Quinine

This is a powerful product, which acts upon the schizonts of the parasites in the blood (it is a schizonticide). It thus acts chiefly in the second half of the maturation cycle: on the parasites which are sequestered in the small blood vessels (not on the young ring forms in the peripheral circulation). Quinine also possesses gametocytocidal activity against P. vivax, P. malariae and P. ovale (but not against gametocytes of P. falciparum). Although it was earlier claimed that quinine had a weak antipyretic action (used for example in Latepyrine-quinine®), this is questioned nowadays. Besides treatment of P. falciparum malaria, quinine is also used to reduce muscle cramps. Quinine is available in several forms. It is a substance consisting of 2 parts: a base (the active part) and another chemical group (important for solubility). The 2 components together are called the salt. Some confusion may arise as regards the dosage of quinine, depending on whether this is expressed in mg of the base or in mg of the salt (generally the salt is used).

	Salt in mg	Base in mg
Quinine bisulphate	100	59
Quinine dihydrochloride	100	82
Quinine sulphate	100	82

Quinine base is 82 % of the total substance if the salt is the dihydrochloride or sulphate, but is only 59 % if the salt is the bisulphate. Quinimax® is a product frequently used in Africa. Some 100 mg tablets contain only 59 mg of quinine base, however, and a very small amount of other substances. This may lead to under-dosage.

Quinine sulphate is administered orally. It is absorbed well in the intestines. An obsolete product is Arsiquinoforme®. This combination drug contains 62% quinine in the form of quinine formiate and quinine acetarsolate. Each 225 mg tablet contains 18 mg of pentavalent arsenic. Quinine bihydrochloride is injected, preferably by slow IV (infusion with glucose because of the risk of hypoglycaemia). IM injections may lead to sterile abscesses, but can be used where necessary if there are no alternatives available. For IM injection, it is best to use a diluted solution (60 to 100 mg/ml) in place of the concentrated solution (300 mg/ml). Quinine administered via IM injection is absorbed well even in severe malaria. Treatment with quinine is unpleasant (bitter taste, cinchonism) and poor compliance after the acute phase is common.

Treatment regimens

The basic regimen is 10 mg salt/kg, every 8 hours, orally or slow IV. This should be continued for at least 4 days, preferably 7 to 10 days. This is an unpleasant treatment. Because there is still a risk of relapse if quinine is used in monotherapy, another product is generally combined with it, e.g. tetracycline or vibramycin. Sometimes treatment with Fansidar® is given after a few days, which shortens the treatment period. In the case of cerebral malaria it is best to give a loading dose (first administration = double dose or quinine bichlorhydride 7 mg salt/kg IV over 30 minutes; or once 20 mg/kg IV over 4 to 8 hours). P.S. Please note that the bichlorhydride is given, and not the monochlorhydride. The latter is less water-soluble. Sometimes there is a brief increase in the parasitaemia after beginning therapy. This does not directly mean that the therapy has failed.

If a patient vomits within an hour after swallowing the medication, the whole dose should be repeated. If vomiting occurs longer than one hour after ingestion, no new dose is necessary. In hepatic or renal insufficiency the normal dose of quinine is administered for the first 48 hours. The dose is then reduced to half or one third (administration of quinine is then every 24 hours). There is controversy over this, however, (probably much less of a reduction is necessary). ECG monitoring is recommended during quinine therapy in patients with existing kidney failure (watch in particular for QTc-prolongation and arrhythmia). If haemodialysis is required, quinine should be administered after (rather than before) although little or no quinine is removed by this procedure. Dose adjustment during haemodialysis is not necessary. Classic haemodialysis cannot be used therapeutically in quinine intoxication.

Category: Medicine Notes