Anti-coagulation drugs Flashcards
MoA of warfarin
Competitively inhibits reduction of oxidised vitamin K to prevent synthesis of factors 2,7,9,10
Why can increasing vitamin K reverse warfarin
Warfarin is a competitive inhibitor so increasing vitamin K counteracts warfarin action
Indications for warfarin and target INR for each
2-3 for DVT, PE, AF, stroke
2.5-4.5 for mechanical heart valves, thrombophilia
Consequences of warfarin onset and offset speed
Slow onset so need initial heparin cover
Slow offset so should stop 3-5 days before surgery
Consequences of warfarin use in pregnancy
Early - teratogenic
Late - brain haemorrhage
Warfarin potentiators and their MoA
i.e things which will raise INR
CYP450 inhibitors - amiodarone, quinolone, cemetidine, alcohol, metronidazole
Platelet inhibitors - aspirin
Displace protein bound warfarin - NSAIDs
Decrease vitamin K from gut flora - cephalosporin
Warfarin inhibitors and their MoA
i.e things that will decrease INR
CYP450 inducers - rifampicin, St. John’s wort, anti epileptics
What should be considered before initiating warfarin treatment
Falls risk score INR LFT Platelets Drug history Compliance likely?
What needs monitoring in warfarin therapy
INR
Prothrombin time
People with thyroid disease need close monitoring
Side effects of warfarin
Bruising
Bleeding - intracranial, GI, epistaxis
Warfarin reversal protocol for different INR ranges
INR 4-8 with no bleeding: withhold 1 or 2 doses of warfarin
INR 4-8 with minor bleeding or INR >8 with no bleeding: stop warfarin and give oral vitamin K
INR >8 with minor bleeding: stop warfarin and give IV vitamin K
Major bleeding: stop warfarin, give IV vitamin K, give prothrombin complex concentrate
Need cardiology advice if patient has mechanical valve
Action of heparin
Activates antithrombin-III which inhibits thrombin and factors 9,10,11,12
Differences between types of heparin drugs MoA
Explain why this is the case
Unfractionated - inhibits thrombin and factor Xa
Low molecular weight - only inhibits factor Xa
Inhibition of thrombin by AT-III requires heparin and thrombin to bind simultaneously, only unfractionated heparin is large enough
Route of heparin administration
Parenterally as poor GI absorption
Dose response of heparin drugs
Unfractionated - non linear
Low molecular weight - predictable
