Three Drugs with Distinct Mechanisms

Metronidazole, nitazoxanide, tinidazole

Mechanism of action. Metronidazole is selectively absorbed
by anaerobic bacteria and sensitive protozoa. Once
taken up by anaerobes, it is nonenzymatically reduced by
reacting with reduced ferredoxin, which is generated by pyruvate/
ferredoxin oxido-reductase. This reduction causes the
production of metabolites that are toxic to anaerobic cells,
resulting in inhibition of DNA synthesis, degradation of existing
DNA, DNA strand breaks, and inhibition of nucleic acid
synthesis, all of which lead to bacterial cell death. Similarly,
nitazoxanide interferes with pyruvate/ferredoxin oxidoreductase
enzyme-dependent electron transfer, a reaction essential
for anaerobic metabolism. Tinidazole is believed to
cause cytotoxicity by damaging DNA and inhibiting further
DNA synthesis. Because of their actions, these drugs may
be mutagenic and possibly carcinogenic. Both tinidazole
and metronidazole are contraindicated during the first trimester
of pregnancy.