Rifampin (oral)
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2]
Overview
Rifampin was introduced in 1967,[1] as a major addition to the cocktail-drug treatment of tuberculosis and inactive meningitis, along with pyrazinamide, isoniazid, ethambutol and streptomycin ("PIERS"). It requires a prescription in North America. It must be administered regularly daily for several months without break; otherwise, the risk of drug-resistant tuberculosis is greatly increased.[1] In fact, this is the primary reason it is used in tandem with the three aforementioned drugs, particularly isoniazid.[2] This is also the primary motivation behind directly observed therapy for tuberculosis.
Category
Antimycobacterial
US Brand Names
RIFADIN®
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
Rifampin inhibits bacterial DNA-dependent RNA synthesis by inhibiting bacterial DNA-dependent RNA polymerase.[3]
Crystal structure data and biochemical data indicate that rifampicin binds to RNA polymerase at a site adjacent to the RNA polymerase active center and blocks RNA synthesis by physically preventing extension of RNA products beyond a length of 2-3 nucleotides ("steric-occlusion" mechanism).[4][5]
Resistance to rifampin arises from mutations that alter residues of the rifampin binding site on RNA polymerase, resulting in decreased affinity for rifampin.[5] Resistant mutations map to the rpoB gene, encoding RNA polymerase beta subunit.
References
- ↑ Jump up to: 1.0 1.1 Long, James W. (1991). Essential Guide to Prescription Drugs 1992. New York: HarperCollins Publishers. pp. 925–929. ISBN 0-06-273090-8.
- ↑ Erlich, Henry, W Ford Doolittle, Volker Neuhoff, and et al. . Molecular Biology of Rifomycin. New York, NY: MSS Information Corporation, 1973. pp. 44-45, 66-75, 124-130.
- ↑ Calvori, C.; Frontali, L.; Leoni, L.; Tecce, G. (1965). "Effect of rifamycin on protein synthesis". Nature. 207 (995): 417–8. doi:10.1038/207417a0. PMID 4957347.
- ↑ Campbell, E.A., Korzheva, N., Mustaev, A., Murakami, K., Nair, S., Goldfarb, A., Darst, S.A. (2001). "Structural mechanism for rifampicin inhibition of bacterial RNA polymerase". Cell. 104 (6): 901–12. doi:10.1016/S0092-8674(01)00286-0. PMID 11290327.
- ↑ Jump up to: 5.0 5.1 Feklistov, A., Mekler, V., Jiang, Q., Westblade, L.F., Irschik, H., Jansen, R., Mustaev, A., Darst, S.A., Ebright, R.H. (2008). "Rifamycins do not function by allosteric modulation of binding of Mg2+ to the RNA polymerase active center". Proc Natl Acad Sci USA. 105 (39): 14820–5. doi:10.1073/pnas.0802822105. PMC 2567451. PMID 18787125.