Thrombolytic (Fibrinolytic) Drugs: Uses, Side Effects

Thrombolytic drugs are used to dissolve blood clots (thrombi). Blood clots can occur in any vascular bed; however, when they occur in coronary, cerebral or pulmonary vessels, they can be immediately life-threatening – coronary thrombi are the cause of myocardial infarctions, cerebrovascular thrombi produce strokes, and pulmonary thromboemboli can lead to respiratory and cardiac failure. Therefore, it is important to rapidly diagnose and treat blood clots.

Specific Thrombolytic Drugs

Tissue Plasminogen Activators

This family of thrombolytic drugs is used
in acute myocardial infarction, cerebrovascular thrombotic stroke and pulmonary
embolism. For acute myocardial infarctions, tissue plasminogen activators are
generally preferred over streptokinase.

  • Alteplase (Activase®; rtPA) is a recombinant form of human tPA. It
    has a short half-life (~5 min) and therefore is usually administered as an
    intravenous bolus followed by an infusion.
  • Retaplase (Retavase®) is a genetically engineered, smaller
    derivative of recombinant tPA that has increased potency and is faster acting
    than rtPA. It is usually administered as IV bolus injections. It is used for
    acute myocardial infarction and pulmonary embolism.
  • Tenecteplase (TNK-tPA) has a longer half-life and greater binding
    affinity for fibrin than rtPA. Because of its longer half-life, it can be
    administered by IV bolus. It is only approved for use in acute myocardial
    infarction.

Streptokinase

Streptokinase and anistreplase are used in
acute myocardial infarction, arterial and venous thrombosis, and pulmonary
embolism. These compounds are antigenic because they are derived from
streptococci bacteria.

  • Natural streptokinase (SK) is isolated and purified from
    streptococci bacteria. Its lack of fibrin specificity makes it a less desirable
    thrombolytic drug than tPA compounds because it produces more fibrinogenolysis.
  • Anistreplase (Eminase®) is a complex of SK and plasminogen. It has
    more fibrin specificity and has a longer activity than natural SK; however, it
    causes considerable fibrinogenolysis.

Urokinase

Urokinase (Abbokinase®; UK) is sometimes
referred to as urinary-type plasminogen activator (uPA) because it is formed by
kidneys and is found in urine. It has limited clinical use because, like SK, it
produces considerable fibrinogenolysis; however, it is used for pulmonary
embolism. One benefit over SK is that UK is non-antigenic; however, this is
offset by a much greater cost.

Side Effects and Contraindications

Common adverse effects of all the thrombolytic drugs is bleeding complications related to systemic fibrinogenolysis and lysis of normal hemostatic plugs. The bleeding is often noted at a catheterization site, although gastrointestinal and cerebral hemorrhages may occur. Therefore, patients who have experienced trauma injury or who have a history of cerebral hemorrhagic stroke are not usually administered thrombolytics. Re-thrombosis can occur following thrombolysis, and therefore anticoagulants such as heparin are usually co-administered and continued after thrombolytic therapy for a period of time.

Keyword: thrombolytic (fibrinolytic) drugs.

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