Bronchospasmolytic drugs used in emergency therapy of bronchial asthma in children

1. Beta-2 adrenergic agonists

1.1 Beta-2 short-acting adrenergic agonists:

Salbutamol 90./44/6

(Ventolin 00238 / 16.01.95, Ventolin Easy breathing, Ventolin nebula P8242-011022. 04/06/99 Ventodisk 007978 / 25.11.96. Salben 95/178/11) Phenoterol (Berotek N 011310 / 01-1999, 08/10/99) Terbutalin (Brikanil 00427 / 26.01.93) Hexoprenaline (Ipradol 002557 / 14.07.92)

1.2 Beta-2 long-acting adrenergic agonists:

Clenbuterol (Spiropent 007200 / 05/28/96) Formoterol (Foradil 003315 / 09/10/93, Oxis 011262 / 07/21/99) Salmeterol (Serevent 006227 / 06/28/95, Salmeter 006936 / 12/21/95) Salbutamol (Volmaks 003100 / 28.06.93 Saltos 94/294/9)

2. Methylxanthines

2.1 Aminophylline (Eufillin 72/631/8. 72/334/32; Aminophylline 002301 / 10.12.91; 002365 / 27.01.92)

2.2 Theophylline (Ventax 006205 / 21.06.95, Spofillin Retard 007135 / 12.03.96; 007136 / 12.03.96, Eufillong 002314 / 09.01.92, Teotard 008019 / 03.02.97, Teopec 88/677/5)

3. M-cholinergic blockers

Ipratropium bromide (Atrovent 00943 / 09.22.93; 007175 / 04.04.96; 007655 / 22.07.96)

4. Combined drugs:

beta-2 adrenergic agonist + ipratropium bromide

fenoterol + ipratropuim bromide (Berodual 01104 / 04.05.95)

beta-2 adrenergic agonist + cromoglicic acid

fenoterol + cromoglycic acid (Ditec 008030 / 02.25.97) salbutamol + cromoglicicic acid (Intal plus 006261 / 11.07.95)

1. Beta-2 adrenergic agonist

1.1. Short-acting beta-2 adrenergic agonist

Salbutamol

(Ventolin, Ventolin nebula, Vetodisk, Ventolin Easy breathing, Salben) Pharmacological action

Salbutamol is a selective agonist of beta-2 adrenergic receptors localized in the bronchi, myometrium, and blood vessels. In therapeutic doses, acting on the beta-2 adrenergic receptors of the smooth muscles of the bronchi, has a pronounced bronchodilator effect and does not significantly affect or even does not affect the beta-1 adrener myocardium

With the inhalation route of administration, it is absorbed by the tissues of the lungs without being metabolized in the lungs into the bloodstream. The drug is metabolized during the “first passage” through the liver, and then excreted mainly in the urine unchanged or in the form of phenolic sulfate

The bronchodilating effect occurs after 4-5 minutes, the maximum effect is up to 40-60 minutes, the elimination half-life is 3-4 hours, the duration of action is 4-5 hours. Composition and form of release 

Salbutamol preparations are available in various forms and with various devices for delivery to the respiratory tract

The ventolin dosing aerosol inhaler contains 100 μg of salbutamol (in the form of salbutamol sulfate) in a single dose. Ventolin is sprayed with tetrafluoroethane (norflurane), which is not a chlorofluorocarbon. 

Ventolin dosing inhaler Easy Respiration is activated by respiration, which facilitates inhalation, does not require synchronization; it contains 100 μg of salbutamol (salbutamol sulfate) in a single dose 

Ventolin Nebula (plastic ampoules), 2.5 ml each , containing 2.5 mg of salbutamol in saline (in the form of salbutamol sulfate) for inhalation through a nebulizer The product does not include preservatives and dyes 

Ventodisk – powder for inhalation of 200 micrograms of salbutamol sulfate in 1 dose complete with a disk inhaler “Ventolin-Diskhaler” 

Salbenum – dry powder for 200 μg needles, injected with an individual cyclohaler inhaler 

Dosage regimen

Ventolin, Ventolin, metered-dose aerosol Easy breathing, Ventodisk, Salben powder, 100-200 mcg (1 or 2 inhalations), 3-4 times a day

Ventolin Nebula must be used under the supervision of specialists using a special inhaler (nebulizer). Ventolin Nebula is intended for undiluted use only for inhalation. annex 2)

Side effects

Salbutamol can cause mild skeletal muscle tremor, which is usually most pronounced in the hands, sometimes excitement and increased motor activity. In some cases, in 16 patients, headache, peripheral vasodilation, and a slight compensatory increase in heart rate are noted. Patients with a predisposition to the development of arrhythmias may have cardiac arrhythmias. Inhaled drugs may cause irritation of the oral mucosa and pharynx

– The use of large doses of salbutamol, as well as other beta-2 agonists, can cause hypokalemia, so if you suspect an overdose, you should monitor the level of potassium in the blood serum

Like other beta-adrenoreceptor agonists, salbutamol can cause reversible metabolic changes, for example, an increase in blood glucose concentration. In patients with diabetes, decompensation may develop and, in some cases, the development of ketoacidosis

Fenoterol hydrobromide (Berotek) Pharmacological action

Fenoterol – short-acting beta-2-adrenostimulator. High bronchodilator effect is associated with selectivity for beta-2-adrenergic receptors, as well as activation of adenylate cyclase, the accumulated cAMP relaxes the smooth muscles of the bronchi; causes stabilization of the membranes of mast cells and basophils (reduces the release of biologically active substances), improves mucociliary clearance; possesses tocolytic effect Composition and form of release 

Berotek N metered-dose inhaler (with freon-free propellant) – in 1 dose 100 μg phenoterol hydrobromide 

Berotek’s solution for nebulizer therapy – in 1 ml of solution contains 1.0 mg of phenoterol hydrobromide 

Dosage regimen

a) An acute attack of bronchial asthma

In most cases, a single inhalation dose is sufficient to relieve symptoms, but if breathing is not relieved within 5 minutes, inhalation can be repeated.

If the effect is absent after two inhalations, and additional inhalations are required, you should immediately seek medical help from the nearest hospital

b) Prevention of asthma physical effort

1-2 inhalation doses at a time, up to 8 doses per day

c) Bronchial asthma and other conditions accompanied by reversible narrowing of the airways

1-2 inhalation doses per dose, if repeated inhalations are required, then no more than 8 inhalations per day

For children, Berotek N dosage aerosol should be prescribed only on the advice of a doctor and under the supervision of adults

A solution for inhalation is prescribed through a nebulizer under strict medical supervision (doses of Berotek for a nebulizer are given in Appendix 2)

Side effect

As a result of an overdose, there may be sensations of a rush of blood to the face, finger tremors, nausea, anxiety, palpitations, dizziness, increased systolic blood pressure, decreased diastolic blood pressure, agitation and possibly extrasystoles

Terbutaline (Brikanil) Pharmacological action

Terbutaline is a short-acting selective beta-2 agonist. Bronchodilator effect due to stimulation of beta-2 adrenergic receptors;

a decrease in the tone of smooth muscle cells and the expansion of the muscles of the bronchi.

Composition and form of release Dosing aerosol inhaler Brikanil – in 1 dose 250 μg terbutaline sulfate Tablets Brikanil – 1 tablet contains: terbutaline sulfate – 2.5 mg   

Dosage regimen

Inhalation using a metered dose inhaler for 1-2 breaths (0.25) every 6 hours. Dose for oral administration 2.5 mg 3-4 times a day.

Hexoprenaline (Ipradol) Pharmacological action

Ipradol is a short-acting selective beta-2 agonist – catecholamine assembled from two noradrenaline molecules linked by a hexamethylene bridge. Common to all these molecules is selective beta-2 receptor affinity.

Composition and form of release:

Ipradol Dosing Aerosol Inhaler – 1 dose 200 mcg hexoprenaline sulfate 

Tablets – 1 TB – 500 mcg hexoprenaline sulfate. 

Dosage regimen

Ipradol in inhalations is prescribed to children older than 3 years of age by 1 breath, with an interval of at least 30 minutes.

Ipradol in tablet form is prescribed for children with mild to moderate asthma, with mild attacks of difficulty breathing in a dose

3-6 months 0.125 mg (1 / 4tb) 1-2 times / day

7-12 months 0.125 mg (1/4 TB) 1-Zraza / day

1-3 years 0.125-0.25 mg (1 / 4-1 / 2 TB) 1-Zraza / day

4-6 years 0.25 mg (1/2 TB) 1-3 times / day  

7-10 years 0,5mg (1tb) 1-Zraza / day Side effect 

Among the side effects in young children, increased excitability, irritability, sleep disturbance, and a change in the rhythm of sleep are rarely observed.

1.2. Long-acting beta-2 agonists

Salmeterol (Serevent, Salmeter) Pharmacological action

Selective agonist of beta-2 adrenergic receptors of prolonged action. The onset of action after 5-10 minutes from the moment of inhalation with a long-lasting up to 12 hours expansion of the bronchi. Salmeterol is rapidly hydroxylated in the liver, the main part of the administered dose is eliminated within 72 hours.

Release form

Serevent Rotadisk – in the form of round blisters (rotadisks) made of foil with 4 cells with powder located around the circumference. In one cell is a dose of 50 μg of salmeterol xinafoate and lactose as a filler. Serevent Rotadisk is used with a special device for inhalation – “Serevent Diskhaler”. The entire dose of the drug enters the respiratory tract even at a very low inspiration rate. 

The Serevent metered dose aerosol inhaler contains 25 μg of salmeterol xinafoate in a single dose. 

Dosage regimen

Assigned to children over 3 years of 25-50 mcg (1-2 breaths) 2 times a day.

Regular (2 times a day) use of Serevent is indicated in cases where the patient needs to use short-acting inhaled bronchospasmolytics more than 1 time per day or in combination with inhaled corticosteroids. Side effect 

Perhaps the development of paradoxical bronchospasm, headache, tachycardia, tremor;

hypokalemia is possible.

Salbutamol prolonged action (Volmax, Saltos) Pharmacological action

The prolonged action of the beta-2-adrenergic agonist is due to the osmotically controlled mechanism of the gradual release of the drug from the tablet core within 9-12 hours.

Release form

Volmax – tablets of 4 mg and 8 mg of salbutamol sulfate. 

Saltos – tablets of 7.23 mg of salbutamol sulfate. 

Dosage regimen

Children aged 3-12 years, 4 mg 2 times a day. Tablets should be swallowed whole, washed down with water, without biting or chewing. Older than 12 years – the dose of necessity may be increased to 8 mg 2 times a day.

Formoterol (Foradil, 0xis) Pharmacological action

Selective beta-2-adrenergic agonist. The onset of bronchospasmolytic action after inhalation after 1-3 minutes, the therapeutic effect persists for 12 hours. The active substance and its metabolites are completely eliminated from the body. The pharmacokinetic characteristics of formoterol for oral and inhalation are largely similar.

Composition and form of release Dosing inhaler Oksis in torbuhaler – 1 dose contains: formoterol fumarate – 4.5-9 mcg. Foradil – powder for inhalation in capsules – 1 capsule contains: formoterol fumarate – 12 mcg   

Dosage regimen Children 5 years of age and older are prescribed 1-2 times a day. 

Clenbuterol (Spiropent) Pharmacological action

Spiropent selective beta-2 agonist. It has a long biological half-life and rapid and complete absorption after oral administration. It has an effect after administration for 10-12 hours. 

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Composition and form of release

Tablets – 1 TB contains 0.02 mg of Clenbuterol Hydrochloride

Syrup – in 5 ml of 0.005 mg of Clenbuterol hydrochloride

Dosage regimen

Tablets are prescribed for children over 12 years of age and adults for 1 TB (0.02 mg 2 times / day. With prolonged therapy, the dose can be reduced to 0.02 mg / day.

For children under 12 years of age, the dose of spiropent is 0.0012 mg / kg body weight.

The syrup syrup is prescribed for children:

6-12 years 15 ml (0.015 mg) 2 times / day.

4-6 years 10 ml (0.01 mg) 2 times / day.

2-4 years 5 ml (0.005 mg) 3 times / day.

younger than 2 years 5 ml (0.005 mg) 2 times / day.

Side effect

Spiropent can cause tremor of the fingers, rarely agitation, tachycardia, extrasystoles.

2. Methylxanthines

2.1 Eufillin, Aminophylline Pharmacological action

Methylxanthines have a pronounced bronchodilator effect, improve diaphragm contraction, increase mucociliary clearance, reduce pulmonary vascular resistance, and have a positive inotropic and moderate diuretic effect. Theophyllines inhibit the release of allergy mediators from mast cells, stimulate the central nervous system, respiratory center, and increase adrenaline secretion by the adrenal glands. The effect of the drugs is due to the inhibition of phosphodiesterase and, as a consequence, an increase in the accumulation of cyclic adenosine monophosphate in the tissues. The clinical effect depends on the concentration of the drug in serum. When taken orally, theophylline is rapidly and completely absorbed, but bioavailability depends on the dosage form of the drug. The main way to eliminate theophylline is its biotransformation in the liver, 10% of the unchanged drug is excreted in the urine.

Release form

Eufillin solution – for intravenous administration – 10 ml 2.4% in ampoule 

Eufillin tablets – 1 tablet contains – 150 mg 

Dosage regimen

The loading dose for intravenous administration is 4.5-5 mg / kg for 20-30 minutes. Subsequently, aminophylline can be administered with continuous infusion at a dose of 0.6-0.8 mg / kg / hour or fractionally at appropriate doses every 4-5 hours under the control of theophylline concentration in the blood.

The daily oral dose is on average 7-10 mg / kg. Side effect 

Anxiety, sleep disturbance, headache, tremor, nausea, vomiting, diarrhea, palpitations, rhythm disturbance.

2.2 Theophylline prolonged action

Theophylline is released from prolonged-release dosage forms in such a way that the concentration is maintained at therapeutic limits (8-15 mg / l) for almost all days with a smooth maximum in the night and early morning hours

Release form Theopec – tablets -1 tablet – 100, 200, 300 mg of theophylline anhydrous Retafil – tablets -1 tablet – 200, 300 mg of theophylline anhydrous Theotard – capsules -1 capsule – 200, 350, 500 mg of theophylline anhydrous Eufilong – capsules – 1 capsule – 250, 375 mg of theophylline anhydrous. Ventax – capsules of 100, 200, 300 mg of theophylline anhydrous theophylline anhydrous Sporophyllin retard – tablets of 100, 250 mg of theophylline anhydrous           

Dosage regimen

The daily dose for children 6-8 years old is 200-400 mg in 1-2 doses, 8-12 years old 400-600 mg, over 12 years old 600-800 mg

Side effect

Palpitations, arrhythmias, anxiety, agitation, tremors, sleep disturbance, headache, nausea, vomiting, diarrhea

3. M-cholinergic blockers

Ipratropium bromide (ATROVENT) Pharmacological action

The active substance is ipratropium bromide – a competitive antagonist of the acetylcholine neuroradiator Atrovent blocks the smooth muscle receptors of the tracheobronchial tree and suppresses reflex bronchoconstriction, prevents acetylcholine-mediated stimulation of sensitive vagus nerve fibers when exposed to various prophylactic bronchitis and causes a decrease in bronchial arteriolitis and

The effect of the drug is manifested 25-50 minutes after inhalation, reaches a maximum by the end of 1 hour and lasts for 6-8 hours

Composition and form of release

Dosing aerosol inhaler, 1 dose – 20 mcg ipratropium bromide 

Inhalation solution 1 ml (20 cap) – 250 mcg ipratropium bromide Dosage regimen  

Dosing aerosol – 1-2 inhalations 3-4 times / day 

A solution for inhalation by nebulization (Appendix 2) Side effects 

Systemic effects are unknown, in some cases, dry mouth may appear, in contact with eyes, slight reversible accommodation disturbances.

4. Combined drugs

Beta-2 adrenergic agonist + ipratopium bromide (BERODUAL) Pharmacological action

Berodual is a combined bronchodilator drug, which includes phenoterol (beta-2 agonist) and ipratropium bromide – a blocker of M-cholinergic receptors. Ipratropium bromide blocks cholinergic receptors, a beta-2 agonist stimulates beta-receptors of smooth muscle cells and rapid bronchodilation. The combination of substances with different mechanisms of action potentiates the bronchodilator effect and increases its duration. Composition and form of release 

Berodual dosage aerosol inhaler – 1 dose contains 50 mcg phenoterol and 20 mcg ipratropium bromide 

Berodual inhalation solution – 20 ml in a nebulizer therapy vial ‘1 ml (20 drops) contains 500 μg of fenoterol and 250 μg of ipratropium bromide Dosage regimen  

Berodual dosing aerosol is prescribed for children over 3 years of age, 1-2 doses 3 times a day (up to 8 doses per day).

Berodual solution for nebulizer (Appendix 2)

Side effect

Side effects are insignificant. In case of relative or absolute overdose, finger tremors, palpitations associated with the presence of phenoterol in the preparation are possible. In some cases, dry mouth, mild and reversible accommodation disturbances associated with the presence of ipratropium bromide in the preparation

Beta-2 adrenergic agonist + cromoglicic acid (Ditec) Pharmacological action

Combined drug with bronchodilator and antiallergic action. Prevents and eliminates bronchospasm, improves the function of the ciliated epithelium, preventing the degranulation of mast cells and the release of biologically active substances from them.

Composition and form of release

Dosing aerosol inhaler – 1 inhalation dose contains phenoterol hydrobromide – 50 μg and disodium cromoglycate – 1 mg

Dosage regimen Children 4-6 years of age at 1 dose 4 times a day. Children over 6 years of age; 2 inhalation doses 4 times a day 

Side effects Finger tremors, palpitations, restlessness possible 

Beta-2 adrenergic agonist + cromoglicic acid (Intal plus) Pharmacological action

Sodium cromoglycate prevents bronchospasm, preventing mast cell degranulation and the release of biologically active substances from them Salbutamol – beta-adrenergic agonist with a primary effect on beta-2 receptors, has a bronchodilating effect

Composition and form of release

Dosing aerosol inhaler – 1 dose contains sodium cromoglycate – 1 mg, salbutamol – 100 mi- Dosing regimen        

Children from 6 years of age 1-2 inhalations 4 times a day. In more severe cases or in contact with an allergen, a dose increase of up to 6-8 inhalations per day is possible.

Side effect

Possible sore throat, cough, bronchospasm, headache, transient muscle cramps, extremely rare angioedema, arterial hypotension, collapse.

event_note May 24, 2020

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