Alteplase (Activase) (Last Updated - 4/6/2005)

-aka t-PA (tissue plasminogen activator) or Reteplase (Retavase)
-serine protease
-endogenously released from endothelial cells during stasis (can preclude to vascular occlusion)

-Mechanism Of Action:
     -binds fibrin (Ia) & activates bound plasminogen --> plasmin (by ~100x normal)
     -is specific for fibrin (Ia) --> limits sytemic plasmin formation --> prevents systemic lytic state
     -is a poor activator of plasminogen --> plasmin in the absence of fibrin (Ia)
     -overwhelms the alpha-2-anti-plasmin regulatory system --> inducing clot lysis

-1/2-Life:
     -5-10 mins.

-Clearance:
     cleared rapidly by the liver via plasminogen activator inhibitors 1 & 2

-Uses:
     1) Acute MI

-Dosing:
     -15 mg IV bolus then
          -0.75 mg/kg over 30 mins. (not to exceed 50 mg) then
          -0.5 mg/kg (up to 35 mg accumulated dose) over the next 1 hr.

-Side Effex:
     1) Hemorrhage

-t-PA vs. Streptokinase:
     -t-PA (plus Aspirin) vs. Streptokinase (plus Aspirin) for Acute MI's:
          -PTCI (Percutaneous Transluminal Coronary Intervention) is still superior to either
          -NO statistically significant differences
          -both t-PA & Streptokinase (both along w/ Aspirin) decreased death & reinfarction rates by ~30%
     -t-PA more expensive than Streptokinase (Streptase)

     -Streptokinase (Streptase) --> DOC (unless pt. has already received it in the past --> increased Ab titers --> then t-PA is DOC

=================================
References:

Goodman & Gilman's: The Pharmacologic Basis Of Therapeutics - 10th Edition - 2001. Chapter 55.