Abstract:
:The development of nonsteroidal anti-inflammatory drugs (NSAIDs) selective for cyclooxygenase (COX)-2 (named coxibs) has been driven by the aim of reducing the incidence of serious gastrointestinal (GI) adverse events associated with the administration of traditional (t) NSAIDs - mainly dependent on the inhibition of COX-1 in GI tract and platelets. However, their use has unravelled the important protective role of COX-2 for the cardiovascular (CV) system, mainly through the generation of prostacyclin. In a recent nested-case control study, we found that patients taking NSAIDs (both coxibs and tNSAIDs) had a 35% increase risk of myocardial infarction. The increased incidence of thrombotic events associated with profound inhibition of COX-2-dependent prostacyclin by coxibs and tNSAIDs can be mitigated, even if not obliterated, by a complete suppression of platelet COX-1 activity. However, most tNSAIDs and coxibs are functional COX-2 selective for the platelet (ie, they cause a profound suppression of COX-2 associated with insufficient inhibition of platelet COX-1 to translate into inhibition of platelet function), which explains their shared CV toxicity. The development of genetic and biochemical markers will help to identify the responders to NSAIDs or who are uniquely susceptible at developing thrombotic or GI events by COX inhibition. We will describe possible strategies to reduce the side effects of etoricoxib by using biochemical markers of COX inhibition, such as whole blood COX-2 and the assessment of prostacyclin biosynthesis in vivo.
journal_name
Ther Clin Risk Managjournal_title
Therapeutics and clinical risk managementauthors
Patrignani P,Tacconelli S,Capone MLdoi
10.2147/tcrm.s3209subject
Has Abstractpub_date
2008-10-01 00:00:00pages
983-97issue
5eissn
1176-6336issn
1178-203Xjournal_volume
4pub_type
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journal_title:Therapeutics and clinical risk management
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journal_title:Therapeutics and clinical risk management
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journal_title:Therapeutics and clinical risk management
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journal_title:Therapeutics and clinical risk management
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journal_title:Therapeutics and clinical risk management
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doi:10.2147/TCRM.S7688
更新日期:2012-01-01 00:00:00
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journal_title:Therapeutics and clinical risk management
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journal_title:Therapeutics and clinical risk management
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journal_title:Therapeutics and clinical risk management
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journal_title:Therapeutics and clinical risk management
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更新日期:2005-09-01 00:00:00
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journal_title:Therapeutics and clinical risk management
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更新日期:2007-08-01 00:00:00
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journal_title:Therapeutics and clinical risk management
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更新日期:2020-05-19 00:00:00
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journal_title:Therapeutics and clinical risk management
pub_type: 杂志文章,评审
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journal_title:Therapeutics and clinical risk management
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更新日期:2011-01-01 00:00:00
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更新日期:2016-11-18 00:00:00
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journal_title:Therapeutics and clinical risk management
pub_type: 杂志文章,评审
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更新日期:2014-05-02 00:00:00