Combined drug Ascoril in the treatment of cough and bronchial obstruction

Ascoril

Release form

Pills. White, round, flat tablets with a bevel and a one-sided score.

Compound

Active ingredients : bromhexine hydrochloride (8 mg); guaifenesin (100 mg); salbutamol sulfate (equivalent to salbutamol, 2 mg).

Excipients : calcium hydrogen phosphate; corn starch; methyl parahydroxybenzoate (methylparaben); propyl parahydroxybenzoate (propylparaben); purified talc; colloidal silicon dioxide; magnesium stearate.

Pharmacological group

A drug with mucolytic, expectorant and bronchodilator effects, a combined expectorant

Action

Mucolytic, expectorant, bronchodilator.

Bromhexine is a mucolytic agent that has an expectorant effect. Increases the serous component of bronchial secretions; activates the cilia of the ciliated epithelium, reduces the viscosity of sputum, increases its volume and improves discharge.

Bromhexine - description of the substance

Guaifenesin is a mucolytic agent that reduces the surface tension of the structures of the bronchopulmonary apparatus; stimulates secretory cells of the bronchial mucosa that produce neutral polysaccharides, depolymerizes acidic mucopolysaccharides, reduces the viscosity of sputum, activates the ciliary apparatus of the bronchi, facilitates the removal of sputum and promotes the transition of an unproductive cough to a productive one.

Salbutamol is a bronchodilator that stimulates beta2-adrenergic receptors of the bronchi, blood vessels and myometrium. Prevents or eliminates bronchospasm, reduces resistance in the respiratory tract, increases the vital capacity of the lungs. Causes expansion of the coronary arteries, does not reduce blood pressure.

Indications

As part of combination therapy for acute and chronic bronchopulmonary diseases, accompanied by the formation of a difficult to separate viscous secretion:

• bronchial asthma;
• tracheobronchitis;
• obstructive bronchitis;
• pneumonia;
• emphysema;
• whooping cough;
• pneumoconiosis;
• pulmonary tuberculosis.

Contraindications and restrictions

• Hypersensitivity to the components of the drug;
• tachyarrhythmia, myocarditis;
• heart defects;
• decompensated diabetes mellitus;
• thyrotoxicosis;
• glaucoma;
• liver or kidney failure;
• peptic ulcer of the stomach and duodenum in the acute stage;
• stomach bleeding;
• arterial hypertension;
• pregnancy;
• lactation period;
• children under 6 years of age.

with caution to patients with diabetes mellitus, gastric and duodenal ulcers in remission.

during pregnancy . If treatment with the drug is necessary during lactation, breastfeeding should be discontinued.

Application and dosage

Inside, 3 times a day.

• Adults and children over 12 years old - 1 tablet each;
• children from 6 to 12 years old - 1/2 or 1 tablet;
• Children under 6 years of age are recommended to use Ascoril Expectorant syrup.

Side effect

From the immune system: rarely - hypersensitivity reactions; frequency unknown - anaphylactic reactions, including anaphylactic shock, angioedema and itching.

From the side of the central nervous system: rarely - headache, dizziness, increased nervous excitability, sleep disturbance, drowsiness, tremor, convulsions.

From the cardiovascular system: rarely - rapid heartbeat, collapse.

From the respiratory system, chest and mediastinal organs: rarely - bronchospasm.

From the gastrointestinal tract: rarely - nausea, vomiting, diarrhea, exacerbation of gastric and duodenal ulcers.

From the kidneys and urinary system: rarely - urine may turn pink.

From the skin and subcutaneous tissues: rarely - rash, urticaria; frequency unknown - severe skin adverse reactions (including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis and acute generalized exanthematous pustulosis associated with the use of ambroxol (ambroxol is a metabolite of bromhexine).

Overdose

Symptoms: increased side effects. Treatment: symptomatic therapy.

special instructions

There have been reports of severe skin reactions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis and acute generalized exanthematous pustulosis associated with the use of ambroxol. Since ambroxol is a metabolite of bromhexine, the risk of anaphylactic and severe skin reactions may also be considered for bromhexine.

If symptoms of a progressive skin reaction occur (sometimes associated with damage to the mucous membranes of the mouth, throat, nose, eyes, genitals), you should immediately stop using the drug Ascoril and consult a doctor.

Guaifenesin turns urine pink.

Drug interactions

• It is not recommended to take alkaline drinks at the same time as the drug.
• Other beta2-adrenergic agonists and theophylline enhance the effect of salbutamol and increase the likelihood of side effects.
• Ascoril is not prescribed simultaneously with drugs containing codeine and other antitussives, because this makes it difficult to clear liquefied sputum.
• Bromhexine, which is part of the drug Ascoril, promotes the penetration of antibiotics (erythromycin, cephalexin, oxytetracycline) into the lung tissue.
• It is not recommended to use Ascoril simultaneously with non-selective beta-adrenergic blockers, such as propranolol.
• Salbutamol, which is part of the drug Ascoril, is not recommended for patients receiving MAO inhibitors.
• Diuretics and corticosteroids enhance the hypokalemic effect of salbutamol.

Storage

Store out of the reach of children at room temperature no higher than 25°C. Shelf life: 2 years.

Production

Glenmark Pharmaceuticals Ltd (India)

Package

10 pieces. in cellular contour packaging. 1, 2 or 5 packages in a cardboard box.

Recipe

Available without a prescription.

Combined drug Ascoril in the treatment of cough and bronchial obstruction

• bronchodilator (by acting on β2 receptors of bronchial smooth muscle); • antiallergic (suppresses the release of histamine induced by exposure to an allergen, since it stabilizes mast cell membranes to some extent); • affects the function of the bronchial epithelium and improves mucociliary clearance (activates the function of the ciliated epithelium, increasing the movement of cilia, which improves mucociliary transport); • reduces the synthesis of leukotrienes; • reduces capillary permeability. The effect of β2-agonists on mucociliary clearance should be especially emphasized: stimulation of β2-receptors present in mucosecreting cells occurs, which leads to an increase in bronchial secretion and improved evacuation. So, salbutamol relaxes the smooth muscles of the bronchi and blood vessels, prevents the development of bronchospasm caused by the effects of histamine, methacholine, cold air and allergens. The drug also inhibits the release of inflammatory mediators from mast cells. In addition, salbutamol enhances mucociliary transport. An equally important component of the drug Ascoril is bromhexine hydrochloride, a mucolytic agent that has an expectorant and antitussive effect. Bromhexine with its active metabolite ambroxol is a mucolytic drug in its pharmacological action. Its mucolytic effect is associated with the depolymerization of mucoprotein and mucopolysaccharide fibers. By increasing the serous component of bronchial secretions, the drug activates the cilia of the ciliated epithelium, reduces the viscosity of sputum, increases its volume and improves discharge. By stimulating the serous cells of the glands of the bronchial mucosa, bromhexine normalizes the ratio of the serous and mucous components of sputum, stimulates the production of enzymes that break down the bonds between mucopolysaccharides of sputum, the formation of surfactant, which also normalizes the rheological parameters of sputum, reducing its viscosity and adhesive properties. Ambroxol (the main metabolite of bromhexine) directly stimulates the movement of cilia and prevents their adhesion, promoting the evacuation of sputum. Bromhexine also has a slight antitussive effect, which is of great importance in the treatment of a number of pathologies where it is undesirable to stimulate the cough reflex. The unique properties of bromhexine are stimulation of the synthesis of endogenous surfactant and improvement of the penetration of the antibiotic into the lung tissue. Such unique qualities of bromhexine often make it the drug of choice for the treatment of pneumonia and brochiectasis. The third active component of Ascoril is guaifenesin, a unique substance that combines mucolytic and reflex effects. It irritates the stomach receptors and thereby stimulates the gastropulmonary reflex, thereby increasing the secretion of the bronchial glands and the activity of the cilia of the ciliated epithelium. Another property of guaifenesin is its ability to reduce the surface tension of the structures of the bronchopulmonary apparatus and stimulate secretory cells of the bronchial mucosa that produce neutral polysaccharides. Guaifenesin depolymerizes acidic mucopolysaccharides, reducing the viscosity of sputum. This multicomponent mechanism of action of guaifenesin facilitates the removal of sputum and promotes the transition of a nonproductive cough to a productive one. So, guaifenesin stimulates the secretion of the liquid part of bronchial mucus, reduces the surface tension and adhesive properties of sputum. An important additional effect of guaifenesin is its mild sedative effect. Guaifenesin reduces anxiety and psychogenic autonomic symptoms. The fourth component of Ascoril syrup is racementol (menthol), a local irritant that gently stimulates the secretion of the bronchial glands, has antiseptic properties, and restores the function of the ciliated epithelium of the bronchial mucosa. It has a coronary dilating, reflex, venotonic, antianginal, analgesic and anti-inflammatory local effect. The effect is mainly due to reflex reactions associated with irritation of sensitive receptors of the mucous membranes, and stimulation of the formation and release of endogenous biologically active substances (enkephalins, endorphins, peptides, kinins) involved in the regulation of pain, vascular permeability and other processes, which provides pain relief and distracting action. Antimicrobial activity is manifested by indiscriminate damage to microbial cells. The irritating (distracting) effect helps reduce pain. Thus, Ascoril is a drug containing a unique combination of substances that simultaneously have a bronchodilator, expectorant and mucolytic effect. Let's consider the area of ​​clinical application of the drug Ascoril. It is most often used for acute and chronic lung diseases accompanied by broncho-obstructive syndrome (BOS). The main manifestations of BOS are shortness of breath, suffocation, a feeling of chest congestion and cough. Differential diagnosis of BOS is a complex medical task. The most common manifestations of biofeedback occur in asthma, COPD and CB. But it should be noted that BOS is often observed in ARVI, acute bronchitis, pneumonia, tuberculosis, post-tuberculosis pneumosclerosis and other acute diseases of the respiratory system. BOS is based on various pathogenetic mechanisms, which can be divided into reversible (inflammation, edema, bronchospasm, mucociliary insufficiency, hypersecretion of viscous mucus) and irreversible (expiratory collapse of small bronchi - “air trap” in pulmonary emphysema, COPD, bronchiolitis), congenital or acquired tracheobronchial pathology (dyskinesia of the membranous part of the trachea and main bronchi), bronchial remodeling, etc. Manifestations of both acute and chronic biofeedback are the same, they intensify with physical activity. The need to prescribe bronchodilators arises in patients suffering from acute and chronic respiratory diseases accompanied by biofeedback. Ascoril for biofeedback in children Most often, bronchial obstruction occurs during acute respiratory viral infections (ARVI). Age-related characteristics play a certain role (in children of the first three years of life): • narrowness of the bronchi and the entire respiratory apparatus, which significantly increases aerodynamic resistance (according to Poiseuille’s rule, the resistance of the airways is inversely proportional to their radius to the 4th power); • pliability of bronchial tract cartilage; • insufficient rigidity of the bone structure of the chest, which freely reacts by retracting compliant places to increase resistance in the airways; • features of the position and structure of the diaphragm; • features of the bronchial wall: a large number of goblet cells that secrete mucus; • rapid reaction of the mucous membrane of the trachea and bronchi - swelling and hypersecretion of mucus in response to the development of a viral infection; • increased viscosity of bronchial secretions associated with high levels of sialic acid; • imperfection of immunological mechanisms: the formation of interferon in the upper respiratory tract, serum immunoglobulin A, secretory immunoglobulin A, and the functional activity of the T-immune system are significantly reduced. Functional disorders of the respiratory system in a small child are also influenced by factors such as longer sleep, frequent crying, and a predominant position lying on the back in the first months of life. In addition, the occurrence of obstruction in childhood can be caused by: • maternal smoking, which has a direct effect on the caliber of the airways developing in the fetus, which affects the lungs (especially by reducing the development of alveoli) in the postnatal period. Maternal smoking leads to a decrease in IL-4 and INF-γ in cord blood and increases the sensitivity of cord blood mononuclear cells to house dust. Other studies of cord blood cells show that maternal smoking leads to an increase in IL-13 and a decrease in the INF-γ mRNA response after stimulation, as well as TNF-α production; • Maternal atopy is also associated with decreased pulmonary function in the newborn, although the exact mechanism is not yet known. Epidemiological studies show that maternal smoking and atopy are also associated with subsequent bronchiolitis in children in the first year of life. Cord blood IL-12 and sCD30 are lower in children who develop bronchiolitis, which may be due to bronchial obstruction preceding bronchiolitis. Thus, maternal smoking has a major impact on the immune response in newborns and on the anatomical features of their lungs. • Infants of mothers with preeclampsia and hypertension and diabetes are at increased risk of transient early obstruction, persistent obstruction, and later obstruction. • Prescription of antibiotics during labor is associated with both early transient obstruction and persistent obstruction. • Respiratory viral infections in early life may be a significantly more important risk factor for bronchial obstruction than atopy. • Severe adenovirus infection can lead to long-term bronchial obstruction in a previously healthy child. Respiratory viruses damage the ciliated epithelium of the mucous membrane of the respiratory tract, increase its permeability to allergens, toxic substances and the sensitivity of the receptors of the submucosal layer of the bronchi, which causes an increase in bronchial hyperreactivity and the occurrence of obstructive manifestations in children. The bronchial epithelium can respond to signals from immune cells that are involved in the initiation and maturation of the innate and adaptive immune response, including structural changes in the airways and angiogenesis. Taking into account the variety of clinical symptoms and their severity, when treating children with ARVI accompanied by biofeedback, it is necessary to influence various components of the pathological process. Modern trends include the use of combined drugs with multidirectional but complementary effects. In young children with severe and moderate obstruction, inhaled use of a combination of a bronchodilator and a mucolytic is effective. Complex treatment of children with respiratory diseases, especially with chronic recurrent inflammatory diseases of the lungs, along with other pathogenetic therapy, includes drugs that help increase the lumen of the bronchi, reduce the viscosity and elasticity of sputum. According to N.A. Geppe et al., the use of Ascoril expectorant in children aged 2 to 10 years with mild or moderate acute respiratory viral infection has a pronounced positive effect on the course of the disease, as assessed by doctors, as well as according to the results of a parent survey. The study included children with acute respiratory diseases that occurred with cough due to the involvement of various parts of the respiratory tract in the inflammatory process (laryngitis, pharyngitis, tracheitis, bronchitis). For children under 6 years of age, Ascoril expectorant was prescribed 5 ml (1 teaspoon) 3 times a day, from 6 to 10 years - 5–10 ml (1–2 teaspoons) 3 times a day. The duration of treatment was 7–10 days, depending on the dynamics of the patients’ condition. In children over 6 years of age, external respiratory function was assessed according to spirography (FVC, FEV1, PEF, minimum volumetric flow rate at the level of 25, 50, 75% VC). All children, including young children, underwent bronchophonography to study the function of external respiration. In children who received the combined drug (Ascoril), compared with the control group of children who received only the mucolytic (bromhexine), faster positive dynamics were observed. In children receiving Ascoril expectorant, the disappearance of cough symptoms was observed 3–4 days earlier than in patients in the comparison group (p<0.05). It is important that the symptoms of night cough disappear 1–2 days faster. A decrease in the severity of cough symptoms was accompanied by improved sleep, increased activity in children, and an improvement in their emotional state. The total score of clinical symptoms during treatment showed a faster effect of Ascoril expectorant compared to the comparison group. The positive dynamics of clinical symptoms was accompanied by a significant improvement in bronchophonography and spirography indicators, indicating normalization of bronchial patency. Tolerability of Ascoril was good in all age groups. One child had an allergic reaction to the drug in the form of a rash. No side effects or adverse reactions were noted in the remaining children. 4% of children receiving the combination drug and 10% of children receiving only the mucolytic (p<0.05), due to insufficient effectiveness of treatment, antibacterial therapy was added. It should be remembered that repeated phenomena of biofeedback during acute respiratory viral infections in childhood require a comprehensive clinical examination of the child to exclude diseases accompanied by biofeedback, and especially asthma. Ascoril in adults, in patients with chronic disease and a history of smoking According to studies conducted on the effectiveness and safety of Ascoril expectorant in patients with various respiratory diseases (ARVI, acute and chronic disease, asthma, COPD, pneumonia) in Russia and abroad, high effectiveness was noted drug (78–96%). This effect is especially clearly seen in patients with chronic broncho-obstructive diseases, for example, against the background of an exacerbation of ARVI [21], which is expressed by a significant improvement in bronchial patency [21], a decrease in the intensity of cough, and easier expectoration of sputum. The onset of action of the drug was registered by the end of the 1st day of administration. ARVI in patients with chronic disease and smokers is quite severe and is accompanied by severe obstruction. In contrast to the course of ARVI in practically healthy individuals, in this case doctors note the development of a productive cough. It should be emphasized that smokers suffer from infectious diseases (including ARVI) much more often than non-smokers. This is largely due to significant disturbances in mucociliary clearance under the influence of tobacco smoking. Tobacco smoke contains a significant amount of free radicals, which, when inhaled into the respiratory tract, upset the balance in the oxidant-antioxidant system. In the process of the formation of this imbalance, which is characterized as oxidative stress, damage occurs to the biological membranes of cells included in the structure of the lung tissue. Acute damage to lung tissue during chronic smoking is transformed into a chronic inflammatory process. Symptomatic treatment of ARVI should be aimed at reducing fever, manifestations of biofeedback, and improving sputum discharge. Overproduction of viscous bronchial mucus requires the use of mucolytic drugs, and bronchial obstruction requires bronchodilator drugs. Therefore, it is desirable to use combination drugs, the action of which is aimed at the main links in the pathogenesis of acute cough during ARVI in smokers. In this regard, the drug Ascoril is of some interest. Its components can reduce cough and symptoms of biofeedback, because all components of the drug have a synergistic effect, improving mucociliary clearance, regulating the secretion of bronchial mucus and its rheological properties, reducing excess bronchial tone. As a result, rapid cleansing of the bronchi from altered bronchial secretions and reduction/cessation of cough occur. Conclusion The combined drug Ascoril expectorant is an effective and safe treatment for acute respiratory diseases occurring with symptoms of bronchial obstruction in children and adults. The results of the studies demonstrated the effectiveness and safety of the use of the drug Ascoril for ARVI with symptoms of biofeedback in adults. Taking Ascoril in the first days of acute respiratory infection reduces the duration of the disease, manifestations of bronchial obstruction, bronchial hyperreactivity, and promotes faster clinical recovery. The work of Russian pediatricians also showed that when treated with Ascoril, its effectiveness was good and high in 96% of cases. These studies showed that Ascoril is a safe drug for the treatment of ARVI in long-term and frequently ill children. Thus, the administration of Ascoril expectorant in children shortens the duration of respiratory viral diseases, reduces the manifestations of bronchial obstruction, and promotes faster clinical recovery. But the most important thing: if children and adults have BOS, they should be thoroughly examined to make a diagnosis. An important aspect of the use of the drug is its good tolerability. It is extremely rare that some patients experience tremors and palpitations that go away immediately after stopping the drug or reducing the dose. These side effects are primarily due to the salbutamol contained in Ascoril syrup, which has high absorption when taken orally. In this regard, Ascoril should be prescribed with caution to patients taking methylxanthines, monoamine oxidase inhibitors and tricyclic antidepressants (possibility of tachyarrhythmia, drop in blood pressure). It is not recommended to take simultaneously with non-selective β-blockers. The use of the drug in adults is also highly effective. When using the drug Ascoril in elderly people, as well as in patients with concomitant cardiovascular diseases, one should remember the side effects of salbutamol. Literature 1. Belevsky A.S. 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