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102 Cards in this Set
- Front
- Back
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Heparin
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Direct acting anticoagulant
1 USP unit Binds and accelerates ATIII Acts on Xa and IIa = inactivation |
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LMWH
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Direct acting anticoagulant
Binds and accelerates ATIII Acts only on Xa (not IIa also like heparin) |
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Protamine
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Heparin antagonist
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Warfarin
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Indirect acting anticoagulant
Acts on epoxide reductase in the Vitamin K regeneration pathway Time Lag due to existing factor half lives |
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Aspirin
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Cyclooxygenase inhibitor (irreversible)
Prevents production of TXA2 TXA2 initiates aggregation of platelets |
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Dipyridamole
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Inhibitor of phosphodiesterase
Prevents degradation of cAMP into AMP Want to keep cAMP levels high because cAMP inhibits aggregation and activation of platelets |
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Clopidogrel
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Plavix
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Eptifibitide
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Selectively blocks GPIIb-IIIa
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Tirofiban
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Inhibitor of gp receptor IIb/IIIa
Inhibits fibrinogen binding |
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Epoprostenol
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Prostacyclin
Causes synthesis of cAMP |
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Lepirudin
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Hirudin: direct thrombin inhibitor from the salivary glands of medicinal leech
recombinant hirudin structure Use in heparin-induced thrombocytopenia |
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Streptokinase
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complex with plasminogen, cleaves plasminogen, producing plasmin
Plasmin lyses fibrin |
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Urokinase
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Cultured human fetal kidney cell cultures
Directly converts plasminogen to plasmin |
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Alteplase (rtPA)
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Serine protease produced by human endothelial cells
Bind to fresh thrombus, undergoes conformational change, THEN activates plasminogen Poor activator of plasminogen in the absence of fibrin binding |
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3 phases of hemostasis
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1. vascular
2. platelet 3. coagulation |
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What happens to blood vessels in vascular phase of hemostasis?
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Vascular spasm = local blood vessel constriction
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Platelet adhesion is mediated by what factor?
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von Willebrand Factor
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What happens to platelets in platelet phase of hemostasis?
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Platelet aggregation and adhesion
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What do platelets bind to on a damaged blood vessel (2 things)
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1. Exposed collagen
2. vWF |
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Two major pathways in coagulation phase of hemostasis:
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1. Intrinsic pathway (Contact activation pathway)
2. Extrinsic pathway (Tissue Factor Pathway) |
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Conversion common point of intrinsic and extrinsic pathways:
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Xa (Thrombin)
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How many factors are involved in clotting?
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13
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Hereditary lack of clotting factors leads to what disease?
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Hemophilia
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Suspended fibrinogen is converted to what?
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Large insoluble fibrin fibers
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What converts fibrinogen to fibrin?
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Thrombin (IIa)
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What factor number is fibrin?
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Ia
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What factor activates receptor that causes x-linking of fibrin?
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Thrombin (IIa)
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What mineral is present at every stage of the coagulation pathway?
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Calcium
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Factors are high/low in plasma concentration?
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Low. They are synthesized as needed
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Direct acting anti-coagulant (3)
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Heparin
LMWH Hirudin |
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Indirect acting anti-coagulant (3)
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Warfarin
Coumadin Anisindione |
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Removal of calcium prevents coagultion. Does this work in vivo?
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No, it does not. Useful only in vitro
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Therapeutic effect of heparin
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2x increase aPTT
2x longer for blood to clot |
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Complications of anticoagulant heparin, warfarin, coumadin:
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Bleeding
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Heparin Induced Thrombocytopenia is caused by
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Development of IgG antibodies against complexes of heparin:platelet factor IV
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Heparin is highly charged positive or negative?
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Negative charged
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Heparin is made from porcine intestinal mucosa or bovine lung. What problem can this cause?
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Allergy hazard
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Half-life of heparin is constant or dose dependant?
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Dose dependant. Higher dose = longer half life
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Increased dose of heparin does what to heparin half life
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Increase half life
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Why do we have to use 1 USP for heparin dosage?
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Heparin has a heterogeneous molecular weight
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Name two LMWH
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Dalteparin
Ardeparin |
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Dalteparin
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LMWH
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Ardeparin
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LMWH
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How are LMWH (Dalteparin, Ardeparin) administered?
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SubQ
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What is the difference b/w heparin and LMWH?
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smaller molecular weight and more homogenous in size
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Where does heparin act on?
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Antithrombin III
Accelerates antithrombin III reactions. |
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Action of antithrombin III
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Interacts and deactivates factor Xa (MAJOR) and IIa (thrombin)
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What sequence is important in heparin structure?
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Pentasaccharide
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Pentasaccharide structure in heparin has what kinds of charges?
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Lots of negative charges
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Pentasaccharide structures in heparine binds to ATIII and causes conformational change at reactive center. What are the results?
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Acceleration (1000x) of binding AT to Factor Xa and Thrombin (IIa) = inactivation of clot formation
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What is the ratio of factor Xa and IIa that is inhibited
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3:1 (Xa:IIa)
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3:1 (Xa:IIa) ratio is the anti-thrombin activity for which anticoagulant?
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Heparin
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LMWH has activity on which factor only?
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Xa only (No IIa like heparin does)
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What would you give to a patient with heparin overdose?
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Protamine
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Name a low molecular weight polycationic protein:
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Protamine
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Protamine forms what kind of complex (stable/unstable) through what kind of bond?
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Stable complex with negative charged heparin = covalent electrostatic bond
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How would you administer protamine to a patient in heparin overdose?
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IV
Rapid reversal of effects of heparin |
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Indirect acting anticoagulants are/are not orally effective?
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Are orally effective
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Main disadvantage of indirect acting anticoagulants (Warfarin, Coumadin, Anisindione)
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Time lag
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Which anticoagulants (direct or indirect) are teratogenic?
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Indirect acting anticoagulant: warfarin, coumadin, anisodione
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What is required to catalyze conversion of clotting factors (II, VII, IX, X) to active form?
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Vitamin K
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What is the mnemonic to rememver Vitamin K factors?
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2+7=9+1=10
(II, VI, IX, X) |
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What enzyme regenerates vitamin K?
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Epoxide reductase
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What does warfarin/coumadin act on?
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Epoxide reductase
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Why is there a time lag with warfarin/coumadin?
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Warfarin/coumadin prevents regeneration of factors II, VII, IX, X. Must wait for the existing factors to get used up.
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What is the main physiological interaction of warfarin/coumadin in body?
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99% of drug is bound to plasma albumin
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How are warfarin/coumadin eliminated from the body (or metabolized)?
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CYP450 in the liver
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Why should you never use warfarin/coumadin in pregnancy?
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Teratogenic to fetus
Can cross the placenta, cause hemorrhage d/o in fetus, facial deformities |
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Cholestyramine diminishes/enhances warfarin's anticoagulant effect?
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Diminishes.
Inhibits warfarin absorption in GI tract |
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Barbiturates diminishes/enhances warfarin's anticoagulant effect?
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Diminishes.
Accelerates warfarin metabolism by inducing CYP450 enzymes |
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Vitamin K (reduced form) diminishes/enhances warfarin's anticoagulant effect?
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Diminishes.
Bypasses warfarin-induced epoxide reductase inhibition |
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Chloral hydrate diminishes/enhances warfarin's anticoagulant effect?
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Enhances. Displaces warfarin from plasma albumin = increase effectiveness
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Chloramphenicol diminishes/enhances warfarin's anticoagulant effect?
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Enhances.
Inhibits CYP450 = decreases warfarin metabolism |
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Broad spec antibiotics diminishes/enhances warfarin's anticoagulant effect?
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Enhances.
Reduces availability of gut produced vitamin K in the GI tract |
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Anabolic steroids diminishes/enhances warfarin's anticoagulant effect?
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Enhances.
Inhibits synthesis of clotting factors and increases degradation of clotting factors |
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What is the onset of heparin and LMWH?
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Immediate onset
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What is the onset of warfarin/coumadin?
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1-3 days.
Time lag |
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What is the route of administration of heparin vs LMWH vs. warfarin?
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IV - heparin
SubQ - LMWH Oral - warfarin |
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What are the routes of elimination of heparin, LMWH, and warfarin?
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Hepatic
CYP450 |
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What is the major toxicity associated with heparin, LMWH and warfarin?
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Bleeding
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Which of the three drugs are teratogenic: heparin, LMWH, warfarin?
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Warfarin
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What is the antidote for heparin and LMWH overdose?
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Protamine
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What is the antidote for warfarin overdose?
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Vitamin K
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What is the action of cAMP on platelets?
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Prevents aggregation and activation
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Prostacyclin increases/decreases cAMP?
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Increases cAMP
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Where is prostacyclin produces?
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Healthy, intact endothelial cells
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Thromboxane A2 is released from what?
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Activated platelets
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When thromboxane A2 released from activated platelets binds to other platelets, what happens?
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Initiate release of aggregating agents
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Balance between what two chemicals modulates the balance of platelet aggregation vs. free circulating platelets?
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Prostacyclin and TXA2
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What drug is given to prevent arterial thrombosis that could lead to MI and stroke?
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ASA 81 mg
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What is the antiplatelet dose of ASA?
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81 mg
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What are two unique toxicities from ASA?
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1. ASA induced airway hyperreactivity (Asthmatics)
2. Reyes syndrome (children) |
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ASA has a permanant/temporary effect on platelets?
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Permanent
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ASA has a permanent/temporary effect on endothelium?
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Temporary
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What does prostacyclin do to adenylyl cyclase?
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Signals it to produce cAMP
cAMP Inhibits platelet aggregation and activation |
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What happens to adenylyl cyclase when you bind and block purinergic receptors (P2Y12)
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Elimination and inhibition of adenylyl cyclase
No breakdown of cAMP to AMP Keep cAMP levels high |
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What is a purinergic receptor?
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ADP receptor
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What is a specific purinergic receptor?
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P2Y12
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What antiplatelet drug should you give to patients with atherosclerotic vascular disease?
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Clopidogrel (plavix)
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Prasugrel
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P2Y12 Irreversible antagonist
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What is the receptor for fibrinogen?
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GPIIb-IIIa Receptor
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GPIIb-IIIa receptor binds what ligand?
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Fibrinogen
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