Antiplatelet drugs Flashcards
Aspirin - MOA of antiplatelet effect
In low doses aspirin selectively inhibits thromboxane A2 (TXA2) synthesis (promotes aggregation). Prostacyclin (platelet aggregation inhibiting) inhibition: higher doses.
Irreversible inhibition of COX.
Aspirin - indications
Ischemic heart disease & stroke: Secondary prevention.
Angina: prevent MI
Primary prevention: men>45, women>55 with risk factors for heart disease/stroke (diabetes).
Acute MI, TIA (prevent stroke), artificial heart valves, percutaneous coronary angioplasty.
Peripheral occlusive disease, chronic limb ischemia.
Aspirin - adverse effects
Bleeding (esp GI, inhibition of prostaglandins = inhibition of bicarbonate & mucus secretion).
High doses: hypoprothrombinemia
Antiplatelet drugs - 3 drugs, 2 groups
Aspirin Dipyridamole Cilostazol ADP inhibitors Glycoprotein IIb/IIIa antagonists
Dipyridamole - MOA
Coronary vasodilator and weak antiplatelet.
Inhibits platelet adhesion to the vessel wall, and platelet aggregation (latter by increasing cAMP and decreasing Ca in platelets)
Dipyridamole - indications
Vasodilation: myocardial perfusion imaging (thallium imaging).
Antiplatelet: with aspirin for prevention of ischemic (thrombotic) stroke in pts who had this or have TIA.
Cilostazol - MOA
Inhibits phosphodiesterase III and increase cAMP in platelets & blood vessels. This causes vasodilation and inhibition of platelet aggregation
Cilostazol - Indications
Intermittent claudication (limb weakness & pain)
Cilostazol - interactions
Metabolized by CYP3A4 (e.g. erythromycin may increase antiplatelet effect)
ADP inhibitors - 4 drugs
Clopidogrel
Prasugrel
Ticlopidine
Ticagrelor
ADP inhibitors - interactions
Ticlopidine, clopidogrel, prasugrel: metabolized into active metabolite by CYPs.
Clopidogrel: activation is potentially inhibited by PPI (but they can be given together).
Ticagrelor does not need activation.
Which ADP inhibitor has greater potency?
Prasugrel
ADP inhibitors - MOA
Clopidogrel requires in vivo biotransformation to an active thiol metabolite. The active metabolite irreversibly blocks the P2Y12 component of ADP receptors on the platelet surface, which prevents activation of the GPIIb/IIIa receptor complex, thereby reducing platelet aggregation. Platelets blocked by clopidogrel are affected for the remainder of their lifespan (~7 to 10 day)
Clopidogrel, ticlopidine, prasugrel: irreversible antagonists
Ticagrelor - reversible antagonists.
When is ticagrelor better to use than other ADP-inhibitors
E.g. surgery - when irreversible inhibition is not needed.
Clopidogrel & prasugrel - indications
Pts who cannot take aspirin: Prevent thrombotic stroke.
With aspirin: ACS.
Clopidogrel also in: Intermittent claudication of blood vessels, chronic arterial occlusion, atrioventricular shunts/fistulas, open heart surgery, sickle cell anemia.
