Ethylhydrocupreine has actions and uses similar to those of quinine, but because of a specific bactericidal effect upon all forms of the pneumococcus it has come into use in the treatment of pneumonia. In vitro a solution of as little as 1: 10,000,000 may be inhibitory to the pneumococcus, and 1: 500,000 is bactericidal. In serum this activity is reduced to one-fifth or one-tenth. In lobar pneumonia the method of Moore and Chesney at the Rockefeller Institute is to administer daily by mouth a beginning dose of 7 1/2 grains (0.5 gm.) of the hydrochloride, followed by 2 1/2 grains (0.15 gm.) every three hours till a total of 22 1/2 grains (1.5 gm.) have been given for the day. It is the consensus of opinionthat this amount should not be exceeded. It represents about 0.024 gm. per kilo per twenty-four hours. They found that with this dosage "a specific pneumococcidal action appears in the blood within a few hours and can be maintained more or less constant for several days." It has been noted that pneumococci not destroyed early may rapidly acquire complete resistance to the drug. The "pure alkaloid" may be given intramuscularly in solution in oil.

Locally, in pneumococcus eye infections, as in ulcus cornea serpens, which is highly destructive to the sight, the drug has a decidedly curative effect in twenty-four to forty-eight hours. It is used in 1 per cent. solution applied for half a minute every hour following cleansing with boric acid solution. There is a primary pain followed soon by comparative analgesia.

Toxicology

The poisonous symptoms are those of quinine, but amaurosis has occurred in so many instances from therapeutic doses that this is especially to be watched for. Adler reports one case after only two 4-grain (0.25 gm.) doses. At the Rockefeller Institute, after four 7 1/2-grain (0.5 gm.) doses at eight-hour intervals, a patient was unable to distinguish light for six days, and at the end of five months, as reported by Weeks, had slightly reduced fields of vision with color vision very indefinite, many of the retinal arteries narrowed and their walls irregularly thickened, and optic disks and retinae pale.

Antirheumatic Antipyretics Salicylic Acid

Salicylic acid (acidum salicylicum, C6H4OH,Cooh) is chemically orthosalicylic acid, and is an organic acid which exists naturally in combination in the volatile oils of birch and wintergreen. It is generally prepared synthetically from phenol. The reputed superiority of salicylate made from the natural oils is not substantiated by the experimental work of Eggleston and others. Engelhardt found phenol present in a number of samples of both the artificial and the natural oil. Salicylic acid has a biting taste, and is soluble in 460 parts of water and in 2.7 parts of alcohol. The salts of the alkali metals are readily soluble in water.

Preparations And Doses

Salicylic acid; dose, 7 1/2 grains (0.5 gm.); sodium salicylate and strontium salicylate; dose, 15 grains (1 gm.).

The salicylates of ammonium, quinine, bismuth, and physos-tigmine are official, but in the available dosage do not give a salicylic action.

Microorganisms

In a solution of 1 in 500 salicylic acid is antiseptic, and will inhibit or retard the growth of bacteria, yeasts, and molds; and as in these dilutions it is not corrosive to living tissue, or poisonous to human beings, except in large amounts, it is safe for use in and about the body. But because it is not readily soluble in water, its use as an antiseptic is confined largely to the preservation of foods, the treatment of parasitic skin diseases, and the preparation of a mild antiseptic wash known as "boro-sal." Leach says that quantities sufficient to preserve milk affect the taste of the milk. It belongs to the phenol group of antiseptics, but does not possess the destructive properties and the penetrating power of carbolic acid, and it retains its antiseptic power in fatty and alcoholic preparations.

The alkaline salicylates, though less antiseptic than the acid itself, are freely soluble in water and are used in the preservation of foods. The Hygienic Laboratory recommends a 1 per cent. solution of sodium salicylate as a fly-poison.

Enzymes

The action of these is inhibited or retarded, a 1 per cent. solution being sufficient to stop the ptyalin action on starch. Pepsin is somewhat lessened in its activity, and probably also the other digestive ferments. Very weak solutions seem to favor ferment action.

Local Action

Besides its antiseptic action, it tends to stop local sweating, as of the hands or feet; to soften and facilitate the removal of accumulations of horny epithelium, as of corns or warts, without causing inflammatory changes in the healthy underlying tissues; and in chronic skin diseases, such as eczema, to promote the growth of healthy skin. It is irritant to mucous membranes.

Methyl salicylate and the volatile oils of wintergreen and birch are counterirritants.

Alimentary Tract

Its taste is biting, and it is locally irritant. Its tendency is to retard gastric fermentation and the action of the digestive ferments. Whether or not it can reduce intestinal putrefaction is a question, for while Strasburger claims that the number of bacteria in the feces is distinctly reduced, other observers have been unable to detect any diminution in the indican of the urine. (See Salol.) By large quantities the production of bile is increased, but the use of the drug for this purpose in therapeutics has not been shown to have any value.

The volatile oil salicylates have a typical carminative action, and in moderate dosage are well borne; the other salicylates are irritant and frequently produce nausea and even vomiting.

Absorption is rapid from the stomach and duodenum.

Systemically, it resembles acetanilid in its analgesic properties, but is much milder. It increases metabolism, yet is antipyretic by dilating the vessels and promoting sweating, and so increasing heat loss. Whether there is an effect on the heat-regulating center or not is not proved. Mandel found that it would prevent a rise of temperature from xanthine.