Systemic glucocorticoid therapy in the treatment of bronchial asthma

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

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

Indications

Systemic glucocorticoid therapy is carried out only according to strict indications:

• very severe course of bronchial asthma with no effect from all other methods of treatment;
• corticosteroid-dependent bronchial asthma (i.e. when the patient has already been treated with glucocorticoids for a long time and it is currently impossible to stop them);
• asthmatic status (glucocorticoids are administered parenterally);
• coma in bronchial asthma (glucocorticoids are administered parenterally);

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The treatment protocol

Systemic glucocorticoid therapy has the following mechanisms of action:

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

After penetrating the cell, glucocorticoids bind to specific cytoplasmic receptors, forming a hormone-receptor complex that interacts with chromatin in the cell nucleus. 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 asthma attacks during exacerbation of bronchial asthma; they act no earlier than 6 hours after their administration.

There are 3 groups of glucocorticoids used:

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

Treatment method according to M.E. Gershwin (1984):

• in case of exacerbation, start with high doses (for example, 40-80 mg of prednisolone daily);
• after symptoms have subsided, slowly reduce the dose (over 5-7 days) to a maintenance dose, 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 first half of the day;
• at the beginning of treatment, divide the daily dose into 2-3 doses;
• if more than 7.5 mg of prednisolone per day is required, try intermittent therapy (eg, 15 mg of prednisolone every other day instead of 7.5 mg daily);
• To reduce the daily oral dose of prednisolone, part of the drug taken orally can be replaced by inhalation of becotide, based on the fact that 6 mg of prednisolone is equal in activity to 400 mg of becotide.

V. I. Trofimov (1996) recommends starting therapy with glucocorticoid tablets with a daily dose of 20-40 mg prednisolone or 16-32 mg methylprednisolone, triamcinolone 2/3 - 3/4 of the daily dose the patient should take in the morning after breakfast, the rest - after lunch (before 15.00) in accordance with the circadian rhythms of glucocorticoid production and sensitivity of tissues and cells of the body to them. After a significant improvement in the patient's condition (absence of asthma attacks for 7-10 days), the dose of glucocorticoids can be reduced by 1/2 tablet every 3 days, and when the dose of 10 mg of prednisolone or an equivalent dose of another drug is reached - by 1/4 tablet 3 days before complete cancellation or maintaining the maintenance dose (usually 1.1/2 tablets). If the patient has been receiving glucocorticoids for a long time (more than 6 months), the dose should be reduced more slowly: by 1/2 - 1/4 tablet over 7-14 days or more.

It is recommended to combine oral administration of glucocorticoids with the use of their inhalation forms, which allows for a significant reduction in the therapeutic and maintenance doses of oral drugs.

If long-term use of glucocorticoids is required to control severe asthma, it is advisable to use an alternating regimen (double the daily dose every other day once a day in the morning), which reduces the risk of adrenal suppression and the development of systemic side effects. The short half-life of oral glucocorticoids of the prednisolone and triamcinolone group allows the use of an alternating regimen. It should be emphasized that an alternating regimen of glucocorticoid administration is usually acceptable when daily administration has already improved the course of asthma and reduced the daily dose of prednisolone to 5-7.5 mg / day; however, if the condition worsens, it is necessary to return to daily administration of the drug. In very severe asthma, an alternating regimen is ineffective; glucocorticoids have to be used 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. Global Strategy" - a short course of treatment with oral glucocorticoids (5-7 days) can be used as "maximum therapy" to achieve control of the course of asthma in a patient. This course can be used either at the beginning of treatment of a patient with uncontrolled asthma or during the 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, glucocorticoids can be discontinued immediately after short courses.

If there are contraindications to taking glucocorticoid drugs orally (erosive gastritis, gastric ulcer and duodenal ulcer), Kenolog-40 (extended-release triamcinolone drug) can be used intramuscularly at a dose of 1-2 ml (40-80 mg) once every 4 weeks.

The number of injections per course of treatment and the intervals between injections are determined individually, however, unfortunately, with prolonged treatment the duration of the effect decreases and more frequent injections become necessary. Some patients suffering from the corticosteroid-dependent variant of bronchial asthma, instead of systematic oral administration of glucocorticoids, use intramuscular administration of kenalog once every 3-4 weeks.

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

In case of glucocorticosteroid-dependent bronchial asthma, it is impossible to completely discontinue glucocorticoids; a daily dose of prednisolone of 5-10 mg is quite effective.

Glucocorticoid treatment of pregnant women with bronchial asthma

Most pulmonologists consider systemic oral glucocorticoid therapy contraindicated in the first trimester of pregnancy due to the high risk of fetal malformations. Inhaled glucocorticoids can be used to treat bronchial asthma (at a dose of no more than 1000 mcg per day) throughout pregnancy, since their systemic side effects are minor, and the risk of fetal death due to hypoxia during asthma attacks is high.

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

Complications

Side effects of systemic glucocorticoid therapy:

• obesity, mainly in the chest, abdomen, cervical spine, the appearance of a moon-shaped, hyperemic face;
• psychosis, emotional lability;
• thinning, dry skin, purple-violet stretch marks;
• acne, hirsutism;
• muscle atrophy;
• osteoporosis, including of the spine (spinal fractures are possible);
• hypersecretion and increased acidity of gastric juice, development of ulcers of the stomach and duodenum;
• hyperglycemia (steroid diabetes mellitus);
• arterial hypertension;
• sodium retention, edema;
• posterior subcapsular cataract;
• activation of the tuberculosis process;
• adrenal suppression.

Abrupt discontinuation of glucocorticoids after prolonged use, especially in high doses, leads to the rapid onset of withdrawal syndrome, which manifests itself as:

• worsening of bronchial asthma, resumption of asthma attacks, possible development of asthmatic status;
• a significant drop in blood pressure;
• sudden weakness;
• nausea, vomiting;
• arthralgia, myalgia;
• abdominal pain;
• headache.

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

• try to use smaller doses of the drug;
• combine treatment with inhalations of Intal;
• prescribe short-acting drugs (prednisolone, urbazone, polcortolone) and do not use long-acting glucocorticoids (kenalog, dexazone, etc.);
• prescribe glucocorticoid in the first half of the day, 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;
• It is advisable to give the maintenance dose of the drug (1.5-2 tablets) intermittently (i.e. take the double maintenance dose once in the morning, but every other day). This method of administration reduces the possibility of adrenal suppression and the development of side effects;
• to reduce corticosteroid dependence at the time of reducing the dose of prednisolone and switching to maintenance doses, take etiol 0.1 g 3 times a day (under the control of blood pressure), glycyrrhiza 0.05 g 2-3 times a day orally. These drugs stimulate the adrenal glands. To reduce corticosteroid dependence, you can also use tincture of Caucasian dioscorea 30 drops 3 times a day;
• use RDT in combination with acupuncture;
• to prevent or reduce side effects of oral glucocorticoid therapy, it is advisable to replace part of the dose with inhaled glucocorticoids;
• use plasmapheresis, hemosorption.

One of the most severe complications of systemic glucocorticoid therapy is osteoporosis. For its prevention and treatment, drugs containing the thyroid gland C-cell hormone calcitonin - calcitrin, miacalcik are used. Calcitrin is prescribed 1 U subcutaneously or intramuscularly daily for a month with breaks every 7th day (a course of 25 injections) or 3 U every other day (a course of 15 injections). Miacalcik (salmon calcitonin) is administered subcutaneously or intramuscularly 50 U (a course of 4 weeks). Miacalcik can also be used as an intranasal spray 50 U every other day for 2 months followed by a two-month break. Treatment with calcitonin preparations should be carried out in combination with oral calcium gluconate at 3-4 g / day. Calcitonin preparations promote the entry of calcium into bone tissue, reduce the symptoms of osteoporosis, have an anti-inflammatory effect, reduce mast cell degranulation and corticosteroid dependence.

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