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Chapter: Medical Microbiology: An Introduction to Infectious Diseases: Introduction to Pathogenic Parasites: Pathogenesis and Chemotherapy of Parasitic Diseases

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Quinones - Parasites Chemotherapy Drugs

Atovaquone is a novel hydroxynaphthoquinone that shows promise in the treatment of malaria and toxoplasmosis.

Quinones

Atovaquone is a novel hydroxynaphthoquinone that shows promise in the treatment of malaria and toxoplasmosis. In the search for effective antimalarial agents during World War II, a number of hydroxynaphthoquinones were found to have antimalarial activity in experimental animals; however, all were rapidly metabolized in humans and proved inef-fective in the treatment of malarious patients. In the 1980s a single hydroxynaphtho-quinone, atovaquone, was found to be both highly effective in vitro against P. falciparum and metabolically stable in humans when administered orally. Its antiparasitic activity appears to result from the specific blockade of pyrimidine biosynthesis secondary to the inhibition of the parasite’s mitochondrial electron transport chain at the ubiquinol– cytochrome c reductase region (complex III). Its long half-life (70 hours) and lack of seri-ous adverse reactions suggested that it would be of great value in the treatment of malaria. Efficacy trials established its capacity to effect rapid clearance of parasitemia in patients with chloroquine-resistant falciparum malaria. Frequent parasitic recrudescences were eliminated when atovaquone was administered in combination with proguanil or tetracycline. Subsequently, this agent has shown to be effective for the treatment of toxo-plasmosis in patients with acquired immunodeficiency syndrome (AIDS). Unlike other antitoxoplasma agents, atovaquone has been found to be active against T. gondii cysts as well as tachyzoites, suggesting this agent may produce radical cure. Supporting this is the infrequency with which cessation of atovaquone treatment of toxoplasmic cerebritis in AIDS patients has resulted in relapse. Relapse following atovaquone treatment of pneu-mocystosis in this same patient population appears similarly uncommon.

 

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