Nitroimidazoles - Parasites Chemotherapy Drugs

Nitroimidazoles

Metronidazole, a nitroimidazole, was introduced in 1959 for the treatment of trichomonia-sis. Subsequently, it was found to be effective in the management of giardiasis, amebiasis, and a variety of infections produced by obligate anaerobic bacteria. Energy metabolism in all of them depends on the presence of low-redox-potential compounds, such as ferre-doxin, to serve as electron carriers. These compounds reduce the 5-nitro group of the imi-dazoles to produce intermediate products responsible for the death of the protozoal and bacterial cells, possibly by alkylation of DNA. Resistance, although uncommon, has been noted in strains of T. vaginalis lacking nitroreductase activity. Of greater concern is in vitro evidence of mutagenicity. Metronidazole is the drug of choice for trichomoniasis and invasive amebiasis. It is effective in giardiasis although not yet approved by the Food and Drug Administration for use in this infection. Tinidazole, a newer nitroimidazole not yet available in the United States, appears to be both a more effective and less mutagenic antiprotozoal agent. Its greater lipid solubility improves cerebrospinal fluid levels and in vitro activity.