USMLE

Pyrazinamide

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Antibiotics / Antiparasitics
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  24. Fluoroquinolones
  25. Daptomycin
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  27. Rifamycins (Rifampin, Rifabutin)
  28. Isoniazid
  29. Pyrazinamide
  30. Ethambutol
  31. Chloroquine

Summary

Pyrazinamide is an antibiotic used to treat active tuberculosis. Its exact mechanism is unknown, but it is thought to be active in macrophagic phagolysosomes, which play an important role in the pathogenesis of tuberculosis.  Adverse effects of pyrazinamide use include hepatotoxicity, which can manifest with jaundice, liver tenderness, and elevated liver enzymes. Hyperuricemia and gout are also side effects seen with the drug.

Key Points

  • Pyrazinamide (PZA)
    • Mechanism
      • Exact mechanism is unknown
        • Activated by conversion to pyrazinoic acid by the mycobacterial enzyme pyrazinamidase
        • Thought to be more active at acidic pH (e.g. in macrophage phagolysosomes)
    • Clinical Use
      • Mycobacterium tuberculosis
        • Part of RIPE regimen of rifamycin, isoniazid, pyrazinamide, and ethambutol
    • Adverse Effects
      • Hepatotoxicity
        • Dose-dependent hepatotoxicity that is synergistic with rifampin’s hepatotoxic effect (also in RIPE treatment for TB)
        • Manifests as increased AST/ALT, jaundice, and liver tenderness
      • Hyperuricemia/Gout
        • Pyrazinamide competes with uric acid for secretion by the kidneys, resulting in increased uric acid levels
      • Arthralgias