S10) Anti-Coagulant and Anti-Platelet Therapy Flashcards
What is warfarin’s mechanism of action?
Warfarin inhibits the production of Vitamin K dependent clotting factors by stopping the conversion of Vit K to active reduced form
Warfarin is the preferred drug choice for long term anti-coagulation.
How is warfarin administered?
Orally – due to good GI absorption
Briefly, describe the pharmacokinetics of warfarin
- Slow onset of action (needs Heparin initially)
- Slow offset (t1/2 48 hrs)
- Heavily protein bound
How is warfarin metabolised and what is the clinical significance of this?
Mixed function Oxidase cytochrome p450 system:
- Caution with liver disease
- Caution if used with drugs that affect p450 system
Warfarin crosses the placenta.
What is the clinical signicance of this?
- Do not give in 1st Trimester → Teratogenic
- Do not give in 3rd Trimester → Brain Haem
How can one monitor the effects of warfarin?
- Extrinsic Pathway Factors
- Prothrombin Time
- INR (International Normalised Ratio)
Provide some examples of drugs which potentiate the actions of warfarin
- Amiodarone, quinolone, metronidazole – inhibit hepatic metabolism
- Aspirin – inhibit platelet function
- Cephalosporin antibiotics – reduce Vitamin K from gut bacteria
Provide some examples of drugs which inhibit the actions of warfarin
Inducing hepatic enzymes, thus increasing metabolism of warfarin:
- Anti-epileptics (except Na+ valproate)
- Rifampicin
- St Johns Wort
What are the usual indications for warfarin?
- DVT (3-6 months)
- PE (6 Months)
- Atrial fibrillation (Until risk > benefit)
What are the adverse drug reactions of warfarin?
- Teratogenic
- Bleeding/bruising (intracranial, epistaxis, injection, GI loss)
In seven steps, describe the clinical approach one takes before prescribing warfarin
⇒ Indication
⇒ PMH e.g PUD, SAH, bleeding disorder
⇒ Medications (interactions)
⇒ Age, Mobility (blood tests and clinics)
⇒ Review blood tests (LFTs, Plt, INR),
⇒ Consider loading dose and heparin cover
⇒ Prescribe
How does one manage a patient on warfarin with increasing INR levels of 3.0 < INR < 6.0 (no bleeding)?
- Reduce warfarin dose and stop
- Restart warfarin when INR < 5.0
How does one manage a patient on warfarin with increasing INR levels of 6.0 < INR < 8.0 (no bleeding / minor bleeding)?
- Stop warfarin
- Restart warfarin when INR < 5.0
How does one manage a patient on warfarin with increasing INR levels of INR > 8.0 (no bleeding / minor bleeding)?
- Stop warfarin
- Restart warfarin when INR < 5.0
- If other risk factors for bleeding, give patient oral Vitamin K
How does one manage a patient on warfarin who experiences major bleeding?
- Stop warfarin
- Give prothrombin complex
- Give oral Vitamin K