Chapter 167 - antiplatelet drugs

Question 1

Drug class of clopidogrel? (Plavix) and other drugs in this class?
How does it work?

Answer 1

thienopyridine, (ticlopidine, prasugrel) 
irreversible ADP (P2Y12) receptor antagonist

Clopidogrel binds to the platelet P2Y12 receptor and prevents ADP-induced platelet aggregation.

Question 2

MOA of adenosine diphosphate receptor antagonists

Answer 2

prodrug requiring hepatic biotransformation via P-450 enzymes, active drug irreversibly blocks the P2Y12 ADP receptor, preventing integrin activation, platelet granola secretion and ADP induced thromboxane A2 production, all of which reduce activation of GPIIb/IIIa fibrinogen receptors

Question 3

Platelets are thought to play a major role in arterial thromboembolic disease. Explain this with the platelet physiology.

Answer 3

The shear stress from the fast-flowing arterial blood exposes platelet binding sites on vWF that increase the affinity for the platelet glycoprotein Ib receptor. This is a reason that platelets are associated more with arterial thrombosis.

Question 4

MOA of COX inhibitors as an antiplatelet agent?

Answer 4

Thromboxane A2 (TXA2) plays an important role in the recruitment and activation of platelets to the site of vascular injury. TXA2 is produced by activated platelets via a COX (cyclooxygenase) enzyme in the platelet cytosol.

Acetylsalicylic acid (ASA, aspirin) blocks COX-1, resulting in long-lasting platelet inhibition. It is thought that platelets cannot manufacture additional copies of COX, and so blockade by ASA is permanent for the life of the platelet.