Antithrombotics
Terms
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- Drugs that inhibit platelet activation act primarily where?
- Arteries
- Drugs that inhibit thrombin and fibrin act primarily where?
- Veins
- What is released with platele activation
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ADP, Serotoning and TXA2
Leads to conformation change in GP IIb/IIIa to bind fibrinogen (RGD) - Aspirin (ASA)
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Irreversible inhibits platelet TXA2 production (which triggers plately aggregation)
SE GI distress, ulcer and bleeding - Dipyridamole
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Increase adenosine which increases cAMP levels and inhibits PDE (which breaks down cAMP)
Potentiates aspirin - Acts increase adenosine and inhibit PDE
- Dipyridamole
- Clopidogrel (Plavix)
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Blocks ADP (which aggregates platelets) Takes 4-6 days to take effect. Safe, and more effective than aspirin
CI in active bleeders - ADP inhibitor
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Clopidogrel (Plavix)
4-7 days to take effects - Abciximab
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mAb that blocks GP IIb/IIIa
adjunct to heparin and aspirin for the usual + PCI - Eptifibatide
- Synthetic peptide GP IIb/IIIa inhibitor
- Tirofiban
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synthetic non-peptide GP IIb/IIIa inhibitor
Reduce MI death 22% when used with heparin and aspirin - Three GP IIb/IIIa inhibitors
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Abciximabe
Eptifibatide
Tirofiban -
MOA heparin
Measure its effects -
binds antithrombin III to block factor Xa and thrombin (IIa)
PTT - UFH vs LMWH
- LMWH more specific for Xa, twice daily dosing safely and less incidence of HIT
- Tx for HIT
- protamine sulfate plus switch to direct thrombin inhibitor
- lepirudin
- Direct thrombin inhibitor, originially for leeches. May develop antibodies to it which decrease renal clearance
- Bivalirudin
- VERY expensive direct thrombin inhibitor with short half life (25 mins) for coronary angioplast in pts with prior HIT
- Argatroban
- Inhibits free and fibirin bound thrombin...excreted via liver
- Three direct thrombin inhibitors
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Lepirudin
Bilvalirudin
Argatroban - Warfarin MOA
- competitive inhibitor of vit K. Vit K needed for carboxylation of factor VII, IX, X, II and protein C. Inhibits synthesis, so it needs days for already synthesized factors to be removed
- Risk factors for hemorrhage on warfarin
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Prior history
Cigarette smoking
Renal insufficieny
Anemia
HTn - Contraindication for warfarin
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Preganacy
Active bleeding - Streptokinase
- complexes with plasminogen to convert other plasminogen to plasmin. Not selective, increased risk of bleed
- Problems with streptokinase
- Not selective for fibrin and resistant to antiplasmin so can cause massive thrombolysis. Also, pt may have preformed Ab's from Strep infection
- t-PA - Alteplase
- normal t-PA that converts plasminogen and overwhelms plasminogen activator inhibitor causing quick thrombolysis.
- t1/2 for t-PA
- 3 minutes and rapid liver clearance
- Reteplase
- Lower fibrin affinity and longer half life than t-PA. Can be given in two bolus injections
- Tenecteplase
- Mutated t-PA for longer half life, high specificity for fibrin bound plasminogen. Given in 1 daily bolus
- Fibrinolytics
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Streptokinase
t-PA
Reteplase
Tenecteplase