Glucocorticoids- This is a type of hormone produced as a result of the work of the adrenal cortex. One of the hormones is cortisone, which, during the work of the liver, is converted into another hormone - hydrocortisone (cortisol). Cortisol is the most famous and important for human body hormone. Medicines based on these hormones have been used since the 40s of the last century.

Today, in addition to natural glucocorticoids, there are a number of drugs based on synthetic hormones, which are divided into two types:

• fluorinated (dexamethasone, betamethasone, etc.);
• non-fluorinated (prednisone, prednisolone).

They are characterized by higher efficiency when consuming a smaller dose. In addition, fluorinated glucocorticoids have the lowest rate of occurrence side effects.

The use of glucocorticoid drugs

Preparations containing glucocorticoids are used with a fairly large amount serious illnesses, because have different effects on the body.

Common indicators for prescribing drugs in this group are:

• rheumatoid arthritis;
• leukemia;
• mononucleosis;
• skin diseases(dermatitis, eczema);
• anemia;
• pneumonia;
• allergic diseases;
• pancreatitis;
• hepatitis.

The mechanism of action is not fully understood, but the effect of the use of glucocorticoids can be anti-inflammatory, immunoregulatory, anti-allergic, anti-shock. Preparations are available in various forms:

• sprays;
• tablets;
• lotions;
• ointments;
• liquids for injections and inhalations.

List of glucocorticoid drugs

The list of such funds is quite extensive. The most famous and effective are:

• Cortisone - participates in replacement therapy;
• Prednisolone - 4 times more effective than hydrocortisone;
• Prednisone - not recommended for liver problems;
• Methylprednisolone - suitable for the treatment of patients with obesity, mental disorders, ulcers;
• Triamcinolone - has a more prolog effect than prednisolone, with pronounced side effects on the muscles and skin;
• Dexamethasone - effective drug for short term use;
• Betamethasone is the closest drug to dexamethasone in terms of effectiveness.

Side effects of glucocorticoids

With a number of positive medicinal properties, glucocorticoids have no less impressive side effects. That is why they are often prescribed in short courses or used in particularly difficult cases. Drugs of the glucocorticoid group can cause the following adverse reactions.

• Mechanism of action

  Glucocorticosteroids by diffusion penetrate into the cytoplasm of the cell and interact with intracellular steroid receptors.

  Inactive glucocorticosteroid receptors are heterooligomeric complexes, which, in addition to the receptor itself, include heat shock proteins, various types of RNA, and other structures.

  The C-terminus of steroid receptors is associated with a large protein complex that includes two subunits of the hsp90 protein. After the interaction of the glucocorticosteroid with the receptor, hsp90 is cleaved off, and the resulting hormone-receptor complex moves to the nucleus, where it acts on certain DNA regions.

  Hormone-receptor complexes also interact with various transcription factors or nuclear factors. Nuclear factors (eg, activated transcription factor protein) are natural regulators of several genes involved in immune response and inflammation, including genes for cytokines, their receptors, adhesion molecules, and proteins.

  By stimulating steroid receptors, glucocorticosteroids induce the synthesis of a special class of proteins - lipocortins, including lipomodulin, which inhibits the activity of phospholipase A 2.

  Main effects of glucocorticosteroids.
  

  Glucocorticosteroids, due to their multilateral influence on metabolism, mediate the adaptation of the organism to stressful influences from the external environment.

  Glucocorticosteroids have anti-inflammatory, desensitizing, immunosuppressive, anti-shock and antitoxic effects.

  The anti-inflammatory effect of glucocorticosteroids is due to the stabilization of cell membranes, suppression of the activity of phospholipase A 2 and hyaluronidase, inhibition of the release of arachidonic acid from phospholipids of cell membranes (with a decrease in the levels of its metabolic products - prostaglandins, thromboxane, leukotrienes), as well as inhibition of mast cell degranulation processes (with the release of histamine , serotonin, bradykinin), platelet activating factor synthesis and proliferation connective tissue.

  The immunosuppressive activity of glucocorticosteroids is the total result of the suppression of various stages of immunogenesis: the migration of stem cells and B-lymphocytes, the interaction of T- and B-lymphocytes.

  The anti-shock and antitoxic effect of glucocorticosteroids is mainly due to an increase in blood pressure (due to an increase in the concentration of catecholamines circulating in the blood, restoration of adrenoreceptor sensitivity to them, and vasoconstriction), a decrease in vascular permeability and activation of liver enzymes involved in the biotransformation of endo- and xenobiotics.

  Glucocorticosteroids activate hepatic gluconeogenesis and enhance protein catabolism, thereby stimulating the release of amino acids - substrates of gluconeogenesis from peripheral tissues. These processes lead to the development of hyperglycemia.

  Glucocorticosteroids enhance the lipolytic effect of catecholamines and growth hormone, as well as reduce the consumption and utilization of glucose by adipose tissue. An excessive amount of glucocorticosteroids leads to stimulation of lipolysis in some parts of the body (limbs) and lipogenesis in others (on the face and trunk), as well as an increase in the level of free fatty acids in plasma.

  Glucocorticosteroids have an anabolic effect on protein metabolism in the liver and a catabolic effect on protein metabolism in muscles, adipose and lymphoid tissues, skin, and bones. They inhibit the growth and division of fibroblasts, the formation of collagen.

  In the hypothalamus-pituitary-adrenal system, glucocorticosteroids inhibit the formation of corticotropin-releasing hormone and adrenocorticotropic hormone.

  Biological effects glucocorticosteroids persist for a long time.

  
  By duration of action allocate:
  • Glucocorticosteroids short action(hydrocortisone).
  • Intermediate-acting glucocorticosteroids (methylprednisolone, prednisolone).
  • Glucocorticosteroids long-acting(betamethasone, dexamethasone, triamcinolone acetonide).

• Pharmacokinetics By route of administration distinguish:
  • Oral glucocorticosteroids.
  • Inhaled glucocorticosteroids.
  • Intranasal glucocorticosteroids.
  Oral glucocorticosteroids.
  

  When taken orally, glucocorticosteroids are well absorbed in the gastrointestinal tract and actively bind to plasma proteins (albumin, transcortin).

  The maximum concentration of drugs in the blood is reached after about 1.5 hours. Glucocorticosteroids undergo biotransformation in the liver, partly in the kidneys and in other tissues, mainly by conjugation with glucuronide or sulfate.

  About 70% of conjugated glucocorticosteroids are excreted in the urine, 20% - in the feces, the rest - through the skin and with other biological fluids.

  The half-life of oral glucocorticosteroids averages 2-4 hours.

  
  Some pharmacokinetic parameters of glucocorticosteroids

  A drug	Plasma half-life, h	Tissue half-life, h
  Hydrocortisone	0,5-1,5	8-12
  Cortisone	0,7-2	8-12
  Prednisolone	2-4	18-36
  Methylprednisolone	2-4	18-36
  fludrocortisone	3,5	18-36
  Dexamethasone	5	36-54

  
  Inhaled glucocorticosteroids.
  

  Currently, beclomethasone dipropionate, budesonide, mometasone furoate, flunisolide, fluticasone propionate and triamcinolone acetonide are used in clinical practice.

  
  Pharmacokinetic parameters of inhaled glucocorticosteroids

  Preparations	Bioavailability, %	The effect of the first passage through the liver, %	Half-life from blood plasma, h	Volume of distribution, l/kg	Local anti-inflammatory activity, units
  beclomethasone dipropionate	25	70	0,5	-	0,64
  Budesonide	26-38	90	1,7-3,4 (2,8)	4,3	1
  Triamcinolone acetonide	22	80-90	1,4-2 (1,5)	1,2	0,27
  fluticasone propionate	16-30	99	3,1	3,7	1
  Flunisolide	30-40		1,6	1,8	0,34

  
  Intranasal glucocorticosteroids.
  

  Currently, beclomethasone dipropionate, budesonide, mometasone furoate, triamcinolone acetonide, flunisolide, fluticasone propionate are used in clinical practice for intranasal use.

  After intranasal administration of glucocorticosteroids, part of the dose that settles in the pharynx is swallowed and absorbed in the intestine, part enters the blood from the mucous membrane respiratory tract.

  Glucocorticosteroids entering the gastrointestinal tract after intranasal administration are absorbed by 1-8% and are almost completely biotransformed to inactive metabolites during the first passage through the liver.

  That part of glucocorticosteroids, which is absorbed from the mucous membrane of the respiratory tract, is hydrolyzed to inactive substances.

  Bioavailability of glucocorticosteroids with intranasal administration

  A drug	Bioavailability during absorption from the gastrointestinal tract,%	Bioavailability upon absorption from the mucous membrane of the respiratory tract,%
  Beclomethasone dipropionate	20-25	44
  Budesonide	11	34
  Triamcinolone acetonide	10,6-23	There is no data
  mometasone furoate
  Flunisolide	21	40-50
  fluticasone propionate		0,5-2

• Place in therapy Indications for the use of oral glucocorticosteroids.
  • Replacement therapy for primary adrenal insufficiency.
  • Replacement therapy of secondary chronic adrenal insufficiency.
  • Acute adrenal insufficiency.
  • Congenital dysfunction of the adrenal cortex.
  • Subacute thyroiditis.
  • Bronchial asthma.
  • Chronic obstructive pulmonary disease (in the acute phase).
  • Severe pneumonia.
  • Acute respiratory distress syndrome.
  • Interstitial lung disease.
  • Nonspecific ulcerative colitis.
  • Crohn's disease.
  Indications for the use of intranasal glucocorticoids.
  • Seasonal (intermittent) allergic rhinitis.
  • Perennial (persistent) allergic rhinitis.
  • Nasal polyposis.
  • Non-allergic rhinitis with eosinophilia.
  • Idiopathic (vasomotor) rhinitis.

  Inhaled glucocorticosteroids are used to treat bronchial asthma, chronic obstructive pulmonary disease.

• Contraindications Glucocorticosteroids are prescribed with caution in the following clinical situations:
  • Itsenko-Cushing's disease.
  • Diabetes.
  • peptic ulcer or duodenum.
  • Thromboembolism.
  • Arterial hypertension.
  • Severe renal failure.
  • Mental illness with productive symptoms.
  • Systemic mycoses.
  • herpetic infection.
  • Tuberculosis (active form).
  • Syphilis.
  • period of vaccination.
  • Purulent infections.
  • Viral or fungal diseases eye.
  • Corneal diseases associated with epithelial defects.
  • Glaucoma.
  • lactation period.
  Intranasal administration of glucocorticoids is contraindicated in the following cases:
  • Hypersensitivity.
  • Hemorrhagic diathesis.
  • History of repeated nosebleeds.

• Side effects Systemic side effects of glucocorticosteroids:
  • From the side of the central nervous system:
    • Increased nervous excitability.
    • Insomnia.
    • Euphoria.
    • Depression.
    • Psychoses.
  • From the side of cardio-vascular system:
    • Myocardial dystrophy.
    • Increase in blood pressure.
    • Deep vein thrombosis.
    • Thromboembolism.
  • From the side digestive system:
    • Steroid ulcers of the stomach and intestines.
    • Bleeding from the gastrointestinal tract.
    • Pancreatitis.
    • Fatty degeneration of the liver.
  • From the sense organs:
    • Posterior subcapsular cataract.
    • Glaucoma.
  • From the endocrine system:
    • Inhibition of function and atrophy of the adrenal cortex.
    • Diabetes.
    • Obesity.
    • Cushing's syndrome.
  • From the side of the skin:
    • Thinning of the skin.
    • Striae.
    • Alopecia.
  • From the side musculoskeletal system:
    • Osteoporosis.
    • Fractures and aseptic necrosis of bones.
    • Growth retardation in children.
    • Myopathy.
    • Muscle hypotrophy.
  • From the reproductive system:
    • Violations menstrual cycle.
    • Violations of sexual functions.
    • Delayed sexual development.
    • Hirsutism.
  • From the side of laboratory indicators:
    • Hypokalemia.
    • Hyperglycemia.
    • Hyperlipidemia.
    • Hypercholesterolemia.
    • Neutrophilic leukocytosis.
  • Others:
    • Sodium and water retention.
    • Edema.
    • Exacerbations of chronic infectious and inflammatory processes.
  local side effects.
  Inhaled glucocorticosteroids:
  • Candidiasis of the oral cavity and pharynx.
  • Dysphonia.
  • Cough.
  Intranasal glucocorticosteroids:
  • Itching in the nose.
  • Sneezing.
  • Dryness and burning of the nasal and pharyngeal mucosa.
  • Nosebleeds.
  • Perforation of the nasal septum.

• Precautionary measures

  In patients with hypothyroidism, cirrhosis of the liver, hypoalbuminemia, as well as in elderly and senile patients, the effect of glucocorticosteroids may increase.

  When prescribing glucocorticosteroids during pregnancy, the expected therapeutic effect for the mother and the risk of negative effects on the fetus should be taken into account, since the use of these drugs can lead to impaired fetal growth, some developmental defects (cleft palate), atrophy of the adrenal cortex in the fetus (in the third trimester pregnancy).

  In children and adults taking glucocorticosteroids, infectious diseases such as measles, chicken pox, can be difficult.

  Patients taking immunosuppressive doses of glucocorticosteroids should not receive live vaccines.

  Osteoporosis develops in 30-50% of patients who take systemic glucocorticosteroids for a long time (oral or injectable dosage forms). As a rule, the spine, pelvic bones, ribs, hands, feet are affected.

  Steroid ulcers during treatment with glucocorticosteroids may be asymptomatic or asymptomatic, manifesting bleeding and perforation. Therefore, patients receiving oral glucocorticosteroids for a long time should periodically undergo fibroesophagogastroduodenoscopy and fecal occult blood analysis.

  In various inflammatory or autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus and bowel disease), cases of steroid resistance can be observed.

Glucocorticoids are steroid hormones synthesized by the adrenal cortex. Natural glucocorticoids and their synthetic analogues are used in medicine for adrenal insufficiency. In addition, in some diseases, anti-inflammatory, immunosuppressive, anti-allergic, anti-shock and other properties of these drugs are used.

The beginning of the use of glucocorticoids as medicines(LS) refers to the 40s. XX century. Back in the late 30s. of the last century, it was shown that hormonal compounds of a steroid nature are formed in the adrenal cortex. In 1937, the mineralocorticoid deoxycorticosterone was isolated from the adrenal cortex, in the 40s. - glucocorticoids cortisone and hydrocortisone. Wide spectrum pharmacological effects of hydrocortisone and cortisone predetermined the possibility of their use as drugs. Their synthesis was soon carried out.

The main and most active glucocorticoid formed in the human body is hydrocortisone (cortisol), others, less active, are cortisone, corticosterone, 11-deoxycortisol, 11-dehydrocorticosterone.

The production of adrenal hormones is under the control of the central nervous system and is closely related to the function of the pituitary gland. Pituitary adrenocorticotropic hormone (ACTH, corticotropin) is a physiological stimulant of the adrenal cortex. Corticotropin enhances the formation and release of glucocorticoids. The latter, in turn, affect the pituitary gland, inhibiting the production of corticotropin and thus reducing further stimulation of the adrenal glands (by the principle of negative feedback). Long-term administration of glucocorticoids (cortisone and its analogs) into the body can lead to inhibition and atrophy of the adrenal cortex, as well as to inhibition of the formation of not only ACTH, but also gonadotropic and thyroid-stimulating hormones of the pituitary gland.

Cortisone and hydrocortisone have found practical use as drugs from natural glucocorticoids. Cortisone, however, is more likely than other glucocorticoids to cause side effects and, due to the advent of more effective and safer drugs, is currently of limited use. In medical practice, natural hydrocortisone or its esters (hydrocortisone acetate and hydrocortisone hemisuccinate) are used.

A number of synthetic glucocorticoids have been synthesized, among which are non-fluorinated (prednisone, prednisolone, methylprednisolone) and fluorinated (dexamethasone, betamethasone, triamcinolone, flumethasone, etc.) glucocorticoids. These compounds tend to be more active than natural glucocorticoids and act at lower doses. The action of synthetic steroids is similar to the action of natural corticosteroids, but they have a different ratio of glucocorticoid and mineralocorticoid activity. Fluorinated derivatives have a more favorable ratio between glucocorticoid/anti-inflammatory and mineralocorticoid activity. Thus, the anti-inflammatory activity of dexamethasone (compared to that of hydrocortisone) is 30 times higher, betamethasone - 25-40 times, triamcinolone - 5 times, while the effect on water-salt metabolism is minimal. Fluorinated derivatives differ not only high efficiency, but also low absorption when applied topically, i.e. less likely to develop systemic side effects.

The mechanism of action of glucocorticoids at the molecular level is not fully understood. It is believed that the effect of glucocorticoids on target cells is carried out mainly at the level of regulation of gene transcription. It is mediated by the interaction of glucocorticoids with specific intracellular glucocorticoid receptors (alpha isoform). These nuclear receptors are capable of binding to DNA and belong to the family of ligand-sensitive transcriptional regulators. Glucocorticoid receptors are found in almost all cells. In different cells, however, the number of receptors varies, they can also differ in molecular weight, hormone affinity, and other physicochemical characteristics. In the absence of the hormone, intracellular receptors, which are cytosolic proteins, are inactive and are part of heterocomplexes, which also include heat shock proteins (heat shock protein, Hsp90 and Hsp70), immunophilin with molecular weight 56000 and others. Heat shock proteins help to maintain the optimal conformation of the hormone-binding domain of the receptor and provide a high affinity of the receptor for the hormone.

After penetration through the membrane into the cell, glucocorticoids bind to receptors, which leads to the activation of the complex. In this case, the oligomeric protein complex dissociates - heat shock proteins (Hsp90 and Hsp70) and immunophilin are detached. As a result, the receptor protein included in the complex as a monomer acquires the ability to dimerize. Following this, the resulting “glucocorticoid + receptor” complexes are transported to the nucleus, where they interact with DNA regions located in the promoter fragment of the steroid-responding gene - the so-called. glucocorticoid response elements (GRE) and regulate (activate or suppress) the process of transcription of certain genes (genomic effect). This leads to stimulation or suppression of mRNA formation and changes in the synthesis of various regulatory proteins and enzymes that mediate cellular effects.

Recent studies show that GC receptors interact, in addition to GRE, with various transcription factors, such as transcription activator protein (AP-1), nuclear factor kappa B (NF-kB), etc. It has been shown that nuclear factors AP-1 and NF-kB are regulators of several genes involved in the immune response and inflammation, including genes for cytokines, adhesion molecules, proteinases, and others.

In addition, another mechanism of action of glucocorticoids has recently been discovered, associated with the effect on transcriptional activation of the cytoplasmic inhibitor of NF-kB, IkBa.

However, a number of effects of glucocorticoids (for example, the rapid inhibition of ACTH secretion by glucocorticoids) develop very quickly and cannot be explained by gene expression (the so-called extragenomic effects of glucocorticoids). Such properties may be mediated by non-transcriptor mechanisms, or by interaction with glucocorticoid receptors on the plasma membrane found in some cells. It is also believed that the effects of glucocorticoids can be realized at different levels depending on the dose. For example, at low concentrations of glucocorticoids (>10 -12 mol/l), genomic effects are manifested (their development requires more than 30 minutes), at high concentrations, they are extragenomic.

Glucorticoids cause many effects, tk. affect most cells in the body.

They have anti-inflammatory, desensitizing, anti-allergic and immunosuppressive effects, anti-shock and anti-toxic properties.

The anti-inflammatory effect of glucocorticoids is due to many factors, the leading of which is the suppression of the activity of phospholipase A 2 . At the same time, glucocorticoids act indirectly: they increase the expression of genes encoding the synthesis of lipocortins (annexins), induce the production of these proteins, one of which, lipomodulin, inhibits the activity of phospholipase A 2 . The inhibition of this enzyme leads to the suppression of the liberation of arachidonic acid and inhibition of the formation of a number of inflammatory mediators - prostaglandins, leukotrienes, thromboxane, platelet activating factor, etc. In addition, glucocorticoids reduce the expression of the gene encoding the synthesis of COX-2, further blocking the formation of pro-inflammatory prostaglandins.

In addition, glucocorticoids improve microcirculation in the focus of inflammation, cause capillary vasoconstriction, and reduce fluid exudation. Glucocorticoids stabilize cell membranes, incl. membranes of lysosomes, preventing the release of lysosomal enzymes and thereby reducing their concentration at the site of inflammation.

Thus, glucocorticoids affect the alterative and exudative phases of inflammation and prevent the spread of the inflammatory process.

Limiting the migration of monocytes to the focus of inflammation and inhibition of fibroblast proliferation determine the antiproliferative effect. Glucocorticoids inhibit the formation of mucopolysaccharides, thereby limiting the binding of water and plasma proteins in the focus of rheumatic inflammation. They inhibit the activity of collagenase, preventing the destruction of cartilage and bones in rheumatoid arthritis.

The antiallergic effect develops as a result of a decrease in the synthesis and secretion of allergy mediators, inhibition of the release of histamine and other biologically active substances from sensitized mast cells and basophils, a decrease in the number of circulating basophils, suppression of the proliferation of lymphoid and connective tissues, a decrease in the number of T- and B-lymphocytes, mast cells , reducing the sensitivity of effector cells to allergy mediators, inhibition of antibody formation, changes in the body's immune response.

A characteristic feature of glucocorticoids is their immunosuppressive activity. Unlike cytostatics, the immunosuppressive properties of glucocorticoids are not associated with a mitostatic effect, but are the result of suppression of various stages of the immune response: inhibition of the migration of bone marrow stem cells and B-lymphocytes, suppression of the activity of T- and B-lymphocytes, and inhibition of the release of cytokines (IL -1, IL-2, interferon-gamma) from leukocytes and macrophages. In addition, glucocorticoids reduce the formation and increase the breakdown of the components of the complement system, block the Fc receptors of immunoglobulins, and suppress the functions of leukocytes and macrophages.

The anti-shock and antitoxic effect of glucocorticoids is associated with an increase in blood pressure (due to an increase in the amount of circulating catecholamines, restoration of the sensitivity of adrenoreceptors to catecholamines and vasoconstriction), activation of liver enzymes involved in the metabolism of endo- and xenobiotics.

Glucocorticoids have a pronounced effect on all types of metabolism: carbohydrate, protein, fat and mineral. From the side carbohydrate metabolism this is manifested by the fact that they stimulate gluconeogenesis in the liver, increase the content of glucose in the blood (glucosuria is possible), and contribute to the accumulation of glycogen in the liver. The effect on protein metabolism is expressed in the inhibition of protein synthesis and the acceleration of protein catabolism, especially in the skin, in muscle and bone tissue. This is manifested by muscle weakness, atrophy of the skin and muscles, and slower wound healing. These drugs cause a redistribution of fat: they increase lipolysis in the tissues of the extremities, contribute to the accumulation of fat mainly in the face (moon-shaped face), shoulder girdle, and abdomen.

Glucocorticoids have mineralocorticoid activity: they retain sodium and water in the body by increasing reabsorption in the renal tubules, and stimulate the excretion of potassium. These effects are more typical for natural glucocorticoids (cortisone, hydrocortisone), to a lesser extent - for semi-synthetic ones (prednisone, prednisolone, methylprednisolone). The mineralocorticoid activity of fludrocortisone predominates. Fluorinated glucocorticoids (triamcinolone, dexamethasone, betamethasone) have practically no mineralocorticoid activity.

Glucocorticoids reduce the absorption of calcium in the intestine, promote its release from the bones and increase the excretion of calcium by the kidneys, resulting in the development of hypocalcemia, hypercalciuria, glucocorticoid osteoporosis.

After taking even one dose of glucocorticoids, changes in the blood are noted: a decrease in the number of lymphocytes, monocytes, eosinophils, basophils in the peripheral blood with the simultaneous development of neutrophilic leukocytosis, an increase in the content of erythrocytes.

At long-term use glucocorticoids inhibit the function of the hypothalamus-pituitary-adrenals system.

Glucocorticoids differ in activity, pharmacokinetic parameters (degree of absorption, T 1/2, etc.), methods of application.

Systemic glucocorticoids can be divided into several groups.

According to their origin, they are divided into:

Natural (hydrocortisone, cortisone);

Synthetic (prednisolone, methylprednisolone, prednisone, triamcinolone, dexamethasone, betamethasone).

According to the duration of action, glucocorticoids for systemic use can be divided into three groups (in brackets - biological (from tissues) half-life (T 1/2 biol.):

Short-acting glucocorticoids (T 1/2 biol. - 8-12 hours): hydrocortisone, cortisone;

Glucocorticoids of medium duration of action (T 1/2 biol. - 18-36 hours): prednisolone, prednisone, methylprednisolone;

Long-acting glucocorticoids (T 1/2 biol. - 36-54 h): triamcinolone, dexamethasone, betamethasone.

The duration of action of glucocorticoids depends on the route / site of administration, the solubility of the dosage form (mazipredone is a water-soluble form of prednisolone), and the dose administered. After oral or intravenous administration, the duration of action depends on T 1/2 biol., With intramuscular administration - on the solubility of the dosage form and T 1/2 biol., After local injections - on the solubility of the dosage form and the specific route / site introductions.

When taken orally, glucocorticoids are rapidly and almost completely absorbed from the gastrointestinal tract. C max in the blood is noted after 0.5-1.5 hours. Glucocorticoids bind in the blood to transcortin (corticosteroid-binding alpha 1-globulin) and albumin, and natural glucocorticoids bind to proteins by 90-97%, synthetic ones by 40-60% . Glucocorticoids penetrate well through histohematic barriers, incl. through the BBB, pass through the placenta. Fluorinated derivatives (including dexamethasone, betamethasone, triamcinolone) pass through the histohematic barriers worse. Glucocorticoids undergo biotransformation in the liver with the formation of inactive metabolites (glucuronides or sulfates), which are excreted mainly by the kidneys. Natural drugs are metabolized faster than synthetic drugs and have a shorter half-life.

Modern glucocorticoids are a group of drugs widely used in clinical practice, incl. in rheumatology, pulmonology, endocrinology, dermatology, ophthalmology, otorhinolaryngology.

The main indications for the use of glucocorticoids are collagenosis, rheumatism, rheumatoid arthritis, bronchial asthma, acute lymphoblastic and myeloid leukemia, Infectious mononucleosis, eczema and others skin diseases, various allergic diseases. For the treatment of atopic autoimmune diseases glucocorticoids are the basic pathogenic agents. Glucocorticoids are also used for hemolytic anemia, glomerulonephritis, acute pancreatitis, viral hepatitis and respiratory diseases (COPD in the acute phase, acute respiratory distress syndrome, etc.). In connection with the anti-shock effect, glucocorticoids are prescribed for the prevention and treatment of shock (post-traumatic, surgical, toxic, anaphylactic, burn, cardiogenic, etc.).

The immunosuppressive effect of glucocorticoids makes it possible to use them in organ and tissue transplantation to suppress the rejection reaction, as well as in various autoimmune diseases.

The main principle of glucocorticoid therapy is to achieve maximum therapeutic effect at minimum doses. The dosage regimen is selected strictly individually, to a greater extent depending on the nature of the disease, the patient's condition and the response to the treatment, than on age or body weight.

When prescribing glucocorticoids, it is necessary to take into account their equivalent doses: according to the anti-inflammatory effect, 5 mg of prednisolone correspond to 25 mg of cortisone, 20 mg of hydrocortisone, 4 mg of methylprednisolone, 4 mg of triamcinolone, 0.75 mg of dexamethasone, 0.75 mg of betamethasone.

There are 3 types of glucocorticoid therapy: substitution, suppressive, pharmacodynamic.

Replacement therapy glucocorticoids is necessary for adrenal insufficiency. In this type of therapy, physiological doses of glucocorticoids are used, in stressful situations (for example, surgery, trauma, acute illness), the doses are increased by 2-5 times. When prescribing, the daily circadian rhythm of endogenous secretion of glucocorticoids should be taken into account: at 6-8 o'clock in the morning, most (or all) of the dose is prescribed. At chronic insufficiency adrenal cortex (Addison's disease) glucocorticoids can be used throughout life.

Suppressive therapy glucocorticoids is used for adrenogenital syndrome - congenital dysfunction of the adrenal cortex in children. At the same time, glucocorticoids are used in pharmacological (supraphysiological) doses, which leads to suppression of ACTH secretion by the pituitary gland and a subsequent decrease in the increased secretion of androgens by the adrenal glands. Most (2/3) of the dose is administered at night in order to prevent the peak of ACTH release, according to the principle of negative feedback.

Pharmacodynamic therapy used most often, incl. in the treatment of inflammatory and allergic diseases.

There are several types of pharmacodynamic therapy: intensive, limiting, long-term.

Intensive pharmacodynamic therapy: used in acute, life-threatening conditions, glucocorticoids are administered intravenously, starting with large doses (5 mg / kg - day); after the patient exits the acute state (1-2 days), glucocorticoids are canceled immediately, simultaneously.

Limiting pharmacodynamic therapy: prescribed for subacute and chronic processes, incl. inflammatory (systemic lupus erythematosus, systemic scleroderma, polymyalgia rheumatica, bronchial asthma severe course, hemolytic anemia, acute leukemia, etc.). The duration of therapy is usually several months, glucocorticoids are used in doses exceeding physiological (2-5 mg / kg / day), taking into account the circadian rhythm.

To reduce the inhibitory effect of glucocorticoids on the hypothalamic-pituitary-adrenal system, various schemes for the intermittent administration of glucocorticoids have been proposed:

- alternative therapy- use glucocorticoids of short / medium duration of action (prednisolone, methylprednisolone), once, in the morning (about 8 hours), every 48 hours;

- intermittent circuit- glucocorticoids are prescribed in short courses (3-4 days) with 4-day breaks between courses;

-pulse therapy- rapid intravenous administration of a large dose of the drug (at least 1 g) - for emergency therapy. The drug of choice for pulse therapy is methylprednisolone (it enters inflamed tissues better than others and causes less side effects).

Long-term pharmacodynamic therapy: used in the treatment of diseases chronic course. Glucocorticoids are prescribed orally, the doses exceed the physiological ones (2.5-10 mg / day), the therapy is prescribed for several years, the abolition of glucocorticoids with this type of therapy is carried out very slowly.

Dexamethasone and betamethasone are not used for long-term therapy, since with the strongest and longest, compared with other glucocorticoids, anti-inflammatory action, they also cause the most pronounced side effects, incl. inhibitory effect on lymphoid tissue and corticotropic function of the pituitary gland.

During treatment, it is possible to switch from one type of therapy to another.

Glucocorticoids are used orally, parenterally, intra- and periarticularly, inhalation, intranasally, retro- and parabulbarly, in the form of eye and ear drops, externally in the form of ointments, creams, lotions, etc.

For example, in rheumatic diseases, glucocorticoids are used for systemic, local or local (intraarticular, periarticular, external) therapy. In bronchial obstructive diseases, it is especially important inhaled glucocorticoids.

Glucocorticoids are effective therapeutic agents in many cases. However, it must be taken into account that they can cause a number of side effects, including Itsenko-Cushing's symptom complex (sodium and water retention in the body with the possible appearance of edema, loss of potassium, increased blood pressure), hyperglycemia up to diabetes(steroid diabetes), slowing down the processes of tissue regeneration, exacerbation peptic ulcer stomach and duodenum, ulceration of the digestive tract, perforation of an unrecognized ulcer, hemorrhagic pancreatitis, a decrease in the body's resistance to infections, hypercoagulability with the risk of thrombosis, the appearance of acne, a moon-shaped face, obesity, menstrual irregularities, etc. When taking glucocorticoids, there is an increased excretion of calcium and osteoporosis (with long-term use of glucocorticoids in doses of more than 7.5 mg / day - in the equivalent of prednisone - osteoporosis of long tubular bones may develop). Prevention of steroid osteoporosis is carried out with calcium and vitamin D preparations from the moment you start taking glucocorticoids. The most pronounced changes in the musculoskeletal system are observed in the first 6 months of treatment. One of the dangerous complications is aseptic bone necrosis, so it is necessary to warn patients about the possibility of its development and when “new” pains appear, especially in the shoulder, hip and knee joints, it is necessary to exclude aseptic necrosis of the bone. Glucocorticoids cause changes in the blood: lymphopenia, monocytopenia, eosinopenia, a decrease in the number of basophils in the peripheral blood, the development of neutrophilic leukocytosis, an increase in the content of red blood cells. There may also be nervous and mental disorders: insomnia, agitation (with the development of psychosis in some cases), epileptiform convulsions, euphoria.

With prolonged use of glucocorticoids, one should take into account the probable inhibition of the function of the adrenal cortex (atrophy is not excluded) with the suppression of hormone biosynthesis. The introduction of corticotropin simultaneously with glucocorticoids prevents atrophy of the adrenal glands.

Frequency and strength side effects caused by glucocorticoids can be expressed to varying degrees. Side effects, as a rule, are a manifestation of the actual glucocorticoid action of these drugs, but to a degree exceeding the physiological norm. With proper dose selection, necessary measures precautions, constant monitoring of the course of treatment, the incidence of side effects can be significantly reduced.

To prevent undesirable effects associated with the use of glucocorticoids, it is necessary, especially with long-term treatment, to carefully monitor the dynamics of growth and development in children, periodically conduct an ophthalmological examination (to detect glaucoma, cataracts, etc.), regularly monitor the function of the hypothalamic-pituitary-adrenal systems, blood glucose and urine (especially in patients with diabetes mellitus), monitor blood pressure, ECG, electrolyte composition blood, monitoring the state of the gastrointestinal tract, the musculoskeletal system, monitoring the development of infectious complications, etc.

Most complications in the treatment of glucocorticoids are treatable and disappear after drug withdrawal. Irreversible side effects of glucocorticoids include growth retardation in children (occurs when treated with glucocorticoids for more than 1.5 years), subcapsular cataract (develops in the presence of a family predisposition), steroid diabetes.

Abrupt withdrawal of glucocorticoids can cause an exacerbation of the process - a withdrawal syndrome, especially when long-term therapy is stopped. In this regard, treatment should end with a gradual decrease in dose. The severity of the withdrawal syndrome depends on the degree of preservation of the function of the adrenal cortex. In mild cases, the withdrawal syndrome is manifested by fever, myalgia, arthralgia, and malaise. In severe cases, especially severe stress, an Addisonian crisis (accompanied by vomiting, collapse, convulsions) may develop.

In connection with side effects, glucocorticoids are used only if there are clear indications and under close medical supervision. Contraindications for the appointment of glucocorticoids are relative. In emergency situations, the only contraindication for short-term systemic use of glucocorticoids is hypersensitivity. In other cases, when planning long-term therapy, contraindications should be taken into account.

The therapeutic and toxic effects of glucocorticoids are reduced by inducers of microsomal liver enzymes, enhanced by estrogens and oral contraceptives. Digitalis glycosides, diuretics (causing potassium deficiency), amphotericin B, carbonic anhydrase inhibitors increase the likelihood of arrhythmias and hypokalemia. Alcohol and NSAIDs increase the risk of erosive and ulcerative lesions or bleeding in the gastrointestinal tract. Immunosuppressants increase the chance of developing infections. Glucocorticoids weaken the hypoglycemic activity of antidiabetic drugs and insulin, natriuretic and diuretic - diuretics, anticoagulant and fibrinolytic - derivatives of coumarin and indandione, heparin, streptokinase and urokinase, the activity of vaccines (due to a decrease in antibody production), reduce the concentration of salicylates, mexiletine in the blood. When using prednisolone and paracetamol, the risk of hepatotoxicity increases.

There are five known drugs that suppress the secretion of corticosteroids by the adrenal cortex. (inhibitors of synthesis and action of corticosteroids): mitotane, metyrapone, aminoglutethimide, ketoconazole, trilostane. Aminoglutethimide, metyrapone and ketoconazole inhibit the synthesis of steroid hormones due to the inhibition of hydroxylases (cytochrome P450 isoenzymes) involved in biosynthesis. All three drugs have specificity, tk. act on different hydroxylases. These drugs can cause acute adrenal insufficiency, so they should be used in strictly defined doses and with careful monitoring of the state of the patient's hypothalamic-pituitary-adrenal system.

Aminoglutethimide inhibits 20,22-desmolase, which catalyzes the initial (limiting) stage of steroidogenesis - the conversion of cholesterol to pregnenolone. As a result, the production of all steroid hormones is disrupted. In addition, aminoglutethimide inhibits 11-beta-hydroxylase as well as aromatase. Aminoglutethimide is used to treat Cushing's syndrome caused by unregulated excess cortisol secretion by adrenal cortical tumors or ectopic ACTH production. The ability of aminoglutethimide to inhibit aromatase is used in the treatment of hormone-dependent tumors such as cancer. prostate, mammary cancer.

Ketoconazole is mainly used as an antifungal agent. However, at higher doses, it inhibits several cytochrome P450 enzymes involved in steroidogenesis, incl. 17-alpha-hydroxylase, as well as 20,22-desmolase, and thus blocks steroidogenesis in all tissues. According to some data, ketoconazole is the most effective inhibitor of steroidogenesis in Cushing's disease. However, the feasibility of using ketoconazole in case of excessive production of steroid hormones requires further study.

Aminoglutethimide, ketoconazole, and metyrapone are used to diagnose and treat adrenal hyperplasia.

TO glucocorticoid receptor antagonists refers to mifepristone. Mifepristone is a progesterone receptor antagonist that blocks glucocorticoid receptors in high doses, prevents inhibition of the hypothalamic-pituitary-adrenal system (by a negative feedback mechanism) and leads to a secondary increase in the secretion of ACTH and cortisol.

One of the most important areas clinical application glucocorticoid is a pathology of various parts of the respiratory tract.

Indications for appointment systemic glucocorticoids in respiratory diseases are bronchial asthma, COPD in the acute phase, severe pneumonia, interstitial diseases lungs, acute respiratory distress syndrome.

After systemic glucocorticoids (oral and injection forms), they immediately began to be used to treat severe bronchial asthma. Despite the good therapeutic effect, the use of glucocorticoids in bronchial asthma was limited to the development of complications - steroid vasculitis, systemic osteoporosis, diabetes mellitus (steroid mellitus). Local forms of glucocorticoids began to be used in clinical practice only some time later - in the 70s. XX century. The publication of the successful use of the first topical glucocorticoid, beclomethasone (beclomethasone dipropionate), for the treatment of allergic rhinitis dates back to 1971. In 1972, a report appeared on the use of a topical form of beclomethasone for the treatment of bronchial asthma.

Inhaled glucocorticoids are basic drugs in the treatment of all pathogenetic variants of persistent bronchial asthma, are used in moderate and severe COPD (with a spirographically confirmed response to treatment).

Inhaled glucocorticoids include beclomethasone, budesonide, fluticasone, mometasone, triamcinolone. Inhaled glucocorticoids differ from systemic glucocorticoids in pharmacological properties: high affinity for GK receptors (act in minimal doses), strong local anti-inflammatory effect, low systemic bioavailability (oral, pulmonary), rapid inactivation, short T 1/2 from the blood. Inhaled glucocorticoids inhibit all phases of inflammation in the bronchi and reduce their increased reactivity. Very important is their ability to lower bronchial secretion (reduce the volume of tracheobronchial secretion) and potentiate the action of beta 2-adrenergic agonists. The use of inhaled forms of glucocorticoids can reduce the need for tableted glucocorticoids. An important characteristic of inhaled glucocorticoids is the therapeutic index - the ratio of local anti-inflammatory activity and systemic action. Of the inhaled glucocorticoids, budesonide has the most favorable therapeutic index.

One of the factors that determine the efficacy and safety of inhaled glucocorticoids are systems for their delivery to the respiratory tract. Currently, metered-dose and powder inhalers (turbuhaler, etc.), nebulizers are used for this purpose.

With the right choice of inhalation system and technique, systemic side effects of inhaled glucocorticoids are insignificant due to the low bioavailability and rapid metabolic activation of these drugs in the liver. It should be borne in mind that all existing inhaled glucocorticoids are absorbed to some extent in the lungs. Local side effects of inhaled glucocorticoids, especially with prolonged use, are the occurrence of oropharyngeal candidiasis (in 5-25% of patients), less often - esophageal candidiasis, dysphonia (in 30-58% of patients), cough.

It has been shown that inhaled glucocorticoids and long-acting beta-agonists (salmeterol, formoterol) have a synergistic effect. This is due to stimulation of the biosynthesis of beta 2 -adrenergic receptors and an increase in their sensitivity to agonists under the influence of glucocorticoids. In this regard, combination drugs intended for long-term therapy, but not for relief of attacks, are effective in the treatment of bronchial asthma, for example, a fixed combination of salmeterol / fluticasone or formoterol / budesonide.

Inhalations with glucocorticoids are contraindicated in fungal infections of the respiratory tract, tuberculosis, and pregnancy.

Currently for intranasal applications in clinical practice use beclomethasone dipropionate, budesonide, fluticasone, mometasone furoate. In addition, dosage forms in the form of nasal aerosols exist for flunisolide and triamcinolone, but they are not currently used in Russia.

Nasal forms of glucocorticoids are effective in the treatment of non-infectious inflammatory processes in the nasal cavity, rhinitis, incl. medical, professional, seasonal (intermittent) and year-round (persistent) allergic rhinitis, to prevent the recurrence of the formation of polyps in the nasal cavity after their removal. Topical glucocorticoids are characterized by a relatively late onset of action (12-24 hours), slow development of the effect - it manifests itself by the 3rd day, reaches a maximum on the 5-7th day, sometimes after a few weeks. Mometasone begins to act most quickly (12 hours).

Modern intranasal glucocorticoids are well tolerated; when used at recommended systemic doses (part of the dose is absorbed from the nasal mucosa and enters the systemic circulation), the effects are minimal. Among the local side effects in 2-10% of patients at the beginning of treatment, nosebleeds, dryness and burning in the nose, sneezing and itching are noted. Perhaps these side effects are due to the irritant effect of the propellant. Isolated cases of perforation of the nasal septum have been described with the use of intranasal glucocorticoids.

Intranasal use of glucocorticoids is contraindicated in hemorrhagic diathesis, as well as in repeated nosebleeds in history.

Thus, glucocorticoids (systemic, inhaled, nasal) are widely used in pulmonology and otorhinolaryngology. This is due to the ability of glucocorticoids to stop the main symptoms of diseases of the ENT and respiratory organs, and in the case of a persistent course of the process, to significantly prolong the interictal period. The obvious advantage of using topical dosage forms of glucocorticoids is the ability to minimize systemic side effects, thus increasing the effectiveness and safety of therapy.

In 1952, Sulzberger and Witten first reported the successful use of 2.5% hydrocortisone ointment for the topical treatment of dermatosis. Natural hydrocortisone is historically the first glucocorticoid used in dermatological practice, subsequently it became the standard for comparing the strength of different glucocorticoids. Hydrocortisone, however, is not effective enough, especially in severe dermatoses, due to relatively weak binding to skin cell steroid receptors and slow penetration through the epidermis.

Later, glucocorticoids were widely used in dermatology for treatment various diseases skin of non-infectious nature: atopic dermatitis, psoriasis, eczema, lichen planus and other dermatoses. They have a local anti-inflammatory, anti-allergic effect, eliminate itching (use for itching is justified only if it is caused by an inflammatory process).

Topical glucocorticoids differ from each other in chemical structure, as well as in the strength of the local anti-inflammatory action.

The creation of halogenated compounds (the inclusion of halogens - fluorine or chlorine in the molecule) made it possible to increase the anti-inflammatory effect and reduce systemic side effect when applied topically due to less absorption of drugs. Compounds containing two fluorine atoms in their structure are characterized by the lowest absorption when applied to the skin - flumethasone, fluocinolone acetonide, etc.

According to the European classification (Niedner, Schopf, 1993), there are 4 classes according to the potential activity of local steroids:

Weak (class I) - hydrocortisone 0.1-1%, prednisolone 0.5%, fluocinolone acetonide 0.0025%;

Medium strength (class II) - alklomethasone 0.05%, betamethasone valerate 0.025%, triamcinolone acetonide 0.02%, 0.05%, fluocinolone acetonide 0.00625%, etc.;

Strong (class III) - betamethasone valerate 0.1%, betamethasone dipropionate 0.025%, 0.05%, hydrocortisone butyrate 0.1%, methylprednisolone aceponate 0.1%, mometasone furoate 0.1%, triamcinolone acetonide 0.025%, 0 .1%, fluticasone 0.05%, fluocinolone acetonide 0.025%, etc.

Very strong (class III) - clobetasol propionate 0.05%, etc.

Along with the increase in therapeutic effect when using fluorinated glucocorticoids, the incidence of side effects also increases. The most common local side effects when using strong glucocorticoids are skin atrophy, telangiectasia, steroid acne, striae, and skin infections. The likelihood of developing both local and systemic side effects increases when applied to large surfaces and long-term use of glucocorticoids. Due to the development of side effects, the use of fluorine-containing glucocorticoids is limited if long-term use is necessary, as well as in pediatric practice.

V last years by modifying the steroid molecule, local glucocorticoids of a new generation were obtained, which do not contain fluorine atoms, but are characterized by high efficiency and a good safety profile (for example, mometasone in the form of furoate, a synthetic steroid that began to be produced in 1987 in the USA, methylprednisolone aceponate, which has been used in practice since 1994).

The therapeutic effect of topical glucocorticoids also depends on the dosage form used. Glucocorticoids for local application in dermatology, they are available in the form of ointments, creams, gels, emulsions, lotions, etc. The ability to penetrate the skin (depth of penetration) decreases in the following order: fatty ointment> ointment> cream> lotion (emulsion). With chronic dry skin, the penetration of glucocorticoids into the epidermis and dermis is difficult; moisturizing the stratum corneum of the epidermis with an ointment base increases the penetration of drugs into the skin several times. In acute processes with pronounced weeping, it is more expedient to prescribe lotions, emulsions.

Since topical glucocorticoids reduce the resistance of the skin and mucous membranes, which can lead to the development of superinfection, in case of secondary infection, it is advisable to combine in one dosage form glucocorticoid with an antibiotic, for example, Diprogent cream and ointment (betamethasone + gentamicin), Oxycort aerosols (hydrocortisone + oxytetracycline) and Polcortolone TS (triamcinolone + tetracycline), etc., or with antibacterial and antifungal agent, for example Akriderm GK (betamethasone + clotrimazole + gentamicin).

Topical glucocorticoids are used in the treatment of complications of chronic venous insufficiency (CVI), such as trophic skin disorders, varicose eczema, hemosiderosis, contact dermatitis, etc. Their use is due to the suppression of inflammatory and toxic-allergic reactions in soft tissues that occur in severe forms of CVI. In some cases, local glucocorticoids are used to suppress vascular reactions that occur during phlebosclerosing treatment. Most often, ointments and gels containing hydrocortisone, prednisolone, betamethasone, triamcinolone, fluocinolone acetonide, mometasone furoate, etc. are used for this.

The use of glucocorticoids in ophthalmology based on their local anti-inflammatory, antiallergic, antipruritic action. Indications for the appointment of glucocorticoids are inflammatory diseases of the eye of non-infectious etiology, incl. after injuries and operations - iritis, iridocyclitis, scleritis, keratitis, uveitis, etc. For this purpose, hydrocortisone, betamethasone, desonide, triamcinolone, etc. are used. The use of local forms is most preferable ( eye drops or suspension, ointments), in severe cases - subconjunctival injections. With systemic (parenteral, oral) use of glucocorticoids in ophthalmology, one should be aware of the high probability (75%) of developing steroid cataracts with daily use for several months of prednisolone at a dose of more than 15 mg (as well as equivalent doses of other drugs), while the risk increases with increasing the duration of treatment.

Glucocorticoids are contraindicated in acute infectious diseases eye. If necessary, for example, in case of bacterial infections, combined preparations containing antibiotics are used, such as Garazon eye / ear drops (betamethasone + gentamicin) or Sofradex (dexamethasone + framycetin + gramicidin), etc. Combined drugs, which include HA and antibiotics, are widely used in ophthalmic and otorhinolaryngological practice. In ophthalmology - for the treatment of inflammatory and allergic eye diseases in the presence of concomitant or suspected bacterial infection, for example, with certain types of conjunctivitis, in postoperative period. In otorhinolaryngology - with otitis externa; rhinitis complicated by a secondary infection, etc. It should be borne in mind that the same bottle of the drug is not recommended for the treatment of otitis media, rhinitis and eye diseases in order to avoid the spread of infection.

Preparations

Preparations - 2564 ; Trade names - 209 ; Active ingredients - 27

Often a person finds the optimal solution to any problems in himself. Where, for example, does the body get the strength to fight diseases?

As scientific studies carried out in the middle of the 20th century showed, an important role in this matter belongs to the hormones glucocorticoids.

They are produced by the adrenal glands for almost all cells of the human body, and it is these hormones that help fight various inflammatory processes.

Synthesized analogues of the hormone are now successfully used in medicine.

Glucocorticosteroids (GCS) - what is it in medicine

Glucocorticoids and glucocorticosteroids are the same, synonymous words for hormones produced by the adrenal cortex, both natural and synthetic, sometimes use the abbreviation GCS for short.

Together with mineralocorticoids, corticosteroids make up an extensive group of corticosteroids, but it is corticosteroids that are especially in demand as medicines. You can read about what these drugs are - corticosteroids.

They provide the doctor with great opportunities for the treatment of serious diseases, "extinguish" foci of inflammation, can enhance the effect of other medications, relieve swelling, dull the feeling of pain.

By artificially increasing the amount of corticosteroids in the patient's body, doctors solve problems that previously seemed impossible.

Medical science has also achieved GCS today can be used "addressed"- act exclusively on the problem area, without disturbing others, healthy ones.

As a result of such topical application, the risk of side effects is reduced.

The scope of glucocorticoid drugs is quite wide. These funds are used:

In addition, corticosteroids are used in the treatment of injuries ( they have an effective anti-shock effect), and also to restore body functions after complex operations, radiation and chemotherapy.

The regimen for taking GCS takes into account the possible syndrome of glucocorticoid withdrawal, that is, the risk of a deterioration in the patient's well-being after stopping these drugs.

The patient may even develop a so-called glucocorticoid deficiency.

To prevent this from happening treatment with glucocorticoids is usually completed smoothly, carefully reducing the dose of the drug at the end of the treatment course.

All the most important, systemic processes take place under the influence of GCS at the cellular, including the genetic level.

It means that work with medical preparations only specialists of this kind can, self-medication is strictly prohibited, since it can cause all sorts of complications.

The mechanism of action of glucocorticoids on the body is not yet fully understood. GCS, as scientists managed to find out, are formed according to the “command” of the pituitary gland: it secretes a substance called “corticotropin” into the blood, which already sends its own signal - about how much GCS the adrenal glands should give out.

One of their main products is an active glucocorticoid called cortisol, also called the “stress hormone”.

Such hormones are produced for various reasons, their analysis helps physicians to identify violations in endocrine system, serious pathologies and select such drugs (including corticosteroids) and treatment methods that will be most effective in each specific situation.

Glucocorticoids affect the body in several ways at once. One of the most important is their anti-inflammatory effect.

GCS can reduce the activity of enzymes that destroy body tissues, isolating the affected areas from healthy ones.

GCS affect the cell membranes, making them coarser, and therefore complicate the metabolism, as a result, the infection does not give a chance to spread throughout the body, put it in a "hard frame".

Among other ways of the influence of GCS on the human body:

• immunoregulatory effect- under different circumstances, immunity increases slightly or, on the contrary, immunity suppression occurs (this property of GCS is used by doctors during tissue transplantation from donors);
• antiallergic;
• anti-shock - effective, for example, in anaphylactic shock, when medication should provide lightning-fast results to save the patient.

GCS can affect the production of insulin (this helps patients with hypoglycemia), accelerate the production of a substance such as erythropoietin in the body (with its participation in the blood, the hemoglobin content increases), can raise arterial pressure affect protein metabolism.

When prescribing drugs, doctors have to take into account many nuances, including the so-called resorptive effect, when the drug, after absorption, enters the general bloodstream, and from there into the tissues. Many types of corticosteroids allow the use of drugs more locally.

Unfortunately, not all "activities" of glucocorticoids are 100% beneficial to a person.

An excess of GCS as a result of long-term use of the drug leads, for example, to the fact that internal biochemistry changes - calcium is washed out, bones become brittle, osteoporosis develops.

Glucocorticoids are distinguished by how long they work inside the body.

Short acting drugs remain in the patient's blood from two hours to half a day (examples - Hydrocortisone, Cyclesonide, Mometasone). You can read the instructions for using Hydrocortisone.

GCS medium action- up to one and a half days (Prednisolone, Methylprednisolone), long-term action - 36-52 hours (Dexamethasone, Beclomethasone).

There is a classification according to the method of administration of the drug:

Fluorinated glucocorticoids have a particularly powerful effect on the patient's body. These funds also have their own classification.

Depending on the amount of fluorine contained in them, they are monofluorinated, di- and trifluorinated.

A variety of drugs using corticosteroids gives physicians the opportunity to choose the right form of medication (tablets, cream, gel, ointment, inhaler, patch, nose drops) and the appropriate “content” in order to get exactly those pharmacological effects that are necessary, and in no case aggravate the patient's condition by causing any side effects in the body.

Pharmacology is the lot of specialists, only a doctor understands in all the subtleties what effect a particular drug can have on the body, when and according to what scheme it is used.

As an example, we give the names of glucocorticoid drugs:

Treatment Methods

Developed different types methods of treatment with GCS:

• replacement - is used if the adrenal glands cannot independently produce the amount of hormones the body needs;
• suppressive - for children with congenital abnormalities in the functioning of the adrenal cortex;
• pharmacodynamic(it includes intensive, limiting and long-term treatment) - in anti-allergic and anti-inflammatory therapy.

In each case, certain doses of the drug taken and the frequency of their use are provided.

So, alternating therapy involves taking glucocorticoids once every two days, pulse therapy means the prompt administration of at least 1 g of the drug for urgent care to the patient.

Why are glucocorticoids dangerous for the body? They change its hormonal balance and sometimes cause the most unexpected reactions., especially if for some reason an overdose of the drug has occurred.

The diseases provoked by corticosteroids include, for example, hyperfunction of the adrenal cortex.

The fact is that the use of a drug that helps the adrenal glands perform their functions, gives them the opportunity to “relax”. If the drug is abruptly stopped, the adrenal glands can no longer engage in full-fledged work.

What other troubles can await after taking GCS? This:

If the danger is noticed in time, almost all the problems that have arisen can be safely resolved. The main thing is not to aggravate them with self-medication, but act only in accordance with the recommendations of the doctor.

Contraindications

The standards of treatment with glucocorticoids suggest only one absolute contraindication for the use of corticosteroids once - this is an individual intolerance to the drug by the patient.

If treatment is required for a long time, then the list of contraindications becomes wider.

These are diseases and conditions such as:

• pregnancy;
• diabetes;
• diseases of the gastrointestinal tract, kidneys, liver;
• tuberculosis;
• syphilis;
• mental disorders.

Pediatric glucocorticoid therapy provided only in very rare cases.

MEDICINES WITH ACTIVITY OF GLUCOCORTICOID AND MINERALOCORTICOID HORMONES, INHIBITORS OF STEROID HORMONES SYNTHESIS.

The doctor must first of all ask himself the question of how much the disease in which corticosteroids are supposed to be used is more dangerous for the patient than the Cushing's syndrome developing during their treatment.

J. M. Liddle, 1961

The adrenal glands are paired endocrine organs that are located at the upper pole of the kidneys. The adrenal glands are divided into cortex and medulla. The medulla produces epinephrine, norepinephrine, and adrenomedullin, hormones that control blood pressure in humans.

The adrenal cortex produces steroid hormones. Adrenal hormonal steroids can be divided into 3 groups:

Hormones that control interstitial metabolism (glucocorticosteroid hormones) - the main ones are cortisol and corticosterone (hydrocortisone);

Hormones that control sodium and potassium metabolism (mineralocorticoid hormones). The main representative of this group is aldosterone;

The hormones that control reproductive function (sex steroids) are progesterone and dihydroepiandrosterone. The main source of this group of hormones are not the adrenal glands, but the gonads. In men, the main androgen, testosterone, is produced in the testicles, and in women, estrogens (estrone, estradiol and estriol) and gestagens (progesterone) are produced in the ovaries.

Glucocorticosteroid drugs

Synthesis and secretion of glucocorticoid hormones. Synthesis of corticosteroids is under the control of the pituitary and hypothalamus. The hypothalamus secretes corticoliberin in a pulsating mode, and secretion stimuli are food intake and the beginning of daylight hours. Under the influence of corticoliberin, the hypothalamus produces ACTH, which activates receptors on the surface of the cells of the adrenal cortex. Under the influence of ACTH, 3 key proteins involved in the synthesis of glucocorticosteroids are activated:

Cholesterol esterase is an enzyme that releases cholesterol from intracellular depot esters.

The StAR protein is a shuttle that transports cholesterol to the mitochondria, where the first step in the synthesis of steroid hormones (the formation of pregnenolone) takes place.

P 450 SCC is an enzyme that cleaves off the side chain of cholesterol during the synthesis of pregnenolone.

After the formation of pregnenolone, the synthesis of steroid hormones proceeds along 3 relatively independent pathways (see Fig. 1):

With the help of 17--hydroxylase, pregnenolone is converted to 17-hydroxypregnenolone, from which, under the influence of 21- and 11-hydroxylases, glucocorticosteroids (cortisol) are formed. This is the main pathway for the synthesis of glucocorticosteroids.

Part of the 17-hydroxypregnenolone, which was formed in the previous step, is subjected to repeated action of 17--hydroxylase and is converted into the main adrenal androgen - dihydroepiandrosterone. This is the main pathway for the synthesis of sex steroids in the adrenal glands. In the sex glands, dihydroepiandrosterone is further exposed to the action of 17-ketoreductase and testosterone is formed. In the testicles of men, synthesis is interrupted at this stage. In women, with the help of the aromatase enzyme, which is located in the ovaries, adipose tissue, breast tissue, testosterone is converted into estrogens.

Under the influence of 3-hydroxy- 5  4 -isomerase, pregnenolone is converted into progesterone. Which is subsequently converted into aldosterone under the influence of 21- and 11-hydroxylases. This is the main pathway for the synthesis of mineralocorticoids. Part of aldosterone is able to convert into the weak glucocorticoid corticosterone, so it is also an additional pathway for the synthesis of glucocorticoids.

Glucocorticoids, which are released into the blood by the adrenal glands in the form of 8-10 peaks (with the maximum 2 peaks occurring at 5-8 am), reduce the synthesis and secretion of corticoliberin and ACTH by a negative feedback mechanism.

Classification of drugs with the activity of glucocorticosteroid hormones.

Means with the activity of natural hormones: hydrocortisone.

Synthetic glucocorticoid agents: prednisolone, methylprednisolone, dexamethasone, triamcinolone.

Synthetic glucocorticoid agents for topical use: flumethasone, beclomethasone, budesonide.

Figure 1. Scheme of steroid hormone biosynthesis. In the adrenal glands, biosynthesis proceeds in 3 ways: 5  4 -isomerase pathway (mineralocorticoid synthesis), 17 -hydroxylase pathway (synthesis of glucocorticoids), double 17 -hydroxylase pathway (synthesis of sex steroids). The testicles have a 17-ketoreductase step in testosterone synthesis, and the ovaries have an aromatase conversion of androgens to estrogens.

Mechanism of action. Glucocorticosteroids enter the target cells and penetrate through their membrane into the cytoplasm, where they bind to specific receptors. At rest, glucorticoid receptors are bound to the heat shock protein (hsp90) in an inactive complex. Under the influence of the glucocorticoid hormone, the receptor is released from the protein, attaches the hormone, after which the hormone-receptor complexes combine in pairs and the resulting pairs enter the cell nucleus, where they bind to the receptor nucleotide sequences on the DNA surface. A palindrome acts as such a receptor sequence. GGTACAxxxTGTTCT. Activation of DNA receptors leads to changes in the processes of transcription of a number of genes.

Physiological effects of glucocorticoid hormones. This group of effects occurs even at the physiological concentration of hormones in the body.

Influence on carbohydrate metabolism. Glucocorticoids cause an increase in blood glucose concentration in several ways:

reduce the uptake of glucose by tissues by inhibiting the work of glucose transporters GLUT-1 and GLUT-4;

stimulate the processes of gluconeogenesis from amino acids and glycerol (increase the synthesis of key enzymes of gluconeogenesis - phosphoenolpyruvate carboxykinase, fructose-2,6-bisphosphatase, glucose-6-phosphatase);

stimulate the synthesis of glycogen due to the formation of additional molecules of glycogen synthetase.

Influence on lipid metabolism. Hyperglycemia, which is caused by glucocorticosteroids, leads to an increase in insulin secretion and, therefore, adipose tissue is affected simultaneously by 2 hormones - glucocorticoid and insulin. Adipose tissue on the extremities is more sensitive to glucocorticoids, so here corticosteroids inhibit glucose uptake and increase lipolysis (fat breakdown). As a result, the fat content on the limbs decreases.

On the trunk, adipose tissue is more sensitive to the action of insulin and therefore lipogenesis (fat synthesis) is enhanced in its cells. As a result, under the influence of glucocorticosteroids, fat is redistributed in the body: fat is deposited on the chest, abdomen, buttocks in a person, the face is rounded, and a “bull withers” appears on the back of the neck. At the same time, the limbs of such people are practically devoid of fat.

Effect on amino acid metabolism. Glucocorticosteroids stimulate the synthesis of RNA and protein in the liver, increase the breakdown of proteins in muscle tissues, skin, connective, adipose and lymphoid tissues (lymph nodes, thymus gland, spleen). That. glucocorticoids have a catabolic effect.

mineralocorticoid activity. Glucocorticosteroid hormones are able to activate mineralocorticoid receptors (although to a lesser extent than mineralocorticoid hormones). As a result, in the collecting ducts of the nephron, the genes for the synthesis of the permease protein are activated, which forms channels for the reabsorption of sodium ions. As a result of sodium reabsorption, fluid is retained in the body, the volume of circulating blood increases, and the secretion of potassium ions into the urine increases.

Pharmacological effects of glucocorticoids. This group of effects occurs only at supraphysiological concentrations of the hormone in the body.

Anti-inflammatory effect. Glucocorticoids suppress all phases of both acute and chronic inflammation. The exact mechanism of the anti-inflammatory effect has not yet been established. It is believed that several processes play a role in its implementation:

Figure 2. Schematic of the biosynthesis of eicosanoids from arachidonic acid. COX- I, II- cyclooxygenasesIandIItypes, 5-LOG– 5-lipoxygenase,Pg- prostaglandins,LT– leukotrienes, 5- and 12-HPETE- 5- and 12-hydroperoxyeicosatetraenoic acids, GCS - glucocorticosteroids, NSAIDs - non-steroidal anti-inflammatory drugs. The diagram shows the receptors for prostaglandins:

EP- relaxation of smooth muscles, increased secretion of water in the intestine, inhibition of secretionHCl, natriuresis, decreased release of ADH, pyrogenesis.

D.P.- platelet aggregation.

FP- contraction of smooth muscles, increased secretion of water in the intestine, the release of FSH, LH, prolactin, inflammation.

IP- relaxation of smooth muscles, decreased platelet aggregation, natriuresis, decreased renin secretion.

TP- contraction of smooth muscles and increased platelet aggregation.

In the focus of inflammation, the activity of phospholipase A 2 and cyclooxygenase-II (COX-II) increases, which are involved in the synthesis of inflammatory mediators - prostaglandins and leukotrienes. Corticosteroids inhibit the genes responsible for the synthesis of COX-II. In addition, under the influence of glucocorticoids, the genes responsible for the synthesis of a special protein, lipocortin, are activated. This protein is able to bind phospholipase A 2 into inactive complexes. Therefore, with the introduction of glucocorticosteroids, the activity of phospholipase A 2 and cyclooxygenase-II type decreases, the synthesis of pro-inflammatory cytokines decreases (see Fig. 2.).

In the focus of inflammation, cell adhesion molecules are formed in large quantities - special proteins that are synthesized by endothelial cells and are necessary to attract leukocytes and macrophages to the focus of inflammation. Glucocorticosteroids reduce the synthesis of cell adhesion molecules, the migration of leukocytes and macrophages to the focus of inflammation stops.

In the focus of inflammation, mitogenic factors (TNF) are formed, which stimulate the reproduction of fibroblasts (the main cells of the connective tissue) and the processes of scarring of the inflamed tissue. This process can be very dangerous, because. in the process of scarring, normal cells can die in the tissue (for example, in rheumatic inflammation of the joints, the scarring process leads to the destruction of the cartilage and bone of the joint and the cessation of movement in the joint). Glucocorticoids inhibit TNF genes and reduce fibrosis processes in the focus of inflammation.

immunosuppressive effect. Glucocorticosteroids have a multilateral inhibitory effect on immune system associated with the suppression of a number of cytokines:

Impact on the immune system	Called effect
Inhibition of synthesis genes:	There is no activation of T-helpers T-helpers do not transmit a signal to working lymphocytes B-lymphocytes do not mature into plasma cells for antibody synthesis There is no maturation of T-lymphocytes and NK cells, the effect of IL-2 is weakened.
Apoptosis of B-lymphocytes	Inhibition of humoral immunity (impaired antibody synthesis), reduced resistance to bacterial infections.
Apoptosis of T-lymphocytes, macrophages and natural killers	Inhibition of cellular immunity: antiviral immunity, delayed-type allergic reactions, transplant rejection reactions.
Suppression of the synthesis of -interferon	Violation of antiviral immunity.
Suppression of antigen production in damaged tissues	Decrease in autoimmune processes.
Inhibition of synthesis and increase in the breakdown of components of the compliment system	Violation of the processes of lysis of foreign cells (membrane attack complex is not formed)

1. Influence on the cardiovascular system. Glucocorticoids increase blood pressure and stabilize it on this elevated level. The effect is associated, on the one hand, with an increase in BCC against the background of fluid retention due to mineralocorticoid activity, on the other hand, with an increase in the sensitivity of the myocardium and blood vessels to catecholamines.

   Influence on hematopoiesis. Glucocorticoids inhibit the synthesis of hematopoietic factors - IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF), which are necessary for the process of bone marrow stem cell division. Therefore, against the background of the introduction of glucocorticoids in the blood, the level of lymphocytes, monocytes, basophils, eosinophils decreases. At the same time, the formation of neutrophils in bone marrow and their concentration in the blood increases. After a single administration of glucocorticoids, this effect reaches its maximum value by the 6th hour and decreases by the end of the day.

   Influence on the respiratory system. In the last month of pregnancy in the fetus, glucocorticoids activate the genes responsible for the synthesis of surfactant, a surfactant that covers the alveoli of the lungs and is necessary both for their opening at the time of the first breath and for subsequent protection of the lung tissue from collapse (fall).

The use of glucocorticoids. There are three types of glucocorticoid therapy.

Compensatory therapy - is carried out in chronic adrenal insufficiency (Addison's disease) and acute adrenal insufficiency, for example, in shock (Waterhouse-Fridrekssen syndrome). As a rule, glucocorticoids with mineralocorticoid activity are recommended for compensatory therapy.

Suppressive (suppressive) therapy. Applies to the following conditions:

To suppress the production of androgens in girls with adrenogenital syndrome. In adrenogenital syndrome, there is a congenital defect in the 21-hydroxylase enzyme, which provides the last steps in the synthesis of glucocorticosteroids. Therefore, in the body of girls with this syndrome, the level of glucocorticoids is low and, according to the negative feedback mechanism, this deficiency stimulates the cells of the hypothalamic-pituitary zone and the level of corticoliberin and ACTH increases. If the activity of the 21β-hydroxylase enzyme were normal, this would cause an increase in the synthesis of glucocorticoids, but in this case, the synthesis process stops at an earlier stage - at the level of progesterone and 17-hydroxypregnenolone, which undergo conversion to dihydroepiandrosterone via the androgenic pathway (see Fig. one). That. in the body of children with adrenogenital syndrome, there is an excess of androgens. In girls, this is manifested by virilization (hirsutism, male-type voice mutation, male physique, clitoral hypertrophy and underdevelopment of the uterus). The administration of small doses of glucocorticoids in such patients leads to the fact that the release of ACTH is suppressed by the feedback mechanism and the excess production of androgens by the adrenal glands stops.

To suppress transplant rejection in organ transplant patients. Glucocorticosteroids suppress the reactions of cellular immunity, which are caused by antigens of a foreign organ.

Corticosteroids are included in almost all modern chemotherapy regimens for malignant blood tumors and breast cancer. In this case, their use serves as the basis of synchronizing therapy. Tumor cells are located on different stages maturation and division and therefore have different sensitivity to chemotherapy drugs. The use of glucocorticosteroids stops the development of the cell at the moment when it passes the G 2 phase life cycle(premitotic). Therefore, when glucocorticoids are prescribed, all cells gradually synchronize - they freeze in the G 2 phase. As soon as synchronization is achieved, glucocorticosteroids are canceled, and all tumor cells simultaneously enter mitosis and become highly sensitive to chemotherapy drugs.

Pharmacodynamic (pathogenetic) therapy. It exists in two forms:

Intensive glucocorticoid therapy. Glucocorticoids are administered in high doses (5 mg/kg per day as prednisolone) usually intramuscularly or intravenously. In the absence of effect, the dose is increased by 25-50% every 4 hours. After stabilization of the condition, after 1-2 days, treatment is stopped immediately. This type of therapy is used for:

anaphylactic shock (steroids interrupt the allergic reaction and stabilize blood pressure);

traumatic shock (steroids stabilize blood pressure);

status asthmaticus (a condition in which asthma attacks follow each other without periods of improvement);

toxic pulmonary edema caused by asphyxiant substances (in this case, steroids are used by inhalation - within 15 minutes, the patient needs to inhale 200-400 standard doses of the steroid, i.e. 1-2 aerosol cans).

Limiting (long-term) therapy. It is carried out for several months, years or even for life. In this case, the doses of cortisteroids are selected individually, but, as a rule, they do not exceed 5-10 mg / kg per day for prednisolone. This therapy aims to suppress a chronic inflammatory or autoimmune process. It is used for:

connective tissue diseases (systemic lupus erythematosus, rheumatoid arthritis, systemic scleroderma, dermatomyositis, periarteritis nodosa, etc.);

diseases of the gastrointestinal tract (ulcerative colitis, Crohn's disease, hepatitis);

respiratory diseases (severe bronchial asthma);

kidney diseases (chronic glomerulonephritis, nephrotic syndrome);

blood diseases (thrombocytopenic purpura or Werlhof's disease);

autoimmune diseases thyroid gland (autoimmune thyroiditis, subacute thyroiditis);

allergic diseases (angioedema angioedema, hay fever, atopic dermatitis, Stevens-Jones syndrome, Lyell's syndrome), psoriasis, eczema;

inflammatory diseases of the choroid of the eyes (uveitis).

The effect of glucocorticoids on the hematopoietic system is sometimes used in the treatment of agranulocytosis, a condition in which there are no neutrophils in the blood (in this case, immunity is sharply reduced, necrotic tonsillitis, colitis, pneumonia). Agranulocytosis is usually caused by exposure to ionizing radiation (radiation sickness) or toxic factors (toxic agranulocytosis).

In women with miscarriage, the introduction of glucocorticoids is used to induce the synthesis of surfactant in the fetus and prepare the lungs of the unborn child for spontaneous breathing. If the birth occurred prematurely and the baby is premature for more than 2 weeks, then there is no surfactant in his lungs and the lung tissue cannot straighten out at the time of the first breath (newborn distress syndrome occurs). Subsequently, inflammation occurs in such a collapsed lung tissue (atelectatic pneumonia) and the alveoli die, being replaced by cartilaginous membranes (hyalinosis of the lungs). The introduction of corticosteroids before childbirth allows you to start the process of surfactant synthesis ahead of time and prepare the lung tissue of the fetus for spontaneous breathing.

Dosing regimen of glucocorticosteroids. As a rule, in the treatment of a disease, doses of steroids are indicated in terms of prednisolone. If it is necessary to prescribe another steroid, a scale of equivalent doses is used (see table). Currently, three principal schemes for the administration of glucocorticosteroids are used.

Continuous introduction. Glucocorticoids are used daily daily dose administered in 2 doses: ⅔ dose in the morning at 7-8 o'clock and ⅓ dose at 14-15 o'clock in the afternoon. With this mode of administration, the natural circadian rhythm of glucocorticoid secretion is modeled and they less often cause atrophy of the adrenal cortex.

alternative therapy. The patient in the morning every other day receives a double daily dose of glucocorticoids. Such a regimen of therapy is used only after the course of the disease has become stable. This type of therapy rarely causes unwanted effects, because. between doses of the drug, a sufficient period of rest is maintained to restore impaired functions.

Pulse therapy. In this mode, the patient is administered intravenously 1000 mg of methylprednisolone once a week for 30-60 minutes. In the following days, the patient either does not receive steroids at all, or he is prescribed minimal doses. This mode of administration is used for heavy course of the disease, refractoriness to conventional therapy.

Undesirable effects of steroid therapy. With short-term use (less than 1 week), even moderately large doses, serious undesirable effects usually do not develop. Long-term treatment with glucocorticoids is accompanied by the occurrence of undesirable effects in 50-80% of patients. All undesirable effects of steroid therapy can be grouped into several groups:

Endocrine and metabolic disorders:

Exogenous Itsenko-Cushing syndrome (hypercorticism). Characterized by an increase in body weight appearance(moon face, bull's withers, hirsutism, acne, purple-red stretch marks on the skin) arterial hypertension, in the blood of such patients neutrophilia, the level of eosinophils and lymphocytes is sharply reduced.

Atrophy of the adrenal cortex and depression of the hypothalamic-pituitary-adrenal system. When taking steroids in physiological doses (2.5-5.0 mg / day for prednisolone), the risk of developing adrenal atrophy is minimal, but if higher doses are used, then after 1-2 weeks, inhibition of the adrenal cortex is observed. Moreover, it should be remembered that if the course lasted 2-3 weeks, then it takes from 6 to 12 months to fully restore the function of the cortex.

The "withdrawal" syndrome is characterized by a sharp deterioration in the course of the disease with a sudden cessation of steroid use, signs of adrenal insufficiency: weakness, fatigue, loss of appetite, muscle and joint pain, fever. In severe cases, an adrenal crisis is possible - vomiting, convulsions, collapse.

"Steroid diabetes" - is characterized by a typical picture of diabetes mellitus, due to an increase in blood glycemia, contrainsular action of steroids.

Hyperlipidemia, progression of atherosclerotic vascular lesions.

Changes in the musculoskeletal system: osteoporosis, pathological bone fractures - this effect is associated with inhibition of calcitonin synthesis and an increase in parathyroid hormone production, acceleration of calcium metabolism in patients who take glucocorticoids.

Skin changes: there is thinning and atrophy of the skin. Most often, this effect occurs when hormones are injected intramuscularly into the shoulder.

Gastrointestinal: The emergence of "dumb", i.e. asymptomatic ulcers of the duodenum and stomach. Asymptomatic ulcers are due to the effect of steroids, which suppress the inflammatory process and pain that occurs during the formation of an ulcer.

Cardiovascular system: edema and hypokalemia, which are caused by the mineralocorticoid component of the action of steroids. In severe cases, arterial hypertension may occur.

CNS: general agitation, psychotic reactions (delusions, hallucinations) when administered in large doses. It is possible to increase intracranial pressure with nausea and headache (pseudo brain tumor syndrome).

Organs of vision: glaucoma, posterior capsular cataract.

Immunity and regeneration: taking glucocorticoids leads to disruption of wound healing, weakening of antibacterial and antiviral immunity: the patient develops disseminated bacterial and viral infections, whose clinic is erased, because steroids eliminate typical inflammation, pain, hyperemia. Quite often, taking steroids and the resulting immunodeficiency lead to the development of candidiasis of the mucous membranes and skin, the occurrence of tuberculosis.

Teratogenic effect.

It should be remembered that all glucocorticoids do not differ in their effectiveness, but the differences are in the activity, duration of action of drugs, the features of their pharmacokinetics and the frequency of development of undesirable effects (see also Table 1).

Glucocorticoid agents for systemic use.

Hydrocortisone (Hydrocortisone). Natural glucocorticoid hormone. In terms of glucocorticoid activity, it is inferior to prednisolone, but in terms of mineralocorticoid activity it is 3 times superior.

F K: Available in the form of 2 esters: 1) hydrocortisone succinate - is a readily soluble powder that can be used for intramuscular and intravenous administration; 2) hydrocortisone acetate - a fine-grained suspension, which can only be administered intramuscularly or into the joint cavity.

In the blood, hydrocortisone is 90% bound to blood proteins (80% to transcortin and 10% to albumin). Biologically active are only 10% of the free fraction of hydrocortisone. Hydrocortisone can penetrate well into all organs and tissues, incl. and through the placenta. However, the placenta contains the enzyme 11β-dehydrogenase, which converts more than 67% of hydrocortisone to inactive 11-keto-hydrocortisone. Therefore, this drug can be used for health reasons in pregnant women, because. its effect on the fetus will be minimized.

Application and dosing regimen. Currently, hydrocortisone is used quite rarely, mainly in the replacement therapy of acute adrenal insufficiency (intravenously at a dose of 100-500 mg / day, usually no more than 48-72 hours), as well as locally:

• retrobulbarno with inflammatory diseases of the eyes, 5-20 mg 1 time per week;

  skin in the form of ointments, creams, lotions for skin allergic diseases, psoriasis, eczema 2-3 times a day is applied to the affected area without rubbing it, the duration of the course of treatment is no more than 2-3 weeks;

  rectally in the form of microclysters for ulcerative colitis, Crohn's disease, 5-50 mg per enema daily or every other day;

  intra-articular in rheumatoid arthritis and other systemic collagenoses, 5-25 mg into the cavity of a “dry” joint (i.e., in the absence of exudate in the joint cavity) 1 time in 1-3 weeks for a total of up to 6 injections.

FV: 0.5 1 and 2.5% eye ointment, 2.5 and 3.0 g each; 0.1% cream 15.0 g each and 0.1 lotion 20 ml each;

suspension of hydrocortisone acetate 2.5% in ampoules of 1 and 2 ml;

hydrocortisone succinate powder 500 mg in vials.

Prednisolone (Prednisolone). Synthetic glucocorticoid, which is considered as a reference agent in this group. Combines high glucocorticoid activity and moderate mineralocorticoid activity.

F K: phosphate and hemisuccinate esters of prednisolone are readily soluble salts that can be administered both intramuscularly and intravenously; prednisolone acetate ester is a microcrystalline suspension, so it can only be administered intramuscularly.

After administration, prednisolone is 90% bound to blood proteins (50% with transcortin and 40% with albumin). It penetrates well into all organs and tissues, like hydrocortisone, 51% of prednisolone is destroyed by 11-dehydrogenase of the placenta to 11-keto-prednisolone. Therefore, it is relatively safe for the fetus and can be used for health reasons in pregnant women.

Application and dosing regimen. Prednisolone is used for all types of glucocorticoid therapy. At oral administration doses are 15-100 mg / day (in the case of treatment of hemoblastoses - 40-60 mg / m 2 of body surface per day). When injected into the joint cavity, it is prescribed in doses of 5-50 mg once a week. Intravenous administration is used for severe systemic allergic reactions or status asthmaticus, while the dose can reach 400-1200 mg (currently it is believed that there is no maximum dose of prednisolone in asthmatic status, the only criterion for the dose is stopping the status). Local applications of prednisolone for skin and eye diseases are carried out 2-3 times a day (the drug is applied to the lesion without rubbing it).

VW: tablets of 5, 10 and 20 mg; ointment 0.5% -10.0; solution of prednisolone phosphate 30 mg / ml (3%) ampoules of 1 ml; prednisolone hemisuccinate powder in ampoules of 10, 25, 50 and 250 mg; suspension of prednisolone acetate in ampoules of 10, 20, 25 and 50 mg; drops in vials of 0.5% -10 ml.

M ethylprednisolone(Methylprednisolone, Medrol). Compared with prednisolone, it has a 20% greater glucocorticoid effect and is practically devoid of mineralocorticoid activity. Unlike prednisolone and other corticosteroids, it rarely causes undesirable effects on the cardiovascular system, gastrointestinal tract and central nervous system, therefore methylprednisolone is recommended for high-dose glucocorticoid therapy, pulse therapy.

Application and dosing regimen. Inside, methylprednisolone is used at a dose of 4-96 mg / day, the depot form can be administered intramuscularly 40-120 mg once a week (for a course of 1-4 injections). When conducting pulse therapy, 1000 mg of methylprednisolone is dissolved in 100 ml of saline and administered for 30-60 minutes once a week.

Sometimes methylprednisolone is used to prevent vomiting during the treatment of cytostatic agents in cancer patients. In this case, methylprednisolone is prescribed at a dose of 250 mg 20 minutes before taking the chemotherapy drug and again at the same dose 6 hours after taking them.

VW: 4 and 16 mg tablets; powder in vials of 250, 500, 1000 and 2000 mg; suspension of methylprednisolone acetate 40 mg vials.

Dexamethasone(Dexamethasone, Dexasone). Fluorinated synthetic glucocorticosteroid. One of the most powerful glucocorticoid compounds - 7 times stronger than prednisolone in glucocorticoid activity, devoid of mineralocorticoid activity.

V causes a strong and prolonged inhibition of the hypothalamic-pituitary-adrenal system, pronounced disorders of carbohydrate and fat metabolism, it is often capable of inducing psychotic reactions. Dexamethasone has a strong dehydrating effect on tissues, especially on brain tissue. In this regard, it is recommended to include it in the treatment regimens for cerebral edema.

FC: Unlike non-fluorinated glucocorticoids, after absorption, it is only 60% bound to blood proteins (mainly albumin, not transcortin). The share of biologically active free fraction is about 40%.

Dexamethasone (like other fluorinated steroids) is resistant to placental 11-dehydrogenase and only 2% of the substance that enters the placenta is converted into inactive 11-keto-dexamethasone, so dexamethasone penetrates well into fetal tissues and effectively stimulates the processes of surfactant synthesis and lung maturation.

Application and dosing regimen. Inside, 2-15 mg / day is prescribed in 1 or 2 doses, intravenously or intramuscularly administered at 4-20 mg / day, into the joint cavity 2-8 mg every 3 days - 3 weeks.

With cerebral edema, dexamethasone is administered intravenously at a dose of 10 mg, then the administration is repeated every 6 hours at a dose of 4 mg intramuscularly until symptoms disappear. Treatment is continued for at least 2-4 days after the stabilization of the condition, and then dexamethasone is gradually withdrawn over 5-7 days.

For the prevention of vomiting in patients receiving cytostatic therapy, dexamethasone is administered at a dose of 10 mg 20 minutes before taking the cytostatic and 6 hours after its administration.

To stimulate the synthesis of surfactant in the fetus during miscarriage, dexamethasone is prescribed to a pregnant woman at a dose of 5 mg 3 times a day (the optimal course is 5 days).

VW: tablets of 0.5 and 1.5 mg; solution of dexamethasone phosphate 0.4% in ampoules of 1 and 2 ml.

Triamcinolone(Triamcinilone, Polcortolon). It is a fluorinated synthetic glucocorticoid agent. The activity is comparable to methylprednisolone. When it is used, undesirable effects often occur on the part of the skin (stretch marks, hemorrhages, hirsutism) and muscles ("triamcinolone" myopathy).

P dexamethasone resembles pharmacokinetic parameters, however, it binds extremely weakly to plasma protein: 40% of the drug is bound to plasma albumins, and 60% is a free biologically active fraction. During the metabolism of triamcinolone, 3 metabolites are formed, and 2 of them have pharmacological activity.

Dosage regimen: taken orally at a dose of 4-48 mg / day in 2 doses, intramuscularly and into the joint cavity, 40-80 mg is administered once a month (in the form of a Kenalog depot drug), topically applied in the form of an ointment, which is applied to the affected area 2-3 times a day.

VW: tablets of 2, 4 and 8 mg, suspension of triacinolone cetonide 10 and 40 mg / ml (1 and 4%) in 1 ml ampoules ( Kenalog), ointment 0.1% -15.0.

Table 1. Comparative characteristics of drugs with glucocorticoid activity.

Note: * - when applied topically in comparison with hydrocortisone.

Glucocorticoid agents for topical use.

beclomethasone(Beclometasone, Becotide). It is used for inhalation use in the treatment of allergic diseases of the respiratory tract: hay fever, bronchial asthma. Currently, the use of corticosteroids in the form of inhalation is considered as one of the most effective methods of preventing attacks in the treatment of bronchial asthma, which has a number of advantages compared to oral administration (see Table 2)

F K: After the introduction of the steroid into the respiratory tract, the maximum concentration of beclomethasone in the receptor area is reached after 5 minutes. With inhalation administration, only 10-20% of the drug reaches the lower respiratory tract, and 80-90% of the dose taken is deposited in the oral cavity and then swallowed. Therefore, to reduce the likelihood of corticosteroids entering the gastrointestinal tract, it is recommended to rinse the mouth after inhalation.

Dosing regimen. Beclomethasone is taken at 200-1600 mcg / day in 2-3 injections. Doses above 1000 mcg/day should be used under strict medical supervision.

NE: With inhaled corticosteroids at a dose of less than 1000 mcg / day, systemic adverse effects do not develop. For inhalation administration, local undesirable effects associated with exposure to corticosteroids on the mucous membranes of the respiratory tract, oral cavity, pharynx and esophagus are most characteristic:

Candidiasis of the oral cavity, esophagus, respiratory tract;

Dry mouth, destruction of tooth enamel;

VW: aerosols Inhaler 200 doses (1 dose = 50 mcg), Easyhaler 200 doses (1 dose = 200 mcg), Diskhaler (1 dose = 100 and 200 mcg); nasal spray 200 doses (1 dose = 50 mcg).

Table 2. Comparative characteristics of inhaled and oral

route of administration of corticosteroids.

Budesonide (Budesonide, Pulmicort). It has an increased affinity for glucocorticoid receptors (15 times greater than prednisone), so it has a pronounced effect even in minimal doses.

F K: After inhalation, the maximum concentration in the receptor area is reached after 0.5-1.0 hours. Budesonide has low systemic bioavailability - that part of its dose that enters the gastrointestinal tract is rapidly metabolized by the liver by almost 90% and only 1- 2% of the administered dose.

Applied inhalation in the treatment of allergic diseases of the respiratory tract and topically in atopic dermatitis, psoriasis, eczema, discoid lupus.

NE: Similar to the effects of beclomethasone, but much less common.

VW: Turbuhaler aerosols 100 and 200 doses (1 dose = 100 and 200 mcg), inhaler 200 doses (1 dose = 50 mcg mitte and 200 mcg forte); ointment and cream 0.025% -15.0.

Table 3 Classification of topical corticosteroids.

flumethasone(Flumetasone, Lorinden). Steroid for external use. It has a powerful anti-inflammatory and anti-allergic effect. It is practically not absorbed from the surface of the skin, therefore it does not have a systemic effect.

P application and dosing regimen. Flumethasone is used in the treatment of allergic skin diseases, eczema, neurodermatitis, discoid lupus and psoriasis. Cream and ointment are applied in a thin layer to the affected areas 3-5 times a day without rubbing into the skin. The procedure is recommended to be carried out with a glove. After stabilization of the process, the ointment can be applied 1-2 times a day.

NE: As a rule, these are skin manifestations in the form of skin atrophy, striae, acne, perioral dermatitis (more often affects women), hirsutism and frontal alopecia. In severe cases, the development of obliterated forms of streptococcal and fungal skin infections is possible.

VW: lotion and ointment 0.02% -15 ml.