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2010-09-27 19:11:45

Chapter 51
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  1. hemostasis
    • 1) formation of a platelet plug
    • 2) reinforcement of the platelet plug with fibrin.

    *response to blood vessel injury.
  2. Contact (intrinsic) vs. Tissue Factor (extrinsic) Cascade
    • intrinsic - can be altered by heparin and warfarin, has more steps
    • extrinsic - only altered by warfarin

    *both lead to formation of Xa and from there follow the same path.
  3. Thrombosis
    a clot formed in a blood vessel or the heart.

    *pathologic function of hemostasis
  4. heparin sources
    mostly cow lung and pig intestine
  5. heparin mechanism of action
    helps antithrombin inactivate clotting factors thrombin and Xa. This inhibits the formation of fibrin in veins, preventing venous thrombosis. Quick acting after injection (highly polar, not good for PO).
  6. heparin pharmacokinetics
    • absorption - large and polar, must be given IV or subQ, no risk to breast-milk or baby
    • protein and tissue binding - nonspecific binding to protein and cells, levels of free drug highly variable, need close monitoring
    • metabolism/excretion - hepatic metabolism, renal excretion, half-life increased in liver or renal pts.
  7. adverse effects of heparin
    hemorrhage is the main one. Pts should be monitored closely for signs of bleeding and PTT should be maintained at no more than 2x control. Overdose treated with protamine sulfate.
  8. heparin drug interaction
    use in caution with anti-platelet drugs because platelet aggregation is the last remaining defense against hemorrhage.
  9. Contraindications for heparin
    Pts with thrombocytopenia and bleeding tendencies, during and after eye, brain or spinal cord surgery. Pts getting lumbar puncture.
  10. Warfarin and heparin used together
    Warfarin is usually started 3-5 days before discharge and heparin in continued to bridge the gap until warfarin reaches therapeutic range.
  11. monitoring heparin
    aPTT is the test most often employed. normal is 40 seconds. Dose should be adjusted so aPTT is 1.5 to 2 times normal. Initally test every 4-6 hours until dose is correct, then daily.
  12. unfract vs LMW heparins
    LMW heparins don't require monitoring of aPTT and dose is fixed. Can be given at home. High bioavailability so longer half-live, more stable blood levels.
  13. Warfarin uses, contraindications
    • Long-term prophylaxis of thrombosis (prosthetic heart valves, atrial fibrilllation, DVT).
    • Do not give to pregnant/lactation, CAT X! Careful with bleeders, vit K deficiency, liver disease, alcoholism
  14. warfarin mechanism of action
    warfarin inhibits conversion of Vit K to the active form. It takes up to 5 days for full therapeutic effect because all of the existing clotting factor in the body has to be depleted before effects will be seen. Factor II and X take the longest, these are the last steps in the clotting chain.
  15. warfarin kinetics
    • rapid absorption, 99% protein bound, free drug crosses placenta and breastmilk, inactivated by
    • 2C9 of P450.
  16. Protein binding and liver metabolism
    The high protein binding of warfarin means that hypoalbuminemia can increase drug levels. Competition for binding sites can alter drug levels as well. liver disease or drugs that inhibit/enhance P450 can alter drug levels. BE VERY CAREFUL!!!
  17. drug-drug interactions with warfarin
    heparin obviously, aspirin can incr bleeding and cause GI ulcers...bad, acetaminophen inhibits warfarin metabolism and incr levels. Inhibit - phenobarb, Vit K, rifampin. Increase - aspirin, cimetidine
  18. herb/vitamin interactions with warfarin
    • Increase - caffiene, cranberry/grapefruit juice, ginger, Vit A and E, fish oil
    • Decrease - Ginseng, Green tea, Soy, Spinach,Vitamins C & K
  19. drug-food interactions with warfarin
    green leafy vegetables are high in vit K, watch out for grapefruit juice
  20. warfarin overdose
    excessive bleeding, purple toe syndrome, leukopenia, agranulocytosis. Hold dose for 1-2 days then start back lower. If needed admin Vit K.
  21. warfarin monitoring
    PT is the test but isn't standardized so INR also run. Should be run daily x5, then 2x a week for several, then weekly for a few months, then every two to four weeks. And always after dosage change or change in other meds.
  22. warfarin for kids
    dosage is individualized based on weight. Use in extreme caution in neonates due to low Vit K levels.
  23. warfarin for pregos?
    NOOOOO! use LMW heparins until pregnancy is over.
  24. antiplatelet therapy
    primarily used to prevent platelet aggregation in arteries. Used a lot in people with CAD and the like.
  25. Aspirin (salicylates)
    suppresses platelet aggregation by causing irreversible inhibition of cyclooxygenase (and at higher doses prostacyclin); reduces risk of death from MI, stroke; major adverse effect is GI bleeding; Category D
  26. ADP Inhibitors (Plavix, Ticlid)
    cause irreversible blockade of ADP receptors on platelet surface; prevention of or after recent stroke; GI complaints most common; Category B
  27. Glycoprotein Receptor Antagonists
    reversible blockade of GP receptors that is the last step in aggregation; most effective antiplatelets but expensive; bleeding is the major side effect. category B