Description
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.
Chemical Properties
Streptokinase is a white or off-white amorphous powder, easily soluble in water and saline, very unstable in dilute solution. It is very unstable in dilute solution. The aqueous solution should be inactivated in the refrigerator for more than 12h, and should be used immediately at room temperature. Optimum ph7.3～7.6, reversible inactivation can occur when the solution is in ph5.0, irreversible inactivation occurs above ph9.0. The powder can be stored in 2～80C and sealed for 2 years. This product itself has no enzyme activity, it and the blood fibrinogen pre-activator interact with each other to form a complex, only with protease properties, so that the fibrinogen into fibrinolytic enzymes, not only due to the activation of the plasma fibrinolytic system to make the outside of the thrombus dissolved, but also can be mixed with fresh thrombus to make the fibrin within the clot to dissolve the clot disintegration. The product should not be violently shaken when dissolving, so as not to reduce the vitality.
Originator
Streptase,Hoechst,France,1970
Uses
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.
Uses
Streptokinase is commonly used as a thrombolytic agent in the therapy of ischemic stroke. This therapy carries the important risk of intracerebral hemorrhage. Streptokinase is also used in the treatment of complicated parapneumonic effusions and empyema where adverse reactions, allergic type, are rare. Streptokinase has been used in a study to compare primary coronary intervention and thrombolytic therapy in myocardial infarction patients.
Therapeutic Function
Enzyme
General Description
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.
Biochem/physiol Actions
DKK1 (dickkopf WNT signaling pathway inhibitor 1) functions as a pure inhibitor of Wnt signaling, and was identified as an essential factor for head induction during early Xenopus embryogenesis by suppressing Wnt signaling. In skin, this protein plays a role in determining the pigmentation pattern of the human hand. In colon cancer cells, this protein is inactivated by CpG island promoter hypermethylation. Mesenchymal stem cells (MSCs) have an anti-proliferative effect on cancer cells, as they secrete DKK1 which blocks Wnt signaling.
Mechanism of action
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.
Pharmacokinetics
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).
Clinical Use
Fibrinolytic:
Thrombolysis in DVT, PE, acute arterial
thromboembolism, acute MI, thrombosed A-V
shunts
Side effects
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.
Veterinary Drugs and Treatments
Streptokinase may be useful for the adjunctive treatment of serious
thromboses. The use of thrombolytics (streptokinase, t-PA) in cats
is controversial.
Drug interactions
Potentially hazardous interactions with other drugs
Anticoagulants should not be given with
streptokinase.
Heparin infusions should be stopped 4 hours
before streptokinase infusion. If this is not possible,
protamine sulphate should be used to neutralise
the heparin; heparin infusions can be restarted 4
hours post streptokinase infusion followed by oral
anticoagulants.
Metabolism
A small proportion of the dose is bound to antistreptokinase antibodies and metabolised with a half-life
of 18 minutes, whilst most of it forms the streptokinaseplasminogen activator complex and is biotransformed
with a half-life of about 80 minutes.
Description
Streptokinase Recombinant produced in E.Coli is a non-glycosylated polypeptide chain containing 414 amino acids and having a molecular weight of 47.3kDa.
The Streptokinase is purified by proprietary chromatographic techniques.
Background
Dickkopf-related protein 1 (DKK1) antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by creating a ternary complex with the transmembrane protein KREMEN which promotes internalization of LRP5/6. DKKs have a significant role in vertebrate development, where they locally inhibit Wnt controlled processes for instance antero-posterior axial patterning, limb development, somitogenesis and eye formation. Furthermore, Dkks are involved in bone formation and bone disease, cancer and Alzheimer disease in Adults.
