Antiplatelet agents clopidogrel

Shi D, Yang J, Yang D, LeCluyse EL, Black C, You L, Akhlaghi F, Yan B (2006) Anti-influenza prodrug oseltamivir is activated by carboxylesterase human carboxylesterase 1, and the activation is inhibited by antiplatelet agent clopidogrel. J Pharmacol Exp Ther 319 1477-1484... 

STATINS ANTIPLATELET AGENTS -CLOPIDOGREL Atorvastatin and possibly simvastatin 1 the antiplatelet effect of dopidogrel in a dose-dependent manner Atorvastatin and simvastatin inhibit CYP3A4-mediated activation of dopidogrel Use these statins at the lowest possible dose otherwise consider using an alternative statin... 

Kalinski and coworkers explored the potential of different powerful MCRs (Ugi, Petasis, and Passerini) in the production of generic drugs such as the antiplatelet agent clopidogrel 42 synthesized in the racemic form (Scheme 4.20) [36]. Although the use of Ugi 3-component reaction afforded better yields in this synthesis, the PBM reaction allowed the preparation of the desired product 42 in 44% overall yield. 

SCHEME 4.20 Synthesis of the antiplatelet agent clopidogrel 42 through PBM strategy. 

When given in combination with warfarin or thienopyri-dine class of antiplatelet agents the ASA dose is usually lowered to 80 to 100 mg based on a post hoc analysis of data from the clopidogrel in unstable angina to prevent recurrent events (CURE), which showed similar efficacy but less major bleeding with the low dose (< 100 mg) of ASA (38). 

Antiplatelet therapy reduces the risk of recurrent vascular events after TIA and ischemic stroke, although few trials have distinguished between different etiological subtypes (Antithrombotic Trialists Collaboration 2002). Most trial data concern aspirin, but other antiplatelet agents such as clopidogrel (CAPRIE Steering Committee 1996) or extended-release dipyridamole (Sivenius et al. 1991) have also been shown to be effective although mechanisms of action may differ (Table 24.2). 

The AHA/ASA guidelines recommend that antiplatelet therapy as the cornerstone of antithrombotic therapy for the secondary prevention of ischemic stroke and should be used in noncardioembolic strokes. Aspirin, clopidogrel, and extended-release dipyridamole plus aspirin are aU considered first-line antiplatelet agents (see Table 13-1). The combination of aspirin and clopidogrel can only be recommended in patients with ischemic stroke and a recent history of myocardial infarction or coronary stent placement and then only with ultra-low-dose aspirin to minimize bleeding risk. 

CLOPIDOGREL ANTIPLATELET AGENTS Risk of bleeding when clopidogrel is co-administered with other antiplatelet agents Additive effect Closely monitor effects watch for signs of excess bleeding... 

Anticoagulant (warfarin) and antiplatelet agents (ticlopidine, clopidogrel) reduced platelet adhesiveness and G1 tract damage by NSAIDs increase risk of alimentary bleeding (notably with azapropazone). Phenylbutazone, and probably azapropazone, inhibit the metabolism of warfarin, increasing its effect. 

Ginseng ASA, NSAIDs Antidiabetic agents Clopidogrel, ticlopidine CNS stimulants, caffeine Corticosteroids Digoxin MAO inhibitors Warfarin Additive antiplatelet effects Additive hypoglycemia Additive antiplatelet effects Additive CNS toxicity Additive CNS toxicity Falsely elevated levels Increased toxicity Increased risk of bleeding... 

Peelers PA, Crijns HJ, Tamminga WJ, Jonkman JH, Dickinson JP, Necciari J. Clopidogrel, a novel antiplatelet agent, and digoxin absence of pharmacodynamic and pharmacokinetic interaction. Semin Thromb Hemost 1999 25(Suppl 2) 51. ... 

Antiplatelet therapy plays a key role in the treatment of ACS, such as Ml. Aspirin has been shown to decrease overall mortality and reinfarction and is recommended for all patients in this setting unless contraindicated. Aspirin should be given at the lowest effective dose, to ensure efficacy and to limit adverse reactions. If aspirin is contraindicated or not tolerated, thienopyridines (clopidogrel or ticlopidine) may be used. Comparisons of oral antiplatelet agents are summarized in Thumbnail. 

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