CHEST-2012 Antiplatelet Drugs

Question 1

Aspirin MOA

Answer 1

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

Question 2

How long does platelet-inhibitory effect of ASA last?

Answer 2

Lasts the lifespan of the platelet (about 10 days)

Question 3

Dipyridamole MOA

Answer 3

Inhibits uptake of adenosine into platelets and increases cAMP levels –> indirectly reduces platelet aggregation

Question 4

Cilostazol MOA

Answer 4

Vasodilatory and antiplatelet properties

Question 5

Common side effects of cilostazol after starting therapy

Answer 5

GI side effects, headache within 2 weeks of starting therapy

Other effects are palpitation, tachycardia

Question 6

Cilostazol contraindicated in which patients?

Answer 6

Heart failure

Due to cilostazol’s risk of triggering ventricular tachycardia from its ability to increase in cAMP

Question 7

P2Y12 inhibitors

Answer 7

Thienopyridines: Ticlopidine (1st gen), clopidogrel (2nd gen), prasugrel (Effient, 3rd gen)

Ticagrelor (Brilinta)

Question 8

MOA of thienopyridine antiplatelet drugs

Answer 8

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

Question 9

Why ticlopidine is generally not used

Answer 9

Bone marrow toxicity

Question 10

Half-life of ticlopidine

Answer 10

24-36hr after single dose

96hr-14 days after repeated dosing

Question 11

Enzyme that affects clopidogrel’s effectiveness

Answer 11

CYP2C19 activates clopidogrel

Poor metabolizers will reduce clop’s efficacy; also avoid drugs that inhibit 2C19 (omeprazole, esomeprazole)

Question 12

Prasugrel time to peak level after dose

Answer 12

within 30 minutes

Question 13

Half-life of prasugrel’s active metabolite

Answer 13

4 hours

Question 14

Is prasugrel absorption affected by food or CYP2C19 polymorphisms?

Answer 14

NO

No affect by CYP2C19, so ok to take PPIs

Question 15

Route of elimination of prasugrel

Answer 15

Renally eliminated

Question 16

Why does prasugrel have a shorter onset of action?

Answer 16

Hepatic conversion requires only 1 step to activate it, clopidogrel requires 2-step activation

Question 17

Glycoprotein IIb/IIIa inhibitor drugs

Answer 17

Abciximab (Reopro)
Tirofiban (Aggrastat)
Eptifibatide (Integrilin)

Question 18

Abciximab MOA

Answer 18

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

Question 19

Half-life of abciximab

Answer 19

30 minutes, indicating that it binds to receptors quickly

Question 20

Risk of abciximab

Answer 20

Thrombocytopenia that can occur 2-24hr after treatment that will resolve after the drug is discontinued

Platelet transfusions can be given if needed

Question 21

Tirofiban half-life

Answer 21

1.5-2 hours

Question 22

Elimination of tirofiban

Answer 22

Renal and biliary, but dose reduction only needed for renal impairment

Question 23

Can tirofiban cause thrombocytopenia?

Answer 23

Yes, antibodies can generate against the conformational change in the GpIIb/IIIa receptor after drug binding

Question 24

GPIIb/IIIa inhibitor modeled after a compound found in snake venom

Answer 24

Eptifibatide

Question 25

How is Ticagrelor different from the other P2Y12 inhibitors?

Answer 25

Active drug, binds reversibly to receptor

Question 26

Aspirin dose if taking Ticagrelor

Answer 26

Keep dose below 100mg/day