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 (early in the 19th century) that plants owe their remedial and History.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. 1708) 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 in 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 1809 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 Archiv, and the principal medical periodicals of all countries. In 1873 the Archiv für experimentelle Pathologie 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. It 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 itAction of Drugs. is immediately applied, or which it may reach through the blood; and indirect when one organ 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. Prolonged 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 at 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 administered. 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
