Thrombolytic Agents Flashcards
What are the activators of the fibrinolytic system?
t-PA
Urokinase
Factor VIIa
What are the inhibitors of the fibrinolytic system?
PAI-1
TAFI
α2-antiplasmin
α2-macroglobulin
What is plasminogen?
Zymogenic form of the active enzyme plasmin (zymogen is a proenzyme)
What is plasmin and its function?
Active protease capable of digesting both fibrinogen and fibrin.
Why has plasmin not been used directly as a drug?
It causes too much bleeding
What are the degradation products of fibrinogen?
X, Y, D degradation products
What are the split products of fibrin?
Froms D-dimers like DD/E, YY/E, YD/DY
What stabilizes formed fibrin?
XIIIa
What are some factors that promote fibrinolysis?
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
What are some factors that limit fibrinolysis?
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
What is the general mechanism of most of the thrombolytic drugs?
They are plasminogen activators
What are the 3 classes of currently approved thrombolytic agents?
a. Urokinase (Canada and EU)
b. Streptokinase
c. Recombinant tissue plasminogen activators
What are the thrombolytic agents still under development?
Pro-urokinase
Plasmin
What are the 3 recombinant tissue plasminogen activators?
Alteplase
Reteplase
Tenecteplase
What is the major effect of thrombolytic therapy?
Degradation (solubilization) of fibrin in the thrombus
What are the major side effects of thrombolytic therapy?
Hypocoaguable state due to degradation of plasma fibrinogen by circulating plasmin which can lead to bleeding.
What are some of the main uses of thrombolytic agents?
- Acute Myocardial Infarction
- Peripheral Arterial Occlusion
- Deep Venous Thrombosis
- Pulmonary Embolism
- Thrombotic Stroke
- Catheter Clearance
What are some absolute contraindications of thrombolytic therapy?
- Intracranial bleeding
2. Massive hemorrhage
What are some drugs that interact with thrombolytic agents?
- Antiplatelet Drugs
- Heparin
- Dextrans
What are the antagonists that are used with thrombolytic overdose?
- EACA (Epsilon-amino caproic acid)
- Tranexemic Acid (Trans-4-Aminoethylcyclohexane 1-Carboxylic Acid)
- Aprotonin
Why have snake venoms been considered to be used as anti-thrombotics?
A number of venoms and biologics contain enzymes which can digest fibrinogen. Ancrod has been tested in stroke.
What is the first line anticoagulant in angioplasty?
Heparin
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
B. Converts plasminogen to plasmin
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
C. Epsilon amino caproic acid
What are the main 3 thrombolytic drugs?
Streptokinase
Urokinase
t-PA
What is the ROA of the thrombolytic drugs?
IV
What are the indications for streptokinase and urokinase?
Thrombolysis, stroke, MI and PE
What are the indications for t-PA?
Thrombolysis, stroke, MI but NOT for PE
EACA/Tranexamic Acid/Aprotonin MOA and ROA
Anti-fibrinolytic
IV
EACA/Tranexamic Acid/Aprotonin Indications
Reversal of bleeding
EACA SE
Hypotension
Tranexamic Acid SE
Retinopathy
Aprotonin SE
Graft thrombosis
Ancrod Indications
Stroke
Ancrod MOA and ROA
Fibrinolytic
IV
Ancrod SE
Allergic Reaction
