Antiplatelet Drugs

Question 1

How do platelets adhere to collagen?

Answer 1

GP1b receptors and vWF

Question 2

What do platelets release upon initial activation and what receptors do they bind to?

Answer 2

ADP - P2Y12 receptor

Thromboxane A2 - TP receptor

Question 3

Activation of what receptor on platelets results in platelet aggregation and thrombus formation?

Answer 3

GPIIb/IIIa

Question 4

What is the mechanism of action of aspirin?

Answer 4

Acetylates serine –> inactivates cyclooxygenase (COX)

–> decreased prostglandin synthesis –> decreased thromboxane A2 –> less platelet aggregation

Question 5

What are indications for aspirin?

Answer 5

Reduced mortality in acute MI and to prevent future MI
Reduced stroke risk
Maintain graft patency in CABG or stent placement

Question 6

What are limitations of aspirin therapy?

Answer 6

Allergy
GI intolerance
Aspirin resistance

Question 7

What are oral antiplatelet therapies?

Answer 7

Aspirin
Clopidogrel
Prasugrel
Ticagrelor
Cilostazol

Question 8

What drugs are in the category of thienopyridines?

Answer 8

Ticlopidine (no longer used)
Clopidogrel
Prasugrel
Ticagrelor

Question 9

What is the mechanism of action of dipyridamole?

Answer 9

Inhibits platelet cAMP phosphodiesterase –> increased cAMP –> inhibit platelet aggregation

Question 10

What is the mechanism of action of thienopyridines?

Answer 10

Inhibit ADP receptor P2Y12 –> inhibit activation of GPIIb/IIa –> inhibit fibrinogen binding

Question 11

Describe the metabolism of Clopidogrel and relative importance of CYP system in the metabolism

Answer 11

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

Question 12

Describe the metabolism of Prasugrel and relative importance of CYP system in the metabolism

Answer 12

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

Question 13

Describe the metabolism of Ticagrelor and relative importance of CYP system in the metabolism

Answer 13

Ticagrelor is not a prodrug
Acts directly on P2Y12 ADP receptor as soon as its ingested
CYP system plays no role for ticagrelor

Question 14

What are indications for clopidogrel?

Answer 14

Acute coronary syndrome (reduced MI, stroke death in patients with recent MI, stroke)
Reduced risk of in-stent thrombosis

Question 15

Do PPIs cause diminished antiplatelet activity of clopidogrel?

Answer 15

No

Just increased risk of GI bleeds if on PPIs and not put on PPIs

Question 16

How does Prasugrel compare to Clopidogrel?

Answer 16

Better anti-platelet effect with Prasugrel, decreased CV death/MI events
However, also have slight increase in major bleeding events

Question 17

Which groups of patients should not use Prasugrel?

Answer 17

Prior stroke
Age >75
Low body weight

Question 18

What are the GPIIb/IIIa receptor antagonists?

Answer 18

Abciximab, eptifibatide, tirofiban

Question 19

What is the mechanism of action of GPIIb/IIIa receptor antagonists?

Answer 19

Inhibit GPIIb/IIIa receptors –> prevent platelet aggregation

Question 20

Why are GPIIb/IIIa receptor antagonists not used often?

Answer 20

Must be given IV

Hence only really used in cath lab now, despite being most potent platelet inhibitors

Question 21

When is abciximab used?

Answer 21

Primary angioplasty in patients with STEMI

Question 22

When is eptifibatide used?

Answer 22

Used in unstable angina/NSTEMI

Question 23

When are GPIIb/IIIa receptor antagonists being used now?

Answer 23

Patients with unstable angina/NSTEMI undergoing PCI and already receiving antiplatelet, anticoagulant , antiischemic agents