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Pharmacology · USMLE Step 1

USMLE Pharmacology: Anticoagulants and Antiplatelets

Heparin, warfarin, direct oral anticoagulants, and antiplatelet drugs with mechanism of action, distinct from the monitoring and antidote focus of the Nursing Pharmacology anticoagulants deck.

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What plasma protein does unfractionated heparin activate to exert its anticoagulant effect?
Antithrombin III (antithrombin)
Which two clotting factors does heparin-activated antithrombin III primarily inactivate?
Thrombin (factor IIa) and factor Xa
What is the route of administration for unfractionated heparin?
IV or subcutaneous injection, not oral
Heparin binds antithrombin through a unique ____ sequence, greatly accelerating antithrombin's activity.
pentasaccharide
Name two low molecular weight heparins.
Enoxaparin and dalteparin
Compared to unfractionated heparin, low molecular weight heparin preferentially inhibits which factor?
Factor Xa, with much less effect on thrombin
Why does LMWH have less effect on thrombin than UFH does?
Its shorter chains are too short to bridge antithrombin to thrombin at the same time
What is fondaparinux?
A synthetic pentasaccharide that selectively inhibits factor Xa through antithrombin
Does fondaparinux have any direct effect on thrombin?
No, it is selective for factor Xa
Warfarin's mechanism of action
Inhibits vitamin K epoxide reductase (VKORC1)
Warfarin's inhibition of vitamin K epoxide reductase prevents ____ of vitamin K-dependent clotting factors.
gamma-carboxylation
Which four clotting factors have reduced synthesis due to warfarin?
Factors II, VII, IX, and X
Besides clotting factors, which two natural anticoagulant proteins does warfarin also reduce?
Protein C and protein S
Why does warfarin have a delayed onset of anticoagulant effect after starting therapy?
Already-circulating clotting factors must degrade according to their own half-lives first
Why can warfarin cause a transient hypercoagulable state early in therapy?
Protein C has a short half-life and falls before the procoagulant factors do

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