2. Anticoagulants
These drugs prevent thrombi from forming and include
- UF heparin (iv)
- Low molecular weight heparin: Enoxaparin s.c. (Clexane)
- VKAs: warfarin (oral)
- DOACS: DabigatraN, Rivaroxaban.
These drugs are used for patients with increased thrombotic risk:
- prolonged immobility (look at virchows triad)
- acute MI
- Coronary artery bypass artery (CABG)
- angioplasty
Heparin
Heparin is a naturally occurring antithrombotic which also exist in drug form. There are 2 main types: unfractionated (UF) heparin, and Lowmolecular weight heparin
Drug: Unfractionated Heparin
Pharmacology
Pharmacodynamics:
Mechanism of action: Reduces formation of fibrin via increasing the action of antithrombin binding with both prothrombin (Xa) and thrombin (IIa)
Pharmacokinetics:
Administration: given via IV due to how large the molecule is Clearance: half life of this drug is 30 mins to an hour
Risks and ADRS:
Danger of haemorrhage or thrombocytopenia leading to necrosis
Interactions:
see overdose for chelation agent
Overdose:
Can reverse with chelation, as a heparin antagonist is protamine sulphate which bindss with it to form an inactive complex
Other notes
Drug: LMWH (low molecular weight heparin) Enoxaparin
Trade name: Clexane
Pharmacology
Pharmacodynamics:
Mechanism of action Facilitates antithrombin binding to prothrombin but not thrombin
Pharmacokinetics:
Administration: subcutaneously so patients can even do it themselves. Always adjusted to body weight. do not give iv or im Distribution: increased bioavailability when compared with UF heparin Metabolism: Excretion: Half life is 4-6 hours (longer than heparin) and is eliminated in urine (so you need a patient with good renal function)
Indications:
Its really fast so used to
- prevent DVT (prophylaxis) post op immobile patients etc
- treat DVT - bridging therapy with warfarin
- coronary syndromes (sometimes)
Contraindications:
Risks and ADRS:
if overcooked haemorrhage bruising
elevated AST ALT and hyperkalaemia
thrombocytopenia not generally considered major
Interactions:
Other notes
not as reversible with protamine sulphate as with UF hepatin action is assessed using antifactor Xa activity
Vitamin K and its antagonists
The name is originally german (Vitamin Koagulation). Vitamin K is needed for the activation (or production? idk) of factors X, IX, VII, II (1972). Vitamin K is present in the diet and a number of vitamin replacement products. So ask patient about supplements
Drug: Warfarin
derived from coumarin (rat poison)
Pharmacology
Pharmacodynamics:
S-isomer of warfarin competitively inhibits Vit k epoxide reductase which recharges Vitamin K into its active form. This prevent factors 1972 from being formed (or activated idk).
In short warfarin prevents formation of fibrin
Pharmacokinetics:
Administration: orally Distribution peak blood conc reached in 1-8 hours but does not coincide with therapeutic effect. To measure effects you must use INR, not blood warfarin level. Warfarin has a very low TI. You want to maintain INR at 2-3 Metabolism: S-warfarin (active one) metabolised through CYP 2C9, R-warfarin Metabolised by CYP 1A2 and 3A4 Excretion
Indications:
to prevent thrombosis
- after surgery
Risks and ADRS:
- Major haemorrhagic risk at high INR
- warfarin can cause inhibition of protein C and S which can induce microvasculature thrombosis
- gi tract loss
- bruising
- teratogen
- skin necrosis
Interactions
Warfarin interacts with just about everything which makes it really unstable
Overdose
Administer vitamin k and or factor concentrates (PCC!)
Other notes
Dabigatran is not good with valvular disease or prothetic valves which is why warfarin is still used
DOACs (covered more in drugs for IHD)
These are direct thrombin inhibitors
Drug: Dabigatran
Pharmacology
Pharmacodynamics:
Mechanism of action: Direct Thrombin inhibitor
Pharmacokinetics:
Mainly cleared through renal clearance. therefore patient must have good renal function. this is checked before prescription and then annually
Indications:
Indicated for DVTs PE prophylaxis and treatment venous thromboembolism post arthroplasty CAD and PAD
Contraindications:
Not great for valvular AF or mechanical valve thrombus formation
Risks and ADRS:
fewer adverse effects then warfarin, drug effect directly propertional to dose so we don’t need to take INR
Overdose:
Can be reversed with mAb - idarucizumab