## Analysis of First-Line Anti-TB Drugs ### Mechanism of Action Review | Drug | Mechanism | Phase | Bactericidal/Static | |------|-----------|-------|--------------------| | Isoniazid (INH) | Inhibits mycolic acid synthesis | Both | Bactericidal | | Rifampicin (RIF) | RNA polymerase inhibition | Both | Bactericidal | | Pyrazinamide (PZA) | Converted to pyrazinoic acid in acidic pH; disrupts membrane potential | Intensive | Bactericidal | | Ethambutol (EMB) | Inhibits arabinosyl transferase; disrupts arabinogalactan synthesis | Both | Bacteriostatic | ### Key Point: **Ethambutol is bacteriostatic, NOT bactericidal.** It is used as a fourth agent in the intensive phase (2 months) to prevent resistance, particularly when INH resistance is suspected. The backbone of first-line therapy is the three bactericidal agents: INH, RIF, and PZA. ### High-Yield: **Standard intensive phase (2 months):** INH + RIF + PZA + EMB (4-drug regimen) **Continuation phase (4 months):** INH + RIF (2-drug regimen) Ethambutol is added to the intensive phase to prevent emergence of INH-resistant mutants, not because it is the preferred agent. The statement that "Ethambutol is bactericidal and is the preferred first-line agent" is doubly incorrect. ### Clinical Pearl: Rifampicin's enzyme induction is clinically significant — it reduces levels of warfarin, oral contraceptives, protease inhibitors, and corticosteroids. Patients on these drugs require dose adjustment or alternative contraception during TB treatment. ### Warning: ~~Ethambutol is bactericidal~~ — it is bacteriostatic. Do not confuse it with the three truly bactericidal first-line drugs (INH, RIF, PZA).
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