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Flashcards in Therapy Deck (45):
1

anticoagulant

drug that works by either 1) inhibiting thrombin or factor Xa or 2) decreasing the level of competent clotting factors

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fibrinolytic agents

drugs that accelerate degradation of existing fibrin clots

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antiplatelet agents

drugs that inhibit platelet plug formation by inhibiting platelet activation or preventing platelets from sticking to each other

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examples of anticoagulants

unfractionated heparin, low molecular weight heparin, direct inhibitors of thrombin/factor X, coumadin

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unfractionated heparin activity

a proteoglycan that indirectly inactivates serine proteases (2,10, 9, 11, 12) by binding to antithrombin and enhancing its activity

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where is heparin synthesized?

mast cells

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difference between unfractionated heparin and LMW heparin?

LMWH isn't long enough to bind both antithrombin and thrombin. LMWH can only inhibit Xa, not thrombin --> so doesn't increase aPTT

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how is unfractionated heparin administered?

IV or SubQ

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half life of unfractionated heparin

short (1hr)

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indications for unfractionated heparin use

treatment of acute arterial and venous thromboembolism, prevention of thromboembolism

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time span of unfractionated heparin effects

works immediately

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toxicities associated with unfractionated heparin

bleeding, osteoporosis, thrombocytopenia, thrombosis

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heparin induced throbocytopenia with thrombosis (HIT)

causes thrombocytopenia and microvascular thrombosis (arterial and venule) in patients on heparin

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mechanism of HIT

antibodies recognize the heparin/PF4 complex, which triggers platelet activation and clumping which leads to occlusion and thrombosis

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how to treat HIT?

stop the heparin! give a different thrombin inhibitor

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consequence of being put on heparin after having had HIT?

rapid onset of thrombocytopenia due to antibody memory response (24hrs rather than 5-10 days)

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how to monitor unfractionated heparin levels

aPTT should be only 1.5-2x normal. and heparin assay should only be 0.2-0.4

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low molecular weight heparin (LMWH)

unfractionated heparin that has been processed to only include molecules of a specific, smaller size

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advantages of LMWH compared to UFH

longer half life, less bleeding and thrombocytopenia, but unfortunately is more expensive

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intravenous direct thrombin inhibitors

lepirudin & argatroban. given to patients with HIT, work immediately, can cause bleeding, very expensive

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lepirudin

recombinant modified hirudin (leech spit), treats HIT, excreted renally

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argatroban

derivative of arginine, treats HIT, hepatic excretion (not for use in liver failure patients)

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orally administered direct thrombin inhibitor

dabigatran

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factor Xa inhibitors

fondaparinux, apixaban, rivaroxaban, edoxaban

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fondaparinux

smallest subunit of heparin side chain, so can only inhibit factor 10a. given IV/SQ

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apixaban, rivaroxaban, edoxaban

orally administered factor 10a inhibitor

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which drugs inhibit factor X?

LMWH, rivaroxaban, apixaban, fondaparinux, UFH

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which drugs inhibit thrombin?

UFH, dabigatran

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warfarin

prevents formation of thrombin by sequestering vitamin K in epoxide form. therefore decreases the synthesis of 2,7,9,10,C/S

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where do we get vitamin k?

green leafy vegetables, gut flora, stored in liver

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warfarin metabolism pathway

travels from gut to blood, where is is bound by albumin. free warfarin gets transported to liver where it is activated

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indications for coumadin use

venous/arterial thromboses recurrence prevention, atrial fibrillation/prosthetic valve clot prevention

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how to monitor coumadin levels

increased PT via INR (internationalized normalized ratio). higher indicates greater bleeding risk/lower indicates clotting risk (narrow therapeutic window!)

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warfarin toxicity

risk of bleeding, embryopathy, coumadin induced skin necrosis

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how do you treat someone on warfarin who is actively bleeding/

give vitamin k and fresh frozen plasma

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examples of fibrinolytic agents

strokinase, urokinase, tissue type plasminogen activator (tPA)

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action of fibrinolytic agents

increase plasminogen cleavage to plasmin

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post phlebitic syndrome

DVT stints veins and sets off inflammatory response, veins never return to normal and risk of developing stasis is higher, setting patient up for another event. chronic local inflammation and swelling

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standard of care for venous thrombosis

UFH or LMWH followed by coumadin, which is maintained for 3-6 mos

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three types of antiplatelets

receptor antagonists, signal blockers, integrin blockers

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clopidogrel (plavex)

antiplatelet agent via ADPY12 receptor blockage.

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aspirin

antiplatelet agent via signal blocking within platelets (irreversible COX1 inhibition so that TxA2 can't be synthesized)

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anti platelet integrin blockers

ReoPro, Integrilin, Tirofiban

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how big is UFH?

varying sizes due to variations in GAG chain length

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why is LMWH supplanting UFH?

longer half life (less frequent administration), more predictable kinetics (less monitoring), reduced cause of thrombocytopenia