Anticoagulant, Antiplatelet & Thrombotic drugs 2 Flashcards
Describe the mechanism of action of Warfarin
Warfarin inhibits vitamin K recycling. Vitamin K usually acts as a cofactor for post-translational carboxylation of glutamic acid groups of Factors II, VII, IX, X, protein S and protein C. This inhibition also prevents decarboxy-prothrombin from being converted to prothrombin, and vit K is a cofactor in this as well.
Describe Heparin’s mechanism of action
Heparin binds to the lysine residue on Antithrombin III, which induces a conformational change that increases its affinity for activated factors of the intrinsic arm, especially Xa and Thrombin. Antithrombin 3 then inactivates these molecules at a faster rate, preventing the conversion of fibrinogen to fibrin, halting clotting propogation
How is warfarin monitored clinically?
Patients blood is taking and time to clot is measured - this is the prothrombin time. The ratio of a patients prothrombin time to normal is called the International Normalised ratio (INR). This needs to be about 2-3 for patients requiring blood-thinning
What are some adverse effects of Warfarin?
Warfarin is teratogenic in pregnancy, it disrupts foetal development
In addition, if you have protein C or protein S heritable deficiency, early depletion of these can occur when you take Warfarin, which can cause skin necrosis
You are also at an increase bleeding risk if you have a peptic ulcer or platelet defects
What are some adverse effects of Heparin?
Heparin can cause bleeding and immune-mediated platelet activation. This can lead to thrombosis (coagulation of blood in part of the circulatory system), and bleeding from thrombocytopaenia
LMW Heparin has more predictable activity and elimination in the body
What are some of the major interactions of affecting warfarin activity in the human body?
Warfarin is metabolised by CYP2C9.
CYP2C9 is induced by barbiturates, decreasing warfarin’s efficacy
CYP2C9 is inhibited by allopurinol, which increases bleeding risk
Absorption of warfarin is decreased by antacids and oil laxatives
The effectiveness of warfarin also depends on the amount of Vit K in the diet and the amount of it being made by gut flora. This can be affected by long term broad spectrum antibiotics.
What is the mechanism of actin of aspirin as a blood thinner?
Aspirin acetylates the NH2-terminal serine of cyclooxygenase. This is irreversible, prevents the conversion of arachindonic acid to prostaglandin G2, which causes permanent loss of TxA2 (Thromboxane A2)
What does Clopidogrel do, and what is it’s mechanism of action?
Clopidogrel is an oral anti-platelet agent, who’s active metabolite irreversibly blocks platelet’s ADP receptors
Explain the mechanism of action of the thrombolytic drug tPA
t-PA is a recombinant human protein, and is a tissue plasminogen activator. IV administration of it relieves blockage of critical vessels.
It operates by converting plasminogen to plasmin, which lyses clots
