Systemic glucocorticoid therapy in the treatment of bronchial asthma

For treatment of patients with bronchial asthma, the drugs of the prednisolone and triamcinolone group are most suitable.

For very severe bronchial asthma and in the absence of effect from other methods of treatment, it is recommended to use short-acting drugs (prednisone, prednisone, methylprednisolone).

Indications

Systemic glucocorticoid therapy is performed only on strict indications:

• very severe course of bronchial asthma in the absence of effect from all other methods of treatment;
• cortico-dependent bronchial asthma (ie when the patient is already treated for a long time with glucocorticoids and at the moment it is impossible to cancel them);
• asthmatic status (glucocorticoids are used parenterally);
• coma with bronchial asthma (glucocorticoids are used parenterally);

[1], [2], [3], [4], [5], [6], [7], [8]

The treatment protocol

Systemic glucocorticoid therapy has the following mechanisms of action:

• stabilizes mast cells, prevents their degranulation and the release of mediators of allergy and inflammation;
• block the formation of IgE (reactin);
• suppress the late asthmatic reaction, which is caused by the suppression of the cellular inflammatory reaction due to the redistribution of lymphocytes and monocytes, suppression of neutrophils ability to migrate from the vascular bed, redistribution of eosinophils. Late asthmatic reaction begins 3-4 hours after exposure to the allergen, its maximum is observed after 12 hours, lasts more than 12 hours; it reflects the mechanisms of progression of bronchial asthma. The hyperreactivity of the bronchus, which persists for a long time (for weeks and months), is associated with a late asthmatic reaction;
• stabilize the lysosomal membranes and reduce the yield of lysosomal enzymes that damage the bronchopulmonary system;
• suppress the vasodilator action of histamine;
• increase the number and sensitivity of bronchial beta-adrenoreceptors to bronchodilator effects of adrenomimetics;
• reduce edema of the bronchial mucosa;
• increase the activity of endogenous catecholamines;

After penetration into the cell, glucocorticoids bind to specific cytoplasmic receptors, forming a hormone-receptor complex interacting in the nucleus of the cell with chromatin. As a result, the synthesis of proteins mediating the effects of glucocorticoids is activated. The entire process takes about 6 hours, so glucocorticoids do not stop attacks of suffocation in case of exacerbation of bronchial asthma, they function not earlier than 6 hours after their administration.

There are 3 groups of glucocorticoids:

• prednisolone group: prednisolone (tablets of 0.005 g; 1 ml ampoules containing 30 mg of the drug); methylprednisolone (metipred, urbazon - tablets of 0.004 g);
• triamcinolone group: triamcinolone, kenacort, polcortolone, berlicort (0.004 g tablets);
• dexamethasone group: dexamethasone, dexon, dexazone (tablets of 0.0005 g, ampoules for intravenous and intramuscular injection of 1 and 2 ml 0.4% solution with a drug content of 4 and 8 mg respectively).

The method of treatment according to M.E. Gershwin (1984):

• when exacerbation begin with high doses (eg, 40-80 mg prednisolone daily);
• after reducing symptoms - slowly reduce the dose (for 5-7 days) to maintenance, for example, by 50% every day;
• for chronic (long-term) treatment, use a daily dose of prednisolone below 10 mg;
• take the drug in the morning;
• at the beginning of treatment, the daily dose should be divided into two or three doses;
• if more than 7.5 mg of prednisolone is required per day, try an intermittent therapy (eg 15 mg of prednisolone every other day, instead of daily 7.5 mg);
• to reduce the daily oral dose of prednisolone, you can replace part of the ingestion of becotide taken internally, on the basis that 6 mg of prednisolone are equal in activity to 400 mg of becotide.

VI Trofimov (1996) recommends starting therapy with tableted glucocorticides from a daily dose of 20-40 mg of prednisolone or 16-32 mg of metipred, triamcinolone 2/3 - 3/4 of the daily dose of the patient should be taken in the morning after breakfast, the rest after lunch (before 15.00) in accordance with the circadian rhythms of production of glucocorticoids and the sensitivity of tissues and cells of the body to them. After a significant improvement in the patient's condition (absence of attacks of suffocation for 7-10 days), one can reduce the dose of glucocorticoids by 1/2 tablets in 3 days, and when the dose of 10 mg Doug of prednisolone or equivalent dose of another drug is given in 1/4 tablets in 3 days until the maintenance dose is completely eliminated or maintained (usually 1.1 / 2 tablets). If the patient received glucocorticoids for a long time (more than 6 months), the dose should be reduced more slowly: by 1/2 - 1/4 tablets in 7-14 or more days.

It is recommended to combine the intake of glucocorticoids inside with the use of their inhalation forms, which can significantly reduce the therapeutic and maintenance doses of oral medications.

If long-term use of glucocorticoids is necessary for the control of severe asthma, it is advisable to use an alternative regimen (twice daily dose once a day, once a day in the morning), which reduces the risk of suppression of adrenal gland and the development of systemic side effects. A short half-life of the oral glucocorticoids of the prednisolone and triamcinolone group allows the use of an alternating regimen. It should be emphasized that the alternating regimen of glucocorticoid intake is usually acceptable when, with their daily intake, it has already been possible to improve the course of asthma and reduce the daily dose of prednisolone to 5-7.5 mg / day; However, if there is a worsening of the condition, it is necessary to return to the daily intake of the drug. With a very severe course of asthma, the alternating scheme is ineffective, you have to apply glucocorticoids daily and even 2 times a day.

According to the joint report of the National Heart, Lung and Blood Institute (USA) and WHO "Bronchial asthma, the Global Strategy", a short course of oral glucocorticoid therapy (5-7 days) can be used as a "maximum therapy" to achieve control of asthma in a patient. This course can be applied either at the beginning of treatment of a patient with uncontrolled asthma or during a period when the patient notes a gradual deterioration of his condition. Side effects with short courses (less than 10 days), as a rule, are not observed, cancellation of glucocorticoids is possible immediately after short courses.

If there are contraindications to taking glucocorticoid drugs inside (erosive gastritis, peptic ulcer of the stomach and duodenum), you can apply a cenolog-40 (a triamcinolone long-acting drug) intramuscularly at a dose of 1-2 ml (40-80 mg) 1 every 4 weeks.

The number of injections per treatment and the intervals between injections are determined individually, however, unfortunately, with prolonged treatment, the duration of the effect decreases and there is a need for more frequent injections. Some patients suffering from a cortex-dependent variant of bronchial asthma, instead of a regular oral intake of glucocorticoids, use an intramuscular injection of the Kenalog once every 3-4 weeks.

With pronounced exacerbations, severe attacks of bronchial asthma threatening the development of asthmatic conditions, it is often necessary to use large doses of glucocorticoids intravenously at short intervals. It is believed that the optimal concentration of glucocorticoids in plasma is achieved with the administration of hydrocortisone hemisuccinate in a dose of 4-8 mg / kg or prednisolone at a dose of 1-2 mg / kg at intervals of 4-6 hours. More efficient intravenous drip glucocorticoids, which can be 1- 4 times a day, depending on the patient's condition. Usually, the course of treatment with intravenous droplets of glucocorticoids until the optimal effect is 3-7 days, after which glucocorticoids are canceled, gradually reducing the dose by 1/4 of the initial daily dose, adding inhaled glucocorticoids.

With glucocorticoid bronchial asthma, it is impossible to completely abolish glucocorticoids, a daily dose of prednisolone of 5-10 mg is quite active.

Treatment of glucocorticoids in pregnant women suffering from bronchial asthma

Most pulmonologists believe that systemic oral glucocorticoid therapy is contraindicated in the first trimester of pregnancy because of the high risk of fetal malformations. Inhaled glucocorticoids can be used to treat bronchial asthma (at a dose of not more than 1000 micrograms per day) during the entire gestation period, because their systemic side effects are insignificant, and the risk of fetal death due to hypoxia in asthma attacks is great.

Small doses of glucocorticoids, if necessary, can be administered internally in the II-III trimesters in combination with inhaled glucocorticoids. With a severe asthma attack and asthmatic status, intravenous glucocorticoids are indicated.

Complications

Side effects of systemic treatment of glucocorticoids:

• obesity, mainly in the chest, abdomen, cervical spine, the appearance of the moon-like hyperemic face;
• psychoses, emotional lability;
• thinning, dry skin, purple-violet striae;
• acne, hirsutism;
• amyotrophy;
• osteoporosis, incl. Spine (spine fractures are possible);
• hypersecretion and increased acidity of gastric juice, development of gastric and duodenal ulcers;
• hyperglycemia (steroid diabetes mellitus);
• arterial hypertension;
• sodium retention, edema;
• posterior subcapsular cataract;
• activation of the tuberculosis process;
• oppression of adrenal function.

Sudden abolition of glucocorticoids after prolonged use, especially in large doses, leads to a rapid appearance of withdrawal syndrome, which manifests itself:

• deterioration of the course of bronchial asthma, resumption of asthma attacks, possible development of asthmatic status;
• a significant drop in blood pressure;
• severe weakness;
• nausea, vomiting;
• arthralgia, malliglia;
• abdominal pain;
• a headache.

To reduce the development of side effects of glucocorticoid therapy and to reduce corticosity, it is recommended:

• try to manage smaller doses of the drug;
• Combine treatment with inhalation intala;
• prescribe short-acting drugs (prednisolone, urbazone, polcortolone) and do not use long-acting glucocorticoids (kenalog, dexazone, etc.);
• appoint a glucocorticoid in the morning, give the largest part of the daily dose in the morning, so that the concentration of the drug in the blood coincides with the greatest release of endogenous cortisol;
• maintaining the dose of the drug (1.5-2 tablets), it is advisable to give in an intermittent way (that is, twice the supporting dose taken once in the morning, but every other day). With such a reception, the possibility of suppressing the adrenal gland and the development of side effects decreases;
• to reduce corticosity at the time of reducing the dose of prednisolone and switching to maintenance doses take etiol by 0.1 g 3 times a day (under the control of blood pressure), glitsirram at 0.05 g 2-3 times a day inside. These drugs stimulate the adrenal glands. To reduce cortico-dependence, you can also use tincture of Caucasian dioscorea for 30 drops 3 times a day;
• apply RDT with a combination with acupuncture;
• to prevent or reduce side effects of oral glucocorticoid therapy, it is advisable to replace a portion of the dose with inhaled glucocorticoids;
• apply plasmapheresis, hemosorption.

One of the most serious complications of systemic glucocorticoid therapy is osteoporosis. For its prevention and treatment, drugs containing the hormone C-cells of the thyroid gland calcitonin-calcitrine, miakaltsik are used. Calcitrine is administered at 1 ED either subcutaneously or intramuscularly daily for a month, with interruptions every 7th day (course of 25 injections) or 3 ED every other day (course of 15 injections). Miakaltsik (calcitonin salmon) is administered subcutaneously or intramuscularly at 50 units (course 4 weeks). You can also use myacaltic in the form of an intranasal spray of 50 units a day for 2 months, followed by a two-month break. Treatment with calcitonin should be done in combination with calcium intake of gluconate by the interior of 3-4 g / day. Calcitonin preparations contribute to the intake of calcium in bone tissue, reduce the phenomenon of osteoporosis, have an anti-inflammatory effect, reduce degranulation of mast cells and corticostependence.

[9], [10], [11], [12], [13], [14]