Antiplatelets

Question 1

What is the role that platelets play in hemostasis?

Answer 1

1. Adhere to regions of injured blood vessel and are activated (shape change)
2. recruit to injured site
3. form a hemostatic plug

Question 2

What are the three phases of platelet activation?

Answer 2

1. adhesion
2. secretion
3. aggregation

Question 3

What is the role of GPIa/GPIb receptors in platelet activation?

Answer 3

GP1a –> binds to collagen
GP1b –> binds to von willebrand factor bridged to collagen

Question 4

What three molecules are secreted by platelets?

Answer 4

ADP
5-HT
TXA2

Question 5

what are the molecules secreted by platelets role in hemostasis?

Answer 5

ADP, 5HT, TXA2 –> activate and recruit other platelets
TXA2 & 5HT –> potent vasoconstrictors

Question 6

Explain the role of fibrinogen and GP IIb/IIIa receptors in platelet function?

Answer 6

• Factors activation induces conformation of G2b/3a receptors to bind fibrinogen

Question 7

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

Answer 7

1. inhibition of TXA2 synthesis in platelets due to cox-1 inhibition
2. irreversible
3. PGI2 production inhibited by higher doses

Question 8

What are the indications for aspirin and its SEs?

Answer 8

1. prophylaxis and tx of arterial thromboembolic disorders
   upper GI bleeding due to inhibition of COX-1

Question 9

what is the mechanism of clopidogrel and its clinical properties?

Answer 9

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

Question 10

what is the mechanism of prasugrel and its clinical properties?

Answer 10

P2Y12 ADP receptor on platelet surface
- prodrug that requires esterases + CYP 3A4/2B6
- high risk of bleeding, not recommended in elderly or before CABG

Question 11

what is the mechanism of ticagrelor and its clinical properties?

Answer 11

P2Y12 ADP receptor on platelet surface
1. doesn’t require bioactivation by metabolic enzymes (CYP3A4 substrate)

Question 12

what is the half-life for cangrelor

Answer 12

3-5 min

Question 13

what structure is this?

Answer 13

Aspirin

Question 14

What structure is this?

Answer 14

clopidogrel

Question 15

What structure is this?

Answer 15

prasugrel

Question 16

What structure is this?

Answer 16

ticagrelor

Question 17

what is the mechanism for abiciximab and its role in therapy?

Answer 17

1. it is a MAB
2. Long duration of action- increased risk of bleeding

Question 18

what is the mechanism of action for eptifibitide and its role in therapy?

Answer 18

1. synthetic peptide
2. inhibits fibrinogen binding to dec. platelet aggregation
3. cyclic heptapeptide derived from rattlesnake venon

Question 19

what is this structure?

Answer 19

eptifibitide

Question 20

Explain the mechanism of action of dipyridamole and differentiate them based on their structures and clinical properties.

Answer 20

1. Opposing P2Y12 action (cAMP PDE inhibition and inhibition of adenosine uptake)
2. with warfarin –> prosthetic heart valves
3. with ASA –> ischemia

Question 21

Explain the mechanism of action of cilostazol and differentiate them based on their structures and clinical properties.

Answer 21

1. Opposing P2Y12 action (cAMP PDE inhibition and inhibition of adenosine uptake)
2. intermittent claudication

Question 22

what is this structure?

Answer 22

dipyridamole

Question 23

what is this structure?

Answer 23

cilostazol

Question 24

Explain the mechanism of action of vorapaxar

Answer 24

reversible PAR-1 receptor antagonist
1. used with aspirin and plavix
2. HL 3-4days ; anti-platelet effect persists for days after d/c

Question 25

what is this structure?

Answer 25

varapaxar

Question 26

T/F platelets have a nucleus?

Answer 26

false

Question 27

what are the two ADP receptor inhibitors? What is their pathway?

Answer 27

1. P2Y1 --> couple to Gq-PLC-IP3-Ca2+ 2. P2Y12 --> couple to Gi and ACP

Question 28

T/F Activation of both ADP receptors is required for platelet activation?

Answer 28

true

Question 29

what is TTP (thrombotic thrombocytopenic purpura)?

Answer 29

1. spurious and excessive platelet aggregation 2. can be fatal

Question 30

what two P2Y12 antagonists have no metabolism necesary?

Answer 30

1. ticagrelor 2. cangrelor

Question 31

what is tirofiban used for?

Answer 31

combined with heparin to treat acute coronary syndrome

Question 32

what are PAR Inhibitors & what is their mechanism?

Answer 32

Mechanism: proteolytic cleavage of PAR-1 on platelet surface 1. they are GPCRs to release CA2+ 2. thrombin activates platelets at nanomolar conc.

Question 33

what are the uses of clopidogrel?

Answer 33

1. recent MI 2. stroke 3. established peripheral vascular disease and coronary stent procedures

Question 34

what structure is this?

Answer 34

Cangrelor