FIBRINOLITIC MEANS (fibrin - j-Greek lysis dissolution, destruction) — the pharmaceuticals dissolving or promoting dissolution of threads of fibrin and causing as a result of it a rassasyvaniye fresh and the blood clots which did not undergo the organization yet. T. pages apply to prevention and treatment of tromboembolic episodes.
T. pages conditionally divide into drugs of direct and indirect action. K F. pages of direct action carry the substances influencing directly fibrinolitic system of in vitro and in vivo blood. T. pages of indirect action cause release of the endogenous substances activating fibrinolitic system at resorptive action. K F. pages of direct action carry such activators of a fibrinolysis (see) as a strentokinaza, a stafilokinaza, an urokinase, Streptoliasum (Streptasum), fibrinolitic enzyme fibrinolysin (see), proteolytic enzymes: trypsin (see), chymotrypsin (see), Thrombolytinum (a complex of trypsin and heparin), and also drugs of proteases from fungi (aspergillin, trikholizin, etc.).
T. pages of the fermental nature apply not only in the form of individual substances, but also in the form of the so-called immobilized enzymes. The last have the prolonged effect and are capable to provide adjustable deposition of medicinal substance in appropriate authority and fabric without increase in its concentration in the general blood-groove. To number immobilized water-soluble F. the page belongs the domestic drug Streptodecasum containing Streptokinasa.
To group F. pages of indirect action carry the substances of a synthetic and natural origin activating a fibrinolysis by release of activators of plasminogen (plasminogen) from a wall of vessels or leukocytes. Nek-ry vasodilating substances, napr, niacin (see), its derivatives can have indirect fibrinolitic effect. In the indirect way activate a fibrinolysis also adrenaline (see), acetylcholine (see), the substances promoting allocation of a histamine (see), the pyrogenic bacterial lipopo-liyeakharida, napr, pirogepat (see).
From a large number of the substances having properties F. the page, in medical
practice for treatment of thromboses is used limited number of drugs. One of the most active among them is drug of natural enzyme of a blood plasma of the person the fibrinolysin splitting fibrin and fibrinogen. It splits such peptide bonds, hydrolysis to-rykh leads to bystry division of a molecule of fibrin into water soluble fragments (fibrinopeptides). Besides, it can destroy peptide bonds of a glucagon in an organism, (5 lactoglobulin, a growth hormone, blood-coagulation factors V, VII, X and XII, nek-ry components of a serumal complement, etc. However these properties are shown at big concentration of fibrinolysin. Fibrinolysin also has the oppressing effect on the aggregation of thrombocytes induced by thrombin. Fibrinolysin influences kinin system that is followed by formation of active pinii (see).
Mechanisms of operation of various activators of a fibrinolysis are not identical. So, the activating action of Streptokinasa is carried out in three various ways: by formation of a complex with plasminogen, formations of a complex with the special pro-activator, and also as a result of direct action of Streptokinasa on a molecule of plasminogen. The urokinase causes splitting in a molecule of plasminogen internal are-ginil-valinovoy of a peptide bond and formation at the same time of a molecule of plasmin. Stafilokinaza activates plasminogen by means of the conformational changes of a molecule of proferment releasing an active center of enzyme. Trypsin activates plasminogen by means of proteolytic splitting of peptide bonds and itself actively splits threads of fibrin.
Streptokinasa and an urokinase are capable to get in blood clot and to activate there the plasminogen adsorbed on fibrin. Lysis of blood clot under the influence of Streptokinasa and an urokinase is process, in Krom an important role is played by both an exogenous, and endogenous lysis of threads of fibrin. Unlike it thrombolytic effect of fibrinolysin develops generally at the edges of blood clot. The central sites of blood clot of a rack to fibrin to a lysine. It is possible that it is to some extent caused by distinctions of the molecular weight (weight) of substances and their abilities to get in blood clot.
In operation Streptokinasas and urokinases on an organism are available also essential distinctions. Streptokinasa is protein, alien for an organism, therefore at repeated introduction it can cause allergic reactions. As a rule, in 1 — 2 week after the first infusion of Streptokinasa there is a substantial increase of a caption of an antistrep-tokinaza reaching a maximum in 3 — 4 weeks. Through 4 — month their contents would decrease to initial level. In this regard repeated use of this drug can be carried out not earlier than in
3 months after the first introduction in the corresponding doses and with addition of corticosteroids. For detection of hypersensitivity of an organism to Streptokinasa it is possible to use definition of a caption anti-streptokinaznykh antibodies.
The urokinase is substance, to endogenous substances of a human body related by origin, in connection with the Czech \1 it does not cause the allergic reactions characteristic of Streptokinasa.
Drugs of proteolytic enzymes (trypsin, etc.) possess strong thrombolytic action. However at parenteral administration they cause serious complications, including destruction of various blood-coagulation factors, the hemorrhagic phenomena that limits a possibility of use of such drugs for resorptive action.
One of methods of increase in a therapeutic effectiveness and decrease in toxicity F. the page is their regional intravascular introduction to a zone of an arrangement of blood clot. It reaches high concentration F. the page in the field of blood clot, and low concentration in the general blood-groove allows to avoid undesirable complications. E. I. Chazov's works and sotr. (1981) the possibility of administration of thrombolytic substances by means of a special catheter even to mouths of coronary arteries is shown.
Other method of increase in thrombolytic activity and safety of the proteolytic drugs received from fungi is additional fractionation of proteins from the proteases formed by fungi. At the same time there is a possibility of receiving more specific to a fibrinolysis and less toxic proteases. To the same purpose can serve researches of genetic variability and selection of mutants of the microorganisms which are producers of more specific fibrinolitic substances.
The main indications to use F. pages are thromboembolisms of peripheral vessels, especially deep veins of extremities, pulmonary arteries, vessels of eyes, an acute myocardial infarction, acute thrombophlebitis, an aggravation hron. thrombophlebitis. Use F. the page at fibrinferments of vessels of a brain is complicated by difficulties of diagnosis. Treatment is carried out only when there are no doubts available at a sick trombotichesky stroke. At treatment of thromboembolisms it is reasonable to combine introduction F. page with anticoagulants and inhibitors of aggregation of thrombocytes. Efficiency of treatment of thromboses using F. the page substantially depends on time which passed from the moment of developing of blood clot, the sizes and localization of blood clot, degree of its retraction, concentration of fibrinogen in blood, conditions of cardiovascular system, etc. It is established that venous blood clots are exposed to a lysis under the influence of F. page during more long term, than arterial blood clots. At a myocardial infarction use F. the page quite often is followed by analgetic effect. The mechanism of easing of pain is connected with spasmolytic action F. page, increase in rate of volume flow of a coronary blood-groove, destruction of secondary blood clots, improvement of microcirculation and reduction in this regard zones of ischemia around the center of a necrosis.
At overdose F. page or the increased reaction of an organism to their introduction as antagonists use inhibitors of a fibrinolysis from among inhibitors of proteases of a natural origin, napr, the sir-tripin (see), Contrykal, ingitril, Trasylolum (see), etc., and also nek-ry synthetic drugs, napr, an aminocaproic pislota (see), naraaminometilbenzoyny to - that (Ambenum), paraaminomet ltsik logeksan-
carboxylic to - that, etc. If necessary apply also fibrinogen (see).
Contraindications to use F. pages are hemorrhagic diathesis, bleedings, open wounds, a peptic ulcer of a stomach and duodenum, nephrite, hepatitis, a fibrinogenopenia, a pulmonary tuberculosis in an acute form, a radial illness. Relative contraindications are defeats of vessels of a brain against the background of the high ABP, heavy atherosclerosis and d e to about megapixel ens and tsi I with e r dechno - from wasps at d isty system, a diabetes mellitus. Appointment F is not recommended. page, in particular Streptokinasas, to pregnant women (in the first 18 weeks of pregnancy) as the fibrinny layer of a trophoblast can be broken that causes premature placental detachment.
Bibliography: Urgent problems of a gemosta-zpologiya, gyud edition of B. V. Petrovsky, etc., M., 1981; JI of yus of V. A., B e l O-at with about in Yu. B. and Bokarev I. N. Treatment of thromboses and hemorrhages in clinic of internal diseases, M., 1976; Mali-to about in with to and y the Item II. and Kozlov V. A. And yes tuko and at l yan t of N and I both tro mbol and tich a mustache and
therapy in surgery, M., 1976; H and -
zo in E. II. and L and to i! and K. M. Anticoagulants and fibrinolitic means, M., 1977, bibliogr. K. M. Lakin.