Therapy

Question 1

anticoagulant

Answer 1

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

Question 2

fibrinolytic agents

Answer 2

drugs that accelerate degradation of existing fibrin clots

Question 3

antiplatelet agents

Answer 3

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

Question 4

examples of anticoagulants

Answer 4

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

Question 5

unfractionated heparin activity

Answer 5

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

Question 6

where is heparin synthesized?

Answer 6

mast cells

Question 7

difference between unfractionated heparin and LMW heparin?

Answer 7

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

Question 8

how is unfractionated heparin administered?

Answer 8

IV or SubQ

Question 9

half life of unfractionated heparin

Answer 9

short (1hr)

Question 10

indications for unfractionated heparin use

Answer 10

treatment of acute arterial and venous thromboembolism, prevention of thromboembolism

Question 11

time span of unfractionated heparin effects

Answer 11

works immediately

Question 12

toxicities associated with unfractionated heparin

Answer 12

bleeding, osteoporosis, thrombocytopenia, thrombosis

Question 13

heparin induced throbocytopenia with thrombosis (HIT)

Answer 13

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

Question 14

mechanism of HIT

Answer 14

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

Question 15

how to treat HIT?

Answer 15

stop the heparin! give a different thrombin inhibitor

Question 16

consequence of being put on heparin after having had HIT?

Answer 16

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

Question 17

how to monitor unfractionated heparin levels

Answer 17

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

Question 18

low molecular weight heparin (LMWH)

Answer 18

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

Question 19

advantages of LMWH compared to UFH

Answer 19

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

Question 20

intravenous direct thrombin inhibitors

Answer 20

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

Question 21

lepirudin

Answer 21

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

Question 22

argatroban

Answer 22

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

Question 23

orally administered direct thrombin inhibitor

Answer 23

dabigatran

Question 24

factor Xa inhibitors

Answer 24

fondaparinux, apixaban, rivaroxaban, edoxaban

Question 25

fondaparinux

Answer 25

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

Question 26

apixaban, rivaroxaban, edoxaban

Answer 26

orally administered factor 10a inhibitor

Question 27

which drugs inhibit factor X?

Answer 27

LMWH, rivaroxaban, apixaban, fondaparinux, UFH

Question 28

which drugs inhibit thrombin?

Answer 28

UFH, dabigatran

Question 29

warfarin

Answer 29

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

Question 30

where do we get vitamin k?

Answer 30

green leafy vegetables, gut flora, stored in liver

Question 31

warfarin metabolism pathway

Answer 31

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

Question 32

indications for coumadin use

Answer 32

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

Question 33

how to monitor coumadin levels

Answer 33

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

Question 34

warfarin toxicity

Answer 34

risk of bleeding, embryopathy, coumadin induced skin necrosis

Question 35

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

Answer 35

give vitamin k and fresh frozen plasma

Question 36

examples of fibrinolytic agents

Answer 36

strokinase, urokinase, tissue type plasminogen activator (tPA)

Question 37

action of fibrinolytic agents

Answer 37

increase plasminogen cleavage to plasmin

Question 38

post phlebitic syndrome

Answer 38

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

Question 39

standard of care for venous thrombosis

Answer 39

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

Question 40

three types of antiplatelets

Answer 40

receptor antagonists, signal blockers, integrin blockers

Question 41

clopidogrel (plavex)

Answer 41

antiplatelet agent via ADPY12 receptor blockage.

Question 42

aspirin

Answer 42

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

Question 43

anti platelet integrin blockers

Answer 43

ReoPro, Integrilin, Tirofiban

Question 44

how big is UFH?

Answer 44

varying sizes due to variations in GAG chain length

Question 45

why is LMWH supplanting UFH?

Answer 45

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