Pharmacology - Antiplatelets

Question 1

Describe the stages of platelets activation and thrombus formation

Answer 1

Vascular endothelium is damaged, exposing collagen, and stimulating the release of Von Willebrand Factor (VWF)

Platelets adhese via VWF bridging between subendothelial macromolecules and GPIb receptors

Platelet shape changes from disks to spheres –> driven by ADP binding to P2Y receptors

Secretion of granule contents (2 types)

Synthesis of release of Platelet-Activating Factor (PAF) and Thromboxane A2 (TXA2)

Aggregation –> caused by expression of GPIIb/IIIa receptors that bind fibrinogen….which links adjacent platelets

Exposure of acidic phospholipids on the platelet surface, promoting thrombin activation via thrombin receptors and fibrin formation

Question 2

How does Clopidogrel work?

Answer 2

Inhibits the P2Y12 (Gi) receptors on platelets, causing a decreasing in Adenylyl Cyclase (AC) –> cAMP –> platelet aggregation

Does this by havings its thiol group forming a disulphide bond with the cysteine on the receptor (irreversible)

Question 3

Why is Prasugrel better than Clopidogrel?

Answer 3

Less dependence on CYP metabolism to become activated

Quicker onset of action

Question 4

What is Cangreolr?

Answer 4

An ATP analogue

Rapid on-set and off-set

Direct acting and and reversible inhibitor of P2Y12 (Gi) receptors

Question 5

How do Glycoprotein IIb/IIIa receptor inhibitors work?

Answer 5

Bind to the receptors on the activated platelet, preventing fibrinogen from binding instead

Prevents the aggregation of activated platelets

Question 6

What are the 3 Glycoprotein IIb/IIIa inhibitors?

Answer 6

Abciximab –> Chimeric monoclonal antibody that is long acting

Eptifibatide –> Synthetic cyclic heptapeptide that is reversible

Tirofiban –> Synthetic non-peptide agent that is a competitive reversible inhibitor

Question 7

How do Phosphodiesterase inhibitors work? (eg, Dipyridamole)

Answer 7

Increase cAMP and cGMP levels by blocking PDEs

This inhibits platelet aggregation and causes vasodilation

Also blocks adenosine uptake by platelets/endothelial cells/blood cells

Question 8

What is a common risk of all antiplatelets?

Answer 8

Haemorrhages

But not for Dipyridamole (slow release)!!!!