Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Platelet aggregation is important for maintaining normal hemostasis. However, aberrant platelet aggregation plays a major role in acute coronary artery diseases, myocardial infarction, unstable angina, and stroke. ADP is one of the earliest and most important platelet agonists. ADP induces platelet aggregation, shape change, secretion, influx and intracellular mobilization of Ca2+, and inhibition of the adenylyl cyclase stimulated by prostaglandins. Binding of ADP to purinergic receptor(s) is required for elicitation of the ADP-induced platelet responses. But the platelet ADP receptor(s) has not been purified, largely due to the unavailability of the reagents that can be used to selectively label the platelet ADP receptor. The ADP receptor responsible for the ADP-induced platelet aggregation and inhibition of stimulated adenylyl cyclase activity has not been cloned due to difficulties in screening responsive clones generated from a cDNA library. Since the purified ADP-receptor protein is not available, antibodies that can be used as alternative tools to purify the ADP receptor or screen the clones expressing the receptor could not be made. In addition, the problem may be compounded by the low copy number and the susceptibility of the receptor to proteolysis. Therefore, signal transduction mechanisms underlying biochemical transformations in ADP-induced platelet responses remain less well defined and/less well understood. In the past decade efforts have been made to identify a platelet ADP receptor(s) by photoaffinity as well as affinity labeling by the ADP-affinity analogs. More recently efforts have been directed to clone the platelet ADP receptors. These investigations, however, have not produced definite results. The purpose of this review is to examine the results obtained by the photoaffinity- and affinity-labeling investigations and cloning experiments to identify a platelet ADP receptor(s).
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PMID:Purinergic receptors in human blood platelets: chemical modification and cloning investigations. 971 39

Clopidogrel, a new platelet ADP receptor antagonist, is more effective than aspirin in reducing the risk of subsequent vascular ischemic events in patients with a broad spectrum of symptomatic atherosclerosis (recent ischemic stroke, recent myocardial infarction, or symptomatic peripheral arterial disease). In CAPRIE (clopidogrel versus aspirin in patients at risk of ischemic events), a randomized, blinded, active control trial in 19,185 high-risk patients, clopidogrel reduced the combined risk of ischemic stroke, myocardial infarction or vascular death by 8.7% compared with aspirin (p = 0.043). The CAPRIE cohort had a mean age of 62.5 years, which was reflected in the high proportion of patients who had medical conditions other than symptomatic atherosclerosis, and in the extensive use of concurrent therapies, including commonly used cardiovascular drugs. For all concomitant medications analysed, there was no evidence of statistically or clinically significant interactions with clopidogrel. The CAPRIE data confirm the findings of earlier clinical studies, which suggested that clinically significant drug interactions with clopidogrel are rare, that it can safely be prescribed with a range of other drugs (including phenobarbital, cimetidine, estrogen, digoxin, theophylline, atenolol, nifedipine, or nifedipine-atenolol in combination), and that the clinically proven dose of 75 mg once daily is suitable for all age groups studied. Moreover, CAPRIE demonstrated that there is no need for an adjustment of clopidogrel dose on the basis of gender, weight or race, and that there is no need for routine hematological monitoring. Additional clinical pharmacology studies have shown that the absorption of clopidogrel is unaffected by food or antacids, and that no dose adjustment is necessary in patients with renal impairment or with mild-to-moderate hepatic impairment. Due to pharmacologic considerations and limited clinical data, clopidogrel should be used cautiously with heparin, warfarin or non-steroidal anti-inflammatory drugs. With a simple regimen of 75 mg once daily indicated for all patients, clopidogrel combines a favorable risk/benefit ratio with ease of use in clinical practice.
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PMID:Clinical aspects of the use of clopidogrel, a new antiplatelet agent. 1044 Apr 29

The central role of platelets in the pathophysiology of arterial vascular disease has focused attention on the development of effective platelet inhibitor modalities to mitigate the clinical consequences of atherothrombotic disease. Aspirin has been the gold standard of therapy and is effective in cerebral, coronary and peripheral arterial disease with a 25% reduction in myocardial infarction, stroke and vascular death. The platelet ADP receptor antagonists were developed to further improve the clinical results of therapy. Ticlopidine provides an additional 10% relative risk reduction over aspirin alone in stroke prevention and coronary stent placement. However, ticlopidine is accompanied by occasional life-threatening adverse hematological events. The action of clopidogrel is similar to that of ticlopidine, and it is comparably effective. However, the side-effect profile of clopidogrel is much more favorable.
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PMID:Platelet ADP receptor antagonists: ticlopidine and clopidogrel. 1517 57

Platelet aggregation inhibitors reduce the risk of complications during and after acute coronary syndromes and after a TIA or stroke. Acetylsalicylic acid plays a major role in secondary prevention; the combination of acetylsalicylic acid and a platelet ADP receptor antagonist, such as clopidogrel, may have added value. In percutaneous coronary intervention, dual platelet inhibition appears to be effective in the prevention of stent thrombosis. Long-term (> 1 year) use of dual platelet inhibition has an unfavourable risk-benefit profile, partly due to an increase in the number of bleeding events, particularly in the stomach. The use of the combination of acetylsalicylic acid and clopidogrel may be helpful after a TIA or minor stroke, but further research is needed to identify the group of patients for whom this combination would be applicable. This article provides an overview of the modern cardiological and neurological indications for platelet inhibition as well as the risk factors for severe bleeding events when using dual antiplatelet therapy.
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PMID:[Added value of clopidogrel in cardiology and neurology]. 2546 21