In multi-bacillary leprosy (MB), dapsone is combined with rifampicin and clofazimine in the WHO MDT regimen. Which unique mechanism does clofazimine employ to exert its anti-mycobacterial effect?

• A Inhibits dihydropteroate synthase preventing folate synthesis
• B Binds to guanine residues in mycobacterial DNA causing strand breaks
• C Inhibits RNA polymerase beta-subunit preventing mycobacterial transcription
• D Undergoes redox cycling generating reactive oxygen species that damage mycobacterial membranes ✓

Explanation

Clofazimine, a riminophenazine, is taken up preferentially by mycobacteria and undergoes redox cycling between oxidised and reduced forms, generating reactive oxygen species (superoxide, hydrogen peroxide) that damage mycobacterial cell membranes and DNA. It also binds to mycobacterial DNA directly. This mechanism is distinct from the other MDT drugs: dapsone inhibits dihydropteroate synthase (DHPS), and rifampicin inhibits RNA polymerase. Clofazimine's anti-inflammatory properties also contribute to the treatment of erythema nodosum leprosum reactions.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.