PH8.5 | PH8.5 | Tuberculosis Pharmacotherapy — SDL Guide — Summary & Reflection

KEY TAKEAWAYS

Why combination therapy: M. tuberculosis grows slowly (15–20h division), exists in multiple populations (aerobic/semi-dormant/intracellular), and natural mutants resistant to any single drug are always present in large bacillary loads → multi-drug therapy prevents resistance amplification.

HRZE roles: H (INH) — most potent early bactericidal (mycolic acid; pyridoxine-dependent); R (rifampicin) — most important sterilising agent (RNA polymerase β-subunit; potent CYP inducer; orange secretions; NEVER monotherapy); Z (PZA) — kills dormant bacilli at acidic pH only; shortens treatment from 12 to 6 months; only used for first 2 months; E (ethambutol) — arabinogalactan inhibitor; resistance prevention companion; optic neuritis (monitor acuity + colour vision monthly; stop if visual changes).

Toxicity-antidote pairs: INH → peripheral neuropathy → pyridoxine; ETH → optic neuritis → stop drug (irreversible if delayed); RIF → orange secretions (warn patient) + CYP induction; PZA → hyperuricaemia + hepatotoxicity.

Standard regimen: 2HRZE / 4HR (6 months total). MDR-TB: bedaquiline + linezolid + levofloxacin/moxifloxacin as core (WHO Group A). XDR-TB: MDR + fluoroquinolone resistance + bedaquiline or linezolid resistance.

REFLECT

Consider a 25-year-old daily-wage labourer diagnosed with pulmonary TB who lives in a shared room with 5 family members, including a young child. He cannot afford to lose a day's work. The DOTS centre is 8 km away. What barriers to adherence does he face, and what adaptations to the DOTS system would you advocate for? How does pharmacology intersect with social determinants of health in TB control?