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Gp IIa IIIb inhibitor- kiran sotang
 

Gp IIa IIIb inhibitor- kiran sotang

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    Gp IIa IIIb inhibitor- kiran sotang Gp IIa IIIb inhibitor- kiran sotang Presentation Transcript

    • GP IIb/IIIa Inhibitors -Kiran sotang
      • GP IIb IIIa antagonist are a new class of potent platelet aggregation inhibitor which act by blocking key receptor involved in platelet aggregation .
      • The GP IIa IIIa inhibitor is an adhesive receptor for fibrinogen and vWF through which agonist like collagen , thrombus TXA2 , ADP , etc , induce platelet aggregation .
      • Thus GP IIb IIIa antagonist block aggregation induced by all platelet agonist.
      GP IIb/IIIa Inhibitors
    • 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)
      • Use
      • Glycoprotein IIb/IIIa inhibitors are frequently used during  percutaneous coronary intervention  ( angioplasty  with or without intracoronary stent placement).
      • They work by preventing  platelet  aggregation and  thrombus  formation. They do so by inhibition of the  GpIIb/IIIa  receptor on the surface of the platelets .
    • 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
    • Atherosclerosis
    • 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.
    • 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
    • ADMIRAL Abciximab before Direct angioplasty and stenting in Myocardial Infarction Regarding Acute and Long-term follow-up
      • Event *Abciximab Placebo (n=150) (n=150) P
      • Death, MI, urgent TVR at 30 d 10.7% 20.0% 0.03
      • TIMI-3 initial 21% 10% <0.01
      • 24 h 86% 78% <0.03
      • LVEF 24 h 55% 51%
      • 30 d 63% 55%
    • Tirofiban
      • Tirofiban ( INN , trade name Aggrastat ) is an antiplatelet drug .
      • It belongs to a class of antiplatelet named glycoprotein IIb/IIIa inhibitors .
      • Tirofiban is the first drug candidate whose origins can be traced to a pharmacophore -based virtual screening lead
    • 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
    • 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.
    • 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
    • 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
    • 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). &quot;Non-Peptide Fibrinogen Receptor Antagonists. 1. Discovery and Design of Exosite Inhibitors&quot;. Journal of Medicinal Chemistry ( American Chemical Society ) 35 (24): 4640–4642. doi : 10.1021/jm00102a020 . PMID   1469694 .  ^ Van Drie, John H. (2007). &quot;Computer-aided drug design: the next 20 years&quot; . 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.  ^ &quot;Saw-Scaled Vipers&quot; . University of Edinburgh . http://www.portfolio.mvm.ed.ac.uk/studentwebs/session2/group13/vipers.html . Retrieved 2008-06-23.
    • TIGER- PA
      • Tirofiban Given in the Emergency Room Before Primary Angioplasty
    • TIGER-PA Pilot
      • Goals
        • To test the safety and efficacy of tirofiban in the setting of an acute MI
        • To compare early adjunctive use of tirofiban before primary PCI with peri-PCI use
    • TIGER-PA Pilot
      • Dosing
        • Tirofiban: 10 µg/kg over 3 minutes, then 0.15 µg/kg/min x 24 hours
        • Heparin
          • Early: 70 U/kg IV bolus, then 7.5 U/kg/h
          • Delayed: 100 U/kg IV bolus, then 10 U/kg/h
        • All other medications including NTG,  -blockers at the investigator’s discretion
    • TIGER-PA Pilot
      • Complications
      • ER Cath Lab
      • Minor bleeding 4 2
      • Major bleeding 1 1
      • 30 d MACE 1 2
      30-day MACE include 1 patient in each group admitted for chest pain and 1 patient who had SAT and repeat PCI at 6 days in the cath lab group with no deaths. INTERIM
    • TIGER-PA
      • Summary
        • Pilot study to determine safety and efficacy of tirofiban given in the ER before primary PTCA
        • ** Tirofiban given early in the ER may lead to further improvement in TIMI flow and frame count compared with tirofiban given in the cath lab
    • Summary
      • GP IIb/IIIa receptor inhibitors may be beneficial as an adjunct in acute MI
      • Safe and well tolerated
      • Further large-scale trials are needed to better delineate a long-term benefit
    • 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 ).
    • 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 .
    • 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.
    • 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.
    • 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)
    • THANK YOU…!!!!