Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Organic nitrates are believed to provide relief from angina principally by dilating the coronary vasculature. Substantial evidence exists, however, to support a potent antiplatelet effect for these agents as well. Each of these compounds ultimately is metabolized to nitric oxide (or an S-nitrosothiol congener thereof), and this metabolite, in turn, is a potent activator of platelet guanylate cyclase. Activation of guanylate cyclase increases platelet cyclic guanosine monophosphate (cGMP), and is accompanied by inhibition of agonist-mediated calcium flux, and, in turn, reduction of fibrinogen binding to the glycoprotein IIb/IIIa receptor. Since fibrinogen binding is essential for platelet aggregation regardless of the agonist involved, its inhibition appears to be the critical mechanism by which platelet function is impaired by these agents. The recently recognized role that platelet-dependent thrombotic processes play in acute coronary syndromes suggests that the inhibition of platelets by nitrates may offer an additional mechanism by which these compounds improve perfusion to ischemic myocardium.
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PMID:Antiplatelet and antithrombotic effects of organic nitrates. 152 22

The pharmacodynamics of intravenous bolus injections of 0.05, 0.10, 0.15, and 0.20 mg/kg of F(ab')2 fragments of the murine monoclonal antibody 7E3, 7E3-F(ab')2, directed against the glycoprotein IIb/IIIa (GPIIb/IIIa) receptor of human platelets, were studied in groups of four patients with unstable angina pectoris. With 0.20 mg/kg, the template bleeding time prolonged from 6.3 +/- 1.9 (mean +/- SD) to greater than 30 min; it subsequently decreased to 13 +/- 7.8 min after 12 h and to 8.3 +/- 1.5 min after 24 h. The number of unblocked GPIIb/IIIa receptors (preinfusion value, 32,000 +/- 3,000 per platelet) decreased to 13 +/- 7% of the preinfusion value 1 h after infusion, and then increased to 33 +/- 10% at 12 h, 44 +/- 8% at 24 h and 67 +/- 7% at 72 h. The logarithm of the bleeding time was inversely proportional with the residual GPIIb/IIIa receptors (r = 0.73, P less than 0.0001). ADP-induced platelet aggregation (measured by changes in light transmittance in percent) decreased from 60 +/- 5% before infusion to 1.5 +/- 3% 1 h after infusion; it then increased to 29 +/- 3% after 24 h and 39 +/- 6% after 72 h. Platelet counts decreased by 16% at 1 h and returned to control values within 24 h. Proportionally smaller effects were seen at lower doses of 7E3-F(ab')2. Antibody injection did not induce spontaneous bleeding. Angina was not observed during the first 12 h when the bleeding time was significantly prolonged, but occurred in 6 of the 16 patients within the next 3 d. 2 of the 16 patients developed low titers of IgG antibodies specific for 7E3-F(ab')2. Thus 7E3-F(ab')2 induces dose-related inhibition of platelet function; at a dose of 0.20 mg/kg, it causes profound inhibition of platelet aggregation and prolongation of the bleeding time, but no spontaneous bleeding.
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PMID:Pharmacodynamic study of F(ab')2 fragments of murine monoclonal antibody 7E3 directed against human platelet glycoprotein IIb/IIIa in patients with unstable angina pectoris. 238 7

Platelet activation and thrombus formation within the coronary artery are major factors in acute myocardial infarction (AMI) and unstable angina (UA), and continuing platelet activation is associated with an adverse prognosis. We assessed platelet activation by using flow cytometry to measure platelet surface expression of P-selectin and glycoprotein IIb/IIIa in 20 patients with AMI and 20 with UA, all of whom were treated with aspirin. Platelet studies were repeated after the infusion of a nitric oxide donor (glyceryl trinitrate or S-nitrosoglutathione) that produced a fall in mean arterial pressure of no more than 10 mm Hg. P-selectin was expressed on 2.5% (range, 1.4% to 6.3%) of platelets from AMI and 2.3% (range, 1.6% to 3.3%) from UA subjects compared with 1.0% (range, 0.6% to 1.9%) of platelets from 20 control volunteers without angina (P < .001). Glycoprotein IIb/IIIa expression was 101.6 +/- 2.7 arbitrary units of relative fluorescence in AMI and 100.2 +/- 3.3 in UA compared with 87.8 +/- 2.5 in control subjects (P < .01). In both AMI and UA, S-nitrosoglutathione reduced P-selectin (P < .001) and glycoprotein IIb/IIIa (P < .05) expression, as did glyceryl trinitrate (P < .02 and P < .01, respectively). In 3 of 20 patients receiving glyceryl trinitrate the lowest dose was not tolerated due to headache or hypotension. These findings show that platelet activation persists in AMI and UA despite aspirin treatment and that this can be inhibited by using glyceryl trinitrate or S-nitrosoglutathione. S-nitrosoglutathione is better tolerated at the doses required.
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PMID:Platelet activation in acute myocardial infarction and unstable angina is inhibited by nitric oxide donors. 854 26

Acute coronary syndromes (unstable angina pectoris, acute myocardial infarction) are still the main cause of mortality and morbidity not only in economically advanced countries. Although coronary angioplasty has become modern treatment of stable angina as well as of acute coronaries, acute occlusion of the vessel is still a serious problem. The prognosis of patients undergoing coronary angioplasty can be substantially improved by accurate evaluation of the risk of possible complications during or shortly after the procedure and by development of more effective anticoagulants. Research provided evidence that platelets play a decisive role in the formation of occlusive thrombi and that the thrombocyte glycoproteins IIb/IIIa are the basic mediator of platelet aggregation. Newly developed inhibitors of these receptors reduce acute ischaemic complications after percutaneous transluminal coronary angioplasty. Conclusions of various trials support the inclusion of glycoprotein IIb/IIIa inhibitors in the standard therapeutic protocol of patients undergoing coronary angioplasty, in particular those with a high risk because of acute occlusion of the vessel after operation.
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PMID:[Clinical use of glycoprotein IIb/IIIa receptor blockers in invasive cardiology]. 974 84

Aspirin is an established therapy for the management of acute myocardial infarction (AMI) and unstable angina. Secondary prevention with chronic aspirin therapy is also indicated for patients with stable angina. Aspirin inhibits cyclo-oxygenase-I, a key enzyme in the biosynthetic pathway leading to the production of thromboxane A2. It therefore inhibits only one of the many activation pathways leading to platelet aggregation. Other antiplatelet agents that have also been evaluated in clinical trials include ticlopidine and clopidogrel, which inhibit adenosine diphosphate-mediated platelet aggregation, but these agents are known to be effective against only one of the 90 known agonists that stimulate platelet aggregation. The final common pathway for platelet aggregation involves the glycoprotein IIb/IIIa receptor combining with fibrinogen. Several inhibitors of the glycoprotein IIb/IIIa receptor have been developed and have an important role as adjunctive therapy in angioplasty. Recent trials have been performed in patients with unstable angina, and trials of adjunctive therapy are currently underway in patients receiving thrombolysis for AMI, and for secondary prevention. These drugs have various different features, including specificity for blockade of the glycoprotein IIb/IIIa receptor, half life, duration of the haemostatic effect and potential for antigenicity. Recently concluded and ongoing trials of both intravenous and oral agents are expected to provide further support for the introduction of these agents into clinical management of patients with acute coronary syndromes.
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PMID:New antiplatelet agents. 977 40

Unstable angina is a high-risk phase of coronary heart disease defined by clinical symptoms. Electrocardiographic findings are heterogeneous and creatine kinase is only rarely elevated. However, troponin T and troponin I are found in about 30-40% of patients with angina at rest disclosing minor myocardial cell injury. Several studies in recent years have documented that troponins are the best markers to identify high-risk patients when other life-threatening, non-cardiac diseases are excluded. In addition, first evidence is provided that only these patients benefit from prolonged treatment with low molecular weight heparin or glycoprotein IIb/IIIa receptor blockers. Therefore, this new diagnostic potential should be made available to emergency rooms for risk stratification and in the future to guide therapeutic decision making.
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PMID:Progress in the diagnosis of unstable angina and perspectives for treatment. 985 40

Fibrinogen is the major ligand of platelet glycoprotein IIb/IIIa platelet receptor. Genes coding for platelet fibrinogen receptor glycoprotein IIb/IIIa are polymorphic. The PLA alloantigen has two antigenic determinants, PLA1 and PLA2, located in a 17-23 kD fragment of glycoprotein IIIa. We analyzed whether PLA genotype has any effect on plasma fibrinogen concentration and investigated if the effect has different magnitude in myocardial infarction patients compared with subjects free of angina or myocardial infarction. One hundred sixteen consecutive patients who suffered a myocardial infarction and 136 subjects recruited by random sampling from the local census were included in the study. PLA genotype distribution and allele frequencies in patients did not significantly differ from those in the control group. Mean fibrinogen concentration tended to be higher in controls with genotype PLA1PLA1 than in those with genotype PLA1PLA2 or PLA2PLA2, and in patients this difference reached statistical significance (p < 0.001). We conclude that the PLA polymorphism may be in linkage disequilibrium with another functional mutation in or near the promoter area of the fibrinogen gene or even in another gene, which controls the production or the clearance of fibrinogen.
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PMID:Platelet glycoprotein IIb/IIIa genetic polymorphism is associated with plasma fibrinogen levels in myocardial infarction patients. The REGICOR Investigators. 987 97

In patients with ongoing angina, despite optimal medical therapy, the best therapeutic alternative is coronary angiography followed by emergency coronary revascularization with surgery or angioplasty. However, whether or not all patients should have early angiography and revascularization is a matter of debate. This paper reviews the advantages of modern medical therapy in this setting and the problems associated with early coronary revascularization. In particular, it analyses the data from the main clinical trials that have specifically compared an early invasive procedure with a conservative strategy in unstable coronary syndromes. Finally, it assesses the impact of the new antithrombotic agents, such as glycoprotein IIb/IIIa receptor blockers, particularly during coronary percutaneous interventions. The data reviewed suggest that early invasive intervention should be reconsidered, and that patients should be controlled (if possible) under medical treatment until non invasive stratification tests allow the identification of those patients who would benefit most from revascularization.
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PMID:[Early percutaneous revascularization in patients with unstable angina. Current results and comparison with conservative medical treatment]. 1036 21

This article focuses on the optimal treatment of postinfarction, refractory, or recurrent angina based on the results of recent clinical trials. Many of our recommendations hold true for the general management of unstable angina, but special considerations for the high-risk subsets are emphasized. Specifically, we discuss acute medical management and suggest that an early aggressive strategy that leads to early coronary angiography with the goal of revascularization when feasible best serves this subset. A special emphasis on the emerging role of glycoprotein IIb-IIIa antagonists is made because the important role of platelets in coronary thrombosis has dominated recent views on the pathophysiology of unstable angina.
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PMID:Management of high-risk subsets in unstable angina. 1038 36

The emergency department (ED) evaluation of patients with potential acute coronary syndromes (ACS) has traditionally included initial cardiac marker testing for suspected acute myocardial infarction (AMI). While ED management decisions for patients with ACS have largely been based on history, physical examination, and a presenting 12-lead electrocardiogram (ECG), there is ample evidence that markers impact treatment decisions and provide risk stratification. Newer, more sensitive markers of myocardial necrosis have blurred the distinction between patients with and without classically defined AMI, and have focused attention on the continuum of ACS from angina to transmural Q-wave MI. Newer antiplatelet agents, the glycoprotein IIb/IIIa receptor blockers, are likely to receive increased ED utilization. This use will be partially driven by ED cardiac marker determination. Bedside, point-of-care testing is reliable technology that may shorten time to diagnosis and treatment of ACS in the emergency setting. The ED-based chest pain center (CPC) has become a popular tool to evaluate patients at low- to moderate-risk for ACS and a non-diagnostic ECG. Such centers use serial cardiac marker testing as a mainstay for evaluation and risk stratification. Cost issues have driven many diagnostic patient evaluations from the inpatient setting to such ED observation units. As this becomes more common for low- to moderate-risk patients with chest pain, serial assessment of cardiac markers, and their interpretation by emergency physicians, will become essential.
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PMID:The role of cardiac markers in the emergency department. 1045 Dec 45


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