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Therapeutics 2 - Fall 2017 > Wendt - AntiCoag > Flashcards

Wendt - AntiCoag Flashcards

1
Q

role of plasmin?

A

degrades fibrin – and dissolves clot

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2
Q

all thromboembolytics work to increase the conversion of ______ to ______?

A

plasminogen; plasmin

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3
Q

What activates plasminogen to plasmin

A

t-PA

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4
Q

t-PA cleaves a ______ bond to activate plasmin

A

arg-val bond

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5
Q

Thrombolytics:

______ cleaves a arg-val bond to activate plasmin

A

t-PA

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6
Q

t-PA is inhibited by what things?

A

PAI-1 and PAI-2

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7
Q

plasmin is a ________ that digests fibrin and fibrinogen

A

proteolytic enzyme

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8
Q

Plasminogen is an anticoagulant protein that circulates in _______ form and is deposited on to a growing clot.

A

inactive

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9
Q

t-PA is known as a _______ protease

A

serine

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10
Q

plasmin is inactivated by _________

A

a2-antiplasmin

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11
Q

indications for thrombolytic therapy:

acute or chronic?

A

acute!

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12
Q

indications for thrombolytic therapy:

3 things

A
  • acute MI
  • acute ischemic thrombotic stroke
  • PE
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13
Q

what are the 5 options of thrombolytic drugs

A
  • Alteplase
  • Reteplase
  • Tenecteplase
  • Streptokinase
  • Urokinase
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14
Q

which thrombolytic drugs are known to be recombinant t-PA drugs

A
  • Alteplase
  • Reteplase
  • Tenecteplase
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15
Q

Thrombolytic drug:

Streptokinase makes a complex with _______

A

plasminogen

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16
Q

Thrombolytic drug:

Streptokinase promotes ________ by the _________ molecule

A

promotes plasminogen activation; by adjacent plasminogen molecule

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17
Q

T or F: Streptokinase has intrinsic enzyme activity

A

FALSE! it does not directly degrade clots — it makes a complex that catalyzes conversion of inactive plasminogen to active plasmin

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18
Q

Anti-Fibrolytic Agents are?

A
  • Lysine
  • Tranexamic acid
  • Aminocaproic acid (EACA)
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19
Q

plasmin binds to fibrin through a ______ binding site to activate fibrinolysis

A

lysine

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20
Q

anti-fibrinolytic agents are used to stop _____ caused by _______ drugs

A

stop bleeding; caused by thrombolytic drugs

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21
Q

how does plasminogen get converted to plasmin?

A

t-PA

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22
Q

how does Alteplase work?

A

its a thrombolytic drug that is a recombiant human t-PA

binds to fibrin

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23
Q

how does Reteplase work?

A

recombinant human t-PA

LESS FIBRIN specific/lacks fibrin binding domain

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24
Q

is Reteplase more or less fibrin specific than Alteplase?

A

less fibrin specific

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25
Q

is Tenecteplase more or less fibrin specific than Alteplase?

A

more specific!

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26
Q

Tenecteplase:

short or long 1/2 life?

A

long

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27
Q

-plase thrombolytic drug lacks fibrin binding domain

A

Reteplase

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28
Q

t-PA binds to _____ and activates bound ________ 100x more rapidly than in circulation

A

fibrin; plasminogen

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29
Q

Mutations in Tenecteplase lead to:
______ half life
reduce __________
enhance activity at ______

A

LONGER half life;
reduce INHIBITION by PAI
enhance activity at THROMBI

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30
Q

______ drug is a recombinant t-PA with the 527 aa residue

A

Altelplase

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31
Q

_______ drug is a recombinant t-PA with the 527 aa residue deletion

A

Reteplase

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32
Q

Anti-fibrinolytic agents act as a ________ to bind to the receptor on plasminogen and plasmin - leads to a ______ of plasmin binding to target fibrin

A

lysine analog; blockade

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33
Q

is Tranexamic Acid or Aminocaproic Acid (EACA) more potent as being a anti-fibrinolytic agent

A

Tranexamic Agent

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34
Q

do platelets have a nucleus?

A

no

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35
Q

are platelets made of granules?

A

yes

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36
Q

do platelets have organelles?

A

yes (but no nucleus)

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37
Q

Thrombus Formation is also known as what?

A

platelet plug or white thrombus

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38
Q

3 main steps for Thrombus formation are…

A

1 - platelet adhesion/Shape change
2 - platelet secretion
3 - Platelet aggregation

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39
Q

Thrombus Formation: STEP 1

Adhesion is mediated by what 2 things binding

A

GP1a; GP1b

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40
Q

GP 1a binds to ________

GP1b binds to _______

A

1a - collagen

1b - von willebrand factor (bridged to collagen)

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41
Q

Platelet adhesion mediated by:
_____ binding to collagen
_____ binding to VonWillebrand Factor (bridged to collagen)
________ facilitates receptor binding

A

GP1a
GP1b
Shape change

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42
Q

platelet adhesion:

intact ______ cells secret _____ to inhibit thrombogenesis

A

intact ENDOTHELIAL; secret PGI2 (prostacyclin)

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43
Q

Platelet secretion:

Platelet granules release what 3 things?

A
  • ADP
  • TXA2 (thromboxane A2)
  • 5-HT (serotonin)
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44
Q

ADP, 5-HT, TXA2 activate and recruit what

A

other platelets

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45
Q

Platelet Aggregation:

ADP/5-HT/TXA2 activate/induce conformation of ______ receptors to bind _____

A

GP11b/111a receptors

bind fibrinogen

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46
Q

Platelets get cross linked by ______

A

fibrinogen

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47
Q

_____ is used to stabilize and anchor aggregated platelets

A

Fibrin

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48
Q

Platelet Activation:

1) _______ injury
2) exposed ______
3) Platelet ______
4) platelet _______
5) ______ activation
6) Platelet ______
7) Platelet ______

A 
vascular injury
exposed collagen
adhesion
activation
integrin activation
aggregation
plug
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49
Q

what are the 5 options for Antiplatelet drugs

A 
COX1 inhibitors
ADP receptor inhibitors
blockers of GP11b/111a receptors
PDE3 inhibitors
Protease Activated Receptor inhibitors
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50
Q

what drug is a COX 1 inhibitor

A

Aspirin

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51
Q

Aspirin (ASA):

inhibits platelet COX1 by ______

A

acetylation

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52
Q

Aspirin (ASA):

Blocks the conversion of ___ to ___

A

AA to PGG2

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53
Q

Aspirin (ASA):

Interferes with platelet ______

A

aggregation

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54
Q

Aspirin (ASA):

Prolongs _____ time

A

bleeding

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55
Q

Aspirin (ASA):

Prevents ________ formation

A

aterial thrombi

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56
Q

Aspirin (ASA):

Inhibition of _______ in platelets is the key to anti-platelet activity of ASA

A

TXA2 synthesis

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57
Q

Aspirin (ASA):

(reversible or irreversible) inhibition by acetylation of COX1

A

IRREVERSIBLE;

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58
Q

Aspirin (ASA):

end up having permanent loss of platelet cox1 activity bc of decreased ______

A

TXA2

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59
Q

Aspirin (ASA):

Irreversible inhibition by acetylation of _____

A

COX1

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60
Q

Aspirin (ASA):

(reversible or irreversible) inhibition by ________ of COX1

A

acetylation

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61
Q

at higher doses of aspirin, _______ production in tissue is inhibited

A

prostacyclin

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62
Q

T or F: aspirin increases PT time

A

FALSE (aspirin prolongs bleeding time but no PT time…)

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63
Q

is it used in Platelet Adhesion or Platelet Aggregation?

GP1a

A

platelet adhesion (binds to collagen)

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64
Q

is it used in Platelet Adhesion or Platelet Aggregation?

GP2a

A

platelet adhesion

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65
Q

is it used in Platelet Adhesion or Platelet Aggregation?

GP11b

A

platelet aggregation (it is an integrin)

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66
Q

is it used in Platelet Adhesion or Platelet Aggregation?

GP111a

A

platelet aggregation (it is an integrin)

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67
Q

what are the 2 ADP receptors involved in activating platelets

A

P2Y1; P2Y12

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68
Q

which ADP receptor is coupled to Gq-PLC-IP3-Ca2+ pathway

A

P2Y1

69
Q

which ADP receptor is coupled to Gi & Inhibition of adenylyl cyclase

A

P2Y12

70
Q

ADP comes from _______ and will bind to ______

A

from GRANULES;

binds to P2Y1 and P2Y12

71
Q

what are the ADP receptor inhibitors (both direct and prodrugs)

A

Direct: Ticagrelo; Cangrelor
Prodrugs: Prassugrel; Clopidogrel; Ticlodipine

72
Q

how do the “Thienopyridine” P2Y12 ADP receptors work?

A

irreversibly block ADP receptor on platelet & subsequent activation of GP11b/GP111a (action will last for a couple days)

73
Q

Brand/Generic:

Prasugrel

A

Effient

74
Q

Brand/Generic:

Effient

A

Prasugrel

75
Q

Brand/Generic:

Brilinta

A

Ticagrelor

76
Q

Brand/Generic:

Ticagrelo

A

Brilinta

77
Q

How does Ticagrelor work?

A

binds to allosteric site;
REVERSIBLE binding
NOT a prodrug

78
Q

which ADP receptors have REVERSIBLE binding AND do NOT require bioactivation

A

Ticagrelor (Brilinta)

Cangrelor (Kengreal)

79
Q

what are the PDE3 inhibitors are used for decrease platelet activation

A

Dipyridamole; Cilostazol

80
Q

how do PDE3 inhibitors act as an antiplatelet?

A

if cAMP levels are increased (which they are when PDE3 inhibitors are used) more cAMP leads to decreased intracellular calcium = decreases platelet aggregation and activation

81
Q

do PDE3 inhibitors act as an antiplatelet or anticoagulant

A

antiplatelet

82
Q

both Dipyridamole and Cilostazol:

work to inhibit ________ by prevent degradation of _____ to _____

A

PDE3; cAMP; AMP (equals more cAMP = equals less platelet aggregation)

83
Q

which drugs are known as glycoproteins IIb/IIIA receptor inhibitors

A
  • Tirofiban (Aggrastat)
  • Abciximab (ReoPro)
  • Eptifibitide
84
Q

how does thrombin activate platelets

A

proteolytic cleavage of PAR-1 receptors on platelet surface

85
Q

what drugs are known as Protease Activated Receptor Inhibitors

A

Vorapaxar

Atopaxar

86
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
COX1 Inhibitors

A

Anti-platelet

87
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Alteplase

A

Thrombolytic

88
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Aspirin

A

Antiplatelet

89
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Ticagrelor

A

Anti-Platelet

Brilinta/ADP Receptor Inhibitor

90
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Cangrelor

A

Antiplatelet

ADP Receptor inhibitor

91
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
ADP Receptor Inhibitors

A

Anti Platelet

92
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Cilostazol

A

Antiplatelet

PDE3 inhibitor

93
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
PDE 3 Inhibitors

A

Antiplatelet

94
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Dipyridamole

A

Antiplatelet

PDE 3 inhibitor

95
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Atopaxar

A

Antiplatelet

Protease Activated Receptor Inhibitor

96
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Warfarin

A

Anticoag

97
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Direct Thrombin inhibitor

A

Anticoag

98
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
t-PA analogs

A

Thrombolytic

99
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Direct Factor Xa Inhibitors

A

Anticoag

100
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Fondaparinux

A

AntiCoag

Indirect Factor Xa Inhibitors

101
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Rivaroxaban

A

Anticoag

102
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Apixaban

A

Anticoag

103
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Edoxaban

A

Anticoag

104
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Xarelto

A

Anticoag

105
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Eliquis

A

Anticoag

106
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Savasya

A

Anticoag

107
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Clopidogrel

A

Antiplatelet

108
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Prassugrel

A

Antiplatelet

109
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Ticlodipine

A

Antiplatelet

110
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Abciximan

A

Antiplatelet

GPIIB/GPIIIa receptor inhibitors

111
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Eptifibitide

A

Antiplatelet

GPIIB/GPIIIa receptor inhibitors

112
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Tirofiban

A

Antiplatelet

GPIIB/GPIIIa receptor inhibitors

113
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Tenecteplase

A

Thrombolytic

t-PA Analog

114
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Reteplase

A

Thrombolytic

t-PA Analog

115
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Protease activated receptor inhibitor

A

Antiplatelet

116
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
ADP receptor inhibitor

A

Antiplatelet

117
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Vit. K Antagonist

A

Anticoag

118
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Warfarin

A

Anti Coag

119
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Heparin Agents

A

Anticoag

120
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Enoxaparin

A

Anticoag

121
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Dalataparin

A

Anticoag

122
Q

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent?
Vorapaxar

A

Antiplatelet

Protease activated receptor inhibitors

123
Q

which GPIIb/GPIIIa receptor inhibitor is a chimeric mouse human monoclonal Ab

A

Abciximab

124
Q

which GPIIb/GPIIIa receptor inhibitor is a

synthetic peptide

A

Eptifibitide

125
Q

which GPIIb/GPIIIa receptor inhibitor is a nonpeptide tyrosine analogue

A

Tirofiban

126
Q

GPIIb/IIIa Receptor is:

  • known to be a receptor for ________
  • known to anchor _______ to foreign surfaces and to each other
A

fibrinogen; platelets;

127
Q

GPIIb/IIIa Receptors are activated by what 3 things?

A

TXA2 (thromboxane); thrombin; Collagen

128
Q

Are GPIIb/IIIa Receptors take by oral or IV route

A

IV!

129
Q

All clotting factors are made in the _____ (Except ________)

A

made in lifer; Except Von Willebrand Factor

130
Q

Protein C: is it pro-coagulant factor or anti-coagulant

A

(self made) ANTI-coagulant

131
Q

what is Transglutaminiase’s role in the clotting cascade

A

Cross link fibrin fibers

132
Q

what are glycoproteins used for in the clotting cascade?

A

they are COFACTORs for activation of proteases

133
Q

Factors XII, XI, X, IX, VII, II are known as _____coagulants that are work by cleaving down stream factors to activate them (aka a _________)

A

known as PRO-coagulant; they are SERINE PROTEASES

134
Q

The extrinsic pathway needs ______ to get activated:

The intrinsic pathway needs ______ to get activated

A

Extrinisic - needs Tissue Factor

Intrinsic - collagen gets exposed in wall of the blood vessels

135
Q

Notable things apart of the Extrinisc Pathway

A

Factors VII and X

Tissue Factor

136
Q

what are the notable parts of the common pathway

A

X, Thrombin; Fibrin

137
Q

Step by Step of Extrinsic Pathway:

  • TF found on _________
  • Factor VII normally resides in ______
  • ____ binds to _____ to activate it
  • Factor __ binds and cleaves factor ____
A

found on surface of cells outside; resides in blood;
TF binds to Factor VII (activates VII to VIIa)
VIIa binds/cleaves X

138
Q

_______ changes fibrinogen to fibrin

A

Thrombin

139
Q

Factor _____ changes prothrombin to thrombin

A

Factor Xa

140
Q

______ activates factor XIII

A

Thrombin

141
Q

Activated Factor XIII leads to _______

A

cross linking of fibrin = fibrin clot

142
Q

What are some things that be produced by the body that prevent the coagulation cascade

A
  • AT (antithrombin)
  • Protein C:
  • A tissue Factor Pathway Inhibitor
143
Q

what is a POSITIVE Feedback mechanism for Regulating Coagulation

A

Thrombin!

144
Q

what are the NEGATIVE feedback mechanisms for Regulating Coagulation

A
  • Antithrombin
  • Protein C system
  • Factor Xa
145
Q

How does Antithrombin act to DECREASE coagulation:

A

neutralizes procoagulant serine proteases (aka thrombin, Xa, IXa)

146
Q

Antithrombin decrease coagulation is accelerated by ______

A

heparin

147
Q

how does Protein C decrease coagulation

how does the system get activated and what does it do?

A

Protein C system gets activated by thrombin binding to thrombomodulin

Activated Protein C complex (APC) forms a complex with Protein S = inactivates factors Va and VIIIa

148
Q

how does Factor Xa activate tissue factor pathway inhibitor

A

activates tissue factor pathway inhibitor (TFPI) to block initial activation of Factor VII

149
Q

what drugs are direct factor Xa inhibitors

A

Rivaroxaban
Apixaban
Edoxaban

150
Q

what drugs are direct thrombin inhibitors

A

Argatroban
Dabigatran
Bivalirudin

151
Q

which drugs are vit. k antagonists

A

warfarin

152
Q

Normal Prothrombin Time (PT)?

A

12 - 14 seconds

153
Q

Normal aPTT?

A

26 - 33 seconds

154
Q

Normal recalcification time?

A

2 - 4 minutes

155
Q

aPTT or PT?

measures intrinsic pathway

A

aPTT

156
Q

aPTT or PT?

measures extrinsic pathway

A

PT

157
Q

Possible Tests for hemostatic function

A
  • platelet count
  • PT/INR
  • aPTT
  • D-Dimer
  • Fibrinogen
158
Q

warfarin inhibits _____ of vit. K

A

REDUCTION

159
Q

why is it relevant that warfarin inhibits vit. K?

A

vit. k is essential for post translation modification of clotting factors

160
Q

Warfarin inhibits ___________ thus blocking it to get back to its active form

A

Vit. K epoxide reductase

161
Q

warfarin acts by inhibiting synthesis of which factors?

A

II, VII, IX, X

2,7,9,10

162
Q

How is warfarin metabolized

A

in liver by CYP2C9

163
Q

Idea behind Warfarin Necrosis:

A

Protein C decreases initially before the pro-coag levels decrease and puts pt at an increased risk for coagulation (esp of pt is protein C deficient before therapy)

164
Q

use warfarin in pregnancy?

A

hellll no

165
Q

what drugs decrease warfarins effect

A
  • VIT K
  • Cholestyramine
  • Carbamazepine; Rifampin; Barbituates
166
Q

what common drug can ENHANCE warfarins anticoag effects

A

Broad-Spectrum Abx

167
Q

what drugs are low molecular weight heparins

A

Enoxaparin; Daltaparin

168
Q

Heparin and heparin related drugs are known as ____________ inhibitors

A

indirect factor Xa

Therapeutics 2 - Fall 2017 (22 decks)

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