Selection tactics and features of the use of antitussive, expectorant and mucolytic drugs in pediatric practice

Expectorants are a group of medications that thin mucus and facilitate its evacuation.

Under physiological conditions, in the bronchial tree, goblet cells constantly produce mucous substances called mucopolysaccharides. They have a softening effect and protect the bronchial mucosa from excessive drying. The constantly produced mucus is removed by the ciliated epithelium of the bronchi, and, rising along the trachea, is subsequently swallowed.

Under pathological conditions, with inflammatory diseases of the bronchi, including those of an infectious nature, there is more sputum, and its physical properties change. It becomes more viscous and difficult to separate, as a result of which its physiological evacuation is disrupted, and sputum begins to accumulate in the lumen of the bronchi.

The accumulating mucus begins to exert direct pressure on the so-called bronchial baroreceptors. This type of receptor is activated by mechanical pressure and triggers the cough reflex. Thus, the body, through the cough reflex, tries to exfoliate and remove excess amounts of mucus formed.

If the sputum is sufficiently viscous and difficult to separate, a paroxysmal painful cough develops, which may be accompanied by chest pain, shortness of breath, and wheezing.

To facilitate the removal of mucus and, accordingly, reduce coughing, expectorants are prescribed.

How to treat a wet cough?

November 4, 2022
16700

4.7

3

Content

• Causes of wet cough
• Symptoms of a wet cough
• How to treat a wet cough
• 8 most effective drugs for wet cough
• Ascoril
• Ambrohexal
• Fluimucil
• Mukaltin
• ACC
• Ambrobene
• Plantain and coltsfoot syrup from Evalar
• Lazolvan
• Traditional methods of treating wet cough

A cough is called “wet” when it is accompanied by the formation of sputum. And the main task of antitussives in this case is to liquefy this sputum and remove it. In the first days of treatment, a wet cough may intensify, but it will no longer be as severe. Today, pharmacies offer a variety of cough medications: these include syrups, tablets, and lozenges. Such drugs should be prescribed exclusively by a doctor who will determine the cause of the cough; self-medication is inappropriate here.

Causes of wet cough

A wet cough occurs when there is inflammation in the respiratory system. Coughing is a reflex defense reaction of the body designed to clear the airways of sputum and germs.

Among the most common causes of wet cough are:

• respiratory viral diseases;
• bronchitis;
• pneumonia (pneumonia);
• bronchial asthma;
• whooping cough.

In addition, a wet cough is possible with chronic diseases such as tuberculosis, heart failure, bronchiectasis, and cystic fibrosis.

Read also How to treat dry cough: top 5 drugs The best drugs for dry cough in adults.

Symptoms of a wet cough

With the help of a wet cough (with the release of thick sputum), the bronchi and lungs are cleared of mucus. In addition to coughing, a person may experience chest pain and wheezing in the lungs. Usually a person coughs most at night, which significantly impairs his sleep. In addition to a debilitating cough, there is a deterioration in general health, dizziness, shortness of breath, lacrimation, runny nose and increased body temperature.

A wet cough must be treated, because it is fraught with complications. If sputum stagnates in the bronchi and lungs, bacteria will begin to multiply in it (in this case, ARVI will be complicated by purulent bronchitis or pneumonia). If a bacterial infection is added to a viral infection, the person will have the following symptoms: fever, deterioration in general health, sputum mixed with pus. In such cases, the doctor prescribes antibiotics.

How to distinguish a dry cough from a wet one

Photos from open sources

How to treat a wet cough

Treatment of wet cough is aimed at stopping the development of the inflammatory process, liquefying and removing mucus, and relieving bronchial spasm. In each specific case, the doctor selects an individual cough treatment regimen, taking into account its causes, the severity of symptoms, existing chronic diseases, etc. Typically, the treatment of a wet cough involves prescribing the following drugs (one or more):

• Mucolytics.
  These drugs stimulate the formation of sputum, thin it and help it come out faster.
• Expectorants.
  Such drugs stimulate the cough reflex, due to which mucus leaves the bronchi faster.
• Bronchodilators (antispasmodics).
  They are used to expand the lumen of the bronchi, relieve spasms, due to which the airways are quickly cleared of thick mucus.
• Anti-inflammatory and antiviral agents.
  Such drugs can be in tablets, spray or syrup form.
• Antibiotics.
  Prescribed if the cause of the cough is a bacterial infection (or a bacterial infection has joined the viral one).

In order to improve the general condition while treating a wet cough, a person needs to consume enough fluids and eliminate foods that irritate the throat from the diet. Now let’s look in more detail at each medicine that is prescribed for cough.

1. Mucolytics.
   Mucolytics increase the volume of sputum, dilute it and remove it from the respiratory tract. Active ingredients of mucolytics: bromhexine, acetylcysteine, ambroxol, carbocisteine. If the drug is chosen correctly, you can get rid of a wet cough in a week.
2. Expectorants.
   If the sputum is excessively viscous, expectorants help thin it and remove it faster. Typically, such preparations contain extracts of plantain, marshmallow, and thyme. The active synthetic substances are bromhexine, chymotrypsin, trypsin.
3. Bronchodilators.
   These are serious medications that should only be prescribed by a doctor. Similar cough medications relieve spasms in the bronchi. Typically, spasm is observed with bronchitis, asthma, bronchopulmonary dysplasia. Bronchodilators can also be used as inhalations.
4. Anti-inflammatory drugs.
   Such drugs are prescribed for both wet and dry coughs, the cause of which is viruses, bacteria or allergens.
5. Antihistamines.
   Remedies from this group are used if the cause of the cough is an allergy.
6. Drugs to inhibit cough receptors.
   These drugs affect the cough centers located in the brain, as well as the cough receptors and nerves located in the respiratory tract. They also work as anesthetics and are prescribed to adults and children to treat both wet and dry coughs.
7. Combined drugs.
   These cough remedies are the most effective and relieve negative symptoms literally on the second or third day. Combination cough medications contain expectorants, bronchodilators, mucolytics and antihistamines. Some even have an antipyretic effect, so they are prescribed for influenza and ARVI.

   
   Causes of wet cough

   Photos from open sources

Mucolytic therapy: a rational choice

Table 1. Classification of mucolytic drugs according to their effect on bronchial secretion (according to [7] as modified)

In response to exposure to a damaging infectious or non-infectious agent, the first reaction of the mucous membrane of the tracheobronchial tree is the development of an inflammatory reaction with hypersecretion of mucus. One of the constant signs of inflammatory diseases of the respiratory system is cough, aimed at protecting and restoring the patency of the tracheobronchial system by removing secretions [1]. The effectiveness of the drainage function of the tracheobronchial tree is largely determined by the amount and rheological properties of sputum (viscosity, elasticity, adhesiveness), which can be improved by using expectorants and mucolytics [2, 3].

The use of expectorants (expectants), mainly preparations based on medicinal plants, is not always justified due to their short-term effect (small doses are required every two to three hours). An increase in their single dose causes dyspeptic disorders (nausea, less often vomiting and diarrhea), and an increase in the volume of sputum leads to a significant impairment of the drainage function of the lungs [4].

Mucolytic (secretolytic) therapy is aimed at inhibiting the formation of bronchial secretions, liquefying, rehydrating sputum and stimulating its removal from the lumen of the tracheobronchial tree. Mucolytics are the main component in the complex therapy of chronic bronchopulmonary diseases [5, 6].

Mucolytic agents (N-acetylcysteine, bromhexine, ambroxol, carbocysteine, erdosteine ​​and guaifenesin) act on the gel phase of bronchial secretions and effectively dilute sputum without significantly increasing its quantity [4]. The mechanism of action of individual representatives of mucolytics is different, so they have different effectiveness (Table 1).

Based on their origin, mucolytic drugs are divided into two groups:

• synthetic (bromhexine, ambroxol, acetylcysteine, carbocysteine, mesna and erdosteine);
• natural origin:
• enzymes (trypsin, chymotrypsin, pankypsin, ribonuclease, deoxyribonuclease, elastolin, caripazin);
• herbal remedies that, along with mucolytic, also have an expectorant effect [8].

Some of the mucolytic drugs have several dosage forms that provide different methods of drug delivery (inhalation, oral, injection, endobronchial), which is extremely important in the complex therapy of respiratory diseases.

N-acetylcysteine

(
acetylcysteine, ACC, muconex, fluimucil, etc.
) is an active mucolytic drug. The mechanism of its action is based on the rupture of disulfide bonds of acidic mucopolysaccharides of sputum, which helps to reduce the viscosity of mucus [9]. The drug also helps to liquefy pus and thereby increases its evacuation from the respiratory tract [4, 10]. N-acetylcysteine ​​increases the secretion of less viscous sialomucins and alveolar surfactant by type II alveolocytes, enhances the motor activity of cilia by reducing the viscosity of sputum, and can increase antiviral immunity [11]. In addition, N-acetylcysteine ​​promotes the synthesis of glutathione, the body’s main antioxidant, which enhances cell protection from the damaging effects of free radical oxidation, which is characteristic of an intense inflammatory reaction [12, 13].

When using N-acetylcysteine, it is necessary to take into account the possible danger of developing bronchospasm, as well as a decrease in the production of lysozyme and secretory immunoglobulin A (IgA) [4]. Long-term treatment with the drug causes suppression of the activity of ciliated cells [13]. Taking N-acetylcysteine ​​is contraindicated for gastric and duodenal ulcers in the acute stage, during pregnancy and breastfeeding [14].

Mucolytics-mucoregulators (carbocysteine) and vasicinoids (bromhexine and ambroxol) do not cause bronchial constriction.

Bromhexine

(
Bisolvon, Solvin, Flegamine, etc.)
– a synthetic derivative of the alkaloid vasicine. Bromhexine is one of the first synthetic mucolytic drugs and has been widely used in the treatment of respiratory diseases for several decades. When taken orally, bromhexine, which in the body turns into an active metabolite - ambroxol, has an expectorant and mucolytic effect.

The pharmacodynamic effects of bromhexine are less pronounced than those of ambroxol [4]. The mechanism of the mucolytic action of the drug is associated with depolymerization and destruction of acidic mucoproteins and mucopolysaccharide polymer molecules of bronchial secretions, which leads to a decrease in its viscosity [15]. Also important is the ability of bromhexine to restore mucociliary clearance by stimulating the synthesis of endogenous surfactant by type II alveolocytes [5]. In addition, the drug stimulates the synthesis of neutral polysaccharides and the release of lysosomal enzymes [7], promotes the release of sputum from the respiratory tract, increasing the activity of the ciliated epithelium of the bronchi [16], and has a weak antitussive effect [2].

Among the side effects, gastrointestinal disorders and skin reactions, which are observed quite rarely, attract attention. Bromhexine is not recommended for pregnant women and nursing mothers [14, 17].

The second representative of vasicinoids is ambroxol

(
Ambrobene, Ambrohexal, Ambrosan, Bronchopront, Lazolvan, Medox, Flavamed, Halixol, etc.)
belongs to the new generation of mucolytic agents. Ambroxol causes depolymerization of mucoproteins and mucopolysaccharides, providing a mucolytic effect. The drug activates the movements of the cilia of the ciliated epithelium, providing a secretomotor effect and restoring mucociliary transport [4, 16]. Ambroxol is able to increase the synthesis of surfactant and inhibit its breakdown under the influence of unfavorable factors [18, 19].

The drug has an anti-inflammatory effect due to inhibition of neutrophil chemotaxis and suppression of the production of anti-inflammatory cytokines (interleukin-1, tumor necrosis factor), as well as anti-edematous and antioxidant effects [12, 20]. Ambroxol, by suppressing the production of anti-inflammatory cytokines by O2-activated neutrophils, prevents the accumulation of hypochlorous acid in neutrophils [21]. The drug enhances the natural defense of the lungs by activating tissue macrophages and increasing the production of secretory IgA [22]. Ambroxol does not have a teratogenic effect, and therefore can be used in pregnant women and children, in particular for the prevention and treatment of respiratory distress syndrome [23].

Side effects when using ambroxol are rare and manifest themselves in the form of nausea, abdominal pain, allergic reactions, dry mouth and nasopharynx. The drug is not used in conjunction with antitussives, as this contributes to the accumulation of bronchial secretions in the respiratory tract [1].

For inflammatory diseases of the respiratory tract, combination drugs are often used, including in combination with antibiotics. When prescribing mucolytics and antibiotics simultaneously, their compatibility must be taken into account: bromhexine and ambroxol increase the penetration (penetration) of antimicrobial agents into the bronchial secretions and bronchial mucosa (primarily this applies to amoxicillin, ampicillin, cefazolin, cefuroxime, erythromycin, doxycycline and sulfonamides) [17 ]. A number of studies have shown an increase in the concentrations of antibiotics of various groups (penicillins, cephalosporins, macrolides, tetracyclines and fluoroquinolones) in the alveoli and bronchial mucosa under the influence of ambroxol [24, 25]. This may be a significant factor influencing the effectiveness and duration of antibiotic therapy for respiratory tract infections.

Carbocisteine

(
Bronchobos, Libexin Muco, Mucodin, Fluifort (carbocysteine ​​lysine salt), Fluditek, etc.
) is a representative of mucolytic-mucoregulators. Carbocysteine ​​activates sialic transferase of goblet cells of the bronchial mucosa, under the influence of which the production of acidic mucins involved in the organization of bronchial secretions slows down and, as a result, helps improve its viscosity and elasticity [26]. The drug also restores impaired IgA secretion, normalizes and stimulates the secretion of glutathione in the epithelial cells of the mucous glands, and has pronounced anti-inflammatory and immunomodulatory activity [2, 7].

Considering the existing data on the ability of carbocysteine ​​to increase the activity of regeneration of the bronchial mucosa and reduce the number of goblet cells, especially in the terminal bronchi, to potentiate the activity of ciliated cells in the chronic nature of the inflammatory process in the tracheobronchial tree, the combined use of ambroxol and carbocysteine ​​is possible [8, 26].

Possible side effects of carbocisteine ​​include nausea, stool disorders, epigastric pain and allergic reactions. Carbocisteine ​​is not advisable to combine with antitussive drugs; it is not recommended for pregnant women and nursing mothers [2, 14].

Erdostein

(
Erdosteine
) is a new mucolytic drug, is a derivative of homocysteine, has mucolytic and antioxidant properties, as well as a moderate antitussive effect. Unlike acetylcysteine, it reduces the formation of reactive oxygen species [27]. Erdostein prevents the adhesion of bacteria to the mucous membrane of the respiratory tract due to the fact that the sulfhydryl groups of its active metabolites destroy disulfide bonds in the protein molecule that is part of the bacterial cell [28]. Erdostein also prevents the inhibition of α1-antitrypsin synthesis and increases the concentration of IgA in the mucosa in patients with obstructive airway diseases [29].

The simultaneous administration of erdosteine ​​and amoxicillin in patients with infectious exacerbation of chronic bronchitis led to an increase in the concentration of the antibiotic in sputum, a decrease in its viscosity and a more rapid disappearance of clinical symptoms compared to ambroxol and placebo [30].

Erdostein does not have a damaging effect on the gastrointestinal tract; in case of renal failure and impaired liver function, accumulation of drug metabolites in the body is possible [27].

Guaifenesin

(
Jocet, Toussin, etc.
) is a derivative of guaiacol (o-methoxyphenol). Guaifenesin, in its characteristics, occupies an intermediate position between expectorants and mucolytic drugs. It stimulates mucus secretion and reduces its viscosity [15]. Unlike expectorants of reflex and resorptive action, the pharmacological effect of guaifenesin is based on reducing the surface tension and adhesion of mucus to the bronchial mucosa due to the depolymerization of acidic mucopolysaccharides of mucus, which reduces its viscosity and facilitates evacuation from the respiratory tract [31]. The ability to increase mucus secretion (albeit less viscous) makes guaifenesin similar to expectorants [32].

No side effects have been noted with guaifenesin, however, when taking it, urine may turn pink. The drug is contraindicated in cases of hypersensitivity to the drug, pregnant and lactating women, and children under 3 years of age. Guaifenesin should be used with caution in patients with gastric ulcers [14, 32].

It is advisable to combine guaifenesin with sputum thinners. It is part of such combination cough preparations as Ascoril

,
Hexapneumin
,
Kalmilin for coughs and colds
,
Coldrex broncho
,
Prothiazine expectorant
,
Pulmotin
,
Robitussin
,
Stoptussin
,
Synetos
,
Tussin plus
, and is also found in combination drugs with phenylpropanolamine (sympathomimetic), theophylline (phosphodiesterase inhibitor), codeine (narcotic analgesic) , phenylephrine (α-adrenergic stimulant), pseudoephedrine
( sympathomimetic) [14].
Proteolytic enzymes

(trypsin, chymotrypsin, RNase) reduce both the viscosity and elasticity of sputum, have an anti-edematous and anti-inflammatory effect. However, these drugs are practically not used in pulmonology due to possible damage to the pulmonary matrix and the risk of developing side effects such as bronchospasm, hemoptysis and allergic reactions, especially in pediatric practice. An exception is recombinant aDNase, which is prescribed to patients with cystic fibrosis [4].

Combination drugs

used as symptomatic therapy for acute and chronic inflammatory diseases of the respiratory tract. Due to the bronchodilator and anti-inflammatory effects, when taking these drugs, a dry, obsessive cough is stopped, and thanks to the expectorant and mucolytic effects, it is transformed into a wet one and the respiratory tract is sanitized.

Some combination drugs contain an antitussive drug ( Stoptussin, Hexapneumin, Lorraine

), bronchodilator (
ascoril, solutan
), antipyretic and/or antibacterial agents (
Hexapneumin, Lorraine
).
These drugs should be prescribed only for strict indications, since some of them contain medications that are opposite in their effects or suboptimal doses of active substances, which reduces their effectiveness. But there are also completely justified combinations of drugs (for example, Ascoril expectorant
, which includes guaifenesin, bromhexine and salbutamol) [33].

Thus, the choice of one or another mucolytic agent or their combinations in the complex therapy of inflammatory diseases of the respiratory system, which are accompanied by a productive cough, should be strictly individual and should take into account the mechanism of pharmacological action of the drug, the phase and nature of the pathological process, the patient’s age and the presence of concomitant pathology. The simultaneous use of antitussive and mucolytic drugs is undesirable, but a positive effect can be obtained by using mixed action mucolytics with antitussive properties (erdostein). In acute bronchitis and pneumonia with scanty sputum, a combination of expectorants and mucolytics is possible, or the prescription of guaifenesin, which has both expectorant and mucolytic effects, is justified. For diseases of the respiratory system with an acute and protracted course, accompanied by a cough with copious mucous sputum, the drug of choice can be considered carbocisteine ​​(mucoregulator), and with viscous and (or) purulent sputum - ambroxol. In children, the drugs of choice are also ambroxol and carbocysteine, in a balanced combination of which the drugs complement each other's actions, relieving cough and promoting rapid restoration of the mucous membrane of the respiratory tract. In case of chronic pathology of the respiratory system, N-acetylcysteine ​​is prescribed as maintenance therapy for a long period. In acute diseases of the respiratory system and exacerbation of chronic inflammatory diseases of the lungs, a combination of mucolytic drugs with expectorants is possible, but the effectiveness of the latter in chronic pathology of the respiratory tract is low, which is associated with the presence of irreversible structural changes in the bronchial epithelium.

Ascoril

"Ascoril" is a combination drug for the complex treatment of wet cough, which contains several active substances: salbutamol, guaifenesin and bromhexine. "Ascoril" is a mucolytic and bronchodilator with an expectorant effect. The drug is usually prescribed for such serious problems as obstructive bronchitis and pneumonia, that is, in cases where the sputum is difficult to clear and is very thick. "Ascoril" acts quickly - relief occurs literally in the first days of taking it. But you need to remember about the side effects of Ascoril: some patients experience tachycardia, increased sweating, and dry mouth.

Ascoril

Glenmark Pharmaceuticals, India

As part of combination therapy for acute and chronic bronchopulmonary diseases, accompanied by the formation of difficult-to-separate viscous secretions: bronchial asthma;
tracheobronchitis; obstructive bronchitis; pneumonia; emphysema; whooping cough; pneumoconiosis; pulmonary tuberculosis. from 113

5.0 1 review

1294

• Like
• Write a review

Table of contents

— Mucolytics — Mechanism of action and pharmacology — Pharmacokinetics — Place in therapy — Contraindications, side effects, interactions

Enzyme mucolytics are prescribed intramuscularly, inhalation or endobronchially (trypsin, chymotrypsin, ribonuclease), or only inhalation (deoxyribonuclease, terrilitin) or endotracheally (terridecase). All modern mucolytic drugs can also be used orally and intravenously, except for mesna, the effect of which is manifested only in direct contact with bronchial secretions.

Ambroxol and bromhexine are administered by inhalation, orally, subcutaneously, intramuscularly, and intravenously. They are highly soluble in lipids, quickly and almost completely absorbed from the intestine, but undergo first-pass biotransformation, especially bromhexine. Therefore, the bioavailability of ambroxol is 70-80%, and bromhexine is only 20%. The maximum concentration of ambroxol in the blood plasma is achieved after 0.5-3 hours (on average after 2 hours) and is 88.8 ng/ml when taking a dose of 30 mg. The maximum concentration of bromhexine is observed 0.5-1 hour after administration. The therapeutic concentration of ambroxol ranges from 30 to 135 ng/ml. 75-90% bound to plasma proteins. Bromhexine is also highly protein bound. Both drugs are capable of accumulation. The half-life of ambroxol is 1.3 hours. The half-life of ambroxol from plasma is 6-12 hours, bromhexine is 6.5 hours. The elimination of ambroxol is two-phase: for ambroxol the first phase is 1.3 hours, the second is 8.8 hours, for bromhexine 1 and 15 hours respectively. Bromhexine undergoes demethylation and oxidation in the liver. Ambroxol is an active metabolite of bromhexine. Ambroxol is metabolized to 3,5-dibromoantranilic acid and 6,8-dibromo-3-trans-4-hydroxycyclohexyl)-1, 2, 3, 4-tetrahydroxyquinazoline and their glucuronides. Hepatic clearance is about 53 ml/min. Both drugs are 90% excreted by the kidneys, mainly in the form of metabolites (only 5% of ambroxol is excreted unchanged). They penetrate the blood-brain barrier, the placenta and into breast milk.

Acetylcysteine ​​is administered by inhalation, orally, intramuscularly, intravenously. When taken orally, it is well absorbed from the gastrointestinal tract. The drug undergoes intensive first-pass biotransformation in the liver (deacetylated into the active metabolite - cysteine) and partly in the intestinal wall. Therefore, unavailability is low - no more than 10%. However, this appears to be sufficient to create therapeutic concentrations in the lungs. The maximum concentration in blood plasma (= 2 µmol/l) is achieved 1 hour after administration. 50% bound to proteins. After systemic administration, acetylcysteine ​​is distributed evenly throughout the body, while a significant increase in the number of sulfhydryl groups is observed in tissues and blood plasma (0.33-0.47 l/k). Penetrates through the placenta. T1/2 - 1 hour. In case of liver cirrhosis, it increases to 8 hours. The elimination route is predominantly hepatic. Excreted in the form of active and inactive metabolites: inorganic sulfates, N-acetylcysteine, N,N-diacetylcysteine ​​and cysteine ​​ester. Renal clearance accounts for 30% of the total clearance.

Carbocisteine ​​is administered orally. After oral administration, the maximum concentration in the blood serum and mucous membrane of the respiratory tract is created after 2 hours. The therapeutic concentration is maintained for 8 hours. T1/2 is 3 hours 15 minutes. Complete excretion occurs after 3 days, mainly in the urine unchanged and in the form of metabolites.

Mesna is used only by inhalation.

Ambrohexal

This mucolytic drug is used for wet coughs to thin out mucus and remove it faster. "Ambrohexal" is inexpensive, but quite effective. The remedy is prescribed for acute and chronic bronchitis, pneumonia, asthma and other problems, one of the symptoms of which is a prolonged cough. "Ambrohexal" can be taken by adults and children from 6 years of age. To enhance the positive effect, in addition to the mucolytic, an antiviral or antibacterial agent is usually prescribed (you need to look at the clinical manifestations). Reviews from doctors and patients about the drug are mostly positive due to its complex action - the product removes phlegm in the most natural way possible. The cost of Ambrohexal is quite affordable, and there are no serious contraindications or side effects.

Ambrohexal

Hexal, Germany

Ambrohexal is a mucolytic and expectorant.
Indications for use: Acute and chronic diseases of the respiratory tract, accompanied by the formation of viscous secretions: - acute and chronic bronchitis; - pneumonia; - COPD; - bronchial asthma with difficulty in sputum discharge; - bronchiectasis; - treatment and prevention of respiratory distress syndrome (for syrup and solution for oral administration and inhalation). from 92

5.0 1 review

620

• Like
• Write a review

Mucolytic (sputum thinning) drugs

Home Medical Encyclopedia Medicines Medicines used to treat diseases of the bronchi and lungs

See also bronchicum balm with eucalyptus oil, bronchicum inhalate, sinupret, trisolvin.

ACETYL CYSTEINE (Acetylcystein)

Synonyms: Acetin, Mucomist, Mucosolvin, Broncholysin, Airbron, Fluimucetin, Fluimucil, Inspira, Mucisol, Mucofilin, Mucolytic, Mukobene, Acc, Racomex, etc.

Pharmachologic effect. It has a mucolytic effect - it thins sputum and facilitates its separation.

Indications for use. Diseases of the respiratory tract (bronchitis, pneumonia, bronchiectasis, cystic fibrosis), accompanied by increased viscosity of sputum with the addition of a purulent infection. The drug is effective for infectious-allergic bronchial asthma complicated by bacterial, especially purulent, bronchitis or suppurative bronchiectasis (a lung disease with the formation of cavities in the lung tissue filled with purulent sputum). However, in these cases, caution should be exercised due to the possibility of increased bronchospasm (sharp narrowing of the lumen of the bronchi). As a preventive measure, it is advisable to simultaneously take bronchodilators (dilating the lumen of the bronchi).

Method of administration and dose. Acetylshisteine ​​is used in the form of inhalations of 2-5 ml of a 20% solution 3-4 times a day (for 15-20 minutes); 1 ml of a 10% solution is injected intratracheally (into the tracheal cavity) every hour (in the form of a slow installation - administration by drops); 5-10% solutions are used to wash the bronchi during therapeutic bronchoscopy. If it is impossible to use acetylsteine ​​solution in the form of inhalation and intratracheally (in case of respiratory tract injuries, comatose/unconscious/ state, etc.), as well as in pediatric practice, the drug is administered intramuscularly. Adults are administered intramuscularly with 1-2 ml of a 10% solution 2-3 times a day; infants - at the rate of 10-15 mg/kg 2 times a day; children over 1 year old - 0.5-1 ml of 10% solution 2 times a day. The duration of treatment depends on the nature and course of the disease; usually the course of treatment lasts 1-2 weeks; for tracheobronchitis (combined inflammation of the trachea and bronchi) - 3-4 days, for cystic fibrosis (a hereditary disease manifested by blockage of the respiratory tract, intestines, etc. with viscous secretions) - 7-10 days. If necessary, administer the drug intravenously. Dose for adults 0.5 g (10 ml of 5% solution). 30-90 minutes after administration, the separation of sputum is facilitated, which is removed by coughing or suction. The effect of the drug in a single dose lasts 2-4 hours. During a course of treatment, 10 ml of a 5% solution is administered 2 times a day for 7-10 days. Acetylcysteine ​​is administered to children mainly intramuscularly.

Side effect. The drug is usually well tolerated. In some cases, nausea is possible (associated mainly with the specific smell of the drug). Caution should be observed in persons prone to bronchospasm (when bronchospasm occurs, bronchodilators are prescribed). Acetylcysteine ​​should be used with caution if you are prone to pulmonary bleeding, liver disease, kidney disease, or adrenal dysfunction. With long-term use, the functions of the liver, kidneys and adrenal glands should be monitored, and blood enzyme parameters should be checked.

Contraindications. Individual hypersensitivity, bronchial asthma without thickening of sputum. When working with the drug, you should use glass vessels, avoiding contact with metals and rubber (the formation of sulfides with a characteristic odor is possible).

Release form. 20% solution for inhalation in ampoules of 5 or 10 ml and 10% solution for injection in ampoules of 2 ml and 5% solution in ampoules of 10 ml.

Storage conditions. List B. In a dark place at a temperature from 0 to +5 ° C.

BROMHEXIN

Synonyms: Bromhexine chloride, Bisolvon, Mukovin, Solvin, Brexol, Brodisol, Bromobene, Bromxin, Bisolvon, Brombenzonium, Brokokin, Lizomucin, Mugocil, Fulpen A, etc.

Pharmachologic effect. Increases the secretion of secretions by the bronchial glands and reduces the viscosity of sputum, which gives a pronounced expectorant effect and facilitates the release of sputum. The drug is low toxic. Does not have a significant effect on blood circulation.

Indications for use. Acute and chronic inflammatory diseases of the trachea, bronchi, lungs; bronchiectasis (lung disease with the formation of cavities filled with sputum in the lung tissue), pneumoconiosis (the general name for an occupational respiratory disease); in the pre- and postoperative period, the drug is used for bronchography.

Method of administration and dose. Bromhexine is taken orally (regardless of food intake) in tablet form. Doses for adults - 0.016 g (16 mg = 2 tablets of 0.008 mg) 3-4 times a day; for children from 3 to 4 years old - 0.002 g (2 mg), from 5 to 14 years old - 0.004 g (4 mg) 3 times a day; The drug is not prescribed to children under 3 years of age.

The effect of the drug usually begins to appear 24-48 hours after the start of treatment. The course of treatment is from 4 days to 4 weeks.

When used by inhalation, the solution should be diluted 1:1 with distilled water and heated to body temperature to prevent coughing. In patients with bronchial asthma or asmatic bronchitis, a bronchodilator (a drug that dilates the lumen of the bronchi) should be taken before inhalation. Inhalation is carried out twice a day for adults, 4 ml, for children over 10 years old - 2 ml, for children aged 6 to 10 years - 1 ml, for children aged 2 to 10 years - 10 drops and for children under 2 years old - 1 ml. 5 drops per inhalation. Parenteral (bypassing the digestive tract) administration of the drug is recommended for treatment in severe cases, as well as in the postoperative period to prevent the accumulation of thick sputum in the bronchi. Administer 1 ampoule subcutaneously, intramuscularly or intravenously 2-3 times a day slowly for 2-3 minutes. The drug is administered intravenously along with glucose or saline. The drug is incompatible with alkaline solutions.

If necessary, bromtexin is prescribed simultaneously with antibacterial, bronchodilator, cardiac and other drugs.

Side effect. Rarely, with long-term use - nausea, vomiting, dyspeptic symptoms (digestive disorders), exacerbation of peptic ulcer. Extremely rare - angioedema (allergic) Quincke's edema, increased levels of transaminases (enzymes) in the blood serum.

Contraindications. There are no absolute contraindications. Relative: hypersensitivity to the drug, peptic ulcer, recent gastric bleeding, first trimester of pregnancy.

Release form. Tablets: 0.008 g, 0.016 g. Dragees: 0.004 g, 0.008 g, 0.012 g. Syrup (1 ml - 0.0008 g). Medicine (1 ml -0.0008 g). Solution for oral (by mouth) use (1 ml - 0.002 g). Elixir (1 ml - 0.0008 g, or 0.00016 g) Solution for inhalation (1 ml -0.0002 g). Solution for parenteral use (1 ml - 0.002 g).

Storage conditions. Regular.

FLEGAMIN

A combined preparation containing bromhexine, menthol, eucalyptus and peppermint oils, menthol, distilled water.

Indications for use. Used as a mucolytic (sputum thinner) and expectorant.

Method of administration and dose. Take orally 3-4 times a day (dosage using the included measuring spoon).

Side effects and contraindications are the same as for bromhexine.

Release form. In 120 ml orange glass bottles containing 80 mg of bromhexine per 100 ml.

Storage conditions. In a cool place, protected from light.

Bromhexine is also included in the drug mucopararal.

GUAIFENESIN (Guaifenesine)

Synonyms: Children's cough syrup.

Pharmachologic effect. It has a mucolytic (sputum thinning) effect and reduces the viscosity of sputum.

Indications for use. Cough with difficult to separate sputum during colds and acute infectious diseases of the upper respiratory tract.

Method of administration and dose. Children aged 6-12 years are prescribed 0.1-0.2 g (5-10 ml) every 4 hours, no more than 1.2 g per day; from 2 to 6 years - 0.05-0.1 g (2.5-5 ml) every 4 hours, but not more than 0.6 g per day.

For children under 2 years of age, the drug should be prescribed under the strict supervision of a physician. Consultation with a doctor is necessary in the following cases: persistent or chronic cough, which can occur with asthma, chronic bronchitis (inflammation of the bronchi), emphysema (increased airiness and decreased tone of the lung tissue); cough, which is accompanied by copious sputum; if during treatment the cough persists for more than 1 week, has a recurrent (periodically recurring) course, is accompanied by fever (a sharp increase in body temperature), the appearance of a rash, and a constant headache.

Side effect. Rarely - diarrhea, drowsiness, nausea, vomiting, pain in the stomach.

Contraindications. Hypersensitivity to the drug.

Release form. Syrup in bottles. 5 ml of syrup contains 0.1 g of guaifenesin. The syrup has a cherry flavor.

Storage conditions. List B. In a cool, dark place.

Guaifenesin is also included in the drugs Hexapneumin and Coldrex Broncho.

GELOMYRTOL FORTE

Synonyms: Myrtol standardized.

Pharmachologic effect. It has mucolytic (sputum thinning), expectorant and antibacterial effects. The use of the drug leads to the dilution of the viscous secretion (discharge) released during inflammatory diseases of the respiratory tract, as well as to facilitating the separation of sputum. Long-term therapy with the drug improves the condition of patients with chronic respiratory diseases.

Indications for use. Acute bronchitis (inflammation of the bronchi), chronic bronchitis, sinusitis (inflammation of the paranasal sinuses).

Method of administration and dose. Adults and children over 10 years of age are usually prescribed 1 capsule 3-4 times a day. If long-term therapy is necessary, including for chronic diseases, 1 capsule is prescribed 2 times a day.

To facilitate morning mucus discharge in patients with chronic bronchitis, it is recommended to take 1 capsule of the drug in the evening before bed.

Children under 10 years of age are prescribed half the adult dose.

The drug is taken 30 minutes before meals, washed down with plenty of cool liquid.

The duration of treatment is determined by the clinical picture of the disease.

Side effect. Painful phenomena and discomfort in the epigastrium (the area of ​​the abdomen located directly under the convergence of the costal arches and the sternum) and the abdominal area, exacerbation of gallstones and urolithiasis. In rare cases, allergic reactions.

Contraindications. Hypersensitivity to the drug. Avoid using the drug in the first trimester of pregnancy.

Release form. Capsules of 300 mg in packs of 20, 50 and 100 pieces. Standardized composition of the drug: limonene - 75 mg; cineole - 75 mg; alphapinene - 20 mg.

Storage conditions. In a dry, cool place.

CARBOCYSTEIN (Carbocistein)

Synonyms: Bronkatar, Bronchocod, Mukodin, Mucopront, Mukosol, Fluvik, Drill expectorant.

Pharmachologic effect. An effective mucolytic (sputum thinner) agent. It dilutes the bronchial secretion and increases its volume, thereby facilitating its secretion. Normalizes the physical and chemical characteristics of sputum components.

Indications for use. Respiratory diseases (acute and chronic), accompanied by the release of a large amount of viscous secretion. The dosage form of the drug in the form of syrup can be used in patients with diabetes.

Method of administration and dose. Adults are usually prescribed 2 capsules 3 times a day. When a therapeutic effect is achieved, the dose is reduced to 1 capsule 4 times a day. When using syrup, the initial dose is 15 ml 3 times a day; then the dose is reduced to 10 ml 3 times a day.

For children, the dose of the drug is selected depending on age: 5-12 years - 10 ml 3 times a day; 2-5 years - 2.5-5 ml 4 times a day. Children under 2 years of age are prescribed a daily dose of 20 mg/kg (in several doses).

Side effect. Hives. Rare cases of gastrointestinal bleeding have been described.

Contraindications. Exacerbation of gastric and duodenal ulcers; hypersensitivity to the drug. During pregnancy and lactation, the drug is prescribed only for health reasons.

Release form. Capsules in packs of 20 and 1000 pieces; syrup in bottles of 110 ml. I capsule contains 0.375 g of carbocysten; 5 g of syrup contains 0.25 g of carbocisteine.

Storage conditions. List B. In a dry, cool place, protected from light.

MESNA

Synonyms: Mistabron, Mikofluid, Mukolen, etc.

Pharmachologic effect. The action of the drug is close to acetylcysteine. Due to the presence of a sulfhydryl group, it is able to break the disulfide bonds of sputum mucopolysaccharides and reduce its viscosity.

Indications for use. Used in the form of inhalation or intrabronchial infusions for chronic bronchitis, pulmonary emphysema (increased airiness and decreased tone of the lung tissue), pulmonary atelectasis (collapse of the lung tissue), after surgical interventions on the lungs, etc.

Method of administration and dose. For inhalation, use 0.6-1.2 g of the drug (1-2 ampoules of 3 ml of 20% solution) without dilution or in a 1:1 dilution in distilled water or isotonic sodium chloride solution. Inhalations are carried out 2-3 times a day. The course of treatment is 2-24 days. For intratracheal (into the trachea) infusion, the same dose and dilution are used. Enter every hour until

liquefaction and removal of secretions (bronchopulmonary discharge).

In case of inflammation of the maxillary (maxillary) sinus, 2-3 ml of the drug is administered after preliminary washing of the sinus (if necessary, every 2-3 days).

Release form. 20% solution in ampoules of 3 ml (600 mg) in a package of 6 pieces. Ampoules should be opened immediately before use; The remaining solution cannot be used!

Storage conditions. Regular.

Fluimucil

This Swiss drug for wet coughs perfectly thins and removes mucus from the respiratory tract, being an analogue of “ACC”, although they have the same active substances. Some doctors are sure that Fluimucil is better than ACC because it is of better quality. And it costs much less, which is good news. Patients write in reviews that Fluimucil helps quickly remove phlegm from a wet cough. The only disadvantage of this product is that it is not available in all pharmacies.

Fluimucil

Zambon, Italy

Respiratory diseases accompanied by impaired sputum discharge (including bronchitis, tracheitis, bronchiolitis, pneumonia, bronchiectasis, cystic fibrosis, lung abscess, pulmonary emphysema, laryngotracheitis, interstitial lung diseases, pulmonary atelectasis /due to blockage of the bronchi by mucus plug/);
catarrhal and purulent otitis, sinusitis, incl. sinusitis (to facilitate the passage of secretions); for removing viscous secretions from the respiratory tract in post-traumatic and postoperative conditions. from 46

5.0 1 review

819

• Like
• Write a review

Mukaltin

These sour cough tablets have been familiar to us since childhood. The active ingredient “Mukaltina” is marshmallow root (that’s where this herbaceous smell comes from). "Mukaltin" is safe and cheap, it thins mucus and removes it. The positive effect of “Mukaltin” has been confirmed for decades, so doctors continue to prescribe it for coughs. The only drawback is that children often do not want to take these pills because they have a specific sour taste.

Mukaltin

Vifitech/Vilar, Russia; Medisorb, Russia; JSC "Tatkhimfarmpreparaty", Russia; Update, Russia; CJSC "Moscow Pharmaceutical Factory", Russia; JSC Avexima, Russia; JSC Pharmstandard-UfaVITA, Russia

Respiratory tract diseases (including laryngitis, tracheitis, bronchitis, bronchial asthma), gastritis, gastric and duodenal ulcers.
from 6

5.0 1 review

794

• Like
• Write a review

ACC

"ACC" is perhaps the most popular tablet for the treatment of wet cough. "ACC" is prescribed for bronchitis and pneumonia. The product thins mucus and helps it drain better. "ACC" is sold in the form of effervescent soluble tablets, which are prescribed to adults and children over 14 years of age. Doctors note the excellent effectiveness of the drug if you need to get rid of very viscous sputum. But ACC should not be taken at night - this can lead to congestion in the lungs. It is also contraindicated to take ACC alone in combination with other cough medications. Buyers in reviews say it works quickly, treats coughs well, is inexpensive and is available in all pharmacies.

ACC

Hermes Pharma, Germany; Wernigerode Pharma, Germany; Lindopharm, Germany

Respiratory diseases accompanied by the formation of viscous, difficult to separate sputum (acute and chronic bronchitis, obstructive bronchitis, tracheitis, laryngotracheitis, pneumonia, lung abscess, bronchiectasis, bronchial asthma, COPD, bronchiolitis, cystic fibrosis);
acute and chronic sinusitis; Otitis media from 102

5.0 1 review

1464

• Like
• Write a review

It is not advisable to self-medicate with a wet cough, it is fraught with complications

Photos from open sources

Mucoactive cough therapy: what's beyond the horizon?

According to a number of authors, cough is currently perhaps the most common reason for seeking outpatient medical care [1–4]. Thus, in the UK, it is an acute cough that accompanies the course of an acute respiratory viral infection (ARVI) that annually brings about 12 million patients to the doctor [1–2].

Chronic cough is also an extremely important problem for practical healthcare due to the fact that about 11–18% of residents in various countries of the world present this kind of complaint [3–7]. In addition, it is known that chronic cough is the most common symptom of various bronchopulmonary diseases and causes from 10% to 38% of visits to a pulmonologist for medical help [4]. With regard to chronic diseases of the respiratory tract, it is worth noting that the prevalence of, for example, chronic obstructive pulmonary disease (COPD), according to modern epidemiological studies, reaches 4–15% among the adult population of developed countries [8–9]. Thus, according to the BOLD study, which included about 10 thousand respondents from 12 countries, and PLATINO (963 respondents over 40 years of age), the prevalence of COPD was 12% and from 8% to 19% in different cities of South America, respectively [10–11]. Taking into account the results obtained, it is currently predicted that the number of COPD patients in the world reaches 600 million people. According to the CARD study, the diagnosis of COPD was established in 21.8% of respondents, which, using mathematical modeling, indicates that in Russia about 15.3% of the population (21,986,100 people) suffer from this disease [12].

An important component of the cough problem is economic losses associated primarily with the direct costs of purchasing cough medicines [13]. For example, in the UK, the cost of treating acute cough is about £1 million annually. In the United States, annual spending on over-the-counter cough and cold medications reaches $3.6 billion.

Definition and general treatment approaches to managing a patient with cough

Coughing is a protective reflex that helps remove excess secretions and foreign particles from the upper and lower respiratory tract.

Rational antitussive therapy is based primarily on establishing a diagnosis of the disease, analyzing the characteristics of the cough: sputum discharge, the nature of the bronchial secretion - mucous or purulent, viscosity, quantity, etc.; intensity of coughing, its duration; the effect of cough on the patient’s condition, his sleep; the presence of airway obstruction, etc. [3–4, 13].

Treatment of cough should first of all be etiotropic, that is, aimed at eliminating the cause of the cough. For example, effective antibacterial therapy for pneumonia, exacerbations of COPD/chronic bronchitis, compensation for heart failure, withdrawal of drugs that provoke cough, elimination of contact with an allergen.

To eliminate/reduce cough, two main methods are used: pharmacological and non-pharmacological (Fig.) [4, 13].

In a number of cases, cough regression can be achieved without the use of medications. Among non-drug methods, one should mention smoking cessation (allows to reduce the severity of cough in smokers and patients with COPD), increased fluid intake - “hydration” in patients with acute respiratory viral infections [14–15], ensuring sufficient air humidity in the room, abolition cough-provoking drugs.

The actual pharmacological method of treating cough involves prescribing antitussives. Antitussive drugs include two groups [4, 13, 16]:

1) drugs that suppress cough in the central or peripheral level; 2) mucoactive drugs.

It is worth noting that the prescription of drugs that suppress the cough reflex (cough suppressants) can be justified only in the case of a dry cough, which significantly reduces the patient’s quality of life (cough disrupts sleep, reduces daytime activity, and is accompanied by pain) [13].

In turn, the term “mucoactive drugs” unites a whole group of different drugs that allow you to control cough by changing the amount and properties of bronchial secretions - “protussive therapy” [13, 16].

Among them there are three main groups:

• mucokinetics - drugs that affect the rheological properties (volume, viscosity, mobility) of predominantly the sol component of bronchial secretions;
• mucolytics - drugs that affect the rheological properties (viscosity, elasticity, adhesiveness) mainly of the gel component of bronchial secretions;
• mucoregulators are drugs that change the production of bronchial secretions and the ratio of the main types of cells in the bronchial mucosa.

These three groups include stimulants of mucociliary clearance - drugs that restore or maintain the functional activity of ciliary cells of the bronchial mucosa. As a rule, they have a bronchodilator effect.

Mucoactive therapy

Protussive therapy is used in patients with a productive cough (ie, a cough that produces sputum). Mucoactive therapy is an important component of the treatment of patients with chronic respiratory diseases (primarily COPD and bronchiectasis).

The classification of mucoactive drugs is presented in table.

Mucokinetics (expectorants) are divided according to their mechanism of action into drugs of direct and reflex action. It should be noted that this group of drugs has never been subjected to serious clinical study and their therapeutic value is not obvious [13, 16]. In addition, reflex mucokinetics (licorice root, marshmallow, thermopsis herb) in doses sufficient to significantly enhance secretion can cause a number of undesirable reactions - nausea, vomiting, bronchospasm. Therefore, at present, mucokinetics have been largely replaced by much more effective and safe mucolytic drugs.

Mucolytics differ in their effect on bronchial secretions [3–4, 13, 16]. Among this group of drugs are:

1) drugs that realize their effect primarily in the lumen of the bronchi; 2) drugs that normalize the formation of bronchial secretions.

Drugs that normalize the formation of bronchial secretions include bromhexine and ambroxol, as well as the mucoregulator carbocisteine. It is worth noting that bromhexine itself is a prodrug and is metabolized in the body to form an active metabolite - ambroxol, which determines the main effects of the drug. Drugs of this group have a mixed effect, both mucolytic and secretomotor [13, 16–17]. They increase the activity of lysosomes in goblet cells of the respiratory tract epithelium, resulting in the release of lysosomal enzymes that hydrolyze mucoproteins and mucopolysaccharides. Mucociliary clearance is restored due to stimulation of the production of neutral polysaccharides and surfactant. Ambroxol is an active metabolite of bromhexine and therefore has a more pronounced mucoactive effect. The bioavailability of ambroxol is 70–80% (for bromhexine it is 20%). In addition, when taken orally, the effect of ambroxol begins after 30 minutes and lasts for 6–12 hours. Ambroxol affects the synthesis of bronchial secretions secreted by the cells of the bronchial mucosa. The secretion is liquefied by the breakdown of acidic mucopolysaccharides and deoxyribonucleic acids, while the secretion of secretion is improved. In addition, ambroxol can have an anti-inflammatory effect [18]. The drug has a variety of dosage forms and can be used parenterally, per os or inhalation. The presence of a slow-release capsule form allows you to take the drug once a day.

Carbocisteine ​​has both mucoregulatory and mucolytic effects [4, 13, 16]. The mechanism of action of the drug is associated with the activation of sialic transferase of goblet cells of the bronchial mucosa and the normalization of the ratio of acidic and neutral sialomucins in bronchial secretions (restoration of the viscosity and elasticity of mucus), which makes it similar to mucolytics [16]. The mucoregulatory effect itself consists of reducing the excess number of goblet cells in the bronchial mucosa in pathology and reducing the amount of secretion they produce, which is realized with long-term use of the drug. The use of carbocisteine ​​is accompanied by an increase in IgA secretion. The effect of the drug is realized throughout the respiratory tract (nasal cavity, paranasal sinuses, upper and lower respiratory tract), which has a similar epithelial structure and the presence of goblet cells. Carbocisteine ​​is available only in forms for oral use (tablets, capsules, syrup).

The group of drugs acting in the bronchial lumen consists of thiol-containing drugs (acetylcysteine ​​and erdosteine) and proteolytic enzymes (trypsin, chymotrypsin, dornase alpha). Regarding the latter, it should be noted that the use of enzyme preparations is often accompanied by allergic reactions, worsening bronchial obstruction, and increased destruction of interalveolar septa due to α1-antitrypsin deficiency, which potentiates the development of centriacinar pulmonary emphysema. Therefore, they are not currently used in clinical practice, with the exception of dornase alfa. Dornase alfa is capable of destroying extracellular DNA contained in the viscous bronchial secretions of patients with cystic fibrosis, and its use is reserved only for this category of patients. However, the use of dornase alfa in patients with bronchiectasis not caused by cystic fibrosis, contrary to established practice, is not recommended [19].

The mucolytic effect of thiol-containing drugs (acetylcysteine, erdosteine) is realized in the bronchial lumen and is based on the presence of sulfhydryl SH groups, which break the disulfide bonds of sputum mucopolysaccharides, making it less viscous. Acetylcysteine ​​is characterized by a variety of dosage forms, which allows the drug to be used orally, inhaled, intratracheally, intravenously and intramuscularly. It is worth noting that with long-term use of acetylcysteine, the production of lysozyme and secretory immunoglobulin A may decrease; the drug should also be prescribed with caution to patients with broncho-obstructive syndrome.

In addition to the mucolytic effect, thiol-containing drugs have a pronounced direct (due to sulfhydryl groups) and indirect (due to activation of glutathione synthesis) antioxidant effect. The pronounced antioxidant nature of these mucoactive agents is very promising, as it reduces the activity of inflammatory processes in the respiratory tract, which is especially important for patients exposed to tobacco smoke, in whom oxidative processes are activated and antioxidant activity is reduced [3].

In this context, special attention should be paid to a mucolytic containing two sulfhydryl groups that are released during metabolism - erdosteine ​​[4, 13]. Erdosteine ​​is a prodrug; it is rapidly and extensively metabolized in the liver to form three active metabolites that have mucolytic and antioxidant properties. The mechanism of influence on mucociliary clearance is mediated by reducing sputum viscosity (rupture of disulfide bridges), enhancing the secretory function of the respiratory tract epithelium, and stimulating motor function [4, 20–22].

The pharmacokinetics of erdosteine ​​indicate that after its administration at a dose of 300 mg, the maximum plasma concentration is reached in approximately 1 hour [23], the half-life of the drug is more than 5 hours. The optimal daily dose is 600 mg/day, divided into 2 doses (300 mg each). The maximum daily dose may be 900 mg (for example, for exacerbation of COPD). According to research, the effective effect on sputum volume, its viscosity, and cough severity becomes significant on the 3rd day of treatment; the average duration of therapy is about 7 days [21].

Erdostein is able to increase the concentration of antibiotics - amoxicillin and clarithromycin - in bronchial secretions without affecting their concentration in the blood serum, and enhances the effectiveness of treatment compared to antibacterial therapy in combination with placebo [24–25].

Considering the fact that erdosteine ​​is a prodrug that is stable to hydrolysis under acidic conditions, therefore, when passing through the stomach, the drug does not have a direct effect on gastric mucus, i.e., a priori it has a good safety profile [21]. There is no data on the interaction of erdosteine ​​with other drugs [20]. According to the results of a number of studies, erdosteine ​​is safe in the treatment of elderly patients in cases of moderate renal and liver failure. It is worth remembering that in case of severe liver failure, as well as when creatinine clearance decreases to 25 ml/min or less, it is recommended to reduce the dose of erdosteine ​​by 2 times [20].

An important feature of erdosteine ​​is its ability to have a pronounced antioxidant effect, namely to suppress oxidative processes in the respiratory tract that develop during acute and chronic inflammation, and thus have an anti-inflammatory effect [26–27]. It is recognized that the antioxidant activity of erdostein is higher than that of other thiols [28–29].

Interestingly, this property of erdosteine ​​may be realized as a protective effect against the damaging effects of cigarette smoke, leading to the inactivation of α1-antitrypsin. This protein, produced by the liver, controls the activity of elastase, which is produced by neutrophils in response to inflammation. If its activity is not controlled by α1-antitrypsin, it leads to the destruction of interalveolar septa and the occurrence of emphysema.

In addition, erdostein increases the concentration of IgA in the mucous membrane of the respiratory tract in patients with chronic respiratory diseases, and also reduces the inhibitory effect of tobacco smoke on granulocyte function.

Another interesting property of erdosteine ​​is its direct anti-adhesive effect, mediated by the destruction of the pilin protein molecule on the surface of the bacterial cell, which is necessary for the attachment of the bacterium to the epithelium of the respiratory tract [30].

The effectiveness of erdosteine ​​has been studied in a number of well-designed randomized trials, including placebo-controlled protocols. Thus, in the work of G. Ricevuti et al. use of the drug in patients with exacerbation of chronic bronchitis led to a more rapid regression of clinical symptoms of exacerbation compared to placebo [31].

An authoritative meta-analysis [32], which included 15 randomized trials (1046 patients with chronic bronchitis/COPD), demonstrated that erdostein resulted in a faster reduction in the severity of clinical symptoms of exacerbation compared to placebo and other mucoactive drugs. Thus, the frequency of cough and its intensity decreased by 81% and 70%, respectively, which was significantly better compared to those when patients took placebo. According to the researchers, the effectiveness of erdosteine ​​was higher than that of other mucolytics. In a study by A. Bisetti et al. [33] erdosteine ​​therapy was accompanied by a decrease in the intensity and frequency of cough, and sputum viscosity compared to placebo. Another randomized placebo-controlled study in patients with exacerbation of COPD [34] showed that patients taking erdosteine ​​had significantly lower concentrations of C-reactive protein and fibrinogen on the 10th day of therapy. In addition, there was a faster resolution of exacerbation symptoms in the erdosteine ​​group compared to placebo. The researchers concluded that the drug has an anti-inflammatory effect, which has a positive effect on relieving symptoms of exacerbation of COPD.

The mucoactive, antioxidant and anti-inflammatory effects exerted by erdosteine ​​are most clearly reflected in long-term therapy of patients with chronic bronchitis (CB)/COPD [35]. It is worth noting that the prerequisites for large-scale studies of erdosteine ​​in COPD were predetermined by data indicating that the presence of a constant productive cough in this category of patients is associated with both a faster rate of disease progression and an increased risk of developing exacerbations, which in turn determine the prognosis patient [36–37, 44]. Currently, based on a number of studies, it has been proven that sputum overproduction is one of the important factors in the development of the disease, as well as a predictor of the development of frequent exacerbations of the disease and mortality [38–40, 44].

The use of erdosteine ​​in patients with CB/COPD can have a positive effect on the frequency of exacerbations [22, 41]. For example, in a study by M. Fioretti et al. in the group of patients taking erdosteine, the number of exacerbations was significantly lower compared to placebo - 48.9% and 12.6%, respectively [42].

Another 8-month study demonstrated that erdosteine ​​was associated with significantly fewer exacerbations and associated hospitalizations compared with placebo [43]. The total length of hospital stay in patients taking erdosteine ​​was 70 days, while in the placebo group this figure was 163 days. According to the study results, the use of erdosteine ​​was accompanied by a decrease in the frequency of exacerbations of COPD by 36.9%, and a decrease in the duration of hospitalization by 57%. It is very important that the study showed significant improvements in pulmonary function, exercise capacity and quality of life during treatment with erdosteine ​​compared with placebo [43].

It is important that in all studies the authors noted good tolerability of the drug, comparable to that when taking placebo and other mucolytics [32]. This is important, since in the case of managing patients with COPD with a productive cough and frequent exacerbations of the disease, long-term use of the drug is required [43–44]. Very interesting are the results of the placebo-controlled RESTORE trial [45], in which patients with COPD took erdosteine ​​(600 mg per day) or placebo for 12 months. It turned out that the use of the drug leads to a reduction in the frequency of exacerbations by 19.4%. Erdostein also reduced the duration of exacerbation, regardless of its severity, by 24.6%.

Thus, research data indicate that long-term therapy with erdosteine ​​at a dose of 600 mg per day in patients with COPD leads to an improvement in quality of life and a decrease in the number of exacerbations of the disease.

In conclusion, it should be noted that the prospects for the use of erdosteine ​​in Russia are associated with the appearance of a domestic drug (Elmutsin) “on the horizon,” which, obviously, significantly expands the capabilities of a practitioner when prescribing mucoactive therapy.

Literature

1. Morice A. Epidemiology of cough // Pulm Pharmacol Ther. 2002; 15: 253–259.
2. Morice A., McGarvey L., Pavord I. et al. Recommendations for the management of cough in adults // Thorax. 2006; 61:1–24.
3. Chuchalin A. G., Ambrosimov V. N. Cough. M.: Publishing house. "Echo", 2012. 128 p.
4. Zaitsev A. A., Okovity S. V. Cough: differential diagnosis and rational pharmacotherapy // Therapeutic archive. 2014. T. 86. No. 12. P. 85–91.
5. Cullinan P. Persistent cough and sputum: prevalence and clinical characteristics in south east England // Respir Med. 1992; 86: 143–149.
6. Lundback B., Nystrom L., Rosenhall L. et al. Obstructive lung disease in northern Sweden: respiratory symptoms assessed in a postal survey // Eur Respir J. 1991; 4: 257–266.
7. Cerveri I., Accordini S., Corsico A. et al. Chronic cough and phlegm in young adults // Eur Respir J. 2003; 22 (3): 413–417.
8. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2018. Available at https://goldcopd.org/gold-reports/.
9. Fuhrman C., Delmas M. Epidemiology of chronic obstructive pulmonary disease in France // Rev Mal Respir. 2010; 27 (2): 160–168.
10. Buist A. International variation in the prevalence of COPD (the BOLD Study): a population-based prevalence study // Lancet. 2007; 370(9589):741–750.
11. Menezes A. Chronic obstructive pulmonary disease in five Latin American cities (the PLATINO study): a prevalence study // Lancet. 2005; 366 (9500): 1875–1881.
12. Chuchalin A., Khaltaev N., Antonov N. Chronic respiratory diseases and risk factors in 12 regions of the Russian Federation // Int J COPD. 2014; 9:963–974.
13. Zaitsev A. A., Okovity S. V., Kryukov E. V. Cough. Practical guide for doctors. M.: Main Military Clinical Hospital named after. N. N. Burdenko, 2015.
14. Zaitsev A. A. Directions of pharmacotherapy and prevention of acute respiratory viral infections // RMJ. 2009; T. 17. No. 23: 1525–1529.
15. Zaitsev A. A., Sinopalnikov A. I. Rational pharmacotherapy of acute respiratory viral infections // Consilium Medicum. 2008; T. 10. No. 10: 80–86.
16. Okovity S.V., Anisimova N.A. Pharmacological approaches to antitussive therapy // Russian Medical Journal. 2011; No. 23: 1150–1158.
17. Klyachkina I. L. Choice of medications for productive cough // Consilium Medicum. 2007; vol. 9, no. 1.
18. Beeh KM, Beier J., Esperester A., ​​Paul LD Antiinflammatory properties of ambroxol // Eur J Med Res. 2008; 13:12:557–562.
19. Zaitsev A. A., Moiseev S. V. Bronchiectasis not caused by cystic fibrosis: epidemiology, diagnosis and treatment // Clinical pharmacology and therapy. 2022. T. 26. No. 5. pp. 19–24.
20. Balsamo R., Lanata L., Egan CG Mucoactive drugs // Eur. Respira. Rev. 2010. Vol. 19. No. 116. P. 127–133.
21. Moretti M. Pharmacology and clinical efficacy of erdosteine ​​in chronic obstructive pulmonary disease // Expert Rev Respir Med. 2007; 1:307–316.
22. Moretti M. Erdosteine: its relevance in COPD treatment // Expert Opin Drug Metab Toxicol. 2009. Vol. 5. R. 333–343.
23. Savu S., Mitrea M., Silvestro L., Mancini C. HPLC with on-line mass spectrometry detection applicable to elucidate erdosteine ​​metabolism // Int J Clin Pharm Ther. 2000. Vol. 38. R. 415–417.
24. Ricevuti G., Nazzone A., Uccelli E. et al. Influence of erdosteine, a mucolytic agent, on amoxicillin penetration into sputum in patients with an infectious exacerbation of chronic bronchitis // Thorax. 1988. Vol. 43. P. 585–590.
25. Braga PC, Zuccotti T., Dal Sasso M. Bacterial aggression: effects of the SH metabolite of erdosteine ​​(mucoactive drug) plus clarithromycin versus clarithromycin alone // Chemotherapy. 2001. Vol. 47. P. 208–214.
26. Dal Negro R. Erdosteine: antitussive and anti-inflammatory effects // Lung. 2008; 186:70–73.
27. Rahman I. Pharmacological antioxidant strategies as therapeutic interventions for COPD // Biochim. Biophys. Acta. 2012. Vol. 1822. No. 5. P. 714–728.
28. Cogo R. Erdosteine: a new therapeutic weapon beyond the PEACE // Trends in Medicine. 2012. Vol. 12. No. 3. P. 133–142.
29. Moretti M., Marchioni C. An overview of erdosteine ​​antioxidant activity in experimental research // Pharmacol Res. 2007; 55: 249–254.
30. Braga PC, Dal Sasso M., Sala MT, Gianelle V. Effects of erdosteine ​​and its metabolites on bacterial adhesion // Arzneimittelforschung. 1999. Vol. 49. No. 4. P. 344–350.
31. Ricevuti G., Nazzone A., Uccelli E. et al. Influence of erdosteine, a mucolytic agent, on amoxicillin penetration into sputum in patients with an infectious exacerbation of chronic bronchitis // Thorax. 1988. Vol. 43. P. 585–590.
32. Cazzola M., Floriani I., Page CP The therapeutic efficacy of erdosteine ​​in the treatment of chronic obstructive bronchitis: a meta-analysis of individual patient data // Pulm. Pharmacol. Ther. 2010. Vol. 23. No. 2. P. 135–144.
33. Bisetti A., Mancini C. Mucolytic activity of erdosteine ​​double blind clinical trial vs placebo // Arch. Med. Inter. 1995; 47:89–97.
34. Bianchi B., Ballabio M., Moretti M. Effects of erdosteine ​​on serum biomarker concentrations at COPD exacerbation // Eur. Respira. J. 2010; 36:378.
35. Avdeev S.N. Prospects for the use of modern mucoactive drugs in the treatment of patients with chronic obstructive pulmonary disease // Pulmonology. 2014. No. 2. P. 100–108.
36. Burgel P.-R., Nesme-Meyer P., Chanez P. et al. Cough and sputum production are associated with frequent exacerbations and hospitalizations in COPD subjects // Chest. 2009; 135:975–982.
37. Speizer FE, Fay ME, Dockery DW et al. Chronic obstructive pulmonary disease mortality in six US cities // Am. Rev. Respira. Dis. 1989; 140(3):49–S55.
38. Prescott E., Lange P., Vestbo J. Chronic mucus hypersecretion in COPD and death from pulmonary infection // Eur. Respira. J. 1995; 8:1333–1338.
39. Vestbo J., Prescott E., Lange P. Association of chronic mucus hypersecretion with FEV1 decline and chronic obstructive pulmonary disease morbidity. Copenhagen City Heart Study Group // Am. J. Respira. Crit. Care Med. 1996; 153:1530–1535.
40. De Marco R., Accordini S., Cerveri I. et al. Incidence of chronic obstructive pulmonary disease in a cohort of young adults according to the presence of chronic cough and phlegm // Am. J. Respira. Crit. Care Med. 2007; 175: 32–39.
41. Dal Negro R., Visconti M., Tognella S., Micheletto C. Erdosteine ​​affects eicosanoid production in COPD // Int J Clin Pharmacol Ther. 2011; 49:41–45.
42. Fioretti M., Bandera M. Prevention of exacerbation in chronic bronchitis patients with erdosteine ​​// Med. Praxis. 1991. Vol. 12. No. 4. P. 219–227.
43. Moretti M., Bottrighi P., Dallari R. et al. The effect of long-term treatment with erdosteine ​​on chronic obstructive pulmonary disease: The equallife study // Drugs Exp. Clin. Res. 2004, 30: 143–152.
44. Sinopalnikov A.I., Zaitsev A.A. Modern view on pharmacotherapy of exacerbations of chronic obstructive pulmonary disease // Treating Physician. 2009. No. 10. P. 45–49.
45. Dal Negro R., Wedzicha J., Iversen M. et al. Effect of erdosteine ​​on the rate and duration of COPD exacerbations: the RESTORE study // Eur Respir J. 2017; 12; 50 (4).

A. A. Zaitsev, Doctor of Medical Sciences, Professor

FSBI GVKG im. acad. N. N. Burdenko Ministry of Defense of the Russian Federation, Moscow

Contact Information

Mucoactive cough therapy: what's beyond the horizon? / A. A. Zaitsev For citation: Attending physician No. 10/2018; Page numbers in the issue: 22-27 Tags: respiratory tract, inflammation, mucokinetics, mucolytics

Ambrobene

Another popular drug for wet cough. A mucolytic with an expectorant effect contains the active substance ambroxol, which helps to thin and remove mucus from the lungs and stimulates expectoration. Within 30 minutes after taking Ambrobene it begins to act, and the positive effect lasts for 6-12 hours. It is very important to drink plenty of fluids during treatment with Ambrobene. This cough remedy is prescribed to adults and children over two years of age. The duration of treatment with the drug should not exceed 4-5 days.

Ambrobene

Merkle GmbH, Germany

Ambrobene is a mucolytic expectorant.
It is used for acute and chronic diseases of the respiratory tract, which are accompanied by impaired formation and discharge of sputum. from 100

5.0 1 review

1742

• Like
• Write a review

pharmachologic effect

Most expectorants of plant or synthetic origin act by a reflex mechanism. They reflexively enhance the secretion of water and bicarbonates by the goblet cells of the bronchi. In this case, sputum, absorbing water, loses its viscosity, becomes more fluid, is easier to exfoliate and is evacuated both by the cough reflex and by the ciliated epithelium of the bronchi.

A separate group of mucolytic agents is distinguished (from the Latin mucus mucus and lysis decay). This is a group of synthetic substances that have an expectorant effect according to a special mechanism. Unlike expectorants, they directly interact with sputum and cause the breakdown of the viscous gel-like matrix at the chemical level by breaking the disulfide bonds of the mucopolysaccharide. This leads to liquefaction of sputum and easier removal. This type of pharmacological action is called mucolytic.

Plantain and coltsfoot syrup from Evalar

This drug is indicated for both wet and dry coughs. Effective and affordable. “Plantain and coltsfoot syrup” soothes coughs and has a good expectorant and cooling effect. Plantain and coltsfoot are excellent natural anti-inflammatory agents: they relieve irritation, disinfect, thin mucus, soothe and regenerate mucous membranes. To stimulate local immunity, the syrup is enriched with vitamin C. It also contains peppermint essential oil, which reduces the severity of cough, coats the mucous membrane of the throat, and cools it. There is no alcohol in Plantain and Coltsfoot Syrup, so taking it does not affect the speed of reactions. The drug has a pleasant taste.

Plantain and coltsfoot syrup

Evalar, Russia

Plantain and coltsfoot syrup from Evalar helps to liquefy and remove mucus.
Recommended for dry and wet cough. from 85

4.0 1 review

327

• Like
• Write a review

Classification

Expectorants are classified based on the source of their production, natural or synthetic, as well as the type of action - expectorants themselves and mucolytic agents. When talking about herbal products, we mean preparations based on plants specified in the classification.

1. Herbal expectorants
   Marshmallow root
2. Mother-and-stepmother leaves
3. Large/oval/lanceolate plantain leaves
4. Primrose roots
5. Licorice roots
6. Oregano herb
7. violet grass
8. Elecampane root
9. Thyme preparations
10. Thyme preparations
11. Pine buds
12. Anise preparations
13. Ledum shoots
14. Thermopsis grass
15. Expectorants of synthetic origin
    Guaifenesin
16. Terpinhydrate
17. Cineole
18. Myrtol
19. Potassium iodide
20. Sodium iodide
21. Mucolytics
    Bromhexine
22. Ambroxol
23. Acetylcysteine
24. Carbocisteine

Lazolvan

The active ingredient of this mucolytic expectorant for wet coughs is ambroxol hydrochloride. "Lazolvan" is prescribed for acute and chronic bronchitis, pneumonia, obstructive pulmonary disease, asthma, bronchiectasis. The product helps well with non-productive cough - both in complex therapy and as a single drug. Without consulting a doctor, Lazolvan should not be taken for longer than 4-5 days. Lazolvan tablets are indicated for adults and children over 12 years of age.

Lazolvan

Boehringer Ingelheim, Germany

Lazolvan stimulates the serous cells of the glands of the bronchial mucosa, increases the content of mucous secretions and the release of surfactants (surfactant) in the alveoli and bronchi;
normalizes the disturbed ratio of serous and mucous components of sputum. By activating hydrolytic enzymes and enhancing the release of lysosomes from Clara cells, it reduces the viscosity of sputum. Increases the motor activity of the cilia of the ciliated epithelium, increases the mucociliary transport of sputum. After oral administration, the effect occurs within 30 minutes and lasts for 6–12 hours from 94

5.0 1 review

1481

• Like
• Write a review

Mucoactive drugs in the treatment of acute cough

Rice. 1. The most common causes of cough

Table 1. Causes and conditions of ineffective cough

Table 2. Mucoactive drugs and their mechanisms of action

Rice. 2. Chemical structure of erdosteine ​​and its metabolite

Cough: epidemiology, classification, clinical picture

Cough ranks second among the reasons for seeking outpatient medical care [1] and first among symptoms caused by pathology of the respiratory system. Cough as a symptom is characteristic of more than 50 nosological forms [2].

For correct diagnosis and treatment of the underlying disease that caused the cough, it is necessary to formulate a cough syndrome that is pathognomonic for a specific nosological form. To do this, install:

• time of cough onset;
• its duration;
• productivity/unproductivity;
• difficulties in expectoration;
• accompanying symptoms.

According to duration, acute cough (up to three weeks), subacute (from three to eight to ten weeks) and chronic cough (more than eight weeks) are distinguished (Fig. 1) [1, 3, 4]. However, this division is largely arbitrary, since these characteristics of cough are not mutually exclusive.

A cough (initially defined as acute) that develops as a result of an acute respiratory viral infection (ARVI) can in some cases last more than three weeks. If the inflammatory process spreads to the entire mucous membrane of the lower respiratory tract, hyperproduction of bronchial mucus and bronchial hyperreactivity are observed, then the cough acquires a subacute course and is classified as post-infectious [5]. Overproduction of viscous bronchial mucus and hyperreactivity of the respiratory tract lead to significant disturbances in mucociliary clearance, difficulty in expectorating sputum, mucostasis, and bacterial colonization of the respiratory tract. Fever, asthenia, and yellow-green sputum are often observed.

In patients with chronic bronchitis/chronic obstructive pulmonary disease (COPD) during periods of exacerbation due to acute respiratory viral infections/influenza, with proper treatment, a severe cough can last only two to three weeks, recurring several times throughout the year. However, during the period of remission, this symptom may be absent.

At the same time, an acute cough can be a symptom of serious diseases such as pulmonary embolism, edema or lung cancer. This is the most common symptom associated with exacerbations and inevitable hospitalization in patients suffering from bronchial asthma and COPD [3].

Chronic cough is often a symptom of serious chronic respiratory diseases, but it may also be the only sign of extrapulmonary pathology, in particular diseases of the upper respiratory tract or gastrointestinal tract [6].

Productive cough is observed with inflammatory/infectious lesions of the lower respiratory tract, which are accompanied by hyperproduction of bronchial mucus. A productive cough, usually wet, is accompanied by expectoration of sputum - viscous bronchial mucus, pus, tissue decay products, etc. In turn, the absence of expectoration of sputum - a dry cough - can be either a consequence of the ineffectiveness of a productive cough, or the result of a non-productive cough, for example with postnasal drip, gastroesophageal reflux disease and other diseases in which sputum hyperproduction does not occur.

It should be noted that the effectiveness of a productive cough (sputum expectoration) depends on many reasons: the phase of the disease (in pneumonia, a productive cough remains dry for a certain time; in chronic bronchitis, bronchial asthma, an increase in bronchial obstruction may be accompanied by a cessation of sputum expectoration), localization of the process (for example , with different localization of the malignant process or pulmonary tuberculosis - in the lung parenchyma, bronchi, pleura), etc. At the same time, false productivity may be observed - for example, with postnasal drip, nasal mucus is coughed up in patients with rhinitis and/or sinusitis.

Among the reasons for the ineffectiveness of productive cough are [7]:

• insufficiently expressed cough reflex (in the elderly, newborns, etc.);
• high viscosity of sputum;
• low power of the air stream during a cough impulse, due to chest rigidity, low compliance of the lungs or impaired bronchial obstruction;
• insufficiently deep breathing (promotion of secretion in the bronchi is proportional to the depth of breathing).

In addition, in certain situations (with fractured ribs, other traumatic injuries to the chest, after surgical interventions on the chest and abdominal organs, etc.), patients involuntarily resist coughing (Table 1) [8].

Treatment

It should be noted that the problem of acute cough has not been sufficiently studied, as well as the possibilities of its drug therapy [9]. After establishing the causes of cough, etiotropic and pathogenetic treatment of the underlying disease should be carried out. In parallel - symptomatic:

• antitussive – to prevent, manage and/or suppress cough;
• protussive – for greater cough effectiveness.

Antitussive therapy for acute cough associated with respiratory tract infection is not indicated. Nonspecific antitussive therapy is recommended only if the cough does not help clear the airways and is rather symptomatic. It is used mainly in cases of unsuccessful specific therapy, for example, with inoperable lung cancer [10, 11].

Procough therapy is pathogenetically justified if the cough has a protective function and needs to be stimulated - for bronchitis, pneumonia, etc.

Currently, a large number of drugs are known that, by affecting the viscosity, elasticity and adhesiveness of bronchial mucus, facilitate its expectoration. These drugs are called mucoactive. Some mucoactive drugs have been used for more than a century (they are classified as traditional medicine), others - specially synthesized - have become widely used only since the middle of the 20th century. Depending on the predominant mechanism of action, four classes of mucoactive drugs are distinguished: expectorants (expectants), mucoregulators, mucolytics and mucokinetics (Table 2) [12].

This division is somewhat arbitrary, since both the mucokinetic ambroxol and the mucoregulator carbocysteine ​​have the ability to break down the intermolecular bonds of mucopolysaccharides of bronchial mucus, and the mucolytic acetylcysteine ​​has anti-adhesive properties. At the same time, doctors must know the peculiarities of the mechanisms of action of the most frequently and successfully used drugs - ambroxol, carbocysteine, acetylcysteine ​​and erdosteine, in order to consciously make a choice in each specific case.

Next, we will consider in detail the drugs most often used in the treatment of acute cough due to ARVI, acute bronchitis, pneumonia, etc.

Mucoregulators

Carbocisteine

(Bronkatar, Fluditek, etc.),
lysine salt of carbocysteine
​​(Fluifort) have primarily a mucoregulatory effect (Table 2). The mechanism of their action is associated with the activation of sialic transferase, an enzyme of goblet cells of the bronchial mucosa. Carbocisteine ​​reduces the amount of neutral glycopeptides and increases the amount of hydroxysialoglycopeptides. As a result, the viscosity and elasticity of mucus is normalized. Under the influence of the drug, the mucous membrane is regenerated, its structure is restored, the number of goblet cells decreases (normalizes), especially in the terminal bronchioles, and therefore the amount of mucus produced. In addition, the secretion of IgA (specific protection) and the number of sulfhydryl groups (non-specific protection) are restored, mucociliary clearance is improved (the activity of ciliated cells is potentiated). The anti-inflammatory effect is characteristic of all drugs of the thioether group that act on reactive oxygen species [13]. In rhinovirus infections, carbocisteine ​​suppresses the inflammatory process in the mucous membrane of the respiratory tract by reducing the production of cytokines [14].

On average, by the third day of taking carbocysteine, the volume of sputum increases, and in the next two to three days it becomes less viscous and easier to cough up. A good and stable mucolytic effect is observed on the seventh to ninth days of treatment.

The addition of lysine to the carbocysteine ​​molecule increased the effectiveness of the treatment. So, with ARVI, it is possible to stop taking the drug after four days. At the same time, the activity of mucociliary clearance and the normal viscosity of bronchial mucus remain for another eight days [15].

Carbocysteine ​​is equally effective in all parts of the respiratory tract and middle ear, which have a similar epithelial structure and ciliated cells. Due to its anti-inflammatory, mucoregenerative, mucolytic effect, carbocysteine ​​may be indicated for acute rhinitis, rhinosinusitis, and tracheitis.

Carbocisteine ​​is only effective in vivo

Therefore, its preparations are available in the form of tablets, capsules, and syrup. In the form of syrup, it is used in children from five years of age.

Mucokinetics

Bromhexine

– a synthetic derivative of the alkaloid vasicine. It is a prodrug, as it is converted in the liver into an active metabolite – ambroxol. The effect of the drug begins 24–48 hours after administration. The peculiarities of bromhexine are its independent antitussive effect and the ability to provoke bronchial obstruction. The latter is observed when effective doses are used (8–16 mg), which limits the use of the drug. That is why bromhexine is recommended to be used only as part of combination drugs (Bromhexine 8, Bronchosan, Ascoril, etc.) [10].

Ambroxol

(Lazolvan, Ambrobene, Halixol, etc.) reduces the viscosity of the secretions of the bronchial glands, has a mucolytic (secretolytic) and expectorant effect, which is associated with depolymerization and destruction of acidic mucoproteins and mucopolysaccharides of sputum (Table 2). In addition, ambroxol stimulates the production of neutral polysaccharides and, by acting on the bronchial glands, causes the release of lysosomal enzymes. However, the most important is the ability of the drug to stimulate the synthesis of surfactant and the motor activity of the cilia of the ciliated epithelium by alveolar pneumocytes of the second order and Clara cells, which leads to the restoration of mucociliary clearance. In addition, the drug activates the formation of tracheobronchial secretion of low viscosity through a change in the chemistry of sputum mucopolysaccharides. As a result, viscous bronchial mucus thins, its adhesiveness decreases, and its movement through the respiratory tract is facilitated [16].

Ambroxol, to a greater extent than bromhexine, helps to increase the synthesis and secretion of surfactant and prevent its breakdown. This makes ambroxol necessary in patients undergoing long-term inhalation therapy, in particular oxygen therapy (which destroys surfactant), or mechanical ventilation. Thus, ambroxol indirectly increases mucociliary transport (reducing the adhesion of bronchial mucus), which, in combination with increased secretion of glycoproteins (mucoregulatory effect), causes a pronounced expectorant effect. The drug significantly affects the viscosity of sputum, its purulence and patency [17]. Ambroxol is equally effective in in vivo

, and in
vitro
, which allows it to be administered orally, parenterally and inhaled. This explains the wide variety of dosage forms: tablets, solutions for oral administration and inhalation, retard capsules for administration once a day, ampoules for injection and inhalation. The drug begins to act within 36–72 hours. If it is necessary to quickly liquefy excessively viscous sputum, inhalation administration of the drug is possible simultaneously with oral administration [17].

The drug is indicated both for ARVI and for the prevention of exacerbations of chronic diseases, for example, bronchial asthma, COPD. Ambroxol penetrates the placental barrier and is excreted in breast milk, so it is not recommended for use in the first trimester of pregnancy and during breastfeeding [18].

Mucolytics

N-acetyl-L-cysteine

(Fluimucil, ACC Long, etc.), a derivative of L-cysteine ​​(Table 2), belongs to the group of thiols. The reactive thiol sulfhydryl (SH) groups contained in its molecule break the disulfide bonds of sputum mucopolysaccharides, exerting a direct mucolytic effect. As a result of depolymerization of macromolecules, sputum, including purulent one, becomes less viscous and adhesive. Stimulation of the activity of mucosal cells, the secretion of which is capable of lysing fibrin, blood clots, and pus, also leads to liquefaction of sputum [10, 12].

In 1989, OT Auroma et al. discovered a powerful antioxidant effect of N-acetyl-L-cysteine, both direct (neutralization of free radical groups) and indirect (increasing glutathione synthesis) [19]. This property of N-acetyl-L-cysteine ​​is widely used in the treatment of paracetamol overdose [20]. In addition, the anti-inflammatory properties of N-acetyl-L-cysteine ​​are based on the antioxidant effect [21]. In addition, N-acetyl-L-cysteine ​​indirectly affects the production of bronchial mucus, having a mucoregulatory effect. However, the antioxidant effect of the drug is manifested in doses significantly higher than recommended - 1200–1800 mg.

N-acetyl-L-cysteine ​​is equally effective as in vivo

, and under
in vitro
. The variety of dosage forms (tablets, powder, solutions, injection ampoules) allows you to vary the route of drug administration and individualize therapy. The average daily dose is 600 mg. The drug begins to act in 30–90 minutes. It should be noted that oral administration of N-acetyl-L-cysteine ​​can inactivate the effect of antibiotics, so at least two hours should elapse between doses of drugs [16].

It should also be taken into account that inhalation of N-acetyl-L-cysteine ​​can cause bronchial obstruction in bronchial asthma. Rare adverse events include mild dyspeptic disorders. Taking the drug for a dry, unproductive cough is rather unjustified, since it contributes to the intensification of a severe hacking cough. N-acetyl-L-cysteine ​​should be prescribed with caution to patients with a reduced cough reflex in order to avoid “flooding” of the lungs due to an excessive decrease in the viscosity and elasticity of bronchial mucus (people of older age groups, children) [10].

Erdostein

(Erdomed) was synthesized in the 1990s. Chemical structure: N-(carboxy-methyl-thioacetyl) homocysteine ​​thiolactone. Is a prodrug. Has two blocked thiol groups. During the initial passage through the liver, it is metabolized to form at least three active metabolites, the main role of which is played by N-thiodiglycolyl-homocysteine ​​(metabolite 1) (Fig. 2).

Erdostein has mucolytic, antioxidant, anti-inflammatory, antiadhesive and mucoregulatory effects [22].

The thiol groups of the metabolite break the disulfide bridges that bind glycoprotein fibers, which leads to a decrease in the elasticity and viscosity of bronchial mucus. Erdostein enhances and accelerates the release of secretions from the respiratory tract, improves the secretory function of the epithelium and increases the efficiency of mucociliary clearance in the upper and lower respiratory tract [12].

Due to the presence of sulfhydryl groups, erdostein has a pronounced antioxidant effect, both direct and indirect. The direct antioxidant effect is to reduce the production of reactive oxygen species such as hypochloric acid, hydrogen peroxide, superoxide anion and peroxynitrite [23]. The indirect effect involves the prevention of tissue damage as a result of exposure to oxidative stress products [24], increases the level of glutathione in bronchoalveolar lavage fluid [25] and the liver, and increases alpha-1-antitrypsin activity in the lungs of smokers [26]. The antioxidant effect, both direct and indirect, is observed when taking an average therapeutic dose. The pronounced antioxidant effect of erdostein allows it to be recommended to patients with chronic bronchopulmonary diseases, as well as active and passive smokers.

The anti-inflammatory effect of erdostein is to reduce the level of inflammatory markers (albumin, IgG, deoxyribonucleic acid) and increase the level of anti-inflammatory mediators (IgA, lactoferrin, lysozyme) [27].

The antiadhesive effect of erdostein is to reduce bacterial adhesion to the cells of the host body [28]. The drug blocks microfilaments and microfimbriae of bacteria: through its thiol (SH) groups, it destroys protein (pilin) ​​in bacterial microfimbriae. As a result, adhesion of the bacterium to the host cell becomes impossible.

In addition, erdostein increases the concentrations of antibiotics (amoxicillin, ciprofloxacin) in bronchial mucus, providing an aftereffect, enhances the antiadhesive effect of clarithromycin and other antibiotics and increases the aftereffect period of the antibiotic to eight hours. At the same time, the drug increases the concentration of the antibiotic in sputum without reducing serum concentrations [29].

Thus, the drug potentiates the effect of antibiotics for respiratory infections, and is also used in cases of viral origin of the disease, preventing their prescription.

In addition to the mucolytic effect characteristic of thiols, erdostein enhances the mucoregulatory effect of the epithelium of the respiratory tract and stimulates their motor function. Due to the direct effect on the functional state of the ciliated epithelium of the respiratory tract, it increases the efficiency of mucociliary clearance (mucokinetic effect). At the same time, the drug has a moderate antitussive effect.

Erdosteine ​​is rapidly absorbed from the gastrointestinal tract and metabolized in the liver to three active metabolites. The half-life is more than five hours. Food intake does not affect pharmacokinetic parameters. The maximum concentration is 3.46 μg/ml, the time to reach the maximum concentration is 1.48 hours, the area under the concentration-time curve from 0 to 24 hours is 12.09. 64.5% of erdosteine ​​binds to blood plasma proteins. The drug is excreted in the form of inorganic sulfates through the kidneys and intestines [16].

Appointed to adults over 18 years of age. It is administered orally (capsules 300 mg No. 20 and granules for preparing a suspension 35 mg/ml).

The use of the drug is indicated for the development of cough with difficult to separate sputum during ARVI, acute bronchitis, pneumonia, for the prevention of pneumonia and partial atelectasis after surgical interventions. Clinical effects (reduction in the frequency and severity of cough, positive dynamics of auscultatory data: hard breathing and wheezing) are observed already by the end of the first day of taking the drug [30]. In patients with exacerbation of chronic bronchitis during therapy with erdosteine, a significant dilution of bronchial mucus was achieved and its good expectoration by the second day of therapy [31].

Please note: unlike the other mucoactive drugs described above, erdosteine ​​is well tolerated with a dry, unproductive cough, which is characteristic of most acute respiratory viral infections. This is primarily due to the antitussive effect of the drug [12].

An important role is played by the indirect antioxidant effect of the drug - an increase in the level of glutathione in the liver - in connection with the widespread use of paracetamol for acute respiratory viral infections. Increasing glutathione levels prevents the development of liver failure with an absolute or relative overdose of paracetamol.

The effectiveness of erdosteine ​​in the complex treatment of exacerbations of COPD has been shown in several randomized placebo-controlled studies. Thus, in an international multicenter randomized, placebo-controlled, double-blind study in parallel groups, synergy between erdosteine ​​and amoxicillin was noted in patients with infectious exacerbation of COPD [32]. The controlled randomized trial EQUALIFE confirmed the effectiveness of erdosteine ​​in the treatment of patients with COPD: the number of exacerbations decreased by 32%, hospitalizations by 44%, forced expiratory volume in the first second increased by 14% [33].

The drug does not have a damaging effect on the gastrointestinal tract. Cumulation of metabolites is possible in renal failure. Contraindicated in case of impaired liver function, renal failure, homocysteinuria, phenylketonuria. Taking the drug during pregnancy and lactation is possible only under very strict indications.

Conclusion

Erdostein is a new effective mucoactive drug with pronounced anti-adhesive activity. Erdostein potentiates the effect of antibiotics in respiratory infections, and is also used in cases of viral genesis of the disease in order to avoid their prescription. Erdosteine ​​is prescribed for the purpose of earlier and lasting regression of respiratory symptoms and reducing the risk of bacterial complications in patients at risk (elderly, immunocompromised, active and passive smokers), as well as in the following cases:

• when coughing with difficult to separate sputum;
• lingering cough;
• pathologies of the stomach and duodenum;
• combating tobacco addiction and quitting smoking.

Traditional methods of treating wet cough

In addition to medications for wet coughs, there are proven folk methods that help thin and remove mucus. Here are some of them.

1. Milk with honey.
   You need to heat a glass of milk, add a couple of teaspoons of honey and a pinch of soda. This drink perfectly thins and removes phlegm. Another recipe is milk with butter. This recipe is suitable if you have an irritated throat (the drink eliminates soreness and soothes the mucous membranes).
2. Milk with banana.
   Add banana puree and a couple of teaspoons of cocoa to a glass of heated milk. Children will definitely appreciate this cough remedy. You need to drink the drink before going to bed.
3. Black radish.
   Radish contains an essential oil with a bactericidal effect, plus black radish is an excellent stimulant for mucus discharge. To treat a cough, take 1 teaspoon of radish juice five times a day. To “extract” the juice of a black radish, you need to cut it into two parts, remove some of the pulp, and put honey in the resulting holes. If you don't have honey, you can simply grate the radish and add a little sugar.
4. Honey compress.
   To relieve a cough, you can rub liquid honey on your chest, put parchment paper on top, and then cover yourself with a warm blanket. After half an hour, wipe off the honey with a damp cloth and wrap yourself up.
5. Chocolate for cough.
   Another recipe that kids will love. Melt 100 g of butter, add 100 g of chocolate and 2 tbsp. l. cocoa. Warm everything over low heat or in a water bath until the ingredients are well mixed. Cool and you can spread this chocolate spread on bread or cookies for your child. It’s great if the baby agrees to drink it with warm milk.