Clopidogrel thienopyridines

Ticlopidine is associated with neutropenia that requires frequent monitoring of the complete blood cell count during the first 3 months of use. For this reason, clopidogrel is the preferred thienopyridine for ACS and PCI patients. 

Pharmacology Clopidogrel is a thienopyridine derivative, chemically related to ticlopidine, that inhibits platelet aggregation. It acts by irreversibly modifying the platelet ADP receptor. Conseguently, platelets exposed to clopidogrel are affected for the remainder of their lifespan. 

P2Y12 receptor is required for complete aggregation response to ADR Nevertheless, both (Fig. 6) receptors interact to lead the full response. ADP potentiates platelet secretion and irreversible aggregation, Enzymatic conversion of released ADP to inactive AMP by endothelial ecto-ADPase limits platelet activation by ADR Thienopyridines (ticlopidine, clopidogrel, prasugrel, cangrelor) are used for inhibiting ADP-induced platelet function in the prevention of acute coronary events,... 

Thienopyridines (ticlopidina, clopidogrel, prasugrel, cangrelor, AZD6140) Inhibit platelet activation by preventing binding of ADP with it receptors, mainly P2Y12... 

Thienopyridines are inactive in vitro. Absorbed in the upper gastrointestinal tract, clopidogrel is converted to an active metabolite by the hepatic cytochrome P450 system (3,4). 

In addition to the risk of bleeding, which will be detailed in the different studies, thienopyridines are able to cause skin disorders (rashes or prurit) and gastrointestinal disorders (diarrhea). In the CLASSICS study, these side effects were observed in 8.2% of patients treated with ticlopidine and in 3.5% of those taking clopidogrel treatment. The most serious problem was related to hematologic disorders neutropenia or thrombocytopenia. These disorders are much less frequent with clopidogrel than with ticlopidine 0.04% of neutropenia in the CAPRIE study and 0.05% in the CURE trial, Thrombotic thrombocytopenic purpura are exceptional one for 200,000 patients. 

Wiviott SD, Antman EM, Winters KJ, et al. Randomized comparison of prasugrel (CS-747, LY640315), a novel thienopyridine P2YI2 antagonist, with clopidogrel in percutaneous coronary intervention results of the Joint Utilization of Medications to Block Platelets Optimally (JUMBO)-TIMI 26 trial. Circulation 2005 I I 1 3366-3373. 

The thienopyridines include clopidogrel, ticlopidine, and prosugel. Clopidogrel is the only member of this class in clinical use at this time. A second generation of this drug, Prosugel, is undergoing trials (27). Ticlopidine is not used... 

Sankyo Co. Ltd. Tokyo, Japan) is a new thienopyridine derivative that produces more potent platelet inhibition, and a rapid onset of action. The latter properties may provide a superior alternative to clopidogrel, with less response variability and a decreased prevalence of nonresponsiveness (I I I). 

The most important safety concerns are the potential for perforation which could result in tamponade or compromise of collaterals which can result in infarction. In current PCI practice with its reliance on drug eluting stent (DES), dual antiplatelet therapy with aspirin (ASA) and a thienopyridine (usually clopidogrel) is standard. These should be used in all patients. Pre-procedure administration of the thienopyridine should be given, if possible. 

Clopidogrel is part of the thienopyridine class of antiplatelet drugs that are widely used to treat patients with cardiovascular disease. The American College of Cardiology has recommended antiplatelet medications for patients after angioplasty... 

Clopidogrel is also a thienopyridine derivative which is also more effective than aspirin for the prevention of ischaemic stroke, MI or vascular death in patients at high risk but it is not associated with neutropenia. It is more expensive than aspirin though safer than ticlodipine. 

Ticlopidine is a thienopyridine derivative with potent antiplatelet activity associated with inhibition of ADP-induced platelet aggregation. It was first used in Europe in 1978 in the secondary prevention of stroke and coronary events, the treatment of peripheral vascular disease, and after vascular stent placement. However, the use of ticlopidine has been progressively restricted in some countries because of its serious adverse effects. It has largely been superseded by clopidogrel. 

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. 

Ticlopidine is a thienopyridine antiplatelet agent, similar in structure and mechanism of action to clopidogrel. It has been shown to reduce the risk of stroke by 30% compared with placebo and by 21% compared with aspirin 325 mg/day inpatients at risk. The use of ticlopidine has been severely restricted by its side-effect profile, however. It causes bone marrow suppression, rash, diarrhea, and elevation of the serum cholesterol concentration. Neutropenia occurs in up to 2% of patients and generally is reversible. More problematic, however, is the increased risk of aplastic anemia and thrombotic thrombocytopenic purpura. Ticlopidine 250 mg twice daily is stiU available as an alternative in patients who fail or are intolerant of other therapies but is rarely needed. 

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