Pharmacology of Haemostasis and Coagulation Flashcards
Types of anticoagulants
Oral
Hearings
Direct oral anticoagulants (DOACs)
What is warfarin?
Oral anticoagulants
Vitamin k antagonist
What does warfarin do?
Blocks vitamin k reductase which is needed for vitamin k to act as a cofactor
Inhibits post-translational modification, therefore no carboxylation of glutamic acid residues
Production of proper coagulation factor is inhibited
What is warfarin used for?
Prevent thrombosis:
Patients with replaced heart valves, atrial fibrillation, PE, DVT
How long does it take for warfarin to take effect?
Several days
What is warfarin monitored by?
International normalised ratio with a specific target value and adjust dose
Problems with warfarin
Many drug interactions - may be potentiated by a range of drugs
- may be reduced by enzyme inducers
Increased risk to bleeding
Give an example of injectable anticoagulants
Unfractionated heparin or Low Molecular Weight Heparin
Eg. Enoxaparin, tinzaparin
What do injectable anticoagulants do?
Activate antithrombin III (natural protein)
Antithrombin inactivates some clotting factors and thrombin by complexing with serine protease of the factors
Difference between injectable anticoagulants and warfarin
IAs are immediate and subcutaneous
Use of heparin
Prevent thrombosis (particularly DVT), used to prevent clots
Used while warfarin takes effect
Unfractionated heparin monitored with APTT
Example of DOAC
Dabigatran - oral thrombin inhibitor
What do DOACs do?
prevents thromboembolism by inhibiting the coagulation factors in the cascade
Why are DOACs better than warfarin?
less bleeding
fewer drug interactions
does not require monitoring
equally as effective
Why are DOACs not better than warfarin?
effects are less easily reversed
expensive antidote
What are prostacyclin/nitric oxide?
endothelial derived vasodilators
What does prostacyclin do?
PGI2 - prevents platelet aggregation
acts on platelets to increase cAMP
What does thromboxane do?
promotes aggregation, decreases cAMP
What does nitric oxide do?
prevents both platelet adhesion and aggregation by increasing platelet cGMP
Give examples of antiplatelet drugs?
low dose aspirin (75mg)
dipyridamole
What is low dose aspirin used for?
prevent MI in ps who have previously had a MI
(not for primary prevention)
reduces incidence of stroke
How does low dose aspirin work?
inhibits cyclo-oxygenase irreversibly so free arachidonic acid cannot be made into endoperoxides which in turn form PGI2 and thromboxane
thromboxane is a platelet and therefore has no nucleus whereas PGI2 is an endothelial cell and therefore the nucleus regenerates COX
What is dipyridamole?
antiplatelet drug
What is dipyridamole used for?
prevention of thrombosis
used in conjunction with aspirin, enhances effect of aspirin
How does dipyridamole work?
phosphodiesterase inhibitor - prevents breakdown of cAMP and cGMP (which are broken down by phophodiesterase)
therefore inhibits aggregation
also inhibits adenosine uptake
What is GP IIb/IIIa?
expressed from ADP from aggregating platelets
binds fibrinogen which leads to cross-linking of platelets
What does clopidogrel do?
inhibits ADP induced expression of GP, ie prevents ADP activating platelets
When is clopidogrel used?
for ps who can’t take aspirin
used with aspirin after a heart attack
Why is aspirin not used for primary prevention?
risk of gastric bleeding
What is abciximab?
monoclonal antibody against GP IIb/IIIa
When is abiciximab used?
ps undergoing angioplasty (catheter and balloon to open up coronary artery)
Give an example of fibrinolytic drug/protein
alteplase
What is fibrinolysis?
break down of fibrin
endogenous system to dissolve clots, activated with clotting system
plasminogen becomes activated to form plasmin
What is plasmin
part of fibrinolysis
enzyme which digests fibrin of the clot and also some of the clotting factors
dissolves it
What do fibrinolytic agents do?
activate plasminogen to plasmin conversion
What are thrombolytics used for?
given after MI to dissolve thrombus that has caused blockage of coronary arteries and the MI
pulmonary embolism
thromboembolic stroke
What are thrombolytics used with?
with aspirin, but need care can cause bleeding
What is alteplase used for?
ischaemic strokes
dissolves clot and restores blood flow, saving neurons
must be given <4 hours post-stroke
