Drugs Used In Disorders Of Coagulation

Front 1

what is hemostasis?

Back 1

the cessation of blood loss from a damaged vessel

Front 2

what is the first phase of hemostasis?

Back 2

vascular spasm

Front 3

what is the second phase of hemostasis?

Back 3

platelet plug formation - primary hemostasis

Front 4

what is the third phase of hemostasis?

Back 4

blood coagulation - secondary hemostasis

Front 5

what is the fourth phase of coagulation?

Back 5

dissolution of fibrin clot - tertiary hemostasis

Front 6

what does impaired hemostasis lead to?

Back 6

spontaneous bleeding

Front 7

what does over stimulated hemostasis lead to?

Back 7

thrombus formation

Front 8

what is the inital event after injury to a vessel wall?

Back 8

vasoconstriction - transient locally induced
mediated by neurogenic mech
local secretion of endothelin

Front 9

what is endothelin?

Back 9

a vasoconstriciting peptide secreted by endothelium - potentiates reflex vasoconstriction

Front 10

when the endothelium is damaged, what becomes exposed?

Back 10

subendothelial layer
basal lamina
SMCs

Front 11

What does vessel injury expose that promotes healing?

Back 11

Collagen
Von Williebrand Factor

Front 12

where is vWF synthesized?

Back 12

synthesized in endothelial cells and megakaryocytes
located in subendothelial matrix, platelets, circulation

Front 13

how is platelet adhesion mediated?

Back 13

by binding og integrin GPIb to vWF in subendothelial matrix

Front 14

What does integrin GPIa bind to?

Back 14

collagen

Front 15

What is secreted by healthy endothelium

Back 15

prostacyclin and NO - inhibit platelet aggregation

Front 16

what do activated platelets release?

Back 16

ADP, Ca2+, ATP, 5-HT, vWF, platelet factor 4

Front 17

what degrades fibrin?

Back 17

plasmin - inactive plasminogen is converted to plasmin

Front 18

What are the three main types of drugs used to reduce clotting?

Back 18

platelet aggregation inhibitors
anticoagulants
thrombolytics

Front 19

what are the drugs used in bleeding disorders?

Back 19

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

Front 20

what do platelet aggregation inhibitors do?

Back 20

decrease synthesis or action of chemical signals that promote platelet aggregation

Front 21

what are the platelet aggregation inhibitors?

Back 21

COX inhibitors
ADP receptor blockers
phosphodiesterase inhibitors
blocking of platelet GPIIb/IIIA receptors

Front 22

what is the prototypical COX inhibitor?

Back 22

aspirin

Front 23

how does COX lead to platelet aggregation?

Back 23

synthesizes thromboxane A2 ---> platelet degranulation and aggregation

Front 24

what does aspirin do?

Back 24

irreversibly acetylates COX --> inhibits thromboxane A2 synthesis

Front 25

How long do the effects of aspirin last?

Back 25

10-days - platelets lack DNA and cannot synthesize new COX once it has been acetylated

Front 26

How does thromboxane A2 lead to platelet aggregation?

Back 26

acts on platelet G protein --> IP3 and DAG -->. increase Ca --> activates PLA2 --> activates GP IIb/IIIa

Front 27

what is the significance of GP IIb/IIIa activation?

Back 27

when it is inactivated it weakly binds fibrinogen, but when activated strongly binds fibrinogen

Front 28

what are the uses of aspirin?

Back 28

prophylactic treatment of transient cerebral ischemia
reduce incidence of recurrent MI
decrease mortality in post MI

Front 29

What are the ADP receptor blockers?

Back 29

CLOPidogrel
tiCLOPidine

Front 30

what is the action of ADP receptor blockers?

Back 30

irreversible inhibitors of P2Y12

Front 31

which ADP receptor blockers is preferred?

Back 31

CLOPidogrel - has few side effects

Front 32

what are the phosphodiesterase inhibitors?

Back 32

dipyridamole
cilostazol

Front 33

what is the MOA of dipyridamole?

Back 33

increases cAMP by inhibiting phosphodiesterase and or blocking uptake of adenosine

Front 34

What does adenosine do in platelet aggregation?

Back 34

acts at A2 receptors to activated platelet adenylyl cyclase

Front 35

when is dipyridamole used?

Back 35

it is a coronary vasodilator - used prophylactically in angina

Front 36

How is dipyridamole used?

Back 36

used in combination with warfarin for prophylaxis of thromboemboli w/ prosthetic heart valves

Front 37

what does cilostazol do?

Back 37

promotes vasodilation and inhibition of platelet aggregation

Front 38

when is cilostazol used?

Back 38

to treat intermittent claudication

Front 39

When are blockers of platelet GP IIb/IIIA used?

Back 39

patients w/ acute coronary syndromes

Front 40

what is the GP IIb/IIIA receptor a receptor for?

Back 40

fibrinogen
vitronectin
fibronectin
vWF

Front 41

what are the blockers of GP IIb/IIIA?

Back 41

Abciximab
Eptifibatide
Tirofiban

Front 42

What is Abciximab?

Back 42

monoclonal antibody directed against GP IIb/IIIA

Front 43

what is Eptifibatide?

Back 43

cyclic peptide - reversible antagonist of GP IIb/IIIA

Front 44

what is Tirofiban?

Back 44

nonpeptide reversible antagonist of GP IIb/IIIA

Front 45

What are the major anticoagulants?

Back 45

unfractured heparin (UFH)
low molec weight heparin (LMWH)
selective factor Xa inhibitors
direct thrombin inhibitors (DTIs)
Coumarin anticoagulants (oral)

Front 46

What is heparin?

Back 46

an injectable, rapidly acting anticoagulant

Front 47

when is heparin used?

Back 47

to interfere with the formation of thrombi

Front 48

what is the MOA of heparin?

Back 48

poteniates the action of Antithrombin III

inhibits thrombin and factor X

Front 49

what is antithrombin III?

Back 49

an a-globulin that inhibits serine proteases (thrombin)
does so very slowly w/o heparin
acts rapildly w/ heparin
inhibits thrombin

Front 50

what is LMWH?

Back 50

lower weight heparin
inhibits activated factor X but has less effect on thrombin

Front 51

How are heparin levels monitored?

Back 51

aPTT - activated partial thromboplastin time

Front 52

what does aPPT test?

Back 52

the integrity of the intrinsic and common coagulation pathways

Front 53

Which heparin has a higher therapeutic index?

Back 53

LMWH - not necessary to monitor aPTT

Front 54

what are the adverse effects of heparin?

Back 54

bleeding
hypersensitivity
thrombosis

Front 55

how does thrombosis occur in the presence of heparin?

Back 55

heparin admin can lead to a reduction in the amount of antithrombin III --> decreases inactivation of coagulation cascade

Front 56

How does heparin induced thrombocytopenia come about?

Back 56

it is a type II hypersensitivity reaction
antibodies recognize complexes of heparin and Platelet factor 4
leads to aggregation and release of platelet contents

Front 57

how is Heparin induced thrombocytopenia type II treated?

Back 57

discontinue heparin
admin of DTI or fondaprinux

Front 58

how is heparin reversed?

Back 58

excessive heparin can lead to bleeding
first remove heparin
if bleeding occurs admin of protamine sulfate

Front 59

What is Danaparoid?

Back 59

low molecular weight heparinoid from porcine gut mucosa
contains heparin sulfate, dermatan sulfate, chondroitin sulfate

Front 60

What does danaparoid do?

Back 60

inhibits Factor X, less effect on thrombin

Front 61

When is danaparoid used?

Back 61

prophylaxis of deep vein thrombosis in hip replacement surgery

effective in treatment of HIT

Front 62

What is fondaparinux?

Back 62

a selective inhibitor of factor Xa, negligible antithrombin activity

Front 63

When is fondaparinux used?

Back 63

prevention and treatment of deep vein thrombosis
1Xdaily SC injection

Front 64

What are the Direct Thrombin Inhibitors (DTIs)?

Back 64

LepiRUDIN
DesiRUDIN
BivaliRUDIN
Argatroban

Front 65

What is Lepirudin?

Back 65

is a specific thrombin inhibitor - actis independently of antithrombin III

Front 66

What type of thrombin can Lepirudin inactivate?

Back 66

free and fibrin bound

Front 67

How is Lepirudin administered?

Back 67

parenterally
monitor aPTT
no antidote exists

Front 68

what is desiRUDIN?

Back 68

recombinant form of hirudin - binds and inactivates thrombin

Front 69

what is bivaliRUDIN?

Back 69

synthetic hirudin - binds and inactivates thrombin

Front 70

what is argatroban?

Back 70

small molecule thrombin inhibitor

Front 71

What are the courmarin anticoagulants?

Back 71

Warfarin and Dicumarol
both oral

Front 72

What is the MOA of warfarin and dicumarol?

Back 72

inhibit vitamin K epoxide reductase

Front 73

what is the net effect of warfarin and dicumarol?

Back 73

inactive clotting factors b/c they lack y-carboxyglutamyl side chains

Front 74

how long do the courmarin anticoagulants take to act?

Back 74

8-12 hrs before effects seen

Front 75

How can the anti-coagulant effects of the coumarin anticoagulants be over-come?

Back 75

admin of vitamin K - takes 24 hrs

Front 76

How is warfarin use monitored?

Back 76

with PT (prothombin time) - tests integrity of extrinsic and common coagulation pathways
has a narrow TI

Front 77

Why does warfarin prolong the PT?

Back 77

decreases the amount of functional facotr VII

Front 78

how is warfarin degraded?

Back 78

by CYP450

Front 79

what are the adverse effects of warfarin?

Back 79

-hemorrhage
-cutaneous necrosis w/ reduced activity of protein C

Front 80

when is warfarin CI?

Back 80

in pregnancy - it crosses the placenta
causes hemorrhagic disorder in the fetus and serious birth defects

Front 81

what are the thrombolytics?

Back 81

fibrinolytic drugs that lyse thrombi by catalyzing conversion of plasminogen into plasmin

Front 82

why use fibrinolytics?

Back 82

fibrinolytic agents reduce mortality of acute MI and used when angioplasty is not readily available

Front 83

what drugs make up the thrombolytics?

Back 83

streptokinase
urokinase
anistreplase
alteplase, reteplase, tenecteplase

Front 84

What does plasmin do?

Back 84

degrades firbinogen and fibrin

Front 85

What are drugs used to treat bleeding?

Back 85

plasminogen activating facotrs
proamine sulfate
vitamin K
serine protease inhibitors
plasma fractions

Front 86

what are the plasminogen activation inhibitors?

Back 86

aminocaproic acid
tranexamic acid

Front 87

what do the plasminogen activation inhibitors do?

Back 87

inhibit plasminogen activation

Front 88

what is the effect of plasminogen activation inhibitors?

Back 88

decrease formation of plasmin which degrades fibrinogen and fibrin

Front 89

what is Protamine sulfate?

Back 89

antagonizes heparin

Front 90

how does proatimine sulfate work?

Back 90

it is high in Arg = is cationic
heparin is anionic
they complex

Front 91

When is vitamin K administered to stop bleeding?

Back 91

can stop bleeding due to oral anticoagulants

Front 92

how long does vitamin K take to work to stop bleeding?

Back 92

effect is delayed for 6 hours and is complete by 24hrs

Front 93

what serine protease inhibitor is used to stop bleeding?

Back 93

aprotinin

Front 94

what does aprotinin do?

Back 94

blocks plasmin

Front 95

what is the adverse effect of aprotinin?

Back 95

increases risk of death

Front 96

what is factor VIII deficiency?

Back 96

Hemophillia - classic or A

Front 97

what is Facotr IX deficiency?

Back 97

Christmas disease of hemophilia B