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