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Cardio 1: Anti-Coagulants
Warfarin (Coumadin)
11
Medical
Graduate
10/04/2013

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Term
Warfarin MOA
Definition
  • Inhibits vitamin-K reduction after its oxidation by inhibiting the enzyme epoxide reductase 
  • This inhibits blood clotting by interfering with hepatic synthesis of vitamin K-dependent clotting factors II (prothrombin), VII, IX, and X, and anti-coagulation proteins C and S
  • Has NO in-vitro anticoagulant effects like heparin
  • Warfarin is an anti-coagulant!!!
Term
Vitamin K-dependent mechanisms
Definition
  • Vitamin-K is activated in the liver by a cycle of oxidation+ reduction to form active vitamin-K 
  • Vitamin-K convert glumatic acid residues in clotting factors II, VII, IX, and X to gamma-carboxygluatmic acid residues
  • Gamma-carboxygluatmic acid has a high affinity for Ca++ and phospholipid
Term

Pharmacokinetics of warfarin 

Onset

Absorption

Duration

Termination

Definition
  • Onset:  Considerably delayed (36-72 hours). Because the shortest half-life of clotting factors is 6 hours (for factor VII)
  • Absorption:  Completely absorbed in the GI tract and HIGHLY fat soluble. 99% is bound to albumin (really well known interaction) 
  • Duration:  Prolonged with a high-life of 36 hours 
  • Termination:  There is slow drug elimination rate so delayed elimination.  Also prothrombin + other factors need to be synthesized (which takes time).  Warfarin is inactivated to a metabolite form in the liver + kidney.  Elimated via stool + urine.  
Term
Warfarin toxicity
Definition
  • Hemorrhage
  • Anorexia/nausea/vomitting/diarrhea 
  • Cutaneous lesions:  

          Skin necrosis

          Dermatitis

          Alopecia

          Purpura 

Term
Warfarin contraindications
Definition
  • Same as heparin but also includes pregnancy + unrealiable patients 
  • Recent eye/brain/spinal cord surgery 
  • Head injury 
  • Uncontrolled bleeding 
  • Severe HTN (high risk for bleeding)
  • Suspected aneurysm (high risk for bleeding) 
Term
Warfarin Indications
Definition
  • General:  Hospitals start patients on heparin in the hospital and follow with warfarin for long-term therapy
  • DVT 
  • PE
  • A. Fib (ONLY in older patients)
  • MI (prevent mural thrombosis + systemic embolism)
  • Rheumatic heart disease (b/c risk of embolism) 
  • Mechanical prosthetic valve/bioprosthetic mitral valve  
Term
Why can you not use warfarin in younger patients who have A. Fib?
Definition

Risk of warfarin toxicity if used over long periods outweights the beneficial effects of using warfarin in younger patients 

Term

Warfarin ROA 

Factors influencing warfarin treatment?

Definition
  • ONLY given orally
  • There are many factors that influence the effectiveness of warfarin:  

          -Differences in absorption

          -Sensitivity to drug

          -Elimination

          -Drug-drug interactions (there are LOTS of these)

          -Age/clinical state/dietary intake of vitamin K/Dietary intake of              fat/presence of vitamin-K synthesizing microflora  

Term
How is warfarin monitored?
Definition
  • Warfarin is monitoried during INR (PT-test)
  • This should be determined BEFORE starting dose and then daily until response is stabilized.  And then weekly until maintenace dose is established
Term
What is the target range for warfarin therapy in terms of INR?
Definition

INR = 2.0-3.0 is the usual target for less intense therapy

This causes a 2X or 3X of the normal clotthing time

Term
How is warfarin OD treated?
Definition
  • Effects can be reversed by:
  1. Withdrawel of the drug (but remember there is a prolonged elimination of the drug)
  2. Administration of vitamin K1 
  3. If necessary, infusion of fresh-frozen plasma or plasma rich in factors II, VII, IX, and X 
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