Thrombolytics

• Thrombolytics


  Drugs used to dissolve dangerous clots in blood vessels, improve blood flow, and prevent damage to tissues and organs

  
• Thromboembolism


  Occlusion of an artery or vein caused by thrombus or embolus, resulting in ischemia (deficient blood flow) that causes necrosis (death) of the tissue near to the occluded area

  
• Normally the blood clots disintegrate by natural fibrinolytic mechanisms at about 1 to 2 weeks, but the body cannot wait that long to reestablish normal blood flow

  
• Thrombolytics - Mechanism of Action

  1. Activates the production of enzyme, serine protease Plasmin which is generated from plasminogen

  2. Plasmin is responsible for digesting fibrin

  3. Converts plasminogen to plasmin (also known as fibrinolysin), which digests fibrin

  4. The clot is then dissolved, restoring blood flow to the area

  
• Alteplase (t-PA)


  • Clot specific & binds to the fibrin surface of a clot, promoting the conversion of plasminogen to plasmin
  • Plasmin - enzyme that digests the fibrin in the clot, degrades fibrinogen, prothrombin & other clotting factors
  • Induces fibrinolysis (fibrin breakdown)
• Streptokinase


  • Obtained from β haemolytic Streptococci group C
  • No intrinsic enzyme activity
  • Forms a stable non covalent 1:1 complex with plasminogen, causing limited proteolysis of other plasminogen molecules to generate the active enzyme plasmin
  • Causes conversion of plasminogen to plasmin
• Therapeutic Uses of Thrombolytics

  • Alteplase is used to treat acute MI, pulmonary embolism, acute ischemic stroke, and peripheral artery occlusion and to restore patency to clotted grafts and IV access devices
  • Streptokinase is used to treat acute MI, pulmonary embolism and DVT
  • Reteplase and tenecteplase are used to treat acute MI
  • Urokinase is used to treat pulmonary embolism and coronary artery thrombosis and to clear catheters