Clofazimine, used in multibacillary leprosy and MDR-TB regimens, exerts its antimycobacterial effect through which mechanism?

• A Inhibition of mycobacterial RNA polymerase beta subunit, preventing transcription
• B Inhibition of mycobacterial 30S ribosomal subunit protein synthesis
• C Intercalation into mycobacterial DNA and generation of reactive oxygen species via a riminophenazine redox cycling mechanism, causing membrane disruption ✓
• D Selective inhibition of mycobacterial phospholipase C, disrupting cell wall phospholipid turnover

Explanation

Clofazimine is a riminophenazine compound that intercalates into mycobacterial DNA, inhibiting replication. More importantly, it undergoes redox cycling with intracellular reactive oxygen species (ROS) generation, particularly in anaerobic conditions. The resulting oxidative stress damages the mycobacterial membrane. It also has anti-inflammatory properties by inhibiting TNF-alpha and prostaglandin synthesis, contributing to its benefit in ENL reactions in leprosy.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.