The place of intranasal glucocorticoids in the treatment of allergic rhinitis. Glucocorticosteroids: what they are, indications for use Intranasal corticosteroids

Currently, beclomethasone dipropionate, flunisolide, budesonide, fluticasone propionate, mometasone furoate, and triamcinolone acetonide are used in clinical practice for intranasal use. Flunisolide and triamsinolone in the form of nasal aerosols are not currently used in Russia. Hydrocortisone, prednisolone and dexamethasone should not be used intranasally, as they are characterized by very high bioavailability and can cause side effects characteristic of systemic glucocorticoid therapy. Based on safety data, mometasone furoate and fluticasone propionate are recommended for long-term use.

• After intranasal administration, part of the dose that settles in the pharynx is swallowed and absorbed in the intestines (> 50% of the administered dose), part is absorbed into the blood from the nasal mucosa. With functioning mucociliary transport, already 20-30 minutes after spraying the powder or aerosol, only a small part of the drug 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, important pharmacokinetic characteristics of topical steroids are oral and intranasal bioavailability. These indicators largely determine the therapeutic index of glucocorticoids, i.e. the relationship between their local anti-inflammatory activity and possible systemic effects.
  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, for 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 (%)	Oral bioavailability
  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 effectiveness and safety of topical steroids are largely determined by their delivery systems into the nasal cavity. Characteristics of existing inhalation administration systems are given in the table.

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

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

  
  In our country, dosage forms are currently registered in the form of a metered-dose aerosol and nasal spray. The latter has 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 entry of drugs into the nasal cavity, observed when using metered aerosols.
  

Corticoids are hormonal substances produced by the human adrenal cortex. There are several types of them - mineralo- and glucocorticoids. Drugs that contain only one type of these hormonal substances are called corticosteroids. Intranasal corticosteroids are the most commonly used form of these medications in otolaryngology.

Synthetic glucocorticoids have the same properties as natural ones. Nasal corticosteroids, like other forms of hormonal drugs, have pronounced anti-inflammatory and antiallergic effects. The anti-inflammatory effect is based on inhibition of the production of active substances (leukotrienes, prostaglandin) that take part in the protective function of the body. There is also a delay in the proliferation of new protective cells, which significantly affects local immunity. Hormonal drugs exert their antiallergic effect by inhibiting the release of allergy mediators, in particular histamine. As a result, a long-lasting (during the day) anti-edematous effect is achieved.

Thanks to all the above properties, nasal hormonal preparations are indispensable for many inflammatory and allergic diseases of the nose.

Use of nasal corticosteroids

Currently, in the practice of an ENT doctor, the use of hormonal groups of drugs is widespread, based on their high effectiveness. They are most often prescribed for diseases that arise from contact with an allergen:

• Allergic rhinitis.
• Sinusitis.
• Sinusitis.

Nasal corticosteroids effectively eliminate local allergic manifestations, namely sneezing, nasal congestion, and rhinorrhea.

Drugs are also prescribed for vasomotor rhinitis in pregnant women. In this situation, they significantly improve nasal breathing, but do not contribute to a complete cure.

When polyps are detected in the nasal cavity, the use of nasal hormonal drugs, at the moment, has no alternative among other methods of drug treatment.

Before directly using a nasal hormonal agent, it is important to establish the cause of the disease.

It must be remembered that these drugs do not affect the pathogen itself (viruses, bacteria), but only eliminate the main local manifestations of the disease.

Contraindications

In most cases, glucocorticoid drugs are well tolerated by patients. Despite this, there are a number of restrictions on their use:

• Hypersensitivity to the components of the drug.
• Tendency to nosebleeds.
• Young children's age.

Pregnant women are prescribed hormonal medications with caution, and are not recommended for use during breastfeeding.

Side effects

Most often, undesirable clinical manifestations from the body occur with their prolonged and uncontrolled use.

May be observed:

• Pain in the nasopharynx area.
• Dryness of the nasal mucosa.
• Bleeding from the nasal passages.
• Headaches, dizziness, drowsiness.

If you use corticosteroid drugs in high doses for a long time, the risk of developing candidiasis in the nasopharynx increases.

The possibility of such clinical manifestations remains quite low, since intranasal hormonal drugs, unlike tablets, act only locally and are not absorbed into the bloodstream.

Release forms

Intranasal hormonal drugs are available in the form of drops and sprays. It is necessary to instill the medicine into the nose in a supine position, with the head thrown back and moved to the side for better penetration of the drug into the nasal cavity.

If the technique of instilling the medicine is not followed, a person may experience pain in the forehead and a feeling of the drug’s taste in the mouth. Unlike drops, nasal sprays are much more convenient to use because they do not require any preparation before use.

Their main advantage remains that, thanks to the presence of a dispenser, the drug is difficult to overdose on.

Types of intranasal hormonal drugs

Currently, on the pharmaceutical market there are a large number of hormonal drugs that are similar in their effects, but have varying degrees of pronounced effectiveness.

The table below shows the most common nasal corticosteroid drugs and their analogues.

It is worthwhile to dwell in detail on the features of the main drugs in order to understand the advantages of each of them.

Flixonase

In addition to the main substance - fluticasone propionate, the drug contains a number of auxiliary components: dextrose, cellulose, phenylethyl alcohol and purified water.

Flixonase is produced in bottles with a dispenser of 60 and 120 doses (one dose contains 50 mcg of active substance). The anti-inflammatory effect of the drug is moderate, but it has a fairly strong anti-allergic property.

The clinical effect of the drug develops 4 hours after administration, but a significant improvement in the condition occurs only on the 3rd day from the start of therapy. If the symptoms of the disease decrease, the dosage can be reduced.

The average course duration is 5–7 days. The drug is allowed to be taken for prophylactic purposes during seasonal allergies. Unlike other hormonal drugs, Flixonase does not have a negative effect on the hypothalamic-pituitary system.

The drug is strictly prohibited for use in case of herpetic infection, and, in addition to the adverse reactions common with other hormones, it can provoke the development of glaucoma and cataracts. The drug is approved for use in children only from 4 years of age.

Alcedin

The drug is available in 8.5 g cylinders with a dispenser and mouthpiece in the form of a white, opaque suspension. Contains the active substance - beclomethasone (in one dose - 50 mcg). In addition to anti-inflammatory and anti-allergic properties, it also exhibits an immunosuppressive effect. When using standard doses, the drug does not have a systemic effect.

When injecting Alcedin into the nasal cavity, direct contact of the applicator with the mucous membrane should be avoided. After each dose, you must rinse your mouth. In addition to common indications for use with other hormonal drugs, it can be used as part of complex therapy for bronchial asthma (not used during an attack).

Alcedine can increase blood glucose levels, so it should be taken with caution by people with diabetes. Also, special attention when taking it is given to people with hypertension, dysfunction of the liver and thyroid gland.

The drug is contraindicated for women in the first trimester of pregnancy and during breastfeeding, as well as children under 6 years of age.

Nasonex

The main component of the drug is mometasone furoate, a synthetic glucocorticosteroid with pronounced anti-inflammatory and antihistamine effects. Available in the form of a white suspension in plastic bottles of 60 and 120 doses.

In its action and method of application, Nasonex is similar to Flixonase but, unlike it, it has an effect on the hypothalamic-pituitary system. The first clinical effect after administration of the drug is observed 12 hours later, which is significantly later than when taking Flixonase.

Very rarely, prolonged and uncontrolled use of the drug can lead to an increase in intraocular pressure and disruption of the integrity of the nasal septum (its perforation).

Nasonex is not prescribed to persons with pulmonary tuberculosis, acute infectious diseases, as well as to people who have recently undergone injuries or surgical interventions in the nasopharynx. There are no absolute contraindications to taking this drug in pregnant women.

However, after the birth of a child, he should definitely be examined for the safety of adrenal function. It is prescribed to children from the age of two.

Avamis

A hormonal drug which, unlike others, has a powerful anti-inflammatory effect. It contains fluticasone furoate and excipients. It is produced, like previous drugs, in bottles of 30, 60 and 120 doses.

The clinical effect after the first dose becomes noticeable after 8 hours. If accidentally swallowed during instillation, Avamys is not absorbed into the bloodstream and does not have a systemic effect.

The drug has a number of advantages in comparison with other nasal hormones and, first of all, this is due to the good tolerability of the drug and the absence of serious contraindications to its use.

The only thing that requires caution is the administration of Avamis to people with severely impaired liver function. The use of the drug by pregnant and lactating women is not recommended due to the insufficient number of studies conducted on its effect.

Avaris is prescribed to children from the age of two. Cases of overdose with this drug have also not been recorded.

Polydexa

The drug is significantly different from all previous ones. This is a combination drug that includes drugs from three groups, namely antibiotics (neomycin and polymyxin sulfate), vasoconstrictors (phenylephrine hydrochloride) and hormones (dexamethasone 0.25 mg).

Due to the presence of an antibiotic, Polydex is active against bacterial infections (the only exceptions are representatives of the cocci group). Therefore, its use is justified for persons with allergic nasopharyngeal diseases in the presence of an infectious pathogen.

Polydex is produced in the form of drops and spray. Drops, as a rule, are used only in the treatment of inflammatory ear diseases, but their use for the treatment of inflammatory processes in the nose is also acceptable. The drops are produced in yellow-brown bottles with a capacity of 10.5 ml. The spray, unlike ear drops, contains phenylephrine and is available in a blue bottle (volume 15 ml), protected from daylight.

The average duration of drug therapy is 5-10 days; with prolonged use of the drug, there is a high risk of developing candidiasis and nasopharyngeal dysbiosis.

The use of Polydex is absolutely contraindicated for viral diseases of the nasopharynx, closed-angle glaucoma, severe renal impairment, as well as during pregnancy and breastfeeding.

The drug is not prescribed for children under two years of age. It is prohibited to use Polydex simultaneously with antibacterial aminoglycoside drugs.

Comparative characteristics of nasal corticosteroids

Given the variety of nasal hormonal drugs, it is often difficult for a person to distinguish between them by action and to give preference to any of them. The following table is presented, the main purpose of which is to simplify the understanding of the main differences between nasal corticosteroids.

Despite the fact that hormonal drugs in the form of nasal sprays do not enter the general bloodstream, the risk of adverse reactions remains high. Given this, the choice of corticosteroids should be approached with the utmost seriousness.

Only the attending physician can prescribe these medications. The patient should take only the prescribed dosage and observe the duration of taking the drug.

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.

Glucocorticoids 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 proinflammatory 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 if “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 long-term therapy is stopped. 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 in case of excess 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 using systemic (parenteral, orally) 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 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.

Drugs

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

Active ingredient	Trade names
No information available

Allergic rhinitis (AR) is a disease of the nasal mucosa, the basis of which is allergic inflammation caused by causal allergens. Although AR itself is not a serious disease, it can change the social life of patients, affect attendance and performance at school, and work performance.

Epidemiology of AR

AR is a disease that is growing every year throughout the world. Over the past 30 years, the incidence in economically developed countries has increased by 100% in every decade. The increase in the frequency and severity of allergic diseases is associated with many factors, among which environmental deterioration is in the first place. According to the Russian Ministry of Health, from 13% to 35% of the population of our country suffer from allergic diseases, of which AR accounts for 60-70%. The prevalence of AR is especially high in the pediatric population, where, according to various studies, it reaches from 10% to 28.7%. An increase in incidence occurs at early school age; boys are more often affected. An increased risk of AR is observed in children with a hereditary predisposition to atopy: it has been found that the likelihood of AR increases to 70% if both parents suffer from atopic diseases. Bronchial asthma (BA) and AR are often comorbidities. According to H. Milgrom, D. Y. Leung, up to 78% of patients with asthma suffer from AR and 38% of patients with AR have asthma.

Pathogenesis of AR

AR is an IgE-mediated inflammation of the nasal mucosa. Sensitization can be caused by a variety of allergens. In the nasal mucosa, the allergen binds to allergen-specific IgE antibodies, which triggers the activation of mast cells. In the early phase of the allergic response, histamine, tryptase, prostaglandin D2, leukotrienes (B4 and C4), kinins, thromboxane A2 (cyclooxygenase pathway), hydroxyeicosatetraenoic acids, lipoxins (5-lipoxygenase pathway) and platelet activating factor are released. Mediators of the allergic reaction stimulate the nerve endings of the parasympathetic nerves, which carry impulses to the central nervous system, from where they travel to the conjunctiva of the eyes (nasoocular reflex). Symptoms of AR (vasodilation, hyperemia, increased vascular permeability, edema, cellular infiltration by basophils and mast cells) are also realized by eosinophils, macrophages, and T-lymphocytes. With an exacerbation of allergic rhinitis, the activity of the cilia of the ciliated epithelium of the nasal mucosa decreases by more than 1.5 times.

Clinical picture of AR

Allergic inflammation of the nasal mucosa is manifested by rhinorrhea, sneezing, itching, and nasal congestion. Intermittent (seasonal) AR develops more often in children aged 4-6 years, but can occur earlier. Symptoms appear during the flowering period of plants to which the patient is sensitive. Other allergic reactions may occur: conjunctivitis, uveitis, damage to the gastrointestinal tract, etc. Clinical symptoms of the disease recur during the flowering period of certain plant species. Persistent (year-round) AR is characterized by constant nasal congestion, as well as frequent sneezing. The most common allergens are household allergens and mold spores. Exacerbations of year-round AR are associated with exposure to nonspecific irritating factors (pungent substances, perfumes, smoke, etc.). Patients' sense of smell decreases, they complain of increased fatigue, headache, frequent nosebleeds, and dry cough. During rhinoscopy, swelling and pallor of the mucous membrane and mucous discharge are observed. Constant nasal congestion can interfere with sleep. Breathing through the mouth leads to dry mucous membranes and lips. If the disease develops at an early age, changes in the facial skeleton and malocclusion may occur. Prolonged swelling of the mucous membrane contributes to the occurrence of sinusitis.

AR classification

1. According to the frequency of manifestations of AR, there are:
   a) acute (episodic) AR - symptoms develop acutely as a result of contact with allergens (waste products of domestic or wild animals, mites, house dust);
   b) persistent (year-round) AR;
   c) seasonal AR (hay fever, pollen allergy) is characterized by annual seasonality of symptoms (during the flowering period of specific plants). In central Russia there are three peaks of hay fever:
   • spring (April-May, flowering of bushes and trees);
   • summer (June-July, grass flowering);
   • autumn (July-October, allergies to pollen of wormwood, ragweed).
2. Depending on the duration of AR, it can be:
   a) intermittent AR (symptoms are observed< 4 дней в неделю или < 4 недель в году);
   b) persistent (year-round) AR: symptoms appear > 2 hours/day, > 4 days a week and > 4 weeks a year.
3. By severity (assessed subjectively depending on the quality of life): mild, moderate and severe.
4. Depending on the presence or absence of complications: uncomplicated and complicated (sinusitis, nasal polyposis, eustachian tube dysfunction, otitis media, etc.).
5. Depending on the type of allergen: pollen, fungal, household, food, epidermal.

Diagnosis of AR

The diagnosis of AR is established on the basis of complaints, medical history, clinical manifestations, endoscopic picture and specific allergological diagnostics aimed at identifying the causative allergens (IgE determination and cytological examination of nasal discharge, skin testing). It is necessary to pay attention to the family history. Nasal provocation test, active anterior rhinomanometry and acoustic rhinometry allow objective assessment of nasal breathing. According to WHO recommendations, patients with persistent AR should be carefully examined for the presence of asthma. Differential diagnosis of AR is carried out with acute respiratory infections, nasal polyps, anatomical abnormalities, adenoiditis and other diseases.

AR treatment

Elimination of allergens

Therapeutic measures should be, first of all, aimed at eliminating etiologically significant factors. It is recommended to limit your stay outside during the flowering period of plants, especially in dry, hot and windy weather; use air conditioners and air filters indoors; If possible, go to other climatic zones during the flowering period. To eliminate the symptoms of AR, it is recommended to exclude from the diet those food groups that have cross-allergenic properties with plant pollen.

Drug therapy

Cromony

Cromones (sodium cromoglicate and sodium nedocromil) have a moderate anti-inflammatory effect on the mucous membrane of the upper respiratory tract and are used to prevent allergic diseases of the nose, eyes and bronchi. Cromones generally have a high safety profile. They reduce the release of mediators of allergic inflammation. The short duration of their action requires frequent administration (up to 4-6 times a day), which significantly reduces compliance; it is recommended to use them in the initial stages of the disease, as well as in mild forms of rhinitis.

Topical corticosteroids

Topical corticosteroids have a pronounced anti-inflammatory effect, are most effective for all types of AR, and reduce all symptoms, in particular nasal congestion. However, their long-term use can lead to undesirable reactions, primarily to atrophy of the mucous membrane with possible nosebleeds.

Antileukotriene drugs

Antileukotriene drugs are divided into leukotriene antagonists and leukotriene synthesis inhibitors. Leukotrienes are mediators of the early phase of an immediate allergic reaction. Leukotriene receptor antagonists are effective in relieving symptoms of AR. These drugs are also widely used for the treatment of mild forms of asthma in combination with AR.

Decongestants

Decongestants (oxymetazoline, xylometazoline, naphazoline, etc.) restore nasal breathing. Vasoconstrictor drugs can only be used in short courses. Their use for more than 3-5 days can lead to the development of “rebound syndrome” and drug-induced rhinitis.

Allergen-specific immunotherapy (ASIT)

ASIT consists of introducing an allergen to which the patient is hypersensitive in increasing doses into the patient’s body, resulting in a decrease in the formation of specific IgE.

Antihistamines

Antihistamines are divided into two generations. 1st generation drugs are characterized by incomplete and reversible binding to H1 receptors, so they often need to be taken again during the day. 1st generation antihistamines, in addition to histamines, block other receptors, including M-cholinergic and α-adrenergic receptors, which leads to a decrease in exocrine secretion and an increase in the viscosity of secretions; rapid development of tachyphylaxis. Due to their high lipophilicity, these drugs penetrate well through the blood-brain barrier, causing drowsiness, loss of coordination, lethargy, and dizziness. 2nd generation drugs, as a rule, do not have the disadvantages of 1st generation drugs. Their features are:

• good tolerability, high safety profile and effectiveness;
• less pronounced sedative effect (varies for different drugs in this group), high selectivity;
• more active inhibition of the development of the inflammatory process;
• rapid onset of action;
• prolonged action (up to 24 hours);
• rare development of tachyphylaxis;
• inhibition of the release of inflammatory mediators; decreased expression of adhesion molecules (ICAM-1) on epithelial cells, influence on cytokines.

Local antihistamines are used in the acute stage of AR. Since the drug acts directly at the site of allergic inflammation, it is characterized by a rapid onset of therapeutic action - 5-20 minutes after use. Topical antihistamines also have some anti-inflammatory effects. Although this effect is less pronounced than that of topical corticosteroids, the likelihood of side effects is lower. H1-histamine blockers for topical use include azelastine, antazoline, demitendene and levocabastine (Table).

Currently, levocabastine and azelastine are the most widely used drugs in the world for the treatment of AR. They are prescribed as monotherapy for mild forms of AR. When prescribed early, drugs can prevent the development of seasonal AR. For moderate and severe forms of AR, simultaneous use of oral antihistamines is recommended.

The 2nd generation antihistamine drug levocabastine selectively blocks H1-histamine receptors, thereby reducing the severity of allergic reactions mediated by the action of histamine. It quickly eliminates the symptoms of AR. With a single intranasal administration of the drug (50 mcg/dose), 30-40 mcg of levocabastine is absorbed. The half-life is 35-40 hours. In a multicenter, randomized, double-blind study that included 244 patients with AR, it was shown that levocabastine and azelastine have comparable efficacy, but the rate of onset of effect was higher for levocabastine. In a pilot study involving patients with a history of AR, it was shown that intranasal administration of levocabastine 5 minutes before allergen exposure significantly reduced the severity of the allergic reaction. In this case, the duration of the protective effect is at least 24 hours. The high clinical efficacy and safety profile of levocabastine in AR have been shown in a number of double-blind, placebo-controlled studies. Evidence-based studies have found that levocabastine in the form of a nasal spray is superior in clinical effectiveness to sodium cromoglycate in a similar form. Of great interest are studies in which levocabastine was compared with a systemic antihistamine. A multicenter randomized clinical trial involving 207 patients with perennial allergic rhinoconjunctivitis compared the effectiveness of levocabastine (nasal spray and eye drops) and cetirizine (oral). In general, the therapeutic efficacy in both groups was comparable, but it was noted that the effect when using levocabastine occurred much faster (after 5 minutes). In particular, 1 hour after using the drug, relief of AR symptoms was noted by 76% of patients receiving levocabastine, and only 38% of patients receiving cetirizine. Another clinical study included 30 children aged 6 to 16 years with year-round AR. The main group received cetirizine, the control group received levocabastine in the form of a nasal spray. The clinical efficacy of the drugs was comparable, with fewer adverse events noted in the group of patients receiving levocabastine. According to a study in adult patients with year-round AR, after three months of use of levocabastine, a significant reduction in symptoms was observed, with no adverse effects recorded. Unlike intranasal corticosteroids, levocabastine has a high safety profile. On the Russian market, the drug levocabastine in the form of a nasal spray is presented under the trade name Tizin® Alergy. Vials of 10 ml (100 doses) contain levocabastine hydrochloride at a concentration of 0.54 mg/ml, in terms of levocabastine - 0.5 mg/ml. Contraindications to its use are hypersensitivity to any of the components of the drug and age under 6 years. Apply intranasally 2 doses (100 mcg) in each nasal passage 2-4 times a day after cleansing the nasal passages before use.

The incidence of AR is increasing every year. There is a large selection of drugs to treat this pathology. All of them are aimed at different parts of the pathogenesis of AR. Levocabastine (Tizin® Alergy) selectively blocks H 1 -histamine receptors, thereby reducing the severity of allergic reactions mediated by the action of histamine.

Since levocabastine (Tizin® Alergy) eliminates the symptoms of AR (sneezing, itching in the nasal cavity, rhinorrhea), improves nasal breathing, acts pathogenetically and has a high level of safety, its use in this disease is recommended.

Literature

1. Aberg N., Sundell J., Eriksson B., Hesselmar B., Aberg B. Prevalence of allergic disease in schoolchildren in relation to family history, upper respiratory tract infections, and residential characteristics // Allergy. 1996; 51: 232-237.
2. Allergic diseases. Diagnosis and treatment. Pract. hand-ed. R. Petterson. Per. from English M., 2000, p. 733.
3. Geppe N. A., Snegotskaya M. N., Konopelko O. Yu. New in the prevention and treatment of seasonal allergic rhinitis in children // Attending Physician. 2010. No. 1. P. 20-26.
4. Geppe N. A., Ozerskaya I. V., Malyavina U. S. Mucociliary system of the respiratory tract in bronchial asthma and allergic rhinitis // Treating Doctor. 2011. No. 9. pp. 17-20.
5. Geppe N. A., Farber I. M., Starostina L. S. and others. Selection of rational methods of treatment for acute infectious and persistent allergic rhinitis of mild and moderate severity in children // District pediatrician. 2010. No. 4. P. 10-11.
6. Milgrom H., Leung D. Y. M. Allergic rhinitis. In: Kliegman R. M., Stanton B. F., St. Gemell J. W. Schor N. F., Behrman R. E, eds. Nelson Textbook of Pediatrics. 19 th ed. Philadelphia, Pa: Saunders Elsevier; 2011: chapter 137.
7. Belousov Yu. B. Allergy. Mechanisms of development of allergic reactions. 2007
8. Astafieva N. G., Udovichenko E. N., Gamova I. V. and others. Allergic and non-allergic rhinitis: comparative characteristics // Attending Physician. 2013. No. 5.
9. Lopatin A. S., Gushchin I. S., Emelyanov A. V. et al. Clinical recommendations for the diagnosis and treatment of allergic rhinitis // Consilium medicum. 2001; adj.: 33-44.
10. Revyakina V. A. Modern view on the problem of allergic rhinitis in children // Attending Physician. 2001. No. 3. P. 22-27.
11. Drannik G. N. Clinical immunology and allergology. M.: Medical Information Agency, 2003. 604 p.
12. Hampel F. C. Jr., Martin B. G., Dolen J., Travers S., Karcher K., Holton D. Efficacy and safety of levocabastine nasal spray for seasonal allergic rhinitis // Am J Rhinol. 1999, Jan-Feb; 13 (1): 55-62.
13. Lange B., Lukat K. F., Rettig K. et al. Efficacy, cost-effectiveness, and tolerability of mometasonefuroate, levocabastine, and disodium cromoglycate nasal sprays in the treatment of seasonal allergic rhinitis // Ann. Allergy Asthma Immunol. 2005, Sep; 95 (3): 272-282.
14. Knorr B., Matz J., Bernstein J. A. et al. Montelucast for Chronic Asthma in 6 to 14 year old Children. A randomized, double-blind trial // JAMA, 1998, vol. 279, no. 15, p. 1181-1186.
15. Geppe N. A., Kolosova N. G. Directions for non-drug treatment of rhinitis in children // Pediatrics. Supplement to the journal Consilium Medicum. 2012. No. 3. P. 71-74.
16. Bousquet J., Annesi-Maesano I., Carat F. et al. DREAMS Study Group, Characteristics of intermittent and persistent allergic rhinitis // Clin Exp Allergy. 2005; 35: 728-732. Fokkens W. J., Lund V. J., Mullol J. et al. European Position Paper on Rhinosinusitis and Nasal Polyps 2012 // Rhinol.Suppl. 2012. Vol. 23. 3. P. 1-298.
17. Borisova E. O. Antihistamines: stages of development // Pharmaceutical Bulletin. 2005, No. 17, 380.
18. Korsgren M., Andersson M., Borg O. et al. Clinical efficacy and pharmacokinetic profiles of intranasal and oral cetirizine in a repeated allergen challenge model of allergic rhinitis // Ann. Allergy Asthma Immunol. 2007, Apr; 98 (4): 316-321.
19. Okubo K., Uchida E., Nogami S. Levocabastine nasal spray significantly improves perennial allergic rhinitis: a single-blind placebo-controlled study // Auris Nasus Larynx. 2010, Aug; 37 (4): 436-442.
20. Corren J., Rachelefsky G., Spector S., Schanker H., Siegel S., Holton D., Karcher K., Travers S. Onset and duration of action of levocabastine nasal spray in atopic patients under nasal challenge conditions // J Allergy Clin Immunol. 1999, Apr; 103(4):574-580.
21. Bachert C., Wagenmann M., Vossen-Holzenkamp S. Intranasal levocabastine provides fast and effective protection from nasal allergen challenge // Rhinology. 1996, Sep; 34 (3): 140-143.
22. Dahl R., Pedersen B., Larsen B. Intranasal levocabastine for the treatment of seasonal allergic rhinitis: a multicentre, double-blind, placebo-controlled trial // Rhinology. 1995, Sep; 33 (3): 121-125.
23. Schata M., Jorde W., Richarz-Barthauer U. Levocabastine nasal spray better than sodium cromoglycate and placebo in the topical treatment of seasonal allergic rhinitis // J Allergy Clin Immunol. 1991, Apr; 87 (4): 873-878.
24. Drouin M. A., Yang W. H., Horak F. Faster onset of action with topical levocabastine than with oral cetirizine // Mediators Inflamm. 1995; 4(7):S5-S10.
25. Arreguín Osuna L., García Caballero R., Montero Cortés M. T., Ortiz Aldana I. Levocabastine versus cetirizine for perennial allergic rhinitis in children // Rev Alerg Mex. 1998, May-Jun; 45 (3): 7-11.
26. Pacor M. L., Biasi D., Maleknia T., Carletto A., Lunardi C. Efficacy of levocabastine in perennial rhinitis // Clin Ter. 1996, Jun; 147(6):295-298.
27. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA (2)LEN and AllerGen) // Allergy. 2008; 63, Suppl 86: 8-160.
28. Lopatin A. S. Rhinitis: pathogenetic mechanisms and principles of pharmacotherapy. M.: Litterra, 2013. 368 p.

M. N. Snegotskaya 1, Candidate of Medical Sciences
N. A. Geppe,Doctor of Medical Sciences, Professor
I. A. Dronov,Candidate of Medical Sciences
M. D. Shakhnazarova,Candidate of Medical Sciences
M. V. Penkina

Synthetic and natural corticosteroids come to the rescue when other anti-inflammatory drugs are powerless.

Corticosteroids

This is the collective name for a group of steroid hormones. They are produced only by the adrenal glands. These hormones do not have androgenic, estrogenic or progestin activity.

Types

The type of hormone is determined by its primary activity.

Glucocortisoids

They are glucocorticoids. The main hormones of this type that are synthesized in the human body are cortisone and hydrocortisone (aka cortisol).

They affect carbohydrate metabolism in the human body, as well as the metabolism of proteins and fats.

It is synthetic drugs of this type that are used, among other things, for the treatment of ENT diseases.

Mineralocortisoids

They are also mineralocorticoids. The main hormone of this type produced by the adrenal glands is aldosterone. Hormones of this type affect the water-salt balance of the body.

Indications

Among the diseases for which corticosteroids are used:

• Purulent processes in the maxillary sinuses
• Bronchitis
• Bronchial asthma
• Pneumonia
• Long-term spastic conditions of the bronchi
• Fibrosing alveolitis
• Some types of malignant tumors

For information on corticosteroid drugs, watch our video:

Drugs

The European classification distinguishes four groups of synthetic corticosteroids: weak, moderate, strong, very strong. The main properties of such drugs are anti-inflammatory and immunosuppressive. Additional properties include:

• Antiallergic
• Adjusting water-salt balance
• Regulation of calcium metabolism
• Regulation of carbohydrate metabolism
• Regulation of protein metabolism
• Regulating fat metabolism
• Effect on the cardiovascular system
• Effect on blood
• Effect on the hormonal system

There are the following treatment options with these drugs:

• Intensive
• Alternating
• Pulse therapy
• Limiting
• Intermittent

Injections

List of drugs:

The use of intra-articular injections for the treatment of corresponding inflammatory diseases of the musculoskeletal system is popular. Local (intramuscular) injections are also performed in exceptional cases to combat respiratory problems and oncology.

Medicines to treat breathing problems

Intranasal

Most often used for allergic rhinitis and purulent inflammation in the maxillary sinuses.

They quickly make breathing through the nose easier and stop the development of pathogenic microflora on the mucous membranes.

They have one of the most modest negative effects on the body among all dosage forms.

List of drugs:

• Nasonex
• Nasobek
• Flixonase
• Aldecin
• Nazarel
• Rinoclenil
• Tafen nasal
• Beclomethasone
• Avamis
• Fluticasone
• Flunisolide

Nasal corticosteroids

Drops

Drops are used to treat diseases of the nose and eyes, often with allergies or viral, bacterial, fungal, and infectious inflammatory processes. Short courses are used.

Creams, ointments

These drugs are used mainly for dermatological diseases. Most often, these are combination medications - in addition to topical corticosteroids, they contain components with antiseptic, anti-inflammatory and antibiotic effects:

Topical corticosteroids

Inhalations

Inhalations are done for bronchial asthma and prolonged spastic conditions of the bronchi.

List of drugs:

• Budesonide
• Fluticasone propionate
• Triamcinalone
• Flunisolide
• Beclazon Eco
• Beclamethasone dipropionate
• Klenil
• Benacort
• Beclospira
• Budenit Steri-Neb
• Pulmicort Turbuhaler
• Depo-Medrol
• Diprospan
• Tafen Novolizer
• Bekodisk

Inhaled corticosteroid preparations

Medicines come in the forms of ready-made solutions, emulsions and powders. In accordance with the doctor's instructions, prepare the filler for the inhaler and use it according to the prescribed regimen.

This option for the use of corticosteroids is also very safe compared to other

Instructions for use

The instructions depend on the chosen drug and its dosage form. Consult with your doctor and do not neglect the information from the attached instructions when purchasing.

They try to use drugs during the natural activity of the adrenal glands.

It is necessary to competently stop treatment with corticosteroids and consider a withdrawal plan.

Side effects

When using weak and moderate drugs, side effects occur less frequently and are less pronounced. Possible side effects include:

• High blood sugar (even for corticosteroid diabetes)
• Osteoporosis
• Aseptic necrosis of bone tissue
• (exacerbation or occurrence)
• Increased thrombus formation
• Weight gain
• Secondary immunodeficiency (the appearance of infections, often fungal and bacterial)
• Menstrual irregularities in women
• Neurological disorders
• Development or worsening of glaucoma
• Development or worsening of cataracts
• Increased sweating
• Appearance or exacerbation
• Slowing down tissue regeneration processes (for example, long wound healing)
• Increased facial hair growth
• Suppression of adrenal function
• Unstable emotional state
• New or worsening depression
• Itsenko-Cushing syndrome

Side effects from corticosteroid use:

Overdose

Overdose rarely causes life-threatening conditions. Most often, one or another side effects occur.

In case of overdose, the doctor adjusts the dosage or replaces the drug, and symptomatic treatment is carried out taking into account drug interactions.

Special instructions

• Diabetes mellitus
• Liver failure
• Hypothyroidism
• Cirrhosis
• Glaucoma
• Cataract
• Recent vaccination
• , Isoniazid slows down the metabolism of corticosteroids in the liver
• Corticosteroids accelerate the removal from the body of salicylates, Butadione, barbiturates, Digitoxin, Diphenin, Chloramphenicol and Isoniazid
• Concomitant use with isoniazid causes mental disorders
• Concomitant use with reserpine causes depression
• Tricyclic antidepressants with corticosteroids increase intraocular pressure
• With long-term use, corticosteroids increase the effectiveness of adrenergic agonists
• Theophylline enhances the anti-inflammatory effect and promotes the cardiotoxic effect
• Amotericin, diuretics can enhance the diuretic effect, lead to sodium retention or a decrease in potassium in the blood
• Concomitant use of mineralocorticoids and glucocorticoids aggravates hypokalemia and hypernatremia, and hypokalemia increases the side effects and effects of cardiac glycosides
• Decrease in effectiveness
• Reduced antiviral effect of Idoxuridine
• Estrogens enhance the effect of corticosteroids
• Androgens and iron supplements increase the formation of red blood cells, reduce the excretion of hormones, increase side effects, especially increased blood clotting, menstruation disorders, sodium retention
• Requires reduction to
• The initial stage of anesthesia is longer, the total duration is shorter.