Coagulation drugs

Question 1

drugs used to reduce clotting

Answer 1

platelet aggregation inhibitors; anticoagulants; thrombolytics

Question 2

drugs used in bleeding disorders

Answer 2

plasminogen activation inhibitors; protamine sulfate; vitamin k; serine protease inhibitors; plasma fractions

Question 3

platelet aggregation inhibitors

Answer 3

dec synth/chemical signals for platelet aggregation; aspirin/other cox inhibitors; ADP receptor blockers; phosphodiesterase inhibitors; GP IIb/IIIA receptor blockers on platelets

Question 4

aspirin characteristics

Answer 4

prototype cox inhibitor -> inhibits thromboxane A2 synth

Question 5

ADP receptor blockers

Answer 5

1st gen - ticlopidine; 2nd gen - clopidogrel; 3rd gen - prasugrel

Question 6

ticlopidine, clopidogrel, prasugrel pk

Answer 6

prodrugs; slow onset; loading dose may be req’d

Question 7

ticlopidine, clopidogrel, prasugrel pd

Answer 7

irreversible inhibitor of P2Y12 (ADP receptor on platelet surface)

Question 8

ticlopidine, clopidogrel, prasugrel uses

Answer 8

pt’s intolerant to aspirin; combo w/aspirin; prevention

Question 9

phosphodiesterase inhibitors - dipyridamole pd

Answer 9

inhibit phosphodiesterase -> inc cAMP; block adenosine uptake (acts at A2 receptors - activate platelet adenylyl cyclase)

Question 10

dipyridamole uses

Answer 10

combo w/aspirin/warfarin - preventative (prosthetic heart valves); test coronary reserve; NOT anti-anginal (could provoke acute attack - coronary steal)

Question 11

phosphodiesterase inhibitors - cilostazol characteristics

Answer 11

newer; promotes vasodilation, inhibition of platelet aggregation; treat intermittent claudication (window shopper disease)

Question 12

blockers of GP IIb/IIIA receptors characteristics

Answer 12

for acute coronary syndromes

Question 13

blockers of GP IIb/IIIA receptors

Answer 13

ABCIXIMAB; eptifibatide; tirofiban

Question 14

ABCIXIMAB characteristics

Answer 14

monoclonal antibody against human GP IIb/IIIa

Question 15

eptifibatide characteristics

Answer 15

cyclic peptide reversible antagonist of GP IIb/IIIa

Question 16

tirofiban characteristics

Answer 16

nonpeptide reversible antagonist of GP IIb/IIIa

Question 17

anticoagulants

Answer 17

unfractioned heparin (UFH) -> lead to low molecular weight heparins (LMWH) -> lead to selective factor Xa inhibitors; direct thrombin inhibitors (DTIs); coumarin anticoagulants

Question 18

heparin characteristics

Answer 18

injectable; fast anticoag; used acutely to stop thrombi formation

Question 19

heparin pd

Answer 19

binds to antithrombin III to allow more rapid inhibition of thrombin EXCEPT those already bound to fibrin; inhibits ongoing coag, but can’t dissolve pre-existing thrombi; effect directly dose-dependent

Question 20

low molecular weight heparin characteristics

Answer 20

heterogeneous compounds from depolymerization of UFH; inhibit factor Xa, less effect on thrombin vs UFH; higher therapeutic index vs UFH -> no monitoring needed -> better

Question 21

heparin adverse effects

Answer 21

bleeding; HYPERSENSITIVITY rxns; thrombosis from longterm use -> dec ATIII (use low-dose heparin); heparin-induced thrombocytopenia type II

Question 22

heparin-induced thrombocytopenia (HIT) type II

Answer 22

antibodies recognize complexes of heparin, platelet protein (platelet factor 4) -> platelet aggregation, release of platelet contents -> life-threatening; treat: sub heparin w/direct thrombin inhibitor (DTI) or fondaprarinux

Question 23

reversal of heparin action

Answer 23

excessive anticoag from heparin - treat by stopping drug; if bleeding -> give protamine sulfate

Question 24

danaparoid characteristics

Answer 24

low molecular weight heparinoid from pig; similar to LMWH -> inhibit factor X; approved for prophylaxis of deep-vein thrombosis in hip replacement surgery; effective in treat of HIT

Question 25

selective factor Xa inhibitors - fondaparinux characteristics

Answer 25

synthetic pentasaccharide -\> binds to ATIII -\> conformational change to bind to factor Xa; negligible ATIII activity; for prevention/treat deep-vein thrombosis; daily subQ injection

Question 26

direct thrombin inhibitors

Answer 26

direct bind active site of thrombin; lepirudin, desirudin, bivalirudin, argatroban

Question 27

lepirudin characteristics

Answer 27

recombinant form of hirudin - powerful thrombin inhibitor from leeches; can reach/inactivate fibrin-bound thrombin in thrombi; parenterally; no antidote (blood transfusion only)

Question 28

desirudin characteristics

Answer 28

another recombinant form of hirudin

Question 29

bivalirudin characteristics

Answer 29

synthetic derivative of hirudin

Question 30

argatroban characteristics

Answer 30

small molecule thrombin inhibitor

Question 31

coumarin anticoagulants

Answer 31

warfarin, dicumarol

Question 32

warfarin, dicumarol pk

Answer 32

oral unlike heparin

Question 33

warfarin, dicumarol pd

Answer 33

inhibit vit K epoxide reductase -\> production of inactive clotting factors (lack gamma-carboxyglutamyl side chains); overcome anticoag effects with vit K

Question 34

warfarin monitoring

Answer 34

narrow TI; many drug interactions; with prothrombin time (extrinsic, common pathways); warfarin dec fxn'l factor VII -\> inc PT

Question 35

warfarin, dicumarol adverse effects

Answer 35

hemmorrhage; cutaneous necrosis w/dec protein C; crosses placenta -\> hemorrhagic disorder in fetus

Question 36

warfarin, dicumarol contraindications

Answer 36

pregnancy

Question 37

thrombolytics (fibrinolytics)

Answer 37

lyse thrombi; streptokinase; urokinase; anistreplase; alteplase, reteplase, tenecteplase

Question 38

thrombolytics pd

Answer 38

lyse thrombi by catalyzing conversion of plasminogen to plasmin; dec acute MI mortality;

Question 39

thrombolytics uses

Answer 39

when angioplasty not readily available

Question 40

drugs used to treat bleeding

Answer 40

plasminogen activation inhibitors; protamine sulfate; vit k; serine protease inhibitors; plasma fractions

Question 41

plasminogen activation inhibitors

Answer 41

aminocaproic acid; tranexamic acid

Question 42

protamine sulfate pd

Answer 42

antagonizes heparin (from fish sperm/testes); high arginine (cationic) -\> complex w/anionic heparin -\> dec anticoag activity

Question 43

vitamin K characteristics

Answer 43

stop bleeding due to oral anticoags (warfarin)

Question 44

serine protease inhibitors - aprotinin pd

Answer 44

blocks plasmin; inc death risk (w/drawn)