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Flashcards in Thrombolytic Agents Deck (24):
1

What is the main endogenous enzyme for lysing clots? What is its zymogenic form?

Plasmin

Plasminogen is the inactive form.

2

What are the two general types of activators for the conversion of plasminogen to plasmin?

tPA (tissue Plasminogen activator)

Streptokinase

3

What drug inhibits the conversion of plasminogen to plasmin?

Aminocaproic Acid

4

What are two chronic conditions that can cause defective fibrinolysis?

Diabetes and HTN

5

Physiological activators of plasminogen conversion to plasmin

tPA
Urokinase
Factor 12a

6

Physiological Inhibitors of plasminogen conversion to plasmin

PAI-1 (rapid acting plasminogen activator inhibitor)

TAFI (thrombin activatable fibrinolytic inhibitor)

Alpha-2-antiplasmin

7

Why is time an important factor for the use of thrombolytic agents?

Waiting longer to administer thrombolytic agents allows Factor 13a (transamidase) to cross link and stabilize the fibrin clot, making it much more difficult to digest with plasmin

8

What is a positive D dimer result indicative of?

DIC (disseminated intravascular coagulation) will have high D dimer

Could also diagnose DVT (small increase in D dimers)

9

What does the D dimer test actually measure?

Fragments of fibrin formed by the action of plasmin on the polymerized fibrin monomers

10

List some factors that PROMOTE fibrinolysis

Plasminogen incorporation into the thrombus via fibrin binding

Binding of tPA to fibrin

Local release of tPA
Enhanced tPA or urokinase activity in presence of fibrin
Protection of bound plasmin from antiplasmin

11

List some factors that INHIBIT fibrinolysis

Fibrin crosslinking by Factor 13a

Binding of alpha-2-antiplasmin to fibrin

PAI-1 increase (plasminogen activator inhibitor)

12

Degradation of the clot by thrombolytic agents will lead to....

-Reduction in thrombus size
-Reduction of fibrinogen levels
-Increase in fibrinogen and fibrin degradation products
-Antiplatelet activators

13

What is the mechanism of streptokinase? (Very general)

Activates plasminogen to plasmin

14

What are the recombinant tissue plasminogen activators?

Alteplase
Reteplase
Tenecteplase

15

What is alteplase?

Recombinant form of Human t-PA

16

What is reteplase?

Mutant form of human t-PA with a longer half life

17

What is tenecteplase?

Mutant form of human t-PA with a long half life and high fibrin specificity

18

What is the main difference in functionality with a streptokinase and a recombinant tissue plasminogen activator?

Less bleeding with t-PA

More bleeding with streptokinase

19

Side effects and complications of Thrombolytic agents

Systemic lytic state
Bleeding is most likely

Re-occlusion
Stroke --> improper lysis of a clot may embolize

20

Clinical Uses of Thrombolytic Agents

Acute MI (thrombus in coronary vessels)
Peripheral Arterial Occlusion (like a DVT)
Pulmonary Embolism
Thrombotic Stroke
Ischemic Stroke
Catheter Clearance

21

When should thrombolytic agents NEVER be given?

Intracranial bleeding
Massive hemorrhage

The drugs will just cause more bleeding!

22

What are the pharmacologic antagonists of thrombolytic agents?

-EACA (epsilon-aminocaproic acid)
-Tranexemic Acid

23

Snake venoms have what kind of effect on coagulation?

Anticoagulant effects

Many venoms contain enzymes that digest fibrinogen

24

When are thrombolytic antagonists used clinically?

Overdose of a thrombolytic drug

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