Pyrazinamide

Question 1

Pyrazinamide

Answer 1

First line drug for TB

Part of initial four drug regimen; allows overall duration of therapy to be shortened from 9 months to 6 months

Has cidal activity against even slow growing M. tuberculosis

Generally used only in first 2 months of TB therapy

Active only against M. tuberculosis

Question 2

Pyrazinamide MOA

Answer 2

Prodrug with an unclear MOA

In active form, thought to prevent production of mycolic acids by inhibiting the enzyme fatty acid synthetase 1; likely has other effects as well

Question 3

Pyrazinamide Adverse Effects

Answer 3

Key ones are hyperuricemia and hepatotoxicity

Hepatotoxicity (chiefly hepatitis) is dose dependent and less common at lower doses given today

Hyperuricemia- predictable and can rarely precipitate gout- leading to withdrawal from regimen and extension of duration of TB therapy

Arthralgias can occur; separate from hyperuricemia; can be managed with OTC meds

Question 4

Pyrazinamide Important Facts

Answer 4

Active only in acidic environment (pH<6); is perfect for caseous granulomas that active TB forms; also works intracellularly in phagocytes

Only use is in initial phase of active TB

Have patients report any signs of hepatitis (dark urine, abdominal pain, loss of appetite) when on pyrazinamide or any first line TB therapy