Medical application of urokinase

The basic information of urokinase

Urokinase is an enzyme protein isolated from healthy human urine, or obtained from human kidney tissue culture. (LMW-tcu-PA) and 54000 (HMW-tcu-PA), respectively, with the molecular weight of 33000 (LMW-tcu-PA) and 54000 (HMW-tcu-PA) respectively. This product directly on the endogenous fibrinolytic system, can catalyze the splitting of plasminogen plasminogen, which not only degrades fibrin clot, but also degrades the blood circulation of fibrinogen, coagulation factor V and coagulation Factor Ⅷ, etc., to play a thrombolytic effect. The goods on the new formation of thrombosis rapid onset, the effect is good. This product can also increase blood vessel ADP enzyme activity, inhibition of ADP-induced platelet aggregation, prevention of thrombosis. This product after intravenous infusion, patients with plasmin activity increased significantly; withdrawal a few hours later, plasmin activity to restore the original level.

Pharmacology and toxicology of urokinase

Pharmacology:

1, direct role in the endogenous fibrinolysis system, can catalyze the splitting of plasminogen plasmin.

Endogenous fibrinolysis system can not only degrade fibrin clot, but also degrade fibrinogen, blood coagulation factor V and blood coagulation factor Ⅷ and so on, so as to play thrombolysis effect on the newly formed thrombus, the effect it is good.

2, increased vascular ADP enzyme activity, inhibition of ADP-induced platelet aggregation, prevention of thrombosis.

After intravenous infusion, the fibrinolytic activity was significantly increased in patients; fibrinolytic activity returned to its original level after a few hours of discontinuation, but plasma fibrin or fibrinogen levels were reduced and their degradation products increased persistently 12-24 hours.

Toxicology:

Urokinase toxicity is very low, mice intravenous injection of half lethal dose greater than 100 million international units / kg body weight. No obvious antigenicity, teratogenicity, carcinogenicity and mutagenicity.

Clinical application of rare allergic reactions reported; however, in view of urokinase will increase plasmin activity, reducing blood circulation of unbound plasminogen and fibrin-bound plasminogen, may be a serious risk of bleeding.

Pharmacokinetics of urokinase

Pharmacokinetic characteristics of urokinase in the human body has not been fully elucidated. Urokinase after intravenous administration of rapid clearance by the liver, plasma half-life of not more than 20 minutes. A small amount of drugs by bile and urine. Liver cirrhosis and other liver damage in patients with prolonged half-life.

Urokinase to adapt to the symptoms

Urokinase is mainly used for thrombolytic thrombolytic therapy.

1, fresh thromboangiitis disease.

Including acute generalized pulmonary embolism, chest pain within 6-12 hours of coronary artery thrombosis and myocardial infarction, symptoms of less than 3-6 hours of acute cerebral thrombosis, retinal artery embolism and other peripheral arterial embolism severe skeletal-femoral vein Thrombosis.

Urokinase on the old thrombus no significant effect.

2, for artificial heart valve after surgery to prevent thrombosis, to maintain intubation and chest cavity and pericardial drainage tube patency. The efficacy of thrombolysis are required to be followed by heparin anticoagulation to be maintained.

3, for kidney transplantation, plastic surgery and other thrombosis, have a good effect.

Adverse reactions of urokinase

1, the use of large doses, a small number of patients may have bleeding, mild bleeding such as skin, mucous membranes, gross and microscopic hematuria, blood sputum or a small amount of hemoptysis, hematemesis, to take appropriate measures, the symptoms can be alleviated. If severe bleeding, such as massive hemoptysis or gastrointestinal bleeding, retroperitoneal hemorrhage and intracranial, spinal cord, mediastinal or pericardial hemorrhage, should be discontinued, blood transfusion can be whole blood (preferably with blood, do not use plasma) Can be effectively controlled, emergency state can be considered with aminocaproic acid, aminotoluene against urokinase.

2, a small number of patients may be allergic reactions: general performance is light, such as bronchial spasm, rash and so on. Even visible anaphylactic shock.

3, fever: about 2% to 3% of patients can be seen in varying degrees of fever. Acetaminophen can be used as antipyretics. Do not use aspirin or other anti-platelet antipyretics.

4, other: still visible nausea, vomiting, loss of appetite, fatigue, there may be elevated ALT. Can cause bleeding, a small number of allergic reactions, headache, nausea, vomiting, loss of appetite, etc. should be immediately discontinued.

Urokinase administration instructions

1, only for intravenous and intracardiac injection, not for intramuscular injection or local injection.

2, the use should be required for euglobulin dissolution time (ELT) test and thrombin time and prothrombin time determination, during the administration should be observed for the monitoring of coagulation.

3, medication should be closely observed during the patient response, such as pulse rate, body temperature, respiratory rate and blood pressure, bleeding tendency, at least once every 4 hours.

4, pulmonary embolism dissolved often accompanied by changes in hemodynamics, should pay attention to maintaining blood pressure measures.

5, urokinase solution must be prepared with fresh before use, with the allocation with the use.

Bottle of 250,000 units of urokinase, 5ml of sterile water for injection can be dissolved (not dissolved with other solutions), made of liquid to allow pale straw yellow (color depth or can not be completely dissolved are not applicable). Dissolve the bottle should be gently rotated, do not shake (forced to produce insoluble material), the resulting liquid required by 0.45μm terminal filter or small celluloid filter to remove the insoluble particles, according to the usage within the Dilution is required.

6, easy decomposition in the acidic liquid drops. The diluent used should be close to neutral. Dilution with glucose infusion should choose the product of pH ≥ 4.5. Dissolved good liquid easy to inactivate, unused liquid should be discarded, should not be saved and reused.

7, urokinase can cause injection site pinhole hemorrhage, during the treatment is generally not suitable for puncture and other operations.

Intravenous administration requires a successful puncture to avoid local bleeding or hematoma. Arterial puncture administration, administration completed, the puncture should be local pressure at least 30 minutes, and with a sterile bandage and dressing pressure dressing to avoid bleeding.