Pharm: Antiplatelet Drugs Flashcards
What is the general mechanism of anti-platelet drugs?
Inhibition of primary hemostatic plug formation, aggregation, activation and release mechanisms
Describe the contents of light and dark granules
Light: PF4, beta-thromboglobulin, PDGF
Dark: Ca2+, Serotonin, ATP/ADP
What are the products of platelet activation and endothelial interaction?
Prostaglandin derivatives
Endoperoxides
Thromboxanes
What site do anti-platelet have activity in that anticoagulants do not?
The arterial circulation
What are the main classes of antiplatelet agents?
1) Aspirin
2) COX inhibitors
3) NSAIDs
4) ADP receptor inhibitors
5) Dipyridamole
6) Cilostazol
7) GPIIb/IIIa inhibitors
8) Prostacyclin analogue
What are the most widely used ADP receptor inhibitors?
Clopidogrel and prasugrel
Which ADP receptor inhibitors are prodrugs that require liver transformation?
Ticlopidine, Clopidogrel and prasugrel
What is the effect of dipyridamole?
Coronary vasodilatation
What is the indication for Ciostazol?
Management of intermittent claudication
What are the drugs that inhibit GPIIb/IIIa receptors?
Tirofiban
Eptifibatide
Abciximab
What is the risk with aspirin resistance?
May cause recurrent ischemic vascular events in patients taking low dose aspirin
What is the mechanism of action of clopidogrel?
Selective inhibition of the ADP receptor, leading to inhibition of platelet aggregation
Describe the population variation of clopidogrel and prasugrel
Prasugrel has less population variation than clopidogrel. A significant portion of the population is non-respondant to clopidogrel due to a polymorphism.
Is antiplatelet monotherapy typically used?
No, dual antiplatelet therapy is often used because single target therapy is not sufficient.
What are the clinical applications of antiplatelet drugs?
Cerebrovascular disease (TIA, stroke)
Coronary artery disease (MI, unstable angina)
Saphenous vein coronary artery bypass grafts
Peripheral vascular disease
Small vessel disease
Prevention of thrombosis on artificial surfaces
What drugs interact with anti-platelet drugs?
Thrombolytic agents
Heparin/LMW heparin/Oral anticoagulants
Warfarin
Antithrombin agents
What are the two pathways of arachadonic acid metabolism?
Cyclooxygenase pathway to form PGs
Lipoxygenase pathway to form LTs
What are the main regulators of prostacyclin and thromboxane synthesis?
Endothelial lining
Lipoproteins and other blood components
Diet, drugs, hemodynamics
Describe the balance between PGI2 and TXA2 and how it is modulated
Healthy individuals should COX pathways that favor PGI2 over TXA2 in order to prevent clotting.
Aspirin blocks TXA2 formation in order to tip the balance in favor of PGI2
Describe the pharmacology of omega 3 fatty acid
Contains acids that compete with AA in the PG pathway in order to inhibit the effects of TXA2
Which antiplatelet drugs must be given via IV?
The GP IIb/IIIa inhibitors are the only antiplatelet drugs not given orally
What is the mechanism of action of dipyridamole and cilostazol?
Phosphodiesterase inhibitors
What are the eicosanoids?
Monteleukast
Zafirleukast
Zieuton
What is the mechanism of action of monteleukast and zafirleukast?
Leukotriene receptor inhibitors
