Ambroxol – more than mucolytic agent. Reasons to utilize ambroxol in respiratory treatment Review article
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Published:
Mar 31, 2024
Keywords:
mucolytics, mucokinetics, ambroxol, COPD
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Abstract
Mucolytics and their mechanisms of action are a source of diverse concerns on the part of patients and doctors alike. Some of us believe them to be very important in the treatment of many diseases, while others are sceptical as to their indications and possibilities of use. According to some, they may lead to an excessive production of secretion, whereas others claim that mechanism to be a well-grounded one. In some conditions, mucolytics are not administered at all, while in other cases they are applied with great conviction by a great many specialists. Nevertheless, they are not always administered in compliance with the current guidelines or clinical studies. In an attempt to address those reservations, the present brief review discusses the use of a mucoactive drug – ambroxol.
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Pawliczak, R. (2024). Ambroxol – more than mucolytic agent. Reasons to utilize ambroxol in respiratory treatment. Medycyna Faktow (J EBM), 17(1(62), 77-81. https://doi.org/10.24292/01.MF.0124.12
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References
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4. Malerba M, Ragnoli B. Ambroxol in the 21st century: pharmacological and clinical update. Expert Opin. Drug Metab Toxicol. 2008; 4(8): 1119-29.
5. Stetinova V, Herout V, Kvetina J. In vitro and in vivo antioxidant activity of ambroxol. Clin Exp Med. 2004; 4(3): 152-8.
6. Gillissen A, Nowak D. Characterization of N-acetylcysteine and ambroxol in anti-oxidant therapy. Respir Med. 1998; 92(4): 609-23.
7. Krenke K, Doniec Z, Mastalerz-Migas A et al. Zalecenia postępowania diagnostyczno-terapeutycznego w kaszlu u dzieci. Lekarz POZ. 2022; 3: 173-92.
8. Wiessmann KJ, Niemeyer K. [Clinical results in the treatment of chronic obstructive bronchitis with ambroxol in comparison with bromhexine (author’s transl)]. Arzneimittelforschung. 1978; 28(5a): 918-21.
9. Wu X, Li S, Zhang J et al. Meta-analysis of high doses of ambroxol treatment for acute lung injury/acute respiratory distress syndrome based on randomized controlled trials. J Clin Pharmacol. 2014; 54(11): 1199-206.
10. Gibbs BF, Wolff HH, Grabbe J. Ambroxol inhibits the release of histamine, leukotrienes and cytokines from human leukocytes and mast cells. Inflamm Res. 1999; 48(2): 86-93.
11. Peroni DG, Moser S, Gallo G et al. Ambroxol inhibits neutrophil respiratory burst activated by alpha chain integrin adhesion. Int J Immunopathol Pharmacol. 2013; 26(4): 883-7.
12. Nowak D, Antczak A, Krol M et al. Antioxidant properties of Ambroxol. Free Radic Biol Med. 1994; 16(4): 517-22.
13. Nowak D, Antczak A, Pietras T et al. Protective effect of ambroxol against heat- and hydrogen peroxide-induced damage to lung lipids in mice. Eur Respir J. 1994; 7(9): 1629-34.
14. Nowak D, Pierscinski G, Drzewoski J. Ambroxol inhibits doxorubicin-induced lipid peroxidation in heart of mice. Free Radic Biol Med. 1995; 19(5): 659-63.
15. Nowak D, Pietras T, Antczak A. Ambroxol inhibits endotoxin-induced lipid peroxidation in mice. Pol J Pharmacol. 1993; 45(3): 317-22.
16. Principi N, Zavattini G, Daniotti S. Possibility of interaction among antibiotics and mucolytics in children. Int J Clin Pharmacol Res. 1986; 6: 369-72.
17. Yamaya M, Nishimura H, Nadine LK et al. Ambroxol inhibits rhinovirus infection in primary cultures of human tracheal epithelial cells. Arch Pharm Res. 2014; 37(4): 520-9.
18. Kantar A, Klimek L, Cazan D et al. An overview of efficacy and safety of ambroxol for the treatment of acute and chronic respiratory diseases with a special regard to children. Multidiscip Respir Med. 2020; 15(1): 511.
19. Lu Q, Yu J, Yang X et al. Ambroxol interferes with Pseudomonas aeruginosa quorum sensing. Int J Antimicrob Agents. 2010; 36(3): 211-5.
20. Schulz M, Hammerlein A, Hinkel U et al. Safety and usage pattern of an over-the-counter ambroxol cough syrup: a community pharmacy-based cohort study. Int J Clin Pharmacol Ther. 2006; 44(9): 409-21.
21. Teramoto S, Suzuki M, Ohga M et al. Effects of ambroxol on spontaneous or stimulated generation of reactive oxygen species by bronchoalveolar lavage cells harvested from patients with or without chronic obstructive pulmonary diseases. Pharmacology. 1999; 59(3): 135-41.
22. Jahnz-Rozyk K, Kucharczyk A, Chcialowski A et al. [The effect of inhaled ambroxol treatment on clinical symptoms and chosen parameters of ventilation in patients with exacerbation of chronic obstructive pulmonary disease patients]. Pol Merkur Lekarski. 2001; 11(63): 239-43.
23. Paganin F, Bouvet O, Chanez P et al. Evaluation of the effects of ambroxol on the ofloxacin concentrations in bronchial tissues in COPD patients with infectious exacerbation. Biopharm Drug Dispos. 1995; 16(5): 393-401.
24. Nowak D. [Antioxidative features of ambroxol – usefulness in COPD]. Pneumonol Alergol Pol. 2001; 69(9-10): 590-3.
25. Malerba M, Ponticiello A, Radaeli A et al. Effect of twelve-months therapy with oral ambroxol in preventing exacerbations in patients with COPD. Double-blind, randomized, multicenter, placebo-controlled study (the AMETHIST Trial). Pulm Pharmacol Ther. 2004; 17(1): 27-34.
26. Yamada T, Takemura Y, Niisato N et al. Action of N-acylated ambroxol derivatives on secretion of chloride ions in human airway epithelia. Biochem Biophys Res Commun. 2009; 380(3): 586-90.
27. Liu H, Wang W, Gao X. Comparison of the efficacy of ambroxol hydrochloride and N -acetylcysteine in the treatment of children with bronchopneumonia and their influence on prognosis. Exp Ther Med. 2020; 20(6): 130. http://doi.org/10.3892/etm.2020.9260.
28. Lu Q, Yu J, Bao L et al. Effects of combined treatment with ambroxol and ciprofloxacin on catheter-associated Pseudomonas aeruginosa biofilms in a rat model. Chemotherapy. 2013; 59(1): 51-6.
29. Rene HD, Jose MS, Isela SN et al. Effects of ambroxol on Candida albicans growth and biofilm formation. Mycoses. 2014; 57(4): 228-32.
30. Wang W, Yu J, He Y et al. Ambroxol inhibits mucoid conversion of Pseudomonas aeruginosa and contributes to the bactericidal activity of ciprofloxacin against mucoid P. aeruginosa biofilms. APMIS. 2016; 124(7): 611-8. http://doi.org/10.1111/apm.12542.
31. Leffler A, Reckzeh J, Nau C. Block of sensory neuronal Na+ channels by the secreolytic ambroxol is associated with an interaction with local anesthetic binding sites. Eur J Pharmacol. 2010; 630(1-3): 19-28.
2. Michnar M, Milanowski J. Ocena kliniczna skuteczności i tolerancji doustnego leczenia ambrosolem u chorych na przewlekłe zapalenie oskrzeli. 7Pneumonol Alergol Pol. 1996; 64(suppl 1): 90-6.
3. Paleari D, Rossi GA, Nicolini G et al. Ambroxol: a multifaceted molecule with additional therapeutic potentials in respiratory disorders of childhood. Expert Opin Drug Discov. 2011; 6(11): 1203-14.
4. Malerba M, Ragnoli B. Ambroxol in the 21st century: pharmacological and clinical update. Expert Opin. Drug Metab Toxicol. 2008; 4(8): 1119-29.
5. Stetinova V, Herout V, Kvetina J. In vitro and in vivo antioxidant activity of ambroxol. Clin Exp Med. 2004; 4(3): 152-8.
6. Gillissen A, Nowak D. Characterization of N-acetylcysteine and ambroxol in anti-oxidant therapy. Respir Med. 1998; 92(4): 609-23.
7. Krenke K, Doniec Z, Mastalerz-Migas A et al. Zalecenia postępowania diagnostyczno-terapeutycznego w kaszlu u dzieci. Lekarz POZ. 2022; 3: 173-92.
8. Wiessmann KJ, Niemeyer K. [Clinical results in the treatment of chronic obstructive bronchitis with ambroxol in comparison with bromhexine (author’s transl)]. Arzneimittelforschung. 1978; 28(5a): 918-21.
9. Wu X, Li S, Zhang J et al. Meta-analysis of high doses of ambroxol treatment for acute lung injury/acute respiratory distress syndrome based on randomized controlled trials. J Clin Pharmacol. 2014; 54(11): 1199-206.
10. Gibbs BF, Wolff HH, Grabbe J. Ambroxol inhibits the release of histamine, leukotrienes and cytokines from human leukocytes and mast cells. Inflamm Res. 1999; 48(2): 86-93.
11. Peroni DG, Moser S, Gallo G et al. Ambroxol inhibits neutrophil respiratory burst activated by alpha chain integrin adhesion. Int J Immunopathol Pharmacol. 2013; 26(4): 883-7.
12. Nowak D, Antczak A, Krol M et al. Antioxidant properties of Ambroxol. Free Radic Biol Med. 1994; 16(4): 517-22.
13. Nowak D, Antczak A, Pietras T et al. Protective effect of ambroxol against heat- and hydrogen peroxide-induced damage to lung lipids in mice. Eur Respir J. 1994; 7(9): 1629-34.
14. Nowak D, Pierscinski G, Drzewoski J. Ambroxol inhibits doxorubicin-induced lipid peroxidation in heart of mice. Free Radic Biol Med. 1995; 19(5): 659-63.
15. Nowak D, Pietras T, Antczak A. Ambroxol inhibits endotoxin-induced lipid peroxidation in mice. Pol J Pharmacol. 1993; 45(3): 317-22.
16. Principi N, Zavattini G, Daniotti S. Possibility of interaction among antibiotics and mucolytics in children. Int J Clin Pharmacol Res. 1986; 6: 369-72.
17. Yamaya M, Nishimura H, Nadine LK et al. Ambroxol inhibits rhinovirus infection in primary cultures of human tracheal epithelial cells. Arch Pharm Res. 2014; 37(4): 520-9.
18. Kantar A, Klimek L, Cazan D et al. An overview of efficacy and safety of ambroxol for the treatment of acute and chronic respiratory diseases with a special regard to children. Multidiscip Respir Med. 2020; 15(1): 511.
19. Lu Q, Yu J, Yang X et al. Ambroxol interferes with Pseudomonas aeruginosa quorum sensing. Int J Antimicrob Agents. 2010; 36(3): 211-5.
20. Schulz M, Hammerlein A, Hinkel U et al. Safety and usage pattern of an over-the-counter ambroxol cough syrup: a community pharmacy-based cohort study. Int J Clin Pharmacol Ther. 2006; 44(9): 409-21.
21. Teramoto S, Suzuki M, Ohga M et al. Effects of ambroxol on spontaneous or stimulated generation of reactive oxygen species by bronchoalveolar lavage cells harvested from patients with or without chronic obstructive pulmonary diseases. Pharmacology. 1999; 59(3): 135-41.
22. Jahnz-Rozyk K, Kucharczyk A, Chcialowski A et al. [The effect of inhaled ambroxol treatment on clinical symptoms and chosen parameters of ventilation in patients with exacerbation of chronic obstructive pulmonary disease patients]. Pol Merkur Lekarski. 2001; 11(63): 239-43.
23. Paganin F, Bouvet O, Chanez P et al. Evaluation of the effects of ambroxol on the ofloxacin concentrations in bronchial tissues in COPD patients with infectious exacerbation. Biopharm Drug Dispos. 1995; 16(5): 393-401.
24. Nowak D. [Antioxidative features of ambroxol – usefulness in COPD]. Pneumonol Alergol Pol. 2001; 69(9-10): 590-3.
25. Malerba M, Ponticiello A, Radaeli A et al. Effect of twelve-months therapy with oral ambroxol in preventing exacerbations in patients with COPD. Double-blind, randomized, multicenter, placebo-controlled study (the AMETHIST Trial). Pulm Pharmacol Ther. 2004; 17(1): 27-34.
26. Yamada T, Takemura Y, Niisato N et al. Action of N-acylated ambroxol derivatives on secretion of chloride ions in human airway epithelia. Biochem Biophys Res Commun. 2009; 380(3): 586-90.
27. Liu H, Wang W, Gao X. Comparison of the efficacy of ambroxol hydrochloride and N -acetylcysteine in the treatment of children with bronchopneumonia and their influence on prognosis. Exp Ther Med. 2020; 20(6): 130. http://doi.org/10.3892/etm.2020.9260.
28. Lu Q, Yu J, Bao L et al. Effects of combined treatment with ambroxol and ciprofloxacin on catheter-associated Pseudomonas aeruginosa biofilms in a rat model. Chemotherapy. 2013; 59(1): 51-6.
29. Rene HD, Jose MS, Isela SN et al. Effects of ambroxol on Candida albicans growth and biofilm formation. Mycoses. 2014; 57(4): 228-32.
30. Wang W, Yu J, He Y et al. Ambroxol inhibits mucoid conversion of Pseudomonas aeruginosa and contributes to the bactericidal activity of ciprofloxacin against mucoid P. aeruginosa biofilms. APMIS. 2016; 124(7): 611-8. http://doi.org/10.1111/apm.12542.
31. Leffler A, Reckzeh J, Nau C. Block of sensory neuronal Na+ channels by the secreolytic ambroxol is associated with an interaction with local anesthetic binding sites. Eur J Pharmacol. 2010; 630(1-3): 19-28.