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What are the prototype anticoagulant drugs?
- Warfarin Sodium (coumadin)
- Heparin (unfractionated)
- Enoxaparin (lovenox)
- Direct Thrombin inhibitors
What are the prototype Thrombolytic drugs?
What are the prototype Antiplatelet drugs?
- Clopidogrel (plavex)
- Abeiximab (ReoPro)
Describe how ANTICOAGS work:
Block caog cascade, prevent formation of venous thrombosis
Describe how ANTIPLATELETS work:
block platelet aggregation, prevent formation of arterial thrombus
Describe how THROMBOLYTICS work:
dissolution of existing thrombus
Warfarin inhibits Vit ___ dependent __ _________, leading to a ______ in circulating levels of mature, active clotting factors.
What inhibits active clotting factors, specifically Xa and thrombin (IIa)?
- heparin (Low MW- enoxaparin- less active against thrombin than Xa)
- antithrombin III (endogenous)
What drugs act to directly target active, catalytic or substrate-binding site of active thrombin?
Lepirudin, argatroban, ximelagatran.
Aspirin inihibits _________ irreversibly. This also blocks synthesis of TXA2 and _________.
- prostacyclin (PGT)
Aspirin has greater effect on platelets than ___________, lowering the ration to inihbit __________ _____________.
- platelet aggregation
How does Clopidogrel work? Is this a pro-drug?
- Irreversibly modifies platelet ADP receptor and impairs ADP-mediated activation of glycoproetin II/III receptor expression.
Abeiximab (IV) mode of action?
PRevents fibrinogen binding to glycoprotein II/III receptors.
What are the Therapeutic uses of antiplatelet drugs in art thromboembolitic disorders?
- prevent transient ischemic attacks and cerebral vasc thrombosis
- tx angina pectoris
- prophylaxis of myocardial infarctions
- prevention of acute arterial re-occlusion after vasc surgery
Adverse effects of antiplt drugs
prolonged bleeding time, risk of hemorrhage.
Adverse fx of ABEIXIMAB
adverse fx of CLOPIDOGREL
thrombotic thrombocytopenic purpura
What is the mech of action of thrombolytic drugs?
Convert plasminogen ot plasmin, leading to clot dissolution
streptokinase is a _________ drug. It is a non-________ plasminogen activator, forms autocatalytic proactivator with plasminogen. ______ clot selective. Can cause _______ response. relatively __________.
Alteplase is a __________ drug. it is a _________ human tissue plasminogen activator. binds to fibrin, kinetcially activating nearby plasminogen. clot _________. ____________.
Theraputic uses of thrombolytics
- emergency MI- heparin
- emergency DVT or PE
- emergenc AIS
- reverse occlusion of cannulas/ catheters
adverse fx of thrombolytics
hemorrhage- used only in hospital settings.
contraindications of thromboembolytics
- healing wounds or internal bleeding
- history of CA
- clotting disorders
- severe HTN
how to treat an overdose of thromboembolytics
aminocaproic acid- competitive inhibitor that prevents plasminogen and t-PA from binding fibrin and inhibits thrombolysis.