Week 10-fibrinolytics

Question 1

what is the fibrinolytic system?

Answer 1

-Clot removal
 Fibrinolytic pathway
 Plasmin formation
 Potent proteolytic enzyme
 Attacks fibrin
 50 different sites
-Plasmin formed by plasminogen (proenzyme)
-Has affinity for fibrin but must be activated
 tissue plasmin activators (tPA)
 urokinase plasminogen activator (uPA)
 Kallikrein

Question 2

how does the fibrinolytic system work?

Answer 2

• plasminogen is the proenzyme which is inactive and gets cleaved to plasminogen activators
• plasmin is the free to degrade fibrin clots then lead to fibrin degradtion products being released

Question 3

what drugs are used to stimulate fibrinolysis?

Answer 3

 Convert plasminogen to plasmin
-Streptokinase
 Recombinant human tPA
- Reteplase
- Alteplase
- Tenecteplase
- Urokinase

Question 4

what is Streptokinase?

Answer 4

 From streptococci
 Cleared by the liver
 Antigenic antibodies form after 4 days
 Half life = 20 minutes
 Can’t use for a year after dose given

Question 5

what is alteplase?

Answer 5

-Reduce mortality in MI
 Treatment of acute ischemic stroke, DVT and PE
 More active on fibrin-bound plasminogen than plasma plasminogen, therefore “clot selective”
 Not antigenic
 Given iv – half life of 5 min
 Given within 6-12h, ideally within 1 h

Question 6

what is Reteplase and Tenecteplase?

Answer 6

 Reduce mortality in MI
 More active on fibrin-bound plasminogen than plasma
plasminogen, therefore “clot selective”
 Not antigenic
 Reteplase given within 12h, ideally <1h
 Tenecteplase given within 6h, ideally <1h

Question 7

what is urokinase?

Answer 7

 uPA

 Not selective for clot-bound fibrin so less useful