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
Block ADP P2Y12 receptors and inhibits expression of GP IIb/IIIa receptors. This prevents ADP-induced platelet aggregation.
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.
Ticagrelor - indications
Prevention of thrombotic events in MI or STEMI (with aspirin unless contraindicated).
Ticagrelor - adverse effects
Dyspnea
Ticlopidine - adverse effects
Severe neutropenia (complete blood count evr 2 weeks).
Glycoprotein IIb/IIIa antagonists - 3 drugs
Abciximab
Tirofiban
Eptifibatide
GP IIb/IIIa antagonists - MOA
Binds to platelet GP IIb/IIIa reveptors and prevents fibrinogen to bind and crosslinking of platelets.
Tirofiban and eptifibatide: competitive, reversible inhibitors.
Abciximab - indications
Combo with aspirin and heparin/LMWHs: Percutaneous coronary interventions (coronary angioplasty, stent placement).
Adjunct to thrombolysis
Abciximab - adverse effects
Bleeding, thrombocytopenia, hypotension, bradycardia.
Tirofiban and eptifibatide - indications
Unstable angina and MI (often combo with LMWHs).
Eptifibatide - STEMI, coronary angioplasty/stent placement
Aspirin - interactions
Sulfonylureas: increased hypoglycemic effect.
Methotrexate, valproate: increased GI bleeding+ ulceration.
Probenecid: inhibits uricosuric effect.
