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what is the MOA for heparin?
it has a pentasaccharide sequence which potentiates the action of antithrombin III: that INACTIVATES IIa and Xa
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what is heparin used for?
- rapid initiation of anticoagulation needed
- used to maintain anticoag until warfarin is EFFECTIVE (NB warf takes time)
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what type of anticoagulation is used in pregnancy and why?
heparin (LMWH) and not warfarin as warfarin is teratogenic
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when is UFH used over LMWH?
used as a 'bridging anticoagulation' in patients with mechanical heart valves who are having non cardiac surgery and their warfarin is stopped for this
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what is the MOA of warfarin?
inhibits vitamin K epoxide reductase: so inhibits vit K dependent gamma carboxylation of factors 2, 7, 9, 10
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what is the half life of warfarin?
prolonged, reflecting the half life of the factors
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what is the duration of warfarin therapy and INR target for 1st DVT/PE?
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what is the duration of warfarin therapy and INR target for 2nd DVT/PE?
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what is the duration of warfarin therapy and INR target for DVT/PE whilst on warfarin?
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what is the duration of warfarin therapy and INR target for AF pericardioversion
- 6 weeks before and after
- INR: >2.0
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what is the duration of warfarin therapy and INR target for AF?
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what is the duration of warfarin therapy and INR target for mechanical valves?
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name 4 absolute contraindications to warfarin?
- 1. active bleeding
- 2. bleeding disorder
- 3. pregnancy: esp. 1st trimester and last 4 weeks
- 4. surgery for SOL in CNS
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name 5 relative contraindications to warfarin?
- 1. history of bleed e.g. from ulcer
- 2. pregnancy
- 3. uncontrolled hypertension
- 4. high risk of head injury: epilepsy/falls (esp. elderly)
- 5. poor compliance e.g. IVDU
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what are the pharmacokinetic interactions of warfarin in the gut, with which drug and what are the effects on warfarin handling?
- cholestyramine
- decreased absorption of warfarin so less effect
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what are the pharmacokinetic interactions of warfarin in the liver, with which drug and what are the effects on warfarin handling?
- rifampicin and carbamazepine: increase warfarin metabolism so less warf effect
- amiodarone and erythromycin: decrease warfarin metabolism so more warf effect
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how is warfarin initiated and monitored?
- loading dose often used for day1 and 2
- dose adjustment according to INR which is measured daily for 4-5days
- once got stable dose, monitor every 2-12 weeks
- can get home testing of INR
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in the case of over anticoagulation, what is to be done?
- DO NOT GIVE VIT K immediately! because it may be difficult to re-anticoag for a week or 2!
- only give vitK if major active bleed: 0.5-1mg
- normally if over anticoag give: PCC (prothrombin complex concentrate) or FFP
- this reverses warfarin effect RAPIDLY but TRANSIENTLY
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name 3 uses of thrombolysis and the treatment regimen for each
- 1. acute STEMI: pt within 12 h onset chest pain with STE/new LBBB and no contraindications
- Rx: streptokinase or alteplase (tPA)
- 2. acute ischaemic stroke: present within 3h onset of symptoms, ICH excluded on imaging and no CI
- Rx: tPA (not streptokinase)
- 3. major PE with haemodynamic disturbance (drop BP)
- Rx: tPA/streptokinase but lower dose than STEMI
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what is the main difference between tPA and streptokinase?
- tPA is clot selective as it activates plasminogen BOUND to fibrin
- whereas streptokinase binds BOTH free and bound plasminogen
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what is streptokinase made from and what are the possible consequences?
- B haemolytic strep
- so antistrep Ab will neutralise it!
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