L34 Pharmacology of Thrombolytic Agents

Question 1

What are the physiologic activators of plasmin?

Answer 1

t-PA I (also urokinase and factor 12a)

Question 2

What are the physiologic inhibitors of plasma?

Answer 2

PAI-1, alpha2-antiplasmin (also TAFI, alpha2-macroglobulin)

Question 3

What is the precursor to plasmin?

Answer 3

Plasminogen

Question 4

What is the active protease capable of digesting both fibrinogen and fibrin?

Answer 4

Plasmin

Question 5

What is a D-dimer?

Answer 5

Clot lysed by plasmin

Question 6

How is fibrin formed?

Answer 6

Thrombin acting on fibrinogen

Question 7

How is fibrin stabilized?

Answer 7

Factor 13a

Question 8

What is a D-dimer test used for?

Answer 8

DVT or DIC

Question 9

What factors promote fibrinolysis?

Answer 9

1. Plasminogen incorporation into the thrombus via fibrin binding
2. Clot retraction
3. Local release of t-PA by endothelial cells
4. Binding of t-PA to fibrin
5. Enhanced t-PA activity in the presence of fibrin
6. Protection of bound plasmin from antiplasmin

Question 10

What factors limit fibrinolysis?

Answer 10

1. Fibrin crosslinking by 13a

2. Binding of alpha-2 antiplasmin to fibrin

Question 11

What do thrombolytic agents do?

Answer 11

Degrade clots, generally via activation of plasminogen

Question 12

What are the effects of clot degradation?

Answer 12

1. Reduction in thrombus size
2. Reduction in fibrinogen levels
3. Increase in fibrinogen and fibrin degradation products
4. Antiplatet activation

Question 13

What are the clinically approved thrombolytic agents?

Answer 13

1. Urokinase (not in US)
2. Streptokinase
3. Recombinant tissue plasminogen activators

Question 14

What are the 3 recombinant tissue plasminogen activators?

Answer 14

1. Alteplase (recombinant t-Pa)
2. Reteplase (more fibrin specific t-Pa)
3. Tenecteplase (longer half-life, high specificity)

Question 15

What is the most specific thrombolytic agent?

Answer 15

t-PA

Question 16

What are the major clinical uses of thrombolytic agents?

Answer 16

1. Acute MI
2. Peripheral arterial occlusion
3. DVT
4. Pulmonary embolism (not t-PA)
5. Thrombotic and ischemic stroke
6. Catheter clearance

Question 17

Acute occlusion of a coronary artery may lead to the formation of a ___.

Answer 17

Fibrin-rich clot

Question 18

Older clots are ___ susceptible to thrombolytic agents.

Answer 18

Less

Question 19

What are the major complications of thrombolytic therapy?

Answer 19

Bleeding, re-occlusion, stroke

Question 20

What are the two major contraindications of thrombolytic therapy?

Answer 20

Intracranial bleeding and massive hemorrhage

Question 21

What 3 drugs interact with thrombolytic agents?

Answer 21

Antiplatelet drugs, heparin, dextrans

Question 22

What are the antidotes to thrombolytic agents?

Answer 22

EACA and tranexemic acid, also aprotinin