Cinchona, q. v., has been separately considered; but quinine and quinine derivatives are so important as to require detailed and individual study.

One can break out about thirty alkaloids from cinchona; how many exist in the plant structure and how many are produced by chemical manipulation I shall not pretend to say, but there are only five of any importance. Their formulae, according to Henry ("The Plant Alkaloids") are:

Quinine and quinidine............

Cinchonine and cinchonidine.......

Cuprein........................

C19H21ON2.OCH3 C19H21ON2.H C19H21ON2.OH

The important differences depend upon the amount of the contained base, and their solubility in water.

Pharmacology

The various alkaloids are, qualitatively, very similar in their pharmacologic bearings; all are protoplasmic poisons. Quinine possesses the greater antiseptic power, being followed by quinidine, conchonidine, and cinchonine. Cinchonidine is the most active as a muscle poison, being followed by quinine, conchonine, and quinidine. As is to be expected from the action on muscle, the toxic influence on the heart follows a similar order in relative activity. Conchonidine, and to a less degree conchonine, manifest convulsant activity. All of the alkaloids other than quinine are inferior to it in their action on the malarial parasite, though some are not markedly inferior to quinine.

Quinine, in very small doses or in dilute solutions, transiently exalts protoplasmic activity; but the final action, and the only one in ordinary dosage or strength of solution, is to depress such activity. Certain molds and bacteria are resistant to quinine. There is no selective action as regards particular organs or body cells, but ferment action is retarded.

In small doses quinine is a stomachic bitter in action: large doses induce pain in the stomach, with vomiting in some cases. Absorption occurs principally in the duodenum, being retarded in disease of the liver and bowel. Elimination is by the kidneys and is rapid, most of the alkaloid passing out unchanged, only a small portion being oxidized. So rapid is elimination that it is rare for the blood-serum, even under heavy dosage, to carry over 1 per cent of the drug: more than this damages the cells of the kidney.

In medicinal dosage quinine has little influence on nervous, circulatory, or respiratory organs; but large doses produce excitation followed by depression: very large doses are sometimes convulsant. Fatal poisoning manifests collapse, with failure of the respiration and circulation.

Cinchonism - buzzing in the head and deafness - is an irregular manifestation, susceptibility thereto being individual, though common. It is a peripheral effect.

Unstriped muscle is stimulated and then relaxed. Rather irregularly the uterus may be stimulated to contract.

Quinine retards nitrogenous metabolism and lessens heat production. This latter is not compensated by diminished heat loss. In this way quinine is antipyretic. Small doses stimulate the production of red corpuscles in the blood, as also the polymorphonuclears: large doses have the opposite effect.

Therapeutics

Externally quinine is a little-used antiseptic, employed from 0.5 per cent, in the eye, as in conjunctivitis, to the powdered quinine sulphate in full-strength application to chancroids. Five per cent, strength has been used as an injection in gonorrhea. In hay-fever 4 to 8 grains quinine hydrochloride to the ounce of water is used as a spray. As an application to the skin previous to irradiation with the X-ray, 8 grains quinine to the ounce of cod-liver oil has been commended.

In digestive troubles cinchona, q. v., is used in preference to quinine; but 2-grain doses of quinine salts are used as general tonic medication. Undoubtedly such doses are a bitter stomachic tonic, but a solution in weak acid is preferable for such purposes to the common quinine pill.

Quinine acts as an antipyretic by inhibiting nitrogenous metabolism and diminishing heat production. The vogue of the coal-tar derivatives has, of recent years, pushed quinine to the background as an antipyretic; but it is returning to favor again. It is coming to be well understood that the aniline derivatives depress the respiratory and circulatory systems: quinine, in medicinal dosage, does not depress, or rarely does so. In bronchitis and the milder febrile states, quinine is quite effective as an anti-pyretic, if given in fairly full dosage. In surgical fever quinine is especially valuable. The disagreeable tinnitus produced by full dosage is much reduced by the use of bromides or diluted hydro-bromic acid.

In general infectious diseases quinine may not be expected to possess distinct bactericidal effects; but that it does to a certain degree in some affections is probable. In continued fever of no defined type or specific etiology, quinine seems to be of value. It is rather empirically given in pneumonia, but results seem to justify the practice.

In influenza there is reason to believe that the drug is of value. Binz was the main advocate of the use of quinine in the treatment of whooping cough. He gave the hydrochloride in doses of 1-6 to 2 grains in the course of twenty-four hours to a child under one year of age, 3 grains during twenty-four hours at two years of age, 4 1/2 grains at three years, 6 1/4 at four years, 7 3/4 at five years, and 15 1/2 at ten years, all of these being twenty-four hour dosage.

Quinine kills the malarial parasite; it is a specific prophylactic and curative agent in malarial fever, or, as it is now known, "mosquito fever." As a prophylactic enough must be kept in the circulation to inhibit the development of the Plasmodium malariae, usually from 5 to 15 grains a day, though more is required in a malarial district.

As a curative agent, quinine should be so administered as to be in greatest concentration in the blood just before the sporulation of the parasite occurs, when it is least resistant. A large dose (10 to 15 grains) should be given thrice daily for two days before the expected onset of the paroxysm, the last dose being administered about six hours before that event; then continue in smaller dosage. Small and divided doses should not be continued for long, however, the effort being made to meet the next paroxysm with adequate dosage. It is necessary to give opium to some persons, with these large doses of quinine, in order to limit gastric distress. Arsenic and smaller doses of quinine should be given during the interval.

In remittent fever, give from 20 to 30 grains in a single dose once or twice in a day until the temperature falls to about normal. In pernicious malarial fever, very large doses are demanded, even hypodermatically in some cases. Be on guard against hematuria, however. In the chronic malarial cachexia, quinine may not produce a cure. Change of climate is imperative in some cases. The patient needs tonics and cholagogues, good food and every possible care.

Subcutaneous, intramuscular, and even intravenous administration are used in tropical countries in the treatment of the pernicious forms of the disease found there. The method is not without danger, tissue necrosis being readily induced by the irritation produced. Indeed, it has been claimed that quiescent tetanus organisms may be in the tissues and be lighted up to virulent activity by intramuscular injections of quinine salts. The intravenous use of, say, 10 grains in isotonic salt solution is safer.

Hemaglobinuria is aggravated, and it is said is produced, by quinine. The plasmodia should be definitely proven to exist, in a hemaglobinuric case, before the risk is run of intensive quinine administration.

Quinine is valuable in the treatment of malarial neuralgia. Some of the neuroses are dependent upon malaria and are benefited by quinine, as is the jaundice of malaria.

As an adjuvant to other medication, quinine often serves a useful purpose. In most any enfeebled state of the system its tonic influence helps wonderfully in restoration.

As an emmenagogue quinine is not of direct value, but after labor has begun it may promote the sluggish uterine muscle to greater activity of function.

In the amenorrhea of anemia, quinine and iron are often of service.

Administration

Quinine alkaloid is relatively insoluble and tasteless. It is easily masked. The sulphate is not very soluble and is inferior to the hydrochloride when prompt effects are desired. The alkaloid is readily masked by licorice, yerba-santa, or chocolate syrup. The bisulphate is readily soluble.