Medicine & USMLE


Antibiotics / Antiparasitics
  1. Penicillin Overview
  2. Penicillinase-Sensitive vs. Penicillinase-Resistant Penicillins
  3. Anti-Pseudomonal Penicillins
  4. Cephalosporins Overview
  5. 1st Generation Cephalosporins
  6. 2nd Generation Cephalosporins
  7. 3rd Generation Cephalosporins
  8. 4th Generation Cephalosporins
  9. 5th Generation Cephalosporins
  10. Carbapenems
  11. Monobactams (Aztreonam)
  12. Vancomycin
  13. Aminoglycosides
  14. Tetracyclines
  15. Tigecycline
  16. Chloramphenicol
  17. Clindamycin
  18. Linezolid
  19. Macrolides
  20. Polymyxins
  21. Sulfonamides
  22. Dapsone
  23. Trimethoprim
  24. Fluoroquinolones
  25. Daptomycin
  26. Metronidazole
  27. Rifamycins (Rifampin, Rifabutin)
  28. Isoniazid
  29. Pyrazinamide
  30. Ethambutol
  31. Chloroquine


Isoniazid (INH)  is an antibiotic commonly used to treat tuberculosis by inhibiting the synthesis of mycolic acid. It is activated in the body by the enzyme catalase-peroxidase, also called KatG. Remember that KatG is encoded upstream by a gene, also called KATG. Isoniazid is metabolized in the liver through acetylation, so the side effects of isoniazid will be more prevalent in slow acetylators. Isoniazid often causes a vitamin B6 deficiency, so vitamin B6 supplements are often taken along with the drug. Isoniazid inhibits CYP450 enzymes, so it can cause drug-to-drug interactions with other medications that are metabolized by the CYP enzymes, such as  warfarin and theophylline. Other adverse side effects include a lupus-like reaction, hepatotoxicity, and an anion gap metabolic acidosis.

Key Points

  • Isoniazid (INH)
    • Mechanism
      • Impairs synthesis of mycolic acid
        • Mycolic acid is a key component of mycobacterial cell wall
      • Must be activated by bacterial catalase-peroxidase (encoded by KatG)
        • Isoniazid is an inactive pro-drug that must be converted into its active drug by an mycobacterial enzyme
    • Clinical Use
      • Mycobacteria (especially M. tuberculosis)
        • Major component of RIPE therapy for active TB
        • Monotherapy for latent TB, TB prophylaxis
    • Adverse Effects
      • Side effects more common in slow acetylators
        • INH is metabolized by acetylation, so drug has higher effective dosing and longer half-life in slow acetylators
      • Vitamin B6 (pyridoxine) deficiency
        • Isoniazid inhibits pyridoxine phosphokinase, which normally activates vitamin B6 into its active form (PLP)
        • Presents as peripheral neuropathy, sideroblastic anemia, seizures (in high doses)
        • Many patients on INH will require vitamin B6 supplementation
      • Inhibits CYP450 Enzymes
        • May lead to drug interactions (e.g. warfarin, theophylline)
      • Drug-induced lupus-like reaction
      • Hepatotoxicity
      • Anion gap metabolic acidosis
    • Resistance
      • Mutations cause underexpression of KatG
        • Reduces catalase-peroxidase, which prevents conversion of drug into active form
      • Mutations of binding site on mycolic acid synthase enzyme is also possible