Genotoxic Potential of Some Commonly Used Antimalarials: a Review

Malaria caused mostly by P. falciparum and P. vivax, remains one of the most important infectious diseases in the world. The numbers of antimalarial drugs in use are very small. Drug toxicity must be acceptable to patients and should cause less harm than the disease itself. Assessment of hazard and risk varies throughout drug development as more persons are exposed for longer periods of time and more nonclinical information on the hazard is collected and evaluated. Cancer risk for human pharmaceuticals is important because drugs are taken at pharmacologically active doses and often on a chronic basis. Epidemiologic studies on patient populations have limited value because of the long latency period for most cancers and because these studies lack sensitivity. Besides the mutagenicity and genotoxicity testing of antimalarial drugs as a part of pre-clinical trials, there are several literatures confirming the mutagenicity and genotoxicity of marketed antimalarial drugs. Genetic abnormalities may also play a part in the incidence and severity of adverse reactions to drugs. In this paper, a comprehensive review of literature pertaining to the mutagenic and genotoxic properties of some commonly used antimalarial drugs is presented. INTRODUCTION: Malaria is a mosquito borne infectious disease caused by eukaryotic protist of the genus Plasmodium. It is widespread in tropical and subtropical regions, including parts of Asia, America and Africa. Each year there are approximately 250-500 million cases of malaria, killing between one and three million people, the majority of whom are young children . Several drugs are used for the treatment of malaria. Use of prophylactic drugs are seldom practical for full time residents of malarial endemic areas, and their use are usually restricted to short term visitors and travelers to malarial regions. This is due to the cost of purchasing drugs, negative side effects from long term use, and because some effective antimalarial drugs are difficult to obtain outside the wealthy nations. Quinine was used starting in the 17 centuary as a prophylactic against malaria. The development of more effective alternatives such as Chloroquine, Primaquine and Quinacrine in the 20 centuary reduced the reliance on quinine. Today, quinine is still used to treat chloroquine resistant Plasmodium falciparum, as well as severe and cerebral stages of malaria but is not generally used for prophylaxis. There are three potential ways to control malaria: elimination of vector, drug therapy and vaccination. Elimination of the vector currently is the simplest and most cost effective. The current antimalarial drugs, while effective against certain species, also have significant adverse reaction, and resistance is