Antithrombotic Therapy
Terms
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- Thrombotic Treatment
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Prevention: anticoagulants, anti-platelet drugs (after MI or Afib and during angiplasty)
Treatment: Fibrinolytics (PE, DVT, MI)
Replacement: Help clotting (hemophilia, aneurysm, postop GI bleed) - Physiological Regulatory Mechanism
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1. Inhibition of platelet aggregation by increasing cAMP (PFI2, prostacyclin)
2. Inhibition of clotting enzymes by plasma protease inhibitors.
3. Fibrinolysis by plasmin (controlled by t-PA) - Aspirin
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Mechanism: irreversible COX inhibitor, block formation of thromboxane A2
Clinical Use: stable and unstable angina, acute MI, trasient ischemic attack (TIA), stroke prevention after carotid artery surgery
Side Effects: GI bleed - Dipyridamole
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Mechanism: oral anti-platelet, increases cAMP by blocking uptake of adenoise and inhibits phosphodiesterase
Clinical Use: prophylaxis of thrombemboli with prostethic heart valves, stroke survivors - Clopidogrel
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Mechanism: irreversibly inhibits ADP receptors, 4-7 days for 50-60% platelet inhibition
Clinical Use: better than aspirin in preventing MI and stroke, acute coronary syndrome (ACS: unstable angine and MI), recent stroke, peripheral arterial disease
Side Effects: contraindicated in patients with bleeds e.g. ulcer or intracranial hemorrhage - Abciximab
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Mechanism: I.V. anti-platelet, monoclonal AB that blocks glycoprotein IIb/IIIa -> prevents fibrinogen binding
Clinical Use: adjunct to heparin and aspirin, percutaneous coronary interventions (PCI: angioplasty, stenting), prevention of acute cardiac ischemia, refractory unstable angina - Eptifibatide
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Mechanism: I.V. antiplatelet, KGD sequence, more specific for GP IIb/IIIa
Clinical Use: acute coronary syndrome, PCI
Side Effects: - Tirofiban
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Mechanism: I.V. anti-platelet, GP IIb/IIIa inhibitor, basedon RGD sequence
Clinical Use: use with heparin for ACS and PCI -
Heparin
LMWH- Enoxaparin, Dalteparin -
Mechanism: injectable Anticoagulant, binds antithrombin III to stimulate anti-protease activity
Clinical Use: prevention DVT, PE, thrombosis after MI, used in unstable angina, non-Q wavw MI, coronary stents
Side Effects: Bleeding, Heparin Induced Thrombocytopenia (HIT)
Less side effects with LMWH -
Lepirudin
Bivalirudin
Argatroban -
Mechanism: direct thrombin inhibitor
Clinical Use: patients with HIT - Warfarin
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Mechanism: oral anticoagulants; structure related to vit K act as competetive inhibitor -> prevents gamma-carboxylation of factors II, VII, IX, X
Clinical Use: prevention of DVT, thromboembolism, Afib, MI
start low, stabilize, monitor, adjust
Side Effects: bleeding, antidote is vit K and hold warfarin - Streptokinase
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Mechanism: Fibrinolytic, when complexed with plasminogen can convert other plasminogen to plasmin (autocatalytic reaction
Clinical Use: not used much anymore for VTE, MI
Side Effects: bleeding - Alteplase
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Mechanism: recombinant t-PA
short T1/2 of 3min
Clinical Use: DVT, PE, MI
Side Effects: lysis at vascular injury sites, excessive plasmin, hemorrhage - Reteplase
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Mechanism: t-PA with 176 a.a. deleted -> longer T1/2 (15 min)
Clinical Use: specificity for coronary thrombi - Tenecteplase
- Mechanism: t-PA with 3 mutations, more resistant to PAI-1, prolonged T1/2 enables single bolus dosing and 14x specificity for fibrin