Local glucocorticoid therapy in the treatment of bronchial asthma

Currently, bronchial asthma is considered as a chronic inflammatory process in the bronchi leading to hyperreactivity and bronchial obstruction. In this regard, the main direction in the treatment of bronchial asthma is anti-inflammatory (basic) therapy. The anti-inflammatory drugs used in the treatment of bronchial asthma include glucocorticoid (inhalation forms) and mast cell stabilizers (intal, lomudal, nedocromil, tileed, ditek).

Anti-inflammatory therapy with inhaled glucocorticoids is recommended as the primary step in the treatment of moderate to severe bronchial asthma with the addition of beta2-adrenomimetics, if necessary.

When treating patients with mild persistant course of bronchial asthma, in the absence of the effect of occasional use of beta-adrenomimetics, it is recommended to regularly use inhalations of glucocorticoids.

In severe cortical dependent bronchial asthma after achieving remission with the help of glucocorticoids taken orally, it is recommended to switch to inhalation of glucocorticoids using large doses.

Admission of glucocorticoids in inhalations is the most important stage of treatment of bronchial asthma, since inhaled glucocorticoids exert an active local anti-inflammatory effect, while systemic side effects practically do not develop.

The mechanism of anti-inflammatory action of inhaled glucocorticoids:

• drugs have a high affinity for the glucocorticoid receptors of cells involved in inflammation and interact with these receptors;
• The complex formed directly affects the transcription of genes through interaction with the DNA molecule. In this case, the function of mRNA responsible for the synthesis of inflammation proteins is suppressed and a new mRNA molecule is formed that is responsible for the synthesis of anti-inflammatory proteins (lipocortin or lipomodulin, neutral peptidase, etc.). The newly synthesized peptides directly inhibit the phospholipase A2, responsible for the production of pro-inflammatory prostaglandins, leukotrienes, platelet aggregation factor.

There are two generations of glucocorticoids in inhalations:

• preparations of the first generation: becotide, beclometh, bacodisc;
• preparations of the second generation: budesonide, flunisolide, fluticasone dipropionate.

Inhalational glucocorticoids of the 1st generation

Beclamethasone dipropionate (beclometh, becotide) is 9-alpha-chloro-1b-beta-methvlenisolone-17,21-dipropionate. The drug is available in the following dosage forms:

• dosed microaerosol containing 50-100 μg in one dose;
• suspension for use in a nebulizer (in 1 ml of 50 μg);
• disk forms (100 and 200 μg bekodiski), inhaled with the help of the Diskhairer disk inhaler.

Beclomethasone dipropionate is a "pro-drug". It is metabolized into a more active metabolite of beclomethasone monopropionate in many tissues, including. In the lungs and liver.

Upon inhalation of beclomethasone dipropionate, 30% of its quantity enters the lungs and is metabolized in them, about 70% is deposited in the mouth, pharynx, swallowed and activated in the liver to beclomethasone monopropionate. When using large doses of beclomethasone, systemic side effects are possible.

Bekotid (beclometh) in the form of aerosols for inhalations is intended for long-term regular use. The drug is not used to stop attacks of bronchial asthma, its therapeutic effect manifests itself only a few days after the start of treatment. Patients who had previously been prescribed systemic corticosteroid therapy should continue it for another 1 week after starting the application of becotide, then you can try to gradually lower its dose.

The usual therapeutic dose of becotide is 400 μg per day, it should be divided into 2-4 single doses (2-4 breaths). With a severe course of bronchial asthma, you can increase the daily dose to 1000-1500 μg and even 2000 μg. This dose is effective and does not cause systemic side effects, does not depress the adrenal cortex. If it is necessary to use large doses of becotide, it is advisable to use the preparation bekotid-250 (1-2 inhalations 2-3 times a day).

The maintenance dose of the drug is 200-400 mcg per day with a double application (morning and evening). The dose reduction to the maintenance dose is gradual (for 1 inhalation every 3-7 days).

When treating bekotidom (beclometh), it is possible to precipitate the drug on the oral mucosa, which contributes to the development of candidomycosis and pharyngitis. For the prevention of oral candidiasis, the inhalation of becotide is carried out using a special dispenser-spacer, which is put on the inhaler, as a result of which the particles of the drug deposited in the oral cavity are retained in the spacer chamber. After inhalation of becotide, it is advisable to rinse the mouth. When using the dispenser-spacer, the amount of the drug reaching the lungs increases.

Becotide inhalations may partially replace the dose of glucocorticoids taken orally, and reduce corticostensity (400 μg of becotide is equivalent to 6 mg of prednisolone).

Bekodisk - in one dose contains 100 and 200 μg of becotide, in the form of a dry substance, it is inhaled at a daily dose of 800-1200 μg (ie 1-2 inhalations 4 times a day) with a special inhaler.

Beclomethasone dipropionate is available in the form of Beclocort preparation in 2 forms: Mite and Forte. Beclocort-mite is used in the same doses as becotide. Beklokort-forte, 1 dose of which contains 250 micrograms of beclomethasone dipropionate, has a longer action than beclocorti mite, it should be applied 1-2 inhalations 2-3 times a day.

Beclomethasone dipropionate is also available as an aldecin preparation. It is indicated for the treatment of patients with bronchial asthma combined with vasomotor allergic rhinitis, polyposis of the nose. The package contains a replaceable nozzle for nasal inhalations of beclomethasone, as well as a nozzle for inhalation through the mouth. Aldecin used for 1 inhalation (50 mcg) in each nasal passage 4 times a day or through oral nozzle inhaled through the mouth (1-2 inhalations 4 times a day).

Ventid is a combined metered aerosol containing glucocorticoids beta2-adrenomimetic (ventolin). Inhaled 1-2 breaths 3-4 times a day.

Inhalational glucocorticoids of the 2nd generation

Inhaled glucocorticoids of the 2nd generation have a greater affinity for glucocorticoid receptors in the bronchopulmonary system. It is believed that the drugs of this generation are more effective than becotide, and last longer.

Budesonide (Gorakort) - aerosol (200 doses of 160 micrograms) is a prolonged-action drug in capsules, it lasts about 12 hours, it is inhaled 2 times in 200 micrograms. In case of severe bronchial asthma, the daily dose rises to 1600 μg.

Flunisolide (inhacort) is available as an aerosol for inhalation.

One dose of aerosol contains 250 μg of flunisolide. The initial dose of the drug is 2 breaths in the morning and in the evening, which corresponds to 1000 μg of flunisolide. If necessary, the dose can be increased to 4 inhalations 2 times a day (2000 μg per day).

After inhalation of flunisolide, only 39% of the administered dose enters the total blood flow. At the same time, more than 90% of the drug that has undergone resorption in the lungs turns into a liver in an almost inactive metabolite - 6β-hydroxyflunisolid. Its activity is 100 times lower than that of the original preparation.

Unlike beclomethasone dipropionate, flunisolide is initially biologically active, does not undergo metabolism in the lungs, at a dose of 2000 mcg per day does not exert a depressing effect on the hypothalamic-pituitary-pituitary-preexisting axis and does not have systemic side effects. The balloon with flunisolide is equipped with a specially developed speyser which contributes to a more effective and deep intake of the drug into the bronchi, reduces its deposition in the oral cavity and, consequently, the frequency of complications from the mouth, pharynx (candidomycosis, hoarseness, bitterness in the mouth, cough) .

Fluticasone propionate (fliksomide) - available in the form of a dosed aerosol with a content of 1 dose of 25, 50, 125 or 250 μg of the drug. Inhalation is used in a dose of 100 to 1000 mcg 2 times a day, depending on the severity of the patient's condition. The maintenance dose is 100-500 μg 2 times a day. The preparation practically does not give systemic side effects, it is the most effective and safe inhalation glycocorticoid.

Fluticasone has high local activity, its affinity for glucocorticoid receptors is 18 times greater than that of dexamethasone and 3 times that of budesonide.

When inhaling flutacazone 70-80% of the drug is swallowed, but it absorbs no more than 1%. At the first passage through the liver, almost complete biotransformation of the drug takes place with the formation of an inactive metabolite, a 17-carboxylic acid derivative.

All three drugs (beclomethasone dipropionate, flunisolide, fluticasone propionate) reduce the number of attacks of bronchial asthma during day and night, the need for sympathomimetics and the frequency of relapses. However, these positive effects are more pronounced and occur faster with the use of fluticasone, and there is practically no danger of developing systemic side effects of glucocorticoids.

With light and moderate forms of bronchial asthma, you can use any inhaled glucocorticoids in doses of 400-800 μg / day. In a more severe course of the disease, requiring the use of high doses of inhaled glucocorticoids (1500-2000 μg / day or more), fluticasone propionate should be preferred.

Side effects of inhaled glucocorticoid therapy

1. Development of pharyngitis, dysphonia due to atrophy of the muscles of the larynx, candidomycosis of the oral mucosa. To prevent this side effect due to the sedimentation of glucocorticoid particles on the oral mucosa during inhalation, rinse your mouth after inhalation and use a spencer.
2. Systemic side effects. The development of systemic side effects is due to the partial absorption of inhaled glucocorticoids by the mucous membrane of the bronchopulmonary system, the gastrointestinal tract (part of the drug is swallowed by the patient) and its entry into the bloodstream.

Absorption of an inhaled glucocorticoid through the bronchopulmonary system depends on the degree of inflammation of the bronchi, the intensity of glucocorticoid metabolism in the respiratory tract and the amount of the drug entering the respiratory tract during inhalation.

Systemic side effects occur with the use of large doses of inhaled glucocorticoids (more than 2000 micrograms of becotide per day) and may manifest as the development of a cushingoid syndrome, oppression of the pituitary-adrenal system, a decrease in the intensity of bone formation processes, and the development of osteoporosis. The usual therapeutic doses of inhaled glucocorticoids do not cause systemic side effects.

Flunisolide (Ingocort) and Flucazone dipropionate very rarely show systemic side effects compared to becotide.

Thus, the use of inhalation forms of glucocorticoids is a modern and active method of treating bronchial asthma, which reduces the need for oral glucocorticoids, as well as beta-adrenomimetics.

It is advisable to combine inhalations of glucocorticoids and bronchodilators according to the scheme: first inhalation of sympathomimetics (beroteka, salbutamol), and after 15-20 minutes - inhalation of glucocorticoid. Combined use of an inhaled glucocorticoid with another inhalation anti-inflammatory drug (intal, tileed) allows many patients to reduce the therapeutic dose of a glucocorticoid drug.