First-Line Anti-Tubercular Drugs (HRZE): MOA, Toxicities & KD Tripathi Pearls
High-Yield Clinical Pearls & Exam Keys
Isoniazid (INH) is a prodrug activated by mycobacterial catalase-peroxidase enzyme (KatG), which then inhibits mycolic acid synthesis by targeting InhA.
Rifampicin binds to the beta subunit of bacterial DNA-dependent RNA polymerase, blocking transcription. Causes benign orange-red discoloration of body fluids.
Pyrazinamide is active in acidic intracellular environments (caseous necrosis), converted to pyrazinoic acid by pyrazinamidase. Most hepatotoxic first-line ATT.
Ethambutol is the ONLY bacteriostatic first-line ATT drug. Inhibits arabinosyl transferase (embB), causing dose-dependent Retrobulbar Optic Neuritis (loss of red-green vision).
First-Line ATT (HRZE) Quick Summary Matrix
| Drug Name | Mechanism of Action (MOA) | Key Toxicity / Clinical Pearl |
|---|---|---|
| Isoniazid (H) | Inhibits mycolic acid synthesis via KatG activation | Peripheral neuropathy (prevented with Pyridoxine Vit B6), Hepatotoxicity, Drug-induced SLE |
| Rifampicin (R) | Inhibits DNA-dependent RNA Polymerase (beta subunit) | Potent CYP3A4 enzyme inducer, Orange-red urine/sweat, Hepatotoxicity |
| Pyrazinamide (Z) | Disrupts mycobacterial membrane potential in acidic pH | Hyperuricemia (Gout), Highest hepatotoxicity among all first-line drugs |
| Ethambutol (E) | Inhibits arabinosyl transferase (blocks arabinogalactan) | Retrobulbar optic neuritis (Decreased visual acuity, red-green color blindness), Safe in renal/hepatic failure with dose adjustments |
Viva Examiner Traps & Model Answers
Oral Exam PrepIsoniazid combines chemically with pyridoxal phosphate to form an inactive hydrazone and also promotes renal excretion of pyridoxine. This depletes active Vitamin B6, impairing GABA synthesis and causing severe peripheral neuropathy.
Interactive Clinical Vignette Practice
Rule-Out EngineA 45-year-old male with pulmonary tuberculosis on HRZE therapy complains of difficulty reading newspapers and distinguishes traffic light colors poorly. Visual acuity testing reveals decreased bilateral central vision. Which drug is responsible?
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