What is Quinine?

Quinine is a cinchona alkaloid that belongs to the aryl amino alcohol group of drugs. It is an extremely basic compound and is, therefore, always presented as a salt. Various preparations exist, including the hydrochloride, dihydrochloride, sulphate, bisulphate, and gluconate salts; of these the dihydrochloride is the most widely used. Quinine has rapid schizonticidal action against intra-erythrocytic malaria parasites. It is also gametocytocidal for Plasmodium vivax and Plasmodium malariae, but not for Plasmodium falciparum. Quinine also has analgesic, but not antipyretic properties. The anti-malarial mechanism of action of quinine is unknown.

Quinine is rapidly absorbed both orally and parenterally, reaching peak concentrations within 1-3 hours. It is distributed throughout the body fluids and is highly protein bound, mainly to alpha-1 acid glycoprotein. The binding capacity in plasma is concentration dependent, but also depends on the levels of alpha-1 acid glycoprotein, which therefore makes comparisons between different studies difficult. Quinine readily crosses the placental barrier and is also found in cerebral spinal fluid. Excretion is rapid - 80% of the administered drug is eliminated by hepatic biotransformation and the remaining 20% is excreted unchanged by the kidney. The half-life of quinine ranges between 11-18 hours. Several pharmacokinetic characteristics of quinine differ according to the age of the subject and are also affected by malaria. The volume of distribution is less in young children than in adults, and the rate of elimination is slower in the elderly than in young adults. In patients with acute malaria the volume of distribution is reduced and systemic clearance is slower than in healthy subjects; these changes are proportional to the severity of the disease. As a result, plasma quinine levels are higher in patients with malaria. Protein binding of quinine is increased in patients with malaria as a result of an increased circulating concentration of alpha-1 acid glycoprotein.

Quinine has a low therapeutic index, and adverse effects with its use are substantial [16]. The side effects commonly seen at therapeutic concentrations are referred to as cinchonism, with mild forms including tinnitus, slight impairment of hearing, headache and nausea. Impairment of hearing is usually concentration dependent and reversible. More severe manifestations include vertigo, vomiting, abdominal pain, diarrhea, marked auditory loss, and visual symptoms, including loss of vision. Hypotension may occur if the drug is given too rapidly, and venous thrombosis may occur following intravenous injections. Intramuscular administration is painful and may cause sterile abscesses. Hypoglycaemia is yet another common side effect of quinine therapy [15, 18] and is a particular problem in pregnant women[19]. Hypoglycaemia has been reported to occur in up to 32% of patients receiving quinine therapy[18]. However in more recent studies, hypoglycaemia occurred in only 3% of adults and 2.8% of African children receiving quinine. Less frequent but more serious side effects of quinine therapy include skin eruptions, asthma, thrombocytopaenia, hepatic injury and psychosis.

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