Antileprotic Drugs (Leprosy)

Introduction

• Leprosy (Hansen disease) — a chronic granulomatous infection by Mycobacterium leprae (discovered by Armauer Hansen, 1873) affecting skin, mucous membranes and peripheral nerves; carries heavy social stigma but is now entirely curable with multidrug therapy — though deformities already incurred may not reverse.
• M. leprae is an obligate intracellular pathogen with a very long doubling time (~14 days) — mandating prolonged, months-to-years therapy — and cannot be cultured in vitro; drugs were historically evaluated in the mouse footpad model.
• Therapeutic barriers — the lipid-rich (>60% mycolic-acid) waxy cell wall, efflux pumps, and intracellular + avascular localisation of bacilli all impede drug penetration.
• Drug evolution — dapsone has been the sheet-anchor since the 1940s; clofazimine added in the 1960s; rifampicin (developed for TB) is the most rapidly cidal; newer activity later found in fluoroquinolones, minocycline and clarithromycin.