Thrombolytics

Overview

• Thrombolytics catalyze the formation of endogenous plasmin from plasminogen precursor
  • plasmin is a serine protease that degrades clots (thrombi)
• Drugs
  • tPA (alteplase)
  • streptokinase
  • urokinase
  • APSAC (anistreplase)
• Mechanism
  • catalyze conversion of plasminogen to plasmin
    • cleaves fibrin clots
    • cleaves thrombin
  • clot-specificity
    • tPA is clot-specific
      • acts only on fibrin-bound plasminogen
    • streptokinase is not clot specific
      • depletes circulating plasminogen, factor V, factor VIII
  • ↑ PT, ↑ PTT, no change in platelet count
• Clinical use
  • administer as early as possible following
    • ischemic stroke (tPA)
    • MI
    • DVT
    • pulmonary embolism
• Toxicity
  • bleeding and intracerebral hemorrhage
    • contraindicated in patients with history of bleeding, surgery, hypertension
  • streptokinase may cause hypersensitivity
    • derived from β-hemolytic streptococci
• Antagonist
  • aminocaproic acid and tranexamic acid 
    • lysine analog that prevents conversion of plasminogen to plasmin 
    • inhibitor of fibrinolysis