It is an interesting fact that various cells, under the influence of quinine, will undergo asymmetric cell division, e. g., the ova. In certain low vertebrates, as the salamander, dilute solutions of quinine applied to the epithelium will produce cells of atypical mitosis like those of cancer. This effect is produced by other protoplasmic poisons, such as chloral and cocaine (Wilson).

The enzymes seem to be slightly retarded, but are not nearly so much affected as the living organisms. Of the digestive ferments, ptyalin and diastase are little, if any, affected, and pepsin and trypsin are distinctly retarded in their activity. Other ferments, such as the blood-coagulating and the oxidizing, are retarded; and it is said that quinine will prevent blood or fresh vegetables from giving the guaiac test, which depends on oxidation.

The leukocytes, which resemble amebae so closely, are affected in the same way as amebae. With 1 part of quinine in 4000 of blood they lose their ameboid movements, become spheric, die, and soon disintegrate. In the intact animal, a strong solution prevents the emigration of leukocytes and their gathering to form pus at the site of inflammation. And while, in man, such doses as can be administered do not show this pronounced effect, still there is some effect upon the leukocytes, for their number may be reduced to one-half or one-fourth the normal (2000 to 4000 per cubic millimeter instead of 8000), the polynuclears being reduced out of proportion to the lymphocytes. Roth (1913) found a primary slight increase in the lymphocytes, which after several hours changed to a decrease. In a dog an intravenous dose markedly contracted the spleen and caused a decided decrease in the white cells, especially of the polynuclears. He thought the primary rise in man might be due to squeezing out the splenic leukocytes by its contraction. These are notably of the lymphocyte type.

Locally, the inorganic salts are distinctly irritant to raw surfaces and mucous membranes, as when its solutions are used in the rectum or hypodermatically. After a hypodermatic of the hydrochloride of quinine and urea there soon ensues a pronounced local anesthesia which lasts for some hours. Quinine is said to stimulate the growth of hair, and is an ingredient of rum and quinine, eau de quinine, and other mixtures which are sold as hair-stimulants.

Alimentary Tract

It is intensely bitter, and, given before meals, acts as a bitter to promote appetite. Large doses irritate the stomach and may cause nausea and even vomiting. There is slight retardation in the activity of pepsin and trypsin, while the other digestive ferments are probably not affected. It is to be borne in mind that quinine sulphate, the alkaloidal salt almost universally employed, requires an acid medium for its solution; therefore it is administered after meals.

Quinine is said to retard the absorption of salts, and also probably of other substances (foods and medicines), from the stomach (Sollmann).

A Bsorption

If the quinine salt goes into solution it is rapidly absorbed from the intestine and may appear in the urine in fifteen minutes. If the stomach is not acid, the quinine may not dissolve.

Circulation

In ordinary therapeutic doses there is probably a slight increase in the rate of the heart and a tendency to a rise in the blood-pressure from mild stimulation of the heart muscle and of the arterial muscles. The arterial action is a peripheral one, for on perfusing an isolated viscus, there is contraction of the arterioles, followed in a short time by their dilatation. In large doses there is direct depression of the muscles of the heart and of the arteries, with slow pulse (which occurs after atropine, so is due to muscular depression), and a fall in blood-pressure. From ordinary therapeutic doses the effect on the circulation is negligible.

The blood we have already spoken of. Its coagulability is decreased and its white cells are lessened in number and probably also in activity. In bleeding experiments on dogs, de Sandro (1911) noted that dogs given quinine recovered their hemoglobin and red cells less readily than those without quinine.

Cerebrum

It has the same tendency as the other antipyretics, but not to so great a degree, to allay the pains of neuralgia and those associated with the onset of influenza and other acute illnesses. Large doses produce cinchonism, spoken of later.

Medulla

Affected only in poisoning. Then, after a brief stimulation, the respiratory center is depressed, and death takes place from its paralysis.

Spinal Cord

In the frog the reflexes are increased. In mammals there is probably no effect.

Peripheral Nerves

After hypodermatic administration there is a slow and prolonged abolition of sensation at the site of injection.

The Eye

In some persons there have been marked changes in the sight after a therapeutic dose. There are diminished acute-ness of vision, contraction of the field of vision, color-blindness, and dilated pupil.

In the fundus there are seen irregular contractions of the retinal and choroidal arteries, edema and anemia of the retina, pallor of the optic discs, thrombosis of the central vein, and in some cases atrophy of the optic nerve, with more or less permanent blindness, the patient sometimes appearing to see through a veil. The diminished vision is known as "quinine amblyopia." The blindness is known as "quinine amaurosis." DeSchweinitz reports a case of temporary blindness after 12 grains of quinine sulphate, though usually the doses have been large. According to this author the contracted field of vision does not regain its normal limits; but Parker (1912) reported the case of a man who took 240 grains (15 gm.) by mistake, was completely blind for a time, and had recovered full vision in three and one-third months. Weeks reports cases showing permanence of arterial contraction with paleness of optic discs and retinae.