Flashcards in Therapy Deck (45):
drug that works by either 1) inhibiting thrombin or factor Xa or 2) decreasing the level of competent clotting factors
drugs that accelerate degradation of existing fibrin clots
drugs that inhibit platelet plug formation by inhibiting platelet activation or preventing platelets from sticking to each other
examples of anticoagulants
unfractionated heparin, low molecular weight heparin, direct inhibitors of thrombin/factor X, coumadin
unfractionated heparin activity
a proteoglycan that indirectly inactivates serine proteases (2,10, 9, 11, 12) by binding to antithrombin and enhancing its activity
where is heparin synthesized?
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
how is unfractionated heparin administered?
IV or SubQ
half life of unfractionated heparin
indications for unfractionated heparin use
treatment of acute arterial and venous thromboembolism, prevention of thromboembolism
time span of unfractionated heparin effects
toxicities associated with unfractionated heparin
bleeding, osteoporosis, thrombocytopenia, thrombosis
heparin induced throbocytopenia with thrombosis (HIT)
causes thrombocytopenia and microvascular thrombosis (arterial and venule) in patients on heparin
mechanism of HIT
antibodies recognize the heparin/PF4 complex, which triggers platelet activation and clumping which leads to occlusion and thrombosis
how to treat HIT?
stop the heparin! give a different thrombin inhibitor
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)
how to monitor unfractionated heparin levels
aPTT should be only 1.5-2x normal. and heparin assay should only be 0.2-0.4
low molecular weight heparin (LMWH)
unfractionated heparin that has been processed to only include molecules of a specific, smaller size
advantages of LMWH compared to UFH
longer half life, less bleeding and thrombocytopenia, but unfortunately is more expensive
intravenous direct thrombin inhibitors
lepirudin & argatroban. given to patients with HIT, work immediately, can cause bleeding, very expensive
recombinant modified hirudin (leech spit), treats HIT, excreted renally
derivative of arginine, treats HIT, hepatic excretion (not for use in liver failure patients)
orally administered direct thrombin inhibitor
factor Xa inhibitors
fondaparinux, apixaban, rivaroxaban, edoxaban
smallest subunit of heparin side chain, so can only inhibit factor 10a. given IV/SQ
apixaban, rivaroxaban, edoxaban
orally administered factor 10a inhibitor
which drugs inhibit factor X?
LMWH, rivaroxaban, apixaban, fondaparinux, UFH
which drugs inhibit thrombin?
prevents formation of thrombin by sequestering vitamin K in epoxide form. therefore decreases the synthesis of 2,7,9,10,C/S
where do we get vitamin k?
green leafy vegetables, gut flora, stored in liver
warfarin metabolism pathway
travels from gut to blood, where is is bound by albumin. free warfarin gets transported to liver where it is activated
indications for coumadin use
venous/arterial thromboses recurrence prevention, atrial fibrillation/prosthetic valve clot prevention
how to monitor coumadin levels
increased PT via INR (internationalized normalized ratio). higher indicates greater bleeding risk/lower indicates clotting risk (narrow therapeutic window!)
risk of bleeding, embryopathy, coumadin induced skin necrosis
how do you treat someone on warfarin who is actively bleeding/
give vitamin k and fresh frozen plasma
examples of fibrinolytic agents
strokinase, urokinase, tissue type plasminogen activator (tPA)
action of fibrinolytic agents
increase plasminogen cleavage to plasmin
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
standard of care for venous thrombosis
UFH or LMWH followed by coumadin, which is maintained for 3-6 mos
three types of antiplatelets
receptor antagonists, signal blockers, integrin blockers
antiplatelet agent via ADPY12 receptor blockage.
antiplatelet agent via signal blocking within platelets (irreversible COX1 inhibition so that TxA2 can't be synthesized)
anti platelet integrin blockers
ReoPro, Integrilin, Tirofiban
how big is UFH?
varying sizes due to variations in GAG chain length