Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clopidogrel is a new thieno-pyridine derivative and has a more potent inhibitory effect on platelet aggregation, dependent on ADP rather than ticlopidine. In a phase I study performed in Japan, significant inhibition of ADP-induced platelet aggregation and prolongation of bleeding time was observed in the dose range of 25, 50 and 75 mg. These effects were comparable to 200 or 300 mg of ticlopidine. Antithrombotic effects have also been shown in experimental animal models. Clopidogrel is expected to reduce the incidence of neutropenia since smaller doses are sufficient to suppress platelet aggregation compared to ticlopidine. Clopidogrel has been proven to be a potent and well-tolerated antiplatelet agent for atherosclerosis patients at risk of thrombosis, in Europe.
 ...
PMID:[Antiplatelet effect of clopidogrel]. 161 93

Clopidogrel is a thienopyridine that irreversibly inhibits platelet aggregation by selectively binding to adenylate cyclase-coupled ADP receptors on the platelet surface. In animal models, clopidogrel reduced the formation of both arterial and venous thrombi. After oral administration, clopidogrel is rapidly absorbed and undergoes metabolic activation in the liver. The principal circulating metabolite is SR 26334, an inactive carboxylic acid derivative. The active metabolite is not yet known. Findings of a large, well controlled study of clopidogrel versus aspirin in patients with atherosclerotic vascular disease (CAPRIE study) indicate that clopidogrel has superior efficacy in terms of prevention of ischaemic stroke, myocardial infarction and vascular death. Clopidogrel-treated patients experienced less frequent gastrointestinal upset, abnormal liver function and gastrointestinal haemorrhage than patients who received aspirin, but more frequent rash and diarrhoea. Neutropenia and thrombocytopenia occurred rarely and at similar rates in both groups.
 ...
PMID:Clopidogrel. 2642 34

Ticlopidine and clopidogrel achieve antiplatelet effects by inhibiting the binding of adenosine 5'-disphosphate to its platelet receptor. Ticlopidine was first shown to decrease major events compared with placebo or aspirin in patients with stroke or recent transient ischemic attack. Randomized studies in patients undergoing coronary artery stenting have shown that ticlopidine reduces the risk for subacute stent thrombosis compared with warfarin-based regimens. Smaller studies have also shown this drug to have benefit during follow-up in patients with unstable angina, peripheral arterial disease, saphenous vein coronary bypass grafts, and diabetic retinopathy. Clopidogrel was recently approved by the U.S. Food and Drug Administration for the reduction of ischemic events in patients with recent myocardial infarction, stroke, or peripheral arterial disease (incidence, 5.32% per year compared with 5.83% per year for aspirin; P = 0.043) with no added risk for neutropenia. The combination of clopidogrel and aspirin, as well as the utility of clopidogrel in other patient populations and in stenting, requires further study. Ticlopidine and clopidogrel seem to have beneficial effects compared with aspirin (the current standard) in a broad range of patients. These observations highlight the importance of antiplatelet therapy in cardiovascular disease.
 ...
PMID:The antiplatelet effects of ticlopidine and clopidogrel. 973 68

Effective antiplatelet drugs--aspirin, ticlopidine, dipyridamole, and clopidogrel--are reviewed. Aspirin has remained the pharmacologic foundation of stroke prevention, primarily because of its low cost. It has been shown to provide a 22% relative risk reduction of stroke in high-risk patients. Its principal adverse effect is gastrotoxicity. Ticlopidine has been widely used in patients with a high risk of stroke who are sensitive to aspirin or in whom aspirin has failed. It has been associated with a median reduction in adenosine diphosphate-induced platelet aggregation of 70% in about 8-11 days. Ticlopidine has been shown to be superior to aspirin at three years in preventing stroke. The principal adverse effects are diarrhea and rash; there has been a 2.4% occurrence of neutropenia. In a trial comparing aspirin, dipyridamole, and a combination of the two, the risk of stroke was 18% lower with aspirin, 16% lower with dipyridamole, and 37% lower with combination therapy compared with placebo. The adverse-effect profile of dipyridamole has proven to be less problematic than that of aspirin or ticlopidine. In a trial comparing clopidogrel with aspirin, patients receiving clopidogrel had an annual 5.32% risk of ischemic stroke, myocardial infarction, or vascular death compared with 5.83% for patients receiving aspirin. Clopidogrel has been associated with a small occurrence of rash and diarrhea, and gastrointestinal intolerance and hemorrhage were less frequent with clopidogrel than with aspirin. Both aspirin and clopidogrel are associated with a low occurrence of neutropenia. Aspirin, ticlopidine, dipyridamole, and clopidogrel have earned a role in stroke prevention; the different adverse-effect profiles of the drugs will influence the choice of agent.
 ...
PMID:Clinical considerations in selecting antiplatelet therapy in cerebrovascular disease. 978 98

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.
 ...
PMID:Ticlopidine and clopidogrel. 1051 40

Clopidogrel and ticlopidine are antiplatelet agents used in the treatment of patients with cerebrovascular and peripheral vascular disease and to reduce the risk for thrombosis in patients undergoing coronary artery stenting. Ticlopidine has been reported to have major hematologic adverse effects, including neutropenia and thrombotic thrombocytopenic purpura or hemolytic uremic syndrome (HUS). Clopidogrel, an analogue of ticlopidine, was developed because it did not show bone marrow toxic effects in either tissue culture or animal models. In human studies, to date, clopidogrel has been associated with a low incidence of severe neutropenia and no reported cases of thrombotic thrombocytopenic purpura or HUS. For these reasons, clopidogrel has been increasingly used in place of ticlopidine after coronary artery stenting. We report a case of clopidogrel-associated HUS. This observation implicates clopidogrel as a possible causative agent in HUS.
 ...
PMID:Hemolytic uremic syndrome associated with clopidogrel: a case report. 1080 43

Five randomized trials have conclusively demonstrated that aspirin and ticlopidine are more effective than aspirin and Coumadin (DuPont Merck Pharmaceutical Co., Wilmington, DE), or aspirin alone, at preventing thrombosis and other ischemic complications after stent placement. However, side effects from ticlopidine are common, the most serious of which are neutropenia and thrombotic thrombocytopenic purpura. Another problem with ticlopidine is its slow onset of action. Recent observational data from several centers and data from a randomized trial indicate that clopidogrel, which can be administered with large loading doses that are well tolerated and speed the onset of action, is at least as effective as ticlopidine. Clopidogrel has far fewer side effects as well. Questions remain about the most appropriate loading dose of clopidogrel and duration of therapy after stent placement.
 ...
PMID:Clopidogrel After Coronary Stenting. 1109 33

Aspirin inhibits platelet activation by irreversibly inhibiting platelet cyclooxygenase and thromboxane production, and reduces the odds of serious vascular events (stroke, myocardial infarction or vascular death) by about one quarter in a range of patients with symptomatic atherosclerosis at high risk of a subsequent event. The adenosine diphosphate (ADP) receptor antagonists clopidogrel and ticlopidine are significantly more effective than aspirin in high-risk vascular patients, further reducing the odds of serious vascular events by about 10% (95% CI 2-19%) over the benefit provided by aspirin. The ADP receptor antagonists are also associated with a significant 30% reduction in the odds of gastrointestinal haemorrhage (odds ratio 0.71, 95% CI 0.59-0.86). Ticlopidine increases the odds of skin rash and of diarrhoea by more than twofold compared with aspirin, whereas clopidogrel is associated with a one-third increase in the odds of rash and of diarrhoea. Only ticlopidine increases the odds of neutropenia compared with aspirin. There is no clear evidence as yet for the benefit of dipyridamole or an oral GP IIb/IIIa receptor antagonist as single antiplatelet agents in atherothrombotic patients. Amongst high vascular risk patients, the combination of low-dose aspirin and high-dose dipyridamole is associated with about a 10% (95% CI 0-20%) reduction in the odds of a serious vascular event. Most of this reduction is due to a 23% reduction in non-fatal stroke. The size of this estimate continues to be investigated in an ongoing study of patients with transient ischaemic attack and stroke. The combined use of aspirin and ticlopidine is markedly superior to heparin, warfarin and aspirin for reducing thrombotic complications after coronary artery stenting. Clopidogrel plus aspirin has been shown to be safer than aspirin and ticlopidine in coronary stenting, and is now under long-term evaluation in unstable angina, and other conditions in which patients are at high risk of atherothrombotic events.
 ...
PMID:Current oral antiplatelet agents to prevent atherothrombosis. 1131 17

In patients with transient ischemic attack (TIA) or ischemic stroke of noncardiac origin, antiplatelet drugs are able to decrease the risk of stroke by 11% to 15%, and decrease the risk of stroke, myocardial infarction (MI), and vascular death by 15% to 22%. Aspirin leads to a moderate but significant reduction of stroke, MI, and vascular death in patients with TIA and ischemic stroke. Low doses are as effective as high doses, but are better tolerated in term of gastrointestinal side effects. The recommended aspirin dose, therefore, is between 50 and 325 mg. Bleeding complications are not dose-dependent, and also occur with the lowest doses. The combination of aspirin (25 mg twice daily) with slow release dipyridamole (200 mg twice daily) is superior compared with aspirin alone for stroke prevention. Ticlopidine is effective in secondary stroke prevention in patients with TIA and stroke. For some endpoints, it is superior to aspirin. Due to its side effect profile (neutropenia, thrombotic thrombocytopenic purpura ), ticlopidine should be given to patients who are intolerant of aspirin. Prospective trials have not indicated whether ticlopidine is suggested for patients who have recurrent cerebrovascular events while on aspirin. Clopidogrel has a better safety profile than ticlopidine. Although not investigated in patients with TIA, clopidogrel should also be effective in these patients assuming the same pathophysiology than in patients with stroke. Clopidogrel is second-line treatment in patients intolerant for aspirin, and first-line treatment for patients with stroke and peripheral arterial disease or MI. A frequent clinical problem is patients who are already on aspirin because of coronary heart disease or a prior cerebral ischemic event, and then suffer a first or recurrent TIA or stroke. No single clinical trial has investigated this problem. Therefore, recommendations are not evidence-based. Possible strategies include the following: continue aspirin, add dipyridamole, add clopidogrel, switch to ticlopidine or clopidogrel, or switch to anticoagulation with an International Normalized Ratio (INR) of 2.0 to 3.0. The combination of low-dose warfarin and aspirin was never studied in the secondary prevention of stroke. In patients with a cardiac source of embolism, anticoagulation is recommended with an INR of 2.0 to 3.0. At the present time, anticoagulation with an INR between 3.0 and 4.5 can not be recommended for patients with noncardiac TIA or stroke. Anticoagulation with an INR between 3.0 and 4.5 carries a high bleeding risk. Whether anticoagulation with lower INR is safe and effective is not yet known. Treatment of vascular risk factors should also be performed in secondary stroke prevention.
 ...
PMID:Antithrombotic Secondary Prevention After Stroke. 1148 59

Clopidogrel has replaced ticlopidine (in the United States but not worldwide). Clopidogrel can either be used independently or in combination with other antiplatelet agents. Clopidogrel has a lower frequency of associated thrombotic thrombocytopenic purpura than ticlopidine, a lower rate of neutropenia, and better gastrointestinal tolerance. We describe a case of thrombotic thrombocytopenic purpura associated with the use of clopidogrel after percutaneous transluminal angioplasty and stent placement. Discontinuation of the drug and transfusion of 17 units of cryodepleted plasma resulted in resolution of the hematological abnormalities. Clinicians should be alert to this adverse effect of clopidogrel and monitor platelet counts in patients receiving it.
 ...
PMID:Thrombotic thrombocytopenic purpura associated with clopidogrel administration: case report and brief review. 1157 Jul 85


1 2 3 Next >>