Anticoagulants Flashcards
Unfractioned heparin
Indication: anticoagulation
- moderate renal imapairment and v.fine control
Route:
- i.v bolus and infusion
- s.c for prophylaxis but low bioavailability
Action:
- binds to ATIII causing conformational change and increased activity
- needs to simultaneously bind to ATIII and IIa
- Xa inhibition only needs ATIII binding
Adverse effects:
- bruising/bleeding (intracranial,site of injection,GI,epistaxis)
- heparin induced thrombocytopenia (higher risk)
- hyperkalamia - inhibition of aldosterone secretion
- osteoporosis - rare (higher risk)
Warnings:
- clotting disorders
Interactions:
- other antithrombotic drugs
- ACEi/ARB, amiloride, spironolactone - hyperkalaemia
Other:
- fast onset
- mixed elimination - 1/2 life 30 mins low dose, 2h at high
- unpredictable dose response - binds to endothelial cells, plasma proteins and macrophages
Dalteparin/enoxaparin
Indication: anticoagulant
- perioperative prophylaxis of venous thromboembolism
- pregnancy - large size does not cross the placenta
- long term/cancer related VTE (DVT/PE)
- ACS - PCI, reduce recurrence of coronary artery thrombosis post STEMI/NSTEMI
Class: LMWH
Route: almost always s.c
Action: inhibition of Xa specifically by enhancing ATIII activity
(Not long enough to inactivate thrombin IIa)
Adverse effects:
- bruising/bleeding (intracranial,site of injection,GI,epistaxis)
- heparin induced thrombocytopenia (lower risk)
- hyperkalamia - inhibition of aldosterone secretion
- osteoporosis - rare (lower risk)
Warnings:
- clotting disorders
- RENAL IMPAIRMENT
Interactions:
- other antithrombotic drugs
- ACEi/ARB, amiloride, spironolactone - hyperkalaemia
Other:
- more predictable dose response - does not bind to endothelial cells, plasma proteins and macrophages (isnt long enough)
- 90% bioavailibility
- longer half life - 2+ hrs
UFH vs LMWH
Dose response: non linear vs predictable
Bioavailibility: s.c variable around 30% vs predictable 90%
Metabolism: dose dependant (protein binding, depolymerisation, desulfation) vs rapid liver or slower renal excretion
Monitoring: unpredictable (aPTT) vs no monitoring
Administration: i.v.i vs s.c
Initiation: i.v bolus then i.v.i vs OD/BD s.c
Half life: 30min low dose, 2hr high dose vs 2+ hrs
Action: i.v infusion fast anticoagulation vs s.c slower onset
Use: moderate renal impairement and v.fine control vs most situations
Fondaparinux
Indication: anticoagulation
Class: SYNTHETIC pentasaccharide
Action: selectively inhibits Xa by enhancing ATIII
route: s.c
Adverse effects:
- bruising/bleeding (intracranial,site of injection,GI,epistaxis)
- heparin induced thrombocytopenia (lower risk)
- hyperkalamia - inhibition of aldosterone secretion
- osteoporosis - rare (lower risk)
Warnings:
- clotting disorders
- RENAL IMPAIRMENT
Interactions:
- other antithrombotic drugs
- ACEi/ARB, amiloride, spironolactone - hyperkalaemia
Other: Half life 18hr
Protamine sulphate
Indication: heparin reversal
Action:
- forms inactive complex with heparin
- dissociates heparin from ATIII
- irreversible binding
Other:
- greater effect on UFH than LMWH
- no effect on fondaparinux
Warfarin
Indication: longer term anticoagulation
- VTE (DVT,PE)
- AF with high risk of stroke
- heart valve replacment
Class: vitamin K antagonist
Action:
- competitive inhibition of VKOR
- inhibits conversion of vitamin k to active reduced form
- stop hepatic synthesis of factors II, VII, IX, X
Pharmacokinetics:
- 95% oral availability - good GI absoprtion
- CYP2C9 polymorphisms cause interindividual variability
- mixture or R and S enantiomers - different potency and metabolism
- response affcted by CYP2C9, vitamin K inatke, alcohol
Adverse effects:
- bleeding (epistaxis and spontaneous retroperitoneal)
Warnings:
- pregnancy - crosses the placenta (1st trimester tetragoneic, 3rd trimester haemorrhage)
- hepatic disease
Interaction:
- amiodarone, clopidogrel - CYP2C9 inhibtion - increase warfarin - increase INR
- barbituates, st jhons wart, rifampicin, phenytoin - CYP2C9 inducers - decrease warfarin - decrease INR
- cephalosprin antibiotics - reduce vitamin K by eliminating gut bacteria
- NSAIDs - displacement of warfarin from plasma albumin (increase INR)
- drugs that decrease GI absoprtion of vitamin K (increase INR)
Other:
- slow onset - circulating active clotting factors present for several days so must be cleared and replaced with non-carbocylated forms (use heparin if anticoagulation needed immediately)
- half life 36-48 hr
- antidote = prothrombin complex concentrate i.v
Apixaban/edoxaban/rivaroxaban
Indication: anticoagulant
Class: DOAC
Action: Inhibit both free Xa and that bound with ATIII, do not directly effect thrombin (IIa)
Route: oral
Adverse effects: bleeding
Warnings:
- VERY LOW creatinine clearance (<15ml/min)
- pregnancy and breastfeeding
Interactions: less frequent than warfarin
- affected by CYP inhibitors and inducers
- carbamazepine,phenytoin,barbituates decrease [plasma]
- macrolides increase [plasma]
Other: andexanet and idarucizumab antidotes
Dabigatran
Indication: anticoagulant
Class: DOAC
Action: Selective direct competitive thrombin inhibitor, both circulating and thrombus bound IIa
Route: oral
Adverse effects: bleeding
Warnings:
- LOW creatinine clearance (<30ml/min)
- pregnancy and breastfeeding
Interactions: less frequent than warfarin
- affected by CYP inhibitors and inducers
- carbamazepine,phenytoin,barbituates decrease [plasma]
- macrolides increase [plasma]
Other: andexanet and idarucizumab antidotes
