Anticoagulation: Oral, direct thrombin and factor Xa inhibitors Flashcards
What is the mode of action of warfarin?
Inhibits synthesis of vitamin K dependent coagulation factors II (thrombin), VII, IX, X
Warfarin’s side effects are fatal as they do too much blood thinning. This is why we develop new (anticoagulant) drugs.
Where do we get new ideas and leads to develop a novel anticoagulant?
Hot countries
e.g. mosquito, mongolian camel tick + kissing bug
What is Hirudin?
Which type of DTI is Hirudin?
How are they produced?
How is hirudin administered to a patient?
Hirudin is a natural product - produced in the parapharyngeal glands of medicinal leeches
Bivalent DTI - block both the active site + exosite 1 in an irreversible 1:1 stoichiometric complex
Given parentally, by intravenous injection
Bleeding is a side effect
What is the mode of action of Hirudin?
Hirudin binds to thrombin
When binded, it inhibits fibrinogen converting to fibrin upon blood clotting.
Describe the function of thrombin.
How do different anticoagulants use the surface binding pockets?
What is bivalirudin?
Which type of DTI is it?
20 amino acid polypeptide - synthetic analogue of hirudin
Bivalent DTI
It has a lower rate of bleeding compared to hirudin
