Salbutamol

General characteristics. Structure:

Active ingredient: 0,1 mg of salbutamol (in the form of sulfate) in one dose or 0,024 g in 1 cylinder.

Excipients: oleyl alcohol, ethanol (the alcohol rectified), R 134a propellant (1,1,1,2-tetraftoretan, HFA 134a). Drug does not contain chlorofluorocarbon propellants.

Pharmacological properties:

Pharmacodynamics. Salbutamol is the selection agonist of ß2 adrenoceptors. In therapeutic doses it acts on ß2 adrenoceptors of smooth muscles of bronchial tubes, exerting insignificant impact on myocardium ß1 adrenoceptors. Renders the expressed bronkhodilatiruyushchy effect, warning or stopping a spasm of bronchial tubes, reduces resistance in respiratory tracts. Increases the vital capacity of lungs.

In the recommended therapeutic doses does not exert negative impact on cardiovascular system, does not cause increase in arterial pressure. To a lesser extent, in comparison with medicines of this group, renders positive hrono-and inotropic action. Causes expansion of coronary arteries. Has a number of metabolic effects: reduces potassium concentration in plasma, influences a glycogenolysis and secretion of insulin, renders hyper glycemic (especially at patients with bronchial asthma) and lipolytic effect, increasing risk of development of acidosis.

After use of inhalation forms action develops quickly, the beginning of effect – in 5 min., at most – in 30-90 min. (75% of the maximum effect are reached within 5 min.), duration – 4-6 h.

Pharmacokinetics. Absorption. After inhalation introduction of 10-20% of a dose of salbutamol reach the lower respiratory tracts. Other part of a dose remains in an inhaler or settles on a mucous membrane of a stomatopharynx and then is swallowed. The fraction which settled on a mucous membrane of respiratory tracts is absorbed in pulmonary fabrics and blood, but not metabolized in lungs.

Distribution. Extent of linkng of salbutamol with proteins of plasma makes about 10%.

Metabolism. Salbutamol is metabolized in a liver and excreted preferential with urine in not changed look and in the form of phenolic sulfate. The swallowed part of an inhalation dose is absorbed from digestive tract and is exposed to active metabolism at the first passing through a liver, turning into phenolic sulfate. Not changed salbutamol and a conjugate are excreted preferential with urine.

Removal. Elimination half-life of salbutamol of 4-6 h. It is removed by kidneys partially in not changed look and partially in the form of an inactive metabolite of 4-O-sulfata (phenolic sulfate). An insignificant part is removed with bile (4%), with a stake. The most part of a dose of salbutamol is excreted during 72 h.

Indications to use:

1. Bronchial asthma:
 - stopping of attacks of bronchial asthma, including at an exacerbation of bronchial asthma of a heavy current;
 - prevention of the attacks of a bronchospasm connected with influence of allergen or caused by an exercise stress;
 - use as one of components at a long maintenance therapy of bronchial asthma.

2. The Chronic Obstructive Pulmonary Disease (COPD) which is followed by reversible obstruction of respiratory tracts, chronic bronchitis.

Route of administration and doses:

Salbutamol an aerosol for inhalations dosed 100 mkg / a dose is intended only for inhalation introduction. To resolve an issue of increase in a dose or frequency of use of drug only the doctor can. It is not recommended to use drug more often than 4 times a day. The need for frequent use of the maximum doses of drug or for sudden increase in a dose demonstrates deterioration in a course of a disease.

Adults (including patients of advanced age). A long maintenance therapy at bronchial asthma and HOBL as a part of complex therapy: the recommended dose makes to 200 mkg (2 inhalations) 4 times a day.

Stopping of an attack of a bronchospasm: the recommended dose makes 100-200 mkg (1-2 inhalations).

Prevention of the attacks of a bronchospasm connected with influence of allergen or caused by an exercise stress: the recommended dose makes 200 mkg (2 inhalations) in 10-15 min. prior to influence of a provocative factor.

Children. A long maintenance therapy at bronchial asthma and HOBL as a part of complex therapy: the recommended dose makes to 200 mkg (2 inhalations) 4 times a day.

Stopping of an attack of a bronchospasm: the recommended dose makes 100-200 mkg (1-2 inhalations).

Prevention of the attacks of a bronchospasm connected with influence of allergen or caused by an exercise stress: the recommended dose makes 100-200 mkg (1-2 inhalations) in 10-15 min. prior to influence of a provocative factor.

Rules of use of drug. Preparation for the first use: Before the first use of drug it is necessary to remove a protective cap from a nozzle inhaler. Then vigorously to stir up a cylinder the vertical movements, to turn a cylinder a nozzle inhaler down and to make two sprayings in air to be convinced of adequate operation of the valve. At a break in use of drug for several days it is necessary to make one spraying in air after careful stirring of a cylinder.

Use:
 1. To remove a protective cap from a nozzle inhaler. To be convinced of purity of internal and external surfaces of a nozzle inhaler.
 2. To vigorously stir up a cylinder the vertical movements.
 3. To turn a cylinder a nozzle inhaler down, to hold a cylinder vertically between a thumb both average and index fingers so that the thumb was under a nozzle inhaler.
 4. To make the deepest exhalation, then to place a nozzle inhaler in a mouth between teeth and to capture it lips, without biting at the same time.
 5. Beginning a breath through a mouth, to press an upper part of a cylinder to make delivery of a dose of drug, at the same time to continue to inhale slowly and deeply.   

6. To hold the breath, to take out a nozzle inhaler from a mouth and to remove a finger from an upper part of a cylinder. To continue to hold the breath as far as it is possible.
7. If it is necessary, to execute the following inhalation. For this purpose it is necessary to wait about 30 seconds, holding a cylinder vertically. After that to execute inhalation according to the instructions stated in points 2-6.
To close a nozzle inhaler a protective cap.

IMPORTANT: to perform operations according to points 4, 5 and 6, slowly. Important, just before delivery of a dose to begin to inhale as it is possible more slowly. The first several times it is necessary to use drug after the training in front of the mirror. If on each side a mouth there is "cloudlet", then it is necessary to begin with point 2 again.

Cleaning: the nozzle inhaler should be cleaned at least once a week.
1. To remove a protective cap from a nozzle inhaler, and to remove a nozzle inhaler from a cylinder.
2. To carefully wash out a nozzle inhaler and a protective cap under warm flowing water.
3. To carefully dry up a nozzle inhaler and a protective cap inside and outside.
4. To put on a nozzle inhaler a cylinder and a rod of the valve, to close a free opening of a nozzle inhaler a protective cap. Not to place a cylinder in water!

Features of use:

Pregnant women can appoint salbutamol only in that case when the expected advantage for the patient exceeds potential risk for a fruit. The probability of penetration of salbutamol into breast milk is not excluded therefore are not recommended to appoint it the feeding women unless the expected advantage for the patient exceeds potential risk for the child. There are no data on whether harmful action renders the salbutamol which is present at breast milk on the newborn.

It is necessary to instruct patients about the correct use of the drug Salbutamol. The correct use of drug and accurate implementation of the instruction is necessary to provide hit of salbutamol in bronchial tubes. In an initiation of treatment it is necessary to use drug under observation of medical personnel and after the training in front of the mirror.

As well as at use of other inhalation drugs, the therapeutic effect can decrease when cooling a cylinder. Therefore before use the cylinder with drug has to be heated-up to room temperature (to warm a cylinder hands for several minutes, it is impossible to apply other ways!).

Contents of cylinders are under pressure therefore cylinders cannot be heated, broken, pierced or burned, even when they will be empty.

In case of unpleasant feelings in a mouth and irritations in a throat after inhalation of companies it is necessary to rinse water.

Bronchodilators should not be the only or main component of therapy of bronchial asthma of an unstable or heavy current.

If action of a usual dose of drug becomes less effective or less long (effect of drug has to remain not less than 3 hours), the patient should see a doctor. Increase in a dose or frequency of reception of salbutamol should be carried out only under control of the doctor. Reduction of an interval between reception of the following doses is possible only in exceptional cases and has to be strictly proved. Increase in need for use of inhalation agonists of alfa2-adrenoceptors with a short duration of action for treatment of bronchial asthma testifies to an exacerbation of a disease. In such cases it is necessary to reconsider treatment planning of the patient. Reception of high doses of salbutamol at an exacerbation of bronchial asthma can cause a syndrome of "ricochet" (each following attack becomes more intensively). At a heavy attack of suffocation the break between inhalations has to be not less than 20 minutes.

The risk of complications increases both with the considerable duration of treatment, and at sharp drug withdrawal. Prolonged use of salbutamol has to be followed by use of antiinflammatory drugs for basic therapy.

The sudden and progressing deterioration in bronchial asthma can pose a threat for the patient's life therefore in similar cases it is necessary to resolve urgently an issue of appointment or increase in a dose of glucocorticosteroids. At such patients it is recommended to carry out daily monitoring of a peak expiratory rate.

Salbutamol needs to be applied with care at patients with a thyrotoxicosis.

Therapy by agonists of alfa2-adrenoceptors, especially at their parenteral administration or at use by means of the nebulizer, can lead to a hypopotassemia. Extra care is recommended to be shown at treatment of heavy attacks of bronchial asthma as in these cases the hypopotassemia can amplify as a result of simultaneous use of derivatives of xanthine, glucocorticosteroids, diuretics, and also owing to a hypoxia. In such cases it is necessary to control potassium level in blood serum.

As Salbutamol can cause such side effects as spasms and dizziness, it is recommended to show the increased care at the first receptions or to refuse control of vehicles and occupations other potentially dangerous types of activity.

Side effects:

On frequency side effects can be divided into the following categories: very often (1/10), it is frequent (1/100 and <1/10), infrequently (1/1000 and <1/100), is rare (1/10 000 and <1/100), is very rare (<1/10 000) meeting.

From immune system: seldom – dermatitis, it is very rare – hypersensitivity reactions, including a Quincke's disease, skin rash.

From exchange processes: seldom – a hypopotassemia.

From a nervous system: often – a tremor, a headache, uneasiness; seldom – dizziness, drowsiness, fatigue; very seldom – a hyperactivity.

From cardiovascular system: often – tachycardia, a heart consciousness; seldom – expansion of peripheral vessels with a dermahemia, discomfort or a stethalgia; very seldom – arrhythmia, including fibrillation of auricles, supraventricular tachycardia, premature ventricular contraction, a lowering of arterial pressure and a collapse.

From respiratory system: seldom – cough, irritation of respiratory tracts; very seldom – a bronchospasm (paradoxical or caused by hypersensitivity to drug).

From digestive tract: seldom – dryness and irritation of a mucous membrane of an oral cavity and throat, change of flavoring feelings, nausea, vomiting.

From a musculoskeletal system: seldom – myotonia.

Interaction with other medicines:

It is not recommended to apply at the same time salbutamol and non-selective blockers of ß adrenoceptors, such as propranolol.

Salbutamol is not contraindicated to patients who receive inhibitors of a monoaminooxidase (IMAO).

Strengthens action of stimulators of the central nervous system.

Theophylline and other xanthines at simultaneous use increase probability of development of tachyarrhythmias; means for inhalation anesthesia, a levodopa – heavy ventricular arrhythmias.

Simultaneous use with m-holinoblokatorami (including inhalation) can promote increase in intraocular pressure.

Diuretics and glucocorticosteroids strengthen gipokaliyemichesky effect of salbutamol.

Contraindications:

 - hypersensitivity to any component of drug. 
 - children's age up to 2 years.

With care: in the presence in the anamnesis the tachyarrhythmia, myocarditis, heart diseases, an aortal stenosis, coronary heart disease, heavy chronic heart failure, arterial hypertension, a thyrotoxicosis, a pheochromocytoma, a dekompensirovanny diabetes mellitus, glaucoma, epipripadka, a renal or liver failure, a concomitant use of non-selective ß adrenoblockers, pregnancy, the lactation period is noted.

Overdose:

Symptoms. More frequent – a hypopotassemia, a lowering of arterial pressure, tachycardia, a muscular tremor, nausea, vomiting; less frequent – excitement, a hyperglycemia, a respiratory alkalosis, an anoxemia, a headache; rare – hallucinations, spasms, a tachyarrhythmia, trembling of ventricles, expansion of peripheral vessels.

Treatment. At salbutamol overdose the best antidotes are cardioselective beta adrenoblockers. However blockers of beta adrenoceptors need to be applied with care (risk of development of a bronchospasm).

Use of high doses of salbutamol can cause a hypopotassemia therefore at suspicion on overdose it is necessary to control potassium concentration in blood serum.

Storage conditions:

To store at a temperature not above 25 °C. Not to freeze. To store in the place, unavailable to children!
To store far from heating system and direct sunshine. To protect from falling and blows. A period of validity - 3 years. Not to apply after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Aerosol for inhalations dosed 100 mkg / a dose. On 200 doses (on 12 ml) in cylinders aluminum monoblock with internal protection, pressurized by the dosing valve and supplied with a nozzle inhaler with a protective cap. Each cylinder together with a nozzle and a protective cap, and also the application instruction is placed in a pack.