Things that thin the blood

Question 1

Aspirin

Answer 1

Irreversibly inhibits COX-1 - inhibits formation thromboxane A2 in platelets, thus inhibiting platelet aggregation

COX is inhibited for the lifespan of the platelet so 7-10 days

Question 2

Clopidogrel

Answer 2

The active metabolite irreversibly blocks the P2Y12 component of ADP receptors on the platelet surface
–>prevents activation of the GPIIb/IIIa receptor complex, thereby reducing platelet aggregation.

Platelets blocked by clopidogrel are affected for the remainder of their lifespan (~7-10 days).

Question 3

Prasugrel

Answer 3

Prodrug that is metabolised to both active (R-138727) and inactive metabolites.

The active metabolite irreversibly blocks the P2Y12 component of ADP receptors on the platelet, which prevents activation of the GPIIb/IIIa receptor complex, thereby reducing platelet activation and aggregation

Question 4

Enoxaparin

Answer 4

Enoxaparin binds to antithrombin to form a complex that irreversibly inactivates clotting factor Xa.

It has less activity against factor IIa (thrombin) compared to unfractionated heparin (UFH) due to its low molecular weight.

Question 5

Unfractionated heparin

Answer 5

Potentiates the action of antithrombin III and thereby inactivates thrombin (as well as activated coagulation factors IX, X, XI, XII, and plasmin) and prevents the conversion of fibrinogen to fibrin

heparin also stimulates release of lipoprotein lipase (lipoprotein lipase hydrolyzes triglycerides to glycerol and free fatty acids)

Question 6

Rivaroxaban

Answer 6

Factor Xa inhibitor

competitive reversible antagonist

Question 7

Apixaban

Answer 7

Factor Xa inhibitor

reversible direct

Question 8

Dabigatran

Answer 8

reversible, direct thrombin inhibitor that inhibits both free and fibrin-bound thrombin.

Inhibits coagulation by preventing thrombin-mediated effects, including cleavage of fibrinogen to fibrin monomers, activation of factors V, VIII, XI, and XIII, and inhibition of thrombin-induced platelet aggregation.

Question 9

Abciximab

Answer 9

Monoclonal Ab binds to platelet IIb/IIIa receptors, resulting in steric hindrance, thus inhibiting platelet aggregation

Question 10

Ticagrelor

Answer 10

Reversibly and non competitively binds the adenosine diphosphate (ADP) P2Y12 receptor on the platelet surface which prevents ADP-mediated activation of the GPIIb/IIIa receptor complex thereby reducing platelet aggregation.

Due to the reversible antagonism of the P2Y12 receptor, recovery of platelet function is likely to depend on serum concentrations of ticagrelor and its active metabolite.

Question 11

Bivalirudin

Answer 11

specific and reversible direct thrombin inhibitor

binds both circulating and clot-bound thrombin

preventing thrombin-mediated cleavage of fibrinogen to fibrin monomers, and activation of factors V, VIII, and XIII.

Shows linear dose- and concentration-dependent prolongation of ACT, aPTT, PT, and TT.

Question 12

Dipyridamole

Answer 12

inhibitors of PDE, an enzyme that catalyzes the hydrolysis of the cyclic nucleotides cAMP and cGMP

Question 13

Why is GPIIbIIIa important in clotting?

Answer 13

When activated, platelets release thromboxane and ADP. This acts in autocrine and paracrine way on other platelets so that membrane bound IIb and IIIa merge. They can then grab on to fibrinogen (factor I) and if more than one plt grabs on to the same bit of factor, helps form clot.

Question 14

Argatroban

Answer 14

Direct thrombin inhibitor

Question 15

Danaparoid

Answer 15

Factor Xa inhibitors

Question 16

Fondaparinux

Answer 16

Factor Xa inhib