Antimalarial Drugs

Abstract

Over the last decade, chloroquine-resistant falciparum malaria has spread to other areas from its original foci in Southeast Asia and South America. Additionally, new knowledge about the life-cycle of the malaria parasite, and about the pharmacokinetic properties of antimalarial drugs, has emerged. It is appropriate to reassess our approach to prevention and management of malaria with these factors in mind. Antimalarial drugs can be classified in two ways: biologically as tissue schizontocides, hypnozoitocides, blood schizontocides, gametocytocides or sporontocides; or by a mixed chemical/biological classification as 8-aminoquinolines, antimetabolites and (again) blood schizontocides. Chloroquine resistance in P. falciparum can now be found in most areas where malaria occurs. Malarial strains moderately resistant to the chloroquine group of drugs (chloroquine and mepacrine) are generally susceptible to the aryl amino alcohols such as quinine. Indeed, quinine is the most widely used drug for treating malaria due to chloroquine-resistant strains, followed by a 7-day course of tetracycline where some resistance to quinine is also found. Alternatively, the course of quinine may be followed by sulfadoxine/pyrimethamine or the newer quinoline derivative, mefloquine. Quinidine has also shown activity against quinine-resistant strains. Prophylaxis of chloroquine-resistant strains is best undertaken with daily proguanil (chloroguanide), and weekly chloroquine. In severe malaria, including cerebral malaria, an intravenous loading dose of quinine should be considered, and plasma concentration monitoring may be advisable to assist with dosage adjustment. In patients with severe renal insufficiency, there is evidence that the elimination of chloroquine is prolonged, and dosage adjustments may be necessary. Other recent findings on the pharmacodynamic properties, mechanisms of action and toxicity of antimalarial drugs are also discussed.

Randomized Controlled Trial of Artesunate Plus Tetracycline Versus Standard Treatment (Quinine Plus Tetracycline) for Uncomplicated Plasmodium falciparum Malaria in Brazil

“…Among the 141 patients who fully complied during both trcatment and follow-up periods only 3 recrudescences occurred (ail type RI), two in the AT group and one in the QT group (Table 5. 12). Therefore, cure rates of97% and 98% would have been obtained in the AT and QT groups respectively 1 if the analysis would have been Iimited to compliant patients alone (n= 141).…”

Inhibition of Plasmodium falciparum dihydropteroate synthetase and growth in vitro by sulfa drugs

“…Important antifolate antimalarial agents include pyrimethamine and chlorguanide, which inhibit dihydrofolate reductase, and sulfadoxine and dapsone, which inhibit dihydropteroate synthetase (DHPS). Activities of combinations of inhibitors of both enzymes, such as sulfadoxine and pyrimethamine (Fansidar), are synergistic (17).…”

Andrographis paniculata: A Review of its Traditional Uses, Phytochemistry and Pharmacology

“…Moreover, P. falciparum has acquired significant resistance and become prevalent in different parts of the world, which is a matter of serious concern [113,114]. Further, mefloquine resistance among P. falciparum has become more common in some of the eastern countries [115]. Even resistance against the novel drug-quinine has been recently reported from certain parts of South East Asia and Brazil [116].…”