Anticoagulants/Antiplatelets Flashcards
Warfarin is metabolised how?
Hepatic metabolism- by CYP450 enzyme
What is Warfarins distribution once absorbed?
Heavily protein bound to albumin 99%
What drugs would increase the conc of warfarin in the blood? (2 mechanisms)
By displacing warfarin bound to albumin- NSAIDs
By inhibiting CYP450- cimetidine, amiodarone, alcohol, metronidazole
How long is Warfarins onset of action?
Slow and so may need heparin to cover initially
How fast or slow is Warfarins offset?
Half life ~48 hrs
Therefore need to stop 3 days prior to surgery to allow for making of new clotting factors
Side effects of Warfarin
Bleeding, epistaxis, GI bleeding, intracranial
How can you reverse warfarin?
Parenteral vitamin K (acts slowly)
Fresh frozen plasma (acts quickly)
Can also give Prothrombin Complex Concentrate (ii, ix, x)
What cautions do you need to be wary of with warfarin?
Teratogenic in 1st trimester
Can cause brain haemorrhage in 3rd trimester
What is INR?
Patients prothrombin time OVER average prothrombin time
Which common drugs should be avoided in warfarin use?
Antiepileptics
St Johns Wort
Rifampicin
(All induce hepatic enzymes)
Mechanism of action of warfarin?
Vitamin K antagonist.
Vitamin K is needed for the production of active factors II, VII, IX, X
What is Virchow triad?
Hypercoaguability
Blood stasis
Endothelial damage
Mechanism of action of heparin
Binds reversibly to anti-thrombin therefore
Almost instant inactivation of factors IIa, Xa
Therefore prevents progression of existing clots
Name two examples of a LMWH
Dalteparin
Enoxaparin
Give three advantages of LMWH over unfractionated
Absorbed better/better absorption predictability Higher bioavailability (90%) More predictable dose response curve
Name three negatives of unfractionated heparin
Non linear dose response curve
Poor absorption from gut therefore needs to be IV or SC
Can’t be eliminated in haemodialysis
Name three adverse drug reCtions of unfractionated heparin
Bruising/bleeding
Osteoporosis
Thrombocytopenia (immune phenomenon)
How can you reverse heparin?
Stop the heparin asap
Use Protamine Sulfate (dissociates the heparin from the antithrombin)
Name an advantage of LMWH over warfarin
Is safe to use in pregnancy
Name three DOACs
Rivoroxaban
Apixaban
Dabigatran
What is the mechanism of action of Rivoroxaban
Competitive antagonist of factor Xa
What is the mechanism of action of Dabigatran
Competitive antagonist of Thrombin
Name a positive of DOACs
No monitoring required
No antidote available
Have more predictable pharmacokinetics
Name one drug you should avoid while taking Dabigatran
PPI
they reduce absorption
How are DOACs excreted?
Renal
Therefore in renal exposure, you will get increased drug exposure
Name three anti-platelet drugs
Aspirin
Clopidogrel
Dipyridamole
Mechanism of action of aspirin
Irreversibly binds to COX enzyme
COX produces pro-inflammatory prostaglandins and thromboxanes
Thromboxanes facilitate platelet aggregation
Side effects of aspirin
Bronchospasm
GI upset
Hypersensitivity reactions
Contraindications of aspirin
Asthma
Peptic ulcer
If pt has hypersensitivity to NSAID
Mechanism of action of clopidogrel
Prevents binding of ADP to platelet receptor which stops the cross linking of fibrin
How is clopidogrel metabolised?
Clopidogrel is a pro drug that is metabolised by CYP450 to become active.
Then metabolised by the liver
Side effects of clopidogrel
Abdo pain
Diarrhoea
Dyspepsia
Bleeding disorder
How is clopidogrel excreted
50% renal, 50% excreted
What is the half life of aspirin
15 minutes but then increases as the dose increases
Mechanism of action of dipyridamole
Adjunct to other antiplatelets
Phsophodiesterase inhibitor, prevents breakdown of cAMP, cAMP usually inhibits platelet function.
Metabolism of dipyridamole
Hepatic and excreted with bile
Side effect of dipyridamole
Positive inotrope and vasodilator(tf flushing and headaches)
