Fibrin-specific thrombolytic agents.
Human plasma contains two physiologic activators of the fibrinolytic system: prourokinase, also called single chain urokinase-type plasminogen activator (scu-PA), and tissue-type plasminogen activator (t-PA). Both activators can catalyze the proenzyme plasminogen to plasmin. Plasmin transforms fibrin into soluble fibrin breakdown products. t-PA is an inefficient plasminogen activator in the absence of fibrin. In the presence of fibrin, t-PA and plasminogen bind to fibrin; the resultant ternary complex increases the efficiency of the transformation of plasminogen to plasmin two to five hundred times. The activity of the fibrinolytic system is modulated by inhibitors. alpha 2-antiplasmin forms 1:1 stochiometric complexes with plasmin and thus neutralizes circulating plasmin with exceptional rapidity. A specific plasminogen activator-inhibitor has recently been described which rapidly inactivates t-PA and urokinase. The fibrin-specific thrombolytic t-PA has undergone intensive clinical trials, particularly in acute myocardial infarction. It has been found that t-PA is better tolerated (bleeding) while being at least as effective, or more so, than streptokinase. Several research groups are attempting through gene manipulation to produce t-PA with even better therapeutic effect (e.g. even better binding to fibrin, longer half life). Clinical trials of prourokinase and combined prourokinase/t-PA are under way and have also provided favourable therapeutic results so far.
D004359:Drug Therapy, Combination; D005342:Fibrinolysis; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy; D010960:Plasminogen Activators / Q000008:administration & dosage / Q000627:therapeutic use; D013300:Streptokinase / Q000627:therapeutic use; D013923:Thromboembolism / Q000188:drug therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use
D005343:Fibrinolytic Agents; D013300:Streptokinase; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator