From Big Medical Encyclopedia

CALCIFEROLS (vitamins of group D) — group of the related chemical compounds having antirachitic activity. In the chemical relation To. are steroids, derivatives of cyclopentanperhydrophenanthrene and differ from each other in structure of a side aliphatic chain.

To. — colourless crystal connections, not water soluble, well soluble in oils and organic solvents (alcohol, ether, etc.), possess a characteristic maximum of absorption at 265 nanometers, rotate the plane of the polarized light to the right. To. are very sensitive to effect of light and oxygen of air, especially during the heating. In this regard drugs K. it is necessary to store in the cold, in dark glass, under vacuum or inert gas.

To. are formed as a result of a photo isomerization of the corresponding provitamins: provitamin of cholecalciferol is 7-degidrokholesterin, formed of cholesterol; provitamin of ergocalciferol — the ergosterol which is present at plants and microorganisms. At industrial receiving To. by photoradiation of provitamins along with To. a number of by-products, in particular a lumisterol and a tachysterol is formed.

Main functions K. in an organism membranes are connected with providing transport of calcium ions and phosphorus through biol. Allocate three processes, participation in which To. can be considered as rather reasonable: 1) transfer of calcium and phosphorus through epithelial cells of a mucous membrane of a small bowel in the course of their absorption; 2) mobilization of calcium from a skeleton by a rassasyvaniye of a preeducated bone tissue; 3) a reabsorption of phosphorus and calcium in renal tubules.

Though the basic patomorfol, disturbance of a mineralization of a bone tissue, nevertheless convincing proofs of direct participation is a consequence of insufficiency of vitamin D To. in processes of calcification are absent. According to most of researchers, defects of a mineralization at rickets are caused by decrease in concentration of calcium and phosphorus in a blood plasma owing to disturbance being under control To. processes of absorption of these elements in intestines, their mobilization from a bone tissue and a reabsorption in kidneys.

Exchange of calciferols

Cholecalciferol is formed in an organism of a 7-degidrokholesterin at radiation of skin by an ultraviolet light with the wavelength of 280 — 320 nanometers. To. can come to an organism in the form of the medical drugs accepted with the preventive or medical purpose.

Chemical structure of calciferols, their provitamins and products of exchange: I \ergosterol (provitamin D 2 ); II \ergocalciferol (vitamin D 2 ); III \7-degidrokholesterin (((((((((provitamin D 3 ); IV \cholecalciferol (vitamin D 3 ); V \25 oxycholecalciferol (((((((((25 oxyvitamin D 3 ); VI \1,25 dioxycholecalciferol (((((((((1,25 dioxyvitamin D 3 ).

To. perform the specific functions in a metabolism not in a look hole-and ergocalciferol, and in the form of the active metabolites which are formed of them in an organism.

To. are soaked up in a small bowel and with chylomicrons come to a liver where are exposed to a hydroxylation, as a result to-rogo cholecalciferol ergocalciferol in 25 oxyergocalciferol turns into 25 oxycholecalciferol, and. This transformation catalyzes 25 hydroxyls for To., localized in an endoplasmic reticulum of hepatocytes. Normal concentration of 25 oxycalciferols in a blood plasma makes 10 — 20 ng/ml, decreasing at rickets and increasing at the persons receiving high doses To.

25 oxycalciferols, coming to kidneys, are exposed to further transformations with formation of a number of metabolites, the most important of which is 1,25-dioksikholekaltsife-rol. Its education from 25 oxycholecalciferols catalyzes enzyme a 1alfa-hydroxylase 25 oxycholecalciferols located in mitochondrions of epithelial cells of renal tubules. Similarly from 25 oxyergocalciferols 1,25 dioxyergocalciferol are formed.

1,25 dioxycholecalciferol and 1,25 dioxyergocalciferol are the main functionally active form K., directly responsible for implementation of functions of vitamin D in processes of transmembrane transfer of calcium and phosphorus. Most of researchers considers 1,25-dioksikho-lekaltsiferol as the major hormone participating in maintenance of a homeostasis of calcium and phosphorus. From this point of view To., of which in an organism 1,25 dioxycalciferols are formed, are pro-hormones. The molecular mechanism of action of 1,25 dioxycalciferols is connected with implementation in biol, membranes of the structural changes giving them ability to transport of calcium. The important role in these mechanisms belongs to protein synthesis, the kaltsiysvyazyvayushchy protein localized on the microvillis of absorbing cells of a mucous membrane of a small bowel connecting and transporting calcium, in particular. Synthesis of 1,25 dioxycalciferols in kidneys is strictly regulated on a feedback mechanism depending on the need of an organism for calcium and phosphorus. The major factors regulating biosynthesis of 1,25 dioxycalciferols are concentration of calcium and phosphorus in a blood plasma and the level of secretion of parathyroid hormone which in relation to 1,25 dioxycalciferols is the tropine stimulating their synthesis. Concentration of 1,25 dioxycalciferols in a blood plasma is very low and makes 0,03 — 0,04 ng/ml.

To. and products of their exchange do not collect in bodies and fabrics in significant amounts, except for fatty tissue, edges, apparently, can deposit them; they are brought from an organism of hl. obr. with a stake, partly in not changed look, partly in the form of the oxygenated products of type deprived of antirachitic activity bilious to - t and their conjugates.

Biol, activity To. it is measured in the international (international) units (ME). 1 ME corresponds to antirachitic activity of 0,025 mkg crystal ergo-or cholecalciferol on rats; respectively 1 mkg ergo-or cholecalciferol supports 40 ME.

Biol, activity of ergocalciferol and cholecalciferol to the person and the majority of animals is identical, except for chickens and some types of subhuman primates in which relations activity of cholecalciferol several times exceeds activity of ergocalciferol.

Biol, activity of 25 oxycalciferols by 1,5 — 2 times, and 1,25 dioxycalciferols by 5 — 10 times exceeds initial K.

Potrebnost' activity of the person in vitamin D at sufficient and regular insolation is provided due to photochemical education To. in skin. For children, pregnant women and nursing mothers the need for vitamin D is defined in 400 — 500 ME, on Far North these norms increase to 1000 ME for pregnant women and feeding, and for children to 2000 ME. Contents To. in food stuffs it is small (tab. 1). Due to the addition in some cases significant amounts To. in a diet of page - x. animals, in particular chickens, contents To. in their meat and other products can significantly increase and be a source of excess receipt To. in a human body.

Insufficient education or receipt in an organism To. is one of the reasons rickets (see). Along with it in a pathogeny of rickets the essential role can belong to disturbances of education and functioning of active forms K. in an organism. Temporary imperfection at children of the first year of life of the fermental systems which are carrying out synthesis 25-oksi-and 1,25 dioxycholecalciferols and also the transport mechanisms participating in absorption of calcium and phosphorus can lead to emergence of some symptoms of rickets even at normal receipt in an organism To.

Disturbance of synthesis of 1,25 dioxycalciferols in kidneys is the reason of renal osteodystrophies at hron, a renal failure (see. Nephrogenic osteopathy ). Disturbance of exchange To., caused by genetic defect of synthesis 1,25 dioxycholecalciferols, vitamin of the D-dependent rickets which is not giving in to treatment by usual doses of vitamin D is the cornerstone inborn. Separate types of disturbances of exchange of vitamin D at children are presented in table 2.

For assessment of security of the person To. investigate concentration of calcium and phosphorus, and also 25 oxycalciferols in serum or a blood plasma.

Drugs of calciferols

To group of specific antirechitic medicines K. several versions among which the greatest practical value have ergocalciferol (vitamin D belong 2 ) and cholecalciferol (vitamin D 3 ).

The medical industry produces the following drugs: 0,5%, 0,125% and 0,0625% solutions of ergocalciferol in oil (200 000 ME/ml, 50 000 ME/ml and 25 000 ME/ml); oil solution of ergocalciferol in gelatin capsules (500 or 1000 ME in piece); 0,5% solution of ergocalciferol in alcohol (200 000 ME/ml); a dragee of ergocalciferol (500 ME in 1 piece).

Drugs K. are specific to lay down. and the prophylactics applied to prevention and treatment rickets (see). However a wide range biochemical, activities To. allows to use them and at some other diseases. At a tubercular lupus of skin, mucous membranes of a nose and an oral cavity drugs K. apply with good therapeutic effect independently and in a combination with other methods of treatment. For treatment inborn vitamin of D-dependent rickets, and also renal osteodystrophies use drugs 1,25 of dioxycholecalciferol, and also its synthetic analog 1 - alpha oxycholecalciferol. Drugs K. are shown also at a tetany because of dysfunction of epithelial bodies.

Use of drugs of D2 vitamin contraindicated at active forms of a pulmonary tuberculosis, diseases went. - kish. path, peptic ulcer of a stomach and duodenum, acute and hron, diseases of a liver, organic lesions of heart and circulatory unefficiency.

At appointment To. with to lay down. the purpose elderly people need to consider that such drugs, increasing the content of cholesterol in blood and strengthening deposits of salts of calcium in an organism, can promote development of atherosclerosis.

To. in the doses significantly exceeding fiziol, requirement, have high toxicity, causing development of a D-hypervitaminosis with a hypercalcemia and calcification of internals and fabrics (kidneys, an aorta, heart) that leads to disturbances of their function (see. Hypervitaminoses ). Expressed a wedge, symptoms of a D-hypervitaminosis are found usually at reception from one to several million ME vitamin D. Big differences of individual sensitivity to toxic action To. and existence at a part of children of hypersensitivity to this action do not allow to establish a marginal dose of this vitamin reliably. In this regard most of researchers believe that, except for special cases of treatment vitamin of D-dependent or resistant forms of rickets, consumption To., considering all sources of their receipt, shall not exceed 400 — 1200 ME a day.



Bibliography: Bremener With, M. Vitamins and their clinical use, M., 1966, bibliogr.; Vitamins, under the editorship of M. I. Smirnov, page 89, M., 1974, bibliogr.; Spirichev V. B. A pathogeny and prevention of rickets in the light of modern ideas of exchange and the mechanism of effect of vitamin D, Pediatrics, No. 12, page 69, 1977, No. 1, page 70, 1978; Physiology of absorption, under the editorship of V. I. Chernigovsky, page 152, L., 1977; Shilov P. I. and Yakovlev T. N. Fundamentals of clinical vitaminology, L., 1974, bibliogr.; De LucaH.F. Recent advances in our understanding of the vitamin D endocrine system, J. Lab. clin. Med., v. 87, p. 7, 1976, bibliogr.; Fermente, Hormone, yitamine, hrsg. v. R. Ammon u. W. Dir-scherl, Bd 3, T. 1, S. 222, Stuttgart, 1974; Norman A. W. Gegenwartige Vorstel-lungen zum biochemischen Wirkungsmecha-nismus von Vitamin D, Munch, med. Wschr., S. 1585, 1974, Bibliogr.

V. B. Spirichev; V. M. Avakumov (pharm.), V. P. Lebedev (ped.).