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. Inorganic 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 in number, 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 (1) 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 Classification. 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 substances 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 substances 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
