Flashcards in Thrombolytic Agents Deck (24):
What is the main endogenous enzyme for lysing clots? What is its zymogenic form?
Plasminogen is the inactive form.
What are the two general types of activators for the conversion of plasminogen to plasmin?
tPA (tissue Plasminogen activator)
What drug inhibits the conversion of plasminogen to plasmin?
What are two chronic conditions that can cause defective fibrinolysis?
Diabetes and HTN
Physiological activators of plasminogen conversion to plasmin
Physiological Inhibitors of plasminogen conversion to plasmin
PAI-1 (rapid acting plasminogen activator inhibitor)
TAFI (thrombin activatable fibrinolytic inhibitor)
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
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)
What does the D dimer test actually measure?
Fragments of fibrin formed by the action of plasmin on the polymerized fibrin monomers
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
List some factors that INHIBIT fibrinolysis
Fibrin crosslinking by Factor 13a
Binding of alpha-2-antiplasmin to fibrin
PAI-1 increase (plasminogen activator inhibitor)
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
What is the mechanism of streptokinase? (Very general)
Activates plasminogen to plasmin
What are the recombinant tissue plasminogen activators?
What is alteplase?
Recombinant form of Human t-PA
What is reteplase?
Mutant form of human t-PA with a longer half life
What is tenecteplase?
Mutant form of human t-PA with a long half life and high fibrin specificity
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
Side effects and complications of Thrombolytic agents
Systemic lytic state
Bleeding is most likely
Stroke --> improper lysis of a clot may embolize
Clinical Uses of Thrombolytic Agents
Acute MI (thrombus in coronary vessels)
Peripheral Arterial Occlusion (like a DVT)
When should thrombolytic agents NEVER be given?
The drugs will just cause more bleeding!
What are the pharmacologic antagonists of thrombolytic agents?
-EACA (epsilon-aminocaproic acid)
Snake venoms have what kind of effect on coagulation?
Many venoms contain enzymes that digest fibrinogen