Pyrazinamide
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2]
Overview
Pyrazinamide is a drug used to treat tuberculosis. The drug is largely bacteriostatic, but can be bacteriocidal on actively replicating tuberculosis bacteria.
Category
Antimycobacterial
US Brand Names
FDA Package Insert
Description | Clinical Pharmacology | Microbiology | Indications and Usage | Contraindications | Warnings and Precautions | Adverse Reactions | Overdosage | Clinical Studies | Dosage and Administration | Compatibility, Reconstitution, and Stability | Directions For Use | How Supplied | Labels and Packages
Mechanisms of Action
Pyrazinamide is a prodrug that stops the growth of Mycobacterium tuberculosis.
Pyrazinamide diffuses into M. tuberculosis, where the enzyme pyrazinamidase converts pyrazinamide to the active form pyrazinoic acid. Under acidic conditions, the pyrazinoic acid that slowly leaks out converts to the protonated conjugate acid, which is thought to diffuse easily back into the bacilli and accumulate. The net effect is that more pyrazinoic acid accumulates inside the bacillus at acid pH than at neutral pH.[1]
Pyrazinoic acid was thought to inhibit the enzyme fatty acid synthase (FAS) I, which is required by the bacterium to synthesise fatty acids[2] although this has been discounted.[3] 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
References
- ↑ Zhang Y, Mitchison D (2003). "The curious characteristics of pyrazinamide: a review". Int. J. Tuberc. Lung Dis. 7 (1): 6–21. PMID 12701830. Unknown parameter
|month=ignored (help) - ↑ Zimhony O, Cox JS, Welch JT, Vilchèze C, Jacobs WR (2000). "Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI) of Mycobacterium tuberculosis" (abstract). Nature Medicine. 6 (9): 1043–47. doi:10.1038/79558. PMID 10973326.
- ↑ Boshoff HI, Mizrahi V, Barry CE (2002). "Effects of Pyrazinamide on Fatty Acid Synthesis by Whole Mycobacterial Cells and Purified Fatty Acid Synthase I". Journal of Bacteriology. 184 (8): 2167–72. doi:10.1128/JB.184.8.2167-2172.2002. PMC 134955. PMID 11914348.