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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 (enoxa parin) 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.
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Lepirudin, bivalirudin
- Hirudin (leeches) derivatives
- directly inhibit thrombin
- alternative to heparin for anticoagulating patients w/ HIT
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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.
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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
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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)
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Clopidogrel, ticlopidine
- inhibit platelet aggregation by irreversibly blocking ADP receptors. inhibit fibrinogen binding by preventing glycoprotein IIb/IIIa expression
- Toxicity: neutropenia (ticlopidine)
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Cilostazol, dipyridamole
- inhibit phosphodiesterase III enzyme that degrade cAMP (inhibit platelet aggregation, vasodilator)
- Toxicity: nausea, headache, facial flushing, hypotension, abdominal pain
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