2.4 Anticoagulants Flashcards
How does heparin work as an anticoagulant?
potentiates the formation of complexes between Antithrombin III and activated factors of the coagulation cascade leading to their inactivation.
How does antithrombin III work
It forms a 1:1 complex with activated factors (thrombin, Xa, IXa, XIIa) via a reactive site
How is heparin administered?
Parenteral (prophylaxis)
Iv infusion with or without bolus for therapy
How is heparin cleared?
Saturable: (rapid) – heparin binds to receptors on endothelial cells and macrophages and is internalized, depolymerized and metabolized into smaller fragments
Non-saturable clearance (slow): Renal
How do you monitor heparin therapy?
APTT - important due to the variability in protein binding and metabolism between individuals
What are the complications of heparin therapy?
Bleeding Heparin induced thrombocytopenia Osteoporosis Transaminitis Hyperaldosteronism Hypersensitivity
What factors does warfarin inhibit?
II (thrombin)
VII
IX
X
How does warfarin work?
It blocks the regeneration of vitamin K which is needed for the addition of gamma-carboxyglutamine acid residues on factors II, VII, IX and X as well as protein C and Protein S
How does warfarin work?
It blocks the regeneration of vitamin K which is needed for the addition of gamma-carboxyglutamine acid residues on factors II, VII, IX and X as well as protein C and Protein S
How is warfarin metabolised and what are the effects of warfarin dependent on?
By CYP2C9
Effects are dependent on the T1/2 of the vitamin K dependent clotting factors in the blood
What do you need to give with warfarin?
It has a delayed onset of anticoagulation effect so commence after a patient is on heparin or LMWH
What will initially happen with warfarin treatment?
Initial hypercoaguable state due to the decreased level of protein C
What are the important drug interactions of warfarin?
Displacement of warfarin from albumin binding sites (anticonvulsants)
Inhibition or acceleration of drug clearance (antibiotics, barbituates)
Reduced absorption (cholestyramine)
What genetic polymorphisms affect warfarin?
CYP2C9 polymorphisms
Vitamin K epoxide reductase polymorphisms
How do you monitor warfarin therapy?
Prothrombin Time
What are the complications of warfarin therapy?
Haemorrhage
Warfarin induced skin necrosis
What causes warfarin induced skin necrosis?
the initial decrease in protein C which results in paradoxical activation of coagulation, resulting in a hypercoagulable state and thrombosis. The blood clots interrupt the blood supply to the skin, causing necrosis
How can you reverse warfarin therapy?
Cessation - 3-5 days
Prothrombin complex concentrate
Vitamin K infusion - complete reversal with 10 mg
Where is the main action of LMWH?
Factor Xa
Where is the main action of LMWH?
Factor Xa
What is the advantage of LMWH?
less binding to plasma, platelet or endothelial derived proteins → more predictable response to weight adjusted dose than heparin
What are the complication of LMWH?
Bleeding, especially in renal impairment
Thrombocytopenia: lower incidence if initial exposure to LMWH rather than heparin
LMWH cannot be recommended once heparin associated thrombocytopenia has occurred
How can you reverse LMWH therapy?
50% reversal with use of protamine
What drug is used when there is heparin associated thrombocytopenia?
Danaparoid - similar to LMWH (blocks Xa)
What are the two direct thrombin inhibitros?
Hirudin and Bivalirudin
What drugs inhibit Xa?
Rivaroxaban and Apixaban
What are the two direct thrombin inhibitors?
Hirudin and Bivalirudin
What drugs inhibit Xa?
Rivaroxaban, Apixaban and Aristotle
How does Rivaroxaban and Apixaban work and what are they used for?
Inhibit Xa - works in the plasma and in the prothrombinase complex within the clot to which heparin cannot reach
used for post surgical prevention
What is usually used in conjunction with anticoagulants?
Antiplatelet drugs such as aspirin
