Anticoagulants Flashcards
(31 cards)
4 key antiplatelets
Aspirin
Clopidogrel
Ticagrelot
IIb/IIIa antagonists
2 key anticoagulants
Warfarin
Heparin (fractioned and unfractionated)
Anticoagulant indications
Arterial disease - CAD - CVD - PVD Thromboembolic disease - AF - DVT/PE - prosthetic cardiac valves
Vircow’s Triad
Hypercoagulability
Circulatory stasis
Vascular damage
Unfractionated heparin uses
Acute coronary syndromes
Thromboembolism (prophylaxis and treatment)
Temporary warfarin replacement (e.g., in pregnancy)
Unfractionated heparin mechanism of action
Binds to and increases activity of anti-thrombin III, which usually inactivates thrombin and Xa
How is unfractionated heparin given?
Intravenously or subcutaneously
No negative charge, therefore no GI absorption
Unfractionated heparin pharmacokinetics
Short half-life
Reticulo-endothelial uptake (rapid and easy to reverse)
Therefore rapid onset and offset of action
Variable bio-availability – unpredictable binding to cells and plasma proteins, therefore needs APTT monitoring
Adverse effects of unfractionated heparin
Bruising and bleeding, especially intracranial and gastrointestinal
Thrombocytopenia (heparin-induced thrombocytopenia) – autoimmune against platelets, can cause bleeding or clotting
Unfractionated heparin reversal
Stop heparin
Protamine
Monitor APTT
Protamine
Dissociates heparin from antithrombin III
Irreversible binding to heparin
Little effect on LMWH
LMWH mechanism of action
Bind to antithrombin III but do not inactivate thrombin, only affect factor Xa
Advantages of LMWH
Better absorbed therefore higher bioavailability and no need for IV
Longer half-life and more predictable dose-response
Lower risk of thrombocytopenia and bleeding
How id LMWH given?
Subcutaneously
Disadvantages of LMWH against UH
Cannot be monitored by APTT
Not fully reversible by protamine
Dose adjustment and reduction required in renal failure patients
LMWH uses
Non-STEMI/STEMI
DVT/PE
Warfarin alternative
Warfarin mechanism of action
Antagonist of vitamin K which is a precursor to factors II, VII, IX and X
Slow onset of anticoagulation action
Warfarin uses
Venous or arterial thrombosis treatment and prophylaxis
AF (to decrease risk of systemic emboli)
Warfarin metabolism
S enantiomer metabolised by CYP450-2C9 which is affected by many other drugs and foods
R enantiomer metabolised by CYP450-1A2 and 3A4
Metabolised by glucuronidation and oxidation
Oral warfarin
High bioavailability and rapid absorption
Long effective half life
Warfarin adverse effects
Haemorrhage
Teratogenic – crosses placenta and uptaken into brain, bones and eyes
- last 4 weeks increased risk of intracranial haemorrhage
Contraindications to warfarin therapy
Pregnancy
Uncontrolled alcohol/drug abuse
Dementia/psychosis
Fall risk
INR
International normalised ratio
Patient’s PT in seconds/Mean normal PT in seconds
Major drugs that potentiate warfarin (decrease CYP450-2C9)
Alcohol (long-term) Erythromycin (and others) Omeprazole Simvastatin NSAIDs and many more
