Metronidazole requires anaerobic activation for its bactericidal effect. The active cytotoxic species formed after reductive activation is:
- A Nitro radical anion and hydroxylamine intermediates that cause single- and double-strand DNA breaks ✓
- B Superoxide radical generated by electron transfer from NADPH oxidase
- C Reactive oxygen species from enhanced mitochondrial electron transport
- D Formaldehyde generated by CYP450-mediated oxidative metabolism in anaerobic organisms
Correct answer: A. Nitro radical anion and hydroxylamine intermediates that cause single- and double-strand DNA breaks
Explanation
In anaerobes and certain protozoa (Trichomonas, Entamoeba, Giardia), ferredoxin or similar electron-transport proteins have sufficiently negative redox potential to donate electrons to the nitro group of metronidazole, generating nitro radical anions and hydroxylamine intermediates. These reactive species cause irreparable single- and double-strand DNA breaks, leading to cell death. Aerobic organisms cannot reduce metronidazole to these toxic intermediates, explaining its selectivity for anaerobes.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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