Clinical Pharmacology Of Malaria

Abstract

Effective chemotherapy of malaria relies on an accurate diagnosis and an appropriate affordable choice of drugs bearing in mind likely adverse effects, patterns of drug resistance, and the degree of host immunity. Choice of Antimalarial Drug: Treatment of multidrug-resistant Plasmodium falciparum malaria prevalent in our environment relies increasingly on combination chemotherapy using blood schizonticides. Chloroquine and Sulfodoxine/Pyremethamine have been cheap and safe options. However widespread resistance to these drugs (and the problem of chloroquine-related pruritus) means that these agents are often ineffective. Quinine has been relied on for multidrug-resistant malaria. However its marked toxicity potential (e.g. cinchonism and ventricular tachyarrhythmias) means that other drugs such as mefloquine, doxycycline, chlorproguanil-dapsone and proguanil-atovaquone are preferred. Halofantrine is not recommended because of its cardiotoxic potential. Increasing problems with drug resistance have led to current recommendations for the use of artemisinin-based combination therapy such as co-artemether (artemether plus lumefantrine). Plasmodium vivax, P. ovale and P. malariae remain sensitive to chloroquine, and likewise the emergent parasite P. knowlesi . Primaquine is used to eradicate hypnozoites of P. vivax and P. ovale . Treatment of malaria: Prompt treatment is of vital importance, especially in patients who lack innate or acquired immunity. Delaying effective treatment increases morbidity and mortality. Circumstances such as pregnancy and infancy should be taken into account, for example to avoid possible teratogenic effects of mefloquine, artemisinins or halofantrine during the first trimester, and to avoid primaquine and halofantrine while breastfeeding. Supportive treatment is important in severe malaria. Fever is part of the host defence against infection and so should not be entirely suppressed. Careful attention should be paid to fluid balance, to postural hypotension and hypoglycemia (which are exacerbated by quinoline antimalarials), to accompanying bacterial infections, renal impairment and the need for anticonvulsants or blood transfusion. Therapeutic failure may be due to a wrong diagnosis, or an additional cause for the febrile illness apart from malaria. Parasite resistance to antimalarials, poor patient compliance, and the use of fake or substandard drugs are alternative explanations. Key Words: Malaria, Drug treatment of Malaria, Clinical Pharmacology Orient Journal of Medicine Vol.16(2) 2004: 59-69