Uses of Uronase: - Heart attack - Pulmonary embolism Acute MI, Pulmonary embolism, Thromboembolism, Deep vein thrombosis Active internal bleeding; history of cerebrovascular accident; recent (within 2 mth) trauma of any kind including surgery; aneurysm; known bleeding diathesis; severe uncontrolled hypertension. Recent history of peptic ulcer disease, oesophageal varices, ulcerative colitis or other bleeding GI lesions; pancreatitis; subacute bacterial endocarditis; coagulation defects including those due to liver or kidney disease, or after recent surgery, childbirth or trauma. Increased risk of cerebral bleeding e.g. recent stroke or cerebral neoplasm. Pregnancy.

Fibrinolytics (Thrombolytics)

Urokinase is used for the treatment of pulmonary embolisms. The low molecular weight form of human urokinase consists of an A chain of 2,000 daltons linked by a sulfhydryl bond to a B chain of 30,400 daltons. Urokinase is an enzyme (protein) produced by the kidney, and found in the urine. There are two forms of urokinase which differ in molecular weight but have similar clinical effects. Urokinase is the low molecular weight form. Urokinase acts on the endogenous fibrinolytic system. It converts plasminogen to the enzyme plasmin. Plasmin degrades fibrin clots as well as fibrinogen and some other plasma proteins.Urokinase acts on the endogenous fibrinolytic system. It cleaves the Arg-Val bond in plasminogen to produce active plasmin. Plasmin degrades fibrin clots as well as fibrinogen and other plasma proteins.

How to use Urokinase: Your doctor or nurse will give you this medicine. Kindly do not self administer. Adult Dose: Intravenous Deep vein thrombosis Adult: Initially, 4400 units/kg dissolved in 15 ml of sodium chloride 0.9%, infused IV over 10 minutes followed by 4400 units/kg/hr for 12-24 hr. Parenteral Acute myocardial infarction Adult: 6000 units/min infused into the coronary artery for 2 hr preceded by IV heparin. Alternatively, 2-3 million units IV is given over 45-90 min. Intravenous Peripheral arterial thromboembolism Adult: As solution containing 2000 units/ml: Infuse into the clot via a catheter at a rate of 4000 units/minute for 2 hr. Monitor response using angiography. If clot is not removed, advance the catheter into the occluded vessel and continue infusion at the same rate for another 2 hr. May repeat procedure, if needed, up to 4 times. Once blood flow is re-established, partially withdraw the catheter and continue infusing at 1000 units/minute until the remaining clot has lysed. Pulmonary embolism Adult: Initially, 4400 units/kg dissolved in 15 ml sodium chloride 0.9%, infused over 10 min followed by 4400 units/kg/hr for 12 hr. Alternatively, 15000 units/kg as bolus Inj into the pulmonary artery; may repeat inj, adjust dose according to plasma fibrinogen concentrations up to 3 times in 24 hr. Injection Clearance of occluded catheters and shunts Adult: 5000 - 25000 units in 2 ml sodium chloride 0.9% instilled into affected IV catheter or shunt and clamped for up to 4 hr. Aspirate the lysate and repeat the procedure if needed. Alternatively, infuse a solution containing 5000 units of urokinase in 200 mL of sodium chloride 0.9% into the device over 30 minutes. Irrigation Break down of clots in hyphaema Adult: To prepare the solution: Dissolve 5000 units in 2 ml of sterile distilled water. Irrigate the anterior chamber slowly with 0.3 ml of the solution; leave solution in situ for 3 minutes and then wash out with saline. Repeat procedure 5 times. If residual clot is still present at the end of the treatment, leave 0.3 ml of the solution in the anterior chamber for 24-48 hr.

Reduced thrombolytic effect when given again some time later due to development of high levels of antibodies. Potentially Fatal: Platelet inhibitors eg, aspirin and indometacin can potentiate the action of urokinase and cause haemorrhage. Heparin and oral anticoagulants may increase risk of bleeding.

Active internal bleeding; history of cerebrovascular accident; recent (within 2 mth) trauma of any kind including surgery; aneurysm; known bleeding diathesis; severe uncontrolled hypertension. Recent history of peptic ulcer disease, oesophageal varices, ulcerative colitis or other bleeding GI lesions; pancreatitis; subacute bacterial endocarditis; coagulation defects including those due to liver or kidney disease, or after recent surgery, childbirth or trauma. Increased risk of cerebral bleeding e.g. recent stroke or cerebral neoplasm. Pregnancy.

Common - Allergic reaction - Nausea - Vomiting - Injection site bleeding Bleeding, pyrexia, haematuria, thromboembolic episodes, hypersensitivity reactions. Potentially Fatal: Severe bleeding, anaphylaxis.

Pregnancy Category B. Either animal-reproduction studies have not demonstrated a foetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1sttrimester (and there is no evidence of a risk in later trimesters).

Precaution: Any vascular punctures or invasive procedures should be avoided as far as possible during, and immediately before and after urokinase therapy and if unavoidable done with great care. External chest compression. Caution in conditions eg, possibility of left heart thrombus, subacute bacterial endocarditis, coagulation defects, cerebrovascular disease, diabetic retinopathy and any conditions in which bleeding could be dangerous. Monitor for reperfusion arrhythmias when used in MI.

If severe haemorrhage occurs, treatment with Urokinase-GCC must be stopped. Aprotinin and synthetic inhibitors eg, epsilon aminocaproic acid, tranexamic acid or p-aminomethylbenzoic acid can be used to inhibit the fibrinolytic action of Urokinase-GCC. In serious cases, human fibrinogen, Factor XIII, Cohn-Fraction I, packed red cells or whole blood can be given, as appropriate.

Urokinase, an enzyme isolated from human urine, directly converts plasminogen into plasmin, which is a proteolytic enzyme with fibrinolytic effects. It is a fibrin non-specific thrombolytic as it affects both unbound and fibrin bound plasminogen.