Flashcards in Pharmacology of Anticoagulants, Antiplatelet drugs & Fibrinolytics Deck (18):
What kind of oral anticoagulant is Warfarin?
Vitamin K antagonist
When Warfarin blocks Vitamin K reductase, how does this inhibit coagulation?
Vit K is essential for production of prothrombin and Factors VII, IX and X. Vitamin K is required as a cofactor in post-translational modification of glutamic acid residues.
Against what type of thrombosis would one use Warfarin?
-in patients with replaced heart walves
However: needs ca. days to act
How does the injectable agent -unfractioned heparin- achieve its anticoagulant therapeutic effect?
It activates Antithrombin III. Antithrombin inhibits serine proteases and thus inhibits Thrombin and Factors X, IX, XI
What are the uses of injected heparin?
prevent thrombisis (venous and unstable angina).
Also used to prevent blood clotting on collection. Has an immediate action.
What side effects can warfarin have, after potentiated by another drug, and what is used to monitor warfarin?
-blood in faeces and urine
One monitors with the INR or also called prothrombin time.
Name an oral thrombin inhibitor that is difficult to reverse.
What are prostacyclins and nitric oxide?
endothelial-derived vasodilators that prevent platelet aggregation.
How does the body synthetise prostacyclin and thromboxane from Arachidonic Acid?
PLA2 converts it to free AA. Then, cyclo oxygenase converts free AA to endoperoxides, which can become PGI2, Prostaglandins and Thromboxane.
What is the action of PGI2?
Prevents platelet aggregation by acting on platelets to increase cAMP.
What is the action of Thromboxane?
Promotes aggregation, decreases cAMP
How does Nitric Oxide influence aggregation?
It prevents both platelet aggregation and adhesion by increasing platelet cGMP
How does aspirin platelet aggregation?
It irreversibly inhibits cyclo-oxygenase. Thus, no PGI2 and Thromboxane can be produced. However, the endothelial cells adjust and produce new COX, wherese the platelets fail to do so (no nuclei). Thus no new thromboxane is produced for 7 days and aggregation is inhibited.
What is the antiplatelet effect of Dipyridamole?
Phosphodiester inhibitor. It would be needed to break down cAMP and cGMP to AMP and GMP. Thus, as a phosphodiesterase, Dipyridamole inhibits aggregation.
How does Clopidogren impact platelets?
It inhibits ADP-induced expression of GP. Glycoprotein IIb/IIIa binds fibrinogen which leads to cross-linking platelets.
For patients who cannot take Aspirin. In combination it also greatly reduces MI risk.
What is fibrinolysis?
Endogenous system that dissolves clots. Plasmin digests the fibrin of the clot.
What are Fibrinolytic agents?
They activate plasminogen to plasmin conversion.