anticoagulation & antiplatelet -Hockerman

Question 1

describe the first step of platelet activation (Adhesion)

Answer 1

-GP Ia binds to collagen
-GP Ib binds to von Willebrand Factor bridged to collagen

Question 2

describe the second step of platelet activation (Secretion)

Answer 2

-platelet secretion factors ADP, TXA2, 5-HT are released and activate & recruit other platelets

Question 3

describe the third step of platelet activation (Aggregation)

Answer 3

ADP, 5-HT, TXA2 activates GPIIb/IIIa which bind fibrinogen
-fibrinogen cross-links platelets together

Question 3

What are the P2Y12 inhibitors?

Answer 3

direct-acting: Ticagrelor (reversible)
indirectly acting (pro-drugs): Prasugrel, Clopidogrel (irreversible)

Question 4

What are the GPIIb/IIIa inhibitors?

Answer 4

Abciximab/REOPRO (chimeric monoclonal antibody)
Eptifibitide/INTEGRILIN (synthetic peptide)
-both inhibit fibrinogen cross-linking of platelets

Question 5

What are the PDE-3 inhibitors?

Answer 5

-platelet aggregation inhibitor
Dipyridamole (Persantine)
Cilostazol (Pletal)

Question 6

What are the PAR Inhibitors?

Answer 6

-cleaves PAR-1 receptors on platelet surface; inhibits thrombin activation
-Vorapaxar

Question 7

What is factor IIa and what does it do?

Answer 7

-Thrombin
-converts Fibrinogen to fibrin (with Ca+2)

Question 8

What is factor II and what does it do?

Answer 8

-Prothrombin
-gets activated to Thrombin via factor factor Xa

Question 9

How is the common pathway activated?

Answer 9

Tissue factor (Thromboplastin) binds to factor VII to activate it
-Factor VIIa binds and cleaves factor X to activate it (Xa)

Question 10

What is factor XIII and what does it do?

Answer 10

factor XIII gets activated by factor IIa (Thrombin) to factor XIIIa
-factor XIIIa converts fibrin to the cross-linked fibrin (clot)

Question 11

What is the MOA of Warfarin?

Answer 11

-inhibition of Vitamin K-epoxide reductase which prevents the reduction of Vitamin K back to its active form
-this prevents production of y-glutamyl carboxylase which produces clotting factors II,VII, IX and X

Question 12

What is the MOA of indirect factor IIa/Xa inhibitors?

Answer 12

UFH
-binds to AT which inactivate many clotting factors(thrombin); Heparin increases rate by 100x
LMWH (enoxaparin, dalteparin)
-bind to Factor Xa and has greater specificity for inhibition of factor Xa

Question 13

What is the MOA of fonaparinux?

Answer 13

-indirectly inhibits factor Xa by binding AT
-SubQ

Question 14

What is the MOA of Lepirudin, Bivalirudin (Angiomax), Argatroban, Dabigatran?

Answer 14

-Direct Thrombin Inhibitors
-can inhibit soluble and fibrin-bound thrombin via directly binding the active site or the exosite or both