Anti-Coagulant Drugs Flashcards
List the common anti-coagulants used
Unfractionated heparins
Low molecular weight heparins (LMWH)
Vitamin K antagonists / Warfarin
DOACs (direct oral anti-coagulants)
List the following for: Unfractionated heparins
- Use
- Example drugs
- Drug class
- Mechanism of action
- Adverse effects
- Warnings / contraindications
- Important drug reactions
Anti-Coagulant
- Prevent venous thromboembolism – DVT or PE or perioperative prophylaxis
- During pregnancy
- Acute coronary syndromes
Unfractionated heparin
Heparin
Large glycosaminoglycan chains (mixture) - unpredictable
- Bind to antithrombin-3 and increase its activity (by causing a conformational change)
- Antithombin-3 then binds to factor 10a – inhibiting factor 10a
- In order to inhibit thrombin, heparin needs to bind simultaneously to antithrombin-3 and thrombin
- Bruising and bleeding
- Heparin-induced thrombocytopenia
- Hyperkalaemia
- Osteoporosis
- Clotting disorders
- Renal impairment
- Other anti-thrombotic drugs
- ACEi/ARB
- Amiloride / Spironolactone
List the following for: Low molecular weight heparins (LMWH)
- Use
- Example drugs
- Drug class
- Mechanism of action
- Adverse effects
- Warnings / contraindications
- Important drug reactions
Anti-Coagulant
- Prevent venous thromboembolism – DVT or PE or perioperative prophylaxis
- During pregnancy
- Acute coronary syndromes
Dalteparin
Enoxaparin
Fondaparinux – longer t ½
Heparin
Typically smaller polysaccharide chains – more predictable
- Bind to antithrombin-3 and increase its activity (by causing a conformational change)
- Antithombin-3 then binds to factor 10a – inhibiting factor 10a
- Doesn’t inactivate thrombin
- Bruising and bleeding
- Heparin-induced thrombocytopenia
- Hyperkalaemia
- Osteoporosis
- Clotting disorders
- Renal impairment
- Other anti-thrombotic drugs
- ACEi/ARB
- Amiloride / Spironolactone
List the following for: Vitamin K antagonists
- Use
- Example drugs
- Drug class
- Mechanism of action
- Adverse effects
- Warnings / contraindications
- Important drug reactions
Anti-Coagulant
- Prevent venous thromboembolism – DVT or PE or superficial vein thrombosis
- AF or cardioversion
- Heart valve replacement
Warfarin
Vitamin K Antagonists
- Inhibit activation of vitamin K dependent clotting factors
- Inhibits conversion of vitamin K to active reduced form (competitive inhibition of VKOR = vitamin K epoxide -> vitamin K)
- Prevents synthesis of clotting factors which require vitamin K:
factors 2, 7, 9 and 10
But delay in onset of action and CYP2C9 polymorphism - BLEEDING – epistaxis and spontaneous retroperitoneal bleeding
- Teratogenic in 1st trimester, haemorrhage risk in 3rd trimester
- Affected by diet (vitamin K rich foods)
LOTS – most increase Warfarin action, but some decrease Warfarin action
- Reduce hepatic metabolism – Amiodarone, Clopidogrel, intoxicating alcohol
- Reduce vitamin K - Cephalosporin
- Displace Warfarin from albumin – NSAIDs
- Accelerate Warfarin metabolism – Barbiturates, Phenytoin, Rifampicin, St Johns Wort
List the following for: DOACs (direct oral anti-coagulants)
- Use
- Example drugs
- Drug class
- Mechanism of action
- Adverse effects
- Warnings / contraindications
- Important drug reactions
Anti-Coagulant
Apixaban
Edoxaban
Rivaroxaban
Dabigatran - direct thrombin inhibitor
DOAC (direct oral anticoagulant)
Direct factor Xa:
- Inhibits both free factor Xa and factor Xa bound with antithrombin-3 (doesn’t affect thrombin)
Direct thrombin - Dabigatran:
- Selective direct competitive inhibition of thrombin, circulating and thrombus bound
- Bleeding – esp. in GI bleed risk groups
- Dabigatran – not for low creatinine clearance (poor renal function)
- Avoid in pregnancy and breastfeeding
CYP inhibitors and inducers
- Increase plasma DOAC – Carbamazepine, Phenytoin and Barbiturates
- Decrease plasma DOAC - Macrolides
List the antidotes for the following drugs:
- Heparins
- Warfarin
- DOACs
Heparins:
Protamine Sulphate
Forms inactive complex with heparin (disassociates heparin from antithrombin-3)
More of an effect with UF than LMWH
Warfarin:
Vitamin K1
DOACs:
- Andexanet (VERY expensive)
- Idarucizumab
