This section is from the book "Materia Medica Pharmacy, Pharmacology And Therapeutics", by W. Hale White. Also available from Amazon: Materia Medica Pharmacy, Pharmacology And Therapeutics..
The action of cinchona bark is due almost entirely to the quinine in it; the other alkaloids act in much the same way as this alkaloid, the sulphate, bisulphate, hydrobromate and hydro-chlorate of which produce the same effect as quinine itself. The following description will be that of the action of quinine sulphate, which is often called quinine. Any differences between it and the bark or the other alkaloids will be mentioned in the course of this description.
Quinine is a very powerful antiseptic. A solution of 1 to 500 destroys many forms of micro-organisms, and a solution of 1 to 250 prevents fermentation and putrefaction. Quinine is very fatal to all low forms of animal and vegetable life. A solution of 1 to 1000 kills many infusoria. No effect is produced upon the sound skin by quinine, but it is irritant to a raw surface.
Alimentary canal. - Quinine acts like any other bitter, such as calumba. The bitter taste is very marked; in the mouth the gustatory nerves, and in the stomach the gastric nerves, are stimulated. This leads reflexly to an increase of the salivary and gastric secretions, and to greater vascularity and peristalsis of the stomach, the appetite is sharpened and digestion is aided. Quinine is, therefore, a stomachic. These effects, of course, bring about a better absorption of food; and hence, if digestion was previously feeble, the patient feels stronger after a course of quinine. In the stomach any quinine salt is converted into a chloride, some of which is probably absorbed here; for in the intestines it would be precipitated by the alkaline secretions. It is often excreted unchanged in the faeces.
Blood. - Quinine, as the chloride, is readily absorbed into the blood; and although this is alkaline, it is not precipitated, being probably held in solution by the gases of the blood. It is not known that it undergoes any alteration there, but it produces some remarkable changes.
(a) White corpuscles. - If the movements of the white corpuscles are being watched in a drop of blood on the warm stage of the microscope, and some quinine is added, they at once cease. Again, if the mesentery of a living frog be put under the microscope, and slightly irritated so as to set up inflammation, emigration of the white corpuscles through the capillary walls, or diapedesis, as it is called, will be observed; if now some quinine be injected into the circulation this ceases, but those white corpuscles that five already passed out wander further from their capillary. If the quinine be applied locally to the mesentery, directly the white corpuscles have passed through their capillaries their movement is stopped, and the motionless corpuscles collect in large numbers around the capillaries. It is clear, therefore, that quinine has the power of arresting the movements of white blood-corpuscles. In sufficient quantity it appears actually to destroy them, for in a cat killed by quinine they are much fewer in number than in a healthy cat.
(b) Red corpuscles. - Quinine is said to cause a diminution in the size of these, but this is most likely not strictly correct. In fever, if the temperature is high, the red corpuscles are probably a little larger than natural. If the temperature be reduced by any means the corpuscles regain their normal size. Quinine will reduce the temperature, but it probably has no special action on the corpuscles.
(c) Acidity of the blood. - Blood outside the body gradually becomes acid. Quinine prevents this.
(d) Ozonizing power. - If ozonized oil of turpentine be mixed with a tincture of guaiacum, nothing occurs; but if a drop of blood be added, that transfers the ozone to the guaiacum,, oxidizes it, and turns it blue. This ozonizing power of blood is prevented by the addition of quinine.
(e) The stability of oxyhaemoglobin is strengthened by quinine, so that the blood does not yield up its oxygen as easily as normally, consequently it cannot absorb oxygen readily. This inability of haemoglobin to take up oxygen in the presence of quinine is parallel with its action on other varieties of protoplasm. For example, fungi absorb oxygen slowly if quinine be present, and thus fermentation may be prevented. Phosphorescent infusoria (the phosphorescence is due to rapid oxidation) lose this property in the presence of quinine. The ozonizing power of fresh vegetable juices is retarded by it. Quinine is, therefore, very constant and very powerful in interfering with oxidation.
Circulation. - Small doses of quinine probably increase the activity of the heart reflexly because they stimulate the stomach; but large doses (larger than are given to man medicinally), either applied to the excised heart or circulating through it, directly paralyze the organ; the pulse becomes slower and more feeble, and the heart is finally arrested in diastole. Whether it acts on the muscle or the ganglia is not known. Large doses lower the blood-pressure considerably; this is owing partly to the effect on the heart, but it is probable that this fall of arterial pressure is due in part also to the action of quinine on the blood-vessels. If the spleen is enlarged as a result of malarial fever, the administration of quinine, curing the fever, leads to a decrease in the size of the spleen, but it has no direct effect on this organ, as is often asserted.
Respiration. - Although, as we have seen, quinine must, because of its retardation of oxidation, have a powerful influence on internal respiration, diminishing the activity of metabolism, it has but a moderate effect on respiratory movements. Small doses slightly increase, large doses depress them.
Temperature. - Quinine has very little power over the healthy temperature, but that of fever is markedly reduced; it is, therefore, an energetic antipyretic. Considering its direct capability of diminishing metabolism in the tissues, it seems fair to assume that the drug diminishes heat production, and that it does so by acting directly on the thermogenetic tissues; but, whether it decreases heat production by also influencing the cerebral thermogenetic centres is not known.
Cerebrum. - Small doses are believed to stimulate cerebral activity. The results of experiments upon the action of quinine on the brain are so discordant as to be at present valueless. The effects of a large dose in man will be described under Cin-chonism.
Spinal cord and nerves. - In frogs, quinine causes a lessening of reflex excitability, which is removed by section below the medulla; but in large doses it produces a permanent diminution of reflex excitability. In these animals quinine also first excites and then paralyzes the sensory nerves or their peripheral endings. The muscles are uninfluenced. These effects are not seen in man.
Uterus. - It has often been stated that quinine will lead to abortion, that it will, when labor has commenced, aid the expulsion of the foetus, and that it will increase the menstrual flow if that is scanty. It appears that the first statement is certainly incorrect, and that the second and third are only correct for some women.
Kidneys. - After a full dose of quinine it is found in the urine in half an hour, and is slowly excreted for several days, but by far the greater part is eliminated within the first forty-eight hours. The excretion of uric acid is greatly diminished, and that of urea and other nitrogenous bodies in the urine is also considerably lessened. This confirms the statement already made that quinine retards considerably the metabolism of the body, but it should be stated that very little alteration is observed in the excretion of carbon dioxide by the lungs. It is said that minute quantities of quinine are gotten rid of by all the secretions, as it may be detected in milk, saliva, bile, tears, etc., and it may be found in dropsical fluids if the patient has been taking it.
Cinchonism. - In many persons a dose of ten grains; .60 gm. or more of quinine produces a train of physiological symptoms, chiefly from its influence on the nervous system. The patient soon complains of ringing in the ears, fullness in the head, and slight deafness. With larger doses these symptoms increase, disturbances of vision and giddiness are added, he may stagger when he walks, and the headache may be very intense.
Quinine is hardly ever given as a poison, but if it should be, all these symptoms of cinchonism will be very severe; the patient may be delirious and comatose, quite deaf and blind, and if he die it will be from collapse due to cardiac and respiratory failure. Great congestion of the middle ear and labyrinth is found in animals poisoned by quinine. The mild degrees of cinchonism pass off directly after the drug is discontinued. Rarely quinine causes an erythematous rash, and it has been known to give rise to epistaxis. Those who work among cinchona barks may have a rash on their skin from the mechanical irritation of the powder. Both hydrobromic acid and ergotin are said to diminish the liability to cinchonism.
Relative Action of the Alkaloids. - The other alkaloids are quite similar in their action to quinine, but they are not so powerful. Their relative antipyretic effect is quinine 100, quini-dine 90, cinchonidine 70, cinchonine 40.