Anticoagulants

Question 1

Two keys sites of pharm intervention. Why?

Answer 1

X: common pathway initiator, activator of thrombin
II: fibrinogen converter to fibrin (block clot)

Question 2

What factors/proteins require Vit K? Why?

Answer 2

II, VII, IX, X, Protein C and S

Need Vit K for gamma-carboxylation of terminal glutamic acid for initial, partial activation in the liver

Question 3

How is heparin bioavailibility decreased?

Answer 3

It binds non-specifically to plasma and cellular proteins

Question 4

What complex causes HIT?

Answer 4

heparin-PF4

Question 5

Why must warfarin be given with heparin (or equivalent) for first few days?

Answer 5

Warfarin is a Vit K inhibitor with delayed onset. Proteins C and S require vit K, but will be inhibited first (shorter T1/2), so clotting will continue. Heparin blocks clotting until warfarin depletes vit K, and decreases clotting factors.

Question 6

Who should NOT be given low MW heparin (enoxaparin, danaproid)

Answer 6

patients with a history of HIT

Question 7

Differences between Argatroban and Dabigatran (admin, half life, CL)

Answer 7

Admin: A (IV), D (oral)
Half life: A(45 min), D (12 hr)
CL: A(liver), D(renal)

Question 8

How do oral DTIs bind thrombin?

Answer 8

reversibly!

Question 9

Main differences between heparin and DTI with regards to binding to thrombin.

Answer 9

DTIs don’t require antithrombin III.

DTIs can bind to free and firbin-bound thrombin (heparin can only bind free thrombin)

Question 10

Why are low MW heparins so much better?

Answer 10

greater affinity for Xa, longer duration, higher bioavailability, less chance of HIT, less platelet activity

Question 11

How does hirudin bind thrombin?

Answer 11

irreversibly