Evolution of Antimalarial Drugs

The effectiveness of the antimalarial drugs may differ with the species and stage of parasite and the parasite load in the liver and blood circulation. The malaria is an intracellular protozoan infection, endemic in tropical and subtropical countries. Four species of the protozoal parasite Plasmodium cause all infections in human beings and these are: Plasmodium vivax, Plasmodium malariae, Plasmodium ovale and Plasmodium falciparum. The parasites are inoculated into the human host by blood sucking female anopheline mosquitoes. The sporozoites from the infected mosquito reach the liver and develop into tissue schizonts. These tissue schizonts then rupture, form free merozoites and invade erythrocytes or red blood cells (RBCs) and develop as erythrocytic schizonts and lead to rupture of RBCs. Antimalarial drugs have undergone a great deal of evolution and at present there are many classifications of antimalarial drugs depending on the stages of malarial parasites in the liver and erythrocytes, on the bases of chemical groups or clinical effectiveness of the drugs.

If we look at the chemical groups of antimalarial drugs the Cinchona alkaloid or Quinine and Quinidine were the very first drugs and there after 4-aminoquinoline (Chloroquine and Amodiaquine), 8-aminoquinoline (Primaquine and Bulaquine), Quinoline-Methanol (Mefloquine) and Biguanides (Proguanil and Chlorproguanil) were developed. Diaminopyrimidines (Pyrimethamine), Sulfonamides (Sulfadoxine and Dapsone), Tetracyclines (Tetracycline and Doxycycline) and Aminoalcohols (Halofantrine and Lumefantrine) are other effective antimalarial drugs. Chloroquine has been used extensively for the treatment and prevention of malaria. It has considerable efficacy for the treatment of Plasmodium vivax, Plasmodium malariae and Plasmodium ovale infections, however, widespread resistance has been seen against Plasmodium falciparum infection. Artemisinin, Artemether, Artemotil and Atovaquone could be called newer antimalarial drugs. Artemisinin or Qinghaosu is a sesquiterpene lactone extracted from the leaves of Artemisia annua known as Sweet Wormwood in China. The extract of the leaves of Artemisia annua or Sweet Wormwood has been used in China for over a thousand years for the treatment of fever. Antifolate combinations like sulfadoxine pyrimethamine and sulfalene pyrimethamine are more safe drugs but are known to have longer elimination half life.

In terms of clinical effect on various stages of malarial parasites, the effectiveness of antimalarial drugs is contested for prophylaxis and anti-parasite activity. Effective suppressive prophylaxis has been documented with chloroquine, mefloquine, proguanil and doxycycline as these are schizonticidal drugs. Proguanil and primaquine are best known for causal prophylaxis as these drugs effectively kill the hepatic stages of the parasite. Quinine, chloroquine, primaquine and artemisnins are established gametocidal drugs also. Sulfonamides (sulfadoxine and dapsone) and aminoalcohols (halofantrine and lumefantrine) are also used in the treatment of malaria but are more toxic drugs. The drug toxicity may lead to acute hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Consult your physician for the diagnosis and treatment of malaria.