Anticlotting agents

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Anticlotting agents
2012-04-11 16:12:05

drugs that prevent clots
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  1. Heparin
    • increase activity of antithrombinIII --> inactivate thrombin and Xa
    • Water soluable therefore acts in seconds, given IV, shorter half life
    • Used acutely (days)
    • Follow PTT (intrinsic pathway)
    • anticoagulate both vitro and vivo
    • Protamine sulfate (+ charged binds -ly chg heparin) reverses heparin
    • Used in pregnancy
    • Bleeding, osteoporosis, Heparin-induced thrombocytopenia (HIT)- heparin binds to platelet factor IV, causing antibody production that binds to and activates platelets leading to their clearance and resulting in a thrombocytopenic hypercoagulable state

    Newer low-molecular weight heparins (enoxaparin) act more on Xa. have better bioavailability and 2-4 times longer t1/2. can be administered subcutaneously and w/out laboratory monitoring. Not easily reversible.
  2. Lepirudin, bivalirudin
    • Hirudin (leeches) derivatives
    • directly inhibit thrombin
    • alternative to heparin for anticoagulating patients w/ HIT
  3. Warfarin (Coumadin)
    • lipid soluble therefore given orally, have high plasma binding, takes 2-5days to fully work (t1/2 of normal clotting factors), have longer half life, crosses placenta
    • doesn't inhibit coagulation in vitro
    • interferes w/ normal synthesis and gamma-carboxylation of vit K- dependent clotting factors II, VII, IX and X and protein C and S.
    • Metabolized by P-450 pathway
    • PT monitor
    • fresh frozen plasma (fast) and vitK (overtime) for reversal
    • Toxicity: skin/tissue necrosis- due to dec in protein C production. given w/ heparin initially to prevent this SE.
  4. Thrombolytics (covert plasminogen --> plasmin)
    Streptokinase, urokinase, tPA (alteplase) APSAC (anistreplase)
    • used in early MI, early ischemis stroke (best if used w/in first 3 hrs)
    • tPA covert fibrin-bound plasminogen thus targeting clots; others are not clot specific
    • inc PT, PTT and no change in platelet count
    • Aminocaproic acid reverses the toxicity
  5. Aspirin
    • acetylates and irreversibly inhibits cyclooxygenase (both COX1 and COX2) to prevent conversion of arachidonic acid to thromboxane A2 (TXA2) <--responsible for platelet aggregation
    • inc bleeding time, no effect on PTT or PT
    • Toxicity: gastric ulceration, bleeding, hyperventilation, Reye's syndrome, tinnitus (CN VIII)
  6. Clopidogrel, ticlopidine
    • inhibit platelet aggregation by irreversibly blocking ADP receptors. inhibit fibrinogen binding by preventing glycoprotein IIb/IIIa expression
    • Toxicity: neutropenia (ticlopidine)
  7. Cilostazol, dipyridamole
    • inhibit phosphodiesterase III enzyme that degrade cAMP (inhibit platelet aggregation, vasodilator)
    • Toxicity: nausea, headache, facial flushing, hypotension, abdominal pain