Antimalarial drugs are used for the treatment and prevention of malaria infection. Most antimalarial drugs target the erythrocytic stage of malaria infection, which is the phase of infection that causes symptomatic illness (figure 1). The extent of preerythrocytic (hepatic stage) activity for most antimalarial drugs is not well characterized.
Treatment of the acute blood stage infection is necessary for malaria caused by all malaria species. In addition, for infection due to Plasmodium ovale or P. vivax, terminal prophylaxis is required with a drug active against hypnozoites (which can remain dormant in the liver for months, and occasionally years, after the initial infection).
The mechanisms of action, resistance, and toxicities of antimalarial drugs will be reviewed here. Use of these agents for prevention and treatment of malaria is discussed in detail separately. (See "Prevention of malaria infection in travelers" and "Treatment of severe falciparum malaria" and "Treatment of uncomplicated falciparum malaria".)
Quinoline derivatives include chloroquine, amodiaquine, quinine, quinidine, mefloquine, primaquine, lumefantrine, and halofantrine. These drugs have activity against the erythrocytic stage of infection; primaquine also kills intrahepatic forms and gametocytes (figure 1). The drugs act by accumulating in the parasite food vacuole and forming a complex with heme that prevents crystallization in the plasmodium food vacuole. Heme polymerase activity is inhibited, resulting in accumulation of cytotoxic-free heme.
Chloroquine — Chloroquine was the first drug produced on a large scale for treatment and prevention of malaria infection. Chloroquine has activity against the blood stages of Plasmodium ovale, P. malariae, and susceptible strains of P. vivax and P. falciparum . Widespread resistance in most malaria-endemic countries has led to decline in its use for the treatment of P. falciparum, although it remains effective for treatment of P. ovale, P. malariae, and, in most regions, P. vivax. (See "Overview of non-falciparum malaria".)