E1: Fibrinolytics

Question 1

Indications of fibrinolytics

Answer 1

1. acute MI
2. ischemic stroke
3. arterial thrombosis
4. pulmonary embolism

Question 2

MOA of fibrinolytics

Answer 2

converts inactive plasminogen to active plasmin which lyse soluble fibrin (in clot)

1. clot specificity
   A. t-PA derivatives preferentially act on plasminogen that is bound to fibrin in a clot
   B. kringles (loop structures) are lysine binding sites by which plasminogen attaches to fibrin
   C. Hydrolysis by t-PA
   at the arrow activates
   the plasmin molecule.

Question 3

Sequence of events in plasmin generation

Answer 3

1. fibrin links GPIIb/IIIa receptors to adjacent platelets
2. plasminogen binds to fibrin by kringles
3. fibrinolytics bind to plasminogen and fibrin then hydrolyze
   plasminogen (inactive) to plasmin (active)
4. plasmin degrades fibrin

Question 4

CI of Fibrinolytics (according to Dr. Potter)

Answer 4

Absolute
1. history of hemorrhagic stroke at any time
2. possible aortic dissection
3. active internal bleeding (not to include menses)
4. intracranial neoplasm

Relative
1. severe uncontrolled HTN (BP >180/110)
2. recent trauma or surgery
3. history of cerebral vascular event
4. active peptic ulcer
5. significant liver dysfunction
6. pregnancy
**oral anticoagulation

Question 5

Tenecteplase
Advantages
Most commonly used in ____

Answer 5

ADV: most potent, most efficacious, single 5-10 second bolus administration is less complex and minimizes medication errors in dose calculations and administration

Used in acute coronary syndrome (STEMI)

Question 6

Which fibrinolytic is the only FDA approved for treatment of acute ischemic stroke and what is its dosing
ADR:

Answer 6

Alteplase (Activase)
0.9 mg/kg (MAX DOSE = 90mg total)
1. 10% as initial IV push bolus over 1min
2. Infuse remaining 90% over 60 min

ADR: Bleeding, orolingual edema

Question 7

Reversal agents for thrombolytics (anti-fibrinolytics)
MOA

Answer 7

Anti-fibrinolytics
1. Aminocaproic acid-Amicar
2. Tranexamic acid-Cyklokapron, Lysteda

MOA
1. analogs that compete for fibrin binding sites on plasminogen and plasmin
2. Block the interaction of plasminogen and plasmin with fibrin
3. Return to a state of clotting