Corticosteroid drugs for the nose. Pharmacological group — Glucocorticosteroids Contraindications to taking glucocorticosteroids

Their use reduces pain, redness and swelling in the joints and surrounding tissues.

GCS is prescribed both inside and in the form of injections.

For intra-articular injections, special preparations are used, the action of which is long enough. GCS begin to act gradually within 24 hours, the positive effect can persist for many days and even months.

When are corticosteroid injections given?

As a rule, the question of the need to prescribe such injections arises in the following cases:

• When the pain in the joint or in the surrounding tissues associated with inflammation is very severe
• If inflammation has affected only a few joints
• If joint pain greatly reduces mobility
• If other drugs for some reason cannot be used
• Local anesthesia can also be used simultaneously with GCS. Its implementation reduces pain, the effect lasts 3-4 hours until the corticosteroids begin to act.

How often are corticosteroid injections given?

What are the benefits of corticosteroid injections?

• Pain and swelling subside fairly quickly.
• The mobility of the joints and the activity of the patient increase.
• Often, after the effect of the injection, the severity of pain decreases, and the need for other drugs is markedly reduced.
• They can be used in combination with other treatments, such as physiotherapy.

injection procedure

The procedure for joint injection is similar to soft tissue injection. Before the injection, a separate syringe is used to remove excess fluid from the joint. The doctor may then examine this fluid and send it to a laboratory for analysis.

Side effects

Since corticosteroids are injected directly into the inflamed area, a very small amount of the drug enters the bloodstream and has an effect on other organs and tissues of the body, especially when compared with oral corticosteroids. Due to this, when injected, the side effects of GCS are minimal.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The antiallergic effect develops as a result of a decrease in the synthesis and secretion of allergy mediators, inhibition of the release of histamine and other biologically active substances from sensitized mast cells and basophils. active substances, reducing the number of circulating basophils, suppressing the proliferation of lymphoid and connective tissue, reducing the number of T- and B-lymphocytes, mast cells, reducing the sensitivity of effector cells to allergy mediators, inhibiting antibody production, 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 response: inhibition of the migration of bone marrow stem cells and B-lymphocytes, suppression of the activity of T- and B-lymphocytes, and inhibition of the release of cytokines (IL -1, IL-2, interferon-gamma) from leukocytes and macrophages. In addition, glucocorticoids reduce the formation and increase the breakdown of the components of the complement system, block the Fc receptors of immunoglobulins, and suppress the functions of leukocytes and macrophages.

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

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

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

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

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

With prolonged use, glucocorticoids suppress the function of the hypothalamus-pituitary-adrenal glands.

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

Systemic glucocorticoids can be divided into several groups.

According to their origin, they are divided into:

Natural (hydrocortisone, cortisone);

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

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

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

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

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

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

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

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

The main indications for the use of glucocorticoids are collagenoses, rheumatism, rheumatoid arthritis, bronchial asthma, acute lymphoblastic and myeloid leukemia, Infectious mononucleosis, eczema and other skin diseases, various allergic diseases. For the treatment of atopic, 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.). In connection with the anti-shock effect, glucocorticoids are prescribed for the prevention and treatment of shock (post-traumatic, surgical, toxic, anaphylactic, burn, cardiogenic, etc.).

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

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

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

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

Replacement therapy glucocorticoids is necessary for adrenal insufficiency. 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 o'clock in the morning, most (or all) of the dose is prescribed. In chronic adrenal insufficiency (Addison's disease), glucocorticoids can be used throughout life.

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

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

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

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

Limiting pharmacodynamic therapy: prescribed for subacute and chronic processes, incl. inflammatory (systemic lupus erythematosus, systemic scleroderma, polymyalgia rheumatica, 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 (2-5 mg / kg / day), taking into account the circadian rhythm.

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

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

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

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

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

Dexamethasone and betamethasone are not used for long-term therapy, since with the strongest and longest anti-inflammatory action 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 parabulbarno, in the form of eye and ear drops, externally in the form of ointments, creams, lotions, etc.

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

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

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

The frequency and strength 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 proper dose selection, necessary measures precautions, constant monitoring of the course of treatment, the incidence of side effects can be significantly reduced.

For a warning unwanted effects associated with the use of glucocorticoids should be, especially when long-term treatment 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 system, blood glucose and urine (especially in patients with diabetes mellitus), control blood pressure, ECG, electrolyte composition of the blood, control the state of the gastrointestinal tract, the musculoskeletal system, control the development of infectious complications, etc.

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

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

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

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

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

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

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

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

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

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

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

After systemic glucocorticoids (oral and injectable forms) were synthesized in the late 1940s, they immediately began to be used to treat severe bronchial asthma. Despite a good therapeutic effect, the use of glucocorticoids in bronchial asthma was limited by the development of complications - steroid vasculitis, systemic osteoporosis, and diabetes mellitus (steroid mellitus). Local forms of glucocorticoids began to be used in clinical practice only some time later - in the 70s. XX century. The publication of the successful use of the first topical glucocorticoid, beclomethasone (beclomethasone dipropionate), for the treatment of allergic rhinitis dates back to 1971. In 1972, a report appeared on the use of a topical form of beclomethasone for the treatment of bronchial asthma.

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

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

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

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

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

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

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

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

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

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

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

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

Later, glucocorticoids were widely used in dermatology for 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 chemical structure, as well as in the strength of the local anti-inflammatory action.

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

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

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

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

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

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

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

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

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

Since glucocorticoids for topical use 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, such as Akriderm GK (betamethasone + clotrimazole + gentamicin).

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

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

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

Preparations

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

Since the middle of the last century, doctors learned that the adrenal cortex synthesizes glucocorticoids, drugs based on this group of hormones have rapidly entered medicine. Unexpectedly, it turned out that unknown hormone lives in almost all cells of the body and helps fight inflammation, suppress aggressive immunity, eliminate the consequences of shock - and this is far from full list actions. Now drugs based on GCS can be found in many forms: tablets, intramuscular and intramuscular injections, ointments, inhaled glucocorticosteroids. Why are these drugs so popular among doctors?

What it is?

Glucocorticoids - it is a certain type of hormone produced by the adrenal cortex. They are part of a larger type of "corticosteroids", a relative - mineralocorticoids. Often, glucocorticoids are referred to as "glucocorticosteroids" because these words are synonymous.

Glucocorticoids are found in almost all tissues human body in different quantities. The main representative of GCS is cortisol, a derivative of hydrocortisone. In smaller doses, corticosterone and cortisone can also be seen. These chemical compounds have an impact on many negative processes occurring in the body.

Expert opinion

Filimoshin Oleg Alexandrovich

Doctor - neurologist, City Polyclinic Orenburg. Education: Orenburg State Medical Academy, Orenburg.

Initially, natural hormones were used in medicine, but their use was associated with a high risk of side effects, so now chemists use more advanced GCS. For example, synthesized Dexamethasone is 30 times more effective than cortisol, and at the same time it causes much less side effects when used.

How do they act?

The answer to this question can be awarded the Nobel Prize, because at the moment the exact mechanism of action of the GCS is unknown. In general, they work in the same way as all hormones - they transmit information to other cells of the body about the processes occurring in the body. The pituitary gland is responsible for the release of glucocorticoids, which can secrete a special substance into the blood - corticotropin. If necessary, this chemical element orders the adrenal glands to release corticosteroids. More corticotropin means more cortisol, and vice versa.

Ask your question to a neurologist for free

Irina Martynova. Graduated from the Voronezh State Medical University. N.N. Burdenko. Clinical intern and neurologist of BUZ VO \"Moscow Polyclinic\".

Expert opinion

Mitrukhanov Eduard Petrovich

Doctor - neurologist, city polyclinic, Moscow. Education: Russian State Medical University, Russian Medical Academy of Postgraduate Education, Ministry of Health of the Russian Federation, Volgograd State Medical University, Volgograd.

How glucocorticoids work inside cells is a medical mystery. It is believed that in the nuclei of all cells there are special receptors that, when a different amount of steroids enter them, begin to behave in a certain way. But this is just a guess.

How do they affect the body?

GCS have a wide spectrum of action. Main directions:

• Anti-inflammatory. Drugs (glucocorticoids) strongly inhibit inflammation by reducing the activity of enzymes that destroy tissues. Under their influence, cell membranes coarsen, as a result of which the exchange of fluids decreases and chemical elements between affected and healthy areas. They also inhibit the synthesis of lipocortin proteins from arachidonic acid, which are responsible for the spread of inflammation.
• Effects on other hormones. GCS affect other mediators, most of all insulin. The release of steroids into the blood during hypoglycemia is the body's main weapon in order to quickly correct the situation.
• Antistress, antishock. This group of hormones, during stress or a state of shock, tells the bone marrow to produce more blood cells (in case of blood loss), and the cardiovascular system to raise blood pressure.
• Immunoregulatory action. At low doses in the blood, GCS slightly increases immunity, at high doses it can suppress it many times over, up to 1% efficiency compared to the norm. This property is used to prevent tissue rejection after transplants.
• Antiallergic. The mechanism of this action is also not completely clear, but glucocorticoids effectively cope with the manifestations of allergies.
• Effect on metabolism. Glucocorticosteroids can interfere with the work of glucose metabolism, glycolysis enzymes, glycogen, various proteins, fats, sodium, chlorine, potassium, calcium, water.

It is worth noting that not in all these cases, GCS is beneficial to the body. For example, with prolonged exposure to a large amount of the hormone, calcium is washed out of the bones, from which the patient develops osteoporosis (an increase in the fragility of the skeleton).

When are they appointed?

The list of diseases treated with these steroids comes from their areas of action listed above. The main indications for use are as follows:

• Allergic reactions, most often asthma. Despite the fact that the mechanism of action on allergic reactions has not yet been elucidated, almost every asthmatic has inhaled glucocorticosteroids (IGCS) in cans.
• Non-infectious inflammation of the skin. The ability of GCS to reduce inflammation has found wide application in dermatology. In the case of infectious inflammation, the glucocorticoid used in the treatment should be combined with a drug that kills the infection.
• Anemia, diseases of the hematopoietic system. Medicines on this basis stimulate the bone marrow to produce blood cells.
• Trauma, rheumatic diseases. Typically, such a diagnosis includes inflammation, stress on the body, and a violation of the body's defense mechanisms.
• The period after tissue and organ transplantation, radiation and chemotherapy. GKS changes the answer immune system on these factors, which has a positive effect on the dynamics.
• Adrenal insufficiency. In this case, the drugs have the most direct effect - they compensate for the lack of hormones in the blood that the adrenal glands should supply.

In addition to these indications, there are more specific ones. In such cases the decision to use glucocorticosteroids should be made by an experienced physician.

Side effects from the use of corticosteroids

Interfering with the hormonal balance of the body means interfering with the normal communication of body parts with each other. Side effects from this action can be quite serious:

• Osteoporosis. Due to changes in metabolism, calcium is excreted from the body faster, which leads to bone fragility.
• Emotional instability, psychoses. Caused by changes in the functioning of the pituitary gland.
• steroid diabetes. Steroids increase blood glucose levels.
• Adrenal insufficiency. This may seem strange, given that a similar disease is an indication for use. But the long-term effect of drugs with GCS on the body makes the adrenal glands work less efficiently, since there are already a lot of hormones in the blood, and with a sharp withdrawal of the drug, the adrenal glands are no longer able to provide the body with the right amount of glucocorticosteroids.
• Bleeding, ulcers. An increase in the production of blood cells leads to a load on circulatory system, and she can "give a breakdown."
• With a long (more than 1.5 year) course of treatment in children, sexual development is sometimes suppressed due to suppression of the adrenal glands.
• Obesity, acne, swollen face, menstrual irregularities. These side effects are caused by hormonal imbalance.
• Various diseases eye.

Local adverse reactions occur when using ointments and inhalers.

Ointments are usually cause dry skin due to low cell permeability and inhalers almost always lead to coughing, dry mouth, and hoarseness.

It is worth noting that almost all the effects of the use of these drugs are reversible. Only diabetes, growth retardation in children, and subcapsular cataracts are irreversible.

Use with caution!

Glucocorticosteroids are a powerful, but dangerous remedy due to adverse reactions. They should be used as short as possible and only under constant medical supervision. Most the right way– treatment in a hospital, under the supervision of doctors who can take necessary tests, do an ultrasound or ECG if necessary.

The drug has a withdrawal syndrome, so treatment should be completed smoothly, gradually reducing the dose of the drug. A mild variant of the withdrawal syndrome is manifested by fever and malaise. Severe can lead to an Addisonian crisis.

Contraindications

If a single use is necessary, the only absolute contraindication is the patient's individual intolerance to GCS. Long-term therapy should not be given to people with:

• diabetes
• pregnancy
• syphilis, tuberculosis, recently cured of infection;
• Itsenko-Cushing's disease;
• psychosis;
• diseases of the liver, kidneys, gastrointestinal tract and circulatory system (each disease is individual, you need to check with your doctor);

Children can be prescribed glucocorticoid drugs only in extreme cases.

Ointments and drops should not be used if there are infections at the sites of use.

Complications after taking

Common complications are diseases from the list of side effects. If they occur, you need to reconsider the dose or stop the drug altogether.

Self-medication with the wrong dose is likely to end hormonal failure or diabetes.

The duration of the GCS

Drugs (glucocorticosteroids) are divided into three types: short-acting, medium duration and long-term. Short-acting corticosteroids remain in the blood for 2-12 hours, medium - for 0.75-1.5 days, long-term - from 36 to 52 hours.

In many ways, the duration of action depends on the route of administration.

Application methods

From the methods of application can be distinguished: tablets(systemic glucocorticosteroids); injections(for diseases of the joints or as an alternative to pills); ointment, gel, cream, patches(topical glucocorticosteroids); inhalers(inhaled glucocorticoids).

In tablets, glucocorticoids are used for acute pulmonary diseases, such as: bronchial asthma, chronic obstructive pulmonary disease, pneumonia, and others. The drug is almost completely absorbed from the stomach, the peak concentration in the blood is reached after an hour and a half.

When it is not possible to give the patient systemic corticosteroids in the form of tablets or you need the drug to act faster, intravenous or soft tissue administration is used. The same tactic is used for joint diseases - corticosteroids are injected directly into the damaged ligament.

Topical application on the skin is successful in subcutaneous inflammation and allergic reactions on the skin. In addition, when used correctly, this option is quite safe in terms of side effects.

Inhalers deliver a dose of medication directly to the bronchi and lungs. This type has become very widespread among asthmatics, since inhaled glucocorticoids are the most convenient and effective way to control asthma.

List of medicines

Active ingredients according to duration are divided into:

• Short-acting corticosteroids: Alclomethasone, Budesonide, Hydrocortisone, Clobetasol, Cortisone, Mazipredone, Mometasone, Flunisolide, Fluocortolone, Fluocinolone acetonide, Fluticasone, Cyclesonide;
• GCS of medium duration: Methylprednisolone, Methylprednisolone aceponate, Prednisolone, Triamcinolone, Fludrocortisone;
• GCS long-acting: Beclomethasone, Betamethasone, Dexamethasone.

Glucocorticoids for oral use

• Budenofalk, Budesonide;
• Decdan, ;
• Dexazon, Dexamethasone;
• Dexamethasone, Dexamethasone;
• Megadexan, Dexamethasone;
• Fortecortin, Dexamethasone;
• cortisone, cortisone;
• , Methylprednisolone;
• Apo-prednisone, Prednisone;
• Prednisol, ;
• prednisolone, prednisolone;
• Berlikort, ;
• Polcortolon, Triamcinolone;
• Triamcinolone, Triamcinolone;
• Tricort, Triamcinolone;
• Cortineff, Fludrocortisone.

Glucocorticoids for injection

• Betamethasone sodium phosphate, Betamethasone;
• Betamethasone dipropionate, Betamethasone;
• Celeston, Betamethasone;
• Decdan, Dexamethasone;
• Dexazon, Dexamethasone;
• Dexabene, Dexamethasone;
• Dexafar, Dexamethasone;
• Fortecortin Mono, Dexamethasone;
• , Hydrocortisone;
• Solu-Cortef, Hydrocortisone;
• Urbazon, Methylprednisolone;
• Medopred, Prednisolone;
• prednisolone, prednisolone;
• prednisolone sodium phosphate, prednisolone;
• Solu-Decortin N, Prednisolone;
• , Triamcinolone;
• Tricort, Triamcinolone.

Glucocorticoids in the form of inhalations

• Beclazone, Beclomethasone;
• Beclodget 250, Beclomethasone;
• beclomethasone, beclomethasone;
• Beclospir, Beclomethasone;
• Bekodisk, Beclomethasone;
• Becotide, Beclomethasone;
• Klenil, Beclomethasone;
• Plibekort, Beclomethasone;
• Rinoclenil, Beclomethasone;
• Benacort, Budesonide;
• Budesonide, Budesonide;
• Asmanex Twisthaler, Mometasone;
• Azmacort, Triacinolone;
• Ingacort, Flunisolide;
• Alvesco, Ciclesonide.

GCS intranasal application

• Aldecin, Beclomethasone;
• Nasobek, Beclomethasone;
• Budoster, Budesonide;
• Tafen nasal, Budesonide;
• Dezrinit, Mometasone;
• nosefrine, mometasone;
• Sintaris, Flunisolide;
• Nazarel, Fluticasone.

GCS topical application in ophthalmology, gynecology, etc.

• Dexamethasone, Dexamethasone;
• Dexoftan, Dexamethasone;
• , Hydrocortisone;
• , Prednisolone;
• prednisolone sodium phosphate, prednisolone;
• Rektodelt, Prednisone;
• Cortineff, Fludrocortisone.

Ointment, gel or cream for external use

• Afloderm, Alclomethasone;
• Akriderm, Betamethasone;
• Betliben, Betamethasone;
• Betnovate, Betamethasone;
• Celestoderm-B, Betamethasone;
• Apulein, Budesonide;
• Novopulmon E Novolizer, Budesonide;
• Dermovate, Clobetasol;
• Powercourt, Clobetasol;
• Acortin, Hydrocortisone;
• Laticort, Hydrocortisone;
• Lokoid, Hydrocortisone;
• Deperzolon, Mazipredone;
• Advantan, Methylprednisolone aceponate;
• Mometasone-Akrikhin, Mometasone;
• Monovo, Mometasone;
• Uniderm, Mometasone;
• Ultralan, Fluocortolone;
• Sinaflan, fluocinolone acetonide;
• Flucort, Fluocinolone acetonide;
• fluocinolone acetonide, fluocinolone acetonide;
• Flucinar, Fluocinolone acetonide.

Glucocorticosteroids are hormones produced by the adrenal glands. They can be found in almost all tissues of the body. They perform many functions, mainly developing (in childhood) and therapeutic effects. For some diseases, it is possible to increase the amount of corticosteroids in the body with the help of medications to cope with a difficult inflammation, immune response, or other medical problem.

• After intranasal administration, part of the dose that settles in the pharynx is swallowed and absorbed in the intestine (> 50% of the administered dose), part is absorbed into the blood from the nasal mucosa. With a functioning mucociliary transport, already 20-30 minutes after spraying the powder or aerosol, only a small part medicinal product remains in the nasal cavity. Up to 96% of the drug is transported by the cilia of the nasal mucosa into the pharynx, swallowed, enters the stomach, and is absorbed into the blood. Therefore, oral and intranasal bioavailability are important pharmacokinetic characteristics of topical steroids. These indicators largely determine the therapeutic index of glucocorticoids, i.e. the ratio of their local anti-inflammatory activity and possible systemic action.
  The low bioavailability of modern topical corticosteroids is explained by their minimal (1-8%) absorption from the gastrointestinal tract and almost complete (about 100%) biotransformation to inactive metabolites during the first passage through the liver. A small part of the drug, which is absorbed from the mucous membrane of the respiratory tract, is hydrolyzed by esterases to inactive substances. The bioavailability of many intranasal corticosteroids is relatively high. For example, in beclamethasone, it is approximately 10%. Modern drugs in this group (fluticasone and mometasone) have a bioavailability of 1% and 0.1%, respectively. That is, among intranasal corticosteroids, mometasone has the lowest bioavailability.
  Bioavailability of nasal glucocorticoids
  

  Glucocorticoids	Bioavailability after intranasal administration (%)	Bioavailability after oral administration
  Beclomethasone dipropionate	44	20-25
  Triamcinolone acetonide	No data	10,6-23
  Flunisolide	40-50	21
  Budesonide	34	11
  fluticasone propionate	0,5-2
  mometasone furoate

  
  Nasal glucocorticoid delivery systems
  The efficacy and safety of topical steroids are largely determined by their delivery systems to the nasal cavity. The characteristics of the existing inhalation administration systems are given in the table.

  Efficiency of drug delivery into the nasal cavity using various dosing devices
  

  Dosing device	The amount of the drug delivered to the patient (% of a single dose)	Amount of drug remaining in the nasal cavity (% of delivered dose)
  Dosing aerosol	64	20
  nasal spray	100	50
  Turbuhaler	70	90

  
  Dosage forms in the form of a metered-dose aerosol and nasal spray are currently registered in our country. The latter has a greater drug delivery efficiency and fewer local side effects that occur in patients when using glucocorticoids (nosebleeds, dryness and burning in the nose, itching and sneezing). It is believed that they are due to the irritating effect of freon and the high rate of drug entry into the nasal cavity, observed with the use of metered-dose aerosols.