Thrombolytic

HEPARINS THROMBOLYTICS Heparin requirements are t when administered after streptokinase Uncertain at present. Monitor APTT closely when starting heparin after streptokinase 

HIRUDINS THROMBOLYTICS t risk of bleeding complications when alteplase or streptokinase is co administered with lepirudin Additive effect on clotting cascade Watch for bleeding complications. Risk-benefit analysis is needed before co-administering this will involve availability of alternative therapies such as primary angioplasty 

THROMBOLYTICS Secondary drug ANTIPLATELET AGENTS Effect Mechanism Precautions 

Also called fibrinolytics, these agents lyse thrombi by catalyzing the formation of the endogenous fibrinolytic plasmin (a serine protease) from its precursor, plasminogen. 

Thrombolytics include tissue plasminogen activator (tPA, recombinant) and streptokinase (bacterial). They are used intravenously for short-term emergency management of coronary thromboses in myocardial infarction (MI), deep venous thrombosis, pulmonary embolism, and ischemic stroke (tPA). 

Thrombolytics (also referred to as fibrinolytics) are of clinical value in the early treatment of fibrin-clot-induced ischemia (e.g., 60% decrease in post-MI mortality if used within 3 hours). 

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Thromb o cy top athy Thrombocytopenia Thromboembolism Thrombolytic agents... 

The success of thrombus lysis depends mainly on how large the thrombus is and whether any blood flow stiU remains. The outcome is better the larger the surface of the entire thrombus exposed to the thrombolytic agent. As the clot ages, the polymerization of fibria cross-linking and other blood materials iacreases and it becomes more resistant to lysis. Therefore, the eadier the thrombolysis therapy starts, the higher the frequency of clot dissolution. Thrombolytic agents available are Hsted ia Table 7 (261—276). 

Prourokinase is a single-chain protein containing 411 amino acids (261,265,274,275). In clinical uses scu-PA does not bind to fibrin only and its use causes a decreased plasma fibrinogen of 80%. Its half-life in the circulation is 5 min. It is cleared by the fiver. It is used at 40—70 mg over 1 h and heparin is needed simultaneously. Fibrin specificity and thrombolytic efficacy are similar to that of t-PA. 

Therapeutic enzymes have a broad variety of specific uses, ie, as oncolytics, thrombolytics, or replacements for inherited deficiencies. Additionally, there is a growing group of miscellaneous enzymes of diverse function. 

Thrombolytic Enzymes. Although atherosclerosis and the accompanying vascular wall defects are ultimately responsible for such diseases as acute pulmonary embolism, arterial occlusion, and myocardial infarction, the lack of blood flow caused by a fibrin clot directly results in tissue injury and in the clinical symptoms of these devastating diseases (54). Thrombolytic enzyme therapy removes the fibrin clot by dissolution, and has shown promise in the treatment of a number of thrombo-occlusive diseases (60). 

Streptokinase has an initial plasma half-life (/ 2 of 18 min, and a P half-life of 83 min (73) it is well recognized that the thrombolytic efficacy of the enzyme decreases as the age of the thrombus increases thus, thrombolysis is significantly decreased when therapy is initiated more than three hours after an occlusion (74). 

Several clinical trials have been conducted with streptokinase adrninistered either intravenously or by direct infusion into a catheterized coronary artery. The results from 33 randomized trials conducted between 1959 and 1984 have been examined (75), and show a significant decrease in mortaUty rate (15.4%) in enzyme-treated patients vs matched controls (19.2%). These results correlate well with an ItaUan study encompassing 11,806 patients (76), in which the overall reduction in mortaUty was 19% in the streptokinase-treated group, ie, 1.5 million units adrninistered intravenously, compared with placebo-treated controls. The trial also shows that a delay in the initiation of treatment over six hours after the onset of symptoms nullifies any benefit from this type of thrombolytic therapy. Conversely, patients treated within one hour from the onset of symptoms had a remarkable decrease in mortaUty (47%). The benefits of streptokinase therapy, especially in the latter group of patients, was stiU evident in a one-year foUow-up (77). In addition to reducing mortahty rate, there was an improvement in left ventricular function and a reduction in the size of infarction. Thus early treatment with streptokinase is essential. 

The thrombolytic efficacy of streptokinase treatment may be compromised by the presence of antibodies to the enzyme in the patient s blood. 

Anistreplase has a considerably longer a half-life than streptokinase, ie, 90 min compared to 20 min (87,88). Moreover, it does not require prolonged infusion to achieve its thrombolytic effects. Anistreplase was found to be highly effective after a single intravenous dose of 30 units over a 5-min period compared to a 60-min infusion of 1.5 million units of streptokinase (89—94). In direct comparative studies, anistreplase was as effective as intracoronary (95,96) and intravenously (96—100) adrninistered streptokinase. In a randomized, double-blind, placebo-controUed study (AIMS trial) with 1004 patients given this modified enzyme, the 30-day mortaUty rate was 12.2% for patients receiving placebo, compared to 6.4% for patients who received 30 units of anistreplase intravenously within six hours of the onset of symptoms (101). 

Compared to streptokinase, urokinase has been less extensively studied because of its high cost, ie, about 10 times that of a comparable treatment with streptokinase. In addition to the indications described for streptokinase, urokinase is indicated for use in patients with prior streptokinase treatment, or prior Streptococcal infection. Urokinase is commonly used at a loading dose of 4400 units /kg, with a maintenance intravenous infusion dose of 4400 units/kg/h for thromboses other than acute myocardial infarction. In the latter case, a much larger dose, ie, 0.5—2.0 million units/h or a bolus dose of 1.0 million units followed by a 60-min infusion with 1.0 million units, has been found optimal (106). An intracoronary dose of 2000 units/min for two hours was used in one comparative study with intracoronary streptokinase (107). In this study, urokinase exhibited efficacy equivalent to streptokinase with fewer side effects. Other studies with intracoronary urokinase have adrninistered doses ranging from 2,000 to 24,000 units/min with a reperfusion efficacy of 60—89% (108—112). In another urokinase trial, 2.0 million units were adrninistered intravenously, resulting in a thrombolytic efficacy of 60% (113). Effectiveness in terms of reduction in mortaUty rate has not been deterrnined because of the small number of patients studied. 

One drawback of thrombolytic therapy is a high incidence of reocclusion. In a report using a canine model, inclusion of heparin [9005-49-6] (anticoagulant therapy) in the treatment prevented this side effect (158). The combination of aspirin [50-78-2] (antiplatelet therapy) and streptokinase (thrombolytic therapy) has also shown significant therapeutic advantages (78). Although additional work is needed to estabUsh the thrombolytic advantage of various combinations, preliminary results in this area indicate promise in terms of increased efficacy and reduced side effects. 

Activase 550/20 mg Thrombolytic encymes lyophilized recombinant tPA Genentech... 

A derivative of 163, 3-(2-morpholinoethylthio)[l,2,4]triazino[5,6-fo]indole dihydrochloride, is used as a thrombolytic (91URP1672373). Derivatives of the pyrazolo[5,l-c][l, 2,4]tria-zines were used as a constituent of silver halide color photographic supported material, which showed good color reproducibility [91JAP(K)03/291649]. The protective action of [l,2,4]triazino[4,3-a]benzimidazoles as corrosion inhibitors was studied (91MI8). 

PA S1 S01.232 /-Plasminogen activator Used as therapeutic thrombolytic agent... 

Discuss the uses, general drug actions, adverse reactions, contraindications, precautions, and interactions of warfarin, heparin preparations, and the thrombolytic drugs. 

Discuss important preadministration and ongoing assessment activities the nurse should perform on the patient taking an anticoagulant or thrombolytic drug. 

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