Membrane stabilizing preparations

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

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

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

Pharmacodynamics

Membrane stabilizing agents include sodium cromoglycate (intal), sodium nedocromil (tileed), ketotifen (zaditen), and calcium antagonists.

Sodium cromoglycate

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

• stabilizes the membrane of mast cells, preventing their degranulation and the release of mediators of inflammation and bronchospasm (gastamina, leukotrienes). This mechanism is due to the suppression of phosphodiesterase activity, which leads to the accumulation of cAMP in the cell. In turn, this facilitates the suppression of the calcium current in the cell or even stimulates its excretion 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 mediators and allergies;
• blocks C1-channels of membranes of mast cells, which inhibits the flow of calcium into the cell, promotes the development of anti-inflammatory effect;
• suppresses the excitation of sensitive endings of the vagus nerve, which prevents the development of bronchoconstriction;
• reduces the increased permeability of the vessels of the mucous membrane and limits access to the allergen and non-specific stimuli to mast cells, nervous and smooth muscle cells of the bronchi.

Medicinal forms of sodium kromoglikata

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

When bronchial asthma sodium cromoglycate is most often used in capsules (1 capsule contains 20 mg of the drug), which are inhaled with a special sphaler inhaler 1-2 capsules 3-4 times a day. The duration of the drug about 5 hours, to enhance the effect is recommended for 5-10 minutes before the application of sodium cromoglicate to make inhalation sympathomimetic short-acting (salbutamol, berotek). The pronounced effect of the drug begins 1 month after the start of the treatment.

Clinical and pharmacological characteristics of intal (sodium cromoglicate):

• is applied prophylactically, and not for relief of an attack of asthma;
• reduces the number of asthma attacks and their equivalents;
• reduces the severity of bronchial hyperreactivity;
• reduces the need for sympathomimetics;
• allows to avoid the appointment of glucocorticoids or reduce the need for them;
• the efficacy does not decrease with prolonged use.

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

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

It is advisable to treat sodium cromoglicate for a long time (3-4 months or more). The best results are observed with seasonal bronchial asthma, but improvement is possible with year-round bronchial asthma.

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

[8], [9], [10], [11], [12]

Ditk

Combined drug in the form of a dosed aerosol, consisting of beta2-adrenostimulator beroteka and intala. It is used both for arresting an attack of asthma, and for preventive treatment of bronchial asthma for the same indications as intal.

With the preventive purpose, the drug is inhaled 4 times a day for 2 doses of aerosol, with the appearance of an attack of suffocation, you can additionally inhale another 1-2 doses.

[13], [14], [15], [16], [17],

Sodium nedokromil (tayled)

The sodium salt of pyranoquinoline dicarboxylic acid, a non-steroidal anti-inflammatory drug, is available in aerosol cans of 56 and 112 doses. 1 dose (1 breath) provides entry into the bronchopulmonary system of 2 mg of the drug. Usually used in a dose of 2 breaths (4 mg) 3-4 times a day, then as the condition improves, you can reduce the intake to 2 times per day.

The mechanism of action of sodium nedocromil (tileeda):

• inhibits the activation and release of mediators from cells involved in the development of inflammation in bronchial asthma (mast cells, eosinophils, neutrophils, macrophages, platelets). For anti-inflammatory activity, nedocromil sodium 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 appointment 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 and physical exertion;
• decrease in the need for glucocorticoids in corticoad-dependent bronchial asthma.

Drug tolerance is good. Possible side effects: a taste disorder, headache, irritation of the upper respiratory tract.

Ketotifen (buried, positane)

Produced in tablets of 0.001 g, affects the pathochemical and pathophysiological phases of the pathogenesis of bronchial asthma.

Mechanism of action:

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

Ketotifen is used to prevent attacks of suffocation. Treatment with ketotifenum reduces the need for beta2-adrenomimetics and theophylline. A full therapeutic effect is observed after 2-3 months from the beginning 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 effective also for extrapulmonary allergic diseases (pollinosis, allergic rhinitis, conjunctivitis, urticaria, Quinck's edema) due to antihistamine effect. Possible side effects: drowsiness, increased appetite, weight gain.

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

Inhalations of furosemide have a therapeutic effect similar to that of intals. Under the influence of furosemide, the intake of sodium and chlorine ions in the bronchial secretion decreases, which changes its ionic composition and osmotic pressure, as a result of which the release of mediators by mast cells is inhibited and the response of sensitive nerve endings of the bronchi decreases.

In addition, furosemide promotes the release of the epithelium of bronchial prostaglandins, which exert a bronchodilator effect.

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

Calcium antagonists

Block potential calcium channels, reduce the intake of Ca ++ in the cytoplasm from the extracellular space and the secretion of inflammatory mediators, allergies and bronchospasm by mast cells. Calcium antagonists have a preventive effect, since they reduce the specific and nonspecific hyperreactivity of the bronchi. In addition, they reduce the need for patients with β2-adrenomimetics and theophylline. Calcium antagonists are most effective in asthma physical effort, they are also shown when combined bronchial asthma with IHD and arterial hypertension.

The most commonly used verapamil (phinoptin, isoptin) to 0.04 g 2-3 times a day, nifedipzh for 0.01-0.02 g 3 times a day.

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

[18], [19]