Page:EB1911 - Volume 22.djvu/775

 Cinchonism is the name applied to the congeries of toxic symptoms which follow the prolonged administration of quinine, but may appear after one small dose in certain persons. The symptoms closely resemble those of salicylism, and also, though in less degree, those of carbolism. The patient is deaf, but complains of ringing in the ears, which may assume various forms, especially in musical people. There is headache, which, with the continuance of the drug, becomes exceedingly severe, the vision and equilibrium are affected, and there is often some gastro-intestinal irritation. In cases where the drug has been deliberately given for its poisonous action the results are still more severe. There may be bleeding from the nose, cutaneous congestion, deafness, blindness, coma or delirium, and even death from cardiac failure. After death there is found one noteworthy lesion, a commencing acute inflammation of the internal ear. In persons who have a marked idiosyncrasy towards cinchonism, the symptoms may often be successfully averted if small doses of hydrobromic acid—10 minims of the dilute solution—are given with the quinine.

A non-official preparation of quinine—Warburg’s Tincture—occasionally succeeds where the ordinary preparations fail. The dose is 1 to 4 drachms. It contains 1 part of quinine in 50. Of the thirteen or more other ingredients, there may specially be noticed the salicylic and benzoic acids.

The, other alkaloids of cinchona bark—quinidine, cinchonidine, and cinchonine—also possess similar properties, but all are much less effective than quinine. This is also the case with the cinchona febrifuge prepared from C. succirubra.

The great disadvantage of the official preparations is the bitter taste and insolubility. It is found, however, that all the soluble salts are bitter, whilst the tasteless ones are insoluble. Substitutes may therefore be divided into those administered orally and those administered hypodermically. Of the insoluble salts we may notice the tannate, the propionic acid ester (euquinine) and carbonic acid ester (aristoquin), the salicylic acid ester (saloquinine); and of the soluble substitutes, quinopyrine (a compound of quinine hydrochloride and antipyrine) and quinine hydrochlorocarbamide (a compound of quinine, urea and hydrochloric acid).

Until 1867 English manufacturers of quinine were entirely dependent upon South America for their supplies of cinchona bark, which were obtained exclusively from uncultivated trees, growing chiefly in Bolivia, Peru, and Ecuador, the principal species which were used for the purpose being Cinchona Calisaya; C. officinalis; C. macrocalyx, var. Palton; C. Pitayensis, C. micrantha and C. lancifolia. Since the cultivation of cinchona trees was commenced in Java, India, Ceylon and Jamaica, several other species, as well as varieties and hybrids cultivated in those countries, have been used. Later, C. lancifolia, var. Calisaya, known as the calisaya of Santa Fé, was strongly recommended for cultivation, because the shoots of felled trees afford bark containing a considerable amount of quinine; C. Pitayensia has been introduced into the Indian plantations on account of yielding the valuable alkaloid quinidine, as well as quinine.

QUINOLINE (Benzopyridine), C9H7N, an organic base first obtained from coal-tar in 1834 by F. Runge (Pogg. Ann., 1834, 31, p. 68), and later by C. Gerhardt by the distillation of cinchonine, quinine and other alkaloids with caustic potash (Ann., 1842, 42, p. 310; 44, p. 279). It also occurs with pyridine and its homologues in bone-oil. It may be prepared by distilling cinchoninic acid with lime; by the reduction of ortho-aminocinnamic aldehyde (A. Baeyer and V. Drewson, Ber., 1883, 16, p. 2207); by passing the vapour of allyl aniline over heated lead oxide; by the condensation of ortho-aminobenzaldehyde with acetaldehyde in the presence of aqueous caustic soda (P. Friedländer and C. F. Gohring, Ber., 1882, 15, p. 2572; 1883, 16, p. 1833); by the action of orthotoluidine on glyoxal at 150° C. (V. Kulisch, Monats., 1894, 15, p. 276); by the action of phosphorus pentachloride on hydrocarbostyril (the inner anhydride of ortho-aminohydrocinnamic acid), the chlorinated compound first formed being then reduced by hydriodic acid (A. Baeyer):

and by the so-called “Skraup” reaction, which consists in oxidizing a mixture of aniline, glycerin and concentrated sulphuric acid, with nitrobenzene (Z. Skraup, Monats., 1880, 1, p. 316; 1881, 2, p. 141). This reaction is a very violent