PZA

Pyrazinamide (PZA) is a first-line antituberculosis medication used in combination therapy for active tuberculosis. It is typically included in the initial intensive phase of treatment alongside isoniazid, rifampicin, and ethambutol (the RIPE regimen). When used in drug-susceptible TB, PZA helps shorten treatment duration from about nine to six months.

Pyrazinamide is a prodrug that is converted by the bacterial enzyme pyrazinamidase to pyrazinoic acid. Its exact mechanism is not fully understood, but it is thought to disrupt bacterial energy production and inhibit fatty acid synthesis in Mycobacterium tuberculosis, particularly under acidic conditions present in macrophage phagolysosomes. It is more active against dormant bacilli than many other first-line drugs.

Typical regimen for drug-susceptible TB includes 2 months of PZA with RIPE, followed by 4 months of continuation therapy with rifampicin and isoniazid (without PZA in most cases). Dosage is adjusted for weight and renal function; resistance can require modification of the standard regimen.

Adverse effects include hepatotoxicity and hyperuricemia, which can precipitate gout. Other possible reactions are rash and rare hypersensitivity. Liver function tests are monitored during therapy, and PZA is contraindicated in severe hepatic impairment. Dosing may require adjustments in renal dysfunction.

Resistance to PZA commonly arises from mutations in the pncA gene encoding the pyrazinamidase enzyme. Susceptibility testing is used where available. PZA can raise uric acid levels; patients with gout or hyperuricemia require monitoring and management as part of therapy.

Pregnancy: PZA is generally continued in standard TB regimens during pregnancy when TB treatment is indicated. It is not used as monotherapy and should be used as part of a supervised multidrug regimen to prevent resistance and ensure efficacy.