Antiplatelet Drugs Flashcards
How do platelets adhere to collagen?
GP1b receptors and vWF
What do platelets release upon initial activation and what receptors do they bind to?
ADP - P2Y12 receptor
Thromboxane A2 - TP receptor
Activation of what receptor on platelets results in platelet aggregation and thrombus formation?
GPIIb/IIIa
What is the mechanism of action of aspirin?
Acetylates serine –> inactivates cyclooxygenase (COX)
–> decreased prostglandin synthesis –> decreased thromboxane A2 –> less platelet aggregation
What are indications for aspirin?
Reduced mortality in acute MI and to prevent future MI
Reduced stroke risk
Maintain graft patency in CABG or stent placement
What are limitations of aspirin therapy?
Allergy
GI intolerance
Aspirin resistance
What are oral antiplatelet therapies?
Aspirin Clopidogrel Prasugrel Ticagrelor Cilostazol
What drugs are in the category of thienopyridines?
Ticlopidine (no longer used)
Clopidogrel
Prasugrel
Ticagrelor
What is the mechanism of action of dipyridamole?
Inhibits platelet cAMP phosphodiesterase –> increased cAMP –> inhibit platelet aggregation
What is the mechanism of action of thienopyridines?
Inhibit ADP receptor P2Y12 –> inhibit activation of GPIIb/IIa –> inhibit fibrinogen binding
Describe the metabolism of Clopidogrel and relative importance of CYP system in the metabolism
Clopidogrel is a prodrug
Undergoes CYP-dependent oxidation twice to be fulling activated (CYP2C19 and CYP3A4)
Any polymorphism is CYP enzymes can have significant effects active metabolism of drug –> excess clopidogrel
Describe the metabolism of Prasugrel and relative importance of CYP system in the metabolism
Prasugrel is a prodrug
Only undergoes CYP-dependent oxidation once
CYP2C19 plays a smaller role in the oxidation
CYP system not as important as in clopidogrel
Describe the metabolism of Ticagrelor and relative importance of CYP system in the metabolism
Ticagrelor is not a prodrug
Acts directly on P2Y12 ADP receptor as soon as its ingested
CYP system plays no role for ticagrelor
What are indications for clopidogrel?
Acute coronary syndrome (reduced MI, stroke death in patients with recent MI, stroke)
Reduced risk of in-stent thrombosis
Do PPIs cause diminished antiplatelet activity of clopidogrel?
No
Just increased risk of GI bleeds if on PPIs and not put on PPIs