Rifampin isoniazid pyrazinamide: Difference between revisions
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Rifampicin is also known as rifaldazine, R/AMP, rofact (in Canada), and rifampin in the United States. There are various types of rifamycins from which this is derived, but the rifampicin form, with a [[piperazine|4-methyl-1-piperazinaminyl]] group, is by far the most clinically effective. | Rifampicin is also known as rifaldazine, R/AMP, rofact (in Canada), and rifampin in the United States. There are various types of rifamycins from which this is derived, but the rifampicin form, with a [[piperazine|4-methyl-1-piperazinaminyl]] group, is by far the most clinically effective. | ||
'''Pyrazinamide''' is a [[drug]] used to treat [[tuberculosis]]. The drug is largely [[bacteriostatic]], but can be [[bacteriocidal]] on actively replicating tuberculosis [[bacteria]]. | |||
==Category== | ==Category== | ||
Revision as of 15:47, 31 December 2013
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2]
Overview
Isoniazid, also known as isonicotinylhydrazine (INH), is an organic compound that is the first-line medication in prevention and treatment of tuberculosis. The compound was first synthesized in the early 20th century,[1] but its activity against tuberculosis was first reported in the early 1950s, and three pharmaceutical companies attempted unsuccessfully to simultaneously patent the drug[2] (the most prominent one being Roche, which launched its version, Rimifon, in 1952). The drug was first tested at Many Farms, a Navajo community, due to the Navajo reservation's dire tuberculosis problem and the fact that the population was naïve with respect to streptomycin, the main tuberculosis treatment at the time.[3] With the introduction of isoniazid, a cure for tuberculosis was first considered reasonable.
Rifampicin (INN) /rɪˈfæmpəsɪn/ or rifampin (USAN) is a bactericidal antibiotic drug of the rifamycin group.[4]
Rifampicin inhibits bacterial DNA-dependent RNA synthesis by inhibiting bacterial DNA-dependent RNA polymerase.Invalid parameter in <ref> tag Rifampicin may be abbreviated R, RMP, RA, RF, or RIF (US).
In 1957, a soil sample from a pine forest on the French Riviera was brought for analysis to the Lepetit Pharmaceuticals research lab in Milan, Italy. There, a research group headed by Prof. Piero Sensi (1920-) and Dr. Maria Teresa Timbal (1925 - 1969) discovered a new bacterium. This new species appeared immediately of great scientific interest since it was producing a new class of molecules with antibiotic activity. Because Sensi, Timbal and the researchers were particularly fond of the French crime story Rififi (about a jewel heist and rival gangs),[5] they decided to call these compounds "rifamycins". After two years of attempts to obtain more stable semisynthetic products, a new molecule with high efficacy and good tolerability was produced in 1959 and was named "rifampicin".
Rifampicin is also known as rifaldazine, R/AMP, rofact (in Canada), and rifampin in the United States. There are various types of rifamycins from which this is derived, but the rifampicin form, with a 4-methyl-1-piperazinaminyl group, is by far the most clinically effective.
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
Laniazid®, Nydrazid®, Rifamate®, Rifater®, Rifinah®, Rimactane/INH®
FDA Package Insert
Description | Clinical Pharmacology | Microbiology | Indications and Usage | Contraindications | Warnings and Precautions | Adverse Reactions | Overdosage | Clinical Studies | Dosage and Administration | How Supplied | Labels and Packages
Mechanisms of Action
Isoniazid is a prodrug and must be activated by a bacterial catalase-peroxidase enzyme that in M. tuberculosis is called KatG.[6] KatG couples the isonicotinic acyl with NADH to form isonicotinic acyl-NADH complex. This complex binds tightly to the enoyl-acyl carrier protein reductase known as InhA, thereby blocking the natural enoyl-AcpM substrate and the action of fatty acid synthase. This process inhibits the synthesis of mycolic acid, required for the mycobacterial cell wall. A range of radicals are produced by KatG activation of isoniazid, including nitric oxide,[7] which has also been shown to be important in the action of another antimycobacterial prodrug PA-824.[8]
Isoniazid is bactericidal to rapidly dividing mycobacteria, but is bacteriostatic if the mycobacteria are slow-growing.[9]
Isoniazid inhibits the P450 system.[10]
References
- ↑ Meyer H, Mally J (1912). "On hydrazine derivatives of pyridine carbonic acids". Monatshefte Chemie verwandte Teile anderer Wissenschaften (in German). 33: 393&ndash, 414. doi:10.1007/BF01517946.PDF fulltext
- ↑ Hans L Riede (2009). "Fourth-generation fluoroquinolones in tuberculosis". Lancet. 373 (9670): 1148&ndash, 1149. doi:10.1016/S0140-6736(09)60559-6. PMID 19345815.
- ↑ Jones, David (2002). "The Health Care Experiments at Many Farms: The Navajo, Tuberculosis, and the Limits of Modern Medicine, 1952-1962". Bulletin of the History of Medicine. 76 (4): 749–790.
- ↑ Masters, Susan B.; Trevor, Anthony J.; Katzung, Bertram G. (2005). Katzung & Trevor's pharmacology. New York: Lange Medical Books/McGraw Hill, Medical Pub. Division. ISBN 0-07-142290-0.
- ↑ "When I Use a Word . . .I Mean It". British Medical Journal 1999;319(7215):972 (9 October). Retrieved 2009-07-10.
- ↑ Suarez J, Ranguelova K, Jarzecki AA; et al. (2009). "An oxyferrous heme/protein-based radical intermediate is catalytically competent in the catalase reaction of Mycobacterium tuberculosis catalase-peroxidase (KatG)". The Journal of Biological Chemistry. 284 (11): 7017–29. doi:10.1074/jbc.M808106200. PMC 2652337. PMID 19139099. Unknown parameter
|month=ignored (help) - ↑ Timmins GS, Master S, Rusnak F, Deretic V (2004). "Nitric oxide generated from isoniazid activation by KatG: source of nitric oxide and activity against Mycobacterium tuberculosis". Antimicrobial Agents and Chemotherapy. 48 (8): 3006–9. doi:10.1128/AAC.48.8.3006-3009.2004. PMC 478481. PMID 15273113. Unknown parameter
|month=ignored (help) - ↑ Singh R, Manjunatha U, Boshoff HI; et al. (2008). "PA-824 kills nonreplicating Mycobacterium tuberculosis by intracellular NO release". Science. 322 (5906): 1392–5. doi:10.1126/science.1164571. PMC 2723733. PMID 19039139. Unknown parameter
|month=ignored (help) - ↑ PMID 19686043 (PMID 19686043)
Citation will be completed automatically in a few minutes. Jump the queue or expand by hand - ↑ Pharmacology, Harvey 4th edition. November 2009.