Detail for pyrazinamide
Basic Information
DrugID 84
DrugName pyrazinamide
DrugDetail Pyrazinamide is a drug used to treat tuberculosis. The drug is largely bacteriostatic, but can be bacteriocidal on actively replicating tuberculosis bacteria. Pyrazinamide is a prodrug that stops the growth of Mycobacterium tuberculosis. M. tuberculosis has the enzyme pyrazinamidase which is only active in acidic conditions. Pyrazinamidase converts pyrazinamide to the active form, pyrazinoic acid which accumulates in the bacilli. Pyrazinoic acid was thought to inhibit the enzyme fatty acid synthase (FAS) I, which is required by the bacterium to synthesise fatty acids although this has been discounted. It was also suggested that the accumulation of pyrazinoic acid disrupts membrane potential and interferes with energy production, necessary for survival of M. tuberculosis at an acidic site of infection. Further studies reproduced the results of FAS I inhibition as the putative mechanism first in whole cell assay of replicating M. tuberculosis bacilli which have shown that pyrazinoic acid and its ester inhibit the synthesis of fatty acids. This study was followed by in vitro assay of tuberculous FAS I enzyme that tested the activity with pyrazinamide, pyrazinoic acid and several classes of pyrazinamide analogs. Pyrazinamide and its analogs inhibited the activity of purified FAS I. Pyrazinoic acid binds to the ribosomal protein S1 (RpsA) and inhibits trans-translation. This may explain the ability of the drug to kill dormant mycobacteria. Mutations in the pncA and rpsA genes are responsible for pyrazinamide resistance in M. tuberculosis.

http://en.wikipedia.org/wiki/Pyrazinamide

Indication For the initial treatment of active tuberculosis in adults and children when combined with other antituberculous agents.

http://www.drugbank.ca/drugs/DB00339

Structure Click to see the orginal picture.
Interaction
Drug Name PMIDLink Reference
Fluconazole Cordeiro Rde A, Brilhante RS, Rocha MF, Medrano DJ, Monteiro AJ, Tavares JL, de Lima RA, de Camargo ZP, Sidrim JJ. (2009) In vitro synergistic effects of antituberculous drugs plus antifungals against Coccidioides posadasii. Int J Antimicrob Agents. 34(3):278-80.
Itraconazole Cordeiro Rde A, Brilhante RS, Rocha MF, Medrano DJ, Monteiro AJ, Tavares JL, de Lima RA, de Camargo ZP, Sidrim JJ. (2009) In vitro synergistic effects of antituberculous drugs plus antifungals against Coccidioides posadasii. Int J Antimicrob Agents. 34(3):278-80.
Voriconazole Cordeiro Rde A, Brilhante RS, Rocha MF, Medrano DJ, Monteiro AJ, Tavares JL, de Lima RA, de Camargo ZP, Sidrim JJ. (2009) In vitro synergistic effects of antituberculous drugs plus antifungals against Coccidioides posadasii. Int J Antimicrob Agents. 34(3):278-80.
Target
PathWay
PathWay Name Path Picture
pathway