Pharmacology of Anticoagulation Therapy Flashcards
Anti-thrombotic drugs either ________, ________, or ________.
prevent formation of thrombi; lyse formed thrombi; inhibit formation of platelet products
Thrombi often form on ___________.
damaged endothelium, frequently from atheroslcerotic plaques; valves in the legs; or in the heart secondary to atrial fibrilation
There are three kinds of heparin: __________.
unfractionated heparin (made from pig intestine), low molecular weight heparin (depolymerized form), and fondaparinux (a synthetic pentasaccharide that corresponds to the smallest component of heparin that is an anti-coagulant)
Heparin works by ______________.
binding to anti-thrombin, which is an enzyme that deactivates the activated forms of serine proteases in the coagulation cascade; thus, heparin prevents thrombin formation
Unfractionated heparin must be given __________; however, it has the advantage of __________.
IV, because it has a poor bioavailability (it is a highly charged molecule); not crossing the placenta
Low molecular weight heparin and fondaparinux can _________.
be given subcutaneously and in outpatient settings
Heparin is used in ___________.
venous thrombosis, pulmonary embolism, abdominal surgery, management of unstable angina, acute myocardial infarction, surgery that requires cardiopulmonary bypass
Heparin can be negated with _________.
protamine sulfate; heparin is negatively charged (because of the sulfate groups) and protamine sulfate is positively charged
Heparin can also cause ____________.
thrombocytopenia, because antibodies can be made in response to platelets bound to heparin; this can be reversed with argatroban and lepirudin
The name Warfarin comes from __________.
Wisconsin alumni research foundation
Warfarin was originally used as rat poison, but it was discovered to be anti-thrombotic when _______________.
an army recruit tried to commit suicide by ingesting lots of rat poison
Warfarin is an ________________.
analog of vitamin K that competes with vitamin K for the enzyme vitamin K epoxide reductase; without vitamin K, the serine proteases cannot be carboxylated and thence cannot bind calcium
Pharmacologically, Warfarin has the advantages of ___________, and the disadvantages of ___________.
being rapidly absorbed, having a long half-life, and having high bioavailability; being teratogenic, causing hemorrhage, having drug interactions, being slow to take effect, and being genetically polymorphic
Warfarin is used to __________.
deep vein thromboses, strokes, and embolism in patients with atrial fibrilation
List the three fibrinolytic agents.
Tissue plasminogen activator, urokinase (from renal cells), and streptokinase (from Streptococcus bacteria)
Fibrinolytic drugs are used in ___________.
emergency treatment for acute myocardial infarctions, ischemic stroke, DVTs, and pulmonary emboli
Aspirin inhibits clot formation by ___________.
irreversibly inhibiting cyclooxygenase 1, which limits the production of thromboxane A2 by platelets; TXA2 activates platelets, so without it platelets will not be activated
Aspirin is used to treat _______.
thrombotic stroke and after acute myocardial infarctions
Why do the coagulation serine proteases require gamma-carboxylation?
Because they use that carboxyl group to bind calcium
In terms of interactions, what drugs increase the action of warfarin?
Aspirin (which inhibits platelet activation); antibiotics (that kill intestinal flora that help deconjugate vitamin K and recirculate vitamin K back to the body); phenytoin and clofibrate (which displace warfarin from proteins and thus increases the free concentration); drugs that decrease its liver metabolism (cimetidine, amiodorone, and phenylbutazone)
Which drugs decrease the action of warfarin?
Rifampin and barbiturates (which stimulate CYP450s); cholestyramine (which decreases absorption from the GI tract)
The newer anti-coagulants are have the advantages of __________.
being faster; not needing monitoring; and no known food/drug interactions
Clopidogrel and ticlodipine are _________.
ADP receptor antagonists
Dabigatran is __________.
a thrombin inhibitor
Abixaban and Rivaroxaban are _________.
Xa inhibitors
Abciximab is _________.
a GPIIb/IIIa inhibitor
