Anticoagulants Flashcards
Antiplatelet drugs
Asprin, Clopidogrel
Antithrombin III catalysts
Heparin
Enoxaparin
Fondaparinux
Thrombin Inhibitors
Dabigatran
Rivaroxaban
(Apixaban) - not on drug list
Clotting factor synthesis inhibitors
Warfarin
Heparin chemistry
Naturally occuring highly acidic polysaccharide. Available as unfractionated or low molecular weight.
Antithrombin III catalysts mechanisms
Activate antithrombin III so it can inactivate IIa and Xa.
Antithrombin III
Complexes with and inhibits the activated protease clotting factors.
Unfractionated heparin
Long chains - bridges thrombin-antithrombin molecules and serves as a template for interaction of antithrombin III and Factor IIa
Low molecular weight heparin
Cannot bridge, but accelerate the interaction of Antithrombin III and Xa
Heparin ADME
IV only Distributed in blood Metabolized by reticuloendothelial system (monocytes and macrophages) Does not cross placenta Renal Excretion
Enoxaparin - what is it?
Low molecular weight heparin
Do you need to routinely monitor activity with Heparin? What about with Enoxaparin? Fondaparinux?
Only HEPARIN!
You must monitor anticoagulant action by checking aPTT - 2x control time.
Fondaparinux ADME
SC
Long T 1/2 - up to 21 hrs.
Fixed doses without monitoring activity.
Adverse effects of LMW heparins and fondaparinux
BLEEDING
Transient thrombocytopenia - 25%
Severe thrombocytopenia - 5%
Heparin induced Thrombocytopenia
Antibody-mediated thrombocytopenia - Antibodies to Platetelet-factor 4 complexes - aggregation and embolism.
WARFARIN IS CONTRAINIDICATED IN HIT
Heparin indications
Prevention of DVT / PE
Acute MI / unstable angina
Prevention of thrombosis in extracorporeal devices.
Heparin Contraindications
Hypersensitivity, active bleeding, threatened abortion, infective endocarditis, and surgery.
Heparin Antagonist - not on drug list
Protamine Sulfate
LMW Heparin Indications
Prevention of DVT, Thromboembolism
Fondaparinux Indications
PE, DVT, Antithrombic therapy for Heparin induced thrombocytopenia
Warfarin Chemistry
Inhibits addition of gamma carboxy groups to clotting factors VII, IX, X, II (prothrombin), making them inactive.
Warfarin ADME
PO
Protein Bound
Hepatic - CYP2C9
Renal
Warfarin Adverse Effects
Bleeding
Hemorrhagic disorder in fetus - birth defects
Procoagulant State due to inhibition of protein C and S, leading to cutaneous necrosis during first week of therapy.
Warfarin DDI’s
All of them
Note - warfarin is a vitamin K antagonist - large amounts of vitamin K can reverse warfarin action.
