Antiplatelets Flashcards
What is the role that platelets play in hemostasis?
- Adhere to regions of injured blood vessel and are activated (shape change)
- recruit to injured site
- form a hemostatic plug
What are the three phases of platelet activation?
- adhesion
- secretion
- aggregation
What is the role of GPIa/GPIb receptors in platelet activation?
GP1a –> binds to collagen
GP1b –> binds to von willebrand factor bridged to collagen
What three molecules are secreted by platelets?
ADP
5-HT
TXA2
what are the molecules secreted by platelets role in hemostasis?
ADP, 5HT, TXA2 –> activate and recruit other platelets
TXA2 & 5HT –> potent vasoconstrictors
Explain the role of fibrinogen and GP IIb/IIIa receptors in platelet function?
- Factors activation induces conformation of G2b/3a receptors to bind fibrinogen
Explain the role of aspirin as an antiplatelet drug and why it has a preferential effect on platelets over the endothelium.
- inhibition of TXA2 synthesis in platelets due to cox-1 inhibition
- irreversible
- PGI2 production inhibited by higher doses
What are the indications for aspirin and its SEs?
- prophylaxis and tx of arterial thromboembolic disorders
upper GI bleeding due to inhibition of COX-1
what is the mechanism of clopidogrel and its clinical properties?
P2Y12 ADP receptor on platelet surface
– thienopyridine class of ADP receptor inhibitors (pro-drug)
– irreversibly block ADP on platelet and subsequent activation of Gp2b/3A complex
what is the mechanism of prasugrel and its clinical properties?
P2Y12 ADP receptor on platelet surface
- prodrug that requires esterases + CYP 3A4/2B6
- high risk of bleeding, not recommended in elderly or before CABG
what is the mechanism of ticagrelor and its clinical properties?
P2Y12 ADP receptor on platelet surface
1. doesn’t require bioactivation by metabolic enzymes (CYP3A4 substrate)
what is the half-life for cangrelor
3-5 min
what structure is this?
Aspirin
What structure is this?
clopidogrel
What structure is this?
prasugrel
What structure is this?
ticagrelor
what is the mechanism for abiciximab and its role in therapy?
- it is a MAB
- Long duration of action- increased risk of bleeding
what is the mechanism of action for eptifibitide and its role in therapy?
- synthetic peptide
- inhibits fibrinogen binding to dec. platelet aggregation
- cyclic heptapeptide derived from rattlesnake venon
what is this structure?
eptifibitide
Explain the mechanism of action of dipyridamole and differentiate them based on their structures and clinical properties.
- Opposing P2Y12 action (cAMP PDE inhibition and inhibition of adenosine uptake)
- with warfarin –> prosthetic heart valves
- with ASA –> ischemia
Explain the mechanism of action of cilostazol and differentiate them based on their structures and clinical properties.
- Opposing P2Y12 action (cAMP PDE inhibition and inhibition of adenosine uptake)
- intermittent claudication
what is this structure?
dipyridamole
what is this structure?
cilostazol
Explain the mechanism of action of vorapaxar
reversible PAR-1 receptor antagonist
1. used with aspirin and plavix
2. HL 3-4days ; anti-platelet effect persists for days after d/c
what is this structure?
varapaxar
T/F platelets have a nucleus?
false
what are the two ADP receptor inhibitors? What is their pathway?
- P2Y1
–> couple to Gq-PLC-IP3-Ca2+ - P2Y12
–> couple to Gi and ACP
T/F Activation of both ADP receptors is required for platelet activation?
true
what is TTP (thrombotic thrombocytopenic purpura)?
- spurious and excessive platelet aggregation
- can be fatal
what two P2Y12 antagonists have no metabolism necesary?
- ticagrelor
- cangrelor
what is tirofiban used for?
combined with heparin to treat acute coronary syndrome
what are PAR Inhibitors & what is their mechanism?
Mechanism: proteolytic cleavage of PAR-1 on platelet surface
1. they are GPCRs to release CA2+
2. thrombin activates platelets at nanomolar conc.
what are the uses of clopidogrel?
- recent MI
- stroke
- established peripheral vascular disease and coronary stent procedures
what structure is this?
Cangrelor
