Streptokinase Anistreplase

Anistreplase (streptokinase- plasminogen complex) streptococci protein streptococci plaminogen, which is then cleaved to form plasmin. Plasmin mediate fibrinolysis. Systemic lytic state and immunogenicity may limit its use. Because antistreplase is aheadly lined to plaminogen, the onset of fibrinolytic is faster. These enzymes are not fibrin-specific. 

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). 

The side effects of anistreplase appear to be similar to those of streptokinase, including immune reactions and a systemic lytic state conductive to hemorrhage. 

The nurse must continually assess the patient for anaphylactic reactions (difficulty breathing, wheezing, fever, swelling around the eyes, hives, or itching) particularly with anistreplase or streptokinase Resuscitation equipment is immediately available... 

ISIS-3. ISIS-3 a randomised comparison of streptokinase vs tissue plasminogen activator vs anistreplase and of aspirin plus heparin vs aspirin alone among 41299 cases of suspected acute myocardial infarction. Lancet 1992 339 753-70. 

Plasminogen, an inactive precursor, is activated to plasmin which as a protease is able to break down fibrin clots. The thrombolytic agents in use promote the conversion of plasminogen to plasmin at the site of a thrombus. Indications include post-myocardial infarction treatment. The thrombolytic must be administered within 6 hours for an optimal effect. Other indications are treatment of acute pulmonary thromboembolism, deep-vein thrombosis, acute arterial thrombosis and thromboembolism, as well as in the clearance of arteriovenous catheters and can-nulae. Agents are streptokinase, anistreplase, urokinase, alteplase, reteplase and tenecteplase. 

E Role in therapy Thrombolytic agents currently licensed for the treatment of AMI in the United States include streptokinase, tissue plasminogen activator, anistreplase, reteplase, and tenecteplase. TNKase and alteplase have similar clinical efficacy for thrombolysis after myocardial infarction (i.e., similar mortality and intracranial hemorrhage rates). However, advantages of TNKase include ease and rapidity of administration, longer half-life, greater fibrin specificity, and lower noncerebral bleeding rates. Reteplase shares some characteristics of tenecteplase (e.g., similar half-life, rapid onset, and ease of administration). 

Anistreplase is a complex of human plasminogen and streptokinase in which an anisoyl group has been introduced in the plasminogen... 

Schematic representation of the fibrinolytic system. Plasmin is the active fibrinolytic enzyme. Several clinically useful activators are shown on the left in bold. Anistreplase is a combination of streptokinase and the proactivator plasminogen. Aminocaproic acid (right) inhibits the activation of plasminogen to plasmin and is useful in some bleeding disorders. t-PA, tissue plasminogen activator.

Anistreplase (anisoylated plasminogen streptokinase activator complex APSAC) consists of a complex of purified human plasminogen and bacterial streptokinase that has been acylated to protect the enzyme s active site. When administered, the acyl group spontaneously hydrolyzes, freeing the activated streptokinase-proactivator complex. This product (recently discontinued in the USA) allows for rapid intravenous injection, greater clot selectivity (ie, more activity on plasminogen associated with clots than on free plasminogen in the blood), and more thrombolytic activity. 

All patients with acute myocardial infarction should be considered for intravenous thrombolytic therapy with streptokinase, tissue plasminogen activator (TPA), or anistreplase because these agents are effective in both preserving cardiac function and reducing mortality. 

Clinical trials One of the trials (ISIS-3) showed that streptokinase plus aspirin performed as well as recombinant tissue-type plasminogen activator (rt-PA) or complex formulations of streptokinase such as anistreplase (APSAC). The GUSTO trial showed a small advantage for the much more expensive t-PA over streptokinase, but with a significantly higher risk of hemorrhagic stroke. Nine clinical trials—each containing over 1000 patients with suspected acute myocardial infarction—... 

Anisoylated plasminogen streptokinase complex (anistreplase) Urokinase Fibrin specific... 

Anistreplase (anisoylated plasminogen streptokinase activator complex, APSAC), is the plasminogen-streptokinase complex (above) in which the enzyme centre that converts plasminogen to plasmin is protected from deactivation, so prolonging its action. 

Streptokinase, anistreplase and urokinase are not well absorbed by fibrin thrombi and are called nonfibrin-selective. They convert plasminogen to plasmin in the circulation, which depletes plasma fibrinogen and induces a general hypocoagulant state. This does not reduce their local thrombolytic potential but increases the risk of bleeding. 

Allergy. Streptokinase and anistreplase are antigenic and anaphylactic reactions with rash, urticaria and hypotension may occur for most people have circulating antibodies to streptococci. Antibodies persist after exposure to these drugs and their reuse should be avoided between 5 days and 12 months as the recommended dose may not overcome immune resistance to plasminogen activation. 

Hemorrhage is the major risk of thrombolytic drugs there are some differences in risks between the various agents, and certain susceptibility factors can be identified. Transient hypotensive reactions have been described with all thrombolytic agents, but they are in principle reversible. Hypersensitivity reactions are most often seen in patients who have been treated with compounds derived from cultures of streptococci (streptokinase and anistreplase). Tumor-inducing effects have not been reported. 

Guillain-Barre syndrome has been reported in patients who were treated with streptokinase and anistreplase (14-18). As streptokinase and anistreplase are derived from streptococci, an immunological reaction is thought to have been responsible. 

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