Ear

The deafness and ringing in the ears which are of such frequent occurrence seem to be due mostly to congestion, though arterial contraction and anemia of the middle ear and labyrinth are reported. Such congestion has been found in animals after large doses. If the quinine administration is continued, permanent deafness may result either from degenerative changes in the spiral ganglia of the cochlea or from a chronic otitis media arising from the continued congestion.

Muscle

Striped and cardiac muscles are stimulated at first, the muscles being more irritable and able to lift a greater load; but they are soon fatigued, and their total work amounts to less than normal. That the muscle itself is the part affected is proved because quinine has the same effect after curare. (Curare paralyzes the motor nerve-endings to voluntary muscle.) Smooth muscle is not so surely affected, except perhaps the spleen and uterus, and perhaps that of the arteries.

Immunity

In persons susceptible to quinine Boerner obtained a positive von Pirquet reaction in fifteen minutes from solutions of 1: 10 to 1: 1000. In other persons there was no reaction.

Elimination

It appears very soon in the urine (fifteen to thirty minutes), and most of it is excreted in a few hours. Traces may be detected for three days or more. From 30 to 90 per cent. of it may be recovered from the urine unchanged, and some is changed to di-hydroxyl quinine. A small amount appears in other secretions. Koldewijn says that traces appear in the milk. Through irritation or circulatory changes of the skin there may be various rashes, notably a scarlatiniform rash, eczema, urticaria, and erythema with itching. So frequent are skin rashes from quinine that a rash of unusual type regularly elicits the physician's question, "Have you taken quinine?"

Fig. 62.

Fig. 62. - Purpuric and vesicular eruption from quinine (W. S. Gottheil in Archives of Diagnosis).

Kidneys

Large doses of quinine irritate the kidneys and cause albuminuria or even hemoglobinuria or hematuria. After the use of quinine for long periods, uroerythrin may be a cause of red urine.

Uterus

Uterine contractions seem to be favored, and the drug is employed in labor to increase theforce of the contraction of the second stage. In the isolated guinea-pig uterus Lieb found that a solution of 1: 100,000 caused an immediate increase in the rate and strength of the contractions, and that 1: 25,000 caused tetanic spasm and rapid death of the organ. From doses of 8 to 15 grains (0.5-1 gm.) Maurer obtained a distinct ecbolic effect in nearly all cases within forty minutes. It is a common belief that quinine may produce abortion in a pregnant women, and I have seen several cases where abortion in the first three months followed, though it may not have been caused by, its use for cold or for malaria. There are also many cases of pregnancy where abortion has not followed its use.

Metabolism is affected by very small doses, even doses small enough to have no other effect. At first there is a slight increase in the nitrogenous content of the urine, probably due to increased leukocyte destruction; but soon there is a marked decrease, and this is especially noticeable in the urea and uric acid. The same amount of nitrogenous food may be absorbed, but less is consumed by the body, so there is a storing-up of proteins. Quinine has, then, just the opposite effect to fever, which is associated with excessive protein destruction. There is no evidence of incomplete oxidation of the nitrogenous products.

Temperature

The normal oxidation processes are changed very little, if at all, the O2 taken in, and the Co2 given off, being about the same. Oxidation is usually taken as a criterion of the amount of heat generated, yet there is less heat generated after quinine, presumably owing to its lessening the destruction of proteins. Quinine lowers the temperature in fever almost entirely by lessening the production of heat; and as it lowers temperature after division of the spinal cord, it does not exert this action through the heat-regulating centers.

Like all antipyretics, it acts best at about the time of a usual remission of temperature, and has but little effect in health. It is not so powerful a reducer of temperature as acetanilid, and in a continuous fever like typhoid has very little effect. As an antipyretic it has largely been supplanted by more effective drugs.

Untoward Symptoms

Cinchonism, skin eruptions, gastric disturbances, diarrhea, and, rarely, hemoglobinuria. In cinchonism there are fulness in the head (headache), ringing in the ears, deafness, dizziness, and mental dulness; and there may be impaired vision, muscular weakness with uncertain gait, and slow, rather weak pulse. The cerebral symptoms are attributed to circulatory changes. Sicard reports 15 cases of sciatic paralysis from the intragluteal injection in soldiers.

In some people there is idiosyncrasy to very small doses, and in these susceptible people the addition of bromides lessens the tendency to cinchonism.

Toxicology

The usual manifestation of overdosage is cinchonism (just described). Very large doses induce gastrointestinal disturbances, mental sluggishness, disturbance of sight and hearing, slow, ineffective respiration, slow, weak heart, muscular weakness, and collapse. One ounce' (30 grams) produced only confusion and noises in the ears, but it may not have been absorbed. Quill reports unconsciousness and severe collapse five minutes after the taking of 1/2 ounce (15 gm.) in solution. Baer-mann reports death after two doses of 8 grains (0.5 gm.). Two drams (8 gm.) have also been reported as causing death. Hartshorn had a case with burning, swollen face, scarlatiniform rash, and fever. The author had a patient in whom the administration of quinine on different occasions was followed by chilliness, sweating, vomiting, and diarrhea.