Ralph Stockman and Harriette Lombard Hennessy

“ 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. ”

“ 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. ”

“ 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. ”

“ 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. ”

“ 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. ”

“ 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. ”

“ 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. ”

“ 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. ”

“ 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. ”

“ In specific germ diseases a similar antitoxin forms, and in cases which recover it counteracts the toxin, while the germs are destroyed by the tissues. Antitoxins can be prepared by immunizing a large animal, such as a horse, by injecting gradually increasing doses of specific toxins into its subcutaneous tissue. In due time the horse is bled, the serum is filtered free of blood corpuscles, and then constitutes the antitoxic serum, which can be standardized to a certain potency. ”

“ 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. ”

“ Group XXVI. Antitoxins.—These are substances which antagonize the toxins formed in the body by pathogenic organisms, the toxins of snake venom and other animal poisons, and vegetable toxins such as abrin, ricin, &c. A healthy person can be rendered insusceptible by gradually accustoming him to increasing doses of these poisons, and this immunity is due to antitoxins which are found in the blood-serum and which are products of the blood cells. The nature of these antitoxic substances is not definitely known, but they combine with and destroy the poisons. ”

“ Once the groups were more or less fixed any new substance could, when 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 résumé 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. ”

“ Potassium and lithium have a depressing action upon the nervous system, ammonium salts have a stimulating action, while sodium practically speaking is indifferent. Calcium and magnesium have actions somewhat similar to that of potassium. Most of these substances are normal constituents of the body, and indispensable for healthy existence. They are contained in sufficient amount in our ordinary dietary to supply the needs of the organism. ”

“ 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. ”

“ All of them injected into the blood in large doses act as muscle and nerve poisons, and during their excretion by the kidney usually irritate it severely, but only a few are absorbed in sufficient amount to produce similar effects when given by the mouth. When iron is injected directly into a vein it depresses the heart's action, the blood pressure and the nervous system, and during its excretion greatly irritates the bowel and the kidneys. ”

“ In morphine, on the higher animals at least, the narcotic action is very marked, the tetanizing action slightly so; while in thebaine there is little narcotic effect, but a tetanizing action like that of strychnine. Morphine exercises its effects chiefly upon the cerebrum and the medulla oblongata in man. It has in addition a markedly depressing action upon the respiratory centre, it lessens all the secretions except the sweat, and diminishes bowel peristalsis and the size of the pupil. Men are much more affected by it than birds, rabbits, dogs and most other 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. ”

“ 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 convenient to divide drugs and other substances used in medicine into groups according to the part of the system on which they chiefly act, though, as stated above, many drugs act in more than one manner and could come under several groups. ”

“ 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. ”

“ 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. ”

“ After absorption their action, speaking generally, is exerted on the brain and spinal cord, and is at first slightly stimulant and afterwards depressing, even to the causing of sleepiness and stupor. Locally applied they depress the terminations of sensory nerves, and may thereby lessen pain. On the heart and circulation the effects are stimulant unless large doses are given, when the pulse becomes slow and blood-pressure much lessened. During excretion they irritate the kidneys and the sweat-glands, and thereby increase the excretion of urine and of sweat. ”

“ 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. ”

“ Group XXIII. Cyanogen.—This includes compounds of cyanogen such as hydrocyanic (prussic) acid, cyanides of potassium, sodium, &c., cherry-laurel water, amygdalin, bitter almonds and other chemical and vegetable substances which readily yield hydrocyanic acid. Hydrocyanic acid is a general protoplasmic poison, all the lower organisms being very susceptible to its action, while in the higher animals it speedily depresses or paralyses all forms of nerve tissue. It enters into combination with haemoglobin, forming a bright scarlet compound and interfering with respiration. ”

“ Arsenic and antimony do not form combinations with albumen, but they both greatly depress the central nervous system and circulation; and, if their action be long continued in large doses, they cause fatty degeneration of the viscera and disappearance of glycogen from the liver. Locally they are both very irritating, and antimony has a special tendency to cause vomiting. ”

“ 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. ”

“ 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 word Sudorific (Lat. sudor, sweat) is applied to them when they act very powerfully. Anhidrotics or Antihidrotics (Gr. ἱδρώς, sweat) diminish the secretion of sweat. Emollients (Lat. mollis, soft) are substances which soften and protect the parts. Demulcents (Lat. demulcere, soften) , soothe the skin or mucous membrane.
IX. Drugs acting on metabolism. Alteratives are drugs which alter the course of a disease, the mode of action being unknown. Tonics are drugs which increase the muscular tone of the body by acting either on the stomach, heart, spinal cord, &c. ”

“ At the same time the non-striped muscles slightly lose their tonicity, and when very large doses are given the haemoglobin of the blood becomes converted into the chocolate-coloured methaemoglobin. The volatile members of the group act much more rapidly and more transiently than the others.
Group XIX. Alkaloids.—This embraces a very large number of important pharmacological substances, which differ a good deal in the details of their action, but they all act upon muscle and nerve tissue. Some of them affect only certain portions of the nervous system, others have a much wider range of action ”

“ Their insoluble compounds are much less active locally than the soluble, and in many cases are only effective to the extent to which they are dissolved by the secretions. Some metals are only absorbed from the alimentary canal to such a very limited amount that they exert no general action, while others readily pass into the blood and give rise to more or less marked effects. ”