Anticoagulants and antiplatelets Flashcards
Example of oral anticoagulant
Warfarin
What does warfarin do
Vitamin K antagonist
Mechanism of action of warfarin
1) New factor formed from liver (it is a precursor)
2) new factor is chemically modified (still the precursor)
3) Precursor undergoes in the coagulation cascade
4) The system is Vitamin K dependent
5) Therefore warfarin blocks Vitamin K reductase which is needed for Vitamin K fo act as a cofactor
6) Therefore the production of the proper coagulation factors is inhibited by warfarin
How long does warfarin take ti impact on the production of coagulation factors
3 days
what is warfarin used for
- In patients with replaced heart valves
- Atrial fibrillation
- DVT
What is the dose of warfarin determined by
INR
What does the INR measure
Anticoagulation of the patient
What are examples of injectable anticoagulants
Unfractionated heparin
Low molecular weight heparins eg enoxaparin
Difference between warfarin and enoxaparin
Enoxaparin acts immediately
What does enoxaparin do
Activates antithrombin III which inactivates some clotting factors and thrombin by complexing with serine protease of the factors (interferes with coagulation factors)
What is the use of heparin
Used to prevent thrombosis and used to prevent blood clotting on collection
When is heparin particularly used
Used whilst warfarin takes effect because warfarin takes 3 days to take effect
What are DOACs
Drugs which directly inhibit the coagulation factors
Benefits of DOACs
Fewer complications and less drug reactions
Drawback of DOACs
Warfarin is reversible but DOACs are expensive and challenging to reverse ie if the patient is bleeding and you want to reverse it
What are prostacyclin and nitric oxide derived from
Endothelial cells
Function of prostacyclin
- Stops platelets from sticking (acts on platelets to increase cAMP)
- Vasodilator
Function fo nitric oxide
Regulate blood pressure and blood flow and also prevents platelets from sticking
How are prostacyclin, prostaglandins and thromboxane synthesises from arachidonic acid
1) arachidonic acid found in membrane
2) PLA2 breaks that down to free AA’s
3) Cyclo-oxygenase (COX) which is an enzyme breaks that down to endoperoxides which in turn form prostacyclin, prostaglandins and thromboxane
Role of thromboxane
Promotes aggregation and decreases cAMP
Effects of aspirin
Antiplatelet drug
What is aspirin used for
Preventing myocardial infarction in patients who have previously had a MI
What else does aspirin do
Inhibits cyclo-oxygenase irreversibly
Aspirin inhibits cyclo-oxygenase which means that the production of prostacyclin is inhibited as well as thromboxane which is counter intuitive. therefore how is aspirin an anticoagulant
The nucleus of the endothelial cell which has been inhibited to produce thromboxane and prostacyclin produced the mRNA for cyclooxyrgenase so prostacyclin is pumped out of the endothelial cells
Why is use of aspirin irreversible in platelets
Because platelets do not have a nucleus and so there is no possibility of producing mRNA for cycle-oxygenase
Therefore overall effect of aspirin
Platelets have no nuclei so can’t produce any more cyclo=oxygenase so no more thromboxane produced until new platelets have been synthesised
-endothelial cells have nuclei so can produce more cycle-oxygenase to produce prostacyclin
Effective anti-platelet drug
Low dose aspirin
What is clopidogrel
-Antiplatelet drug
What does clopidogrel do
Binds to ADP receptors and stops ADP from activating the platelets
When is fibrinolysis activated
When coagulation is taking place
When are thrombolytics used
- In thromboembolic stroke
- Pulmonary embolism
