Anticoagulants Flashcards
What is the mechanism of action of Warfarin?
- Inhibits production of Vitamin K dependant clotting factors (2, 7, 9, 10)
- Stop conversion of Vitamin K to active reduced form so extrinsic pathway is affected
Describe the onset and offset of Warfarin?
- Onset is days due to turnover of clotting factors (slow half-life) so heparin is used to cover initially
- Offset is slow as time is required to synthesise new clotting factors
What are the uses of Warfarin?
- DVT
- PE
- Atrial fibrillation
- Mechanical prosthetic valves (high risk)
- Patients with recurrent thromboses on warfarin
- Thrombosis associated with inherited thrombophilia conditions
What are the factors that should be taken into account when starting warfarin?
- Indication
- PMH
- Medications
- Age, Mobility (blood tests and clinics), Falls risk score
- Review blood tests (LFTs, Plt, INR)
- Consider Loading Dose and Heparin cover
- Prescribe (when to start)
What are the side effects of Warfarin?
Bleeding/Bruising
- Intracranial
- Epistaxis
- Injection
- GI loss
How are the effects of Warfarin reversed?
- Parenteral vitamin K which is slow
- Fresh frozen plasma which is fast
Describe the pharmacokinetics of Warfarin?
- Good GI absorption so give orally. Preferred choice for long term anticoagulation
- Dose dependent reduction in Vitamin K dependent factors
- Heavily protein bound so caution with drugs that displace it
How is warfarin metabolised?
- Hepatic metabolism
- Caution with liver disease
- Caution if used with drugs that affect p450 system
What factors need to be taken into account if administering warfarin to pregnant individual?
-Crosses the placenta so do not give during 1st trimester (tetratogenic) and do not give in the 3rd trimester (brain haem)
How is warfarin monitored?
Extrinsic pathway factors
- Prothrombin time: Citrated plasma clotting time after adding calcium and thromboplastins
- I.N.R = International Normalised Ratio (monitoring)
What are the benefits to INR?
- Allows a standard value between labs
- Corrected from different lab thromboplastins reagents
Which drugs act to increase effects of warfarin?
- Inhibition of hepatic metabolism: Amiodarone, Quinolone, Metronidazole, Cimetidine, Ingesting alcohol
- Inhibit platelet function: Aspirin
- Reduce vitamin K from gut bacteria: Cephalosporin Antibiotics
Which drugs act to inhibit the effects of Warfarin?
Induction of hepatic enzymes increasing metabolism of warfarin
- Antiepileptic
- Rifampicin
- St John’s Wort
What are some features of heparin?
- Glycosaminoglycan
- One of 5 different groups on each glucose, some with sulphate. Produced by mast cells
What are the types of heparin?
- Unfractionated heparin
- Low molecular weight heparins