Metronidazole is effective against anaerobes and protozoa but not against aerobes. This selective toxicity is due to:
- A Aerobes lack the nitroreductase enzyme needed to activate metronidazole
- B Aerobes express efflux pumps specific for nitroimidazoles that are absent in anaerobes
- C Metronidazole is inactivated by aerobic superoxide dismutase before reaching DNA
- D In anaerobes and protozoa, the low intracellular redox potential (Eh) allows reduction of metronidazole's nitro group to a toxic radical; aerobes maintain a high Eh that prevents this reduction ✓
Explanation
Metronidazole is a prodrug; its nitro group acts as an electron acceptor. In anaerobic organisms and protozoa (which have low intracellular redox potential, Eh below −200 mV), electrons from ferredoxin or pyruvate:ferredoxin oxidoreductase are donated to metronidazole, generating highly reactive cytotoxic radical anions and nitroso intermediates that cause DNA strand breakage. Aerobic organisms maintain a high Eh (~+100 to +200 mV), preventing this reduction and explaining selective toxicity.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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