tion. It causes an increased elimination of phosphates, but not of the urates, in the urine.

THERAPEUTICS OF DESICCA1ED HYPOPHYSIS

Since the pituitary body is thought to be hypersecreting in giantism and to be abnormal in acromegaly, this remedy is contraindicated in the former and of use in the latter only when there is a deficiency of the normal internal secretion. It has sometimes relieved the continuous and severe headaches of acromegaly. It would appear that it might be useful, given intravenously, in shock and possibly hypodermatically in hæmoptysis and in paralysis of the intestinal musculature. It has had, however, an extensive employment in obstetrical practice, notably to relieve uterine inertia, for which it is given hypodermatically. The same precautions apply to its use for this purpose as for ergot (see p. 797). The remedy has been employed in epilepsy with no beneficial results.

DIVISION XV.-DRUGS ACTING ON METABOLISM

The action on metabolism of many drugs has already been referred to. As our knowledge of the normal metabolism of the body is as yet limited, the statements made concerning drugs now to be considered are chiefly based upon experience. In this place attention should be called to two names in common use, viz.: alterative and tonic.

Alterative. This is a vague term which cannot be accurately defined. It is often employed to cloak our ignorance of the exact action of a drug, but in general it is applied to agents which appear to modify the nutritive processes and thereby cure or alleviate many diseases of chronic type. They favorably alter morbid processes, as in the use of mercury in syphilis, but the modus operandi, of which almost nothing is definitely known, probably varies greatly in different drugs.

Tonic. A tonic has been stated to be a drug which so influences nutrition as to increase the reconstruction or upbuilding of the tissue or tissues concerned. While this definition is not entirely adequate, it is perhaps as satisfactory as any that can be given. Many of the bitters are also classed as tonics.

This division also includes some substances used as foods; for instance cod liver oil.

IODINE AND THE IODIDES

For the Preparations of Iodine and the Iodides see p. 36.

ACTION OF IODINE AND THE IODIDES

External.-Iodine is an irritant, disinfectant, and parasiticide. The first effect of its application to the skin is a yellowish discoloration, which is removable by alkalies or sodium thiosulphate. It acts more slowly than most other irritants, but on account of its volatility and because it precipitates proteids and enters into easily dissociated compounds with them, its action is both penetrating and prolonged. It produces a sensation of heat, accompanied by local hyperemia and sometimes by more or less oedematous swelling. Some exudation of leucocytes takes place, and the strong absorbent action of iodine has been attributed to this. Unless used in very concentrated solution or in the solid form, which may cause vesication or even corrosion, its irritant action is comparatively mild. By repeated applications, however, it is possible to secure very pronounced counter-irritation without the production of a deep destruction of tissue. The superficial cuticle is usually destroyed, and the skin afterwards exfoliates. As a result of its local application, small quantities are absorbed. The subcutaneous injection of solutions of it causes intense pain and irritation. The inhalation of the vapor of iodine also gives rise to very considerable irritation; exciting sneezing, coughing and some dyspnoea, with smarting, swelling and increased secretion from the nasal mucous membrane, conjunctiva, throat and lower respiratory passages.

The iodides in watery solution are not absorbed from the unbroken skin, but are rapidly absorbed from mucous membranes.

Internal.-Iodine naturally exerts its local irritant action on the gastro-intestinal tract, causing pain and vomiting, and sometimes purging. The drug may be recognized in the vomited matter and in the stools. In very small doses the slight irritation produced on the mucous membrane of the stomach may improve the appetite and digestion, and be followed by a sedative action. In excessive doses it produces marked irritation of the œsophagus and severe gastroenteritis, but death is rarely caused by it. In fatal poisoning the

mucous membrane of the stomach and intestine has been found tumefied and exfoliated. The irritation of the alimentary canal may also prove fatal by inducing collapse and failure of the heart and respiration. In animals, fatty degeneration of the heart, liver and kidneys has been found. Iodine, in the form of iodides and, it may be, in a combination with proteids, is rapidly absorbed by the mucous membranes generally. Its chief effects after absorption may be due to its action on the thyroid gland. The symptoms produced by its continued administration, such as acceleration of the pulse and certain nervous phenomena, are much the same as those caused by large amounts of thyroid extract, and are thought to be probably due to the excessive production of the organic compound, iodothyrin which exists normally in the thyroid gland, and the administration of iodine may lead to an increase in its formation. Iodine is excreted, in the form of iodides, chiefly by the kidneys, but also to some extent in the saliva, perspiration, milk and bronchial secretion. The effects produced by the iodides appear to vary considerably, not only in different individuals, but also in the same individual at different times, and their mode of action is still a matter of great uncertainty. When administered internally the iodides are absorbed unchanged by the stomach and intestine, and it is found that they make their appearance in the secretions within a very short time, being excreted mainly in the urine, in which they are found as salts; also to some extent in the saliva and in various other secretions, as those of the nasal mucous membrane and sebaceous glands, and in the tears, sweat and milk. By the stomach small amounts are eliminated as hydriodic acid and sometimes as free iodine. No free iodine, however, has been found in the saliva, sweat or nasal secretion. There seems to be no question that some of the iodide undergoes decomposition in the body, because formerly much the same therapeutic effects were produced by the internal administration of iodine which are now obtained with the iodides. On the other hand, the secretion of milk is diminished. Infants have been known to suffer with iodism from being nursed by persons under iodide treatment.

The iodides are supposed to lessen the viscosity of the blood, increase the fluidity of the bronchial mucus, and in pulmonary tuberculosis to interfere with connective-tissue formation.

Iodism. This is induced by all the iodides, and the basic ion does not appear to be concerned in the effect. Owing to the fact that

iodine is more readily freed from it, ammonium iodide is said to be more liable than the others to cause iodism. The symptoms may be divided into two groups. (1) Catarrh of the respiratory passage is very common and commences in the nasal mucous membrane, exciting a profuse watery discharge, and extends both upward and downward. Accordingly there is conjunctivitis, and severe headache may result from the invasion of the frontal sinuses. At the same time there is much swelling and irritation about the fauces, the tonsils are liable to become inflamed, and laryngitis or bronchitis may result. Edema of the larynx, which unless promptly relieved may prove fatal, occasionally occurs. The bronchial secretion is increased by massive doses, even pulmonary edema may supervene. At times there is a febrile reaction, rapid pulse and respiration and great prostration which suggests an acute infectious pneumonia, but a careful examination of sputum and urine and an analysis of pulmonary signs establishes the diagnosis. Usually somewhat later, an eruption may appear upon the skin. This most commonly consists of erythematous patches, but instead there may be papules, which sometimes become pustular and, more rarely, as other forms of cutaneous disease. Edema of the face is met with in some instances, and very rarely there is albuminuria. Nervous troubles, neuralgia, singing in the ears, convulsive movements, disturbed cerebration even progressing to delirium, and rarely atrophy of the mamme and testes may be noticed. (2) Iodic cachexia, which is characterized by rapid emaciation, severe cardiac palpitation, and ravenous appetite, occasionally occurs as a late phenomenon. The local manifestations of iodism can sometimes be prevented by the administration of alkalies, and hence it is thought that the variation of their extent in different persons, or in the same person at different times, may perhaps be explained by a different degree of acidity. Children appear to be less subject to iodism than adults. A tolerance may be established, and not infrequently the symptoms disappear while the administration is still being maintained. Although the manifestations may be very severe, a cessation begins soon after the treatment is discontinued, and the chewing of pyrethrum will hasten the elimination of iodine in the chronic forms. However, sometimes the symptoms may not disappear for a considerable time.

THERAPEUTICS OF IODINE AND THE IODIDES

External.-Iodine preparations are much relied upon as irritants, counter-irritants and resolvents. The tincture is one of the most popular of all external applications, while mild in its action, as are also the ointment and compound solution, a sufficient effect may usually be secured by the repetition of its use. The conditions for which these preparations are used are numerous: chronic inflammation of joints, periostitis, enlarged glands, buboes, abscesses, chilblains, pleurisy, and inflammation or retraction of the gums. The tincture, may be painted over an area of tinea or ringworm, and is usually efficacious in pityriasis versicolor. It is sometimes of service in lupus also, and is curative in lentigo and chloasma. Two preparations of iodine are frequently employed in the treatment of diseases of women, namely: Churchill's tincture: iodine, 5; potassium iodide, 1; water, 8; alcohol, 24; and Battey's fluid; iodine, 2; pure phenol, 1. Fatal systemic poisoning has also been known to result from the injection of large quantities of iodine into cysts. The same objections hold true as regards the parenchymatous injections of the tincture in hypertrophied tonsil, goiter, glandular tumors, etc. In some instances of spina bifida a successful result may be obtained by the injection of Morton's fluid, which consists of iodine, 1; potassium iodide, 3; glycerin, 48.

Internal.-Goiter of the colloidal variety may not infrequently be successfully treated by the internal and external use of iodine. For the internal treatment the best mode of administration is to give the tincture in small doses with potassium iodide, freely diluted. Dried thyroids, however, are much more efficient. The compound solution has a good reputation as a remedy in scrofulous affections of the skin and of the lymphatic glands, especially in syphilitic children, and is stated to be useful in some old syphilitic skin diseases attended by thickening and scaling. Judiciously employed, iodine preparations are of some value as inhalations particularly with oil of turpentine, and as adjuvant to other methods of treatment, in laryngeal and pulmonary tuberculosis.

The iodides were largely substituted for iodine in therapeutics for the reason that they are less irritating to the gastro-intestinal tract. Potassium iodide is the one in most general use. The most conspicuous of their applications is in the treatment of syphilis, in which their very great value has long been established. It is in the