External

Salicin and salicylic acid are antiseptics rather more powerful than carbolic acid. They are stimulant and mildly irritant to the skin. Locally applied, they check sweating. The salts of salicylic acid are not strongly antiseptic. Salicylic acid softens and removes epithelium.

Internal

Alimentary tract. - When inhaled or applied to the throat, salicylic acid is irritating, causing sneezing and cough. In the stomach also it is irritant, giving rise to pain, nausea, and vomiting unless well diluted. The sodium and lithium salts and salicin are much less irritating. The gluco-side, salicin, is in the bowel converted into glucose and saligenin (C7H8O2), and this is further decomposed into salicylic acid, salicyluric acid (Hc9h8no4), and salicylous acid (Hc7h6o2). Liver. - The bile is rendered much less viscid; in fact salicylic acid is probably the strongest cholagogue known. Sodium salicylate, like sodium benzoate, increases both the amount and the solids of the bile.

Blood. - Salicylic acid, whether taken directly or formed in the bowel from the decomposition of salicin, is rapidly absorbed in spite of its insolubility, and therefore it is probably taken up as sodium salicylate; at least, this is the form in which it circulates in the blood, and consequently the following description will apply whether salicin, salicylic acid, or sodium salicylate has been taken. It has been thought also to exist in the blood as an albuminate, but of this there is no evidence, nor for the theory that when the sodium salicylate meets with carbon dioxide, salicylic acid is set free. Some of the salicylic acid of the sodium salt unites with glycocoll, forming salicyluric acid, which appears in the urine. Thus: Hc7h5o3+C2H5No2 (glycocoll)=Hc9 H8No4 (salicyluric acid) +H2O. It will be noticed that this change is precisely analogous to the conversion of benzoic into hippuric acid by its union with glycocoll. Binz has suggested that the specific beneficial effect of the salicylates in acute rheumatism is due to setting free of salicylic acid in the inflamed part by the carbon dioxide in it. The beneficial effect of this acid is also seen in a disease of bees known as foul brood, and due to certain schizophytes, for feeding the creatures on syrup containing salicylic acid cures them.

Heart. - Salicin and salicylic acid are often stated to depress the force of the heart and cause a fall of blood-pressure. Careful comparison shows that salicin is not nearly so depressant as the acid - in fact, it is probable that it has not this action at all, unless given in toxic doses. Further, natural salicylic acid is not so depressant as the artificial variety. For example, Char-teris found that 30 gr. 2. gm. of salicin, or 10 gr. .60 gm. of natural salicylic acid, or 32 gr. 2.12 gm. of natural sodium salicylate had no injurious effect on a rabbit, but that much smaller doses than these of the artificial acid or its salt killed the animal. The artificial variety was found to contain orthocreo-sotic and paracreosotic acids, and these are powerful cardiac depressants. Thus it seems probable that the depressing effects commonly ascribed to salicylic acid are really due to the impurities occasionally present in the artificial form.

Respiration. - Moderate doses have very little effect on respiration. Toxic doses strongly depress it.

Temperature. - In medicinal doses salicin and salicylic acid have no influence on the temperature of man, in toxic doses they slightly lower it; but they readily depress a febrile temperature, and are therefore called antipyretics. They cause a slight increase of perspiration, but this is not sufficient to explain the fall.

Salicylic acid and salicin are antiperiodic.

Nervous system. - We know little of the effect of salicylic acid on the individual parts of the nervous system. The clinical symptoms known as salicylism will be described presently.

Kidney. - Salicylic acid escapes chiefly through the kidneys. It, to a much less extent, also leaves the body by the sweat, the saliva, the bronchial secretions, and the faeces. It appears in the urine very soon after its ingestion (in from 10 to 30 minutes), but the elimination goes on slowly. It is excreted as salicyluric acid and sodium salicylate, which is split up by the phosphoric acid in the urine, yielding salicylic acid. The dark greenish color of the urine sometimes seen is due to small quantities of either indican or pyrocatechin. Occasionally salicylic acid causes haematuria, due to congestion of the kidneys. Large doses increase the nitrogenous elimination, the uric acid being especially increased. The sulphur also is increased. It renders the urine aseptic, and the salicyluric acid in that fluid will reduce Fehling's Solution. The urine of patients taking it gives a purple color with ferric chloride.

Salicylism. - In some persons to whom salicylic acid or its salt is given a train of symptoms is produced to which the above name has been applied. They are very like those produced by quinine. It is probable that the cause of at least some of them is the impurities existing in artificial salicylic acid, but it is stated that the natural acid may rarely give rise to them. Orthocreo-sotic acid is certainly toxic, metacreosotic acid has no action, and it is doubtful whether paracreosotic acid is toxic. The commonest is deafness, which is often accompanied by ringing in the ears; these symptoms may be relieved by the administration of a small amount of alcoholic stimulant fifteen minutes before each dose. Headache is also very frequent. The administration of the drug is usually stopped when these symptoms show themselves; but if it is continued the patient becomes violently delirious, there is nausea and vomiting, the face is flushed, and the other symptoms increase in severity. The pulse falls in both frequency and force, it becomes irregular, epistaxis is common, and haemorrhages from other parts of the body have been recorded, such as haematuria and retinal haemorrhages. Albuminuria without haematuria has been observed. One of the rarest symptoms is erythema or urticaria. Very large doses may cause the breathing to become weaker, and death may take place either from cessation of the heart or the respiratory movements.