pyrazinamidi

Pyrazinamide is an antituberculosis medication that forms part of standard first-line therapy for active pulmonary and extrapulmonary tuberculosis. It is a nicotinamide analogue that is administered orally and operates as a prodrug; within Mycobacterium tuberculosis, the enzyme pyrazinamidase (pncA) converts it to the active form, pyrazinoic acid.

The exact mechanism of action is not fully understood. Pyrazinoic acid is more active at acidic pH and is believed to disrupt bacterial energy production and membrane energetics, with additional effects that may inhibit other essential processes. Pyrazinamide is particularly effective against nonreplicating persister populations and thus aids in sterilizing lesions. In standard regimens, it complements isoniazid, rifampicin, and ethambutol to shorten the duration of therapy compared with regimens lacking PZA.

Resistance to pyrazinamide primarily arises from mutations in the pncA gene, which reduce or abolish pyrazinamidase activity and prevent activation of the drug. Because of this, pyrazinamide is used only as part of combination therapy to limit resistance development.

Pharmacokinetics and safety: Pyrazinamide is well absorbed orally, with peak plasma levels reached within a few hours. It is metabolized by the liver and excreted mainly by the kidneys, with an elimination half-life of about 9 to 11 hours. Adverse effects include hepatotoxicity and hyperuricemia, which can lead to gout, as well as nausea, vomiting, and rash. Caution is advised in liver disease and for patients with significant renal impairment.