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Pyrazinamide
See also Antituberculosis drugs
General information
Pyrazinamide is a pyrazine analogue of nicotinamide. It is bactericidal for Mycobacterium tuberculosis in an acid environment and in macrophages [ ]. Pyrazinamide passively diffuses into Mycobacterium tuberculosis , where pyrazinamidase (nicotinamidase) converts it to the active form pyrazinoic acid, which slowly leaves out of the cell at acid pH via a weak efflux pump and is protonated; the protonated form diffuses back into the bacterium and accumulates. Thus, more pyrazinoic acid accumulates in the bacterium at acid pH [ ]. The minimum inhibitory concentration of pyrazinamide for Mycobacterium tuberculosis varies according to pH and the system used to measure it [ ].
General adverse effects and adverse reactions
Most adverse reactions to pyrazinamide are toxic reactions. Reactions involving the liver, hyperuricemia with and without gout, and symptoms of pellagra have particularly been recognized. Fever and urticaria are described. Sideroblastic anemia, thrombocytopenia, anorexia, nausea and vomiting, dysuria, malaise, and aggravation of peptic ulcer can occur [ ].
Drug studies
Observational studies
The combination of pyrazinamide plus levofloxacin is first-line treatment for multidrug-resistant latent tuberculosis. In 17 Canadian patients there were important adverse reactions affecting the musculoskeletal and central nervous systems; hyperuricemia, gastrointestinal effects, and dermatological effects were also common [ ]. This combination may be used with careful monitoring for adverse reactions.
Organs and systems
Cardiovascular
Acute symptomatic hypertension consistently followed the administration of pyrazinamide to a 65-year-old woman with pulmonary tuberculosis [ ].
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