Question
Isoniazid (INH)
Answer
Isoniazid is a first-line antitubercular drug.
MOA: a prodrug, activated by the mycobacterial catalase-peroxidase enzyme KatG, after which the active metabolite inhibits InhA, an enzyme in mycolic acid synthesis — blocking synthesis of the mycobacterial cell wall’s distinctive waxy component, bactericidal specifically against actively dividing organisms.
Uses: pulmonary and extrapulmonary tuberculosis (combination therapy), chemoprophylaxis (monotherapy for 6-9 months in close contacts and latent TB infection).
Adverse effects: peripheral neuropathy (from interference with pyridoxine metabolism — prevented by co-administered pyridoxine), hepatotoxicity (idiosyncratic, risk increases with age and alcohol use), inhibits hepatic microsomal enzymes (opposite direction from rifampicin).