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PHARMACOLOGY

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Originally appearing in Volume V21, Page 350 of the 1911 Encyclopedia Britannica.
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PHARMACOLOGY. Systematic writers on the subject differ considerably in the exact meaning which they attach to the term pharmacology (c/Aap,uaKov, a drug; Aoyos, a discourse), some making it much more comprehensive than others. Hinz, for instance, defines it as treating of the origin, nature, chemical and physical qualities, physiological actions, and therapeutical uses of drugs; in France and in Italy it is restricted to the mere description of medicines and their preparations, the action and uses of which as remedies are included in the term therapeutics. In English-speaking countries, and by the majority of German writers, the meaning is now restricted to the study of the action of chemical substances (as apart from foods) on all kinds of animals, from bacteria up to man; it is, in fact, a comparative study of the action of chemical bodies on invertebrate and vertebrate animals. One of its practical aims is to obtain a wide and accurate knowledge of remedial substances in relation to their application in the treatment of disease, while another is to discover new or improved remedies. This meaning of the word has now become fixed in the English language by use and wont. The term pharmaco-dynamics (4 pµaKov, 5&vaµts, power), which is etymologically more correct, is often used as its equivalent, but it has never become widely adopted. The study of pharmacological actions was at first almost entirely confined to those of remedial agents, and especially to the remedies in the different national pharmacopoeias, but in many cases it has now been extended to substances which are not used for curative purposes. The introduction into practical use of many medicines, such as paraldehyde, phenazone and strophanthus, has followed the study of their actions on animals, and this tends to be more and more the case. Pharmacology is a branch of biology; it is also closely connected with pathology and bacteriology, for certain drugs produce structural as well as functional changes in the tissues, and in germ diseases the peculiar symptoms are caused by foreign substances (toxins) formed by the infective organisms present in the body. The effects of many of these toxins bear a close resemblance to the action of certain well-known drugs, as in the case of tetanus toxin and strychnine, and are studied by the same methods of observation and research. It is impossible also to dissociate pharmacology from clinical therapeutics; the former investigates the agents which are used in the treatment of disease, the latter is concerned with their remedial powers and the conditions under which they are to be used. Hence the word " pharmaco-therapy " has come into use, and most of the newer standard textbooks combine together the consideration of pharmacology and therapeutics. Pharmacology is also related to toxicology, as many remedial and other agents are more or less poisonous when given in large doses, but it does not include the detection, tests, and the other strictly medico-legal aspects of poisoning. Pharmacology proper began as the result of the application of strictly experimental methods to physiology. The discovery History. (early in the 19th century) that plants owe their remedial and poisonous qualities to small quantities of definite active principles, such as alkaloids and neutral bodies, which can be extracted in a chemically pure condition, had also a very important effect on its development. We meet first with experiments made by investigators who perceived that observations on man and animals might lead to a better understanding of the action of drugs. In 1676 Wepfer and Conrad Brunner demonstrated on dogs the tetanizing action of nux vomica, and similar rough experiments were repeated from time to time with other substances by later investigators. In 1755 Menghini published an elaborate study of the action of camphor on a great variety of different kinds of animals. Albert von Haller (b. 17o8) sought to elucidate the action of remedies by observations on healthy men, and in 1767 William Alexander made experiments on himself with drugs, which were, however, brought to an abrupt termination by his nearly killing himself, In 1776 Daries, by observations on himself and on cats, established the mydriatic action of belladonna and other atropaceous plants. Hitherto no attempt had been made to determine what particular parts of the body were especially affected by drugs, but Fontana showed, in his great work (Florence, 1765) on the venom of the viper and on other poisons, that the general symptoms were brought about by an action on particular organs. He performed more than six thousand experiments, more than four thousand of which were on animals, and he determined the effects on the heart and other important structures. These analytical methods of research were well known to the second Monro in Edinburgh, and to his pupils, one of whom, William Alexander, wrote a thesis 'n 1790 entitled " De partibus corporis animalis quae viribus opii parent." His methods were doubtless known also to the French physiologist Magendie, who improved upon them, and who in 1So9 published a research on the Upas Tieute and other strychnine-containing plants, in which he showed that their effects were due to an action on the spinal cord. The researches of his pupil, Claude Bernard, on curare, were equally exact and logical, and have served as the model for many subsequent investigations. In consequence, from the time of Magendie pharmacology may be said to have been put on a more exact basis. By the middle of the 19th century there were many workers on the subject, and the actions of such drugs as digitalis, morphine, alcohol, and many others had been frequently and minutely investigated. About this time Buchheim, professor of materia medica in Dorpat from 1846 to 1879, founded the first pharmacological laboratory on modern lines in Europe, and he introduced a more rational classification of drugs than had hitherto been in use, arranging them in groups according to their pharmacological actions. In the herbals and older treatises on materia medica and therapeutics no explanation is usually offered of the action of medicines, and in such works as that of Cullen (1789) only a few of the more obvious actions are occasionally explained according to the current theories of physiology and pathology. In works such as Pareira's Elements of Materia Medica and Therapeutics (1842), the physiological effects of medicines are usually described, but very briefly as compared with the materia medica. At the present day most textbooks dealing with medicinal agents and treatment devote a large part of their space to pharmacology, and a corresponding change has taken place in the teaching of the subject in universities and medical schools. Since Magendie's time numerous papers dealing with pharmacological subjects have appeared in the Journal of Anatomy and Physiology, the Journal of Physiology, Virchow's Archie, and the principal medical periodicals of all countries. In 1873 the Archiv (ur experimentelle Patholbgie and Pharmakologie first appeared,in 1895 the Archives Internationales de Pharmakodynamie, and in 1909 The Journal of Pharmacology and Therapeutics '(published at Baltimore, U.S.A.), all of which are chiefly or entirely devoted to pharmacology. The methods of research are essentially those employed by physiologists, the action of substances being studied in the usual way on bacteria, leucocytes, frogs, rabbits and other animals. Not only are the general symptoms investigated, but it is necessary to carry out experiments on the nerves, muscles, circulation, secretions, &c., so as to get a more exact knowledge of the reasons of the general action. Ic is true that many of these animals react somewhat differently to drugs, both as regards each other and as regards man, but for the most part the differences are quantitative rather than qualitative. After carrying out a series of observations on animals, the drug can be assigned to its special group, and a good idea can be obtained of its possible practical value or the reverse; hence there is a saving of time and an avoidance of the necessity of testing its effects on man. The action of a drug may be called direct when it acts on any part to which it is immediately applied, or which it may reach through the blood; and indirect when one organ Digs oa is affected secondarily to another, as, for instance, in strychnine poisoning when the muscles are violently contracted as the result of the action of the alkaloid upon the spinal cord. In a few cases the action is merely physical, but most frequently it is chemical in its nature, and is exerted on the living cell, the activity of which is either stimulated or depressed. In some cases the substances actually enter into a chemical combination with the protoplasm, which may be temporary or (much less frequently) permanent; in other cases they seem simply to modify or disturb the usual chemical activity of the cells. Pro-longed or excessive stimulation invariably leads to depression or paralysis, the tissues becoming fatigued, and from this condition they may recover or they may not. When we come to consider more in detail the results of these actions we find that the various secretions of the body, such as the sweat, gastric juice, bile, milk, urine, &c., may be increased or diminished; that the heart may have its muscular or nervous apparatus stimulated or depressed; that the nerve-centres in the brain, medulla and spinal cord may be rendered more sensitive or the reverse; and that the general metabolism of the body may be altered in various ways. In addition, the fluid constituents, such as the lymph and blood, may have their composition and bulk considerably altered, while the special senses, the temperature, and, in short, every function and tissue, may be more or less affected. Some drugs given in excess are poisons to all forms of protoplasm, but when given in doses much short of the lethal they usually exhibit a distinct tendency to affect specially, and it an early period, certain organs or tissues, and hence result differences in action; others may act only on certain organs, leaving the others practically untouched. It is often possible by appropriate dosage to contrive that these special parts or organs may be affected and the rest of the body left practically intact, and it is by taking advantage of these selective actions that remedial or therapeutical effects are usually obtained. Some substances have a very wide range of action, and involve a great variety of structures, while others, such as purgatives, have a very limited sphere. The action of drugs is often modified by circumstances peculiar to the individuals or animals to whom they are ad-ministered. In man the most important of these circumstances is age, but speaking broadly this is really a question of bulk, the child being affected like the adult, but by smaller doses. There are exceptions to this, however, as children are more affected in proportion by opium and some other substances, and less by mercury and arsenic. In old age also the nervous system and the tissues generally do not react so readily as in youth. Habit, race, personal temperament, emotional conditions, disease, the time and. circumstances of administration, and other accidental causes may also modify the action in man. Some species of animals are much more susceptible to the action of certain drugs than others, a condition which depends on obvious or unknown structural or metabolic differences. In the same way some individuals show a special tendency to poisoning by doses of certain drugs which are harmless to the great majority of mankind, and hence we get unexpected or unusual results, these arising from special susceptibility on the part of certain organs. These idiosyncrasies are not confined to drugs, but are seen with a few articles of food, such as eggs and shellfish. It is well known that the habitual consumption of certain drugs, such as tobacco, Indian hemp, opium, arsenic, alcohol and many others, gradually induces a condition of tolerance to their effects, so that large doses can be taken without causing symptoms of poisoning. In all cases, however, there is a limit, and after it is reached the ordinary effects of these substances are seen. Some individuals, however, never become tolerant, and show poisonous effects on each repetition of the dose. The degree of tolerance often differs in individuals at different times and in different circumstances, and may become lost by breaking off the habit for a short time. The explanation generally given is that the nerve and other cells become accustomed to the drug, so that they cease to react, or that an antitoxin is formed which antagonizes the poison, or that the poison is rapidly destroyed in the body. Recent researches on arsenic and atropine, however, point to the leucocytes as playing an important part in the production of tolerance, as these gradually become capable of ingesting large amounts of the foreign substances, and thus render them more or less harmless to the tissues, until they are gradually excreted from the body. When the amount is too large to be dealt with by the leucocytes, poisoning seems to occur even in the most habituated. Tolerance is therefore analogous to, but not identical with, the immunity which takes place with the toxins of infectious diseases and snake poison. Certain substances, notably digitalis, lead, mercury and strychnine, exhibit what is called a cumulative action—that is to say, when small quantities have been taken over a period of time, poisoning or an excessive action suddenly ensues. The explanation in these cases is that the drug is absorbed more rapidly than it is excreted, hence there is a tendency to accumulation in the body until a point is reached when the amount becomes poisonous. Bodies which have a close resemblance in their chemical constitution exhibit a similar resemblance in their pharmacological action, and as the constitution of the substance becomes modified chemically so does its action pharmacologically. Numerous researches have demonstrated these points with regard to individual groups of substances, but hitherto it has not been possible to formulate any fixed laws regarding the relationship between chemical constitution and physiological action. When drugs are swallowed no absorption may take place from the alimentary canal; but, as a rule, they pass from there into the blood. Absorption may also take place from the skin, from the rectum, from the respiratory passages, or from wounds, and from direct injection into the subcutaneous tissue or into a blood vessel. Very rarely, as in the case of silver salts, excretion does not take place; but usually the drug is got rid of by the ordinary channels of elimination. Just as drugs act upon the tissues, so they themselves are in many cases reacted upon, and broken up or altered. While in the alimentary canal they are subjected to the action of the digestive fluids and the varied contents of the stomach and intestines, and after absorption they come under the influence of the constituents of the blood and lymph, and of the chemical action of the tissue cells. In-organic bodies, such as metals, may enter into albuminous combinations which may greatly modify their effects, and organic substances may be split up into simpler compounds by oxidation or reduction, or may be rendered more complex by synthesis. The antagonism between certain drugs has been much studied in relation to their use as antidotes in poisoning, the aim being to counteract the effects rather than to obtain a direct physiological antagonistic action. Substances which directly antagonize each other by acting on the same tissue are few innumber, but there are numerous instances in which the effects or symptoms may be obviated by acting on another tissue. Thus curare may stop strychnine convulsions by paralysing the terminations of motor nerves, and chloroform may exercise the same effect by abolishing the irritability of the spinal cord. If two poisons act on the same tissue, one stimulating and the other paralysing it, the paralysing substance removes the action of the stimulant substance, not by bringing the tissue back to its normal state, but by abolishing its excitability; hence, although life may be saved by such an action, yet it can only be so within certain limits of dosage, because the antagonism is never complete at every point. Speaking in the widest sense, every substance has an action on living protoplasm, but for convenience pharmacological substances have come to be limited to those which are used as drugs, or which have a distinct action upon the animal organism. Such substances are derived from (r) the chemical elements and their compounds; (2) plants; and (3) animals. The first class includes such substances as iodine, mercury, iron, carbon, and their various compounds, and such bodies as alcohol, chloroform and chloral, all of which are found in nature or can be prepared by ordinary chemical processes of manufacture. From plants many substances are obtained which at the present time we are unable to make in the chemical laboratory, and of the constitution or composition of which we are in many cases ignorant. Some of these, such as resins, gums, essential oils and fats, are readily obtained as natural exudations or by very simple manipulations, while others, such as the alkaloids, glucosides and vegetable acids, often require to be extracted by very complex processes. Substances obtained from animals include gland secretions, pepsin and other ferments, musk, cod-liver oil, &c., and to these may be added various antitoxins. The classification of substances having pharmacological actions presents so many difficulties that no satisfactory or universally adopted method has yet been proposed. Our knowledge presents so many gaps, and the mode of action of many remedies is so obscure and imperfectly understood, that any arrangement adopted must be more or less tentative in character. The close alliance between pharmacology, therapeutics and clinical medicine has induced many authors to treat the subject from a clinical point of view, while its relationships to chemistry and physiology have been utilized to elaborate a chemical and physiological classification respectively as the basis for systematic description. Certain writers in despair have adopted an alphabetical arrangement of the subject, while others have divided it up into inorganic, vegetable and animal substances. These last-mentioned methods are far behind our present state of knowledge, and need not be discussed here. The objection to a strictly chemical classification is, that while many sub-stances closely allied chemically have a somewhat similar action in certain respects, yet in others they differ very widely—a striking example of which is given in the case of sodium and potassium. A physiological classification according to an action on the brain, heart, kidney or other important organ becomes still more bewildering, as many substances produce the same effects by different agencies, as, for instance, the kidneys may be acted upon directly or through the circulation, while the heart may be affected either through its muscular substance or its nervous apparatus. A clinical or therapeutical classification into such divisions as anaesthetics, expectorants, bitters, and so on, according to their practical applications, also leads to difficulties, as many drugs are employed for numerous purposes. The ideal method of grouping pharmacological substances would be in reference to their chemical action on living protoplasm, but as yet our knowledge is too scanty for this. At the present time the method adopted by Buchheim, or some modification of it, is the most scientific. As the result of painstaking investigations he grouped together all those sub-stances having similar actions, giving to each group the name of its best-known or most thoroughly investigated member. Once the groups were more or less fixed any new substance could, when Classification. its action was determined, be referred to its own group, and thus be placed or classified. As few substances are absolutely identical in action, but only broadly similar, it is often difficult to divide sharply one group from another. In a resume it is manifestly impossible to pass in review every pharmacological substance, and we shall therefore confine ourselves to those groups which are of practical importance. Many individual drugs are described under their own headings.
End of Article: PHARMACOLOGY
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