Essay: Outline Current, Novel Anti-platelet Therapy

Question 1

Current AP drugs

Answer 1

• COX-1 inhibitor: Aspirin
• ADP-R inhibitor (Including thienopyridines): Clopidogrel, Elinogrel, Parsugrel, Cangrelor
• TXA2-R antagonist: Terutroban, Picotamide

Question 2

COX-1 Inhibitor

Answer 2

• COX-1 produces prostaglandin H2
• Converted to TXA2 by thromboxane-A-synthase
• Aspirin irreversibly binds COX-1 and inhibits it
• No prostaglandin H2, no TXA2

Question 3

ADP-R Inhibitor

Answer 3

• Antagonises P2Y12 receptor to prevent ADP binding

- Thienopyridine drugs are selective irreversible P2Y12 antagonists

Question 4

P2Y12 Receptor

Answer 4

• GPCR
• Inhibits AC/GC
• Lowers cAMP/cGMP
• Lower Pi of vasodilator-stimulated phosphoprotein
• Activation of GPIIIa and GPIIb

Question 5

TXA2

Answer 5

• Binds TP (TXA2-R)
• Activates neighbouring platelets
• Encourages platelet aggregation
• Vasoconstriction

Question 6

TP Antagonists (and other function)

Answer 6

• Terutroban, Picotamide

- Terutroban also a TXA2-synthase inhibitor

Question 7

Best way to prevent thromboembolic event

Answer 7

• Dual anti-platelet therapy

Question 8

Cangrelor (CHAMPION)

Answer 8

• P2Y12 inhibitor that binds reversibly
• Faster onset and offset
• May have advantage in patients undergoing CABG or with unknown angiographic anatomy
• Only used under expert supervision