Quinine

“ It is at the moment even, of this remission, that sulphate of quinine must be administered in a dose of thirty-six grains taken at once in a half cup of black coffee without sugar. When the intermission is complete, its action is marvellous, the disease is immediately moderated; but if there is no remission, it is necessary to be prudent, for sulphate of quinine, because of its powerful action, can do much harm, if it is not indicated. ”

“ The study of the decomposition products of the cinchona alkaloids especially points quite distinctly to the probable existence in quinine of a hydrogen addition product of pyridine, in combination with a methyl-quinoline group. The many experiments that are now being made to test this and other questions that suggest themselves, will not long leave us in the dark. Whether a practical commercial synthesis of quinine will follow is another matter, but it is within the bounds of possibility, or perhaps even of probability. ”

“ Certain it is that, to the common mind, quinine is the reputed cause and is avoided in large doses by men who have once had blackwater, or who are in that low rotten state that predisposes to it. In one point all agree, that one must be saturated with malaria before blackwater can develop. So great is the aversion shown by some men to the big doses of quinine as laid down by regulations, that men have often refused to take their quinine. Others, too, who have protested at first, take their quinine ration only to find themselves in the grip of this disease within twelve hours. ”

“ He notices that it has “a remarkably white color and a peculiarly faint lustre.” Its most striking char­ac­ter­is­tic is its extreme solubility. Pure sulphate of quinine requires nearly thirty times its weight of boiling water for solution, whilst the sulphate of quinidine dissolves in four parts. On the other hand the pure alkaloid crystallizes readily out of proof spirit and out of ether, whilst quinine does not crystallize out of either. A very good test for the presence of cinchonine in sulphate of quinine is also capable of being applied to detect the presence of β quinine. ”

“ We are firm in the opinion that no army, either in the fighting nations of Europe, or in any other land, ever had a medical corps that could surpass our own in skill, dexterity, genuine humanity, and a desire to do their whole duty, but it did seem to us that quinine was the sheet anchor of their faith, and so it came to be a standing joke, that quinine would cure all diseases to which our bodies might be subject. ”

“ It is also less haemolytic so that it may be used with greater safety where blackwater fever is feared.
Euquinine or ethylcarbonate of quinine contains 81% quinine, and is only soluble in 1-12,000 parts of water, hence its comparative tastelessness. It is expensive.
Quinine tannate contains only about 30% of quinine and is practically insoluble in water. It is often given to children in chocolate tablet form. It can often be taken by those who suffer disagreeable effects from other salts. The dose should be 21⁄2 times that of quinine sulphate. ”

“ Tell me where that whisky is, and where you've hidden the quinine, and all shall be forgiven."
"It is forgiven now," Harley said drily. "Even your bitterest enemy would be sorry for you if he caught sight of that face of yours at the present moment. But it's no good, Del Carados. We can't die more than once. Neither can you, but your death promises to be a lingering one." ”

“ Both quinine and quinidine may cause cinchonism (bitter taste, dysphoria, tremor, tinnitus, reversible high-tone hearing loss, headache, nausea, vomiting, and abdominal pain) or pruritus, which should not lead to dose reduction. Both drugs have narrow therapeutic windows. Severe toxicities include cardiac arrhythmias, hypotension, blindness, deafness, and hyper-insulinemic hypoglycemia [ [12] , [33] .
An initial loading dose of quinine or quinidine should be administered as soon as possible, followed by the maintenance dose. ”

“ Put 100 grains in a Florence flask with five ounces of distilled water, heat this to brisk ebullition; the sulphate of quinine ought not to be entirely dissolved; add two ounces more water, and again heat it to ebullition; ought to make a perfectly clear solution. If this be allowed to cool for six hours, and the crystals carefully dried in the open air on blotting paper, they will be found to weigh about ninety grains, the mother-liquor may be evaporated and tested with ether, when any cinchonine or β quinine will be easily detected. ”

“ The idea that quinine might produce blackwater fever originated from a misinterpretation of the fact that the administration of quinine, even in small doses, may provoke the manifestation of blackwater fever in a patient in whom the infection is latent. As quinine, even in toxic doses, never produces blackwater fever in healthy people or in malaria patients elsewhere, its peculiar action in Africa had to be explained by a peculiar hypothetical idiosyncrasy an idiosyncrasy— which, curiously enough, is found only in certain malarious countries and not in others. ”

“ Quinine has considerable powers as an antiseptic, this term defined for some time as indicating the power to kill bacteria. Whilst quinine possesses this power, however, it is far more potently lethal to a particular form of animal organism known as the plasmodium malariae. Against the bacteria quinine is not at all an exceptionally powerful antiseptic, though more powerful than carbolic acid. Many bacteria are killed by a .2% solution of the alkaloid. ”

“ Resistance of Plasmodium falciparum to chloroquine was seen in parts of Southeast Asia and South America by the late 1950s, and was widespread in almost all areas with falciparum malaria by the 1980s. With increasing resistance to chloroquine, quinine again played a key role, particularly in the treatment of severe malaria [6] . To-date quinine continues to play a significant role in the management of malaria. This review, discusses the historical role of quinine, considers its current usage, and provides insight into the appropriate future use of quinine for the treatment of malaria. ”

“ Quinidine or Conquinine—forms crystals having the composition, C20H24N2O2 + 2 OH2; the anhydrous alkaloid melts at 168° C., and requires about 30 parts of ether for solution. Its solutions are strongly dextrogyre; it agrees with quinine as regards bitterness, fluorescence and the thalleioquin test, and forms a neutral and an acid sulphate. The most striking character of quinidine is afforded by its hydriodate, the crystals of which require for solution at 15° C., 1250 parts of water or 110 parts of alcohol sp. gr. ”

“ Quinine and arsenic as prophylactics.——A great deal has been written about the prophylactic use of arsenic and quinine in malaria. Opinions are very much divided on the subject. Most deny that arsenic possesses any prophylactic power whatever. Duncan, after an exhaustive study of the recorded evidence, and after extensive and carefully conducted experiments made by himself on large bodies of troops, concludes that arsenic has no prophylactic virtue whatever; but that quinine, in a daily dose of 3 to 5 gr., lessens the fever admissions by one-half. ”

“ From analyses of the leaves, bark and root, it appears that quinine is present only in small quantities in the leaves, in larger quantity in the stem bark, and increasing in proportion as it approaches the root, where quinine appears to decrease and cinchonine to increase in amount, although the root bark is generally richer in alkaloids than that of the stem. The altitude at which the trees are grown seems to affect the production of quinine, since it has been proved that the yield of quinine in C. officinalis is less when the trees are grown below 6000 ft. ”

“ What are the indications of sulphate of quinine in yellow fever? There must be at least remission, if there is not complete intermission of the fever. Its application is then excluded from the continued type. When the fever has yielded, by the use of the medicines of which we have spoken, or when, with sweat or moisture of the skin, the pulse has sensibly lowered, the employment of quinine is always good. Its effect will be shown, for the strongest reason, in the intermittent type. ”

“ If however the estimation of quinidine (conquinine) and quinamine is required, the residue, or a determined portion of it, should be dissolved in acetic acid just as much as will be necessary for affording a neutral solution. From this the hydroiodate of quinidine is precipitated by means of an alcoholic solution of iodide of potassium. In the filtrate quinine may be precipitated by adding a few drops of dilute sulphuric acid and an alcoholic tincture of iodine. The herapathite thus formed (see p. 360) is collected after a day, dried at 100° and weighed; it then contains 55 per cent. ”

“ Why should we murder live-wires like them to save pasty-faced, big-bellied humans from pneumonia?”
Their first task was to determine with accuracy the tolerated dose of the quinine derivative, and to study its effects on the hearing and vision, and on the kidneys, as shown by endless determinations of blood sugar and blood urea. While Martin did the injections and observed the effect on the monkeys and lost himself in chemistry, Terry toiled (all night, all next day, then a drink and a frowsy nap and all night again) on new methods of synthesizing the quinine derivative. ”

“ A pregnant woman will run more risk of miscarriage and of detriment to her health from repeated ague fits than from a reasonable dose of quinine.
Quinine in the puerperal state.—— It is a wise precaution in malarious countries to give a few 5-gr. doses of quinine during labour or soon after. The puerperal state seems to have the effect, as any other shock or physiological strain might, of waking up the slumbering malaria parasite. A dose or two of quinine in these circumstances does no harm, and may, by choking off a threatening fever, avert suffering and anxiety, not to mention danger. ”

“ Despite these anecdotal observations, there is little evidence for large variations in quinine pharmacokinetics [ [97] and the exact role that variations in drug levels play in quinine treatment responses is unclear.
Quinine drug quality and treatment compliance
The quality of quinine used in routine care could play a key role in clinical outcomes. Poor quality drugs remain a problem worldwide and are a serious public health threat. ”

“ Two successful methods may be adopted. The quinine may be given in a single large dose—30 grains of the sulphate, or 20 of the acid hydrochloride—an hour or two before the attack is due, i.e. just before the parent organism in the red blood corpuscles is about to discharge the new generation of young parasites into the blood-plasma. An equally effective method, which may be combined with the above, is to give the quinine in 10-grain doses of the acid hydrochloride every four hours between the attacks. ”

“ Purified quinine then replaced the bark as the standard treatment for malaria [5] . Quinine and other cinchona alkaloids including quinidine, cinchonine and cinchonidine are all effective against malaria. The efficacies of these four alkaloids were evaluated in one of the earliest clinical trials, conducted from 1866 to 1868 in 3600 patients using prepared sulfates of the alkaloids. With the main outcome measure of "cessation of febrile paroxysms", all four alkaloids were found to be comparable, with cure rates of >98% [ [6] . ”

“ I knew what a delirious wreck an attack can make of a white man in the jungle, and I had impressed upon my young inspectors that I would not forgive any carelessness about quinine—five grains a day as a prophylactic, and at the slightest symptom increase the dose until the temperature swings back to normal. ”

“ This study also reported that treatment failure rates with quinine remained stable over the five-year period of surveillance.
Even with seven-day treatment durations, evaluations of different quinine dosage regimens have revealed interesting trends. Doses of 10 mg/kg/day given twice daily for 7 days were associated with day 28 treatment failure rates as high as 30% [38] . Increasing the quinine dosage to 15 mg/kg/day or 20 mg/kg/day improved treatment outcomes, with failure rates ranging from 8% to 14% [ [38] , although potential increases in toxicity with higher dosages are a concern. ”

“ If sunlight can be regarded as a factor in the formation of alkaloids in the living plant, it has, on the other hand, a decidedly injurious action upon the quinine in the bark stripped from the tree. On drying such bark in full sunlight the quinine is decomposed, and there are formed dark-colored, amorphous, resin-like masses. In the manufacture of quinine the bark is consequently dried in darkness. ”

“ Author of “Action physiologique de la quinine sur la rate. Essai de critique expérimentale;” “Thèse pour le Doctorat, Paris,” 1873.
“All the experiments which we describe on this subject have been made on dogs and on a cat. Some few which are not mentioned [13] were made on rabbits and a few on guinea-pigs. The results obtained amount to little or nothing. We must say once for all that our experiments with strychnine and quinine have also given no exact result.”—Collection de Thèses pour le Doctorat, Paris, 1873, p. 25. ”