Coagulation - Antiplatelets

Question 1

Platelets have ___ but not _____

Answer 1

organelles and secretory granules

but no nucleus

Question 2

First step of platelet activation

Answer 2

Adhesion and shape change

• GP1a -> Collagen
• GP1b –> vWF

Shape change facilitates receptor binding

Question 3

____ secretes prostacyclin to inhibit thrombogenesis

Answer 3

IN-TACT endothelial cells

Question 4

Second step of platelet activation

Answer 4

Secretion, Degranulation

• ADP
• TXA2
• 5HT

These activate other platelets (all) and are vasoonstrictors (TXA and 5HT only)

Question 5

Third step of platelet activation

Answer 5

Aggregation

ADP/5HT/TXA2 induces GP2b3a receptors to bind fibrinogen.

*Temporary hemostatic plug is formed.

Question 6

Aspirin MOA

Answer 6

irrev. acetylation of platelet’s COX-1

• Inhibits TXA2 formation (also PG synthesis if high dose)
• Interferes with bleeding time, NOT PT

Question 7

Inhibition of COX by aspirin is ____ and is maximally effective at a dose of _____

Answer 7

permanent (no nucleus to regenerate)

50-320mg

Question 8

Indication for ASA

Answer 8

Prophylaxis and treatment of arterial thromboembolic disorders

Question 9

P2Y1 receptor pathway

Answer 9

Gq coupled receptor

–>PLC, IP3, Ca++ pathway

Question 10

P2Y12 pathway

Answer 10

Coupled to Gi and inhibition of adenylyl cyclase

Question 11

Activation of _____ is required for platelet activation by ADP

Answer 11

Both P2Y1 and P2Y12

Question 12

P2Y12 inhibitors

Answer 12

Ticlopidine - no longer used d/t TTP

Clopidogrel - Lower tox profile

Effects for days (irrev. inhibition)

Uses: ACS, post-AMI, PVDz, PCI prodecure

Question 13

Ticlopidine, Clopidogrel, and Prasugrel are ______

Answer 13

prodrugs that inhibit P2Y12

Question 14

Prasugrel vs Clopidogrel

Answer 14

Prasugrel = Faster onset, increased potency due to rapid CYP450 metabolism

Question 15

Protease that cleaves circulating vWF

Drug that blocks this process (as an AE)?

Answer 15

ADAMTS13

Ticlid induces antibodies against ADAMTS13 = reduced proteolytic activity = excessie platelet aggregation

Question 16

P2Y12 receptor antagonists that act on platelet surface, and need NO METABOLISM to work

These drugs are ____

Answer 16

Ticagrelor

Cangrelor

Both are REVERSIBLE

Question 17

CYP metabolism of Clopidogrel and Prasugrel

Answer 17

C = 2C19

P = 3A4, 2D6

Question 18

Eptifibatide MOA

• Has what structural component?
• ROA?
• Use?

Answer 18

Inhibits fibrinogen binding to GP2b3a –> decrease platelet agg.

• has RGD motif
• Delivered IV because its a peptide
• Use to prevent TE in unstable angina and PCI

Question 19

Tirofiban MOA

• ROA
• T1/2
• Use?

Answer 19

Reversible inhibitor of fibrinogen binding to GP2b3a

• IV in dilute soln
• 2 hrs
• Combo with HEPARIN for ACS

Question 20

Abciximab structural makeup?

MOA?

PK and implications of this?

Answer 20

Fab fragment of chimeric monoclonal Ab

Binds to GP2b3a receptor to inhibit agg.

LONG duration of action = increased risk of bleed

Question 21

PDE3 inhibitors

Answer 21

Dypyridamole

Cilostazol

Platelet aggregation inhibition. Action related to cAMP PDE inhibition & inhibition of Adenosine uptake

Question 22

Dipyridamole use

Answer 22

combo with warfarin (prevent Embol. from prosthetic valves)

Combo with ASA to prevent ischemic stroke

Question 23

Cilostazol use

Answer 23

intermittent claudication

Question 24

Protease activated receptor inhibitors

Answer 24

Vorapaxar, Atopaxar

Thrombin activates platelets

Proteolytic cleavage of PAR-1 receptors on surface of platelet

(PAR’s are GPCR’s that release Ca++)

Question 25

Reversible PAR1 receptor antagonist

Use?

Contrainications?

Another thing to consider regarding lasting effects?

Answer 25

Vorapaxar

• Combo with ASA or clopidogrel
• CI = Stroke/TIA history
• Antiplatelet effects last for DAYS after discontinuation