pyrazinamid

Pyrazinamide, also known as pyrazinamid, is a first-line antituberculosis medication used in the treatment of active tuberculosis. It is a derivative of pyrazine carboxamide and is commonly included in rifampicin-based regimens during the initial intensive phase. Pyrazinamide is typically given for the first two months of therapy, contributing to shortening the overall treatment duration.

Mechanism: Pyrazinamide is a prodrug activated by the mycobacterial enzyme pyrazinamidase (PncA) to pyrazinoic acid. It is most active at acidic pH, and the precise molecular targets remain incompletely defined. It is thought to disrupt energy production and membrane function in Mycobacterium tuberculosis, particularly affecting semi-dormant bacilli.

Pharmacology: After oral administration, pyrazinamide is well absorbed and widely distributed. It is primarily eliminated by hepatic metabolism and renal excretion of metabolites. Adverse effects include hepatotoxicity and hyperuricemia, which can lead to gout; other common effects are nausea, rash, and arthralgia. Resistance is usually due to mutations in the pncA gene, which reduces conversion to the active form.

Clinical use and safety: Pyrazinamide is generally well tolerated in appropriate regimens but requires monitoring of liver function tests and uric acid levels. It should be used with caution in liver disease and in patients with a history of gout. The drug is included in World Health Organization guidelines as a core component of standard tuberculosis therapy.