Topical glucocorticoid therapy in the treatment of bronchial asthma

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

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

When treating patients with mild persistent bronchial asthma, in the absence of an effect from the episodic use of beta-adrenergic agonists, it is recommended to regularly use glucocorticoid inhalations.

In severe corticosteroid-dependent bronchial asthma, after achieving remission with oral glucocorticoids, it is recommended to switch to inhaled glucocorticoids using high doses.

Taking glucocorticoids by inhalation is the most important step in the treatment of bronchial asthma, since inhaled glucocorticoids have an active local anti-inflammatory effect, while systemic side effects practically do not develop.

The mechanism of anti-inflammatory action of inhaled glucocorticoids:

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

There are two generations of glucocorticoids for inhalation:

• 1st generation drugs: becotide, beclomet, becodisk;
• second generation drugs: budesonide, flunisolide, fluticasone dipropionate.

1st generation inhaled glucocorticoids

Beclomethasone dipropionate (beclomet, becotide) is 9-alpha-chloro-16-beta-methylprednisolone-17,21-dipropionate. The drug is available in the following dosage forms:

• a metered microaerosol containing 50-100 mcg in one dose;
• suspension for use in a nebulizer (50 mcg in 1 ml);
• disc forms (becodisks of 100 and 200 mcg), inhaled using the "Diskhyler" disc inhaler.

Beclomethasone dipropionate is a "prodrug". It is metabolized to the more active metabolite beclomethasone monopropionate in many tissues, including the lungs and liver.

When beclomethasone dipropionate is inhaled, 30% of it enters the lungs and is metabolized there, about 70% is deposited in the oral cavity, pharynx, swallowed and activated in the liver to beclomethasone monopropionate. When using large doses of beclomethasone, systemic side effects are possible.

Becotide (beclomet) in the form of aerosols for inhalation is intended for long-term regular use. The drug is not used to relieve attacks of bronchial asthma, its therapeutic effect is manifested only a few days after the start of treatment. Patients who were previously prescribed systemic corticosteroid therapy should continue it for another week after the start of becotide use, then you can try to gradually reduce its dose.

The usual therapeutic dose of becotide is 400 mcg per day, divided into 2-4 single doses (2-4 inhalations). In severe cases of bronchial asthma, the daily dose can be increased to 1000-1500 mcg and even 2000 mcg. This dose is effective and does not cause systemic side effects, does not suppress the adrenal cortex. If it is necessary to use large doses of becotide, it is advisable to use becotide-250 (1-2 inhalations 2-3 times a day).

The maintenance dose of the drug is 200-400 mcg per day with two-time use (morning and evening). The dose is reduced to the maintenance dose gradually (by 1 inhalation every 3-7 days).

When treating with becotide (beclomet), the drug may settle on the oral mucosa, which contributes to the development of candidiasis and pharyngitis. To prevent oral candidiasis, becotide inhalations are performed using a special spacer dispenser, which is put on the inhaler, as a result of which the drug particles that settle in the oral cavity are retained in the spacer chamber. After inhalation of becotide, it is advisable to rinse your mouth. When using a spacer dispenser, the amount of the drug reaching the lungs increases.

Inhaled becotide can partially replace the dose of glucocorticoids taken orally and reduce corticosteroid dependence (400 mcg becotide is equivalent to 6 mg prednisolone).

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

Beclomethasone dipropionate is available as the drug beclocort in 2 forms: Mite and forte. Beclocort-mite is used in the same doses as becotide. Beclocort-forte, 1 dose of which contains 250 mcg of beclomethasone dipropionate, has a longer effect than beclocort-mite, it should be used 1-2 inhalations 2-3 times a day.

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

Ventide is a combined metered-dose aerosol containing glucocorticoids and beta2-adrenergic agonists (Ventolin). Inhaled 1-2 puffs 3-4 times a day.

2nd generation inhaled glucocorticoids

Second-generation inhaled glucocorticoids have a greater affinity for glucocorticoid receptors in the bronchopulmonary system. These drugs are considered to be more effective than becotide and act longer.

Budesonide (Goracort) - aerosol (200 doses of 160 mcg) - a prolonged-release drug in capsules, acts for about 12 hours, inhaled 2 times at 200 mcg, in severe cases of bronchial asthma the daily dose is increased to 1600 mcg.

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

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

After inhalation of flunisolide, only 39% of the administered dose enters the general bloodstream. At the same time, more than 90% of the drug that has undergone resorption in the lungs is converted in the liver into an almost inactive metabolite - 6β-hydroxyflunisolide. Its activity is 100 times lower than the activity of the original drug.

Unlike beclomethasone dipropionate, flunisolide is initially biologically active, is not metabolized in the lungs, does not have a depressing effect on the hypothalamic-pituitary-adrenal axis at a dose of 2000 mcg per day and has no systemic side effects. The canister with flunisolide is equipped with a specially designed spacer, which facilitates more effective and deep penetration 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 (flixomide) is available as a metered-dose aerosol containing 25, 50, 125 or 250 mcg of the drug per dose. Inhalations are used at 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 mcg 2 times a day. The drug has virtually no systemic side effects and is the most effective and safe inhaled glucocorticoid.

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

When flutacasone is inhaled, 70-80% of the drug is swallowed, but no more than 1% is absorbed. During the first passage through the liver, almost complete biotransformation of the drug occurs with the formation of an inactive metabolite - a derivative of 17-carboxylic acid.

All three drugs (beclomethasone dipropionate, flunisolide, fluticasone propionate) reduce the number of asthma attacks during the day and night, the need for sympathomimetics and the frequency of relapses. However, the above-mentioned positive effects are more pronounced and occur more quickly when using fluticasone, while there is virtually no risk of developing systemic side effects of glucocorticoids.

In mild and moderate forms of bronchial asthma, any inhaled glucocorticoids can be used in doses of 400-800 mcg/day. In more severe cases of the disease, requiring high doses of inhaled glucocorticoids (1500-2000 mcg/day or more), fluticasone propionate should be preferred.

Side effects of inhaled glucocorticoid therapy

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

The absorption of an inhaled glucocorticoid through the bronchopulmonary system depends on the degree of bronchial inflammation, the intensity of glucocorticoid metabolism in the airways, and the amount of drug entering the airways during inhalation.

Systemic side effects occur when using large doses of inhaled glucocorticoids (more than 2000 mcg of becotide per day) and may manifest as the development of Cushing's syndrome, suppression of the pituitary-adrenal system, decreased intensity of bone formation processes, and the development of osteoporosis. Usual therapeutic doses of inhaled glucocorticoids do not cause systemic side effects.

Flunisolide (ingocort) and flucazone dipropionate have very few systemic side effects compared to becotide.

Thus, the use of inhaled forms of glucocorticoids is a modern and active method of treating bronchial asthma, which allows reducing the need for oral glucocorticoids, as well as beta-adrenergic agonists.

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