Week 9 Flashcards
What is the simple coagulation cascade?
Damaged blood vessel releases clotting factors, which cause prothrombin to form thrombin, meanwhile activated platelet attracts others forming a plug, Thrombin causes Fibrinogen to form fibrin, of which adheres the plug.
When is the intrinsic pathway activated?
Linked to changes in the phospholipid membrane of all the cells.
When is the extrinsic pathway activated?
Though the injury of cells. Releasing tissue factor
What does both pathways activate?
Factor 10 and factor 5 which form a complex which processes prothrombin into thrombin.
What is prothrombin and what does its active form do?
Is the inactive form of thrombin which is always circulating, which forms fibrin.
What does fibrin do?
Keeps the planets stuck together and with the endothelium.
What are enzymes called that need to be activated, of which always circulate in the body?
Zymogens, which are in there zymogenic form
What is Atherothrombosis?
Is associated with an atherthroscerotic plaque in the blood vessels, which is formed of macrophages and other cells and lipids.
What happens when there is too low activation of platelets and coagulation?
Bleeding, leading to bleeding Diathesis
What happens when there is over activation of platelets and coagulation?
Clotting, leading to coagulation and thrombophilia
What is the mechanism of action of Warfarin?
It antagonises the antihemorrhagic effect of vitamin K, inhibiting vitamin K dependent coagulation factors II, VII, IX, and X, by inhibiting vitamin K reductase, preventing vitamin K from being reduced to its active form.
How does activated reduced vitamin K affect the coagulation cascade?
It would activate prothrombin from its unactivated form.
What aspect of coagulation does warfarin effect?
It inhibits the vitamin K reductase, which inhibits production of activated vitamin K, inhibiting the activation of coagulation factors
What is the clinical use of Warfarin?
For treatment:
- Venous thrombosis and its extension pulmonary embolism.
- Thromboembolic complications associated with atrial fibrillation and/or cardiac vale replacement.
- Reduce risk or myocardial infarction and stroke
What are the different enzymes with eliminate S and R Warfarin to its inactive form?
S -Warfarin - CYP2C9 R -Warfarin - CYP1A1 - CYP1A2 - CYP3A4
Which enantiomer of warfarin works better and why?
S -Warfarin because it binds better to the Vitamin K reductase receptor
What happens when someone has overactive CYP2C9?
S-Warfarin forms its inactive metabolites more quickly leading to less exposure of the drug, so the patients would need a higher dose of the drug, opposite when under-active
What are the different polymorphisms of CYP2C9 and the effects on warfarin?
- 1 - Associated higher activity, need a higher dose.
- 2 - Associated with medium activity
- 3 - Associated with lower activity, need a lower dose
How much does genetic polymorphisms account for, within an individuals variation in dose responsiveness?
50%
How can you test if someone will respond well to warfarin?
Take a sample of blood stimulate separate the plasma and stimulate the formation of fibrin in vitro, measure how long it takes for the fibrin clot to form, through both pathways.
