what is the MOA for heparin?
it has a pentasaccharide sequence which potentiates the action of antithrombin III: that INACTIVATES IIa and Xa
what is heparin used for?
- rapid initiation of anticoagulation needed
- used to maintain anticoag until warfarin is EFFECTIVE (NB warf takes time)
what type of anticoagulation is used in pregnancy and why?
heparin (LMWH) and not warfarin as warfarin is teratogenic
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
what is the MOA of warfarin?
inhibits vitamin K epoxide reductase: so inhibits vit K dependent gamma carboxylation of factors 2, 7, 9, 10
what is the half life of warfarin?
prolonged, reflecting the half life of the factors
what is the duration of warfarin therapy and INR target for 1st DVT/PE?
what is the duration of warfarin therapy and INR target for 2nd DVT/PE?
what is the duration of warfarin therapy and INR target for DVT/PE whilst on warfarin?
what is the duration of warfarin therapy and INR target for AF pericardioversion
- 6 weeks before and after
- INR: >2.0
what is the duration of warfarin therapy and INR target for AF?
what is the duration of warfarin therapy and INR target for mechanical valves?
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
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
what are the pharmacokinetic interactions of warfarin in the gut, with which drug and what are the effects on warfarin handling?
- decreased absorption of warfarin so less effect
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
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
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
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
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
what is streptokinase made from and what are the possible consequences?
- B haemolytic strep
- so antistrep Ab will neutralise it!