ANTICOAGULANTS (anticoagulantia; Greek anti-against + a coagulant[s]) — the substances oppressing activity of coagulant system of blood.
And. divide conditionally into the following groups: 1) And. direct action — heparin (see), heparinoids (see), hirudine (see) and close to it on structure and the mechanism of action of a girudinoida; 2) And. indirect action — Dicumarinum (see), neodicoumarin (see), atsenokumarol (see), Syncumarum, Phepromaronum (see) and other derivative 4 oxycoumarins, and also Phenilinum (see), Omephinum (see) and other derivatives of an indandion; 3) salts of rare earth metals — compounds of lanthanum, lanthanides, yttrium and scandium; 4) salts of lemon and oxalic acids, fluorides, ethylene diamine tetraacetic to - that (EDTA).
And. direct action interfere with a blood coagulation as in an organism, and in vitro. Among them the main drug is heparin. At intravenous administration of heparin the effect occurs instantly, action continues 4 — 6 hours; at introduction under skin, intramusculary and sublingual its efficiency decreases. Heparinoids are less active and more toxic, than heparin; in this regard their use in medicine is limited. Hirudine and girudinoida at intravenous administration lower coagulability of blood almost instantly, action continues 1 — 2 hour; at hypodermic and intramuscular introduction the effect occurs in 1 — 2 hour and lasts 6 — 8 hours [F. Markwardt, 1963].
And. indirect action slow down a blood coagulation only in an organism. They quickly and, as a rule, completely (except for Dicumarinum) are soaked up from went. - kish. path. In a blood plasma And. a coumarinic row contact proteins, generally albumine. Derivatives of an indandion are less studied in this respect; on reaching a maximum their concentration in blood begins to decrease. So-called time of semi-removal at various substances fluctuates from 7 to 50 hour. Irrespective of a way of introduction the effect occurs in 24 — 72 hours and several days proceed.
Salts of rare earth metals lower coagulability of blood in an organism and in vitro. At intravenous administration the effect occurs instantly, duration of action about days.
Salts of lemon, oxalic, hydrofluoric acids and EDTA interfere with a blood coagulation of in vitro.
On the mechanism of action on coagulability of blood heparin is almost universal And.: exerts antitromboplastinovy, anti-prothrombin and antithrombic impact, interferes with transition of fibrinogen to fibrin, raises a fibrinolysis, in high doses slows down aggregation and adhesiveness of platelets. And. indirect action are antimetabolites of phthiocol. In an optimum dose they break biosynthesis of factors II (prothrombin), VII (proconvertin), IX (Christmas factor), X (styuart-prauer-factor), and activity of factors of VII and IX, then II and X decreases in the beginning (see. Coagulant system of blood ). Speed of approach of effect and duration of action And. are substantially connected with metabolism and speed of their allocation. Slowly metabolized and slowly allocated And. (Dicumarinum, Phepromaronum) give more equal and smooth curve of decrease in coagulability of blood and are inclined to cumulation. Quickly metabolized and quickly emitted substances (neodicoumarin, Phenilinum, Syncumarum) are less inclined to cumulation.
A certain value has also character of a diet: small contents in food of fat and phthiocol leads to strengthening of action and increase in toxicity And. On metabolism And. also some medicines exert impact: barbital, phenobarbital and some other substances accelerate metabolism And. and at long introduction reduce their influence on coagulability of blood, salicylates exponentiate action derivative 4 oxycoumarins. And. indirect action increase permeability of walls of vessels, relax smooth muscles of vessels, especially coronary, muscles of intestines, bronchial tubes, separate oxidizing phosphorylation, increase allocation from an organism of salts uric to - you, reduce the level of lipids in blood, reduce activity of steapsin and amylase, enterokinase and an alkaline phosphatase of a duodenum, reduce ATF-aznuyu activity of a myosin and contractility of aktomiozinovy threads in skeletal and smooth muscles, in high doses can reduce an immune responsiveness.
Salts of rare earth metals reduce activity of factors of II, VII and X. Besides, they promote release of heparin from mast cells. Salts of lemon and oxalic acids, and also fluorides and EDTA form the low-dissociating connections with calcium (the IV factor) and, thus, switch off it from system of a blood coagulation in this connection aggregation and a platelet stickness is slowed down.
And. direct action appoint for bystry decrease in coagulability of blood for the purpose of prevention and treatment of tromboembolic episodes at a myocardial infarction, heart operations and blood vessels, a thromboembolism of pulmonary and brain vessels, the central vein of a retina, thrombophlebitis, etc.; And. indirect action — for long decrease in coagulability of blood for the purpose of the prevention of education or the termination of growth of blood clot if it was already formed. Due to the long latent effect of substances of this group it is reasonable to appoint in the first day of treatment them in a combination with heparin. And. indirect action especially widely apply at a myocardial infarction, thrombophlebitis, a phlebothrombosis, a mesenteric thrombosis, fibrinferment of brain vessels (under a close check of the doctor). They are appointed also for the purpose of prevention of thromboses at organ transplantation to people of advanced age and in some other cases. Salts of rare earth metals in connection with cumulation and toxic action on an organism in clinic do not apply to intravenous administration; they are used outwardly in the form of ointment (flogosa) at thrombophlebitis, dermatitis, eczema and other skin diseases. Salts of lemon and oxalic acids, fluorides, EDTA apply generally in laboratory practice to the prevention of a blood coagulation in tests, and also at production of separate blood preparations.
Use And. demands close laboratory control behind a condition of coagulability of blood. Usually And. appoint in the doses supporting hypocoagulative effect at optimum level that corresponds to a prothrombin indicator from 40 to 60%. At overdose And. the hemorrhagic phenomena connected with decrease in both coagulability of blood, and capillary resistance are possible: microhematuria; gross hematuria; capillary odontorrhagia and nose; emergence on skin of bruises at an insignificant injury; bleedings at small cuts, napr, during the shaving, on site a prick at injections; uterine and gastric bleedings, etc. Treat rare complications: the intolerance of drug which is shown the dispeptic phenomena and vomiting, allergic reactions, dizziness, a hair loss. At emergence of the first symptoms of hemorrhagic diathesis And. indirect action immediately cancel, to the patient appoint drugs of vitamin Κ 1 , the means increasing capillary resistance (citrin, ascorbic to - that, etc.). If it is not enough, make a hemotransfusion. In case of a hair loss vitamin D has favorable effect 2 . At emergence of bleeding in connection with use of heparin and heparinoids his antagonists — pro-that-minsulfat (5 ml of 1% of solution intravenously once or repeatedly with an interval of 15 min.), and also the main dyes appoint (tripanovy blue, toluidine blue, azur And, etc.).
Use And. contraindicated at hemorrhagic diathesis, heavy abnormal liver functions and kidneys, a peptic ulcer of a stomach and a duodenum, pregnancy (especially in the second half), cancer of any localization, a subacute septic endocarditis; it is not recommended to appoint And. to nursing mothers; at treatment And. patients with high arterial pressure, and kidneys it is necessary to be careful with various abnormal liver functions.
Bibliography: Yefimov V. S., etc. Pharmacological impacts on a blood coagulation, in book: Results of science, Pharmacology, t. 3, page 93, M. 1972, bibliogr.; Kudryashov B. A. Problems of a blood coagulation and thrombogenesis, M., 1960, bibliogr.; To at sh e l e in with to and y B. P. Sketches of anticoagulating therapy, M., 1958, bibliogr.; Varnish and K. M N. Medicinal regulation of a blood coagulation, M., 1971; Treatment by anticoagulants and fibrinolitic means, under the editorship of Yu. Danis, Kaunas, 1967; Machabeli M. S. Koagulopaticheskiye syndromes, M. 1970, bibliogr.; Mashkov-with to and y M. D. Pharmaceuticals, p. 2, M., 1972; Sketches practical haemo-staziologii, under the editorship of V. A. Germanov, Kuibyshev, 1971; Panchenko V. M. Clinical koagulologiya, page 113, M., 1970; P e r l and to E. Anticoagulants, the lane with it., L., 1965, bibliogr.; H and z about in E. I. Fibrinferments and embolisms in clinic of internal diseases, page 195, M. — Warsaw, 1966; Douglas A. S. Anticoagulant therapy, Oxford, 1962, bibliogr.; Markwardt F. Blutgerinnungshemmende Wirkstoffe aus blutsaugenden Tieren, Jena, 1963, Bibliogr.; VigranJ.M. Clinical anticoagulant therapy, Philadelphia, 1965, bibliogr.
K. M. Lakin.