стрептокиназы

Описание

Streptokinase is a protein produced by certain strains of hemolytic group C streptococcus, and it was the first clinically useful fibrinolytic. Unlike other plasminogen activators, streptokinase is not an enzyme and cannot break any bonds in a plasminogen molecule by itself. It forms an equimolecular compound with plasminogen, thus forming a streptokinase–plasminogen complex. In the plasminogenic region of the resulting complex, certain conformational changes lead to a break in a few peptide bonds, and transformation of this complex into a streptokinase–plasmin complex, or free plasmin, which also decomposes fibrin.

Использование

This drug has a half-life in the plasma of 15–30 min, and is used intravenously to treat patients with severe, massive pulmonary embolism and thrombus of the veins; it is also used during myocardial infarctions. Recently, a number of streptokinase derivatives have been proposed, in particular acetylated derivatives, which are developed for use as fibrinolytics.

Общее описание

Streptokinase (Kabikinase, Streptase)is a catabolic 47,000-d protein secreted by group Cβ-hemolyticstreptococci. It is a protein with no intrinsic enzymaticactivity. Streptokinase activates plasminogen toplasmin, a proteolytic enzyme that hydrolyzes fibrin andpromotes the dissolution of thrombi. Plasminogen is activatedwhen streptokinase forms a 1:1 stoichiometric complexwith it. Allergic reactions to streptokinase occur commonlybecause of antibody formation in individuals treatedwith it. Furthermore, the antibodies inactivate streptokinaseand reduce its ability to prolong thrombin time.Streptokinase is indicated for acute myocardial infarction,for local perfusion of an occluded vessel, and before angiography,by intravenous, intra-arterial, and intracoronaryadministration, respectively.

Механизм действия

Streptokinase is a protein purified from culture broths of group C β-hemolytic streptococci bacteria. Streptokinase contains a single polypeptide chain of 414-amino-acid residues with a molecular weight of 47 kDa. Streptokinase by itself has no intrinsic enzymatic activity. To be active, it must bind with plasminogen to form an activator complex (1:1 complex). This complex then acts to convert uncomplexed plasminogen to the active fibrinolytic enzyme, plasmin. The streptokinase/plasminogen complex not only degrades fibrin clots but also catalyzes the breakdown of fibrinogen and factors V and VII. As a result, streptokinase is considered to be a fibrinnonspecific drug.

Фармакокине?тика

Unfortunately, the half-life of the activator complex is less than 30 minutes, which frequently is too short to completely lyse a thrombus. Anistreplase (APSAC; Eminase) is a 1:1 streptokinase/lysineplasminogen complex that has been acylated with an anisoyl group at the active-site serine within the lysine-plasminogen. Anistreplase is inactive as such, but following complexation with fibrin, the anisoyl group is slowly cleaved, exposing the active site and, thus, leading to degradation of fibrin. The pro-drug nature of anistreplase exhibits an improved pharmacokinetic profile, with anistreplase acting as a semiselective lysis agent at the clot site. The inactivity of the circulating anistreplase also allows this drug to be given as a very rapid intravenous infusion (typically, 30 U over 3–5 minutes). Tissue reperfusion following anistreplase therapy compares favorably to streptokinase because of the extended half-life (90 minutes).

Побочные эффекты

Because it is a foreign protein, streptokinase is associated with significant hypersensitivity reactions. Most people have, at some point in their lives, had a streptococcal infection and, therefore, have developed circulating antistreptococcal antibodies. These antibodies frequently are active against streptokinase as well. The response of the streptokinase to these antibodies can vary widely, from inactivation of the fibrinolytic properties of the protein to rash, fever, and rarely, anaphylaxis. Significant allergic reactions to streptokinase occur in approximately 3% of patients.