Isoniazid (oral): Difference between revisions
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__NOTOC__ | __NOTOC__ | ||
{{Isoniazid}} | {{Isoniazid}} | ||
{{CMG}} ; | {{CMG}}; {{AE}} {{Chetan}} | ||
==Overview== | ==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,<ref>{{Cite journal|author=Meyer H, Mally J|title=On hydrazine derivatives of pyridine carbonic acids|journal=Monatshefte Chemie verwandte Teile anderer Wissenschaften|volume=33|pages=393–414|doi = 10.1007/BF01517946|language=German|year=1912}}[http://springerlink.metapress.com/content/p7145p063227623j/fulltext.pdf PDF fulltext]</ref> but its activity against tuberculosis was first reported in the early 1950s, and three pharmaceutical companies attempted unsuccessfully to simultaneously patent the drug<ref>{{Cite journal|journal=Lancet|volume=373|issue=9670|pages=1148–1149|year=2009 | |||
|doi=10.1016/S0140-6736(09)60559-6|title=Fourth-generation fluoroquinolones in tuberculosis|author=Hans L Riede|pmid=19345815}}</ref> (the most prominent one being Roche, which launched its version, [http://www.rocheusa.com/about/history.html Rimifon], in 1952). The drug was first tested at [[Many Farms, Arizona|Many Farms]], a [[Navajo Nation|Navajo]] community, due to the Navajo reservation's dire tuberculosis problem and the fact that the population was [[Naïveté|naïve]] with respect to [[streptomycin]], the main tuberculosis treatment at the time.<ref>{{cite journal|last=Jones|first=David|title=The Health Care Experiments at Many Farms: The Navajo, Tuberculosis, and the Limits of Modern Medicine, 1952-1962|journal=Bulletin of the History of Medicine|year=2002|volume=76|issue=4|pages=749–790}}</ref> With the introduction of isoniazid, a cure for tuberculosis was first considered reasonable. | |doi=10.1016/S0140-6736(09)60559-6|title=Fourth-generation fluoroquinolones in tuberculosis|author=Hans L Riede|pmid=19345815}}</ref> (the most prominent one being Roche, which launched its version, [http://www.rocheusa.com/about/history.html Rimifon], in 1952). The drug was first tested at [[Many Farms, Arizona|Many Farms]], a [[Navajo Nation|Navajo]] community, due to the Navajo reservation's dire tuberculosis problem and the fact that the population was [[Naïveté|naïve]] with respect to [[streptomycin]], the main tuberculosis treatment at the time.<ref>{{cite journal|last=Jones|first=David|title=The Health Care Experiments at Many Farms: The Navajo, Tuberculosis, and the Limits of Modern Medicine, 1952-1962|journal=Bulletin of the History of Medicine|year=2002|volume=76|issue=4|pages=749–790}}</ref> With the introduction of isoniazid, a cure for tuberculosis was first considered reasonable. | ||
==Category== | ==Category== | ||
Antimycobacterial | Antimycobacterial | ||
==US Brand Names== | ==US Brand Names== | ||
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==FDA Package Insert== | ==FDA Package Insert== | ||
'''[[Isoniazid description|Description]]''' | |||
''' [[Isoniazid description|Description]]''' | |||
'''| [[Isoniazid clinical pharmacology|Clinical Pharmacology]]''' | '''| [[Isoniazid clinical pharmacology|Clinical Pharmacology]]''' | ||
'''| [[Isoniazid microbiology|Microbiology]]''' | '''| [[Isoniazid microbiology|Microbiology]]''' | ||
| Line 30: | Line 34: | ||
==Mechanisms of Action== | ==Mechanisms of Action== | ||
Isoniazid is a [[prodrug]] and must be activated by a bacterial catalase-peroxidase enzyme that in ''M. tuberculosis'' is called KatG.<ref>{{Cite journal|author=Suarez J, Ranguelova K, Jarzecki AA, ''et al.'' |title=An oxyferrous heme/protein-based radical intermediate is catalytically competent in the catalase reaction of Mycobacterium tuberculosis catalase-peroxidase (KatG) |journal=The Journal of Biological Chemistry |volume=284 |issue=11 |pages=7017–29 |year=2009 |month=March |pmid=19139099 |doi=10.1074/jbc.M808106200 |pmc=2652337}}</ref> 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 [[mycobacterium|mycobacterial]] cell wall. A range of radicals are produced by KatG activation of isoniazid, including [[nitric oxide]],<ref>{{Cite journal|author=Timmins GS, Master S, Rusnak F, Deretic V |title=Nitric oxide generated from isoniazid activation by KatG: source of nitric oxide and activity against Mycobacterium tuberculosis |journal=Antimicrobial Agents and Chemotherapy |volume=48 |issue=8 |pages=3006–9 |year=2004 |month=August |pmid=15273113 |pmc=478481 |doi=10.1128/AAC.48.8.3006-3009.2004}}</ref> which has also been shown to be important in the action of another antimycobacterial prodrug [[PA-824]].<ref>{{Cite journal|author=Singh R, Manjunatha U, Boshoff HI, ''et al.'' |title=PA-824 kills nonreplicating Mycobacterium tuberculosis by intracellular NO release |journal=Science |volume=322 |issue=5906 |pages=1392–5 |year=2008 |month=November |pmid=19039139 |doi=10.1126/science.1164571 |pmc=2723733}}</ref> | Isoniazid is a [[prodrug]] and must be activated by a bacterial catalase-peroxidase enzyme that in ''M. tuberculosis'' is called KatG.<ref>{{Cite journal|author=Suarez J, Ranguelova K, Jarzecki AA, ''et al.'' |title=An oxyferrous heme/protein-based radical intermediate is catalytically competent in the catalase reaction of Mycobacterium tuberculosis catalase-peroxidase (KatG) |journal=The Journal of Biological Chemistry |volume=284 |issue=11 |pages=7017–29 |year=2009 |month=March |pmid=19139099 |doi=10.1074/jbc.M808106200 |pmc=2652337}}</ref> 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 [[mycobacterium|mycobacterial]] cell wall. A range of radicals are produced by KatG activation of isoniazid, including [[nitric oxide]],<ref>{{Cite journal|author=Timmins GS, Master S, Rusnak F, Deretic V |title=Nitric oxide generated from isoniazid activation by KatG: source of nitric oxide and activity against Mycobacterium tuberculosis |journal=Antimicrobial Agents and Chemotherapy |volume=48 |issue=8 |pages=3006–9 |year=2004 |month=August |pmid=15273113 |pmc=478481 |doi=10.1128/AAC.48.8.3006-3009.2004}}</ref> which has also been shown to be important in the action of another antimycobacterial prodrug [[PA-824]].<ref>{{Cite journal|author=Singh R, Manjunatha U, Boshoff HI, ''et al.'' |title=PA-824 kills nonreplicating Mycobacterium tuberculosis by intracellular NO release |journal=Science |volume=322 |issue=5906 |pages=1392–5 |year=2008 |month=November |pmid=19039139 |doi=10.1126/science.1164571 |pmc=2723733}}</ref> | ||
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Isoniazid inhibits the [[P450 system]].<ref>{{Cite book|title=Pharmacology, Harvey 4th edition|date=November 2009}}</ref> | Isoniazid inhibits the [[P450 system]].<ref>{{Cite book|title=Pharmacology, Harvey 4th edition|date=November 2009}}</ref> | ||
==References== | ==References== | ||
{{Reflist|2}} | {{Reflist|2}} | ||
[[Category:Antibiotics]] | [[Category:Antibiotics]] | ||
[[Category:Wikinfect]] | [[Category:Wikinfect]] | ||
Revision as of 15:50, 3 January 2014
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.
Category
Antimycobacterial
US Brand Names
ISONIAZID®, LANIAZID® (DISCONTINUED), NYDRAZID® (DISCONTINUED)
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
Isoniazid is a prodrug and must be activated by a bacterial catalase-peroxidase enzyme that in M. tuberculosis is called KatG.[4] 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,[5] which has also been shown to be important in the action of another antimycobacterial prodrug PA-824.[6]
Isoniazid is bactericidal to rapidly dividing mycobacteria, but is bacteriostatic if the mycobacteria are slow-growing.[7]
Isoniazid inhibits the P450 system.[8]
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.
- ↑ 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.