Quinine toxicity

Mild toxic reactions are characterized by slight reduction of visual acuity, flickering of vision, color vision decrease, impaired night vision, tinnitus, weakness, or confusion. In more severe cases, symptoms consist of sudden complete loss of vision, dizziness, and even deafness. Coma with circulatory collapse characterizes the most severe form of quinine toxicity. Patients may complain of impairment of night vision, but color vision is usually normal. The visual fields usually demonstrate concentric constriction. Improvement of the visual fields after the acute episode may require days or months, but the field loss may show no recovery and become permanent. 

The visual prognosis for patients with acute quinine toxicity is guarded. Visual acuity can improve from no Ught perception to 20/20 within days to several weeks or months. As vision recovers there is progressive constriction of the retinal vessels, and the optic disc becomes pale. Although central vision often retmns to normal levels, the visual fields can remain constricted, and night and color vision changes can be permanent. 

In general, the maximum daily dosage of quinine should not exceed 2 g quinine toxicity is common in dosages over 4 g. The lethal oral dose in adults is approximately 8 g. Toxic reactions to relatively small dosages of quinine are probably idiosyncratic in nature but can result in a clinical picture similar to that caused by higher dosages. 

Because central vision tends to recover spontaneously even without treatment, patients with acute quinine toxicity should generally be managed by supportive measures alone. Hyperbaric oxygen has been used in an attempt to increase oxygen delivery to the retina. The use of oral activated charcoal or any other gastric decontamination procedures does not improve clinical outcome and may, in fact, be harmful to the patient. It is important to emphasize preventive measures, such as patient education and dispensing of quinine in child-resistant containers. 

In a case of quinine poisoning, stellate ganglion block was performed immediately on the basis of the clinical history of visual disturbance without waiting for physical signs to develop. There was no residual field defect despite the presence of toxic concentrations of the drug. The authors suggested that stellate ganglion block may prevent development of visual field defects due to quinine toxicity (13). However, in other cases it was ineffective (14,15). The effectiveness of this treatment may be a function of the speed with which it is instituted. 

Children under 2 years are more vulnerable to quinine toxicity as measured by prolongation of the QRS interval at 2-4 hours after intravenous quinine (SEDA-20, 261). 

Bacon P, Spalton DJ, Smith SE. Blindness from quinine toxicity. Br J Ophthalmol 1988 72(3) 219-24. 

Bateman DN, Dyson EH. Quinine toxicity. Adverse Drug React Acute Poisoning Rev 1986 5(4) 215-33. 

Chloroquine and other aminoquinolines are used in the prophylaxis or therapy of malaria and other parasitic diseases. Chloroquine and hydroxychloroquine are also used in the treatment of rheumatoid arthritis. Drugs in this class include chloroquine phosphate (Aralen ), amodiaquine hydrochloride (Camoquin ), hydroxychloroquine sulfate (Plaquenil ), mefloquine (Lariam" ), primaquine phosphate, and quinacrine hydrochloride (Atabrine ). Chloroquine overdose is common, especially in countries where malaria is prevalent, and the mortality rate is 10-30%. Quinine toxicity is described on p 326. 

I. Mechanism of toxicity. The mechanism of quinine toxicity is believed to be similar to that of quinidine (see p 324) however, quinine is a much less potent car-diotoxin. Quinine also has toxic effects on the retina that can result in blindness. At one time, vasoconstriction of retinal arterioles resulting in retinal ischemia was thought to be the cause of blindness however, recent evidence indicates a direct toxic effect on photoreceptor and ganglion cells. 

AUC by 42%. Peak levels were unchanged. No interaction was seen when cimetidine was replaced by ranitidine 150 mg twice daily. The probable reason for this effect is that cimetidine (a recognised enzyme inhibitor) reduces the metabolism of the quinine by the liver, whereas ranitidine does not. It therefore seems likely that other H2-receptor antagonists will not interact, although this needs confirmation. The clinical importance of this is uncertain, but prescribers should be alert for any evidence of quinine toxicity if cimetidine is also given. 

G.S. Brinton, E.W. Norton, J.R. Zahn, Ocular quinine toxicity. Invest Ophthalmol. 

M.T. Carapancea, Synchronic quinine toxicity in visual retina and superior nervous... 

P. Dickinson, J. Sabto J., R.H. West, Management of quinine toxicity. Aust J. 

So, in a way, it is with quinine, known (29) since antiquity as a potent antimalarial. For chemists, the use of quinicine in 1854 in the first resolution of a racemate (1,3) marks a milestone Stereochemistry as we know it today made its debut in that year. In resolutions, quinine and its diastereomers proved to be safe to handle (compare the extreme toxicity of brucine or strychnine with that of quinine), versatile in their applications, and available in reasonably pure form. Little wonder that even today, 131 years after its first use as a resolving agent, quinine (and brucine) continues to be the chemical of choice when one is attempting a new resolution of a racemic acid (90). 

Colley, J.C., Edwards, J.A., Heywood, R., and Purser, D., Toxicity studies with quinine hydrochloride, Toxicology, 54, 219-226,1989. 

Different antimalarials selectively kill the parasite s different developmental forms. The mechanism of action is known for some of them pyrimethamine and dapsone inhibit dihydrofolate reductase (p. 273), as does chlorguanide (proguanil) via its active metabolite. The sulfonamide sulfadoxine inhibits synthesis of dihydrofolic acid (p. 272). Chlo-roquine and quinine accumulate within the acidic vacuoles of blood schizonts and inhibit polymerization of heme, the latter substance being toxic for the schizonts. 

Zhu. H.. Li. Y. and Trush, M.A. (1995) Characterizatoin of benzo[a]pyrene quinine-induced toxicity to primary cultured bone marrow stromal cells from DBA/2 mice potential role... 

Quinine is an alkaloid produced by various Cinchona species (e.g. Cinchona pubescens or fever tree), which are mainly native to South America. The bark of these trees were initially used to treat malaria. Quinine itself was subsequently isolated in 1820 and found to be toxic not only to the protozoan Plasmodium (which causes malaria) but also to several other protozoan species. 

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