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Pharmacology > Thrombolytic Agents > Flashcards

Thrombolytic Agents Flashcards

1
Q

What are the activators of the fibrinolytic system?

A

t-PA
Urokinase
Factor VIIa

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2
Q

What are the inhibitors of the fibrinolytic system?

A

PAI-1
TAFI
α2-antiplasmin
α2-macroglobulin

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3
Q

What is plasminogen?

A

Zymogenic form of the active enzyme plasmin (zymogen is a proenzyme)

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4
Q

What is plasmin and its function?

A

Active protease capable of digesting both fibrinogen and fibrin.

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5
Q

Why has plasmin not been used directly as a drug?

A

It causes too much bleeding

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6
Q

What are the degradation products of fibrinogen?

A

X, Y, D degradation products

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7
Q

What are the split products of fibrin?

A

Froms D-dimers like DD/E, YY/E, YD/DY

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8
Q

What stabilizes formed fibrin?

A

XIIIa

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9
Q

What are some factors that promote fibrinolysis?

A

a. Plasminogen incorporation into thrombus via fibrin binding
b. Clot retraction
c. Local release of t-PA by endothelial cells
d. Binding of t-PA to fibrin
e. Enhanced t-PA or UK activity in the presence of fibrin
f. Protection of bound plasmin from antiplasmin

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10
Q

What are some factors that limit fibrinolysis?

A

a. Fibrin crosslinking by Factor XIIIa
b. Binding of α2-antiplasmin to fibrin
c. Low ratio of endothelial surface to thrombus volume in large vessels
d. Efficient inhibition of free plasmin by antiplasmin
e. Antiplasmin impairs plasmin binding to fibrin

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11
Q

What is the general mechanism of most of the thrombolytic drugs?

A

They are plasminogen activators

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12
Q

What are the 3 classes of currently approved thrombolytic agents?

A

a. Urokinase (Canada and EU)
b. Streptokinase
c. Recombinant tissue plasminogen activators

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13
Q

What are the thrombolytic agents still under development?

A

Pro-urokinase

Plasmin

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14
Q

What are the 3 recombinant tissue plasminogen activators?

A

Alteplase
Reteplase
Tenecteplase

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15
Q

What is the major effect of thrombolytic therapy?

A

Degradation (solubilization) of fibrin in the thrombus

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16
Q

What are the major side effects of thrombolytic therapy?

A

Hypocoaguable state due to degradation of plasma fibrinogen by circulating plasmin which can lead to bleeding.

17
Q

What are some of the main uses of thrombolytic agents?

A
  • Acute Myocardial Infarction
  • Peripheral Arterial Occlusion
  • Deep Venous Thrombosis
  • Pulmonary Embolism
  • Thrombotic Stroke
  • Catheter Clearance
18
Q

What are some absolute contraindications of thrombolytic therapy?

A
  1. Intracranial bleeding

2. Massive hemorrhage

19
Q

What are some drugs that interact with thrombolytic agents?

A
  1. Antiplatelet Drugs
  2. Heparin
  3. Dextrans
20
Q

What are the antagonists that are used with thrombolytic overdose?

A
  1. EACA (Epsilon-amino caproic acid)
  2. Tranexemic Acid (Trans-4-Aminoethylcyclohexane 1-Carboxylic Acid)
  3. Aprotonin
21
Q

Why have snake venoms been considered to be used as anti-thrombotics?

A

A number of venoms and biologics contain enzymes which can digest fibrinogen. Ancrod has been tested in stroke.

22
Q

What is the first line anticoagulant in angioplasty?

A

Heparin

23
Q

Which of the following mechanisms represents the main effect of thrombolytic agents?
A. Reduces the circulating levels of platelets
B. Converts plasminogen to plasmin
C. Interacts with antithrombin
D. Interacts with heparin cofactor II
E. Decreases the synthesis of fibrinogen in the liver

A

B. Converts plasminogen to plasmin

24
Q 
A elderly patient was accidently overdosed with streptokinase. Which of the following agent can be used to neutralize bleeding complications?
A. Protamine sulfate
B. Vitamin K
C. Epsilon amino caproic acid
D. Factor VIIa
E. Factor VIII concentrate
A

C. Epsilon amino caproic acid

25
Q

What are the main 3 thrombolytic drugs?

A

Streptokinase
Urokinase
t-PA

26
Q

What is the ROA of the thrombolytic drugs?

A

IV

27
Q

What are the indications for streptokinase and urokinase?

A

Thrombolysis, stroke, MI and PE

28
Q

What are the indications for t-PA?

A

Thrombolysis, stroke, MI but NOT for PE

29
Q

EACA/Tranexamic Acid/Aprotonin MOA and ROA

A

Anti-fibrinolytic

IV

30
Q

EACA/Tranexamic Acid/Aprotonin Indications

A

Reversal of bleeding

31
Q

EACA SE

A

Hypotension

32
Q

Tranexamic Acid SE

A

Retinopathy

33
Q

Aprotonin SE

A

Graft thrombosis

34
Q

Ancrod Indications

A

Stroke

35
Q

Ancrod MOA and ROA

A

Fibrinolytic

IV

36
Q

Ancrod SE

A

Allergic Reaction

Pharmacology (74 decks)

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