From Big Medical Encyclopedia

CORTICOSTEROIDS (synonym: corticosteroid hormones, adrenokortikosteroida, adrenosteroids, kortikoida) — specific hormones of cortical substance of adrenal glands. Cortical substance adrenal glands (see) produces a large number of the steroid connections which are derivatives of cyclopentanperhydrophenanthrene, hydroxyls are attached to Krom. Depending on number of carbon atoms the hormones emitted by cortical substance of adrenal glands are divided into three groups of connections: C18 steroids — female sex hormones — is oestrogenic (see), they are allocated with cortical substance of adrenal glands in trace quantities; C19 steroids — male sex hormones — androgens (see); C21 steroids — actually the corticosteroids possessing specific to hormones of cortical substance of adrenal glands biol, action.

On the nature of influence on a metabolism specific hormones of cortical substance (actually To.) are divided into two groups of hormones: glucocorticoid hormones (see), influencing exchange of carbohydrates, proteins, fats, nucleinic to - t, and mineralokortikoidny hormones (see), influencing a water salt metabolism. At the same time glucocorticoid hormones have insignificant mineralokortikoidny activity that needs to be considered at therapy by drugs of these hormones, especially if high doses are appointed. In total actually To. consist of 21 carbon atoms and are derivatives of an allopregnan and pregnane (depending on the alpha or beta provision of hydrogen at C5) which constitutional formula following:

allopregnan and pregnane

From 46 connections allocated from cortical substance of adrenal glands 9 are biologically active hormones: these are glucocorticoid hormones — cortisol (see. Hydrocortisone ), corticosterone (see), cortisone (see), 11-dezoksikortizol, 11 dehydrocorticosterone and mineralokortikoidny hormones — Aldosteronum (see), cortexone (see), 18 oxycortexone, 18 oxycorticosterone (activities are located in decreasing order biol).

The most part To. make cortisol and corticosterone. Cortisol or corticosterone, or both hormones together and different ratios is found in all animals. All animals, except thalassophiluses and eels, cosecrete Aldosteronum. The person has a secretion To. fluctuates in the following limits: kortizo la — 15 — 30 mg/days, corticosterone — 2 — 5 mg/days, Aldosteronum — 75 — 300 mkg/days. Content To. in blood at young animals is much higher, than at old; at females — above, than at males.

The day-night rhythm of secretion of K. U of the person the maximum maintenance of cortisol is found (to 16 mkg of %) and corticosterone (to 1,5 MSC of %) in peripheral blood is defined between 6 and 9 o'clock in the morning; by midnight their concentration decreases by 3 — 4 times. At the animals who are awake at night the return rhythm is observed. At the person the incidental rhythm of secretion is revealed To.: peaks of secretion of cortisol and corticosterone are divided by dormant periods when concentration To. in blood reduces to zero. Aldosteronum also cosecretes periodically, the period of its maximum secretion matches the maximum period of secretion of cortisol in the morning, in the rest of the time synchronism in peaks of secretion of these hormones is absent.

Scheme of formation of biologically active corticosteroids.

To. are synthesized from cholesterol (see) through transient formation of a pregnenolon, at a stage to-rogo there is a branching of highways of a steroidogenesis on 17 oxycorticosteroids (cortisol) and 17-dezoksikortikosteroida (corticosterone and Aldosteronum). The leading value in biosynthesis To. in adrenal glands of the majority of mammals and the person have hydroxylated derivatives of a pregnenolon (17-oksi-, 11-oksi-, 21-oksi-, 18-oksipregnenolon, 17, 21-dioksi-and 11, 21-dioksipregnenolon) which further transformation leads to education biologically active To. (scheme).

Transformation of cholesterol in To. it is provided with two different groups of enzymes. The central place is taken by processes of a hydroxylation: all main stages of transformation of predecessors (eliminating of a side chain of cholesterol, 11 beta, 17 alpha, 21-and 18 hydroxylation) are catalyzed by hydroxylases; only transformation Δ5-3β-ол-стероидов in Δ4-3-кетостероиды is catalyzed by a dehydrogenase and isomerase.

Change of activity of enzymes of a steroidogenesis can serve as an origin of some endocrine diseases. Adrenogenital syndrome (see) it is usually connected with insufficiency of one of enzymes: 21 hydroxylases (in most cases), 11 beta, 17alfa-hydroxylases or Δ5-3бета-ол-дегидрогеназы, isomerases. As a result secretion of glucocorticoids decreases and formation of intermediate products increases, as defines symptomatology of a disease. So, e.g., the solteryayushchy form of an adrenogenital syndrome is caused by disturbance of exchange of electrolytes (a delay of K+ and strengthening of excretion of Na + and Cl - ).

Synthesis and secretion of glucocorticoids are normal regulated by AKTG which stimulates the main stage of biosynthesis To. — transformation of cholesterol in pregnenolon. AKTG regulates also formation of Aldosteronum, defining a day-night rhythm of its secretion. The leading role in regulation of secretion of Aldosteronum belongs K+ and a renin-angiotenzinnoy to system (see. Angiotenzin ), which activate the same stage of a steroidogenesis.

Synthesized To., practically without being deposited in adrenal glands, quickly come to blood.

In a blood plasma cortisol and corticosterone communicate with a corticosteroid the connecting globulin (see). Aldosteronum contacts albumine of plasma and kortikosteroidsvyazyvayushchy globulin, affinity to-rogo to Aldosteronum is much less, than to glucocorticoids. 90% of glucocorticoids and 50 — 60% of Aldosteronum are connected with proteins of plasma. The formed macromolecular proteinaceous and steroid complex promotes delay of an inactivation To. also is as if a tank of hormones, regulating their receipt from blood in cells.

The main place of metabolism To. the liver is; rather intensive exchange of hormones is found in kidneys, intestines, lungs. The general in exchange To. preservation of ring structure, oxygen group at C11 and dominance of reactions of recovery is. Enzymes of a liver reestablish double bonds in a steroid kernel (5 beta and 5alfa-reductases) and transfer ketogroups to oxygroups (3 alpha, 3 beta, 2 alpha and 20beta-oksisteroiddegidrogenaza). The main recovered metabolites are tetra-also K. Nek-roye's dihydroderivatives quantity To., having 17 oxygroup, turns in 17 ketosteroids (see). The recovered metabolites To. in a liver form pair connections with glucuronic and sulfuric to-tami and are excreted with bile and urine. In kidneys the Aldosteronum-18-glucuronide is synthesized. Half-life To. it is various: for cortisol it is equal on average 95 (80—110), for corticosterone — on average 75 (60—90), for Aldosteronum — on average 30 min. (24 — 36).

Glucocorticoids have an inhibiting effect on secretion of AKTG, decrease a cut, in turn, reduces education To. in adrenal glands. Existence of a feedback mechanism provides necessary level K. in blood. The oppressing influence To. it is sent to hl. obr. on a hypothalamus. Decrease in sensitivity of a hypothalamus to overwhelming influence To. as a result of disturbance of a feedback mechanism leads to the hypersecretion of cortisol causing a course of a disease of Itsenko — Cushing (see. Itsenko — Cushing a disease ).

Total influence of glucocorticoids on a metabolism in an organism is expressed as catabolic effect and shown in reduction of body weight (generally at the expense of skeletal muscles) and increase in excretion with urine of all nitrogen-containing fractions: ammonia, urea, uric to - you, amino acids. Increase in adjournment of a glycogen in a liver and concentration of glucose in blood is in parallel observed. Action of mineralokortikoid on a water salt metabolism is expressed in strengthening of excretion of K+, a delay of Na + , Cl - and waters. Aldosteronum selectively stimulates transport of K+ and Na + in kidneys, salivary, sweat glands and glands went. - kish. path.

Many effects of corticosteroids are carried out through activation of the genetic device of cells, through induction of processes of a transcription.

Methods of definition

All methods of definition To. in blood and urine include extraction To., afterpurification, fractionation and quantitative definition. The most reliable methods is the following. 1. Radio isotope: determination of speed of secretion To. on cultivation of a radioactive label entered To. in metabolites of urine; extent of cultivation of specific radioactivity of metabolites of hormones is according to amount of the hormone cosecreted by gland. 2. Radioimmunol. the methods based on replacement of the marked hormone (connected with an antibody) by not marked hormone which is contained in a specimen. There are standard kit sets for quantitative definition of some To. (cortisol, Aldosteronum). 3. The methods of competitive linkng with proteins developed by Murphy (V. E. P. Murphy) with sotr. In this method marked hormone communicates about a corticosteroid - the connecting globulin or other specific protein and also is forced out by not marked hormone of the measured test. For definition To. by this method it is possible to use an integral blood plasma, the cleared corticosteroid the connecting globulin or the kit sets. Methods of competitive binding allow to define nano - and pikogrammovy quantities To.

At quantitative definition separate To. wet, the metabolites which are excreted in the form of pair connections To., it is necessary to carry out preliminary enzymic hydrolysis of conjugates and to allocate connections in pure form. For definition of individual metabolites of 17 oxycorticosteroids of urine and Aldosteronum use methods of thin layer chromatography (see).

There are also group methods of definition To., allowing to measure total quantity of the connections possessing identical reactive groups. 17 oxycorticosteroids in blood and urine are defined by Silber's method — Porter (see. Silbera-Porter methods ); they form the painted chromogens which intensity of coloring is measured on the spectrophotometer with phenylhydrazine; for blood this method modified by N. A. Yudayev and Yu. A. Pankov for urine — M. A. Krekhova is used.

11 oxycorticosteroids of a blood plasma are determined by a flyuorimetrichesky method by intensity of fluorescence of hormones with mix H 2 SO 4 with ethanol.

17-ketogenic steroids call To., turning into 17 ketosteroids as a result of oxidizing eliminating of a side chain under the influence of chemical reagents (periodate of sodium, chromium oxide or a vismutat of sodium). For the first time the method of determination of content of 17-ketogenic steroids in urine was offered by Norimbersky (J. To. Norymberski) in 1953; in this method property K is used. to form at soft oxidation vismutaty sodium 17 ketosteroids (see. Norimbersky method ). Quantity of 17 ketosteroids usually determine by Tsimmermann's method (see. 17 Ketosteroids ). The oxidizing agents along with oxidation of steroids cause simultaneous hydrolysis of glucuronides — metabolites To., what allows not to resort to enzymic or acid hydrolysis of pair connections. Preliminary recovery of steroids of urine borgidridy sodium allows to define one more group of steroids with a side chain of COH — CO — CH 3  ; at the same time C - 20-ketogruppa recover to primary spirit. The formed products are oxidized further vismutaty sodium to 17 ketosteroids.

During the processing of urine borgidridy sodium there is also a recovery of ketogroups at C17 which are contained in urine 17 of ketosteroids thanks to what in this case there is no need to define their quantity in urine before processing its vismutaty sodium. In urine all connections having a hydroxyl at C17 including a hydrocortisone, a cortisone, 11-dezoksi-17-oxycorticosterone and their metabolites, and also 17-oksipregnenolon both 17 pregnenoldione and their derivatives therefore for total 17-ketogenic steroids of urine the name — «the general 17-OHKC» is used sometimes, unlike 17 oxycorticosteroids («17-OHKC») determined usually by reaction with phenylhydrazine by Silber's methods — Porter are defined by this way.

The method of definition of 17-ketogenic steroids in the crude extracts of urine is only relatively specific, than and the large number of various modifications of this method speaks. The maintenance of 17-ketogenic steroids in urine of healthy adults fluctuates (depending on a method of definition) from 8 to 25 mg at men and from 4,6 to 17,9 mg in 24 hours is at women.

Determination of content To. in blood, excretion of steroids with urine allowed to determine the main consistent patterns of secretion To. at people depending on age and a floor to reveal day-night rhythms of their secretion, and also to establish features of their secretion at impact on an organism of various environmental factors and at diseases.

Corticosteroid drugs

apply Corticosteroid drugs of hormones of cortical substance of adrenal glands and their synthetic analogs as pharmaceuticals. From the natural glucocorticoid hormones emitted in a crystal look, practical application as pharmaceuticals was found by drugs hydrocortisone (see) and cortisone (see).

A number of their synthetic analogs which found broad application in therapy of various diseases is received. Synthetic connections are more active, than drugs of natural hormones, work in smaller doses; the fluorinated their derivatives are more convenient for topical administration since they are less soaked up (they are applied in the form of ointments); synthetic analogs almost completely replaced a cortisone. Treat synthetic analogs of glucocorticoid hormones Prednisonum (see), Prednisolonum (see), dexamethasone (see), Triamcinolonum (see), Methylprednisolonum. Synalarum, locacortenum, Ftorokortum, Ultralanum, betamethasone, etc. belong to the synthetic analogs containing fluorine.

From mineralokortikoidny hormones drugs are used cortexone (see), a flyuotsinolona acetonide, in the form of synthetic analogs — acetate of cortexone (DOKSA) and a trimetilatsetat of cortexone; also drug is used Cortinum (see) which does not differ in constancy of mineralokortikoidny action.

Pharm. the industry of the different countries produces corticosteroid drugs under branded names. All corticosteroid drugs are stored according to the list B in the place protected from light.

Forms of release — see articles according to names of drugs, and also the table to article « Hormonal drugs ».

The principles of corticosteroid therapy

At use with to lay down. the purpose of drugs of corticosteroid hormones (corticosteroid hormonal therapy) one of the most important principles of therapy is the aspiration to preservation or recovery of normal function of adrenal glands. Drugs K. are applied as replacement therapy after an adrenalectomy as cure of nonspecific pathogenetic protection for many diseases. How to lay down. means to apply them is possible only according to strict indications when other methods of treatment cannot give positive effect. Use of corticosteroids before establishment of the diagnosis since it can pervert a wedge, a picture is inadmissible and quite often leads to serious consequences; use them is carried out under constant medical control.

Tactics of use shall be strictly individualized, the term of treatment and the choice of a dose are defined by weight of a condition of the patient and the nature of a disease, existence of associated diseases. Due to possible side reactions and complications of a dose shall be selected taking into account obtaining therapeutic effect, but in quantities, the irreversible changes in an organism of the patient allowing to avoid.

During the performing corticosteroid therapy, especially long, it is necessary to consider the following:

1) weight of manifestations and activity patol, process; 2) funkts, condition of cortical substance of adrenal glands; 3) day-night rhythm of products of AKTG and various corticosteroids; 4) half-life of corticosteroids; 5) features pharmakol, actions and pharmacodynamics of the used drugs, possible complications and side effects.

It is necessary to consider also age of the patient. So, in connection with the slowed-down inactivation of a hydrocortisone at newborns in need of purpose of replacement therapy by it smaller doses, than to children of more advanced age, and also use of the corticosteroid having shorter half-life are required considerably. The great value is attached funkts, to a condition of a liver and kidneys. So, at hepatitis, a renal failure the inactivation of the administered drug is slowed down and conditions for strengthening of its side effect are created. At some diseases insufficiency of fermental systems of a liver owing to their overload patol, products of exchange and pharmaceuticals can come to light funkts (salicylates, Resochinum, pyramidon, etc.); in these conditions there is competitive relationship between medicinal substances and metabolism of corticosteroids is slowed down. Especially accurately it is shown at the children having rheumatism with a circulatory unefficiency when functions of a liver are broken, and the child receives hormonal and medicamentous therapy in this connection it is necessary to korrigirovat a dose of drugs K constantly.

At children of preschool age dysfunction of cortical substance of adrenal glands quite often takes place that is connected with age immune reorganization of an organism in response to the postponed infection or vaccination; dysfunction of cortical substance of adrenal glands can be observed during recovery after inf. diseases; purpose of drugs K. in these cases it is inexpedient.

Synthetic To. to a lesser extent natural hormones communicate kortikosteroidsvyazyvayushchy globulin, than; differently it contacts various drugs K. So, if in blood a corticosteroid the connecting globulin has considerable effect on concentration of Prednisolonum, then on Triamcinolonum its influence is excluded.

Efficiency of corticosteroid therapy considerably increases if the daily dose of hormonal drugs is distributed according to fiziol, a rhythm of secretion To. It is necessary to appoint the maximum dose in the morning; the possibility of emergence of side effect and danger of oppression of functions of cortical substance of adrenal glands is minimized by it. Strengthening To. in the second half of day and is one of the reasons of development of a syndrome of Cushing in the evening (see. Cushing syndrome ), and also reason of oppression of secretion of AKTG; the last involves decrease in secretion To. in the morning and development of hypofunction of cortical substance of adrenal glands.

It is established that after massive and especially long therapy by corticosteroid drugs cortical substance of adrenal glands keeps inertness within 6 — 12 months Due to a possibility of development of a hypocorticoidism at prolonged use To. (there is a braking of endogenous secretion of hormones cortical substance of adrenal glands under the law of a feed-back) the termination of treatment shall be carried out carefully and gradually. It is sometimes recommended within 3 — 4 days after drug withdrawal to appoint small doses of corticotropin (10 — 20 PIECES a day) for stimulation of cortical substance of adrenal glands.

Bystry and unprepared cancellation of treatment To. can cause a complication — a so-called withdrawal. This syndrome is characterized by a complex of signs of a hypocorticoidism, and also a recurrence of a basic disease. The possibility of such complication should be considered especially in surgical practice if the immediate surgery at the patient accepting or shortly before this accepting drugs K is performed. In these cases resuming of corticosteroid therapy can be required. For the prevention of development of complications therapy is appointed discontinuous courses with observance of a day-night rhythm of administration of drugs; reasonablly additional appointment ascorbic to - you in usual doses.

Range of doses of drugs K. it is very wide: from 15 mg of Prednisolonum (at rheumatism, a pseudorheumatism, etc.) to 1000 mg (!) in day at an acute lymphoblastoid leukosis of children, some forms of a collapse and other serious conditions. Also widely also terms of use of these drugs — from a short-term single course to months-long, and sometimes lifelong replacement therapy fluctuate. At the same time pharmakodinamichesky features of drugs are considered; e.g., at a cortisone not only glucocorticoid, but also mineralokortikoidny properties therefore drugs of a cortisone are shown at treatment both shock, and an eksikoz clearly are expressed.

The mechanism of action of glucocorticoids, indications, contraindications

Corticosteroid drugs have the expressed influence on carbohydrate, proteinaceous and a lipometabolism, and also versatile action on cellular metabolism, connecting fabric and immune processes. They strengthen inclusion of glucose in energy balance, transformation of amino acids into proteins, synthesis of a cartilaginous matrix. They stimulate synthesis of a glycogen, mobilization of fat from depot, increase activity of transaminases, suppress inflammatory and immune responses of an organism, antibody formation, phagocytosis and a lymphopoiesis, migration of leukocytes in an adenoid tissue, synthesis of mucopolysaccharides. According to modern data, glucocorticoids exert impact on synthesis of protein at the level of the genetic device of a cell, a point of application of their action are ribosomes of a cell and ribosomal RNA.

At use of high doses of these drugs disintegration of proteins to the level of amino acids sharply accelerates and protein synthesis is suppressed; sharply processes of deamination amplify, excretion of nitrogen and amino acids raises. Influence on a lipometabolism is characterized by increase in level of cholesterol and lipids in blood, accumulation ketone bodies (see), an adiposity in a liver. At administration of glucocorticoid drugs without a day-night rhythm of biosynthesis of hormones braking of zhiromobilizuyushchy effect of somatotropic hormone of a hypophysis develops, fat on a face, shoulders and a stomach is selectively laid. It is also necessary to consider their nek-swarm influence on water mineral metabolism (both drugs of natural glucocorticoids, and synthetic analogs influence). Therefore at use of high doses of glucocorticoids there can be a delay of sodium and chlorides, to raise allocation with urine of potassium and calcium, to occur decalcification of bones; there can be hypostases, raise the ABP, arise a hyperglycemia, up to steroid diabetes (see. Diabetes steroid ).

Decrease in education is the cornerstone of the mechanism of antiinflammatory effect of glucocorticoid drugs hyaluronidases (see), suppression of processes of exudation, products of fibroblasts, reticular macrophages, formations of granulomas, etc.

Glucocorticoid drugs lower education patol, antibodies; this mechanism is the cornerstone of their immunodepressive effect (see. Immunodepressive substances ). They can slow down synthesis of the metabolites necessary for normal functioning and cell fission. Ability of glucocorticoid drugs to oppress development patol, (blast) elements of leukemic cells in culture of fabric that is confirmed a wedge, practice is proved; products of the cells producing immunoglobulins are sharply oppressed. These drugs cause elimination from marrow of mature leukocytes (granulocytes) therefore at glucocorticoid therapy the neutrophylic leukocytosis develops (the marrowy reserve of granulocytes will be mobilized); naturally also emergence of an eosinopenia. Glucocorticoid therapy is followed by braking of function of bark of adrenal glands (under the law of a feed-back).

Indications to glucocorticoid therapy: shock of a different origin, heavy widespread burns, a burn of a gullet, a frostbite, acute allergic states, not stopped attack of bronchial asthma, acute hemolysis of erythrocytes (autoimmune, medicamentous, at incompatible blood transfusion), a thrombocytosis, an immune agranulocytosis, acute myocarditis, a system lupus erythematosus in an acute phase. These drugs find the greatest application at collagenoses, often apply them at rheumatism, a pseudorheumatism, Steel's disease (a children's form), a dermatomyositis, a nodular periarteritis, some forms of a glomerulonephritis, at a nephrosis (especially at children), ulcer colitis.

At diseases of the hemopoietic bodies use of glucocorticoid means is obligatory (hemolitic cytopenias, limfoproliferativny diseases and their complications); they are the most important components of treatment of acute leukoses, a lymphogranulomatosis, gemodermiya, an end-stage of a myeloleukemia and a myelofibrosis.

Glucocorticoids are shown at many skin diseases, especially allergic origin, eye diseases locally and in combination with etiol, therapy (antibiotics). They are applied for the purpose of replacement therapy at acute and hron, insufficiency of cortical substance of adrenal glands (at an addisonovy disease, Simmonds's disease, an adrenogenital syndrome, after operation for tumors of adrenal glands, etc.) along with DOKSA. The immunodepressive effect of glucocorticoid drugs allows to use them at allotransplantation of bodies and fabrics for suppression of reaction of rejection.

Contraindications: Cushing's syndrome, severe forms of obesity, a diabetes mellitus, diffusion osteoporosis, severe azotemic forms of acute nephrite, a hypertension with high figures of the ABP, a peptic ulcer of a stomach and duodenum; endogenous psychoses, epilepsy. Only at absolute vital indications it is possible to use these drugs at pregnancy.

All glucocorticoid drugs should be accepted in the crushed look after food; to observe the water-salt mode (a hypochloride table). At long therapy it is reasonable to appoint in addition drugs of anabolic hormones (Nerobolum, retabolil).

The mechanism of action of mineralokortikoid, indications, contraindications

As well as natural hormones, mineralokortikoida exert impact on a water salt metabolism; cause increase in a reabsorption of sodium in kidneys, sialadens and went. - kish. a path, strengthen removal of potassium, detain water in an organism, increase permeability of connective tissue barriers, strengthen inflammatory reactions and an immunogenesis, have anti-toxic properties in relation to a nek-eye to bacterial toxins. The strengthened allocation of potassium ions leads to increase in hydrophily of fabrics, the volume of plasma at the same time increases, increases the ABP, and also a muscle tone. At the same time it is necessary to consider that their Glucocorticoid activity is equal about 1/3 activities of a cortisone that can affect at purpose of high doses.

Indications: DOKSA and trimetilatsetat cortexone is appointed at an addisonovy disease (together with glucocorticoids), relative insufficiency of cortical substance of adrenal glands (at inf. diseases, intoxications, widespread burns, injuries and so forth), a constitutional hypoadrenalism, asthenic states, hypotonia, exhaustion, a hypochloraemia, in the period of reconvalescence after an operative measure and inf. diseases; for prevention and treatment of depressed cases at operation, a burn and freezing injury; at stomach ulcer and a duodenum, at dehydration of an organism (intestinal infections and intoxications), at pernicious vomiting of pregnant women, at the diseases which are followed by muscular dystrophy and an atrophy, Simmoyads's diseases, etc.

Drugs of cortexone are contraindicated at an idiopathic hypertensia, heart failure with hypostases, stenocardia, nephrite, a nephrosis, cirrhosis.

By-effects and complications

Serious complications accompany only prolonged use of considerable doses of drugs K. Their emergence is connected with the main mechanisms of hormonal action. Treat heavy complications: the acute corticosteroid shock developing at sudden cancellation it is long applied To., an atrophy of adrenal glands, a helcomenia of a stomach or duodenum, diffusion osteoporosis, an aggravation hron, infectious processes (in connection with insufficient products of antibodies) and tuberculosis owing to elimination of calcium from the calciphied centers, development of peritonitis, cholecystitis and so forth. Diagnosis of these complications quite often can be difficult since suppression of defense inflammatory reaction erases a wedge, a picture. Delay of processes of regeneration, decrease in resilience to inf can be observed. to agents, development of obesity.

At overdose of mineralokortikoidny drugs can develop hypopotassemia (see), expressed a number of symptoms, especially from a myocardium, electrolytic balance is broken, hypostases and arterial hypertension develop.

Heavy convulsive attacks at children owing to wet brain, and also mental disorders which can arise not only during use of drug, but also after the termination of therapy as one of manifestations of a so-called withdrawal are less often observed. Mental disorders with terms of treatment have no accurate communication; manifestations of these frustration are very diverse. In the most mild cases there is euphoria; perhaps also emergence of the oligothymia accompanied usually with feeling of alarm, excessive fixing on painful feelings. Similar states are usually combined with various symptoms of an adynamy (see. Asthenic syndrome ). Some patients against the background of the lowered mood have phobias (see. Persuasive states ), depersonalization (see) and derealization (see). Emotional variability, easy transition from euphoria to melancholy, uneasiness and vice versa is characteristic. Occasionally there are expressed affective disturbances in a look maniacal syndromes (see) or depressive syndromes (see) with their possible alternation. Emergence is possible hallucinations (see) — hl. obr. acoustical and visual and various crazy ideas (greatness — against the background of the increased mood, self-accusation, the relation, prosecution), hypochiondrial mood against the background of a depression (see. Nonsense ). There can be syndromes of stupefaction, such as delirious syndrome (see) or twilight stupefaction (see), is more rare — an amentia (see. Amental syndrome ), and also convulsive attacks, single or in the form of the epileptic status.

At diagnosis psikhich. complications it is necessary to carry out the differential diagnosis with the somatopsychoses arising in connection with a basic disease and also with schizophrenia and maniac-depressive psychosis which attacks can arise during treatment by drugs K.

The forecast of complications at corticosteroid therapy, as a rule, favorable. At prolonged psychoses apply symptomatic therapy by antidepressants, neuroleptics, tranquilizers, anticonvulsant or hypnagogues.

Prevention of complications consists in gradual drug withdrawal, respect for the principles of corticosteroid therapy (including the accounting of a pharmacodynamics of drug, disease severity and age of the patient).

See also Steroid hormones .

Bibliography: Biochemistry of hormones and hormonal regulation, under the editorship of N. A. Yudayev, page 228, M., 1976, bibliogr.; Goncharova V. N. and d river. Speed of secretion of cortisol at Itsenko's disease — Cushing, Probl, endocrinins., t. 16, No. 2, page 12, 1970; Druzhinina K. V. Chromatographic fractionation of corticosteroids of urine on a thin coat of KSK-2 silica gel, Vopr, medical chemistry, t. And, No. 4, page 81, 1965; Pankova S. S., M and N both and and L. S. and F and N - the p e and to about N. D. Definition of a hydrocortisone in a blood plasma by method competitive proteins of binding, Probl, endocrinins., t. 18, No. 3, page 85, 1972; Modern questions of endocrinology, under the editorship of N. A. Yudayev, century 5, page 9, etc., M., 1975; X e f t-m and E. M. Biokhimiya's N of steroids, the lane with English, M., 1972, bibliogr.; Yudayev N. A. Chemical methods of definition of steroid hormones in biological liquids, page 90, M., 1961; Baxter J. D. a. Forsham P. H. Tissue effects of glucocorticoids, Amer. J. Med., v. 53, p. 573, 1972; Glaz E. a. VecseiP. Aldosterone, Oxford — N. Y., 1971, bibliogr.; Hiibener H. J. a. Staib W. H. Biochemie der Nebennierenrinden-Hormone, S. 174, Stuttgart, 1965; Textbook of endocrinology, ed. by R. H. Williams, Philadelphia, 1974; Trager L. Steroidhormo-ne, Biosynthese, Stoffwechsel, Wirkung, Heidelberg, 1977, Bibliogr.

Corticosteroid drugs — Clays D. X. Kortizonoterapiya, the lane with English, M., 1960; Egorova L. I. Treatment by glucocorticoids and AKTG, M., 1972, bibliogr.; Kassirsky I. A. and Milevskaya Yu. JI. Sketches of modern clinical medicine, page 250, Tashkent, 1970; Kupchinskas Yu. K., Vasilyauskas B. I. and Kempins-k and with V. V. Side effect of drugs, M., 1972, bibliogr.; Mashkovsky M. D. Pharmaceuticals, p.1 — 2, M., 1977; Side effect of pharmaceuticals, under the editorship of I. A. Kassirsky, page 125, M., 1971, bibliogr.; Stolyarov G. V. Medicinal psychoses and psychotomimetic means, page 81, M., 1964; In e i with k e r t A. Die Glukokorticoid-Therapie innerer Erkrankungen einschlisslich ihrer Grundlagen und Nebenwirkungen, Jena, J 964, Bibliogr.; The pharmacological basis of therapeutics, ed. by L. S. Goodman a. A. Gilman, L., 1975.

S. A. Afinogenova; M. A. Krekhova (17-ketogenic steroids), A. I. Vorobyov, Yu. L. Milevskaya (corticosteroid drugs), M. V. Korkina (psikhiat.), V. P. Lebedev (ped.).