Clinical and pharmacological group: & nbsp

Beta-adrenomimetics

Included in the formulation
АТХ:

R.03.A.C   Selective beta-2-adrenomimetics

R.03.A.C.12   Salmeterol

Pharmacodynamics:

Stimulate β2-adrenoreceptors, which are found in the membranes of smooth muscle cells of the bronchi, uterus, gastrointestinal tract, detrusor of the bladder, blood vessels (vessels of skeletal muscles, lungs, coronary vessels). In this case, the smooth muscles of the bronchi relax, the tonus and contractile activity of the myometrium, bladder, gallbladder and bile ducts decrease, motor and stomach and intestine tone, blood vessels expand.

Salmeterol is lipophilic, due to which it not only penetrates well into the membranes of smooth muscle cells of the bronchi, but also lingers in the lipid layer of the membranes, creating a distinctive depot in the immediate vicinity of the receptor. This delays the activation of β2-adrenergic receptors (apparently, a small diffusion rate through the lipid layers of the membrane determines the delayed onset of action of the substance on the receptor and is the cause of the slow development of the drug effect). Relaxation of smooth muscles with stimulation of β2-adrenoreceptors, conjugated with Gs-proteins stimulating adenylate cyclase, is associated with an increase in the level of cAMP and activation of cAMP-dependent protein kinase in smooth muscle cells.cAMP-dependent protein kinase A inhibits the kinase of light chains of myosin, as a result, phosphorylation of light chains of myosin is disrupted and its interaction with actin does not occur. cAMP-dependent protein kinase A inhibits phospholampane (an inhibitor of Ca2 + -ATPase), as a result in the smooth muscle cells the activity of Ca2 + -ATPase transporting Ca2 + from the cytoplasm to the sarcoplasmic reticulum increases and the concentration of cytoplasmic Ca2 + decreases. All this leads to a decrease in the tone and contractile activity of smooth muscles. It is possible to increase blood glucose levels, since β2-adrenoreceptors control the glycogenolysis process in the liver and skeletal muscles and insulin secretion in the pancreas, and when stimulated they activate phosphorylase and increase the breakdown of glycogen, resulting in increased blood glucose levels.

The secretion of insulin with stimulation of β2-adrenergic receptors is increasing.

Pharmacokinetics:

With oral intake, 80-85% is absorbed. After inhalation, 10-20% of the dose reaches the lower respiratory tract. The rest of the dose remains in the inhaler, settles on the mucous membrane of the oropharynx and then is swallowed.Fraction, settled on the mucosa of the respiratory tract, is absorbed into the lung tissue and blood, but not metabolized in the lungs.

The degree of binding to plasma proteins is about 10%.

Metabolised in the liver and excreted mainly with urine in unchanged form and in the form of phenolic sulfate. The swallowed portion of the inhalation dose is absorbed from the gastrointestinal tract and is subjected to active metabolism during "first passage" through the liver, turning into phenolic sulfate. The half-life period is more than 5 hours. It is excreted with feces mainly in the form of metabolites.

Indications:

Reversible obstruction of the respiratory tract: bronchial asthma (prevention of bronchospasm, provoked by physical exertion or nighttime asthma attacks), chronic obstructive bronchitis.

X.J40-J47.J43.9   Emphysema (lung) (pulmonary)

X.J40-J47.J43.8   Other emphysema

X.J40-J47.J43.2   Centrilobular emphysema

X.J40-J47.J43.1   Pancreatic emphysema

X.J40-J47.J43   Emphysema

X.J40-J47.J45.9   Asthma, unspecified

X.J40-J47.J45.8   Mixed asthma

X.J40-J47.J45.1   Non-allergic asthma

X.J40-J47.J45.0   Asthma with predominance of an allergic component

X.J40-J47.J45   Asthma

X.J40-J47.J44.9   Chronic obstructive pulmonary disease, unspecified

X.J40-J47.J44.8   Other specified chronic obstructive pulmonary disease

X.J40-J47.J44.1   Chronic obstructive pulmonary disease with exacerbation, unspecified

X.J40-J47.J44   Other chronic obstructive pulmonary disease

Contraindications:

Hypersensitivity, children under 4 years.

Carefully:

Thyrotoxicosis, arrhythmia, ischemic heart disease, uncontrolled arterial hypertension, hypoxia of various genesis, pheochromocytoma, pregnancy, lactation, elderly age (high risk of side effects).

Pregnancy and lactation:

Action category for the fetus by FDA - C.

In studies on Dutch rabbits, the use of salmeterol was associated with fetal development of the cleft of the upper palate, curvature of the limbs, and delayed ossification of the frontal bones. In studies on New Zealand rabbits, the use of salmeterol inside at a dose 1600 times higher than the recommended dose for treating humans (per 1 m2 of body surface area) only delayed the ossification of the frontal bones. The use of salmeterol in rats at a dose 160 times higher than the recommended dose for treating humans (per 1 m2 of body surface area) was not accompanied by a significant adverse effect on the fetus.

There is no information on the penetration into breast milk.It is found in the milk of lactating rats at a concentration comparable to that in blood plasma.

Dosing and Administration:

Bronchial asthma (long-term treatment), COPD: inhalation of 50 μg every 12 hours, if necessary, increase the dose to 100 μg twice a day.

Bronchial asthma of physical stress or impact, allergic bronchospasm: inhalation of 50 μg not less than 30-60 minutes before the expected physical exertion.

Apply no more than 2 times a day with an interval of at least 12-15 hours.

Side effects:

From the side of the cardiovascular system and blood (hematopoiesis, hemostasis): tachycardia, an increase in systolic blood pressure and / or a decrease in diastolic blood pressure; in predisposed patients - a violation of the heart rhythm (ciliary arrhythmia, supraventricular tachycardia, extrasystole).

On the part of the digestive system: diarrhea, abdominal pain, nausea, vomiting, viral gastroenteritis, irritation of the mucous membranes of the mouth or throat.

From the nervous system and sensory organs: headache, dizziness, tremor, nervousness, agitation, insomnia, a change in taste sensations.

On the part of the respiratory system: paradoxical bronchospasm (requires discontinuation), cough.

Other: arthralgia, hypokalemia, allergic reactions; local reactions: rhinitis, laryngitis.

Overdose:

Symptoms: tachycardia and / or arrhythmia, headache, tremor, hypokalemia and hyperglycemia.

Treatment: transition to alternative drugs, the introduction of cardioselective beta-blockers.
Interaction:

MAO inhibitors and tricyclic depressants increase the risk of side effects from the cardiovascular system.

Xanthine derivatives, glucocorticoids and diuretics increase the risk of hypokalemia, especially in patients with severe bronchial asthma, as well as hypoxia (potassium levels in the blood plasma are mandatory).

Compatible (simultaneous inhalation possible) with corticosteroids and / or cromoglycic acid.

Special instructions:

It is not used to stop bronchospasm.

With caution, prescribe the drug to patients with thyrotoxicosis, patients with severe bronchial asthma, with hypoxia of any genesis.

The therapeutic effect may decrease with cooling of the inhaler.

If the recommended dose does not give an effect, it is necessary to increase them.

With regular use in most patients, the need for additional use of short-acting sympathomimetics is usually reduced.

Avoid contact with eyes.

Instructions
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