Antiplatelet

Question 1

explain the role that platelets play in hemostasis

Answer 1

Platelets form a “plug” to close the injury to blood vessel

Question 2

explain the 3 phases of platelet activation

Answer 2

1. platelet adhesion (GP Ia & GP Ib bind to separate things which causes a shape change, endothelial cells secrete prostacyclin [PGI2] to inhibit thrombogenesis)
2. platelet secretion (ADP, TXA2, and 5-HT secreted)
3. platelet aggregation (release of the 3 molecules induces conformation of GPIIb/IIIa receptors to bind to fibrinogen, platelets cross-linked by fibrinogen, surface is formed for clot formation)

Question 3

explain the role of GP Ia and GP Ib receptors in platelet activation

Answer 3

GP Ia binds to collagen and GP Ib binds to von Willebrand Factor bridged to collagen; shape change facilitates receptor binding

Question 4

list 3 molecules that are secreted by platelets and give their role in hemostasis

Answer 4

1. ADP
2. Thromboxane A2 (TXA2)
3. Serotonin (5-HT)
   * all 3 activate and recruit other platelets
   * TXA2 & 5-HT are potent vasoconstrictors

Question 5

explain the role of fibrinogen and GP IIb/IIIa receptors in platelet function (WATCH VIDEO)

Answer 5

• GP IIb/IIIa receptors: conformation from the 3 molecules to bind fibrinogen
• Fibrinogen: cross-link platelets

Question 6

explain the role of aspirin as an antiplatelet drug and why it has a preferential effect on platelets over the endothelium

Answer 6

• COX-1 inhibitor
• irreversibly inhibits COX-1 by acetylation
• loss of COX-1 activity –> decr in TXA2 synthesis (a promoter of aggregation), PGI2 production inhibited by higher doses

Question 7

explain the mechanism of action of clopidogrel, prasugrel, and ticagrelor and differentiate between them based on their clinical properties

Answer 7

• ADP receptor inhibitors
• ADP receptors P2Y12 and P2Y1: both need activated by ADP for platelet activation
• MOA: blocks P2Y12 component of ADP receptors on platelet surface –> prevents activation of GPIIb/IIIa receptor complex –> reduces platelet aggregation
• Clopidogrel: irreversible
• Prasugrel: irreversible, high risk of bleeding, req bioactivation
• Ticagrelor: reversible, risk of bleeding don’t use immediately before CABG

Question 8

explain the mechanism of action of abciximab and eptifibitide, their role in therapy, and differences in their structure

Answer 8

• GP IIb/IIIa receptor inhibitors
• MOA: binds to the GP IIb/IIIa receptors reversibly blocks platelet aggregation and prevents thrombosis (blood clot)
• Abciximab: Fab fragment of chimeric human-murine monoclonal antibody (large)
• Eptifibitide: cyclic heptapeptide derived from rattlesnake venom; synthetic peptide

Question 9

explain the mechanism of action of dipyridamole and cilostazol and differentiate them based on their structure and clinical properties

Answer 9

• Phosphodiesterase-3 Inhibitors (PDE-III)
• MOA: inhibit phosphodiesterase which causes an accumulation of cyclic AMP, which inhibits platelet aggregation and causes vasodilation; inhibits adenosine uptake
• Dipyridamole: prevent embolization from prosthetic heart valves (combo w/ warfarin), prevent cerebrovascular ischemia (combo w/ ASA)
• Cilostazol: intermittent claudication