Untoward Effects

From idiosyncrasy, antipyrine not infrequently has produced a scarlatiniform rash with edema of the face and fever; or urticaria, or a vesicular, bullous, or eczematous eruption. The chief untoward effects from acetanilid and acet-phenetidin are cyanosis and collapse; a petechial eruption has been noted from acet-phenetidin.

Toxicology

Acute poisoning shows in affections of the alimentary tract and nervous system. There are: burning and swelling of the whole alimentary tract, with stomatitis, nausea, vomiting, gastritis, perhaps enteritis, mental dulness, tremors, convulsions (cerebral), and coma. Death results from failure of the respiration. With acetanilid and acet-phenetidin cyanosis and collapse may occur early. Toxic effects in a girl of twenty have been reported from 10 grains of antipyrine. The treatment is by demulcents for the gastro-intestinal tract, and, if necessary, measures to combat collapse.

A common result of poisoning by acetanilid and acet-phenetidin is a marked cyanosis, with which there may be more or less dyspnea, rapid heart, and even collapse. There is some destruction of red cells, and some formation of methemoglobin by reduction, but the cyanosis seems to be out of proportion to the methemoglobin formation and out of proportion to the patient's symptoms. There is probably some other reduction compound present in the blood, and Bachmann says that it is aniline. Ten grains of acetanilid taken internally have produced cyanosis, also acetanilid powder applied to ulcer of the leg. The author saw one case from a phenacetin powder, probably 10 grains, given by a pharmacist for headache.

Chronic Poisoning

Many nervous patients have the habit of taking these drugs. The habit does not have a hold upon them, like the morphine habit, and can be broken without any systemic rebellion; yet it is a difficult habit to overcome, for the symptoms are never startling, and the friends, not perceiving any harm from the drug, note the apparent suffering when the drug is stopped (headache, irritability, restlessness, sleeplessness). There is a proneness to digestive disturbances, to neuroses, to neuralgic pains, to various skin rashes, as erythema and eczema, or simple itching without a rash, and to mild forms of neuritis. There may be dyspnea on exertion, and other evidences of cardiac weakness. Impotence has been reported. We have had under our care one striking case of chronic poisoning with cyanosis which persisted for weeks after the stoppage of the acetanilid. Many chemic and spectroscopic tests of the blood revealed no foreign chemical other than methemoglobin. Antipyrine does not have this effect upon the blood.

Therapeutics

Antipyrine, in 10 to 25 per cent. solution, is employed locally to stop nasal hemorrhage, and as an application in the painful throat of tuberculous laryngitis. Systemically, it has been used with moderate success as a motor depressant and general sedative in chorea and whooping-cough. It has also some employment in diabetes insipidus and diabetes mellitus. Its other uses are those of acetanilid and acet-phenetidin.

All the drugs of the group are employed very largely for their effects upon the nervous system and in fever. Their general therapeutic powers are:

(a) To overcome fever. In the high temperature of influenza, tonsillitis, etc., these drugs not merely reduce the temperature, but also greatly promote the comfort of the patient by lessening pain, if present, by lessening nervousness and headache, and by promoting quiet and rest. There are cases of typhoid fever in which these antipyretics have a decidedly better effect than the cold bath, as when there are shivering and cyanosis during the bath and for some time afterward, and discomfort both physically from the cold and mentally from the dread of the next bath. The drugs are much used where cold baths are not practicable, and their antipyretic and quieting effects usually last from four to eight hours. In the afternoon fevers of tuberculosis, also, they promote the comfort of the patient.

(b) To relieve pain in conditions without fever, as in dysmenorrhea and muscular rheumatism; headache, migraine, neuralgia, sciatica, peripheral neuritis; the lightning pains of locomotor ataxia, and the pain of an intracranial or spinal tumor. They have little influence on pain from traumatism.

(c) To allay nervous excitability and promote sleep in conditions without fever - emotional shock, hysteria, and nervous conditions in general.

Administration

Usually in capsules or tablets. If they cause too much perspiration, atropine may be added.

The Anti-Malarial Antipyretics Cinchona

There are two medicinal varieties of cinchona, one the bark of several species of calisaya, and known officially as Cinchona, the other the bark of the red cinchona, known as "Peruvian bark," and with the official title, Cinchona rubra. These are natives of South America, but many species are cultivated in various tropical countries.

Constituents

There are about 19 alkaloids, the important ones being quinine, cinchonine, quinidine, and cinchonidine. In addition there are quinic, quinovic, and tannic acids. Red bark contains more tannic acid and less quinine than calisaya, but both are required to contain 5 per cent. of total alkaloid.

Preparations And Doses

Fluidextract (calisaya); dose, 15 minims (1 c.c.). Tincture, 20 per cent. (calisaya); dose, 30 minims (2 c.c.). Compound tincture (tinctura cinchonas composita), 10 per cent. red bark with serpentaria and bitter orange peel; dose,

1 dram (4 c.c.).

The alkaloidal salts, dose, 5 grains (0.3 gm.), are: Quinine sulphate, (C20H24N2O2)2.H2S04, soluble in 725 parts of water and 107 of alcohol. It is readily soluble in dilute hydrochloric, sulphuric, or phosphoric acids, as it forms the soluble double salts, or in the case of sulphuric acid, the soluble bisulphate. Quinine bisulphate, C20H24N2O2.H2So4, soluble in 9 parts of water and 23 of alcohol. Quinine hydrobromide, soluble in 40 parts of water and 0.9 of alcohol. Quinine hydrochloride, soluble in 18 parts of water and 0.8 of alcohol. Quinine dihydrochloride, soluble in 0.6 part of water and 12 parts of alcohol. Quinine and urea hydrochloride, soluble in 0.9 part of water and 2.4 parts of alcohol. Quinine salicylate and quinine tannate, very slightly soluble salts. Cincho-nine sulphate, soluble in 60 parts of water and 12.5 of alcohol. Cinchonidine sulphate, soluble in 65 parts of water and 90 of alcohol. Euquinine, not official, is the ethyl carbonic ester. It is insoluble in water and not bitter. Its dose is twice that of the official quinine salts. Tinctura antiperiodica, N. F. (Warburg's tincture), is a bitter, aromatic laxative, sedative and antimalarial "shot-gun" prescription. It is made of quinine sulphate, aloes, rhubarb, angelica seed, elecampane, saffron, fennel, prepared chalk, gentian, zedoary, cubeb, myrrh, camphor, white agaric, opium, black pepper, cinnamon, ginger, alcohol, and water. Each ounce contains opium, 1/8 grain (0.008 gm.); quinine sulphate, 10 grains (0.6 gm.), and extract of aloes, 8 grains (0.5 gm.). The dose is 1 dram (4 c.c.). Warburg's tincture without aloes (sine aloe) is the same with the omission of the aloes. Pilula antiperiodica, N. F., and Pilula antiperiodica sine aloe, N. F., represent 1 dram (4 c.c.) of the corresponding tinctures. Ethylhydrocupreine hydrochloride, a proprietary remedy with the name optochin, is. a close chemical and pharmacologic relative of quinine. It is derived from the alkaloid cupreine of China cuprea bark or is made from hydroquinine. It is fairly soluble in water and alcohol. Pharmacologic Action. - Quinine is a protoplasm poison. Microorganisms. - Quinine is strongly antiseptic, and retards the development of bacteria and yeasts. In very dilute solution (1: 10,000) its first tendency is to stimulate or irritate protoplasm; but the stimulation is soon followed by depression, and in motile organisms, especially protozoa (ameba, Paramecium) and ciliated cells, all motion very soon ceases. Strong solutions cause instantaneous cessation of movement and kill the organisms. The spirochetes of relapsing fever are more resistant, and can live in a solution of 1: 500. (See page 24.)