Ticlopidine and clopidogrel.
The thienopyridines ticlopidine and clopidogrel are inhibitors of platelet function in vivo. Their mode of action has not been defined, but it appears that they require conversion to as yet unidentified metabolites that are noncompetitive antagonists of the platelet ADP receptor. Inhibition of platelet aggregation with these compounds is delayed until 24 to 48 hours after administration. Maximum inhibition occurs after 3 to 5 days, and recovery is slow after drug withdrawal. Ticlopidine is effective in preventing cardiovascular events in cerebrovascular, cardiovascular, and peripheral vascular disease, with an efficacy that is similar to aspirin. However, its use is associated with significant and sometimes fatal adverse reactions, specifically neutropenia and bone marrow aplasia. Gastrointestinal side effects and skin rashes are common and result in discontinuation of therapy in up to 10% of patients. Clopidogrel is at least as effective as aspirin in preventing cardiovascular events in patients with a history of vascular disease. It appears to be safer than ticlopidine, although its efficacy in acute coronary syndromes or post-coronary-stent insertion has not been reported. Important outstanding issues are whether clopidogrel adds to the benefit of aspirin and whether the combination of these agents is safe. If so, this combination may become the standard for antithrombotic therapy in cardiovascular disease.
Quinn
M J
MJ
Department of Clinical Pharmacology, The Royal College of Surgeons in Ireland, Dublin, Ireland.
Fitzgerald
D J
DJ
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors / Q000502:physiology; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000789:Angina, Unstable / Q000188:drug therapy; D001241:Aspirin / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001855:Bone Marrow Diseases / Q000139:chemically induced; D002220:Carbamazepine / Q000009:adverse effects / Q000493:pharmacokinetics; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D000077144:Clopidogrel; D003131:Combined Modality Therapy; D003327:Coronary Disease / Q000188:drug therapy / Q000601:surgery; D004347:Drug Interactions; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy; D016491:Peripheral Vascular Diseases / Q000188:drug therapy; D010672:Phenytoin / Q000009:adverse effects / Q000493:pharmacokinetics; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D018048:Receptors, Purinergic P2 / Q000187:drug effects* / Q000502:physiology; D012449:Safety; D015607:Stents; D013806:Theophylline / Q000009:adverse effects / Q000493:pharmacokinetics; D015912:Thrombolytic Therapy; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*
D000067956:Adenylyl Cyclase Inhibitors; D010975:Platelet Aggregation Inhibitors; D018048:Receptors, Purinergic P2; D002220:Carbamazepine; D010672:Phenytoin; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013806:Theophylline; D000262:Adenylyl Cyclases; D013988:Ticlopidine; D001241:Aspirin