L14- Drugs affecting blood coagulation, platelet aggregation and fibrinolysis Flashcards
What is a thrombus?
A blood clot made up of a fibrin framework with platelets and cells trapped in this
What are the 2 types of thrombus?
- Venous thrombosis- where coagulation has th majore role. (the fibrin frame)
- Arterial thrombosis- platelet aggregation has the more major role.
What is an embolus?
Where fragment of whole of a thrombus detaches and gets into bloodstream. Then blocks small vessels in pulmonary, cardiac, CNS circulation.
What are the targets for modifying thrombosis process? When are these most successful?
Modify coagulation- important in venous thrombus.
Modify platelet aggregation- important in arterial thrombosis
Modify clot- when prevention fails
What’s the basic outline of coagulation?
Damage to vessel
Activation of prothrombin to thrombin
Thrombin turns fibrinogen to fibrin (insoluble)
Which anticoagulent is naturally occuring and is a family of sulphated mucopolysaccharides?
Heparin.
The functions differ dependign on the molecular weight of the heparin
What does heparin do?
It inhibits the actions of thrombin, factor X and factor IX.
It aids Antithrombin II
What does heparin require and how does it work?
Requires the presence of antithrombin III, an endogenous protease inhibitor.
Normally ATII opposes coagulation.
So stops thrombin from turning fibrinogen into fibrin.
What does heparin increase the rate of?
Heparin increases the rate (1000 fold) of formation of anti-thrombin III-thrombin complex.
Brings anti thrombin 3 to thrombin. nice
What’s the difference in heparins and low molecular weight ones?
Larger heparins- bind to AT3 and factor IIa (thrombin).
LMWH- shorter so can only affect the factor Xa. Don’t bind to thrombin.
Immediate and longer lasting than bigger heparins.
What are the problems with heparin?
Can’t use orally, so can’t use at home easily.
Risk of haemorrhage.
What are the problems with warfarin?
Slow onset- as pre-existing vitamin K must be depleted.
Haemorrhage risk
Teratogenic- birth defects
Travels in blood by binding proteins. If there’s a competitor for the protein, can have too much warfarin in blood.
What does warfarin do?
It’s similar in structure to vitamin K so antagonises vit K role in formation of clotting factors.
Competes with vit K reductase so vit k isnt made.
What’s the advantage of warfarin over heparin?
It can be taken orally.
What do platelets do at damaged area?
- Glycoprotein receptors on surface bind to exposed connective tissue in damaged areas.
- Activated platelet changes shape.
- Releases signals- TXA2 and ADP.
- Express other glycoproteins on surface.
- Chain reaction- more platelets activate and adhere
