramidon, 617 bicamphorate, 618 camphorate, 618 . salicylate, 618 Pyroacetic spirit, (note) 397 Pyrocatechin, 854 Pyrogallic acid, 781 Pyrogallol, 781 Pyrosal, 618 Pyroxylic spirits, 311 Pyroxylin, 796 Pyroxylinum, 796 Quassia, 622 Quassin, 622 Quebrachamine, 277 Quebrachine, 277 Quebracho, 277 Queen's root, 530 euercitron, 408 uercus alba, 409 lusitanica, 406 tinctoria, 408 Quevenne's iron, 448 Quillaja, 739 Buinic acid, 701 uinicine, 555 Quinidinae sulphas, 577 Quinidine sulphate, 577 Qujnina, 556 Quininae bisulphas, 575 hydrobromas, 575 hydrochloras, 575 GENERAL INDEX. Quininae sulphas, 556 Quinine, 556 bisulphate, 575 dihydroxyl, (note) 559 esters, 579 hydrobromate, 575 hydrochlorate, 575 poisoning, 576 salicylate, 575 sulphate, 556 tannate, 577 Quinotropine, 701 Reactions of degeneration, 53 Rectal alimentation, 14 Red cinchona, 555 gum, 582 mercuric iodide, 495 mercuric oxide, 496 precipitate ointment, 496 wine, 289 Reduced iron, 448 Refrigerants, 394 Relation of apothecaries' to metric weights, 881 of apothecaries' weights to meas- ures, 88 1 of metric to apotheca- ries' weights, 881 Remijia pedunculata, 578 purdieana, 578 Rennet, 815 Resin cerate, 708 of jalap, 671 of May-apple, 673 of podophyllum, 673 of scammony, 672 plaster, 421 Resina, 708 jalapae, 671 podophylli, 673 scammonii, 672 Resinae, 62 Resins, 62 Resorcin, 854 Resorcinol, 854 Respiratory depressants, 276 stimulants, 276 Rest-cure, 17 Rhabarbarin, 663 Rhamnus frangula, 655 purshiana, 655 Rhatany, 408 Rhein, 663 Rheum, 662 officinale, 662 Rheumatine, 579 Rhodalline, 529 Rhodeoretin, 670 Rhubarb, 662 Rhus glabra, 409 Ricin, 659 Ricinoleic acid, 659 Ricinolein, 659 Ricinus communis, 659 Rio Janeiro jaborandi, 720 Rochelle salt, 669 Roman chamomile, 631 Rosa centifolia, 409 gallica, 409 Rosemary, oil of, (note) 630 Rose-water, 409 Rosin, 708 Roth-Drager inhaler, (note) 104 Rottlerin, 814 Rubefacients, 772 Rubijervine, 366 Rubraronic acid, 617 Rue, 742 Russian bath. 717 Ruta, 742 graveolens, 742 Rye, 745 Sabadilline, (note) 370 Sabina, 742 Saccharated ferrous car- bonate, 448 ferrous iodide, 450 pepsin, 815 Saccharin, 791 Saccharum, 654 lactis, 654 Sage, 630 Sago jelly, 12 porridge, 12 Saigon cinnamon, 626 Saljcin, 599 Salicyl-acetic acid phene- tide, 618 Salicylate of /i-naphtol ether, 852 Salicylic acid, 587 amylester, 599 methyloxymethyl- ester, 599 Sahcylunc acid, 588 Salines, 667 Salipyrin, 617 Salol, 847 Salophen, 599 Saloquinine, 579 Salseparin, 528 Salt of lemons, essential, 398 of sorrel, 398 Saltpetre, 694 Salvia, 630 officinalis, 630 Sanguinaria, 739 Sanguinarine, 739 Santalum album, 707, 738 Santogenin, 808 Santonica, 807 Santonin, 807 Santoninic acid, 807 Santoninum, 807 Sapo, 765 mollis, 765 viride, 765 Saponin, 528, 739 Sarillinic acid, 528 Sarsaparilla, 528 Sarsaparillin, 528 Sarsaponin, 528 Sassafras, oil of, 629 pith, 785 Saturnine cerebritis, 414 Saturnism, 412 Savine, 742 Scammonin, 671 Scammonium, 671 Scammony, 671 Scheele's green, 479 Schleich's infiltration- anaesthesia, 119 mixture, (note) 106 Schweinfurt green, 479 Scilla, 680, 737 Scillin, 680 Scillipicrin, 680 Scillitin, 681 Scillitoxin, 680 Scoparin, 682 Scoparius, 682 Scopola, 1 86 carniolica, 186 japonica, 186 Scopolamine, 186 hydrobromide, 187 -morphine anaesthesia, 189 Secale cereale, 745 Seidlitz powder, 669 Senega, 739 Senegin, 739 Senna, 666 Serpentaria, 631 Serum antidiphthericum, 545 Sevum, 786 Sex in relation to dose, 66 Shore oil, 515 Sjdonal, 701 Silberol, 439 Silver, 431 acetate, 438 citrate, 438 cyanide, 394, 438 fluoride, 865 iodide, 438 lactate, 438 nitrate, 431, 822 nitrate, diluted, 438 nitrate, fused, 431 GENERAL INDEX. 959 Silver oxide, 438 poisoning, 436 soluble, 439 sulphocarbolate, 439 thiohydrocarbosul- phonate, 440 vitellin, 438 Simaruba, 622 officinalis, 622 Simple bitters, 622 Sinalbin, 772 Sinapis alba, 772 nigra, 772 Sinigrin, 772 Siphon stomach-pump, (note) 136 Slippery elm, 783 poultice, 794 Smilacin, 528 Smilax, 528 Smyrna opium, 125 Snake-poisoning anti- toxin, 550 Soap, 765 liniment, 288 plaster. 421, 796 Soap-bark, 739 Socaloin, 664 Socotrine aloes, 664 Soda, 798 Sodii acetas, Soi arsenas, 482 benzoas, 864 bicarbonas, 801 bicarbonas venalis, Soi boras, 866 bromidum, 248 carbonas exsiccatus, 801 carbonas monohydras, 801 hydroxidum, Soo hypophosphis, 521 nitras, 80 1 nitris, 260 phenolsulphonas, 849 phosphas, 668 phosphas effervescens, 669 phosphas exsiccatus, 669 salicylas, 596 sulphas, 668 Sodium, 798 acetate, 80 1 and caffeine benzoate, 348 and theobromine sali- cylate, 684 arsenate, 482 benzoate, 864 bicarbonate, 801 borate, 866 bromide, 248 carbonate, 801 carbonate, dried, 801 Sodium chlorate, ( note 697 cinnamate, 864 fluoride, 865 hydrate, 8po, 874 hypochlorite, 826 hypophosphite, 521 ichthyo-sulphate, 527 lactate, 457 nitrate, 694, 801 nitrite, 260 phosphate, 668 salicylate, 596 santoninate, 810 sulphate, 668 sulphocarbolate, 849 tartrate, 669 tetraiodophenol- phthalein, 515 theobromine salicyl- ate, 684 Soft soap, 765 Solid extracts, 61 Soluble ferric phosphate, 45 ' ferric pyrophosphate, 45i iron and quinine cit- rate, 451 silver, 439 Solution of ammonium acetate, 728 of arsenic and mer- curic iodide, 507 of arsenous acid, 482 of chlorinated soda, 825 of ferric subsulphate, 449 of ferric sulphate, 449 of formaldehyde, 856 of gutta-percha, 796 of hydrogen dioxide, 828 of hydrogen peroxide, 828 of lead subacetate, 422 of lime, 802 of magnesium citrate, 668 of mercuric nitrate, 779 of persulphate of iron, 449 of potassa, 692 of potassium arsenite, 482 of potassium citrate, 692 of sodium arsenate, 482 of sodium hydrate, 800 of subsulphate of iron, 449 of zinc chloride, 779 Solutions, 61 Somnifacients, 125 minor, 162 Somnoform, 103 Soups, 9 Soziodol, 515 Spanish flies, 769 Sparteinse sulphas, 350 Sparteine, 350 sulphate, 350, 354 Spasmodic ergotism, 755 Spearmint, 630 water, 630 Spermaceti, 786 Sphacelinic acid, 746 Sphacelotoxin, 746 Spjce plasters, 773 Spigeha, 805 marilandica, 805 Spigeline, 806 Spinal anaesthesia, 121 Spirit of ammonia, 282 aromatic, 282 of anise, 630 of camphor, 288 of chloroform, 100 of cinnamon, 626 of ether, 76 of ether, compound, 76 of glonoin, 261 of juniper, 707 of juniper, compound, 707 of lavender, 631 of lemon, 630 of Mindererus, 728 of nitrous ether, 685, 728 of peppermint, 630 of spearmint, 630 Spirits, 61 Spiritus, 6 1 aetheris, 76 aetheris compositus, 76 aetheris nitrosi, 685, 728 ammonise, 282 ammoniae aromaticus, 282 anisi, 630 camphorae, 288 chloroformi, rco cinnamomi, 626 frumenti, 289 glonoini, 261 glycerylis nitralis, 261 jtiniperi, 707 juniperi compositus, 707 lavandulae, 631 limonis, 630 menthae piperitae, 630 vini gallici, 289 Spleen, 543 Squill, 680 as an expectorant, 737 960 GENERAL INDEX. Squirting cucumber, 673 Star anise, 630 Starch, 784 Stearic acid, 788 Sterculia acuminata, 338 Sticking plaster, 422, 708 Stillingia, 530 Stillingine, 530 Stimulating emetics, 643 Stomachics, 621 Stomach-pump, (note) 136 Stovaine, 118 Straits oil, 515 Stramonii folia, 185 Stramonium leaves, 185 seed, 185 Streptococcus antitoxin, 548 toxin, 545 Stronger water of ammo- nia, 282 Strontii bromidum, 249 iodidum, 508 lactas, 704 Strontium, 702 bromide, 249 iodide, 508 lactate, 704 phosphate, (note) 703 salicylate, 596 Strophanthidin, 334 Strophanthin, 334, 338 Strophanthus, 334 hispidus, 334 kombe', 334 Strychnic acid, 214 Strychnina, 212 poisoning by, 222 Strychninae sulphas, 212 Strychnine sulphate, 212, 226 Strychnos nux vomica, 212 Stupes, 774 Styptic collodion, 405 Stypticin, 409 Styptics, 402 Styrax benzoin, 861 Subacute lead-poisoning, 412 Subcutaneous injections, 64 Subcutin, 118 Sublimed sulphur, 657 Succi, 61 Succinic acid, 862 Succus limonis, 396 Suet, 786 Sugar, 687 as a diuretic, 687 of lead, 421 of milk, 654, 687 Sulphites, 862 Sulpho-carbolic acid, 849 Sulphonal, 155 poisoning, 157 Sulphur, 657 Sulphur dioxide, 865 lotum, 657 praecipitatum, 657 sublimatum, 657 Sulphurated lime, 658 potassa, 658 Sulphuretted hydrogen, 740 Sulphuric acid, 453, 874 poisoning, 453 Sulphurous acid, 864 Sumach, 409 Sumbul, 80 Suppositoria, 62 Suppositories, 62, 65 urethral, 65 Suprarenal capsule, 538 Suprarenin, 539 Sweet orange peel, 630 spirit of nitre, 685, 728 tincture of rhubarb, 664 Swertia chirata, 623 Sydenham's laudanum, 141 Syrup, Coxe's hive, 737 of althaea, 785 of ferrous iodide, 450 of garlic, 737 of ginger, 628 of nydriodic acid, 504 of hypophosphites, 521 of iodide of iron, 450 of ipecacuanha, 639 of lactucarium, 80 of lime, 802 of rhubarb, 664 of rhubarb, aromatic, 664 of rose, 409 of sarsaparilla, com- pound, 528 of senega, 739 of senna, 667 of squill, 682, 737 of squill, compound, 737 of sweet orange peel, 630 of tar, 738 of Tplu, 736 of wild cherry, 624 Syrupi, 61 Syrups, 61 Syrupus acidi hydriodici, 504 allii, 737 althseae, 785 aurantii. 630 calcis, 802 ferri iodidi, 450 fuscus, 654 hypophosphitum, 521 hypophosphitum com- positum, 521 Syrupus ipecacuanhae, 639 lactucarii, 80 picis liquicke, 738 pruni virginiance, 624 rhei, 664 rhei aromaticus, 664 rosae, 409 sarsaparilUe composi- tus, 529 scillae, 682, 737 scilke compositus, 737 senegae, 739 sennas, 667 tolutanus, 736 zingiberis, 628 Systemic lavage, (note) 209 Syzygium jambolanum, extract of, (note) 398 Tabacum, 267 Table of apothecaries' weights and meas- ures, 879 Table of composition of foods, 23 Table of cost of various disinfectants, (note) 825 Table of germicides, 874 Table of the proportion of alcohol in different wines, 882 Table of relation of apoth- ecaries' weights to metrical weights, 880 Table of relation of apoth- ecaries' weights and measures to eacli other, 880 Table of weights and measures of the met- rical system, 879 Tachiol, 865 Tamarind, 656 Tamarindus, 656 indica, 656 Tanacetum, 743 vulgare, 743 Tannacol, 405 Tannalbin, 405 Tannate of cannabene, 195 of quinine, 577 Tannic acid, 402 compounds, 405 Tannin albuminate, 405 Tannoform, 405 Tannopine, 405 Tannon, 405 Tansy, 743 Tapioca porridge, 13 Tar, 737 GENERAL INDEX. 961 Tar camphor, 849 Taraxacum, 530 officinale, 530 Tartar, 335 emetic, 360, 733 poisoning, 394 Tartaric acid, 394 poisoning, 395 Tea, 338 Temperament, 66 Terebene, 738 Terebenum, 738 Terebinthina, 708 canadensis, 708 Terpin hydrate, 738 Terpini hydras, 738 Tertiary amyl nitrite, (note) 252 Tetano-cannabene, 191 Tetanus antitoxin, 547 Tetra-iodo-phenol-phtha- lein, 515 Tetra-iodopyrrol, 514 Tetra-methylthionine hy- drochloride, 580 Tetronal, 59 Thebaine, 142 Thebolactic acid, 125 Theine, 338 Theobromine, 684 and sodium salicylate, 684 Theocin, 685 Theocol, 847 Theophyllin, 685 Thermol, 618 Thioresorcin, (note) 854 Thiosinamine, 529 Thymacetin, 853 Thymol, 813, 852 Thymolis iodidum, 514 Thymus serpyllum, (note) 852 vulgaris, (note) 852 Thyreoantitoxin, 535 Thyroid body, 534 Thyroidismus, 536 Thyroiodin, 535 Time for administration of drugs, 67 Tinctura aconiti, 385 aloes, 666 aloes et myrrhae, 666 arnicae, 373 asafcetidae, 76 aurantii amari, 630 aurantii dulcis, 630 belladonnae foliorum, 184 benzoin!, 863 benzoini composita, 863 calumbae, 623 cannabis indicae, 195 cantharidis, 772 capsici, 629 Tinctura cardamomi, 627 cardamomi composita, 627 chiratae, 623 cimicifugae, 79 cinchonas composita, .555 cinnamomi, 626 colchici seminis, 527 digitalis, 330 ferri chloridi, 449 gallse, 407 gambir, 407 gambir composita, 407 gelsemii, 267 gentiame composita, 623 guaiaci, 529 guaiaci ammoniata, 529 humuli, 77 hydrastis, 760 hyoscyami, 186 iodi, 504 ipecacuanhas et opii, i- I4T kino, 407 krameriae, 408 lactucarii, 80 lobelias, 264, 733 matico, 714 moschi, 74 nucis vomicae, 212 opii, 141 opii camphorata, 141 opii deodorati, 141 physostigmatis, 238 quassiae, 622 rhei, 664 rhei aromatica, 662 scillae, 682 serpentarias, 631 stramonii, 185 strophanthi, 338 tolutana, 736 valerianae, 75 valerianas ammoniata, 75 veratn, 370 zingibens, 628 Tincturee, 61 Tincture of aconite, 3.85 of aconite, Fleming's, 385 of aloes, 666 of aloes and myrrh, 666 of arnica, 373 of asafetida, 76 of belladonna leaves, 184 of benzoin, 863 of benzoin, compound, 863 of bitter orange peel, | 630 61 Tincture of cannabis indica, J 95 of cantharides, 772 of capsicum, 629 of cardamom, 627 of cardamom, com- pound, 627 of chirata, 623 of chloride of iron, 449 of cimicifuga, 79 of cinchona, com- pound, 555 of cinnamon, 626 of colchicum seeds, 527 of columbo, 623 of conium, 273 of digitalis, 330 of ferric chloride, 449 of galls, 407 of gambir, 407 of gelsemium, 267 of gentian, compound, 623 of ginger, 628 of guaiac, 529 of guaiac, ammo- niated, 529 of hemp, 195 of hops, 77 of hydrastis, 760 of hyoscyamus, 186 of Indian cannabis, 195 of iodine, 504 of ipecac and opium, 141 of kino, 407 of krameria, 408 of lactucarium, 80 of lobelia, 264, 733 of matico, 714 of mufck, 74 of nutgall, 407 of nux vomica, 212 of opium, 141 of opium, camphor- ated, 141 of opium, deodorized, 141 of physostigma, 238 of quassia, 622 of rhatany, 408 of rhubarb, 664 aromatic, 664 sweet, 664 of serpentaria, 631 of squill, 682 of stramonium, 185 of strophanthus, 338 of sweet orange peel, 630 of Tolu, 736 of valerian, 75 of valerian, ammoni- ated, 75 962 GENERAL INDEX. Tincture of veratrum viride, 370 Tinctures, 61 Tinnevelly senna, 666 Tobacco, 267 Toluifera balsamum, 736 pereirs, 736 Tomato porridge, 12 Tonics, 443 Toxins and antitoxins, 544 Tragacanth, 783 Tragacantha, 783 Trichlor tertiary butyl alcohol, 162 Trichloracetic acid, 780 Trichlorisopropyl alcohol, 163 Trimethylamin, 516 Trimethylethylene, 102 Trimethylxanthin, 683 Trinitro-cellulose, 796 Trional, 159 Trioxymethylanthraqui- none, (note) 663 Triticum, 706 Triturate of elaterin, 674 Trituratio elaterini, 674 Troches, 62 of gambir, 407 of ipecac, 639 of ipecac and mor- phine, 639 of santonin, Sio of tannic acid, 405 Trochisci, 62 acidi tannici, 405 gambir, 407 ipecacuanha?, 639 morphinas et ipecacu- anha?, 639 santonini, 810 Tropacocaine, 117 Tropine, (note) 168 True chamomile, 631 expectorants, 732 Tuberculin, 544 Turkey opium, 125 Turkish bath, 717 Turpentine, 708 as an anthelmintic, 812 enemata, 650 liniment, 774 -phosphoric acid, 467 stupes, 774 Turpeth mineral, 496 U Ulmus, 783 fulva, 783 Unbolted flour, 654 Unguenta, 62 Unguentum acidi tannici, 405 Unguentum aquae ros;e, 409, 786 belladonna;, 184 gallae, 407 hydrargyri, 492 hydrargyri amnio- niati, 496 hydrargyri nitratis, 496 hydrargyri oxidi flavi, 496 oxidi rubri, 496 iodi, 504 iodoformi, 513 mezerei, 529 picis liquidae, 737 plumbi carbonatis, 422 potassii iodidi, 507 stramonii, 185 veratrinae, 372 zinci oxidi, 428 Unslaked lime, 801 Urasol, 702 Urethane, 163 Urethral suppositories, 65 Urginea maritima, 680 Urochloralic acid, 146 Urohaematoporphyrine, 416 Urotropin, 699 Urotropinse quinas, 701 Uva ursi, 705 Valerian, 74 Valeriana, 74 officinalis, 74 Valerianic acid, 74 dimethylamid, 75 Valjdol, 75 Validolum camphoratum, 75 Vapor bath, 717 creosoti, 845 Vaseline, 792 Vegetable acids, 394 astringents, 402 cathartic pills, 672 Veratralbine, 366 Veratrina, 370 Veratrine, 366 ointment, 372 Veratroidine, 366 Veratrum, 366 album, 366 sabadilla, 370 viride, 366 viride, poisoning by, 369 Vermicelli soup, 10 Vermicides, 805 Vermifuges, 805 Veronal, 164 Veronica virginica, 656 Vesicatories, 769 Viburnum opulus, 744 prunifolium, 744 Vienna paste, 778 Vina, 6 1 Vinegar, 396 of opium, 141 of squill, 682 Vinegars, 61, 396 Vinum album, 289 antimonii, 366 colchici radicis, 527 colchici seminis, 527 ergotie, 756 ipecacuanha;, 639 opii; 141 rubrum, 289 Virgin scammony, 672 Virginia snakeroot, 631 Volatile oil of hops, 82 oil of mustard, 772 oil of savine, 742 oils, 61, 860 Volt, 45 Volta's law, 41 W Wahoo, 653 Warburg's tincture, 579 Warming plaster, 775 Washed sulphur, 657 Water as a diuretic, 678 of ammonia, 282 of chloroform, 100 of creosote, 845 of hamamelis, 408 of rosemary, 631 Waters, 61 Wax, 786 white, 772, 786 Weights and measures, 879 West India pepper, 629 Whiskey, 289 White agaric, 409 arsenic, 468 galls, 407 ginger, 628 hellebore, 370 mustard, 772 oak, 408 pepper, 628 precipitate, 496 precipitate ointment, 496 sugar, 654 turpentine, 708 vitriol, 427 wax, 786 wine, 289 Wigger's ergotin, 756 Wild cherry, 624 Williamson's sanitary fluid, 8n Wine, 289 GENERAL INDEX. 963 Wine of antimony, 366 of colchicum root, 527 of colchicum seed, 527 of ergot, 756 of ipecacuanha, 635 of opium, 141 whey, u, 309 Wines, 61 Wormseed, 806 oil, 807 Wood alcohol, 311 Wool fat, 788 X Xanthin, 683 Xanthopuccine, 754 Xanthoxylum, 530 Xylic acid, 831 Yaupon, 338 Yellow cinchona, 555 gentian, 622 jessamine, 264 mercuric oxide, 496 mercuric subsulphate, 496 mercurous iodide, 495 prussiateof potash, 430 wash, 496 wax, 786 Yohimbine, 715 Young's rule for doses, 65 Zinc, 427 acetate, 428 Zinc bromide, 428 carbonate, precipi- tated, 428 chloride, 778, 823 oxide, 427 phosphide, 468 poisoning, 427 sulphate, 427, 643, 823 Zinci acetas, 403 bromidum, 428 carbonas pnecipitatus, 428 chloridum, 778 oxidum, 427 oxidum venale, 427 phosphidum, 468 sulphas, 427 sulphocarbolate, 849 Zincum, 427 Zingiber, 627 officinale, 627 THE END. Kn THE LIBRARY UNIVERSITY OF CALIFORNIA Santa Barbara THIS BOOK IS DUE ON THE LAST DATE STAMPED BELOW. Series 9482