3. GP IIb/IIIa Inhibitors G lycoprotein IIb/IIIa inhibitors , also GpIIb/IIIa inhibitors , is a class of antiplatelet agents . Several GpIIb/IIIa inhibitors exist: abciximab (ReoPro) eptifibatide (Integrilin) tirofiban (Aggrastat)
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5. They may also be used to treat acute coronary syndromes, without percutaneous coronary intervention, depending on TIMI risk. They should be given intravenously. The oral form is associated with increased mortality and hence should not be given. In integrin nomenclature glycoprotein IIb/IIIa is called αIIbβ3
7. Abciximab It is fab fragment of a chimeric monoclonal antibody against GP II b IIIa . Given along with aspirin + heparin during PCI it is markely reduce the incidence of restenosis subsequent MI and dead . After a bolus dose platelet aggregation remain inhibitor for 12-24 hr , while the remaining antibody is cleared from blood with a t ½ of 10 – 30 min.
8. Abciximab risk. 1 .The main risk is hemorrhage , incidence of which can be reduced by carefully managing the concomitant heparin therapy . 2 .Thrombocytopenia is another complication . 3 . Constipation , 4 . ileus and 5 . arrhythmias can occur . It is very expensive , but is being used in unstable angina and as adjuvant to coronary thrombolysis /PCI with stent placement
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11. The drug is marketed under the brand name AGGRASTAT in the US by Medicure Pharma and the rest of the world by Irokocardio International SARL, Geneva . It is sold in parenteral dosage forms intended and readily constituted for IV administration containing 5 mg or 12.5 mg, respectively. Tirofiban has a rapid onset and short duration of action after proper IV administration. Coagulation parameters turn to normal 4 to 8 hours after the drug is withdrawn. ** It is a modified version of an anticoagulant found in the venom of the saw-scaled viper Echis carinatus
12. Dosage regimen Tirofiban is initially given as rapid intravenous infusion at a rate of 0.4 µg/kg and minute for 30 minutes. Upon completion of the initial infusion, the rate is decreased to 0.1 µg/kg and minute delivered as continuous infusion.
13. Duration of therapy Patients who do not show any signs of recurrent ischemic symptoms and do not undergo angiography and angioplasty should be treated for at least 48 hours. Patients proceeding into angiography and angioplasty should continue throughout both procedures and for at least 12 hours, and not more than 24 hours after angioplasty. Once a patient is clinically stable and no further coronary intervention is planned by the treating physician, the infusion should be discontinued
14. Contraindications and precautions * hypersensitivity * internal bleeding * intracranial hemorrhage or neoplasm, * arteriovenous malformation , or aneurysm * thrombocytopenia * platelet disorder * hemorrhagic stroke * major surgical procedure * or severe physical trauma * aortic dissection * hypertension * acute pericarditis * cirrhosis or other clinically significant liver disease
15. Reference; ^ Hartzman, G.D.; Egbertson, M.S.; Halczenko, W.; Laswell, W.L.; Duggan, M.E.; Smith, R.L.; Naylor, A.M.; Manno, P.D.; Lynch, R.J.; Zhang, G.; Chang, C. T.-C.; Gould, R.J. (1992). "Non-Peptide Fibrinogen Receptor Antagonists. 1. Discovery and Design of Exosite Inhibitors". Journal of Medicinal Chemistry ( American Chemical Society ) 35 (24): 4640–4642. doi : 10.1021/jm00102a020 . PMID 1469694 . ^ Van Drie, John H. (2007). "Computer-aided drug design: the next 20 years" . J. Comput Aided Mol Des (Springer) 21 (10–11): 591–601. doi : 10.1007/s10822-007-9142-y . PMID 17989929 . http://www.springerlink.com/content/e2180556p4722000/ . Retrieved 2008-06-23. ^ "Saw-Scaled Vipers" . University of Edinburgh . http://www.portfolio.mvm.ed.ac.uk/studentwebs/session2/group13/vipers.html . Retrieved 2008-06-23.
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22. Eptifibatide(Integrilin) Eptifibatide is an antiplatelet drug of the gp IIb/IIIa inhibitor class. ** Eptifibatide is a cyclic heptapeptide derived from a protein found in the venom of the southeastern pygmy rattlesnake ( Sistrurus miliarius barbouri ).
23. Indications Cardiac ischemic events myocardial infarction unstable angina percutaneous coronary intervention (PCI). The drug is always applied together with aspirin or clopidogrel and (low molecular weight or unfractionated) heparin .
24. Contraindications and precautions Thrombocytopenia . * Renal insufficiency . * Current bleeding tendencies * Coagulation parameters such as ACT, aPTT, TT, and PT should be followed closely during therapy and afterwards. * Allergy * Severe, uncontrolled hypertension . * Pediatric patients : Eptifibatide is not indicated in patients below 18 years of age, because no experience exists.
25. Dosage regimen The recommended adult dosage is an i.v. - of 180 µg/kg over 1 to 2 minutes{ immediately after diagnosis }, - 2 µg/kg per minute until either hospital discharge or initiation of coronary artery bypass grafting, or for up to 72 hours. At least 4 hours before discharge all local or systemic bleedings should have been controlled and terminated.
26. REFERENCE; ^ Gordon W. Gribble (15 December 2010). Heterocyclic Scaffolds II: Indoles: Synthesis, Properties and Applications . Springer. pp. 11–. ISBN 9783642157325 . http://books.google.com/books?id=srxzzUskq4wC&pg=PA11 . Retrieved 12 November 2010. AHFS Database Online Arzneimittel Datenbank (in German) http://www.pharmazeutische-zeitung.de/index.php?id=352&type=0 (in German) http://www.chemsoc.org/chembytes/ezine/1999/berressem_apr99.htm (information on the biological origin of eptifibatide)
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