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Thrombosis Research Sep 2022Eptifibatide is an αIIbβ3 inhibitor that is currently used in the clinic. More than 10 scientific communications indicate that eptifibatide has a Lys-Gly-Asp or...
Eptifibatide is an αIIbβ3 inhibitor that is currently used in the clinic. More than 10 scientific communications indicate that eptifibatide has a Lys-Gly-Asp or Arg-Gly-Asp sequence, while it actually has a hArg-Gly-Asp sequence. We aimed to unravel the importance of the homoarginine residue in eptifibatide in platelet activation and aggregation. Arg- and Lys-eptifibatide were synthesized by solid-phase peptide synthesis and measured in light transmission aggregometry, flow cytometry and whole blood thrombus formation under flow. Interactions of eptifibatide and its variants with αIIbβ3 integrin were studied using molecular dynamics simulations. Eptifibatide showed inhibition of collagen- and ADP-induced platelet aggregation, while Arg- and Lys-eptifibatide did not. Multiparameter assessment of thrombus formation showed suppressed platelet aggregate and fibrin formation upon eptifibatide treatment, in contrast to the other variants. Molecular dynamics simulations revealed that the hArg residue in eptifibatide is crucial to its activity, since the substitution of the hArg to Arg or Lys resulted in the inability to form double H-bonds with Asp224 in the αIIb chain of the αIIbβ3 receptor. The hArg is pivotal for the interaction of eptifibatide for the αIIbβ3 receptor and efficient inhibition of platelet aggregation.
Topics: Blood Platelets; Eptifibatide; Homoarginine; Humans; Peptides; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Thrombosis
PubMed: 35926348
DOI: 10.1016/j.thromres.2022.07.011 -
Cureus Nov 2023ST-Elevation Myocardial Infarction and non-ST Elevation Myocardial Infarction belong to the acute coronary syndrome group of diseases. These conditions are characterized... (Review)
Review
ST-Elevation Myocardial Infarction and non-ST Elevation Myocardial Infarction belong to the acute coronary syndrome group of diseases. These conditions are characterized by the complete or partial blockage of one or several coronary arteries, resulting in myocardial injury or necrosis. Various medications are used in their treatment, with the most recent addition being Glycoprotein IIb/IIIa inhibitors. They work by hindering the activity of glycoprotein IIb/IIIa receptors, which, in turn, prevents the clumping of platelets. Some of the GpIIb/IIIa inhibitors available in this category include abciximab, tirofiban, eptifibatide, roxifiban, and orbofiban. With this comprehensive literature review, we aimed to explore the potential adverse effects of these medications and compare the three in terms of their side effects profile. We searched through PubMed and Google Scholar and pinpointed 13 articles aligned with our inclusion criteria: six articles utilized eptifibatide, four were related to abciximab, and three used tirofiban. In 85% of the cases, a severe drop in platelet count, reaching as low as 1000/μL, was reported. Additionally, several other side effects were noted: one case documented multiple bruising spots appearing around the patient's body, two cases reported diffuse alveolar hemorrhage, and one case described a cardiac tamponade resulting from hemorrhagic pericarditis. Our study highlights the crucial significance of keeping a watchful eye on and comprehending the potential drawbacks linked to these medications in cardiovascular treatment. The necessity of researching these medications and their side effects is also evident, as this will significantly enhance the quality of treatment provided.
PubMed: 38143693
DOI: 10.7759/cureus.49332 -
Yakugaku Zasshi : Journal of the... 2015Drug delivery techniques to tumor cells have attracted considerable attention. For instance, folic acid (FA) as a tumor-targeting ligand is widely used because of... (Review)
Review
Drug delivery techniques to tumor cells have attracted considerable attention. For instance, folic acid (FA) as a tumor-targeting ligand is widely used because of overexpression of folate receptor-α (FR-α) in various kinds of epithelial tumor cells. On the other hand, methyl-β-cyclodextrin (M-β-CyD) is acknowledged to induce cell death through the extraction of cholesterol from lipid rafts. It was recently reported that intraperitoneal administration of M-β-CyD exerted antitumor activity in human tumor xenografted athymic nude mice. However, the cytotoxic activity of M-β-CyD is known to lack tumor cell selectivity. Therefore in the present study, in an attempt to confer tumor cell selectivity to M-β-CyD, we newly synthesized folate-appended M-β-CyD (FA-M-β-CyD) and evaluated its potential as a novel antitumor agent. FA-M-β-CyD showed potent antitumor activity in various FR-α-positive cells such as KB cells, Ihara cells, and M213 cells but not in FR-α-negative cells, A549 cells. FA-M-β-CyD induced the formation of autophagic vacuoles in KB cells. In addition, the antitumor activity of FA-M-β-CyD, but not M-β-CyD, was inhibited by addition of the autophagy inhibitors chloroquine and bafilomycin A1 in KB cells. A single intravenous injection of FA-M-β-CyD drastically inhibited tumor growth and significantly improved survival rate in Colon-26 cells-allografted or M213 cells-xenografted mice. In conclusion, FA-M-β-CyD has potential as a novel tumor-selective anticancer agent due to FR-α-mediated cellular uptake. The present results provide useful information for the design and development of novel antitumor drug carriers and antitumor drugs based on CyDs.
Topics: Animals; Antineoplastic Agents; Antiviral Agents; Autophagy; Eptifibatide; ErbB Receptors; Humans; Mannose-Binding Lectins; Mice; Neoplasms; Peptides
PubMed: 26521878
DOI: 10.1248/yakushi.15-00202 -
Journal of the American College of... Feb 2002This study was designed to test the hypothesis that eptifibatide and reduced-dose tissue plasminogen activator (t-PA) will enhance infarct artery patency at 60 min in... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Eptifibatide and low-dose tissue plasminogen activator in acute myocardial infarction: the integrilin and low-dose thrombolysis in acute myocardial infarction (INTRO AMI) trial.
OBJECTIVES
This study was designed to test the hypothesis that eptifibatide and reduced-dose tissue plasminogen activator (t-PA) will enhance infarct artery patency at 60 min in patients with acute myocardial infarction (AMI).
BACKGROUND
Combination fibrin and platelet lysis improves epicardial and myocardial reperfusion in AMI.
METHODS
Patients were enrolled in a dose finding (Phase A, n = 344) followed by a dose confirmation (Phase B, n = 305) protocol. All patients received aspirin and weight-adjusted heparin and underwent angiography at 60 and 90 min. In Phase A, eptifibatide in a single or double bolus (30 min apart) of 180, 180/90 or 180/180 microg/kg followed by an infusion of 1.33 or 2.0 microg/kg per min was sequentially added to 25 or 50 mg of t-PA. In Phase B, patients were randomized to: 1) double-bolus eptifibatide 180/90 (30 min apart) and 1.33 microg/kg per min infusion with 50 mg t-PA (Group I); 2) 180/90 (10 min apart) and 2.0 g/kg per min with 50 mg t-PA (Group II); or 3) full-dose, weight-adjusted t-PA (Group III).
RESULTS
In Phase A, the best rate of Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 was achieved using 180/90/1.33 microg/kg per min eptifibatide with 50 mg t-PA: 65% and 78% at 60 and 90 min, respectively. In Phase B, the incidence of TIMI flow grade 3 at 60 min was 42%, 56% and 40%, for Groups I through III, respectively (p = 0.04, Group II vs. Group III). The median corrected TIMI frame count was 38, 33 and 50, respectively (p = 0.02). TIMI major bleeding was reported in 8%, 11% and 6%, respectively; intracranial hemorrhage occurred in 1%, 3% and 2% of patients (p > 0.5 for both). The incidences of death (4%, 5% and 7%), reinfarction or revascularization at 30 days were similar among the three treatment groups.
CONCLUSIONS
In comparison with standard t-PA regimen, double-bolus eptifibatide (10 min apart) with a 48-h infusion and half-dose t-PA (Group II) is associated with improved quality and speed of reperfusion. The safety profile of this therapy is similar to that of other combination regimens.
Topics: Adult; Aged; Coronary Vessels; Dose-Response Relationship, Drug; Drug Therapy, Combination; Electrocardiography; Eptifibatide; Europe; Female; Fibrinolytic Agents; Humans; Incidence; Intracranial Hemorrhages; Male; Middle Aged; Myocardial Infarction; North America; Peptides; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Radiography; South Africa; Survival Analysis; Thrombocytopenia; Time Factors; Tissue Plasminogen Activator; Treatment Outcome; Vascular Patency
PubMed: 11823073
DOI: 10.1016/s0735-1097(01)01758-2 -
Critical Reviews in Eukaryotic Gene... 2011Connective tissue growth factor (CTGF) is a 38 kDa, cysteine rich, extracellular matrix protein composed of 4 domains or modules. CTGF has been shown to regulate a... (Review)
Review
Connective tissue growth factor (CTGF) is a 38 kDa, cysteine rich, extracellular matrix protein composed of 4 domains or modules. CTGF has been shown to regulate a diverse array of cellular functions and has been implicated in more complex biological processes such as angiogenesis, chondrogenesis, and osteogenesis. A role for CTGF in the development and maintenance of skeletal tissues first came to light in studies demonstrating its expression in cartilage and bone cells, which was dramatically increased during skeletal repair or regeneration. The physiological significance of CTGF in skeletogenesis was confirmed in CTGF-null mice, which exhibited multiple skeletal dysmorphisms as a result of impaired growth plate chondrogenesis, angiogenesis, and bone formation/mineralization. Given the emerging importance of CTGF in osteogenesis and chondrogenesis, this review will focus on its expression in skeletal tissues, its effects on osteoblast and chondrocyte differentiation and function, and the skeletal implications of ablation or over-expression of CTGF in knockout or transgenic mouse models, respectively. In addition, this review will examine the role of integrin-mediated signaling and the regulation of CTGF expression as it relates to skeletogenesis. We will emphasize CTGF studies in bone or bone cells, and will identify opportunities for future investigations concerning CTGF and chondrogenesis/osteogenesis.
Topics: Animals; Bone Development; Chondrogenesis; Connective Tissue Growth Factor; Eptifibatide; Gene Expression Regulation, Developmental; Humans; Mice; Mice, Transgenic; Neovascularization, Physiologic; Osteogenesis; Peptides; Transforming Growth Factor beta
PubMed: 21967332
DOI: 10.1615/critreveukargeneexpr.v21.i1.40 -
Journal of Medicine and Life 2021Early and complete restoration of blood flow in closed coronary arteries is the main goal in treating patients with myocardial infarction. Primary angioplasty is not... (Randomized Controlled Trial)
Randomized Controlled Trial
Early and complete restoration of blood flow in closed coronary arteries is the main goal in treating patients with myocardial infarction. Primary angioplasty is not always successful in establishing myocardial blood flow. Although the strategy of adding eptifibatide leads to better blood flow, its value as part of a routine strategy is questionable. Therefore, this study was performed to evaluate the efficacy of intravenous eptifibatide in primary percutaneous coronary intervention (PCI) patients. This clinical, randomized, double-blind trial was performed on patients aged 20-80 years undergoing primary PCI. The patients were selected for study by convenience sampling and were randomly divided into two equal groups. The first group was treated with intravenous eptifibatide immediately before angioplasty with heparin. The second group received only coronary angioplasty with heparin. After data collection, statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) software, version 16. A total of 104 patients were enrolled in the study, and there were no statistically significant differences in terms of age (P=0.188), gender (P=0.345), risk factor (P>0.05), or history of PCI (P=0.199). Mean thrombolysis in myocardial infarction (TIMI) score was not significant between the two groups after receiving the drug and performing angioplasty (P>0.05), and the rate of ejection fraction was 46.33±6.69 in patients receiving eptifibatide and 47.54±4.67 in the heparin group, which was not statistically significant (P=0.884). We found that eptifibatide improves clinical indexes in patients undergoing primary PCI, but these differences were not significant in the two groups.
Topics: Angioplasty, Balloon, Coronary; Eptifibatide; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Treatment Outcome
PubMed: 34377204
DOI: 10.25122/jml-2021-0035 -
The American Journal of Cardiology Jan 2021The glycoprotein IIb/IIIa inhibitor eptifibatide, administered as bolus followed by infusion, is an adjunctive antithrombotic treatment during primary percutaneous...
Efficacy and Safety of Abbreviated Eptifibatide Treatment in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.
The glycoprotein IIb/IIIa inhibitor eptifibatide, administered as bolus followed by infusion, is an adjunctive antithrombotic treatment during primary percutaneous coronary intervention (PCI) in selected patients with ST-segment elevation myocardial infarction (STEMI). Whether both bolus and infusion are necessary to improve outcomes is unknown. We hypothesized that primary PCI with eptifibatide bolus only is non-inferior to the conventional treatment (bolus and infusion) with regard to infarct size, while reducing bleeding complications. We analyzed 720 consecutive STEMI patients receiving eptifibatide bolus only or conventional treatment in an observational case-control study utilizing propensity score matching of clinical and intervention-specific confounders. Infarct size was estimated based on myocardial bound creatine kinase, creatine kinase (CK), and CK area under the curve values, with a prespecified non-inferiority margin of 20%. Major bleeding was defined as type 2, 3, or 5 on the Bleeding Academic Research Consortium classification. Eptifibatide bolus only was administered to 147 patients (20%), which were matched 1:1 to patients receiving conventional treatment. Based on peak myocardial bound creatine kinase, CK and CK area under the curve values, infarct size was -8.4% (95% CI [-31.2%, 14.4%]), -11.6% (95% CI [-33.5%, 10.3%]), and -13.9% (95% CI [-34.1%, 6.2%]) after eptifibatide bolus, respectively, reaching prespecified noninferiority compared with conventional treatment. Bolus treatment significantly reduced major bleeding complications (OR 0.48, 95% CI [0.30, 0.79]). In conclusion, eptifibatide given as abbreviated bolus only to selected STEMI patients who underwent primary PCI was noninferior regarding infarct size and resulted in less bleeding complications compared with conventional bolus and infusion treatment.
Topics: Coronary Angiography; Dose-Response Relationship, Drug; Electrocardiography; Eptifibatide; Female; Follow-Up Studies; Humans; Injections, Intravenous; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Preoperative Care; Retrospective Studies; ST Elevation Myocardial Infarction; Treatment Outcome
PubMed: 33065082
DOI: 10.1016/j.amjcard.2020.09.054 -
Journal of Community Hospital Internal... Mar 2021Eptifibatide is a glycoprotein (GP) IIb/IIIa receptor antagonist, used for the treatment of acute coronary syndrome with high-risk features or ongoing ischemia. Several...
Eptifibatide is a glycoprotein (GP) IIb/IIIa receptor antagonist, used for the treatment of acute coronary syndrome with high-risk features or ongoing ischemia. Several case reports have described thrombocytopenia as a rare side effect of eptifibatide administration. The exact mechanism remains unclear but may be due to immune destruction of circulating platelets in the peripheral blood. We present the case of acute-onset severe thrombocytopenia in a 76-year-old female undergoing percutaneous coronary intervention.
PubMed: 33889336
DOI: 10.1080/20009666.2021.1871802 -
Current Cardiology Reviews 2015Patients with advanced chronic kidney disease (CKD), including those treated with dialysis, are at high risk for the development of cardiovascular disease (CVD). CVD... (Review)
Review
Patients with advanced chronic kidney disease (CKD), including those treated with dialysis, are at high risk for the development of cardiovascular disease (CVD). CVD accounts for 45-50% of deaths among dialysis patients. Therapy of acute and chronic coronary heart disease (CHD) that is effective in the general population is frequently less effective in patients with advanced CKD. Drug therapy in such patients may require dose modification in some cases. Oral anti-platelet drugs are less effective in those with advanced CKD than in persons with normal or near normal renal function. The intravenous antiplatelet drugs eptifibatide and tirofiban both require dose reductions in patients with advanced CKD. Enoxaparin requires dose reduction in early stage CKD and is contraindicated in hemodialysis patients. Unfractionated heparin and warfarin maybe used without dose adjustment in CKD patients. Atenolol, acetbutolol and nadolol may require dose adjustments in CKD. Metoprolol and carvedilol do not. Calcium channel blockers and nitrates do not require dose adjustment, whereas ranolazine does. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers may safely be used in CKD patients with close observation for hyperkalemia. The safety of spironolactone in such patients is questionable. Statins are less effective in reducing cardiovascular complication in CKD patients and their initiation is not recommended in dialysis patients. Coronary artery bypass grafting is associated with higher shortterm mortality, but better long-term morbidity and mortality than percutaneous coronary interventions in patients with advanced CKD with non-ST segment ACS and chronic CHD.
Topics: Coronary Artery Disease; Dialysis; Humans; Myocardial Revascularization; Renal Insufficiency, Chronic; Treatment Outcome
PubMed: 25981315
DOI: 10.2174/1573403x1103150514155757 -
Cardiovascular Diabetology Dec 2008The use of abciximab (c7E3 Fab) or eptifibatide improves clinical outcomes in diabetics undergoing percutaneous coronary intervention. These beta3 integrin inhibitors...
BACKGROUND
The use of abciximab (c7E3 Fab) or eptifibatide improves clinical outcomes in diabetics undergoing percutaneous coronary intervention. These beta3 integrin inhibitors antagonize fibrinogen binding to alphaIIbbeta3 integrins on platelets and ligand binding to alphavbeta3 integrins on vascular cells. alphavbeta3 integrins influence responses to insulin in various cell types but effects in human aortic smooth muscle cells (HASMC) are unknown.
RESULTS AND DISCUSSION
Insulin elicited a dose-dependent proliferative response in HASMC. Pretreatment with m7E3 (an anti-beta3 integrin monoclonal antibody from which abciximab is derived), c7E3 or LM609 inhibited proliferative responses to insulin by 81%, 59% and 28%, respectively. Eptifibatide or cyclic RGD peptides completely abolished insulin-induced proliferation whereas tirofiban, which binds alphaIIbbeta3 but not alphavbeta3, had no effect. Insulin-induced increases in c-Jun NH2-terminal kinase-1 (JNK1) activity were partially inhibited by m7E3 and eptifibatide whereas antagonism of alphavbeta3 integrins had no effect on insulin-induced increases in extracellular signal-regulated kinase (ERK) activity. Insulin stimulated a rapid increase in the number of vinculin-containing focal adhesions per cell and treatment with m7E3, c7E3 or eptifibatide inhibited insulin-induced increases in focal adhesions by 100%, 74% and 73%, respectively.
CONCLUSION
These results demonstrate that alphavbeta3 antagonists inhibit signaling, focal adhesion formation and proliferation of insulin-treated HASMC.
Topics: Abciximab; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Cell Proliferation; Cells, Cultured; Diabetic Angiopathies; Eptifibatide; Extracellular Signal-Regulated MAP Kinases; Focal Adhesions; Humans; Immunoglobulin Fab Fragments; Insulin; Insulin Antagonists; Insulin Resistance; Integrin alphaVbeta3; Mitogen-Activated Protein Kinase 8; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Peptides; Platelet Aggregation Inhibitors; Signal Transduction
PubMed: 19108709
DOI: 10.1186/1475-2840-7-36