Ambroxol
Ambroxol is an expectorant used mainly for infectious and inflammatory diseases of the respiratory tract that occur with the formation of viscous and difficult to separate sputum. The drug, in fact, restructures sputum, radically changing its physicochemical characteristics and giving it greater evacuation abilities. Thus, ambroxol breaks disulfide bonds in the molecules of sputum polysaccharides, which leads to their depolymerization and an associated decrease in the viscosity of bronchial secretions. The increased activity of hydrolyzing enzymes and the release of lysosomes from Clark cells also contribute to an increase in the rheological properties of sputum. At the same time, the drug stimulates the activity of the cilia of the ciliated epithelium, which promote the movement of sputum up the respiratory tract, and has a protective effect on the alveoli due to stimulation of the synthesis of pulmonary surfactant. Chronic diseases of the lungs and respiratory tract lead to inhibition of surfactant synthesis and a change in its properties for the worse, so taking ambroxol in these cases is absolutely justified.
Currently, you can find two dosage forms of ambroxol in pharmacies: tablets and syrup.
The effect of taking the drug is noticeable within half an hour from the moment of taking it and lasts for 6-12 hours. The tablets should be taken after meals with plenty of water. When taking ambroxol, in order to quickly achieve therapeutically significant concentrations in the blood of a pharmacologically active substance in adults and children under 12 years of age, the so-called “loading” is practiced: for the first 2-3 days it is recommended to take 1 tablet (30 mg) three times a day, after which You can switch to a two-time dose. Children aged 6 to 12 years should take half a tablet (15 mg) 2-3 times a day. It cannot be said that ambroxol is a risky drug in terms of the presence of many side effects of varying severity; however, it is not recommended to take the drug on your own for more than 4-5 days without supervision from your doctor. It is not recommended to take ambroxol together with drugs that suppress the cough reflex: this can lead to impaired sputum excretion. Another limitation in the use of this drug is evening and night time, i.e. Increasing expectoration during sleep is inappropriate and even dangerous.
AMBROXOL (syrup)
Covered with a measuring cap, with which you can easily dose the medicine.
I consider such a measuring cap or spoon to be a good idea, since not everyone is able to dose medicine using a spoon, especially when it comes to babies. The drug is not diluted; it is sold in finished form. The consistency is liquid syrup, slightly sweet and bitter. And yet, it drinks easily and quickly.
The drug is used for acute and chronic respiratory diseases, bronchitis, pneumonia, bronchial asthma.
The drug is not recommended for use up to two years, and is also contraindicated for people suffering from epilepsy and other brain diseases.
Doses and treatment times are determined by a specialist depending on the age of the child and the severity of the disease. Although the medicine is not recommended according to the instructions until the age of two, we were prescribed it for the first time after a year. This is the huge advantage of Ambroxol syrup over other medications. It can be said that we had practically no side effects either during treatment or after. But someone’s body will be sensitive to the drug, and an allergic reaction, nausea, vomiting, and headaches may occur. Therefore, in any case, consultation with a specialist is necessary.
With an advanced or severe cough, syrup does not help us. In this case, we turn to Lazolvan Solution for oral use and inhalation for help. It is more effective and also versatile. Do not try to take the drug at the same time as inhalations, otherwise there may be an overdose, because both drugs have the same active drug. While the medications pass through the gastrointestinal tract, the solution immediately enters the respiratory system. In other cases, I consider Ambroxol to be an effective remedy that removes mucus from the bronchi quite well. Usually the remedy is prescribed for 5 days, then the specialist himself decides to cancel it or replace it (in the absence of a positive result) with another, more effective remedy.
Thus, Ambroxol has shown itself very well in the treatment of cough. This is an effective medicinal syrup in a convenient form, which has saved us from coughing more than once. It is always in our first aid kit. Better yet, strengthen your immune system, which is what we did this year. And I like the result so far. We get sick less often, and the disease is not as severe. Thanks everyone. Don't get sick and take care of your children.
For various diseases of the respiratory system (acute and chronic bronchitis, bronchial asthma, bronchiectasis and many others), as a rule, special drugs are prescribed that affect cough and thin sputum. Coughing as a protective reflex ensures cleansing of the mucous membrane of the respiratory tract from viruses, bacteria, foreign particles, allergens, etc., not only in full health, but also at the time of illness. Therefore, for diseases that occur with the presence of sputum, it is contraindicated to prescribe cough suppressants. Stopping the protective cough reflex is allowed only in specific cases and for special indications, for example, with whooping cough, measles tracheitis, during surgery, in intensive care, or in the child’s condition, which extremely complicates his well-being.
Another protective mechanism invented by nature is mucus, or so-called. sputum, which must necessarily line the bronchial tree in small quantities from the inside. Harmful agents settle in the sputum, which are then evacuated by coughing. By the nature of the mucus, one can preliminarily judge the etiology of inflammation: for example, with allergies, the mucus is usually transparent, viscous, “vitreous.” With a viral infection, it is liquid and clear or white. You can think about bacterial inflammation if the mucus is viscous, thick, and yellow-green in color. Goblet cells of the bronchial mucosa at the time of inflammation (allergic, infectious or immune) begin to intensively produce additional mucus (or sputum). In the respiratory tract, the amount of sputum not only increases, but its rheological properties also change towards thickening. Sputum becomes viscous, loses elasticity, and its adhesive properties are impaired. It is logical that at such a moment therapeutic tactics boil down to improving the quality of sputum, normalizing its chemical properties, which leads to the restoration of the drainage function of the bronchi and gradual recovery. The quality of sputum also negatively affects the functioning of mucociliary transport. Viscous sputum blocks the work of the ciliated epithelium, which leads to even greater stagnation of mucus, the so-called. mucostasis, a wet cough appears, during which you can hear moist rales in the lungs.
In order to eliminate this situation, the doctor usually selects drugs from three groups of drugs that stimulate coughing - expectorants; mucolytic drugs; combination drugs (contain 2 or more components from different groups). In this case, it is necessary to take into account the characteristics and undesirable effects of each drug, acting on the principle of “maximum therapeutic effect and minimum side effects.” It is important to note that in itself, the increased formation of mucus and its removal from the bronchial tree is not an independent “disease”, but is only a symptom or sign of various pathologies of the respiratory system. Therefore, mucolytic drugs should be used as symptomatic treatment.
The general problem with expectorants is this: they significantly increase the mass of bronchial secretions. In children, especially younger ones, the cough reflex is not perfect, so at the time of illness the child is not able to cough up a large amount of sputum.
Related to this is the so-called the effect of swamping, or flooding, of the lungs, which quickly develops and significantly aggravates the child’s condition. It should also be taken into account that the maximum effect of such drugs usually ends 2-3 hours after administration and it is necessary to constantly add a dose of the drug, which generally leads to its overdose, the development of such adverse reactions as nausea, dizziness, and often vomiting, because The gag reflex in children is usually increased. In addition, allergic reactions often develop when taking expectorants, usually of herbal origin. These drugs are difficult to dose accurately, which is especially important in pediatric practice, due to the fact that they cannot be standardized. It is also necessary to keep in mind that each herbal substance has a systemic effect and, by prescribing it only “for cough”, you can get, for example, a “cure for constipation”. In addition, herbal preparations usually contain not one substance, but a mixture, so it is impossible to predict the consequences of their interaction in the child’s body. It turns out that seemingly simple herbal medicines have rather complex medical features of their use. However, as practice shows, drugs of this particular group, unfortunately, are unreasonably popular among parents, who often prescribe them themselves, which is absolutely unacceptable.
The action of mucolytic agents is aimed at thinning sputum, and unlike expectorants, they do not increase its volume. It should also be noted that mucolytics cannot be prescribed together with expectorants and antitussives, because they have mutually exclusive therapeutic effects. Mucolytics are a group of drugs, which are also divided into subgroups depending on their origin, different chemical structure, have different points of application, mechanisms of action and different therapeutic effects. They increase the fluidity of sputum, normalize its biochemical composition, improve discharge by increasing mucociliary clearance, and can influence goblet cells of the bronchial mucosa, reducing increased secretion. Mucolytics have quite broad indications for use: the presence of viscous, difficult to cough up mucous, mucopurulent or purulent sputum; tracheitis, acute and chronic bronchitis, bronchiolitis, pneumonia, chronic obstructive pulmonary disease, bronchiectasis in adults; cystic fibrosis; atelectasis as a result of mucoid blockage of the bronchi; presence of tracheostomy; as a prophylactic against complications after operations on the respiratory organs, after endotracheal anesthesia; rhinosinusitis, etc.
Mucolytics with a direct type of action include substances of non-enzymatic origin that destroy complex chemical compounds (enzymes and polysaccharides), breaking disulfide bonds between the protein molecules of sputum - these are thiols, acetylcysteine, etc. These drugs contain a thiol group, which makes sputum less viscous, which and facilitates easier removal from the bronchial tree. The main representative of this group is N-acetylcysteine. It is a derivative of L-cysteine and the molecule contains reactive free sulfhydryl groups (SH), which provide a direct mucolytic effect due to the destruction of disulfide bonds of acidic mucopolysaccharides of bronchial mucus. As a result, depolymerization of mucoprotein macromolecules occurs and bronchial mucus becomes less viscous and adhesive. In addition to mucolytic activity, acetylcysteine serves as a powerful direct and indirect antioxidant: it reduces the processes of lipid peroxidation and preserves the integrity of cell walls. Free radicals enhance the development of acute or chronic inflammation in the respiratory tract, causing destruction of lung tissue. The direct antioxidant effect is due to the fact that the free sulfhydryl group of the acetylcysteine molecule interacts with the electrophilic groups of free radicals and reactive oxygen metabolites, neutralizing their effect. Direct antioxidant effects also include protection of α1-antiprotein. The indirect antioxidant effect is due to the fact that acetylcysteine is a precursor of glutathione, which in turn takes part in the processes of detoxification of the body, protecting the mucous membranes of the respiratory tract from external and internal damaging influences. Acetylcysteine can also reduce the ability of microorganisms to colonize on the surface of the mucous membrane of the respiratory tract, exhibiting a sparring effect with antibiotics (the so-called secondary antibacterial effect). When taken orally, acetylcysteine is well absorbed from the gastrointestinal tract. The maximum concentration in the blood plasma is reached within an hour after administration, distributed throughout the body evenly, while a significant increase in the number of sulfhydryl groups is noted in the tissues (including the respiratory tract) and blood plasma. Some proteolytic enzymes are also direct-acting mucolytics (dornase alpha, trypsin, chymotrypsin, ribonuclease, deoxyribonuclease, alpha-chymotrypsin, streptokinase). They are capable of destroying peptide bonds in a protein molecule, breaking down high-molecular protein breakdown products (polypeptides) or nucleic acids (DNA and RNA). It is important to note that the only enzyme approved today for mucolytic purposes in the form of a special solution for nebulizer therapy remains dornase alfa, which is used in the basic therapy of patients with cystic fibrosis. Other drugs are not used today, because their mucolytic effect is very small, and there are quite a lot of complications (damage to the mucous membrane of the respiratory tract, hemoptysis, bronchospasm, allergic reactions, increased destruction of the interalveolar septa, for example, with alpha-antitrypsin deficiency, as well as side effects from other organs).
The group of mucolytics of indirect action is quite diverse. These are drugs that change the adhesiveness of the gel layer (bromhexine, ambroxol, sodium bicarbonate, sodium ethanesulfate); drugs that reduce mucus production and change its composition (S-carboxymethylcysteine, letostein, sobrerol); pinenes and terpenes (camphor, menthol, terpineol, essential oils); drugs that reduce the production of mucus by the bronchial glands (β2-adrenomimetics, glucocorticoids, M-anticholinergics); drugs that act reflexively on the muscles of the bronchi (sodium citrate, ammonium chloride, ipecac, thermopsis) are practically not used in practice today. These drugs are sometimes called mucokinetics.
The action of carbocisteine occurs through a different mechanism. It activates sialic transferase, an enzyme of goblet cells of the bronchial mucosa. This leads to normalization of the quantitative ratio of acidic and neutral sialomucins in sputum: it reduces the amount of neutral glycopeptides and increases the amount of hydroxysialoglycopeptides, restores viscosity and elasticity. The structure and regeneration of the mucous membrane is normalized, the number of goblet cells decreases to a normal ratio, the amount of mucus decreases, and mucociliary transport improves. After oral administration of carbocisteine, the maximum concentration in the blood serum and mucous membrane of the respiratory tract is created after 2 hours and is maintained for 8 hours. Carbocisteine is indicated for acute and chronic bronchitis, for example, against the background of cystic fibrosis. It must be remembered that non-enzymatic mucolytics are contraindicated for pulmonary bleeding, gastric and duodenal ulcers, and can cause dyspeptic symptoms (nausea, heartburn, vomiting, abdominal pain, diarrhea and constipation), hypersalivation or dry mouth, rhinorrhea and allergic reactions.
A prominent representative of non-enzymatic mucolytics of indirect action is ambroxol hydrochloride. Over the past three decades, ambroxol has been widely used as a mucoregulatory agent in various forms - both as monotherapy and in combination with antibacterial drugs. The ambroxol molecule has several mechanisms of action, which determines its complex pharmacology. In addition to its well-known property of clearing mucus from the bronchi, ambroxol has been shown to have antioxidant, anti-inflammatory, analgesic, anesthetic, antiviral, and antibacterial properties [1–5]. Ambroxol is used as mucolytic therapy for acute and chronic diseases of the bronchopulmonary system associated with increased production and impaired formation and separation of sputum. Increased fluid secretion and mucociliary clearance promote coughing [6]. Some foreign publications describe additional properties of this molecule, which are undoubtedly of practical importance in therapy. The local anesthetic effect of ambroxol, observed in a rabbit eye model, has been described; it is regarded as a sodium channel blocker [7]. In vitro studies have shown that ambroxol blocks the cloned neuronal sodium channel, and this binding is reversible and dependent on the concentration of the substance in the serum [8]. Ambroxol has also been shown to significantly reduce the release of cytokines from the blood in vitro [9]. These pharmacological properties are consistent with observations in clinical studies studying the effectiveness of ambroxol therapy for upper respiratory tract pathologies, with a reduction in pain and discomfort associated with pain localized in the ear, nose and trachea [10]. Ambroxol is often combined with antibiotics (amoxicillin), as it increases the concentration of antibiotics in sputum [11]. Due to the properties mentioned above, ambroxol is currently used for pathologies accompanied by hypersecretion of mucus, such as tracheobronchitis, emphysema with bronchitis, chronic inflammatory diseases of the respiratory tract, bronchiectasis and bronchial asthma [6]. Today, a number of data have been published indicating the role of ambroxol in certain diseases of the respiratory tract, accompanied by the development of bacterial films.
Bacterial films are colonies of bacteria attached to an organic or inorganic surface, growing into a self-producing extracellular matrix containing DNA-a, proteins and polysaccharides [12]. Since in these colonies microorganisms grow in a structured community, the bacterial film serves as an organized expression of a kind of bacterial “social” behavior [13]. Therefore, it is not surprising that the process of bacterial film formation is highly regulated by specific mechanisms, among which quorum sensing remains the most important [14]. The term “quorum sensing” refers to a group of regulatory systems through which bacterial populations “sense” the cell density of the colony and trigger adaptive responses to changes in their own density [15]. It is important for physician practice to remember that bacterial films can form on medical objects such as intravenous catheters, urinary catheters, and endotracheal tubes. Therefore, they play a large role in the occurrence of infection, especially for severe patients [16].
In addition to the previously known anti-inflammatory and mucokinetic properties of ambroxol, demonstrated many years ago, several arguments are given indicating the benefits of ambroxol for the prevention and treatment of infections. Thus, it was shown that the ambroxol molecule also has specific activity against bacterial films and the ability to improve mucociliary clearance. Recent studies have shown that ambroxol destroys the structural integrity of the bacterial film; in particular, this was shown in work with isolates of Pseudomonas aeruginosa [17]. The inhibitory effect of ambroxol is not limited only to bacteria: there are indications of its action against fungi. A number of studies have demonstrated that ambroxol interferes with the acquisition of resistance by Candida parapsilosis isolates [18].
Unlike, for example, acetylcysteine, ambroxol is not a true mucolytic drug. Traditionally it is considered as a mucokinetic. The idea that ambroxol affects mucus viscosity not only by directly affecting sputum proteins, but also by interfering with ion transport along the surface of the epithelial membrane has been suggested previously [19]. Despite the fact that to date there are no controlled clinical studies aimed at assessing the effect of ambroxol in intensive care unit patients with ventilator-associated pneumonia, the results of a number of studies in this direction are encouraging. In particular, taking 990 mg of ambroxol per day, dissolved in 500 ml of isotonic solution and administered intravenously over 4–6 hours, reduced the occurrence of postoperative pneumonia and hypoxemia in patients with spinal cord injury after surgical treatment [20]. Ambroxol has a beneficial effect in patients after cardiopulmonary bypass surgery, a condition in which systemic inflammation occurs [21]. There are studies showing the positive effect of taking ambroxol in patients with pulmonary resection [22]. Some studies, although with a low level of evidence, have been described on the effectiveness of ambroxol in cystic fibrosis and exacerbation of chronic obstructive pulmonary disease [23, 24].
Ambroxol has been successfully prescribed in the treatment of respiratory diseases of various etiologies in children and adults for more than 35 years [25–27]. The ambroxol hydrochloride molecule is an exact copy of the natural molecule. In the 13th century. On the territory of Sri Lanka and India, on the island of Java, a plant was known - a shrub, which today has the name Adhatoda vasica (Vascular Adhatoda). Already in those distant times, the medicinal properties of this plant were used in the treatment of nervous diseases (neuralgia) and respiratory diseases (bronchitis, cough, whooping cough, asthma), as well as dysentery, diarrhea, chills, rheumatism and skin inflammation. The specified “medicine” was obtained from the juice of plant leaves, flowers, fruits, roots, and its expectorant, antispasmodic, sedative and anthelmintic effects were used. The active extract of this plant is considered to be alkaloids - the so-called. vasicinoids (vasicin and vasicinone), which have an effect similar to aminophylline and contain essential oil [28].
The main properties of ambroxol: high mucolytic and pronounced expectorant effects, as well as additional (antioxidant, anti-inflammatory) properties to stimulate the synthesis of surfactant and have a damaging effect on bacterial biofilms, improve local immunity [29]. For nonproductive coughs, it relieves chest pain and partially softens the cough reflex. It is important for the pediatrician to know that ambroxol penetrates the placenta into the cerebrospinal fluid and breast milk, but has a high level of safety. The incidence of side effects, such as diarrhea and nausea, when used in syrup dosage form in children with acute and chronic respiratory diseases was 0.46%. If necessary, it can be prescribed to pregnant women in the 2nd and 3rd trimesters. If there is a threat of premature birth, ambroxol is used to prevent distress syndrome from the 28th week of pregnancy and for premature babies - also in case of a threat of distress syndrome [30, 31].
Scientific studies have convincingly shown the positive interaction of ambroxol with antibiotics. It helps to increase the effectiveness of the antibiotic by increasing its concentration in bronchial secretions [32]. When ambroxol and an antibiotic are used together, the rate of passive diffusion of antibiotics from the blood plasma into the lung tissue increases without changing the concentrations of antibiotics in the blood plasma [33]. Further observations showed that ambroxol improves the bioaccumulation of antibiotics in the bronchoalveolar fluid of patients with chronic lung diseases [34].
In the pediatric community, active discussions continue today regarding the comparison of two drugs - ambroxol and bromhexine. It should be said right away that these drugs have similar properties, but unlike bromhexine, it is ambroxol that surpasses it in terms of the strength of its therapeutic effect and clinical effectiveness, because is its active metabolite. The effect of ambroxol begins quickly - within 30 minutes. The therapeutic effect of bromhexine appears on the 4th–6th day of therapy. The drugs have different bioavailability: ambroxol has a high bioavailability (75%), bromhekisne has a low bioavailability (25%). After starting a course of oral ambroxol, its maximum effect appears on the 3rd day of treatment. When treating chronic diseases, within 2 weeks of therapy the amount of sputum and its viscosity are reduced by half.
It is important to remember that in general all mucolytics are contraindicated in the 1st trimester of pregnancy and while breastfeeding. In order to prevent reflex bronchospasm, patients with bronchial asthma should use an inhaled β2-adrenergic agonist before inhalation of mucolytics. You should always consider possible effects when combining mucolytics with other commonly used drugs (see table).
Thus, the group of drugs that affect cough and change the properties of sputum in acute and chronic respiratory diseases is quite large and diverse. And each medicine has its own point of application. Ambroxol has shown its effectiveness and safety in children in the treatment of various respiratory pathologies. The variety of dosage forms of ambroxol makes it especially convenient for use in pediatric practice.
