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N929 Pharmacology > Anti-Thrombolytics > Flashcards

Anti-Thrombolytics Flashcards

1
Q

What is normal hemostasis?

A

a balance between generation of hemostatic clots and uncontrolled thrombus formation

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2
Q

What is the extrinsic pathway?

A

plasma mediated, initiation of hemostasis

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3
Q

What is the extrinsic pathway also known for?

A

primary hemostasis

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4
Q

What is the key to the extrinsic pathway?

A

tissue factor

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5
Q

What is the intrinsic pathway?

A

amplifies and propagates hemostasis

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6
Q

What is the intrinsic pathway also known for?

A

secondary hemostasis

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7
Q

What is the key to the intrinsic pathway?

A

thrombin

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8
Q

What is the common pathway?

A

results in an insoluble fibrin clot

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9
Q

Hemostasis is

A

precisely regulated by interctions between the blood vessel wall, circulating platelets, and clotting proteins in the plasma

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10
Q

Fibrinolysis is

A

the orderly breakdown of a stable blood clot

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11
Q

How many substances that affect blood coagulation have been identified?

A

50

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12
Q

What predominates when a vessel is ruptured?

A

anticoagulants

procoagulants are activated

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13
Q

What consists of normal hemostasis?

A

vasoconstriction
platelet plug
clot formation
clot dissolution

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14
Q

What normally occurs in the vascular endothelium?

A

nonthrombogenic surface

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15
Q

With vasoconstriction, damage to the endothelium exposes

A

the underlying extracellular matrix and elicits contraction

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16
Q

What also induces pro-thrombotic endothelial changes?

A

thrombin, hypoxia, high fluid sheer stress

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17
Q

How does a platelet plug form?

A

when platelets are exposed to the extracellular matrix in a damaged endothelium they undergo a series of biochemical and physical alterations

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18
Q

What are the three major phases of forming a platelet plug?

A

adhesion, activation, aggregation

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19
Q

What is the life of a platelet?

A

8-12 days

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20
Q

What are the normal concentration of platelets?

A

150,000-400,000 per microliter

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21
Q

What are platelet inhibitors?

A

adenosine
insulin
PGIE2
PGI2

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22
Q

Platelet Adhesion

A

exposure to sub-endothelial matrix proteins allows platelet to undergo a conformational change to adhere to the vascular wall

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23
Q

Von Willebrand Factor (vWF) is produced

A

endothelium and platelets

released by endothelial cells and by activated platelets

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24
Q

What is the primary function of Von Willebrand factor?

A

bind to other proteins

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25
Q

What is particularly important about VWF?

A

its a bridging molecule between the subendothelial matrix and platelets forming a cross links
glycoprotein 2B/3A
glycoprotein 1B/ factor IX/ factor V receptor complex

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26
Q

GP1b-V-IX complex

A

binds VWf allowing platelet adhesion and platelet plug formation at sites of vascular injury

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27
Q

What is the absence of GP1b-V-IV receptor known as

A

Bernard- Soulier Syndrome

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28
Q

When is VWF mainly activated?

A

conditions of high blood flow and shear stress

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29
Q

what is type 1 vwd?

A

failure to secrete vWF into circulation or vWF being cleared more quickly than normal
Most common

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30
Q

What is Type 2 VWD?

A

qualitative defect and bleeding varies (4 subtypes)
decreased ability to bind to GP1b
decreased ability to bind to V111

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31
Q

What is type 3 vWD?

A

most severe, homozygous defective gene, complete absence of production of vWF
leads to extremely low levels of Viii since it does not exist to protect VIII from proteolytic degradation

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32
Q

Platelet type vWD is known as

A

psuedo-vWD

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33
Q

What is the platelet type vWD

A

a defect of the platelet’s GPIb receptor

vWF is normal, the platelet receptor GPIB is abnormal

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34
Q

What medications do we use that are GPIIb/IIIa inhibitors?

A

abciximab (reopro)
eptifibatide (integrilin)
tirofiban (aggrastat)

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35
Q

What do GPIIb/IIIa inhibitors do?

A

block the ability of fibrinogen to form around aggregated platelets
does not allow a clot to be formed

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36
Q

The biological half life of abciximab is?

A

12-24 hours

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37
Q

What is the biological half life of eptifibatide?

A

2-4 hours

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38
Q

What is the biological half life of tirofiban?

A

2-4 hours

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39
Q

How does platelet recruitment occur?

A

platelets release granular contents resulting in recruitment and activation of additional platelets

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40
Q

What are thromboxane A2 inhibitors?

A

aspirin and naproxen

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41
Q

Aspirin

A

inhibits the ability of COX enzyme to synthesize the precursors of thromboxane within platelets

42
Q

Naproxen

A

nonselective COX inhibitor

43
Q

P2Y12 receptors

A

further amplify the response to ADP and draw forth the completion of the aggregation

44
Q

What are prodrugs of ADP receptor antagonist medications?

A

ticlopidine (Ticlid)
Clopidogrel (Plavix)
Prasugrel (Efient)

45
Q

What are direct acting ADP receptor antagonist medications

A

ticagrelor (brilinta)

cangrelor (kengrexal)

46
Q

What ADP receptor antagonist has a safer profile?

A

ticlopidine

47
Q

Platelet Aggregation includes

A

newly activated glycoprotein IIb/IIIa receptors on the platelet surface bind fibrinogen to provide for cross-linking with adjacent placement

48
Q

What follows platelet adhesion, activation and aggregation?

A

a blood clot begins to form

49
Q

What is converted and then produces a cross-linked stable mesh?

A

fibrinogen-> fibrin

50
Q

Is fibrinogen soluble or insoluble?

A

soluble

51
Q

Is fibrin insoluble or soluble?

A

insoluble

52
Q

What is the key step in blood clotting?

A

the conversion of fibrinogen (I) to fibrin (Ia) by thrombin (2a)

53
Q

Define the coagulation cascade

A

a classic description of coagulation that includes initiation of this chain reaction via either the intrinsic or extrinsic pathway

54
Q

What triggers the intrinsic pathway?

A

when blood contacts a negatively charged surfcae (exposed to subendothelial collagen)

55
Q

What activates the extrinsic pathway?

A

when blood contacts cells outside the vascular endothelium

56
Q

What protein do nonvascular cells express that initiate the extrinsic pathway?

A

tissue factor (III)

57
Q

What is the common pathway?

A

intrinsic and extrinsic pathways converge with the activation of factor X

58
Q

What are 2 glycoproteins?

A

tissue factor (III) and vWF

59
Q

Where are most coagulation factors synthesized?

A

The liver

60
Q

What are the two coagulation factors not synthesized in the liver?

A

calcium (IV) comes from diet

vWF synthesized in endothelial cells and platelets

61
Q

What factors are dependent in Vitamin K for activation?

A

2 7 9 10

62
Q

Do factors circulate in an active or inactive state?

A

inactive

63
Q

Fibrinogen is clotting factor #

A

I

64
Q

What is the function of fibrinogen?

A

clot formation

65
Q

What is the clotting factor # of prothrombin?

A

II

66
Q

What is the function of prothrombin?

A

Activation of I, V, VII,XI,XIII, protein C and platelets

67
Q

What is the clotting factor # of Tissue factor?

A

III

68
Q

What is the function of tissue factor?

A

co factor of VIIa

69
Q

What is the clotting factor # of calcium?

A

IV

70
Q

What is the function of calcium in the clotting cascade?

A

facilitates the coagulation factor binding to phospholipids

71
Q

What is the clotting factor # for Stuart-Power Factor?

A

X

72
Q

What is the function of Stuart-Power factor?

A

prothrombinase complex with factor V and activates factor 2

73
Q

What is the clotting # of vWF

A

factor XVI

74
Q

What is the function of vWF

A

binds to VIII, mediates platelet adhesion

75
Q

How does the intrinsic pathway of coagulation start?

A

contact activation system

begins with damage to the BV themselves

76
Q

Intrinsic Pathway of coagulation

A

formation of primary complex on collagen and thrombin generation by way of factor XII and utimately merges to the common pathway an activates factor X

77
Q

Extrinsic Pathway of Coagulation

A

Tissue factor pathway
initial step in plasma-mediated hemostasis
following the damage to the BV, factor VII comes into contact with tissue factor adn forms TF-VIIa complex

78
Q

When TF-VIIa circulates the plasma it

A

activates factor X to promote the conversion of X to Xa

79
Q

What is the common pathway of coagulation

A

its common to both extrinsic and intrinsic
it depicts thrombin generation and subsequent fibrin formation- prothrombin (II) is cleaved by activated factor X to produce thrombin (IIa)
signal amplification and thrombin activity

80
Q

Describe the steps (2) of a blood clot

A

prothrombin gets activated to thrombin

thrombin activates fibrinogen to form fibrin

81
Q

How does clot lysis occur?

A

When plasminogen is activated to plasmin

82
Q

How does the activation from plasiminogen to plasmin occur?

A

tissue plasminogen activator (t-PA)

83
Q

tPA

A

is released form tissue, vascular endothelium, plasma and urine

84
Q

Plasmin

A

is an enzyme which digests fibrin fibers, fibrinogen, factor V, factor VIII, prothrombin and factor XII

85
Q

Thrombolytics

A

possess inherent fibrinolytics effects or enhances the body’s fibrinolytic system by converting endogenous pro-enyzme plasminogen to the fibrinolytic enzyme plasmin

86
Q

What do thrombolytics work the best on?

A

more capable of dissolving newly formed clots (platelet rich and weaker fibrinogen bonds)

87
Q

Prothrombin time

A

evaluates the extrinsic pathway
sample of blood plasma is incubated w/tissue factor in the presence of excess Ca2+
it is particularly sensitive to three of the four vitamin-K dependent factors (II,VII, X).

88
Q

Partial Thromboplastin time (Ptt)

A

indicates the performance of the intrinsic pathway

sample of blood is triggered by adding an activator surface plus phospholipid and CA2+

89
Q

ACT

A

performed by mixing of whole blood with an activated substance to initiate activation of the clotting cascade. Widely used and reliable for high heparin concentrations
influenced by hypothermia, thrombocytopenia, coagulation deficiencies

90
Q

THromboelastometry & rotational thromboelastimetry (ROTEM)

A

a global assay for whole blood clotting including coagulation factors, inhibitors, anticoagulation drugs, platelets, and fibrinolysis

91
Q

Bleeding time

A

sensitive test of platelet function

92
Q

Heparin concentration measurements

A

increasing concentrations of protamine are added to samples of heparin containing blood
time to clot is measured in which heparin and protamine are most closely matched will clot first
(1mg protamine will inhibit 1mg (100u) of heparin

93
Q

Platelet function tests

A

the classic method involves centrifugation of patient blood to obtain platelet- rich plasma, which is then analyzed in a cuvette at 37 placed between a light source and photocell

94
Q

Bleeding time

A

3-10 min

95
Q

Platelet count

A

150-350k mm3

96
Q

prothrombin time (pt)

A

12-14 seconds

97
Q

INR

A

0.9-1.2

98
Q

Activated partial thromboplastin time (aPTT)

A

25-35 seconds

99
Q

Thrombin time (TT)

A

<30 seconds

100
Q

Activate coagulation time (ACT)

A

80-150 seconds

101
Q

Fibrinogen

A

> 150mg/dl

N929 Pharmacology (16 decks)

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