Metronidazole is active against anaerobes and certain protozoa but inactive against aerobic organisms. The mechanism underlying this selective toxicity is:
- A Metronidazole's nitro group is reduced by anaerobic ferredoxin electron transport, generating cytotoxic free radicals that disrupt anaerobic DNA ✓
- B Metronidazole is a prodrug activated by mammalian liver enzymes only in tissues with low oxygen tension
- C Anaerobes lack glutathione reductase allowing metronidazole oxidative intermediates to persist
- D Metronidazole inhibits anaerobic-specific thymidylate synthase absent in aerobes
Correct answer: A. Metronidazole's nitro group is reduced by anaerobic ferredoxin electron transport, generating cytotoxic free radicals that disrupt anaerobic DNA
Explanation
Metronidazole enters organisms passively; its nitro group is reduced by low-potential electron carriers (ferredoxin in anaerobes, flavodoxin in some protozoa) only under anaerobic/microaerophilic conditions. This reduction generates cytotoxic nitro radical anions and other reactive intermediates that cause strand breaks in DNA, disrupting replication and transcription. In aerobic organisms, oxygen reoxidizes these intermediates before they can cause damage, explaining the strict selectivity for anaerobes and microaerophiles.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.