Glucocorticosteroids are a group of drugs of synthetic or natural origin (analogues of endogenous hormones) belonging to the subclass of adrenal hormones. It has antitoxic, antishock, immunosuppressive, desensitizing and anti-inflammatory effects.

List of drugs

The group of glucocorticosteroids includes many different substances, here are some of them:

• Alclomethasone (for example, the drug Afloderm);
• Beclomethasone dipropionate (Beclazon Eco, Aldecin, Beclodget, Klenil, etc.);
• Betamethasone (Beloderm, Belogent, Diprospan, Nasobek, Celeston, etc.);
• Budesonide (Pulmicort, Flumethasone, Seretide, etc.);
• Dexamethasone (Maxidex, Ambene, Polydex, Maxitrol, etc.);
• Hydrocortisone (Cortef, Oxycort, etc.);
• Methylprednisolone (Metypred, Advantan, etc.);
• Mometasone furoate (Nasonex, Momat, Elokom, etc.);
• Prednisolone (Dermosolone, Aurobin, etc.);
• Triamcinolone acetonide (Polcortolone, Kenalog, Fluorocort, etc.);
• Fluticasone propionate (Flixotide, Flixonase, etc.);
• Fluocortolone (Ultraproct, etc.).

Glucocorticosteroids are divided into three groups: short-, medium- and long-acting.

Mechanism of action and properties

Glucocorticosteroids are steroids by their chemical nature. In the animal and human body, the place of their formation is the adrenal cortex. The biological significance of these substances lies in their ability to increase the body’s resistance to the influence of various stress factors.

Glucocorticosteroids affect the processes of water, protein, mineral and carbohydrate metabolism in the body.

Created under artificial conditions, glucocorticosteroid drugs act as powerful antishock, antitoxic, immunosuppressive, desensitizing and anti-inflammatory agents.

The mechanism of action of glucocorticosteroids is due to their ability to diffusely penetrate into the cytoplasm through cell membranes. There, by binding to certain intracellular receptors, they influence protein synthesis. Hormones inhibit hyaluronidase and phospholipase A2, which are one of the main inflammatory enzymes.

Glucocorticosteroids stabilize cell membranes, thereby blunting the release of biologically active substances such as thromboxane, leukotrienes and histamine from mast cells. The drugs also significantly slow down the formation of anti-inflammatory cytokines from arachidonic acid.

The antitoxic and antishock effect of glucocorticosteroids is:

• increased blood pressure (the concentration of catecholamines circulating in the blood increases, the sensitivity of antidepressants to them is restored, and blood vessels constrict);
• reducing vascular permeability;
• stimulation of liver enzymes that take part in the biotransformation of endo- and xenobiotics.

Glucocorticosteroids activate protein catabolism and gluconeogenesis in the liver, thereby producing the release of amino acids (substrates for gluconeogenesis) from peripheral tissues. As a result of these processes, hyperglycemia develops.

Glucocorticosteroids have an anabolic effect on protein metabolism in the liver and a catabolic effect on muscle, bone, skin, lymphoid and adipose tissue.

Glucocorticosteroid drugs enhance the lipolytic effect of growth hormone and catecholamines, reduce the consumption and release of glucose by adipose tissue. An excess of these hormones stimulates lipolysis in the extremities and lipogenesis on the body and face, and also helps to increase the level of free fatty acids in the plasma.

The biological effect of glucocorticosteroids lasts for a long time.

Indications for use

When treating with glucocorticosteroids, oral, intranasal, parenteral (inhalation and injection) forms of drugs are used.

Medicines are prescribed in the form of injections and tablets in the following cases:

• Crohn's disease;
• Nonspecific ulcerative colitis;
• Interstitial lung diseases;
• Acute respiratory distress syndrome;
• Severe pneumonia;
• Chronic obstructive pulmonary diseases;
• Bronchial asthma;
• Subacute thyroiditis;
• Congenital dysfunction of the adrenal cortex;
• Acute adrenal insufficiency;
• Replacement therapy for secondary chronic and primary adrenal insufficiency.

Intranasal glucocorticosteroid preparations are prescribed for vasomotor (idiopathic) rhinitis, non-allergic rhinitis accompanied by eosinophilia, nasal polyposis, persistent (year-round) and intermittent (seasonal) allergic rhinitis.

High effectiveness of inhaled glucocorticosteroids in the treatment of chronic obstructive pulmonary disease and bronchial asthma has been noted.

Contraindications

Contraindications to glucocorticosteroids are:

• Glaucoma;
• Diseases of the cornea combined with epithelial disorders;
• Fungal or viral eye diseases;
• Purulent infections;
• Vaccination period;
• Syphilis;
• Active form of tuberculosis;
• Herpes;
• Systemic mycosis;
• Mental illnesses with productive symptoms;
• Severe renal failure;
• Arterial hypertension;
• Thromboembolism;
• Breastfeeding period;
• Stomach and duodenal ulcers;
• Diabetes mellitus;
• Itsenko-Cushing's disease.

Contraindications to glucocorticosteroids in intranasal form:

• Increased sensitivity;
• Hemorrhagic diathesis;
• Frequent nosebleeds.

Side effects

When using glucocorticosteroids, adverse reactions from the body may be observed:

• Central nervous system: psychosis, depression, euphoria, insomnia, increased excitability;
• Cardiovascular system: thromboembolism, deep vein thrombosis, high blood pressure, myocardial dystrophy;
• Digestive system: fatty liver, pancreatitis, bleeding from the gastrointestinal tract, steroid ulcers of the intestines and stomach;
• Sense organs: glaucoma;
• Endocrine system: Cushing's syndrome, obesity, diabetes mellitus;
• Skin: alopecia, stretch marks, thinning of the skin;
• Musculoskeletal system: muscle wasting, myopathy, growth retardation (in children), osteoporosis;
• Reproductive system: hirsutism, sexual function and menstrual cycle disorders.

Local side effects are also possible when using inhaled and intranasal glucocorticosteroids.

Additional information

During treatment with glucocorticosteroids, chickenpox and measles are more severe.

People who are taking immunosuppressive doses of the substance should not receive live vaccines.

In most cases, with long-term use of oral and intranasal glucocorticosteroids, patients develop osteoporosis.

Glucocorticoid drugs (GCS) occupy a special place not only in allergology and pulmonology, but also in medicine in general. Irrational administration of GCS can lead to a large number of side effects and dramatically change the patient’s quality and lifestyle. In such cases, the risk of complications from the administration of GCS significantly exceeds the severity of the disease itself. On the other hand, fear of hormonal drugs, which arises not only among patients, but also among incompetent medical workers, is the second extreme of this problem, requiring advanced training of doctors and special work among patients who need glucocorticoid therapy. Thus, the main principle of GCS therapy is to achieve maximum effect using minimal doses; It must be remembered that the use of insufficient doses increases the duration of treatment and, accordingly, increases the likelihood of developing side effects.

Classification. GCS are classified into short-, intermediate- and long-acting drugs depending on the duration of ACTH suppression after taking a single dose (Table 2).

Table 2. Classification of GCS by duration of action

Preparation		Equivalent dose	ness of GCS	Mineral corticoid activity
Short acting:
Cortisol (hydrocortisone)
Cortisone
Prednisone
Medium duration of action
Prednisolone
Methylprednisolone
Triamcinolone
Long-lasting
Beclamethasone
Dexamethasone

For more than 40 years, glucocorticoid drugs with high activity when used topically have been widely used on the market. The created new class of GCS for inhalation therapy must meet the following requirements: on the one hand, have a high affinity for glucocorticoid receptors and, on the other hand, extremely low bioavailability, the reduction of which can be achieved by reducing the lipophilicity of the GCS and, accordingly, the degree of absorption. Below is a classification of GCS by method of use, indicating release forms, trade names and dose regimens (Table 3).

Table 3 . Classification of GCS by route of administration

Preparation	Trade names		Release forms
GCS for oral use
Betamethasone	Celeston		Tab.0.005 No. 30
Dexamethasone	Dexazone Dexamed Fortecortin Dexamethasone		Tab.0.005 No. 20 Tab.0.005 No. 10 and No. 100 Tab.0.005 No. 20 and No. 100, tab. 0.0015 No. 20 and No. 100, elixir 100 ml in a bottle (5 ml = 500 mcg) Tab. 0.005 No. 100 Tab.0.005 No. 20, 0.0015 No. 50 and 0.004 No. 50 and 100 Tab.0.005 No. 20 and No. 1000
Methyl prednisolone	Metipred		Tab.0.004 No. 30 and No. 100, tab. 0.016 No. 50, tab. 0.032 No. 20 and tab. 0.100 No. 20 Tab.0.004 No. 30 and 100, tab.0.016 No. 30
Prednisolone	Prednisolone Decortin N Medopred Prednisol		Tab.0.005 No. 20, No. 30, No. 100, No. 1000 Tab.0.005 No.50 and No.100, tab.0.020 No.10, No.50, No.100, tab.0.05 No.10 and No.50 Tab.0.005 No. 20 and No. 100 Tab.0.005 No. 100
Prednisone	Apo-prednisone		Tab.0.005 and 0.05 No. 100 and No. 1000
Triamcinolone	Polcortolon Triamcinolone Berlicourt Kenacort		T ab.0.004 No. 20 Tab.0.002 and 0.004 No. 50, 100, 500 and 1000 Tab.0.004 No. 25 Tab.0.004 No. 100 Tab.0.004 No. 50 Tab.0.004 No. 100
GCS for injection
Betamethasone	Celeston		In 1 ml 0.004, No. 10 ampoules of 1 ml
Dexamethasone	Dexaven Dexabene Dexazone Dexamed Dexamethasone Fortecortin mono		In 1 ml 0.004, No. 10 ampoules of 1 and 2 ml 0.004 in 1 ml, 1 ml in a bottle In 1 ml 0.004, No. 3 ampoules of 1 ml and 2 ml In 1 ml 0.004, No. 25 ampoules of 1 ml In 2 ml 0.008, No. 10 ampoules of 2 ml In 1 ml 0.004, No. 5 ampoules of 1 ml In 1 ml 0.004, No. 10 ampoules of 1 ml In 1 ml 0.004, No. 100 ampoules of 1 ml In 1 ml 0.004, No. 3 ampoules of 1 ml and 2 ml, in 1 ml 0.008, No. 1 ampoule of 5 ml
Hydrocortisone	Hydrocortisone Solu-cortef Sopolcourt N		Suspension in bottles, in 1 bottle 5 ml (125 mg)* Lyophilized powder in bottles, 1 bottle 2 ml (100 mg) Solution for injection, 1 ml in ampoule (25 mg) and 2 ml (50 mg)
Prednisolone	Metipred Solu-Medrol		Suspension for injection, 1 ml in ampoule (40 mg) Lyophilized powder in bottles, 40, 125, 250, 500 or 1000 mg in 1 bottle Dry substance with solvent in ampoules No. 1 or No. 3, 250 mg each, No. 1 1000 mg
Prednisolone	Medopred Prednisol Prednisolone hafslund nycomed Prednisolone Prednisolone acetate Prednisolone hemisuccinate Solyu-decortin N		In 1 ml 0.020, No. 10 ampoules of 2 ml In 1 ml 0.030, No. 3 ampoules of 1 ml In 1 ml 0.025, No. 3 ampoules of 1 ml In 1 ml 0.030, No. 3 ampoules of 1 ml In 1 ml 0.025, No. 10 or No. 100 ampoules of 1 ml In 5 ml 0.025, No. 10 lyophilized powder in ampoules of 5 ml In 1 ampoule 0.010, 0.025, 0.050 or 0.250, No. 1 or No. 3 ampoule
Triamcinolone	Triam-denk 40 for injection Triamcinolone		In 1 ml 0.010 or 0.040 in bottles In 1 ml 0.040, No. 100 suspension in ampoules In 1 ml 0.010 or 0.040, suspension in ampoules
Depot – form: Triamcinolone	Triamcinolone acetonide		In 1 ml 0.040, No. 5 in ampoules of 1 ml In 1 ml 0.010, 0.040 or 0.080, suspension in ampoules
Depot form: Methylprednisolone acetate	Depo-Medrol Methylpredni-zolone acetate		In 1 ml 0.040, bottles of 1, 2 or 5 ml In 1 ml 0.040, No. 10 ampoules, 1 ml of suspension per ampoule
Combination of depot form and fast-acting form
Betamethasone	Diprospan Flosteron		In 1 ml 0.002 dinitrate phosphate and 0.005 dipropionate, No. 1 or 5 ampoules of 1 ml The composition is similar to diprospan
GCS for inhalation
Beclamethasone	Aldecin Beclazon Beklomet-Easyhaler Bekodisk Beklocort Becklofort Plybekort		In 1 dose 50, 100 or 250 mcg, in an aerosol 200 doses 1 dose 200 mcg, Easyhaler 200 doses 1 dose 100 mcg or 200 mcg, dischaler 120 doses In 1 dose 50 mcg, in an aerosol 200 doses In 1 dose 50 mcg (mita), in an aerosol 200 doses and 250 mcg (forte), 200 doses in aerosol In 1 dose 250 mcg, in an aerosol 80 or 200 doses In 1 dose 50 mcg, in an aerosol 200 doses
Budesonide	Benacort Pulmicort Budesonide		In 1 dose 200 mcg, in the Cyclohaler inhaler 100 or 200 doses In 1 dose 50 mcg, in an aerosol 200 doses and in 1 dose 200 mcg, in an aerosol 100 doses Similar to pulmicort
Fluticasone	Flixotide		In 1 dose 125 or 250 mcg, in an aerosol 60 or 120 mcg; powder for inhalation in rotadisks: blisters 4 x 15, in 1 dose 50, 100, 250 or 500 mcg
Triacinolone	Azmacort		1 dose 100 mcg, aerosol 240 doses
GCS for intranasal use
Beclomethasone	Aldecin Baconase	The same (see above) aerosol with a nasal mouthpiece In 1 dose 50 mcg, aqueous aerosol for 200 doses for intranasal use 50 mcg in 1 dose, 50 doses in aerosol
Flunisolide	Sintaris	In 1 dose 25 mcg, in an aerosol 200 doses
Fluticasone	Flixonase	50 mcg in 1 dose, 120 doses in aqueous spray for intranasal use
Mometasone	Nasonex	In 1 dose 50 mcg, in an aerosol 120 doses
GCS for local use in ophthalmology
	Prenatsid	Eye drops 10 ml in a bottle (1 ml = 2.5 mg), eye ointment 10.0 (1.0 = 2.5 mg)
Dexamethasone	Dexamethasone	Eye drops 10 and 15 ml in a bottle (1 ml = 1 mg), eye suspension 10 ml in a bottle (1 ml = 1 mg)
Hydrocortisone	Hydrocortisone	Eye ointment in tube 3.0 (1.0 = 0.005)
Prednisolone	Prednisolone	Ophthalmic suspension in a 10 ml bottle (1 ml = 0.005)
Combined drugs: With dexamethasone, framycetin and gramicidin With dexamethasone and neomycin	Sofradex Dexon
GCS for topical use in dentistry
Triamcinolone	Kenalog Orabase	Paste for topical use in dentistry (1.0 = 0.001)
GCS for local use in gynecology
Combined drugs: With prednisolone	Terzhinan	Vaginal tablets of 6 and 10 pieces, containing prednisolone 0.005, ternidazole 0.2, neomycin 0.1, nystatin 100,000 units
GCS for use in proctology
Combined drugs: With prednisolone With hydrocortisone	Aurobin Posterisan forte Proctosedyl	Ointment 20, in tubes (1.0 = prednisolone 0.002, lidocaine 0.02, d-panthetol 0.02, triclosan 0.001) Rectal suppositories No. 10, (1.0 = 0.005) Ointment 10.0 and 15.0 in a tube (1.0 = 5.58 mg), rectal capsules No. 20, 2.79 mg in 1 capsule
GCS for external use
Betamethasone	Betnovate Diprolene Celestoderm -B	Cream and ointment 15.0 each in tubes (1.0 = 0.001) Cream and ointment 15.0 and 30.0 in tubes (1.0 = 0.0005) Cream and ointment 15.0 and 30.0 in tubes (1.0 = 0.001)
Betamethasone + Gentamicin	Diprogent	Ointment and cream 15.0 and 30.0 in tubes (1.0 = 0.0005)
Betamethasone + Clotrimazole	Lotriderm	Ointment and cream 15.0 and 30.0 in tubes (1.0 = 0.0005, clotrimazole 0.01)
Betamethasone + Acetylsalicylic acid	Diprosalik	Ointment 15.0 and 30.0 in tubes (1.0 = 0.0005, salicylic acid 0.03); Lotion 30 ml in a bottle (1 ml = 0.0005, salicylic acid 0.02)
Budesonide		Ointment and cream 15.0 in tubes (1.0 = 0.00025)
Clobetasol	Dermovate	Cream and ointment 25.0 in tubes (1.0 = 0.0005)
Fluticasone	Cutivate	Ointment 15.0 in tubes (1.0 = 0.0005) and cream 15.0 in tubes (1.0 = 0.005)
Hydrocortisone	Laticort	Ointment 14.0 in tubes (1.0 = 0.01) Ointment, cream or lotion 15 ml (1.0 = 0.001) Ointment, cream or lipocrem 0.1%, 30.0 each in tubes (1.0 = 0.001), lotion 0.1%, 30 ml each (1ml = 0.001)
Hydrocortisone + natamycin + Neomycin	Pimafukort	Ointment and cream 15.0 in tubes (1.0 = 0.010), lotion 20 ml in a bottle (1.0 = 0.010)
Mazipredone	Deperzolon	Emulsion ointment 10.0 in tubes (1.0 = 0.0025)
Mazipredon + Miconazole	Mycozolon	Ointment 15.0 in tubes (1.0 = 0.0025, miconazole 0.02)
Methyl prednisolone	Advantan
Mometasone		Ointment, cream 15.0 in tubes and lotion 20 ml (1.0 = 0.001)
Prednicarbate	Dermatol	Ointment and cream 10.0 in tubes (1.0 = 0.0025)
Prednisolone + Clioquinol	Dermozolon	Ointment 5.0 in tubes (1.0 = 0.005 and clioquinol 0.03)
Triamcinolone	Triacort Fluorocort	Ointment 10.0 in tubes (1.0 = 0.00025 and 1.0 = 0.001) Ointment 15.0 in tubes (1.0 = 0.001)

Mechanism of action of GCS: Decryption of the implementation anti-inflammatory effect GCS is extremely complex. Currently, it is believed that the leading link in the action of GCS on the cell is their influence on the activity of the genetic apparatus. Various classes of GCS bind to varying degrees with specific receptors located on the cytoplasmic or cytosolic membrane. For example, cortisol (endogenous GCS, with pronounced mineralocorticoid activity) has a preferential binding to cytoplasmic membrane receptors, and dexamethasone (synthetic GCS, characterized by minimal mineralocorticoid activity) binds to a greater extent to cytosolic receptors. After active (in the case of cortisone) or passive (in the example of dexamethasone) penetration of GCS into the cell, a structural rearrangement occurs in the complex formed by GCS, receptor and carrier protein, allowing it to interact with certain sections of nuclear DNA. The latter causes an increase in RNA synthesis, which is the main stage in the implementation of the biological effects of GCS in the cells of target organs. The determining factor in the mechanism of the anti-inflammatory effect of GCS is their ability to stimulate the synthesis of some (lipomodulin) and inhibit the synthesis of other (collagen) proteins in cells. Lipomodulin blocks cell membrane phospholipase A2, which is responsible for the release of phospholipid-bound arachidonic acid. Accordingly, the formation of active anti-inflammatory lipids—prostaglandins, leukotrienes and thromboxanes—from arachidonic acid is stimulated. Inhibition of leukotriene B4 reduces the chemotaxis of leukocytes, and leukotrienes C4 and D4 reduces the contractile ability of smooth muscles, vascular permeability and mucus secretion in the respiratory tract. In addition, GCS suppress the formation of some cytokines involved in inflammatory reactions in bronchial asthma. Also, one of the components of the anti-inflammatory effect of GCS is the stabilization of lysosomal membranes, which reduces the permeability of the capillary endothelium, improves microcirculation and reduces the exudation of leukocytes and mast cells.

The antiallergic effect of GCS is multifactorial and includes: 1) the ability to reduce the number of circulating basophils, which leads to a decrease in the release of mediators of immediate allergic reactions; 2) direct inhibition of the synthesis and secretion of mediators of immediate allergic reactions due to an increase in intracellular cAMP and a decrease in cGMP; 3) reducing the interaction of allergy mediators with effector cells.

At present, the mechanisms of the antishock effect of glucocorticoids have not been fully deciphered. However, a sharp increase in the concentration of endogenous glucocorticoids in plasma during shocks of various etiologies has been proven, as well as a significant decrease in the body’s resistance to shockogenic factors when the hypothalamic-pituitary-adrenal system is suppressed. The practice-confirmed high effectiveness of GCS in shock is also obvious. It is believed that GCS restore the sensitivity of adrenergic receptors to catecholamines, which, on the one hand, mediates the bronchodilator effect of GCS and the maintenance of systemic hemodynamics, and on the other hand, the development of side effects: tachycardia, arterial hypertension, excitation of the central nervous system.

The effect of GCS on metabolism. Carbohydrate metabolism. Gluconeogenesis increases and glucose utilization in tissues decreases due to antagonism with insulin, which can result in hyperglycemia and glycosuria. Protein metabolism. Anabolic processes in the liver and catabolic processes in other tissues are stimulated, and the content of globulins in the blood plasma decreases. Lipid metabolism. Lipolysis is stimulated, the synthesis of higher fatty acids and triglycerides is enhanced, fat is redistributed with predominant deposition in the shoulder girdle, face, abdomen, and hypercholesterolemia is recorded. Water-electrolyte metabolism. Due to mineralocorticoid activity, sodium and water ions are retained in the body, and potassium excretion increases. The antagonism of GCS in relation to vitamin D causes the leaching of Ca 2+ from the bones and an increase in its renal excretion.

Other effects of GCS. GCS inhibit the growth of fibroblasts and collagen synthesis, cause a decrease in the reticuloendothelial clearance of cells with antibodies, and reduce the level of immunoglobulins without affecting the production of specific antibodies. In high concentrations, GCS stabilize lysosome membranes, increase hemoglobin and the number of erythrocytes in peripheral blood.

Pharmacokinetics. GCS for systemic use are poorly soluble in water, but well soluble in fats. Minor changes in the chemical structure can lead to significant changes in the extent of absorption and duration of action. In plasma, 90% of cortisol is reversibly bound to two types of proteins - globulin (glycoprotein) and albumin. Globulins have high affinity but low binding capacity, while albumins, on the contrary, have low affinity but high binding capacity. The metabolism of GCS occurs in several ways: the main one is in the liver, the other is in extrahepatic tissues and even in the kidneys. Microsomal liver enzymes metabolize GCS to inactive compounds, which are then excreted by the kidneys. Metabolism in the liver increases with hyperthyroidism and is induced by phenobarbital and ephedrine. Hypothyroidism, cirrhosis, concomitant treatment with erythromycin or oleandomycin leads to a decrease in the hepatic clearance of GCS. In patients with hepatic cell failure and low serum albumin, significantly more unbound prednisolone forms circulate in the plasma. There is no correlation between T1/2 and the duration of the physiological action of a particular GCS drug. Different activities of GCS are determined by different degrees of binding to plasma proteins. Thus, most of the cortisol is in a bound state, while 3% of methylprednisolone and less than 0.1% of dexamethasone. Fluorinated compounds (metazones) have the greatest activity. Beclomethasone contains chlorine as a halogen and is especially indicated for local endobronchial use. It was esterification that made it possible to obtain drugs with reduced absorption for local use in dermatology (fluocinolone pivalate). Succinates, or acetonides, are water-soluble and are used in the form of injections (prednisolone succinate, triamcinolone acetonide).

Performance criteria when used orally prednisolone the same as for cromoglycate.

Safety criteria for systemic use glucocorticosteroids the following:

1) Absence of 1 infectious disease, including tuberculosis, due to suppression of the immune response;

2) Absence of osteoporosis, including in postmenopausal women, due to the risk of fractures;

3) Maintaining a sufficiently active lifestyle and the absence of osteomyelitis due to the threat of aseptic bone necrosis;

4) Control of the glycemic profile and exclusion of diabetes mellitus due to the possibility of complications in the form of ketoacidosis, hyperosmolar coma;

5) Consideration of mental status due to the possibility of developing “steroid” psychosis;

6) Monitoring blood pressure and water-electrolyte balance due to sodium and water retention;

7) No history of peptic ulcers, as well as the threat of gastrointestinal bleeding due to impaired rates of repair of the gastrointestinal mucosa;

8) Absence of glaucoma due to the possibility of provoking glaucomatous crises;

9) Absence of superficial wounds, fresh postoperative scars, burn injuries due to suppression of fibroplasia;

10) Absence of puberty due to cessation of growth and exclusion of pregnancy due to possible teratogenic effects.

Features of oral applicationsGKS .

Preference when choosing is given to fast-acting drugs with an average duration of action, having 100% bioavailability when used orally and to a lesser extent inhibiting the hypothalamic-pituitary-adrenal system. A short course (3-10 days) can be prescribed to achieve optimal effect at the beginning of a long course of therapy with a gradual deterioration of the patient's condition or to quickly relieve a severe attack. To treat severe forms of bronchial asthma, long-term therapy with GCS may be required using one of the following regimens:

 Continuous regimen (used most often), with 2/3 of the daily dose given in the morning and 1/3 in the afternoon. Due to the danger of increasing the aggression of the acid-petic factor in conditions of a decrease in the rate of repair of the gastrointestinal mucosa, it is recommended to prescribe GCS after meals, in some cases under the guise of antisecretory drugs and agents that improve reparative processes in the gastrointestinal mucosa. However, combining administration with antacids is not advisable, since the latter reduce the absorption of GCS by 46-60%.

 An alternating regimen involves taking a double maintenance dose of the drug once in the morning every other day. This method can significantly reduce the risk of side effects while maintaining the effectiveness of the chosen dose.

 An intermittent regimen involves the use of GCS in short courses of 3-4 days with 4-day intervals between them.

If indicated, a trial two-week course of GCS is prescribed based on prednisolone from 20 to 100 mg (usually 40 mg). Further treatment with these drugs is carried out only if a repeated study after 3 weeks reveals a significant improvement in respiratory function: an increase in FEV 1 by at least 15% and an increase in FVC by 20%. Subsequently, the dose is reduced to the minimum effective, preference is given to an alternating dosage regimen. The minimum effective dose is selected by sequentially reducing the initial dose by 1 mg every 4-6 days with careful monitoring of the patient. The maintenance dose of prednisolone is usually 5-10 mg; doses below 5 mg are ineffective in most cases. Systemic therapy with GCS leads to the development of side effects and complications in 16% of cases. After stopping the use of corticosteroids, the function of the adrenal cortex is restored gradually, over 16-20 weeks. Systemic corticosteroids are replaced if possible inhalation forms.

Performance criteria use inhaled corticosteroids the same as other means of basic therapy for patients with bronchial asthma.

Safety criteria when applied inhaled corticosteroids the following:

1) Administration of the drug in the minimum effective dose, through spacers or turbohalers, with constant monitoring of the condition of the oral mucosa due to the possibility of developing oropharyngeal candidiasis; in rare cases - prophylactic use of antifungal agents;

2) Absence of professional restrictions associated with the threat of hoarseness (possibly due to local steroid myopathy of the laryngeal muscles, which disappears after discontinuation of the drug); a similar side effect is less often recorded for powder inhalation forms;

3) Lack of cough and irritation of the mucous membrane (mainly due to the additives included in the aerosol).

Conditions for use of inhaled corticosteroids and features of individual drugs.

A 400 mcg inhalation dose of beclomethasone (Becotide) is equivalent to approximately 5 mg of prednisolone taken orally. With an effective maintenance dose of prednisolone of 15 mg, patients can be completely transferred to treatment with inhaled corticosteroids. In this case, the dose of prednisolone begins to be reduced no earlier than a week after the addition of inhaled drugs. Inhibition of the function of the hypothalamic-pituitary-adrenal system occurs when beclomethasone is inhaled at a dose exceeding 1500 mcg/day. If the patient's condition worsens during a maintenance dose of inhaled corticosteroids, the dose must be increased. The maximum possible dose is 1500 mcg/kg; if in this case there is no therapeutic effect, it is necessary to add oral GCS.

Beklofort is a high-dose drug of beclamethasone (200 mcg in one dose).

Flunisolide (Ingacort), unlike beclomethasone, is already in a biologically active form from the moment of administration and therefore immediately manifests its effect in the target organ. In comparative studies on the effectiveness and tolerability of beclomethasone at a dose of 100 mcg 4 times a day and flunisolide at a dose of 500 mcg twice a day, the latter was significantly more effective. Flunisolide is equipped with a special spacer, which ensures a “deeper” penetration of the drug into the bronchi by inhaling most of the small particles. At the same time, there is a decrease in the frequency of oropharyngeal complications, a decrease in bitterness in the mouth and cough, irritation of the mucous membrane and hoarseness of the voice. In addition, the presence of a spacer makes it possible to use metered-dose aerosols in children, the elderly, and in patients with difficulty coordinating the process of inhalation and inhalation of the drug.

Triamcinolone acetonide (Azmacort) is most commonly used in the United States. A fairly wide range of doses used (from 600 mcg to 1600 mcg in 3-4 doses) allows the use of this drug in patients with the most severe asthma.

Budesonide is a long-acting drug and, compared to beclomethasone, is 1.6-3 times more active in anti-inflammatory activity. It is of interest that the drug is available in 2 dosage forms for inhalation use. The first is a traditional metered dose inhaler containing 50 and 200 mcg of budesonide in one puff. The second form is a turbohaler, a special inhalation device that provides the administration of the drug in powder form. The air flow created thanks to the original design of the turbohaler captures the smallest particles of the drug powder, which leads to a significant improvement in the penetration of budesonide into small-caliber bronchi.

Fluticasone propionate (flixotide) is an inhaled GCS with greater anti-inflammatory activity, pronounced affinity for glucocorticoid receptors, and less systemic side effects. The pharmacokinetic features of the drug are reflected in the high threshold dose - 1800-2000 mcg, only when exceeded, systemic adverse reactions can develop.

Thus, inhaled corticosteroids are one of the most effective means of treating patients with bronchial asthma. Their use leads to a reduction in symptoms and exacerbations of bronchial asthma, improvement in functional pulmonary parameters, a decrease in bronchial hyperreactivity, a decrease in the need for taking short-acting bronchodilators, and an improvement in the quality of life of patients with bronchial asthma.

Table 4. Estimated equivalent doses (mcg) inhalation

For the correct, coordinated functioning of each organ and system of the body, it is necessary to maintain normal levels of hormones. The adrenal glands are paired endocrine glands. This is a component of the endocrine regulatory system that controls all processes occurring in the human body. The main function of the adrenal glands is the production of hormones called corticosteroids. They support immune strength, protect the body from harmful external factors, suppress inflammation, regulate metabolism and other important physiological processes. Depending on the functions performed, glucocorticosteroid hormones (glucocorticoids) and mineralocorticoids are distinguished. The role of glucocorticosteroids was first discovered by rheumatologist F. Hench in 1948. He noticed that in a woman suffering from rheumatoid arthritis, the severity of articular syndrome decreased significantly during pregnancy. This gave rise to the creation of analogues of glucocorticosteroids produced by the adrenal cortex and their widespread use in clinical medicine.

What are glucocorticosteroids?

What are glucocorticosteroids? - All drugs included in the group - steroids, have a certain biological activity. They are divided into substances of natural (cortisone, hydrocortisone) and synthetic origin (synthesized analogues of natural hormones, derivatives, including fluorinated ones, of the most active natural hormone hydrocortisone). Artificially created substances are stronger, are used in smaller dosages, and do not affect mineral metabolism. Their use does not pose a high risk of side effects. Most clinically significant classification of glucocorticosteroids– according to the duration of the therapeutic effect. According to these parameters, drugs are distinguished:

• Short-acting - with a biological half-life of 8-12 hours. These are basic remedies for the treatment of skin pathologies, inflammatory and allergic manifestations, usually used externally, in this case they have the least impact on the water-salt balance. Tablets and injections are used primarily as hormone replacement therapy when their natural production is reduced or stopped.

• With an average duration of effect - with a half-life of 18-36 hours. The most used group of drugs in clinical practice. The strength of the effect is 5 times greater than short-acting glucocorticosteroids, inferior to them in mineralocorticoid activity, and is less likely to cause adverse effects for the body.

• Long-acting - drugs with an active component, the concentration of which in the plasma will be halved after 36-54 hours. The anti-inflammatory effect of such drugs is 6-7 times stronger than Prednisolone; they do not affect the processes of mineral metabolism. When using them, various adverse reactions often occur. Not recommended for long-term use.

How do glucocorticosteroids work?

The extensive and multifaceted effects exerted by glucocorticosteroids are due to the ability of the active substance molecule to penetrate the membrane into the cell and act on the genetic apparatus at the level of transcription and processing of ribonucleic acid. By binding to cytoplasmic receptors located inside target cells, they form an active complex that penetrates the cell nucleus and affects the synthesis of activator proteins, which are natural regulators of genes. By interacting with nuclear factors, glucocorticosteroids change the immune response, directly and indirectly reducing the formation of substances that contribute to the development of inflammation - prostaglandins, highly active lipid inflammatory mediators leukotrienes, membrane phospholipid mediators PAF (platelet aggregation factor). The full mechanism of influence has not yet been fully studied.

It takes from half an hour to several hours for genomic effects to develop. At higher doses, non-genomic or receptor-mediated effects are realized. Action of glucocorticosteroids in this case, it appears within 1-2 minutes after application. The ability to quickly, within a few seconds, influence the membranes of target cells, changing their physical and chemical properties and reducing the process of release of allergic and inflammatory mediators, allows you to instantly alleviate the patient’s condition and save his life. The main effects of taking glucocorticosteroids are as follows:

• anti-inflammatory effect – inhibit inflammatory phenomena of any nature and stage of development, reduce the permeability of the cell membrane to inflammatory mediators, and the migration of immune cells to the site of inflammation;

• anti-shock, anti-stress - increase blood pressure, stimulate the production of a large number of blood cells, which allows you to fight a state of shock and quickly replenish blood loss;

• immunoregulatory effect - in low doses they slightly increase immunity, in high concentrations they suppress the functions of the immune system many times, which determines the use of glucocorticosteroids in transplantology for tissue and organ transplantation - bone marrow, kidneys, radiation therapy, chemotherapy of malignant neoplasms, during the treatment of autoimmune diseases ;

• affect metabolism - slow down the excretion of sodium, water, chlorine from the body, increase the leaching of potassium and calcium from the bones, suppress its absorption. They increase glucose levels, impair sugar processing, disrupt protein and lipid metabolism, redistributing subcutaneous fat tissue - increasing its volume on the face, neck, chest and decreasing it in the extremities. Promote muscle atrophy, the appearance of stretch marks on the skin, delayed scarring of wounds, hemorrhages, and the development of osteoporosis;

• anti-allergic effect – suppresses the clinical manifestations of allergies;

• pain relief – reduce the severity of pain, improve the functionality of joints;

• antipyretic, anti-edematous effect - eliminate fever, reduce or completely remove swelling, incl. mucous membranes;

• adaptogenic – increase the body’s resistance to the harmful effects of physical, chemical, biological factors;

• facilitate the work of the heart and blood vessels - reduce capillary permeability, tone, strengthen the walls of blood vessels, normalize the contractile function of the heart muscle;

• affect the endocrine system - reduce the production of sex hormones, suppress the connection between various parts of the brain and the adrenal glands, interact with other hormones, reduce the sensitivity of tissues to them;

• hemodynamic, hematological effect - greatly changes the blood picture, causes a deficiency of lymphocytes, leukocyte cells, stimulates the production of platelets, erythrocytes.

Indications for use

A wide spectrum of pharmacological action makes glucocorticosteroids almost universal drugs. In addition to their independent medicinal properties, they have the ability to enhance the effect of other drugs. This allows them to be used in the treatment of severe diseases of the spine and joints that cannot be treated with non-steroidal anti-inflammatory drugs and require complex therapy. Thus, treatment with glucocorticosteroids is indicated for the following pathologies:

• inflammation of individual joints, small and large, accompanied by severe swelling, severe pain, rapid accumulation of inflammatory fluid released from the blood vessels in the tissues and cavity of the joint, which is fraught with rapid destruction of articular cartilage;

• damage to the connective tissue of joints, tendons and other organs caused by autoimmune or rheumatic diseases - systemic lupus erythematosus, scleroderma, Sjogren's syndrome, Still's syndrome, polymyalgia rheumatica, dermatomyositis, vasculitis;

• non-infectious joint changes - arthrosis deformans, rheumatoid arthritis;

• inflammatory processes in the synovial, joint capsule, spinal cord and membranes;

• spinal injuries, postoperative period;

• damage to the axial skeleton, peripheral joints in ankylosing spondylitis.

Beyond rheumatology glucocorticosteroid therapy prescribed in many other areas of clinical medicine. Indications for use are:

• respiratory failure - interstitial pneumonia, bronchial asthma, status asthmaticus, COPD;

• exudative enteropathy, celiac disease, inflammatory diseases of the gastrointestinal tract - Crohn's disease, ulcerative colitis;

• kidney dysfunction, viral, chronic hepatitis, liver cirrhosis, glomerular nephritis, adrenal insufficiency;

• skin diseases - dermatitis, scaly lichen, eczema, diseases of the neurogenic-allergic type;

• pathologies of the nervous system, optic neuritis, non-infectious inflammation of the cornea, conjunctiva, iris, ciliary body of the eyeball, scleritis of the eye, uveitis;

• acute and chronic inflammation of the ear, nasal mucosa, eczema of the external ear;

• hematological pathologies, thyroid thyrotoxicosis, transplant rejection, myocardial damage;

• allergic reactions, oncological processes, traumatic shock.

Admission rules

The dosage and regimen depend on the route of administration. It is not recommended to divide the daily dose into 3 doses; it is preferable to take GC in the morning or in the morning and evening hours. For each disease, a specific form of the drug is prescribed. There are several of them:

• Glucocorticosteroid tablets are used for systemic diseases and chronic pathologies. This is the main method of application. Depending on the degree of activity of the disease, a one-time dose or a course of treatment is prescribed, lasting no more than a month. The daily dosage is determined based on the patient’s weight and is usually 1 mg/kg. The tablets are quickly and almost completely absorbed. Should be taken separately from food, because it slows down absorption.

• Injectable forms of drugs are the most effective method of administration and have a maximum duration of action. Available in the form of ethers, solutions for intra-articular, intramuscular injections and for intravenous infusion. They do not begin to act immediately - the effect develops after a few hours, and for suspensions that are poorly soluble in water, after 1-2 days, maximum 4-8. The effect lasts up to 1 month. Water-soluble glucocorticosteroids act quickly, but for a short time. Practiced in emergency situations, in cases of shock, severe forms of allergies - they are administered intravenously or intramuscularly. Intra-articular injections are used most often, because... act locally without significantly affecting other systems. The injection is given once, then the body’s response to the hormone is determined within a week, and if the prognosis is favorable, the injection is repeated.

• Inhalation drugs are prescribed for respiratory diseases. Hormones are delivered to the affected organ using a nebulizer, are not absorbed into the blood, and do not act systemically. The effect is slow - it occurs after 7 days, reaching a maximum after 6 weeks.

• Topical – used to treat skin allergies, dermatitis, subcutaneous inflammation. Applied to the skin directly in the affected area - local preparations, available in the form of ointments, lotions, gels, creams. Systemic absorption of the active substance with this method of administration is 5%. Lotions are convenient for applying to the scalp, ointments are greasy - they are chosen for dry skin, creams are quickly absorbed and are recommended for diaper rash. It should be taken into account that the more powerful glucocorticosteroids used in dermatology have fewer adverse reactions than weaker drugs.

To achieve a greater therapeutic effect in the case of severe, progressive inflammatory processes, acute relapses, injections into the joint are combined with a shortened course of tablets.

To quickly relieve painful symptoms during an exacerbation, pulse therapy is also used - a rapid infusion of large doses of the drug over 0.5-1 hour. Systemic diseases often require long-term, multi-year therapy.

Contraindications for use

With a one-time dose, the only limitation is established - individual intolerance to drugs of this series. Long-term use is not allowed for everyone. If it is necessary to use these potent drugs, the following conditions should be excluded:

• diabetes, severe obesity, neuroendocrine disorder;

• infectious blood poisoning, clotting disorders, frequent nosebleeds;

• tuberculosis, immunodeficiency, syphilis, purulent infections, mycoses;

• progressive osteoporosis of bones, infectious arthritis, fractures, joint surgeries;

• mental disorders, hypertension, thromboembolism;

• gastrointestinal diseases, severe renal failure, erosive and ulcerative lesions;

• increased intraocular pressure, corneal diseases;

• the period of bearing a child, breastfeeding, for 8 weeks before and 2 weeks after vaccination.

Side effects

Changes in hormonal balance lead to numerous undesirable consequences. They manifest themselves in varying degrees and forms, so the drug is prescribed only by a qualified doctor and in exceptional cases. Glucocorticosteroids can cause the following side effects:

• neuromuscular diseases, osteoporosis, fractures, bone necrosis;

• thinning of the skin, baldness, delayed scarring, acne;

• mental disorders, depression, insomnia;

• hoarseness, vision problems, cataracts, displacement of the eyeball;

• atherosclerosis, high blood pressure, heart failure;

• adrenal insufficiency, disruption of the endocrine system, metabolism, high glucose levels;

• dysfunction of the digestive system, reproductive system, bleeding, thrush;

• increased swelling, stomach pain, cough, dyspepsia.

Commonly Prescribed Drugs

From the group of short-acting drugs, the following are often prescribed:

• ointment with glucocorticosteroids Hydrocortisone 1%, 10g – 28 rubles, eye ointment 0.5%, 5g – 56, Russia; Laticort 0.1%, 15g – 147 rubles, Poland; Lokoid 0.1%, 30g – 290 rub., Italy;

• suspension for injections Hydrocortisone-Richter, 5 ml bottle – 230 rubles, Hungary;

• emulsion Lokoid Crelo 0.1%, 30g – 315 rub., Italy;

• tablets Kortef 0.01, 100 pcs. – 415 rubles, Canada; Cortisone 0.025, 80 pcs. – 900, Russia;

• lyophilized powder for IV, IM Solu-Cortef 0.1, 100 mg – 94 rubles, Belgium.

The most popular are representatives of the group of glucocorticosteroids with an effect of medium duration:

• tablets Medrol 0.032, 20 pcs. – 660 rub., Italy; Metypred 0.004, 30 pcs. – 204, Finland; Prednisolone 0.05 100 pcs. – 70, Russia; Kenalog 0.004, 50 pcs. – 374, Slovenia; Polcortolon 0.004, 50 pcs. – 393, Poland;

• lyophilisate for IV, IM Solu-Medrol 1.0, 15.6 ml – 473 rubles, Belgium;

• solution for intravenous, intramuscular injections Prednisolone Bufus 0.03, 10 ampoules – 162 rubles, Russia; Medopred 0.03, 10 ampoules – 153, Cyprus; Prednisol 3%, 3 amp. – 33, India;

• Maxidex eye drops 0.1%, 5 ml – 310, Belgium; Oftan-Dexamethasone 0.001, 5 ml – 220, Finland; Dexamethasone 0.1%, 10 ml – 120, Romania;

• injection solution Dexamethasone 0.004, 10 amp. – 76, Russia; 25 amp. – 160, India; Dexamethasone-Vial 0.004, 25 amp. – 116, China.

Safety precautions, drug interactions

Glucocorticosteroids are a powerful therapy; inpatient treatment is recommended for patients who require them. This includes constant medical monitoring, the ability to promptly take all necessary tests (laboratory, ultrasound, ECG), observation of a specialist over the body’s reaction, and, if necessary, adjustment of the treatment regimen. It is important to consider the presence of withdrawal syndrome, which requires a gradual reduction in dosage in order to prevent Addisonian crisis. simultaneous use with other drugs. During treatment with glucocorticosteroids, certain safety precautions should be observed:

• Take the minimum dose, do not exceed the daily dosage and frequency of administration prescribed by your doctor.

• To avoid addiction, avoid unnecessarily prolonged treatment with GCs.

• Before intra-articular administration, it is necessary to remove the exudate accumulated in the joint cavity and prevent the drug from entering the joint cavity and muscle tissue.

• Intra-articular and intravenous injections are performed by a specialist under particularly sterile conditions; the restriction must be observed - no more than 3-4 injections into one joint during the year.

• Do not take it together with any other medicine without first consulting your doctor.

Following these simple rules will allow you to cope with severe inflammation, chronic pathology, allergies, and progressive joint disease without the risk of serious side effects. Self-medication and incorrectly selected dosage can result in various complications - hormonal imbalance, diabetes or osteoporosis.

Often a person finds the optimal solution to any problem within himself. Where, for example, does the body get the strength to fight disease?

As scientific research conducted in the mid-twentieth century showed, glucocorticoid hormones play an important role in this matter.

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 thing, synonymous words that denote hormones produced by the adrenal cortex, both natural and synthetic, sometimes the abbreviation GCS is used for brevity.

Together with mineralocorticoids, GCS make up a large group of corticosteroids, but it is GCS that are especially in demand as medications. You can read about what kind of drugs these are - corticosteroids.

They provide the doctor with great opportunities for treating serious diseases, “extinguish” foci of inflammation, can enhance the effect of other medicinal drugs, relieve swelling, and dull the feeling of pain.

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

Medical science has also achieved that GKS today can be used “targetedly”- act exclusively on the problem area, without disturbing other healthy ones.

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

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

In addition, GCS is 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 withdrawal syndrome of glucocorticoids, that is, the risk of a deterioration in the patient’s well-being after stopping taking these drugs.

The patient may even develop so-called glucocorticoid deficiency.

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

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

This means that Only specialists can work with medicinal drugs of this kind, self-medication is strictly prohibited, as it can cause various kinds of complications.

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

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 doctors identify disorders in the endocrine system, serious pathologies and select medications (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 are able to reduce the activity of enzymes that destroy body tissue, isolating the affected areas from healthy ones.

GCS affect cell membranes, making them rougher, and therefore complicating metabolism; as a result, infections are not given a chance to spread throughout the body, putting it in a “rigid framework.”

Among other ways that GCS influences the human body:

• immunoregulatory effect– under different circumstances, immunity increases slightly or, on the contrary, immunity is suppressed (medics use this property of GCS during tissue transplants from donors);
• antiallergic;
• anti-shock – effective, for example, in anaphylactic shock, when the medication must provide lightning-fast results to save the patient.

GCS can influence 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 blood pressure, and 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 GCS allow the use of drugs more locally.

Unfortunately, not all “activities” of glucocorticoids are 100% beneficial to humans.

Excess corticosteroids as a result of long-term use of the drug leads, for example, to changes in internal biochemistry - calcium is washed out, bones become fragile, and osteoporosis develops.

Glucocorticoids are differentiated 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.

Medium-acting GCS– up to one and a half days (Prednisolone, Methylprednisolone), long-acting – 36-52 hours (Dexamethasone, Beclomethasone).

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

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 they contain, they are monofluorinated, di- and trifluorinated.

The variety of drugs using GCS gives doctors the opportunity to select a drug of the desired form (tablets, cream, gel, ointment, inhaler, patch, nasal drops) and the appropriate “content” in order to obtain exactly those pharmacological effects that are necessary, and in no case do not aggravate the patient’s condition by causing any side effects in the body.

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

As an example, here are the names of glucocorticoid drugs:

Treatment methods

Various types of treatment methods using GCS have been developed:

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

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

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

How dangerous are glucocorticoids for the body? They change his hormonal balance and sometimes cause the most unexpected reactions., especially if for some reason an overdose of the drug occurs.

Diseases provoked by GCS include, for example, hyperfunction of the adrenal cortex.

The fact is that using a drug that helps the adrenal glands perform their required functions gives them the opportunity to “relax.” If you stop taking the drug abruptly, the adrenal glands can no longer engage in full work.

What other troubles can await after taking GCS?? This:

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

Contraindications

Standards of treatment with glucocorticoids suggest only one absolute contraindication for the use of GCS once - this is the individual intolerance of the drug by the patient.

If long-term treatment is required, the list of contraindications becomes wider.

These are diseases and conditions such as:

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

Pediatric glucocorticoid therapy provided only in very rare cases.

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

The beginning of the use of glucocorticoids as medicines dates back to the 40s. XX century. Back in the late 30s. 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, and in the 40s. - glucocorticoids cortisone and hydrocortisone. The wide range of pharmacological effects of hydrocortisone and cortisone predetermined the possibility of their use as drugs. Soon their synthesis was carried out.

The main and most active glucocorticoid produced in the human body is hydrocortisone (cortisol), others, less active, are represented by 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. Adrenocorticotropic hormone of the pituitary gland (ACTH, corticotropin) is a physiological stimulator 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 (based on the principle of negative feedback). Long-term administration of glucocorticoids (cortisone and its analogues) into the body can lead to inhibition and atrophy of the adrenal cortex, as well as 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 application 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 safe drugs, currently has 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, including non-fluorinated (prednisone, prednisolone, methylprednisolone) and fluorinated (dexamethasone, betamethasone, triamcinolone, flumethasone, etc.) glucocorticoids. These compounds are usually more active than natural glucocorticoids and act in 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 relationship 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 are not only highly effective, but also have 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 glucocorticoid intracellular receptors (alpha isoform). These nuclear receptors are capable of binding to DNA and belong to a family of ligand-sensitive transcriptional regulators. Glucocorticoid receptors are found in almost all cells. In different cells, however, the number of receptors varies, and they can also differ in molecular weight, affinity for the hormone and other physicochemical characteristics. In the absence of a hormone, intracellular receptors, which are cytosolic proteins, are inactive and are part of heterocomplexes, which also include heat shock proteins (heat shock proteins, Hsp90 and Hsp70), immunophilin with a molecular weight of 56000, etc. Heat shock proteins help maintain the optimal conformation of the hormone-binding receptor domain and ensure high affinity of the receptor for the hormone.

After penetration through the membrane into the cell, glucocorticoids bind to receptors, which leads to 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, which is part of the complex as a monomer, acquires the ability to dimerize. Following this, the resulting “glucocorticoid + receptor” complexes are transported into the nucleus, where they interact with DNA sections located in the promoter fragment of the steroid-responsive gene - the so-called. glucocorticoid response element (GRE) and regulate (activate or suppress) the process of transcription of certain genes (genomic effect). This leads to stimulation or suppression of m-RNA 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, etc.

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

However, a number of effects of glucocorticoids (for example, 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-transcriptional mechanisms, or by interaction with glucocorticoid receptors found in some cells on the plasma membrane. 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 appear (they require more than 30 minutes to develop), and at high concentrations, extragenomic effects appear.

Glucorticoids cause many effects because... 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 phospholipase A 2 activity. In this case, 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. Inhibition of this enzyme leads to 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, additionally blocking the formation of pro-inflammatory prostaglandins.

In addition, glucocorticoids improve microcirculation in the area of ​​inflammation, cause vasoconstriction of capillaries, 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 influence the alterative and exudative phases of inflammation and prevent the spread of the inflammatory process.

Limiting the migration of monocytes to the site of inflammation and inhibiting the proliferation of fibroblasts determine the antiproliferative effect. Glucocorticoids suppress the formation of mucopolysaccharides, thereby limiting the binding of water and plasma proteins at the site of rheumatic inflammation. They inhibit collagenase activity, 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 tissue, a decrease in the number of T- and B-lymphocytes, mast cells , reducing the sensitivity of effector cells to allergy mediators, suppressing antibody formation, changing 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 reaction: inhibition of migration of bone marrow stem cells and B-lymphocytes, suppression of the activity of T- and B-lymphocytes, as well as 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 components of the complement system, block Fc receptors of immunoglobulins, and suppress the functions of leukocytes and macrophages.

The antishock 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 adrenergic receptors 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 of carbohydrate metabolism, this is manifested by the fact that they stimulate gluconeogenesis in the liver, increase the blood glucose level (glucosuria is possible), and promote the accumulation of glycogen in the liver. The effect on protein metabolism is expressed in inhibition of synthesis and acceleration of protein catabolism, especially in the skin, muscle and bone tissue. This is manifested by muscle weakness, atrophy of the skin and muscles, and delayed wound healing. These drugs cause a redistribution of fat: they increase lipolysis in the tissues of the extremities, promote the accumulation of fat mainly in the face (moon 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), and to a lesser extent for semisynthetic ones (prednisone, prednisolone, methylprednisolone). Fludrocortisone has predominant mineralocorticoid activity. Fluorinated glucocorticoids (triamcinolone, dexamethasone, betamethasone) have virtually 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, which may result in the development of hypocalcemia, hypercalciuria, and 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.

With long-term use, glucocorticoids suppress the function of the hypothalamus-pituitary-adrenal system.

Glucocorticoids differ in activity, pharmacokinetic parameters (degree of absorption, T1/2, etc.), methods of administration.

Systemic glucocorticoids can be divided into several groups.

By 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 parentheses - biological (from tissue) half-life (T 1/2 biol.):

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

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

Long-acting glucocorticoids (T 1/2 biol. - 36-54 hours): 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 administered dose. 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 introduction.

When taken orally, glucocorticoids are quickly and almost completely absorbed from the gastrointestinal tract. Cmax in the blood is observed 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 histohematological barriers worse. Glucocorticoids undergo biotransformation in the liver with the formation of inactive metabolites (glucuronides or sulfates), which are excreted primarily by the kidneys. Natural drugs are metabolized faster than synthetic drugs and have a shorter half-life.

Modern glucocorticoids are a group of drugs that are 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 myeloblastic leukemia, infectious mononucleosis, eczema and other skin diseases, and various allergic diseases. For the treatment of atopic and autoimmune diseases, glucocorticoids are the basic pathogenetic 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.). Due to 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 allows them to be used 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 with minimal doses. The dosage regimen is selected strictly individually, depending more on the nature of the disease, the patient’s condition and response to treatment than on age or body weight.

When prescribing glucocorticoids, their equivalent doses must be taken into account: in terms of the anti-inflammatory effect, 5 mg of prednisolone corresponds 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: replacement, suppressive, pharmacodynamic.

Replacement therapy glucocorticoids are necessary for adrenal insufficiency. With 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 a.m., most (or all) of the dose is prescribed. In chronic adrenal insufficiency (Addison's disease), glucocorticoids can be used throughout life.

Suppressive therapy glucocorticoids are used for adrenogenital syndrome - congenital dysfunction of the adrenal cortex in children. In this case, 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. The majority (2/3) of the dose is given at night to prevent peak ACTH release, using the negative feedback principle.

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

Several types of pharmacodynamic therapy can be distinguished: intensive, limiting, long-term.

Intensive pharmacodynamic therapy: used for acute, life-threatening conditions, glucocorticoids are administered intravenously, starting with large doses (5 mg/kg - day); after the patient recovers from the acute condition (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, severe bronchial asthma, hemolytic anemia, acute leukemia, etc.). The duration of therapy is, as a rule, several months; glucocorticoids are used in doses exceeding physiological ones (2-5 mg/kg/day), taking into account the circadian rhythm.

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

- alternating therapy- use short/medium-acting glucocorticoids (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 reaches inflamed tissues better than others and is less likely to cause side effects).

Long-term pharmacodynamic therapy: used in the treatment of chronic diseases. Glucocorticoids are prescribed orally, doses exceed physiological ones (2.5-10 mg/day), therapy is prescribed for several years, the withdrawal 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-lasting anti-inflammatory effect compared to other glucocorticoids, 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 (intra-articular, periarticular, external) therapy. For broncho-obstructive diseases, inhaled glucocorticoids are especially important.

Glucocorticoids are effective therapeutic agents in many cases. It is necessary, however, to take into account that they can cause a number of side effects, including the Itsenko-Cushing symptom complex (retention of sodium and water in the body with the possible appearance of edema, potassium loss, increased blood pressure), hyperglycemia up to diabetes mellitus (steroid diabetes), slowing down tissue regeneration processes, exacerbation of gastric and duodenal ulcers, ulceration of the digestive tract, perforation of an unrecognized ulcer, hemorrhagic pancreatitis, decreased body resistance to infections, hypercoagulation with the risk of thrombosis, the appearance of acne, moon-shaped face, obesity, menstrual irregularities, etc. When taking glucocorticoids, increased calcium excretion and osteoporosis are observed (with long-term use of glucocorticoids in doses of more than 7.5 mg/day - equivalent to prednisolone - the development of osteoporosis of long tubular bones is possible). Prevention of steroid osteoporosis is carried out with calcium and vitamin D preparations from the moment of starting 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, therefore it is necessary to warn patients about the possibility of its development and when “new” pain appears, especially in the shoulder, hip and knee joints, it is necessary to exclude aseptic bone necrosis. 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 erythrocytes. Nervous and mental disorders are also possible: insomnia, agitation (with the development in some cases of psychosis), epileptiform convulsions, euphoria.

With long-term use of glucocorticoids, one should take into account the possible inhibition of the function of the adrenal cortex (atrophy is possible) with suppression of hormone biosynthesis. Administration of corticotropin simultaneously with glucocorticoids prevents adrenal atrophy.

The frequency and severity of 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 the correct dose selection, compliance with the necessary precautions, and constant monitoring of the progress 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, glucose levels in the blood and urine (especially in patients with diabetes), monitor blood pressure, ECG, electrolyte composition of the blood, monitor the state of the gastrointestinal tract, musculoskeletal system, monitor the development of infectious complications, etc.

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

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

Due to side effects, glucocorticoids are used only if there are clear indications and under close medical supervision. Contraindications for the use 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, and 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 likelihood of developing infections. Glucocorticoids weaken the hypoglycemic activity of antidiabetic agents and insulin, the natriuretic and diuretic activity of diuretics, the anticoagulant and fibrinolytic activity of coumarin and indanedione derivatives, heparin, streptokinase and urokinase, the activity of vaccines (due to a decrease in the production of antibodies), and reduce the concentration of salicylates and mexiletine in the blood. When using prednisolone and paracetamol, the risk of hepatotoxicity increases.

Five drugs are known to suppress the secretion of corticosteroids by the adrenal cortex (inhibitors of the synthesis and action of corticosteroids): mitotane, metyrapone, aminoglutethimide, ketoconazole, trilostane. Aminoglutethimide, metyrapone and ketoconazole suppress the synthesis of steroid hormones due to inhibition of hydroxylases (cytochrome P450 isoenzymes) involved in biosynthesis. All three drugs have specificity, because 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 patient's hypothalamic-pituitary-adrenal axis.

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 for Cushing's syndrome, caused by unregulated excess cortisol secretion by adrenal tumors or ectopic ACTH production. The ability of aminoglutethimide to inhibit aromatase is used in the treatment of hormone-dependent tumors such as prostate cancer and breast cancer.

Ketoconazole is used primarily as an antifungal agent. However, at higher doses it inhibits several cytochrome P450 enzymes involved in steroidogenesis, including. 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 for excessive production of steroid hormones requires further study.

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

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

One of the most important areas of clinical use of glucocorticoids is the pathology of various parts of the respiratory tract.

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

After systemic glucocorticoids (oral and injectable forms) were synthesized in the late 40s of the 20th century, they were immediately used to treat severe bronchial asthma. Despite the good therapeutic effect, the use of glucocorticoids in bronchial asthma was limited by the development of complications - steroid vasculitis, systemic osteoporosis, diabetes mellitus (steroid diabetes). 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, used for moderate and severe COPD (with spirographically confirmed response to treatment).

Inhaled glucocorticoids include beclomethasone, budesonide, fluticasone, mometasone, and triamcinolone. Inhaled glucocorticoids differ from systemic glucocorticoids in their pharmacological properties: high affinity for GK receptors (act in minimal doses), strong local anti-inflammatory effect, low systemic bioavailability (oral, pulmonary), rapid inactivation, short T1/2 from the blood. Inhaled glucocorticoids inhibit all phases of inflammation in the bronchi and reduce their increased reactivity. Their ability to reduce bronchial secretion (reduce the volume of tracheobronchial secretion) and potentiate the effect of beta 2 adrenergic agonists is very important. The use of inhaled forms of glucocorticoids can reduce the need for tablet 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 determining the effectiveness and safety of inhaled glucocorticoids is the system for their delivery to the respiratory tract. Currently, metered-dose and powder inhalers (turbuhaler, etc.), and nebulizers are used for this purpose.

With the correct 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 in the lungs to one degree or another. Local side effects of inhaled glucocorticoids, especially with long-term use, include 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, in the treatment of bronchial asthma, combination drugs intended for long-term therapy, but not for stopping attacks, are effective - for example, the fixed combination of salmeterol/fluticasone or formoterol/budesonide.

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

Currently for intranasal Applications in clinical practice include 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. medicinal, occupational, seasonal (intermittent) and year-round (persistent) allergic rhinitis, to prevent the recurrence of polyps in the nasal cavity after their removal. Topical glucocorticoids are characterized by a relatively late onset of action (12-24 hours), a slow development of the effect - manifests itself by the 3rd day, reaches a maximum on the 5-7th day, sometimes after several weeks. Mometasone begins to act most quickly (12 hours).

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

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

Thus, glucocorticoids (systemic, inhaled, nasal) are widely used in pulmonology and otorhinolaryngology. This is due to the ability of glucocorticoids to relieve the main symptoms of diseases of the ENT and respiratory organs, and if the process persists, to significantly prolong the interictal period. The obvious advantage of using topical dosage forms of glucocorticoids is the ability to minimize systemic side effects, thereby 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 cutaneous dermatosis. Natural hydrocortisone is historically the first glucocorticoid used in dermatological practice, and subsequently became the standard for comparing the strength of different glucocorticoids. Hydrocortisone, however, is not effective enough, especially in severe dermatoses, due to its relatively weak binding to steroid receptors of skin cells and slow penetration through the epidermis.

Later, glucocorticoids found widespread use in dermatology for the treatment of various skin diseases of a 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 their chemical structure, as well as in the strength of their local anti-inflammatory effect.

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

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

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

Medium strength (class II) - alklometasone 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 an 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, stretch marks, and skin infections. The likelihood of developing both local and systemic side effects increases when glucocorticoids are applied to large surfaces and prolonged use. Due to the development of side effects, the use of fluorinated glucocorticoids is limited when long-term use is necessary, as well as in pediatric practice.

In recent years, by modifying the steroid molecule, new generation local glucocorticoids have been obtained that 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 topical use in dermatology are available in the form of ointments, creams, gels, emulsions, lotions, etc. The ability to penetrate the skin (penetration depth) 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, therefore, for dermatoses accompanied by increased dryness and flaking of the skin, lichenification, it is more advisable to use ointments, because 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 advisable to prescribe lotions and 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 a glucocorticoid with an antibiotic in one dosage form, for example Diprogent cream and ointment (betamethasone + gentamicin), Oxycort aerosols (hydrocortisone + oxytetracycline) and Polcortolone TS (triamcinolone + tetracycline), etc., or with an 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 purpose.

The use of glucocorticoids in ophthalmology based on their local anti-inflammatory, antiallergic, antipruritic effect. Indications for the prescription 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, the following are used: hydrocortisone, betamethasone, desonide, triamcinolone, etc. The most preferable is the use of local forms (eye drops or suspension, ointments), in severe cases - subconjunctival injections. When systemically (parenterally, orally) using glucocorticoids in ophthalmology, one should remember the high probability (75%) of developing steroid cataracts with daily use of prednisolone at a dose of more than 15 mg for several months (as well as equivalent doses of other drugs), and the risk increases with increasing the duration of treatment.

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

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