Membrane-stabilizing drugs

In order to influence the pathochemical phase of inflammation of bronchial asthma, the following agents are used:

• membrane stabilizing drugs that prevent mast cell degranulation;
• drugs that block the action of mediators of allergy, inflammation and bronchospasm;
• antioxidants.

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Pharmacodynamics

Membrane stabilizing agents include sodium cromoglycate (Intal), sodium nedocromil (Tyled), ketotifen (Zaditen), and calcium antagonists.

Sodium cromoglycate

Sodium cromoglycate (Intal) is a non-steroidal anti-inflammatory drug, available in the following dosage forms. Mechanism of action of sodium cromoglycate (Intal):

• stabilizes the membrane of mast cells, preventing their degranulation and release of inflammatory and bronchospasm mediators (gastamin, leukotrienes). This mechanism is due to the suppression of phosphodiesterase activity, which leads to the accumulation of cAMP in the cell. In turn, this helps to suppress the flow of calcium into the cell or even stimulates its removal and reduces the functional activity of mast cells;
• stabilizes the membrane of other target cells (eosinophils, macrophages, platelets), inhibits their activity and the release of inflammatory and allergy mediators;
• blocks C1 channels of mast cell membranes, which inhibits the flow of calcium into the cell and promotes the development of an anti-inflammatory effect;
• suppresses excitation of the sensory endings of the vagus nerve, which prevents the development of bronchoconstriction;
• reduces increased permeability of the mucous membrane vessels and limits the access of allergens and non-specific stimuli to mast cells, nerve and smooth muscle cells of the bronchi.

Sodium cromoglycate dosage forms

Dosage form	Compound	Indications for use	Dose
Intal in capsules for spinhaler	One capsule contains 20 mg sodium cromoglycate and 20 mg lactose	As a means of basic therapy and for the prevention of bronchospasm after physical exertion and contact with an allergen	1-2 capsules 3-4 times a day in the form of inhalations using a spinhaper
Intal metered dose inhaler	1 dose of the drug contains 1 mg of sodium cromoglycate	The same	1-2 breaths 3-4 times a day
Intal solution for nebulizer	1 ampoule contains 20 mg sodium cromoglycate in 2 ml isotonic sodium chloride solution	The same	1-2 inhalations 3-4 times a day
Naealcrom	1 ml contains 40 mg sodium cromoglycate	Prevention and treatment of seasonal and year-round rhinitis	1 inhalation in each nasal passage 5-6 times a day
Opticrom	1 ml of solution contains 40 mg of sodium cromoglycate	Treatment of allergic keratitis and conjunctivitis	1-2 drops in each eye 4-6 times a day

In bronchial asthma, sodium cromoglycate is most often used in capsules (1 capsule contains 20 mg of the drug), which are inhaled using a special inhaler, spinhaler, 1-2 capsules 3-4 times a day. The duration of action of the drug is about 5 hours, to enhance the effect, it is recommended to inhale a short-acting sympathomimetic (salbutamol, berotek) 5-10 minutes before using sodium cromoglycate. The pronounced effect of the drug begins 1 month after the start of administration.

Clinical and pharmacological characteristics of Intal (sodium cromoglycate):

• used prophylactically, not to relieve an asthma attack;
• reduces the number of asthma attacks and their equivalents;
• reduces the severity of bronchial hyperreactivity;
• reduces the need for sympathomimetics;
• allows to avoid the prescription of glucocorticoids or reduce the need for them;
• the effectiveness does not decrease with prolonged use.

After inhalation of Intal, about 90% of the drug settles in the trachea and large bronchi, only 5-10% reaches the small bronchi. Indications for the use of sodium cromoglycate:

• as a basic anti-inflammatory agent preventing bronchospasm in patients with any form of bronchial asthma. The greatest effectiveness is noted in the atonic form of bronchial asthma and asthma of physical effort in young and middle-aged patients;
• to reduce the need for glucocorticoids in corticosteroid-dependent bronchial asthma.

Treatment with sodium cromoglycate is advisable to be carried out for a long time (3-4 months or more). The best results are observed in seasonal bronchial asthma, but improvement is also possible in year-round bronchial asthma.

The drug is well tolerated, but in some cases minor side effects are possible (irritation of the respiratory tract, cough, sore throat, pain behind the breastbone). Intal does not have a toxic effect on the fetus and can be used in the II-III trimesters of pregnancy.

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Ditek

A combination drug in the form of a metered aerosol, consisting of the beta2-adrenergic stimulant berotek and intal. It is used both to stop an asthma attack and for the preventive treatment of bronchial asthma for the same indications as intal.

For preventive purposes, the drug is inhaled 4 times a day, 2 doses of aerosol; if an attack of suffocation occurs, an additional 1-2 doses can be inhaled.

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Sodium nedocromil (Tiled)

Sodium salt of pyranoquinoline dicarboxylic acid, is a non-steroidal anti-inflammatory drug, available in aerosol cans of 56 and 112 doses. 1 dose (1 inhalation) provides 2 mg of the drug to the bronchopulmonary system. Usually used in a dose of 2 inhalations (4 mg) 3-4 times a day, later, as the condition improves, the intake can be reduced to 2 times a day.

Mechanism of action of sodium nedocromil (Tyled):

• suppresses activation and release of mediators from cells involved in the development of inflammation in bronchial asthma (mast cells, eosinophils, neutrophils, macrophages, platelets). In terms of anti-inflammatory activity, sodium nedocromil is 4-10 times more effective than intal;
• inhibits the release of chemotactic factors from the bronchial epithelium; suppresses the chemotaxis of alveolar macrophages and eosinophils responsible for inflammatory reactions of allergic genesis;
• inhibits the release of neuropeptides from the endings of nerve fibers that cause bronchospastic reactions, thereby preventing the development of bronchospasm.

Indications for the use of nedocromil sodium are:

• prevention of all types of bronchial asthma. It is effective in the treatment of allergic and non-allergic bronchial asthma in patients of different ages, prevents the development of early and late asthmatic reactions to allergens, as well as bronchospasm caused by cold, physical exertion;
• reducing the need for glucocorticoids in corticosteroid-dependent bronchial asthma.

The drug is well tolerated. Possible side effects: taste disturbance, headache, irritation of the upper respiratory tract.

Ketotifen (zaditen, positan)

It is produced in tablets of 0.001 g and has an effect on the pathochemical and pathophysiological phases of the pathogenesis of bronchial asthma.

Mechanism of action:

• decreased secretion of mediators by mast cells and basophils under the influence of allergens (due to inhibition of phosphodiesterase with subsequent accumulation of cAMP and inhibition of Ca++ transport);
• blockade of H1-histamine receptors;
• inhibition of the action of leukotrienes and platelet activating factor on the respiratory tract;
• inhibition of the activity of allergy target cells (eosinophils and platelets).

Ketotifen is used to prevent asthma attacks. Treatment with ketotifen reduces the need for beta2-adrenomimetics and theophylline. The full therapeutic effect is observed 2-3 months after the start of treatment. The drug can be used continuously for 3-6 months. The usual dosage of ketotifen is 1 mg 2 times a day. It is also effective in extrapulmonary allergic diseases (hay fever, allergic rhinitis, conjunctivitis, urticaria, Quincke's edema) due to the antihistamine effect. Possible side effects: drowsiness, increased appetite, weight gain.

In recent years, the combined use of ketotifen and Intal has been proposed.

Furosemide inhalations have a therapeutic effect similar to that of Intal. Under the influence of furosemide, the entry of sodium and chlorine ions into bronchial secretions decreases, which changes its ionic composition and osmotic pressure, resulting in inhibition of the release of mediators by mast cells and a decrease in the reaction of sensitive nerve endings of the bronchi.

In addition, furosemide promotes the release of prostaglandins from the bronchial epithelium, which have a bronchodilatory effect.

When taken orally, furosemide does not affect bronchial reactivity. However, the question of using furosemide inhalations for the treatment of bronchial asthma has not been finally resolved.

Calcium antagonists

They block potential-dependent calcium channels, reduce the flow of Ca++ into the cytoplasm from the extracellular space and the secretion of inflammation, allergy and bronchospasm mediators by mast cells. Calcium antagonists have a preventive effect, as they reduce specific and non-specific bronchial hyperreactivity. In addition, they reduce the need for patients in β2-adrenomimetics and theophylline. Calcium antagonists are most effective in exercise-induced asthma, they are also indicated in combination of bronchial asthma with ischemic heart disease and arterial hypertension.

The most commonly used are verapamil (finoptin, isoptin) 0.04 g 2-3 times a day, nifedipine 0.01-0.02 g 3 times a day.

As a calcium antagonist, a 6% solution of magnesium sulfate can be used in the form of inhalations (1 inhalation per day or every other day, the course of treatment is 10-14 inhalations).

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