A text-book of materia medica, therapeutics, and pharmacology

Front matter

A TEXT-BOOK

OF

MATERIA MEDICA.

Preface To The Fourth Edition

The following important alterations and additions have been made in this edition, namely : a thorough remodeling of the opening chapters, to bring them into accord with recently discovered biological phenomena and natural interpretation of the disease process as reactive and self-preservative.

The pharmacology and therapeutics of each drug have been carefully revised, incorporating all the recent advances that have been made in pharmacodynamics.

Numerous changes have been made in the expressions of opinion regarding the utility of certain drugs, notably the newer synthetics, which larger experience has modified, resulting in more definite conclusions. Many of them have been introduced, their actions discussed, and their therapeutic uses fully expounded, while considerable attention has been paid to their incompatibles.

The chapters on Organotherapy, Serum-therapy, and cognate subjects have been enlarged and carefully revised.

Perhaps the most important addition is the chapter devoted to the interesting phases of the newer theories of electrolytic dissociation and its relations to the topic of pharmacotherapy, and the relevant discussion added of the simpler relations of chemical structure to drug-action.

The author desires to express his sincere acknowledgment to Dr. Smith Ely Jelliffe, of New York City, for his valuable assistance in the revision of the work, and to Dr. Martin H. Fisher, Associate in Physiology in the University of Chicago, for his interesting contribution, " The Relation of Physical Chemistry to Pharmacology and Therapeutics."

GEORGE FRANK BUTLER.

Alma, Mich., August, 1902.

Preface

The present work has been undertaken with the immediate object of supplying the student of medicine with a clear, concise, and practical text-book, adapted for permanent reference no less than for the requirements of the class-room.

The arrangement — embodying the synthetic classification of drugs based upon therapeutic affinities — the author believes to be at once the most philosophical and rational, as well as that best calculated to engage the interest of those to whom the academic study of the subject is wont to offer no little perplexity.

Should an intelligent and comprehensive understanding of Materia Medica and Therapeutics be facilitated by the author's treatment of the theme, the deductions derived from his experience as a practitioner and instructor will not have been committed to print in vain.

Special attention has been given to the Pharmaceutical section, which there is reason to hope will be found exceptionally lucid and complete. It has been deemed advisable, however, in the general work to include in the descriptive enumeration only such drugs as experience has proved to be of unquestionable value and are of standard and authoritative acceptance in general practice. In accordance with this plan, many new and comparatively untried remedies have been omitted, since, while of established efficacy in certain conditions, they are as yet too imperfectly known to warrant association with remedial agents bearing the sanction of exhaustive scrutiny. So, too, a few official drugs have been excluded because they are practically never used or are employed only in isolated instances.

It will be observed that "Untoward Action" and "Poisoning"

12 PREFACE.

are treated under separate heads. By the former it is intended to record the effects of medicinal doses in developing certain symptoms dependent more or less upon individual susceptibility, not necessarily assuming the aggravated form incident to toxic doses, which exert a definite influence regardless of idiosyncrasy.

In giving the careful Latin accent and quantity of medicinal nomenclature (Foster), so far as practicable with the prosodial signs employed, the design has been to correct a prevalent disregard of proper pronunciation reflecting little credit upon those to whom a knowledge of the subject should be as exact as it is familiar. To the prescription-writer the appropriate Latin genitive, and in a few cases the accusative, will doubtless afford valuable assistance.

During the preparation of the work many important text-books, periodicals, etc. have been freely consulted, and from the U. S. Pharmacopceia chiefly, and from the National Dispensatory, have been adopted almost verbatim the "Origin" and "Description and Properties " of the various drugs under consideration.

In reviewing the progress of the present volume the author desires to express his cordial acknowledgments to Prof. Carl S. N. Hallberg, Ph. G., whose exhaustive contribution of "Weights and Measures" and "Pharmaceutical Preparations" cannot fail to lend permanent interest to the work ; to Dr. Alfred C. Cotton, Dr. Wm. E. Quine, and Dr. James B. Herrick, for friendly suggestions ; to Dr. D. Lee Shaw, Dr. Fred C. ZapfTe, and Dr. Thomas J. Jackson, for assistance in compilation. To Mr. Storrow Higginson the author's personal thanks are due for his scholarly assistance in the revision of the text.

G. F. B.

Chicago, III., 794 West Adams St., September, 1896.

Contents

C AGB

INTRODUCTION 17

Classification of Medicines 32

Introduction

The history of medicine since the time of Hippocrates is the record of a more or less continuous series of experimental researches, having for their paramount object a precise and comprehensive knowledge of the nature of disease and the practical application of remedial science. Regarded sensu latiori, the various " schools " which have arisen from time to time are philosophically co-ordinate, their fundamental principles being referable to one dominating thought — the art of healing.

It is scarcely practicable here, even were it necessary, to review in detail the separate doctrines which have obtained during the evolution of sectarian therapy. From the earliest ideas promulgated by the ancient priests of ^Esculapius, through the subsequent era of Hippocrates, Theophrastus, and the Alexandrian school, influenced by the crude, misguided notions prevailing ere science emerged from its infancy ; discernible in the Galenic and other tentative yet memorable systems, in the epoch of Paracelsus and the Monastic Medicine of the Mediaeval period, and in the radical theories of Rasori and Roeschlaub which attended the development of the eighteenth and have left a passing impress upon the nineteenth century, — through all, the gradual acceptance of empiricism as a legitimate guide to therapeutic truth is manifest. Yet viewed with reference to their underlying animus, these varied expressions of scientific endeavor distinguishing the part are perceptibly linked with the ampler system which has emanated from the more rational methods of modern research.

2 17

The light of inductive reasoning and the marvellous progress in scientific knowledge which characterize the nineteenth century are a living appeal from the idealism of a less enlightened age. The release from tradition — anticipated in the labors of Bichat and others — to which later investigation owes so many signal triumphs has doubtless been profoundly affected by the realistic tendency of modern thought. It is to the startling advancement attained in the natural sciences, however, resulting in a chemical skill and in mechanical appliances of incomparable value, that we must look for the originating impulse which has inspired the therapeutic knowledge of the present day. It needs but little reflection to perceive the immeasurable superiority of actual acquirements over the vague, hesitating — though ardent and laborious — methods to which the theory and practice of medicine were so long subservient.

We have said that, considered in the larger sense, the history of medicine has been a harmonious rather than an intermittent development. It is not to be supposed that, in the evolution of so momentous a scheme as the formulation of a remedial system applicable to the extensive catalogue of human ailments, there should not have occurred spasmodic and ill-adjusted theories, crystallizing in many a strange cultus, which, if ineffectual in retarding the onward sweep of rational progress, has, it may be safely averred, worked incalculable injury to the cause of medical truth. Mesmerism, astrology, spiritualism, even theosophy, however incongruously conjoined, and similar vagaries have not failed to enlist among their votaries many enraptured, even noted, believers ; nor is the mental strabismus with which they are afflicted amenable to any resource of rational treatment. We need, moreover, but contemplate the pitiable hallucinations which urge the pious pilgrimages to Marpingen, Lourdes, and Treves, and the criminal negligence and incredible offence to reason which stultify the so-called " Christian Scientists " (as ironical a misnomer as Ianguage permits), to realize that miraculous cures still hold blighting yet potent sway over the minds of the ignorant and credulous. May not even the assumption of thaumaturgical powers be one day possible with those who arrogate to themselves a knowledge little short of omniscience, and to whose rudimentary intelligence the laws of nature convey no perceptible lesson ? As from the sublime to the ridiculous, so from faith to fanaticism, it is but a step, after all.

It is appropriate here to emphasize the unfailing — nay, ever-

INTRODUCTION. 19

increasing — importance of therapeutics in its relation to the welfare of mankind. Especially imperative is this obligation in an epoch of unprecedented achievement in every department of science which contributes to the perfection of the healing art, in which general advancement medicine has borne no inconspicuous role.

The rapid advance of experimental science, however, applied to medical treatment, culminating in bacteriological discoveries of signal value to mankind, and the remarkable triumphs attending the development of operative surgery, have inevitably tended to disparage the equally noble and far more widely cultivated field of therapeutic science. This result is the more deplorable since it creates in the minds of the young and inexperienced an impression of contrast and divergence in departments of study naturally and indissolubly correlated. It is scarcely surprising that the marvels of the laboratory and the splendid achievements of the arena should possess for the tyro an entrancing interest. Yet it is to be borne in mind that the most brilliant triumphs of diagnostic and surgical skill might prove futile as the means of arresting disease were they not supplemented by the course of treatment which constitutes therapy.

It must be confessed that medical art has too often been discredited by professional incompetence, and consequent failure to effect the cure which with the laity is wont to form, however ignorantly, the only criterion of ability. In America especially — where from defective laws the widest latitude is given to incapacity and imposture — the lack of proper academical training is frequently the cause of serious consequences in practice, little calculated to enhance the popular confidence and esteem. It therefore behooves the student of medicine to master thoroughly the details of the remedial art, become practically conversant with physiological conditions and the manifold phenomena of morbid anatomy, and so familiarize himself with the varying indications of disease that in the presence of whatever malady, his diagnosis and treatment may command respect — not only from the laity, but, what is of far more consequence to him, from the profession.

It is almost superfluous to lay stress upon pharmaceutical knowledge as a powerful weapon in the armament of the medical practitioner. Yet no branch of therapeutic science has, perhaps, been more neglected than a practical acquaintance with the nature and uses of Materia Medica, their origin, potency, and characteristic value, as well as their physiological action, and the incompatible and synergistic agents upon which their efficacy often largely depends.

Thanks to careful and competent training among pharmacists, the skilful preparation and dispensing of drugs relieve the physician of much responsibility ; yet he should be keenly sensible of the fact that the larger share of public confidence is reposed in him, and by diligent study of the subject endeavor to command the minutiae of pharmacology, holding himself morally accountable for errors quite possible in the druggist's dispensary. It may not be irrelevant to add that in all medical procedure a sympathetic yet perfectly controlled nature, ready tact, and sterling common sense are cardinal requisites to professional triumph, it being generally true, as was long since observed by Hufeland, that " successful treatment requires only one-third science and two-thirds savoir faire"

Finally, the author would counsel the utmost seriousness in the pursuit of a calling which might aptly be termed " Christian Science" — the power to alleviate human suffering by means of curative agents with which the laboratory of nature has been mercifully stored. There can be no loftier, more practical manifestation of love to men than is exemplified in the benignant effort to assuage the ills to which mortality is heir ; nor can any devotion be more privileged and inspiring than that which softens the shock of disease, illumines the darkness of mental and physical distress, and from the debris of misfortune, vice, and heredity creates anew the image of divine perfection. It is this uplifting, consecrated zeal, akin to veneration for medical science, which has endeared to the world the masters of the profession — of which the same wise Hufeland said : " To him who fails to make a religion of the healing art it is the most cheerless, wearisome, and thankless labor upon earth ; indeed, in him it must become the greatest frivolity and a sin." And for those — and they are many — to whom the material, possibly mercenary, aspect of their task appeals unduly it is enough to cite in rebuke the elevated maxim of Stigelius ■

PHARMACOLOGY AND GENERAL THERAPEUTICS.

Nature heals, physicians treat — is a truth of old that is constantly forgotten : always by the patient, who expects the patent medicine or the family doctor to cure her ; frequently by the physician, who is often persuaded, against his better judgment, to believe in the supernatural when the mysteries of drug action are involved. A few propositions concerning the general action of the human body in its endeavor to cure itself may not be out of place in an introduction to a work on the practice and art of aiding nature's forces in the treatment of abnormal conditions.

It is a difficult task to express, in a few phrases, the general causes of disease, but the following general agencies may be considered :

1. Trauma, whether the result purely of accident, or brought about in the general struggle for existence.

2. Parasites, both microscopical and macroscopical, acting within and without the body.

3. Poisoning from plants and animals, broken down and decomposed food-stuffs, and poisonous gases taken into the respiratory tract.

4. Bad hygiene, unwise modes of living, including faulty nutrition, faulty modes of dress, eating, and housing, use or abuse of certain organs or their lack of use.

5. Heredity. — Here would be classified not only the directly transmissible diseases, as syphilis, but also those constitutional dyscrasiae that conduce to premature break-down of some part of the human body.

In order to combat these various agencies the individual organs have developed a system of natural cure methods (" natural therapeutics ") that are of interest. These may be summarized briefly, following Kobert, in part, as :

1. Healing by regeneration. Among the lower animals the regeneration of a lost member is not infrequent, but in man it is unusual. In a sense, however, the healing of wounds as a part of the inflammatory reaction is analogous to this process in the lower animals. The hypertrophy of one kidney, compensating for the loss of the other, and the establishment of a collateral circulation are illustrations of what Bachmann, in 1894, pointed out as the law of equivalent compensations.

2. Healing may be brought about by the exercise of an organ. Thus, the old-fashioned system of exposure to wet and weather develops, by exercise of the skin, an increased resistance to agencies that otherwise might react harmfully on the organism.

3. In the struggle against parasites it would appear that the body had developed an extensive array of protective agencies. Thus, antiseptic substances in the saliva, gastric juice, and bile are simple instances of this protective power against parasites from the outside. The doctrine of phagocytosis embodies the principle of the action of the white blood-cell in its office as a protective agent. In the body-fluids are found alexins, antitoxins, immunizing proteids that protect from the actions of poisons which may develop as a result of the life activities of these parasites should they obtain a foot-hold within the body — or even protect from poisons developed in the course of disturbed metabolism. Fever, so frequently regarded as an adverse sign in disease, undoubtedly serves in large part as a means of protection of the body — by killing the agents that have induced the rise in temperature.

4. Healing from certain poisons is brought about by vomiting and diarrhea, by rapid elimination through diuresis, or by excessive perspiration. Within the body a most interesting series of changes often takes place — thus, splitting up of poisons, their oxidation or conversion, or even fixation, into non-toxic products is a constant phenomenon. Thus even so powerful an alkaloid as morphine is said by Faust to be in part oxidized and perhaps used as a foodstuff. The chemical changes that take place in the liver have here their most potent activities, and the pathological chemistry of the twentieth century promises to throw much light on these complicated problems. Poisons also are compensated for by the process of adaptation (habituation), and are frequently rendered inert by the development of specific antitoxic substances. Thus specific anti-morphine bodies have been developed in the blood of some of the lower animals.

5. The physiologicalprocess of rest is an expression of nature healing. Loss of appetite is the indication not to eat. Pain calls for rest.

6. Healing by the casting off of a portion of the organism is a process of nature healing widely made use of in diseases among plants and the lower animals. Abscess formation, the limiting, by fibrinous exudates, of intraperitoneal irritants, and spontaneous gangrene of the extremities are well- recognized examples of such a type of nature's healing.

Treatment is something apart from healing, and in its broad sense comprises all those means, psychical or physical, which the practiser of the healing art has at his command by which he can hope to alter an abnormal condition in the individual he is called on to treat. Thus, nature calls into play the highest of her gifts, intelligence, to aid her in the work of self-preservation, and it is the function of the text-book to aid, in so far as it is able, to train that intelligence in the facts that experience has proved of value — in the present instance, in the fields of materia medica, pharmacodynamics, and therapeutics.

Pharmacology, from the broad point of view, is the science of drugs, and includes the various fields of medical botany, medical zoology, pharmacognosy, pharmacodynamics, and pharmacy. Within recent years, however, following the German school, its meaning has been restricted and made equivalent to pharmacodynamics, or the study of the effects of physical or chemical agencies on living organisms. It is in this sense that it is used in this work.

Materia Medica is the study of the materials, organic and inorganic, used for drugs in their physical and chemical characters.

Pharmacognosy is a division of materia medica, and includes the technical study of the crude materials from which drugs are derived. Its deliberation is limited to the animal and the vegetable kingdoms, but it is not a science with sharply defined boundaries, as it encroaches on so many avenues of knowledge — systematic botany, zoology, gross and minute anatomy, chemistry, and pharmacy.

Pharmacy is largely a chemical study. It deals with those manipulations by which the potent principles of drugs are rendered available for therapeutic purposes.

Therapeutics is the art and practice of treating abnormal bodily states. It has for its object the restitution to the normal, or, if such is impossible, the giving of comparative comfort to the invalid. Its range of activity, therefore, is extremely wide, and a combination of methods is necessary to the resourceful physician. The following general modes of treatment should be considered :

Suggestion Therapy. — --Faith is one of the oldest therapeutic agencies of which anything is known. As Dr. Osier 1 has so well said, " Faith in the Gods or in the Saints cures one, faith in little pills another, hypnotic suggestion a third, faith in a plain common doctor a fourth. In all ages the prayer of faith has healed the sick, and the mental attitude of the suppliant seems to be of more consequence than the powers to which the prayer is addressed. The cures in the temples of ^Esculapius, the miracles of the Saints, the remarkable cures of those noble men, the Jesuit missionaries, in this country, the modern miracles of Lourdes, and the wonderworkings of the so-called Christian Scientists are often genuine and must be considered in discussing the foundations of therapeutics." " Physicians use the same power every day. If a poor lass, paralyzed, apparently helpless, bed-ridden for years, comes to me, having worn out in mind, body, and estate a devoted family, and she in a few weeks or less by faith in me, and faith alone, takes up her bed and walks, the saints of old could not have done more." " The faith with which we work, the faith, indeed, which is available to-day in every-day life, has its limitations : it will not raise the dead : it will not put in a new eye in place of a bad one, nor will it cure cancer or pneumonia or knit a bone ; but in spite of the nineteenth century restrictions, such as we find it, faith is a most precious commodity without which we should be very badly off."

Of the various forms of suggestive treatment it is not necessary here to treat. One form, treatment by hypnosis, is worthy of careful study, but its details are out of place here.

Heliotherapy, exposure to the rays of the sun, or, in Finsen's latest developments, to the activities of the x-rays ; aerotherapy, or exposure to the open air, moist air, dry air, superheated air, etc. — both constitute modes of treating some forms of disease. Much might be said of Climato therapy, the principles of which are not well understood. Dietetic Therapy. — This is also a method of antiquity. Diet — milk cures, vegetarian diet, meat diets, diets for obesity, for diabetes, etc. — has extreme practical importance, and its principles should be thoroughly mastered by the student.

Physicomechanical Therapy. — This includes a large number of useful procedures — Kinesotherapy, or massage and Swedish movements, from which the fantastical osteopathy has developed, is one of the most important. The Chinese and Japanese have used massage for a thousand years, and it constitutes one of their

1 Medicine of the Nineteenth Century, 1901.

most important therapeutic procedures. Tissot, in 1780, brought the methods in use once more in Europe; Schebe, of Germany, in 1847, an d Zander, of Stockholm, in 1865, brought the modern gymnastic procedures to a state of perfection.

Hydrotherapy, involving the use of heat and cold, with modified massage, has justly become a most important therapeutic procedure. E. F. C. Oertel, of Bayreuth, in 1765, and Preissnitz, in 1790, may be regarded as the founders of modern hydrotherapy. Its most useful applications are to be found in reducing temperature, in promoting sleep, and in neurasthenic and weakened nervous states, although its applications in one form or another are numerous. Tonsillitis, pharyngitis, conjunctivitis, abdominal pain, ovarian neuralgias, etc., are all benefited by hot applications.

Hypodermoclysis and enteroclysis are special forms of hydrotherapy which are of great value.

Electrotherapy. — Electricity is a potent agent in the treatment of certain forms of disease. Within recent years more definite ideas have been gained regarding the mode of its action. Space does not permit of more than an indication of the merest outlines in this place, the student being referred to text-books on the subject (Jacoby, " Electrotherapeutics ").

In general, two types of current, galvanic and faradic, are employed both for diagnostic and for therapeutic purposes. The galvanic current is of constant flow, low intensity, and small in quantity. It has little influence in causing muscular contractions, but has marked chemical and thermal properties and promotes metabolism. The faradic current consists of alternating to-and-fro currents, is usually of high intensity, and has marked power to promote muscle contractility. The knowledge of the different modes of application should be gained from a good text-book.

In using electricity for diagnostic purposes it is advisable to use the minimum amount of current to produce a desired effect. The two sides of the body should be carefully compared, and the patient should be at rest. It is advisable to have similar electrodes, and they should be applied to corresponding areas on the well side and the supposedly diseased side.

The condition of muscular contractility is investigated in using the galvanic current by making and breaking the current. Under the influence of small to medium currents the normal reaction of a muscle should be that the anodal clos?ire contraction is less than the cathodal closure contraction, thus, A.C.C. < C.C.C. In a muscle that is just beginning to show signs of a loss of muscular contractility the A.C.C = C.C.C., whereas if the anodal closure contraction is greater than the cathodal closure contraction the reaction is known as the reaction of degeneration, and is an evidence of disease. Reaction of degeneration must result from almost any extensive lesion of the peripheral motor neuron. It is found in extensive neuritis from toxic causes, alcohol, lead, zinc, carbon disulphide, mercury, malarial poisoning, etc., in acute anterior poliomyelitis or other disease involving the cells in the anterior horns of the cord ; it may also occur with extensive muscle disease.

From a therapeutic point of view electricity is having a constantly widening application. The use of the x-rays in lupus and in flat epitheliomata is as certain as it is marvellous, and the application of the Finsen phototherapy is but in its infancy. Electricity is widely employed as an irritant, caustic, and escharotic. In paralyses of spinal and neuritic origin its properties of stimulating metabolism make it a highly desirable therapeutic measure. When combined with massage and infinite pains and tact, continued for long periods of time, seemingly hopeless paralyses may be very markedly relieved. Eternal persistency is sometimes the price of recovery. In sensory affections the static current often is of service. Mental suggestibility is here an important item, and the static machine lends itself very readily to much quackery. Galvanism is often very useful in relieving the deep-seated pains of sciatica and lumbago. By many, electricity is deemed of no value, and by others as a panacea for all ills. The truth lies in the means. In proper hands it is an exceedingly useful agent, but it has fallen very much in the estimation of the profession because of the great use made of electricity by the charlatan and professional parasites on that portion of society that so delights in being humbugged.

Toxicology. — Pharmacology and toxicology are in a sense the same. They represent quantitative variation only. All pharmacological action represents some variation from normal standards. When such variations reach a point where the disturbance of function threatens to be or is fraught with danger to the well-being or life of the organism, then the subject is suffering from the toxic action of such an agent.

Pharmacotherapy .—This includes the study of remedial agents proper or the use of drug substances. It considers the applications of the teachings of pharmacology to the treatment of abnormal

PHARMACOLOGY AND GENERAL THERAPEUTICS. 2 J

body states. It naturally constitutes the most important branch of therapeutics.

It is not to be supposed that our present elaborate systems of pharmacotherapy have come into existence as they now are found. They have had a natural development, and the various methods have merged, the one into another. Certain arbitrary methods have received special names, such as Empirical, Specific, Statistical, Physiological, Rational Therapeutics, etc.

Empirical Therapeutics implies the application of remedies to which experience has ascribed certain specific properties irrespective of systematic value. It is not based upon experimental research, but rather upon formulae established by the accumulation of isolated facts — empiricism — and practical observation, apart from theoretical reasoning and the relations of physiological phenomena as revealed by modern methods of investigation. Were it possible to extend indefinitely the list of remedial agents so as to embrace the entire field of therapeutic knowledge, the empirical method might attain the dignity of an exact science. Such, however, is the complexity arising from the manifold, often contradictory, impressions drawn from human experience that for the evolution of a systematic scheme of therapeutics the empirical system must of necessity prove inadequate.

By Specific Therapeutics is meant a system of treatment that implies that certain diseases have certain definite antidotes. Thus, mercury and the iodides are specifics for syphilis, antitoxin for diphtheria, antivenin for snake-bite, etc.

Statistical Therapeutics implies a method of treatment that is the outcome of the experience of the results observed in a large number of cases under certain restricted lines of treatment. This method arrives at excellent results if sufficient numbers of cases of the same type can be observed, but disease processes vary so widely in different individuals that the statistical method alone is not unlikely to lead to error.

Physiological Therapeutics consists in the application of the strict interpretations of the pharmacodynamic action of drugs to diseased conditions. With increasing knowledge its principles will prove more and more applicable, but the inherent difficulties of interpretation of all biological phenomena will always make this method unsatisfying.

On the General Action of Drugs. — Broadly speaking, the action of drugs is exerted either locally or systemically, whereas the effects which are known as reflex action occupy a middle ground between the two. Many drugs have only a limited action at the point of application, while others possess not only a local, but a systemic, action as well.

The action of drugs is fundamentally a question of protoplasm chemistry, but the investigations of the biologist have not yet reduced the interpretations of nature to a question of molecular physics ; until they do, pharmacology will retain the words irritation, stimulation, depression, paralysis, and death of protoplasm. Hueppe, in 1891, enunciated the doctrine that all remedies first, in small doses, produced an irritant and stimulating action in protoplasm, to be followed, when used in larger doses, by a depressing or paralyzing action, which might go on to death of the protoplasm acted on. Thus the effects of small and large doses were contrasted ; the foundations of the homeopathic idea are closely related to this interesting phenomenon. It is not a universal phenomenon, however, and cannot be designated as a law, as Hueppe claimed. There are a large number of substances that in small and large doses have antagonistic effects, but the antagonism is by no means an equal one. Thus is it a familiar illustration that small doses of morphine increase mental activity by slight stimulation, whereas large doses depress and paralyze and bring about unconsciousness. The grade of excitement cannot at all be made commensurate with the grade of depression by making the doses smaller and smaller. Chloral acts as an irritant to the peripheral nerve-endings, although it depresses and paralyzes the central nervous system. Citations might be multiplied to show the host of inconsistencies and variations.