CHEST-2012 Antiplatelet Drugs Flashcards
Aspirin MOA
Permanently inhibits COX1 and COX2 activity, which decreases production of thromboxane A2 (TXA2 is a vasoconstrictor and facilitates platelet aggregation)
COX1 activity inhibited by low doses (75-150mg)
COX2 activity inhibited by high doses
How long does platelet-inhibitory effect of ASA last?
Lasts the lifespan of the platelet (about 10 days)
Dipyridamole MOA
Inhibits uptake of adenosine into platelets and increases cAMP levels –> indirectly reduces platelet aggregation
Cilostazol MOA
Vasodilatory and antiplatelet properties
Common side effects of cilostazol after starting therapy
GI side effects, headache within 2 weeks of starting therapy
Other effects are palpitation, tachycardia
Cilostazol contraindicated in which patients?
Heart failure
Due to cilostazol’s risk of triggering ventricular tachycardia from its ability to increase in cAMP
P2Y12 inhibitors
Thienopyridines: Ticlopidine (1st gen), clopidogrel (2nd gen), prasugrel (Effient, 3rd gen)
Ticagrelor (Brilinta)
MOA of thienopyridine antiplatelet drugs
Inhibit ADP-induced platelet aggregation by permanently inhibiting the platelet’s P2Y12 receptor
All are prodrugs activated by hepatic CYP450 enzymes and bind to platelets when they pass through the liver
Why ticlopidine is generally not used
Bone marrow toxicity
Half-life of ticlopidine
24-36hr after single dose
96hr-14 days after repeated dosing
Enzyme that affects clopidogrel’s effectiveness
CYP2C19 activates clopidogrel
Poor metabolizers will reduce clop’s efficacy; also avoid drugs that inhibit 2C19 (omeprazole, esomeprazole)
Prasugrel time to peak level after dose
within 30 minutes
Half-life of prasugrel’s active metabolite
4 hours
Is prasugrel absorption affected by food or CYP2C19 polymorphisms?
NO
No affect by CYP2C19, so ok to take PPIs
Route of elimination of prasugrel
Renally eliminated
Why does prasugrel have a shorter onset of action?
Hepatic conversion requires only 1 step to activate it, clopidogrel requires 2-step activation
Glycoprotein IIb/IIIa inhibitor drugs
Abciximab (Reopro)
Tirofiban (Aggrastat)
Eptifibatide (Integrilin)
Abciximab MOA
Humanized antibody that binds to GpIIb/IIIa receptor and makes it unavailable for platelet aggregation
80% receptor blockade abolishes platelet aggregation but only mildly increases bleeding time
90% receptor blockade markedly increases bleeding time
Half-life of abciximab
30 minutes, indicating that it binds to receptors quickly
Risk of abciximab
Thrombocytopenia that can occur 2-24hr after treatment that will resolve after the drug is discontinued
Platelet transfusions can be given if needed
Tirofiban half-life
1.5-2 hours
Elimination of tirofiban
Renal and biliary, but dose reduction only needed for renal impairment
Can tirofiban cause thrombocytopenia?
Yes, antibodies can generate against the conformational change in the GpIIb/IIIa receptor after drug binding
GPIIb/IIIa inhibitor modeled after a compound found in snake venom
Eptifibatide
How is Ticagrelor different from the other P2Y12 inhibitors?
Active drug, binds reversibly to receptor
Aspirin dose if taking Ticagrelor
Keep dose below 100mg/day
