Anti-coagulant drugs Flashcards
Briefly describe the MOA of warfarin
How is it monitored?
- Vitamin K antagonist
- Prevents y-carboxylation of factors 2,7,9,10
- Prolongs the extrinsic pathway (prothrombin time)
- Also inhibits the natural anticoagulants: protein C and S
-INR monitored
How long does it take for warfarin to reach therapeutic levels? Why is this?
> 3 days
The half life of clotting factors 2,7,9,10 vary
That of clotting factor 2 is 60 hours so this is the minimum time it will take to have thereapeutic effect
What is the target INR?
- 5
- for treatment of DVT, PE, AF, recurrent DVT off warfarin, symptomatic inheritied thrombophilia, cardiomyopathy, cardioversion, mural thrombus - 5
- recurrent DVT on warfarin, metal heart valves, antiphospholipid syndrome*
What is antiphospholipid syndrome? Diagnostic test? Why is their target INR higher?
- An autoimmune condition
- Pateints are procoagulant and have a prolonged APTT paradoxically because the autoantibody acts as an inhibitor (Lupus anticoagulant)
- DRVBT test
- Associated with recurrent miscarriages
Discuss warfarin interaction
Give examples
Warfarin is metabolised by cytochrome P450
Drugs which are enzyme inhibitors potentiate warfarin:
- carbazepine, azathiprine, allopurinol, erythromycin, ciprofloxacin, metronidzole, fluconazole
Drugs which induce the enzyme cause warfarin to be eliminated (inhibitory effect)
- Rifampicin, amiodarone, citalopram, phenytoin
- Alcohol increases bleeeding risk
What are the side effects of warfarin?
Is it safe to use in pregnancy?
- Significant haemorrhage risk: intra cranial yearly risk of 1%, increases with elderly and those on higher INR target
- Minor bleeding up to 20%/yr
- Skin necrosis
- Alopecia
Teratogenic in pregnancy
- use LMW heparin
How do you reverse warfarin?
- In life threatening bleeding give activated prothrombin complex (Oxtaplex) to replenish clotting factors 2,7,9,10
- Vitamin K
- FFP
Briefly outline the MOA of Heparin
Formulations?
Pregnancy?
- Mucopolysaccharide that potentiates anti-thrombin
- Irreversibly inactivates factor 2a (thrombin) and 10a
- Given parenterally
LMW heparin as sc injection
Unfractionated heparin as IV infusion
Safe in pregnancy
Describe unfractionated hep
How is it given? How is it monitored? Use in renal failure? Reversal agent? Adverse effects
Rarely used as its inconvenient
- IV: 5000U bolus and 1000U/hour infusion
- APTT monitored with target range maintained with 1.5-2.5x normal
- Safe in renal failure
- Protamine sulphate is partial reversal agent
- Thrombocytopenia, VTE (rare complication of heparin-induced thrombocytopenia)
Describe LMW Heparin
- How is dosing calculated?
- Monitoring?
- Use in renal failure?
- Examples?
- Routine use in hospital?
- Prescribes according to weight
- Not routinely monitored, can use anti-Xa assay
- Requires creatinine clearance/eGFR >30ml/min
- Enoxaparin, Tinzaparin, Dalteparin
- Convenient as given as OD sc injections. Routinely used for thromboprophylaxis in hospital
In heparin induced cytopenia which agents may be used?
Hirudin: snake derived
- Argotroban a direct thrombin inhibitor
Heparinoids: Hep-like
- Danaparoid
Fondaparinux
- Arixtra: potentiates anti-thrombin, inhbites Xa
What are the two classes of DOAC?
Give an example for each
- Direct thrombin (factor 2a) inhibitor e.g. Dabigatran
- Direct factor 10a inhibitor e..g Rivaroxaban, Apixaban
Is there any difference in efficacy between DOACs and warfarin/heparin?
- No difference for VTE and AF
- Inferiority for cardiac valves
When is Rivaroxaban indicated?
Safety in renal failure?
- VTE prophylaxis
- Used for treatment of DVT and PE
- Stroke prevention in AF
Lower dose if CrCl is 15-50ml/min
- Apixaban is an alternative which is less affected by renal function
When is Dabigatran indicated?
Safety in renal failure?
Reversal?
- VTE prophylaxis
- Used for treatment of DVT and PE
- Stroke prevention in AF
Requires a creatinine clearance >30ml/min
Idarucizumbab?
