Quinine

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Pharmacology and toxicology

Quinine is the oldest antimalarial agent. It has a good and rapid sch-izonticide activity against the erythrocytic forms of all Plasmodium species. In spite of relatively high toxicity and a narrow therapeutic range, it is used more often for the treatment of chloroquine-resistant malaria today. Concentrations in the fetus are just as high as in the mother, and arc potentially toxic. There are some reports describing eye defects and hearing loss in children after use of quinine in pregnancy. However, in those cases considerably higher doses had generally been administered than are used nowadays for the treatment of acute malaria. There is no evidence of an increased risk of abortion or preterm delivery with the use of a standard dosage of quinine for treatment of acute malaria (Philips-Howard 1996). In a study on the use of quinine for the treatment of Plasmodium falciparum infection during the first trimester of pregnancy (n = 165) these findings were confirmed, as no increased rates of spontaneous abortion, congenital malformations, stillbirth or low birth weight were found (McGready 2002).

Pregnancy outcome has been compared between mefloquine-treated and quinine-treated pregnant women. Women who were treated with mefloquine in pregnancy had a significant greater risk of stillbirth than did women treated with quinine alone; there was no difference in risk of congenital malformations (Nosten 1999).

A trial comparing quinine-clindamycine (n = 64) with artesunate (n = 65) for the treatment of falciparum malaria during the second or third trimesters of pregnancy found no serious adverse effects, no increase in stillbirths or congenital malformations above expccted rates, and no negative impact on child development for both regimens (McGready 2001A). A small trial comparing quinine with artesunate-atovaquone-proguanil (n = 39) for the treatment of falciparum-malaria during the second or third trimesters of pregnancy found no serious adverse effects and no significant differences in birth weight, gestational age, congenital malformation rates, or in growth and developmental parameters of infants (McGready 2005).

Especially in the last part of pregnancy, severe maternal hypoglycemia has been induced by quinine therapy.

Induction of contractions with high doses of quinine cannot be excluded. Quinine is a component of some analgesic compounds and of certain beverages, although in lower and apparently non-embryotoxic doses.

Recommendation. In pregnancy, quinine can be used for therapy of acute chloroquine-resistant falciparum malaria. The potential risk for the fetus due to the therapy is much less than the hazards due to the severe maternal disease. Attention should be paid to possible maternal hypoglycemia. Even though embryotoxic effects due to quinine in analgesic compounds are not to be expected, these agents should be avoided because they do not conform to good therapeutical practice.

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