Urokinase

Fibrinolytic agent - Urokinase - serves as a dissolving drug that eliminates blood clots by activating plasminogen.

Indications of the urokinase

It is possible to use Urokinase in acute thrombosis of arteries and venous vessels, with thromboembolism of branches of the arteries of the lungs, with thromboses of the vascular shunt.

Urokinase is used for diabetic foot syndrome, which is accompanied by a prolonged formation of ulcers and severe ischemia of the legs. Also, the drug is prescribed in cases of impossibility or inefficiency of conducting operative revascularization, with a fibrinogen level of more than 3.5 g / liter.

[1], [2], [3], [4]

Release form

Urokinase is a pulp-like mass for breeding, followed by injections and infusion infusions.

Urokinase Powder is packaged in vials containing 10,000 IU, 100,000 IU, 500,000 IU, or 1 million IU of Urokinase.

[5], [6], [7], [8], [9], [10]

Pharmacodynamics

Urokinase refers to enzyme substances with the active ingredient serine protease (serine as an amino acid).

Urokinase has much in common with plasminogen and transforms it into plasmin by the hydrolysis of the arginine-valine ligament. Fibrinous thrombi can dissolve under the influence of the thrombolytic properties of the protease plasmin.

The active state of plasma induced by Urokinase promotes a dose-dependent decrease in the amount of plasminogen and fibrinogen, and also increases the content of hydrolysis products of fibrin and fibrinogen. Hydrolysis products affect the reduction of blood clotting and increase the effect of heparin. Such properties appear throughout the day after the administration of Urokinase.

The induced transformation of plasminogen into plasmin can be inhibited by epsilon-aminocaproic, tranexamic and aminobenzoic acids. These inhibitors do not exert a potentiating effect on the anti-coagulation property of fibrin and fibrinogen in the circulation.

[11], [12]

Pharmacokinetics

Urokinase is injected into the arteries or into the veins by injection or infusion.

When carrying out appropriate studies in animals, it was found that Urokinase is degraded by enzymatic substances. The liver is of great importance in the biological transformation of Urokinase. Inactive metabolites are excreted with mucus masses and urinary fluid.

The duration of half-life of Urokinase is estimated at 9-16 minutes. The clinical duration may depend on the period of exposure of the active plasmin.

[13], [14], [15], [16], [17], [18]

Dosing and administration

The solution of Urokinase can be administered intravenously by injection or infusion injections, both in the form of a monopreparation, and as part of a complex treatment together with heparin.

Dosage Urokinase is determined individually, under the control of blood clotting parameters.

• When thrombosis of deeply located venous vessels:
  • the initial amount of the drug Urokinase 4400 IU per kg of weight, for patients at risk of 150 thousand IU for 15 minutes;
  • holding dose of 100 thousand IU per hour, and for patients at risk - from 40 to 60 thousand IU for 2-3 days;
  • After three days, the dosage can be reviewed.
• In severe pulmonary embolism:
  • the initial amount of the drug Urokinase 4400 IU per kg of weight for 15 minutes;
  • retention dosage of Urokinase 4400 IU per kg of body weight / hour for 12 hours;
  • with insufficient efficiency in a day, the dosage can be increased.
• In violation of patency of peripheral vessels:
  • 240 thousand IU per hour is administered as an infusion with the use of an intraarterial catheter for 2-4 hours, or until the blood flow is reached, after which they switch to 1-2 thousand IU per minute;
  • the infusion is completed at the end of thrombolysis, or two days after the start of the infusion.
• With fibrin blocking of hemodialysis shunts:
  • a solution of Urokinase 5-25 thousand IU per ml is introduced into both branches of the vascular shunt;
  • if required, the infusion is repeated after 35-40 minutes;
  • The total period of use of Urokinase should not exceed 120 minutes.

Immediately before the use of Urokinase, the powder is diluted in water for injection according to the following scheme:

• for Urokinase 10 thousand IU, 50 thousand IU or 100 thousand IU, 2 ml of a solvent liquid is required;
• For Urokinase 500 thousand IU, 10 ml of dissolving liquid is required.

Next, the preparation is diluted to the desired consistency with a physiological solution or 5-10% glucose solution. Urokinase is administered immediately after dilution.

[30], [31], [32]

Use of the urokinase during pregnancy

Data on the ingestion of Urokinase in the composition of breast milk, no, as well as information on the possibility of using fibrinolytic in pregnancy. Do not omit the possibility of developing bleeding, the risk of premature onset of labor and the appearance of other complications - for example, premature detachment of the placenta.

It is proved that Urokinase partially passes through the placental barrier.

Given the information available, the use of Urokinase during pregnancy is undesirable, as well as within a month after the birth of the child.

Contraindications

Among the absolute contraindications to the use of Urokinase are:

• recent bleeding (especially those that are related to cerebrovascular events);
• stroke, vascular ruptures that have occurred during the past eight weeks;
• recent surgical intervention, as well as the condition preceding the primary tightening of the wound surface;
• a weak activity of the blood coagulation system, a tendency to bleeding (a variety of hemorrhagic diathesis and fibrinolysis);
• severe forms of hypertension, retinopathy associated with increased blood pressure;
• severe liver diseases and renal filtration systems;
• increased probability of gastrointestinal bleeding (peptic ulcer, tumor processes in the digestive system, etc.);
• increased risk of bleeding in the presence of kidney stones, or tumors of the urinary system;
• tuberculosis, hemoptysis;
• stratification of aneurysm;
• exacerbation of pancreatitis;
• endocarditis;
• microbial sepsis, septic vascular occlusion;
• the first month after the birth of the child, spontaneous or medical abortion, or after the threat of abortion;
• bleeding carcinoma;
• the first month after lumbar aortography;
• the first 8-10 days after uncomplicated spinal puncture.

 Relative contraindications for the use of Urokinase are:

• recent resuscitation, mitral valve pathologies and atrial fibrillation;
• lengthening of thromboplastin period, thrombocytopenia;
• period of pregnancy;
• violation of the integrity of arterial vessels

[19], [20], [21]

Side effects of the urokinase

The most common adverse events following the administration of Urokinase are:

• microvolation;
• bleeding from damaged vessels;
• hematoma.

A number of patients during the treatment of Urokinase experienced severe bleeding in the digestive system, liver, as well as intracerebral and retroperitoneal hemorrhages.

Often a transient increase in the level of transaminases and a decrease in the level of hematocrit without obvious bleeding are recorded.

It is possible to form embolism.

In rare cases, an allergy develops, which reveals itself with reddening of the skin, a violation of breathing, a drop in blood pressure.

[22], [23], [24], [25], [26], [27], [28], [29]

Overdose

The main sign of an overdose of Urokinase is bleeding, which must be stopped by compression. If the application of the compression method does not lead to a stop of bleeding, infusion of Urokinase is stopped and blood-restoring means are introduced.

The initial amount of Aprotinin (antiferment preparation, inhibitor of the fibrinolytic enzyme of the plasmin) should be 500,000-1,000,000 IU per hour intravenously, with a further maintenance dosage of 50-100 thousand Ki per hour, until complete hemostatic stabilization.

When there are profuse bleedings, infusion of Urokinase is stopped urgently. Pass to haemostatic treatment with an infusion of concentrated fibrinogen and other blood products (if required).

Therapy with an overdose of Urokinase is carried out under the supervision of a doctor with experience in the field of transfusion treatment and hemostasiology.

[33], [34], [35], [36],

Interactions with other drugs

The risk of bleeding increases with the combined administration of Urokinase:

• with drugs that inhibit blood clotting (medicines based on heparin or coumarin);
• with drugs that affect the quality and number of platelets (aspirin, allopurinol, phenylbutazone, tetracycline, sulfonamide drugs, antirheumatic drugs, cytotoxic drugs, indomethacin, clofibric acid, dipyridamole, etc .;
• with medications that depress the properties of Urokinase (antifibrinolytic).

[37], [38], [39], [40], [41],

Storage conditions

Keep Urokinase in a place inaccessible to children, away from heating appliances, in rooms with a temperature of up to + 25 ° C.

[42]

Shelf life

Urokinase in a sealed form can be stored for up to 3 years.

The prepared solution should be applied immediately. If the solution of Urokinase was diluted in aseptic conditions, then it can be stored for a maximum of 8 hours.

[43], [44], [45], [46]