Anti thrombotic drugs Flashcards
COAGULATION CASCADE
i) which pathway is the tissue factor pathway? what does tissue factor do?
ii) what is factor X, V, Calcium and phospholipase known as?
iii) what converts fibrogen to fibrin?
iv) which two things does anti thrombin inhibit?
v) what do protein C and protein S do?
i) tissue factor = extrinsic pathway
- potent pro coagulant
ii) prothrombinase
iii) thrombin converts fibrinogen to fibrin
iv) anti thrombin inhibits thrombin and factor Xa
v) protein C and S - naturally occuring anti coagulants
WARFARIN
i) what does it antagonise? by what mechanism does it do this?
ii) which pathway in the coag cascade does it prolong?
iii) how are levels monitored?
iv) what is the target for DVT/PE/AF?
v) what is target for VTE or metal heart valves
i) antag vitamin K
- no vit K means it prevents gamma carboxylation of factors II,VII,IX,X (important step in maturation) > inhib cascade
ii) prolongs extrinsic pathway (PT)
iii) monitored by INR
iv) target INR is 2.5 for PE,DVT
v0 target INR is 3.5 for VTE, metal heart valves
METABOLISM OF WARFARIN
i) which mechanism is it metab by?
ii) how does it work?
iii) how many days can it take to reach therapeutic levels? why?
iv) name two naturally occuring things that warfarin also inhibits?
i) metab by P450/CYP2C9 mech
ii) works by blocking vitamin K epoxide reductase (reduces vit K to version that can mature coag factors) therefore cant gamma carbox vit K dep coag factors
iii) can take 3 days to reach therapeutic levels as the half life of factor II can be 60 hours (longest)
iv) warfarin also inhibits natural anti-coags eg protein C and S
PRESCRIBING WARFARIN
i) what should patients be loaded with? why?
ii) what is the typical loading regime? in which group may this be reduced in?
iii) which organ metabolises it?
iv) what should INR be? how is this ensured
v) what is target INR in DVT, PE, AF? what about reccurent DVT on warfarin, mech heart valves?
i) load with LMW heparin cover as there will be an early fall in protein C and S (due to warfarin inhibiting these) therefore initial pro coagulant state
ii) 10mg, 10mg, 5mg
- may need to be reduced in elderly
iii) metab by liver
iv) need to continue heparin until INR is >2 for 2 consecutive days
v) 2.5 and 3.5
WARFARIN INTERACTIONS
i) why does it have lots of drug interactions?
ii) what effect can binge drinking have on warfarin? what effect does chronic alcoholism have?
iii) name four others factors that can affect warfarin
i) it is metabolised by the cytochrome P450 mech (CYPs)
- enzyme inhibitors can potentiate and inducers can inhibit
ii) binge drinking > potentiates
chronic drinking > inhibits warfarin
iii) also affected by binding to albumin, abs of vit K through GI tract, synth of vit K factor by liver and hereditary resistance
WARFARIN INTERACTIONS CONT
i) name two drugs that depress the action of warfarin
ii) which drug can enhance synthesis of clotting factors?
iii) is warfarin contraindicated in pregnancy
iv) name three drugs that increase action of warfarin
v) why does liver disease increase effect of warfarin?
i) barbiturates and rifampicin
ii) oral contraceptive can enhance clotting factors
iii) yes it is teratogenic
iv) allopurinol, tricyclics, thyroxine, metronidazole
v) liver disease decreases synthesis of vitamin K factors therefore potentiates warfarin effects
SIDE EFFECTS/REVERSAL OF WARFARIN
i) what should be used in pregnancy?
ii) name three other side effects
iii) what should be given in a life threatening bleed?
iv) why is giving vitamin K not much use in an emergency?
v) name one other things that can be given to reverse warfarin
i) LMW heparin
ii) significant haemorrhage risk, minor bleeding, skin necrosis, alopecia
iii) life threat bleed > give activatd prothrombin complex (octaplex)
iv) vit K will reverse INR in 6-12 hrs and patient can become refractory to re loading with warfarin
v) FFP because it contains clotting factors
HEPARIN
i) how does it work?
ii) which two factors does it inactivate?
iii) how is each type admin?
iv) is it safe in pregnancy?
i) mucopolysachhaaride that potentiates anti thrombin (a natural anticoag)
ii) inactivaates factor IIa (thrombin) and factor Xa - irreversibly
iii) unfractionated given by IV infusion
LMW given as SC injection
iv) yes
UNFRACTIONATED HEPARIN
i) why is it not often used?
ii) how is it monitored?
iii) is it safe in renal failure? why?
iv) what can be given to partially reverse heparin if the patient is bleeding?
v) what is a rare complication of heparin use? how is it detected? what happens and how is it rectified?
i) inconvenince of admin (given as bolus then infusion)
ii) monitor by APTT ratio with target 2x normal
iii) yes safe in renal fail as it is metab by the liver
iv) give protamine sulphate
v) heparin induced thrombocytopenia (HIT)
- suspect if plat count falls on heparin
- pro thrombotic condition that can causee VTE
- dx by HIT screen > use alternate anti coag
LMW HEPARIN
i) why is it convenient to use? what is it prescribed according to?
ii) what organ function must be good for LMW to be used?
iii) name three formulations
iv) what can it be used for in hospital patients?
i) convenient as once daily SC injections
ii) need good renal func - creatinine clearance >30ml/min
iii) tinzaparin, enoxaparin, dalteparin
iv) can be used for thromboprophylaxis or for treatment
OTHER PARENTERAL ANTICOAGULANTS
i) name a direct thrombin inhibitor? when may it be used?
i) argatroban - used in place of heparin in patients witth HIT
DIRECT ORAL ANTICOAGULANTS
i) does it require monitoring? how is it dosed?
ii) what are the two types? give an example of each
iii) are they as effective or less effective than warfarin/LMW hep in VTE and AF?
iv) is it suitable for use in cardiac valves?
i) no - flat dosing
ii) direct thrombin (IIa) inhibitor eg dabigatran
direct factor Xa inhibitor eg rivaroxaban, apixaban
iii) non inferiority of DOACs in VTE and AF
iv) should not be used in cardiac valves as it is inferior to warfarin
RIVAROXABAN/APIXABAN
i) how often per day is riv given?
ii) how often per day is apix given? why?
iii) give three indications
i) riv is given once a day
ii) apix is given twice daily due to lower half life
iii) VTE prophylaxis, DVT/PE tx, stroke prevention in AF
DABIGATRAN
i) what is it?
ii) give three indications
iii) what reverses it?
i) direct thrombin inhibitor
ii) VTW prophylaxis, tx of DVT and PE, AF
iii) reversed by praxbind (idarucizumab) - MAB that binds the drug is the patient is bleeding
REVERSAL OF DOACS
i) which two are difficult to reverse?
ii) what can be given to functionally improve a coagulopathy?
iii) what anti fibrinolytic agent can be given to prevent clot breakdown
iv) what can be given in a life threat GI bleed? (expensive)
v) how can dabigatran be reversed
i) riv and apix
ii) give octaplex or FFP/cryoppt
iii) tranexamic acid
iv) adexanent alfa (recombinant Xa)
v) praxbind
