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Anticoagulant Therapy
Lecture 9/26
47
Pharmacology
Professional
09/28/2013

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Term
What are the 5 ways which endothelial cells maintain a nonthrombogenic lining?
Definition
1) protein C activity, 2) Proteoglycan production (similar to warfarin), 3) Transmural electric charge to repel platelets, 4) release of prostacyclin, 5) Release of plasminogen activators
Term
What are the three phases of Hemostasis?
Definition
Vascular, Platelet, and Coagulation
Term
Definition of Thrombosis
Definition
A pathological process in which the platelet aggregate and/or a fibrin clot occludes a blood vessel
Term
Thrombi vs Emboli
Definition
Emboli are migrating Thrombi
Term
Emboli vs Embolism
Definition
Embolism blocks a vessel, Emboli hasn't yet
Term
Name the Anti-Platelet drugs
Definition
Aspirin, Dipyridamole, Ticlopidine, Clopidogrel, Abciximab, Eptifibatide, Tirofiban
Term
What is the mechanism of the antiplatelet drug Aspirin?
Definition
Block of Platelet Cyclooxygenase (COX) to inhibit release of TXA2
Term
COX produces what two prostaglandins and from where?
Definition
PGI2 from endothelial cells (inhibits platelets) and TXA2 from platelets (promotes platelet aggregation)
Term
Why does inhibition of COX not affect endothelial cells as much as platelets?
Definition
Endothelial cells can produce new proteins while platelets cannot (no nucleus)
Term
What is the mechanism of antiplatelet drugs Ticlopidine and Clopidogrel?
Definition
They increase intracellular cAMP through the inhibition of P2Y-12 receptor on Adenylyl cyclase
Term
When is Ticlopidine and Clopidogrel used?
Definition
When the patient has not tolerated aspirin or to use in conjunction with aspirin
Term
What is the mechanism of the antiplatelet drug Dipyridamole?
Definition
Inhibition of Phosphodiesterase activity to increase intracellular cAMP
Term
What is the ideal antiplatelet drug combo for Prosthetic heart valves?
Definition
Dipyridamole + Warfarin
Term
What is the ideal antiplatelet drug combo for a Prior Stroke?
Definition
Dipyridamole + Aspirin
Term
What is the ideal antiplatelet drug combo for Angioplasty?
Definition
Clopidogrel + Aspirin
Term
What are the three Glycoprotein IIb/IIIa ("sticky integrin") inhibitors (Antiplatelet drugs)?
Definition
Abciximab, Eptifibatide, and Tirofiban
Term
When is Abciximab used?
Definition
Precutaneous Angioplasty for coronary thromboses
Term
When is Eptifibatide used?
Definition
Unstable Angina and for angioplastic coronary interventions
Term
What is the main Vit. K Antagonist that is an anticoagulant?
Definition
Warfarin (Vit K analog)
Term
What are the two major side effects of Warfarin?
Definition
Hemorrhage and Birth Defects (because it moves across the placenta)
Term
What can be given for Warfarin overdose?
Definition
Vit K
Term
What factors is Vit. K implicated in?
Definition
II, VII, IX, X, Protein C, Protein S, Z protein (extrinsic and intrinsic pathways)
Term
How does Vit. K act to induce clotting?
Definition
It adds gamma carboxyglutamic residues on to proteases to activate them
Term
What is the normal role of Thrombin?
Definition
It removes small fibrinopeptides from fibrinogen to form the active Fibrin form as well as activation of factor XIII which, in the presence of Ca will strengthen the fibrin links
Term
Thrombin activity on platelets causes what?
Definition
Aggregation and generation of arachidonic acid
Term
How does the anticoagulant Heparin work?
Definition
Heparin accelerates the interaction of Antithrombin with proteases that inhibit Thrombin, IXa, and Xa to prevent blood clots in vitro and in vivo
Term
Where is Heparin absorbed in the body and how is it administered?
Definition
Absorbed in the RES; administered as Heparin Sodium Injection
Term
Does Heparin cross the placenta?
Definition
No, safe to use in pregnancies
Term
What are the major adverse reactions to heparin?
Definition
Hemorrhage and Thrombocytopenia
Term
What compound will inhibit the effect of Heparin in case of overdose?
Definition
Protamine Sulfate
Term
What is Fondaparinux and what is its mechanism (how is it different from heparin)?
Definition
A synthetic derivative of Heparin that only inhibits factor X through antithrombin
Term
Why is Fondaparinux used/what are its indications?
Definition
It is less likely to trigger heparin-induced thrombocytopenia
Term
What are the Newer Antithrombin agents other than Warfarin and Fondaparinux?
Definition
Lepirudin, Bivalirudin, Argatroban, and Drotrecogin alfa
Term
What is the major indication of giving Lepirudin?
Definition
To treat patients with heparin-induced thrombocytopenia
Term
What patients should not be given Lepirudin?
Definition
Renal failure patients
Term
Lepirudin, Bivalirudin, and Argatroban inhibit what factors?
Definition
Factor II
Term
Drotrecogin alpha inhibits what factors?
Definition
VIII and V
Term
What is the natural clot dissolver in the body?
Definition
Plasmin
Term
What drug class dissolves clots/emboli?
Definition
Thrombolytic drugs
Term
What are the Thrombolytic drugs?
Definition
Streptokinase, Urokinase, t-PA: Alteplase
Term
How does Streptokinase work?
Definition
Binds to plasminogen and induces conformational change to expose active sites
Term
How does Urokinase work?
Definition
It is a serine protease enzyme that Activates Plasminogen directly
Term
How todes t-PA work?
Definition
High binding affinity for fibrin so it produces a clot-selective activation of plasminogen
Term
What can be given for inhibition of thrombolytic drugs in case of overdose?
Definition
Aminocaproic acid
Term
When are thrombolytic drugs used?
Definition
Severe pulmonary embolisms, DVTs, or arterial thromboembolisms
Term
What drugs are used in conjunction with Thrombolytic drugs?
Definition
aspirin, beta-blockers, ACE inhibitors
Term
What are some major contraindications for Thrombolytic therapy?
Definition
Recent surgery, hypertension, etc.
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