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Newer Antiplatelet Agents Epifibatide Tirofiban Etc. Benedict R. Lucchesi, M.D., Ph.D. Department of Pharmacology University of Michigan Medical School Epifibatide (Integrelin™) • Integrelin - a cyclic peptide antagonist, has been administered to humans with positive results. • Must be administered by continuous infusion 1.0 to 1.5 mg/kg/min. • Short duration of action - recovery of platelet function within 2-4 hours after termination of the infusion. Tirofiban (Aggrastat™) • Development based on anti-clotting • • • • components in the venom of an African snake, the saw-scaled viper. Antiplatelet function in humans Indicated for use in patients with unstable angina and non-Q-wave myocardial infarction. Used with heparin and aspirin for treatment of acute coronary syndrome. Must be administered by continuous infusion. DMP728 - a Low Molecular Weight Platelet GPIIb/IIIa Fibrinogen Receptor Antagonist Incorporating the RGD Sequence Arginine DMP728 Structure Glycine NH O O H2N N H N H O N OH HN Aspartate 2-Aminobutyrate NH O HN O O •CH3SO3 3-Amino methyl benzoic acid Essential Thrombocythemia Anagrelide (Argylin™) • • • • • A life-threatening condition characterized by elevated blood platelet counts. This condition results in an abnormally high incidence of adverse events associated with thrombosis (blood clotting), including heart attack and stroke - incidence in U.S. is 7 / 100,000 individuals. ANAGRELEIDE is indicated for the treatment of essential thrombocythemia to reduce elevated platelet counts and the risk of thrombosis. Therapeutic doses do not produce significant changes in white or red cell counts and has not been shown to be leukemogenic. The drug's labeling provides guidelines for treatment of asymptomatic young adults with essential thrombocythemia. The most frequently reported adverse reactions were mild and selflimiting and included headache, palpitations, diarrhea, and abdominal pain.