PART II. PHARMACOLOGY AND THERAPEUTICS

DEFINITIONS

Pharmacology. The study of Materia Medica and Therapeutics, including the origin, history, properties and uses of drugs and medicines. It includes:

Pharmacognosy.-The study of the physical and chemical characters of drugs, and the art of identifying and selecting them in accordance with those characters.

Pharmaco-dynamics.-The study of the action of remedial agents upon the organism of man or of the lower animals in a state of health.

Pharmacology. This term, by general acceptance, is now limited to the study of the changes produced in living tissues by the administration of drugs.

Therapeutics. The application of remedial agents in the treatment of disease. It includes:

General Therapeutics.-The application of curative agents other than drugs and medicines. E.g., diet, climate, baths, venesection.

Rational Therapeutics.-Therapeutics based upon Pharmaco-dynamics. E.g., the use of digitalis for mitral disease. Empirical Therapeutics.-Therapeutics based upon clinical

experiences only. E.g., the use of colchicum for gout. Therapeutics. This term is often used as the name of the

branch of study which deals with Therapeutics. Therapodynamics has been used in the same sense, but is faulty. Experimental Therapeutics has been suggested, but is not comprehensive.

With the exception of such incidental allusion to other agents as occasion may require, in this work will be considered only that part of Therapeutics which is concerned with the official drugs.

Toxicology. The study of the nature, effects and detection of poisons, substances which, introduced into the body inopportunely or in excessive amounts, are capable of destroying life. Courses of study and treatises upon Toxicology are, for convenience, commonly made to include the subject of antidotes and treatment, although this is, strictly speaking, a part of Therapeutics.

MODES OF ADMINISTRATION OF DRUGS

(a) Into the blood-vessels by transfusion.-This method, while frequently employed in experimental research upon animals, is resorted to only under extraordinary circumstances in the human subject. Normal salt solution (see p. 64) is most commonly used after profuse hæmorrhage and in various forms of toxæmia. Among the objections to intra-venous injection are the difficulty of finding the collapsed veins and the danger, in puncturing a vein, of wounding the opposite wall of the vessel. Again, phlebitis, thrombosis or embolism may possibly be caused. As a rule, hypodermatoclysis (see below) is therefore preferable; but if the symptoms are very urgent, the tissues oedematous from dropsy, or the circulation too feeble to insure absorption, transfusion should be practised without hesitation. It is the most prompt method in instances of shock, and it has even been proposed, with a view to the prevention of shock, that the free use of intravascular hot saline infusion, injected while the patient is still under the anæsthetic, should be adopted as a matter of routine, after all severe operations, This, however, should not be practised before the operation, unless under exceptional circumstances, for the increased arterial tension would likely cause increased hemorrhage during operative procedures. Intra-arterial, as well as intravenous, infusion is sometimes practised.

(b) Into the subcutaneous tissues (1) by hypodermatic injection.—A sterilized syringe, fitted with an aseptic hollow silver needle, should be used for the injection. A part of the body is selected (commonly the external surface of the fore-arm), where the skin is lax. The skin is raised between the thumb and forefinger of one hand, and with the other hand the needle is inserted under it for about an inch, care being taken to avoid muscles and veins. The syringe is slowly emptied, then withdrawn, and slight pressure is made for a moment over the puncture. The bulk of an injection, as a rule, should be about 0.30 mil (5 m). In order that abscesses may not result, the fluid should be aseptic, non-irritating, and free from solid particles. If not freshly prepared, it is advisable that a little boric acid should be added to it. The most convenient and satisfactory plan is to keep the drugs for hypodermatic use in the form of soluble tablets, and to dissolve one in the required quantity of water at the time the injection is called for. The advantage of this method is that it secures a much more rapid absorption than when the drug is given by the mouth, and it is ordinarily employed when the promptest possible effects are desired. (2) By hypodermatoclysis. By the bedside is placed an aseptic jar containing sterilized warm normal salt saline solution, to which air gains access only by means of a glass tube filled with sterilized cotton. From the lower part of this vessel extends a tube fitted to a trocar, which should be made

aseptic. The skin over the part chosen for the infusion (preferably the iliolumbar region—the space between the highest part of the crest of the ilium and the lower border of the ribs) having also been rendered aseptic, the trocar is thrust into the subcutaneous tissue, and the solution allowed to flow at a rate not exceeding 4 mils (1 fl. dr.) to each 500 gm. (1 lb.) of body weight in each fifteen minutes. The necessary pressure is obtained by the elevation of the container, and absorption of the fluid is aided by gentle massage. This procedure has been employed with advantage to replace the fluid lost from the body through hæmorrhage or through excessive purging, as in cholera; also to wash from the body various impurities circulating in the blood and lymph and to flush the kidneys. It has likewise proved of service in instances of surgical shock and of threatened death from anæsthetics. Hypodermatoclysis, however, is slower than other methods in shock, on account of the poor general circulation, and is also open to the objections that the introduction of a proper amount of fluid (12 to 2 liters-3 to 4 pt.) may require a number of punctures, which subsequently, cause pain and that such a bulk of fluid causes tension of the tissues that, at the temperature best adapted to prevent shock (48.8°C.—120°F.), sloughing may possibly result.

(c) Into serous cavities by injection. This method is employed only to secure certain local effects in such cavities themselves, as to wash out antiseptically the pleura after it has been opened or to cause adhesive inflammation in the tunica vaginalis by the injection of irritants. It has been proposed to introduce hot saline infusion directly into the abdominal cavity by means of a hollow needle for the purpose of combating shock. Also when this cavity is opened, as in cœliotomy, it may be flushed with hot saline infusion for the same purpose.

(d) Into mucous cavities.-The most common way of administering drugs is naturally by the mouth, so that they may be absorbed from the mucous membrane of the stomach or intestine. Circumstances conducive to rapidity of absorption are an empty stomach and a ready solubility of the drug in the gastrointestinal secretions. When it is intended that the drug shall act only in the intestine, pills, made purposely insoluble in the gastric fluids, are administered. It is probable that some drugs are excreted in the bile by the liver, and so never reach the general circulation. Care should be taken to prescribe drugs in so palatable a form as is possible and so combined as not to cause irritation.

It is sometimes advisable to administer drugs by the rectum, suppositories being employed for solids, and enemata or clysters for liquids. The fact must not be lost sight of that they are not then so readily dissolved or absorbed as when given by the mouth.

Enteroclysis is also employed in shock and allied conditions, and not infrequently in association with intravascular infusion. This consists of the irrigation of the intestine, commonly with a saline solution, and it is most satisfactorily practised by means of a double-current tube. With this tube the fluid does not cool, since fresh hot fluid is continually entering to replace the cooler which passes out. The method is of service in warding off shock, and has been resorted to for this purpose after surgical operations.

Drugs are also used for local effects, as by the urethra or vagina (injections, bougies, pessaries), or by the respiratory passage (inhalations, cigarettes, sprays or nebulæ for inhalations; insufflations for blowing into the nose, throat

and larynx; pigmenta, gargarismata, trochisci, for local effect on the mouth and pharynx; nasal douches for the nose). Sprays are given by means of an atomizer. Volatile drugs, as ether, chloroform and amyl nitrite, are usually inhaled for their general effect.

(e) By the skin.-Certain drugs may be absorbed from the skin if mixed with some fatty substance, especially hydrous wool-fat. In this way mercury may be absorbed by being rubbed in (inunction). Some may also be absorbed from the skin when they are volatilized. Thus mercury is introduced into the system by fumigation. The chief purpose, however, for which drugs are applied to the skin, is to secure their local effects, and for this they are employed in ointments, cerates, plasters, etc. To the eye and ear they are applied in washes.

POSOLOGY

The study of doses is called Posology. In determining the dose the following points deserve attention:

1. Age. The adult dose is that for a person between twenty and sixty years old, but for women the dose should be somewhat smaller than for men.

For children under twelve, Cowling's rule-divide age at next birthday by twenty-four-is the simplest and is generally of sufficient exactness. It must be borne in mind, however, that in the use of certain drugs the dose may be relatively larger than for adults, while in that of others they must be relatively smaller. Thus, children bear iron, alcohol, arsenic, belladonna, hydrated chloral, rhubarb, and cod liver oil remarkably well, but can take only very small doses of opium and its preparations.

For persons above sixty the dose should be slightly diminished as the age ad

vances.

2. Weight. In pharmacological experiments upon animals, in which it is customary to express the dose as a proportion of the weight, it has been found that if the same amount of poison be distributed through the tissues of a large individual as of a small one, less is contained in any given organ of the former, and less effect is therefore observed. This no doubt holds true as regards man also; so that somewhat larger doses of drugs should be prescribed for very large persons than for those of ordinary stature, while in the case of persons of unusually small size the dose should be proportionately diminished.

3. Habit. A person who takes a drug continuously usually becomes less and less susceptible to its influence. Thus, an opium habitué after a time finds it necessary to use enormous doses of the drug in order to secure the desired effect. With strychnine and some other similar drugs, however, the susceptibility increases, instead of diminishing, and among purgatives cascara sagrada appears to be an exception as regards habit.

4. Idiosyncrasy.-Many individual differences in the matter of susceptibility are met with. These idiosyncrasies, which have frequently been observed with almost all commonly used drugs, consist of extraordinary sensitiveness, or of tolerance, or of entirely atypical actions.

5. Time of Administration.—Drugs must be given with careful attention to the time which they require to produce their appropriate effects. Thus, some hypnotics have to be administered several hours before it is desired that the