Clopidogrel: Difference between revisions

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==Metabolism==
==Metabolism==
It is metabolized by [[cytochrome P-450]] [http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&TermToSearch=1557 2C19] [[allele]] and so may have drug interactions<ref>''''''[http://www.medicalletter.org/restricted/articles/w1303b.html PPI Interactions with Clopidogrel]. The Medical Letter.</ref> and inherited variations in metabolism.<ref name="pmid19106084">{{cite journal |author=Mega JL, Close SL, Wiviott SD, ''et al'' |title=Cytochrome P-450 Polymorphisms and Response to Clopidogrel |journal=N. Engl. J. Med. |volume= |issue= |pages= |year=2008 |month=December |pmid=19106084 |doi=10.1056/NEJMoa0809171 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19106084&promo=ONFLNS19 |issn=}}</ref><ref name="pmid19108880">{{cite journal |author=Collet JP, Hulot JS, Pena A, ''et al'' |title=Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study |journal=Lancet |volume= |issue= |pages= |year=2008 |month=December |pmid=19108880 |doi=10.1016/S0140-6736(08)61845-0 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(08)61845-0 |issn=}}</ref><ref name="pmid19106083">{{cite journal |author=Simon T, Verstuyft C, Mary-Krause M, ''et al'' |title=Genetic Determinants of Response to Clopidogrel and Cardiovascular Events |journal=N. Engl. J. Med. |volume= |issue= |pages= |year=2008 |month=December |pmid=19106083 |doi=10.1056/NEJMoa0808227 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19106083&promo=ONFLNS19 |issn=}}</ref>
It is metabolized by [[cytochrome P-450]] [http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=DetailsSearch&Term=1559 2C19] [[allele]] and so may have drug interactions<ref>[http://www.medicalletter.org/restricted/articles/w1303b.html PPI Interactions with Clopidogrel]. The Medical Letter.</ref><ref name="pmid19258584">{{cite journal |author=Ho PM, Maddox TM, Wang L, ''et al.'' |title=Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome |journal=JAMA |volume=301 |issue=9 |pages=937–44 |year=2009 |month=March |pmid=19258584 |doi=10.1001/jama.2009.261 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=19258584 |issn=}}</ref> and inherited variations in metabolism.<ref name="pmid19106084">{{cite journal |author=Mega JL, Close SL, Wiviott SD, ''et al'' |title=Cytochrome P-450 Polymorphisms and Response to Clopidogrel |journal=N. Engl. J. Med. |volume= |issue= |pages= |year=2008 |month=December |pmid=19106084 |doi=10.1056/NEJMoa0809171 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19106084&promo=ONFLNS19 |issn=}}</ref><ref name="pmid19108880">{{cite journal |author=Collet JP, Hulot JS, Pena A, ''et al'' |title=Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study |journal=Lancet |volume= |issue= |pages= |year=2008 |month=December |pmid=19108880 |doi=10.1016/S0140-6736(08)61845-0 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(08)61845-0 |issn=}}</ref><ref name="pmid19106083">{{cite journal |author=Simon T, Verstuyft C, Mary-Krause M, ''et al'' |title=Genetic Determinants of Response to Clopidogrel and Cardiovascular Events |journal=N. Engl. J. Med. |volume= |issue= |pages= |year=2008 |month=December |pmid=19106083 |doi=10.1056/NEJMoa0808227 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19106083&promo=ONFLNS19 |issn=}}</ref>


30% of patients may have a reduced-function allele.<ref name="pmid19106084">{{cite journal |author=Mega JL, Close SL, Wiviott SD, ''et al'' |title=Cytochrome P-450 Polymorphisms and Response to Clopidogrel |journal=N. Engl. J. Med. |volume= |issue= |pages= |year=2008 |month=December |pmid=19106084 |doi=10.1056/NEJMoa0809171 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19106084&promo=ONFLNS19 |issn=}}</ref> and patients with a loss of function CYP2C19 allele have higher rates of cardiac events.<ref name="pmid19106084">{{cite journal| author=Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT et al.| title=Cytochrome p-450 polymorphisms and response to clopidogrel. | journal=N Engl J Med | year= 2009 | volume= 360 | issue= 4 | pages= 354-62 | pmid=19106084  
30% of patients may have a reduced-function allele.<ref name="pmid19106084">{{cite journal |author=Mega JL, Close SL, Wiviott SD, ''et al'' |title=Cytochrome P-450 Polymorphisms and Response to Clopidogrel |journal=N. Engl. J. Med. |volume= |issue= |pages= |year=2008 |month=December |pmid=19106084 |doi=10.1056/NEJMoa0809171 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19106084&promo=ONFLNS19 |issn=}}</ref> and patients with a loss of function CYP2C19 allele have higher rates of cardiac events.<ref name="pmid19106084">{{cite journal| author=Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT et al.| title=Cytochrome p-450 polymorphisms and response to clopidogrel. | journal=N Engl J Med | year= 2009 | volume= 360 | issue= 4 | pages= 354-62 | pmid=19106084  

Revision as of 21:02, 8 October 2009

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In medicine, clopidogrel is a thienopyridine class platelet aggregation inhibitor. It is used in the secondary prevention of stroke and coronary heart disease.

Metabolism

It is metabolized by cytochrome P-450 2C19 allele and so may have drug interactions[1][2] and inherited variations in metabolism.[3][4][5]

30% of patients may have a reduced-function allele.[3] and patients with a loss of function CYP2C19 allele have higher rates of cardiac events.[3][5]

Adverse effects

Inadequate effect in patients with coronary heart disease can be due to CYP2C19 loss-of-function alleles which are associated with more cardiovascular events.[3][5] Proton pump inhibitors (especially inhibitors other than pantoprazole[6]), which are metabolized by the CYP2C19 isoenzyme of cytochrome P-450, may[2] or may not[7] increase adverse cardiac events.

External links

The most up-to-date information about Clopidogrel and other drugs can be found at the following sites.


References

  1. PPI Interactions with Clopidogrel. The Medical Letter.
  2. 2.0 2.1 Ho PM, Maddox TM, Wang L, et al. (March 2009). "Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome". JAMA 301 (9): 937–44. DOI:10.1001/jama.2009.261. PMID 19258584. Research Blogging.
  3. 3.0 3.1 3.2 3.3 Mega JL, Close SL, Wiviott SD, et al (December 2008). "Cytochrome P-450 Polymorphisms and Response to Clopidogrel". N. Engl. J. Med.. DOI:10.1056/NEJMoa0809171. PMID 19106084. Research Blogging. Cite error: Invalid <ref> tag; name "pmid19106084" defined multiple times with different content Cite error: Invalid <ref> tag; name "pmid19106084" defined multiple times with different content
  4. Collet JP, Hulot JS, Pena A, et al (December 2008). "Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study". Lancet. DOI:10.1016/S0140-6736(08)61845-0. PMID 19108880. Research Blogging.
  5. 5.0 5.1 5.2 Simon T, Verstuyft C, Mary-Krause M, et al (December 2008). "Genetic Determinants of Response to Clopidogrel and Cardiovascular Events". N. Engl. J. Med.. DOI:10.1056/NEJMoa0808227. PMID 19106083. Research Blogging. Cite error: Invalid <ref> tag; name "pmid19106083" defined multiple times with different content Cite error: Invalid <ref> tag; name "pmid19106083" defined multiple times with different content
  6. Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV, Henry DA, Kopp A, Mamdani MM. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009 Mar 31;180(7):713-8. Epub 2009 Jan 28. PMID 19176635
  7. O'Donoghue ML, Braunwald E, Antman EM, Murphy SA, Bates ER, Rozenman Y et al. (2009). "Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials.". Lancet 374 (9694): 989-97. DOI:10.1016/S0140-6736(09)61525-7. PMID 19726078. Research Blogging.