Metronidazole antiparasitic effects

Anaerobic parasites, such as T. vaginalis and E. histolytica, lack functional mitochondria. Pyruvate generated by the glycolytic pathway is further metabolized within the cytosol of Giardia and Entamoeba species and in the hydrogenosome of these parasites, a subcellular organelle unique to trichomonads (4). Under anaerobic conditions, pyruvate is converted into acetyl Co-A and COj by pyruvateferredoxin oxidoreductase with the concomitant reduction of ferredoxin. Metronidazole and other nitro-imidazole derivatives are toxic to these anaerobes after reduction of the nitro moiety by ferredoxin. As these compounds are not reduced in mamalian cells, selectivity of their antiparasitic effects is assured (see Chapter 3). 

Derivatives of 2-amino-5-nitrothiazole have antiparasitic activity. Niridazole (253) is used in the treatment of schistosomiasis, but its side-effects make it unattractive for treating other diseases, e.g. amoebiasis, for which safer drugs are available. The nitroimidazole metronidazole (254) is particularly useful in amoebiasis and trichomoniasis, and the latter disease may also be treated with nimorazole, l-morpholinoethyl-5-nitroimidazole. 

ANTIPARASITIC AND ANTIMICROBIAL EFFECTS Metronidazole and related nitroimidazoles are active in vitro against a wide variety of anaerobic protozoal parasites and anaerobic bacteria. The drug also has potent amebicidal activity against E. histolytica. 

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