Hitherto our attention has been directed to the influence of quinia, in large doses, upon the circulation, or the cerebral functions.

* In this case, M. Bazire, a practitioner of medicine, in an excited state of imagination bordering on insanity, believing himself to be attacked with pernicious fever, took within a short time 60 grammes (very nearly two ounces Troy) of sulphate of quinia by the mouth and rectum. Symptoms of great prostration, with loss of sight and hearing, came on, which he unfortunately ascribed to the pernicious fever, and hoped to counteract by a continuance of these enormous doses. In the course of nine or ten days, he took additionally five ounces of the salt. Another physician being then called in, found him covered with cold sweat, completely deaf and blind, with difficult and rattling respiration, profound stupor, and an expression of countenance like that of drunkenness. Though partially roused with much difficulty, so as to give rational answers, he quickly became delirious, and died. (Dict. de Med., 2e ed., xxvi. 570).

But it also produces other effects. It has been supposed by some to render the blood more fluid, and to lessen its coagulability by diminishing the proportion of fibrin, or altering its quality; and in some cases, in which death has occurred during its administration, the blood has been found fluid. But this result was ascribable to the existing disease, and not to quinia; and more numerous experiments and observations have proved that, in any quantity in which it can be introduced into the system, it does not impair the coagulability of the blood. Indeed, Briquet found, in his experiments, that it had the opposite effect of increasing the proportion of fibrin.

It has been said that quinia has the property of immediately reducing the bulk of the spleen. This view of it was taken by Piorry, but has not been fully sustained by other observers; and the existence of the property must be considered as doubtful. Enlargement of the spleen is undoubtedly often gradually diminished under the use of quinia, especially in miasmatic fevers; but it is quite as probable that the effect proceeds indirectly from the removal of the cause, as directly from the operation of the remedy on the organ.

In the urinary passages quinia occasionally induces irritation, probably by its direct contact with the mucous membrane of these passages, as it escapes with the urine. Dr. E. Hardy has shown that quinia begins to pass out with the urine in less than seven minutes from its exhibition by the mouth. (Journ. de Pharm. et de Chim., 3e ser., xliv. 160.)*

A case is recorded in the London Med. Times and Gaz. (April, 1864, p. 461), in which one ounce of sulphate of quinia was given, by mistake, to a soldier affected with ague, with no other unpleasant effect than a kind of stupor and complete deafness, which left him after a time; and at the end of a week he was quite well, having lost his ague. No antidote was used. From these two cases it may be inferred that, though quinia may sometimes be taken with impunity, by a strong man, in the quantity of an ounce; yet double the quantity may prove fatal; and a legitimate caution would limit (he dose far within the smaller amount mentioned. (Note to the third edition).

The alkaloid is not generally thought to exercise any special influence on the genital function; though it may no doubt operate beneficially, in certain abnormal states of that function, through its tonic powers. It is, however, believed by Dr. Cochran, on the basis of numerous experiments, that it has the property of exciting the menstrual function by a special influence; accelerating and augmenting the menses when it is given a short time before the regular period, and restoring them when arrested by cold or other cause. (Ann. de Therap., a.d. 1860, p. 194).

Occasional effects are experienced from quinia differing from those which are most common and characteristic. Sometimes it irritates the stomach considerably, causing a sense of weight or oppression, gastric pains, and nausea or vomiting. This is especially the case in febrile diseases, in which the stomach is already not unfrequently in a state of irritation, or strongly disposed to it. Sometimes also it acts similarly on the bowels, causing griping pain, and diarrhoea. It has been accused of producing constipation; but this is doubtful. Its operation, in large doses, is sometimes attended with great oppression of chest and precordial uneasiness, probably dependent upon its irritant influence over the nervous centres. Mr. W. H. Vipan states that, in several eases which have come under his notice, purpura has appeared immediately after the use of quinia. (Lancet, July 8, 1865, p. 37).

The constitutional effects of quinia are essentially the same, by whatever avenue it enters the system, whether taken by the stomach, injected into the rectum, or introduced into the areolar tissue, the serous cavities, or directly into the circulation. When applied to the skin denuded of the cuticle, it produces so much irritation as materially to interfere with its absorption.

The period, after its administration, at which quinia begins to evince signs of its characteristic action on the nervous system, and the length of time during which these signs persist, vary with the dose and the intervals of exhibition. Less than three or four grains, in one dose, rarely produces any sensible effect; six or eight grains usually occasion some cerebral disturbance in half an hour, an hour, or at the latest two hours; while from twelve to sixteen grains, or more, may operate sensibly in so short a time as fifteen minutes. But, when the medicine is given in the dose of a grain or two, repeated at intervals of one or two hours, little or no effect on the nervous system is experienced until nine or ten grains have been taken; and often considerably more is required. The operation of a single dose, just large enough to make itself felt, say five or six grains, continues generally two or three hours; of double the quantity, given through the day, in divided doses, about eight or ten hours; of larger amounts, given in the same way, up to a drachm daily, from twelve to thirty-six hours. {Briquet).

* Some experiments have been made to determine the influence of quinia on the excretion of substances with the urine. Dr. Wm. A. Hammond, of the U. S. Army, found, as the result of his investigations in cases of intermittent fever, that the use of quinia was followed by a diminution of the uric acid in the urine, and an increase of the urea (Am. Journ. of Med. Sci., April, 1858, p. 326); and the same result, as relates to the diminution of uric acid, was obtained by Dr. II. Ranke (Land. Med. Times and Gaz., May, 1857, p. 537). But we have, as yet, insufficient facts to justify any positive inference, as to its general physiological action, from its influence on this secretion. (Note to the second edition).

In animals which have perished under the influence of quinia, no lesion has been discovered, as a general result, sufficient to account for the fatal effect. Almost invariably the pia mater has been found more or less injected; but not to such a degree as to account for the fatal issue, though the appearance may aid in the explanation of its mode of operation. It has already been stated that, in a few instances, traces of meningitis have been noticed. The probability is that, if any characteristic lesion be found, it will be in the nervous centres near the base of the brain, upon which the medicine appears mainly to expend its influence, so far as that organ is concerned. Perhaps a careful examination of these parts, by means of the microscope, might reveal some characteristic abnormal condition.

In relation to Peruvian bark itself, the effects are essentially the same as those of quinia; but, in consequence of its bulk, or of certain non-alkaline principles contained in it, as the cinchonic red and the yellow colouring matter, it is much more disposed to irritate the stomach and bowels. It often, therefore, nauseates, and occasionally causes vomiting or purging, especially if the alimentary mucous membrane is in an irritable state; and in some instances it cannot be borne on the stomach, in quantities sufficient to produce its characteristic effects on the system. When very largely given, it generally becomes intolerably offensive to the stomach; so that it is difficult to obtain from it the sedative and prostrating effects produced by excessive doses of sulphate of quinia; and, when such effects are observed, it is not always easy to discriminate between them, and the sympathetic effects of the attendant nausea. Hence, the highly important property of diminishing the force and frequency of the pulse long escaped attention, and became known only after the discovery of quinia The bark differs also from its alkaloids in another particular; in its occasional tendency, namely, to produce constipation, resulting probably from the tannic acid it contains. This effect is of course evinced only in states of the bowels, in which they are not disposed to be irritated by it.

Cinchonia has been found to be identical in its effects with quinia, except that it is about one-third weaker; in other words, requires to be given in a quantity about one-third greater to produce the same result. Briquet, in his experiments, never obtained from it the effect upon the vision sometimes produced by quinia; but this was probably owing either to the insufficient number of trials, or to the insufficient amount employed.

Quinidia and quinicia appear not to differ from quinia. in their operation on the system, whether physiologically or therapeutically. In relation to cinchonidia and cinchonicia, their effects have not, so far as I know, been separately studied; but the probability is that they would be found to operate identically with cinchonia, to which they hold so close a chemical relation.