Anticoagulant and antiplatelet drugs Flashcards
What are some examples of indications for anticoagulant drugs?
- Venous thrombosis
- Atrial fibrillation
What pathway do anticoagulant drugs target?
Fibrin clot formation pathway
How does heparin work and how is it administered?
- Potentiates the effects of anti-thrombin - negative feedback to thrombin and factors VIIa, V, Xa, VIII, XIa and TF
- Immediate effect
- Parenteral (IV or SC) 2 forms - unfractionated and low molecular weight (LMWH)
How are patients on heparin monitored?
- Activated partial thromboplastin time (APTT) for unfractionated heparin
- Anti-Xa assay for LMWH but usually no monitoring of LMWH is required as more predictable repsonse
What are the potential complications of heparin treatment?
- Bleeding - heparin induced thrombocytopenia (HITT) - monitor FBC in patients on heparin
- Osteoporosis with long term use
How are the effects of heparin reversed?
- Stop the heparin!
- Occassionally in severe bleeding - protamine sulphate, reverses antithrombin effect
- Complete reversal for unfractionated
- Partial reversal for LMWH
Name some examples of coumarin anti-coagulants and describe their mechanism of action
- Drugs - warfarin, phenindione, acenocoumarin, phenprocoumon
- Mechanism of action - inhibition of vitamin K
What are vitamin K dependent coagulation factors and where are they synthesised?
- Factors II (prothrombin), VII, IX and X - protein C and protein S
- Synthesised in liver
- They require vitamin K for final carboxylation step essential for their function
What is the mechanism of action of warfarin?
Acts as an anticoagulant by blocking the ability of vitamin K to carboxylate the vitamin K dependent clotting factors (II, VII, IX + X), thereby reducing their coagulant activity
How is warfarin therapy given?
- Narrow therapeutic window so need to monitor therapy
- Maintenance - dose should be taken at same time every day
What is INR?
- A mathematical correction for differences in the sensitivity of thromboplastin reagents
- Allows for comparison of results between labs and standardizes reporting of the prothrombin time
What is the major adverse effect associated with warfarin and what factors may influence this?
Haemorrhage!
Intensity of anti-coagulation, concomitant clinical disorders, concomitant use of other medications, *beware of drug interactions*
What are some of the bleeding complications associated with warfarin?
- Mild - skin bruising, epistaxis, haematuria
- Severe - GI, intracerebral, significant drop in Hb
How are the effects of warfarin reversed?
Omit warfarin dose -> administer oral vitamin K -> administer clotting factors (FFP) -> clinical and laboratory assessment of response
How effective are the administration of vitamin K and clotting factors in managing a warfarin induced bleed?
- Vitamin K - 6 hours
- Clotting factors - immediate
Name an example of a direct thrombin inhibitor
Dabigatran - targets thrombin
Name examples of activated factor X inhibitors
Rivaroxaban + apixaban
What is the benefit of these new anticoagulants?
- Oral and no monitoring required
- Less drug interactions
- Currently no specific antidote for reversal
What are these new anticoagulants e.g. apixaban and dabigatran used for?
- Used instead of LMWH as prophylaxis in elective hip and knee replacment surgery
- Used for selected patients for stroke prevention in atrial fibrillation
- Used for treatment of DVT/PE
What is atherosclerosis?
- Not the same as arterial thrombosis
- Damage to endothelium
- Recruitment of foamy macrophages rich in cholesterol
- Forms plaques rich in cholesterol
Describe stable atherosclerotic plaques and give examples of what conditions they are seen in
- Hyalinsed and calcified
- Stable plaques are seen in angina and intermittent claudication
Describe unstable atherosclerotic plaques and give examples of what conditions they are seen in
- Plaques rupture, platelets are recruited and cause acute thrombosis
- Sudden onset of symptoms
- Unstable angina or myocardial infarction (coronary arteries)
- Stroke (cerebral arteries)
Describe the relationship between platelets and arterial thrombosis
- Plaque ruptures (more liklely in arteries due to high pressure)
- Platelet adheres to it - exposed endothelium and release of VWF
- Platelets become activated - release granules that active coagulation and recruit other platelets to developing platelet plug
- Platelet aggregation via membrane glycoproteins
What are some risk factors for arterial thombosis?
Factors that cause damage to the endothelium, increase in foamy macrophages and platelet activation
- Hypertension - damage to endothelium, platelet activation
- Smoking - endothelium, platelets
- High cholesterol - accumulated in plaque
- Diabetes mellitus - endothelium, platelets, cholesterol
