Anti-Platelet Drugs Dr. A. Shyam Sundar. M.Pharm., Ph.D, Associate Professor in Pharmacology And Toxicology University Of Nizwa Sultanate of Oman

Unit- 11 Unit Instructional Outcomes: At the end of the lecture, the students will be able to; Classify anti-platelet drugs List uses of anti-platelet drugs Describe the mechanism of actions of anti-platelet drugs State vital information about anti-platelet drugs Apply pharmacological knowledge learned in this unit in a clinical scenario.

Anti-Platelet drugs- Overview Platelets are the main constituents in arterial thrombi. Platelets first adhere to damaged blood vessel wall and aggregation occurs which leads to the release of ADP, TXA2, serotonin and other substances that promote further aggregation by activating Gp IIb/IIIa.

Anti-Platelet drugs- Uses Prophylaxis of MI Prophylaxis of Cerebrovascular disease. Prophylaxis in patients with artificial heart valves.

Classification of Anti-Platelet Drugs CoX inhibitors- Aspirin PDE Inhibitor- Dipyridamole ADP Antagonists: Reversible: Cangrelor, Ticagrelor Irreversible: Ticlopidine, Clopidogrel, Prasugrel GP IIb/IIIa Antagonists: Abciximab, Tirofiban, Eptifibatide

CoX Inhibitors Aspirin inhibits CoX enzyme irreversibly and decreases synthesis of TXA2 and PGI2. Inhibition of TXA2 synthesis leads to anti-aggregatory effects. For anti-platelet action, low doses of aspirin is required.

PDE Inhibitor Dipyridamole acts by inhibiting phosphodiesterase enzyme, that causes increase in the level of cAMP. cAMP potentiates prostacyclines and thus anti- aggregation.

ADP Antagonists Ticlopidine, Clopidogrel and Prasugrel act as irreversible antagonists of P2Y12 receptors of ADP. These drugs interfere with the activation of platelets by ADP and fibrinogen. Ticlopidine, Clopidogrel are prodrugs and are converted to active metabolites in the liver. PPIs interact with these drugs and decrease the anti-platelet effects. Ticlopidine causes severe Neutropenia Clopidogrel causes GI disturbances

ADP Antagonists Prasugrel is more potent than Ticlopidine, Clopidogrel. It is faster acting. Possess higher risk of fatal bleeding and should be avoided in elderly patients (above 75 years) with history of stroke.

GP IIb/IIIa Antagonists Abciximab, Tirofiban, Eptifibatide are the strongest anti-platelet drugs. They block all agonists that causes aggregation. Bleeding and Thrombocytopenia are the most serious complications of these agents.

Newer Anti-Platelet Drugs Ticagrelor & Cangrelor are reversible P2Y12 receptor antagonists. Ticagrelor is orally effective. Safer and more predictable AP actions than clopidogrel. Vorapaxer: Inhibitor of PAR-1 (Protease Activated Receptor-1). Recently approved by FDA for patients with history of MI/ Peripheral artery diseases.