The variety of effects of ambroxol in the treatment of acute respiratory infections in children


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Abstract

The article discusses the main, as well as little-studied effects of ambroxol, a mucoactive drug widely used as a mucokinetic and mucolytic. Modern data on pharmacokinetics, pathogenetic mechanisms of action, efficacy and safety of ambroxol use in children with acute respiratory diseases are presented. Long-term experience of using ambroxol indicates that it has unique properties that actively influence the basic mechanisms of coughing, physiological production and transport of bronchial secretions, and the activity of the surfactant system.

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About the authors

N. A Geppe

Sechenov University

Department of Children's Diseases, N.F. Filatov Clinical Institute of Children's Health Moscow, Russia

Marina D. Shakhnazarova

Sechenov University

Email: marinashakh@mail.ru
Cand. Sci. (Med.), Associate Professor at the Department of Children’s Diseases, N.F. Filatov Clinical Institute of Children’s Health Moscow, Russia

S. I Shatalina

Sechenov University

Department of Children's Diseases, N.F. Filatov Clinical Institute of Children's Health Moscow, Russia

I. M Farber

Sechenov University

Department of Children's Diseases, N.F. Filatov Clinical Institute of Children's Health Moscow, Russia

O. G Sukhovyeva

Sechenov University

Department of Children's Diseases, N.F. Filatov Clinical Institute of Children's Health Moscow, Russia

M. I Mitkina

Sechenov University

Department of Children's Diseases, N.F. Filatov Clinical Institute of Children's Health Moscow, Russia

References

  1. Федеральная служба по надзору в сфере защиты прав потребителей и благополучия человека. Статистические материалы. https://www.rospotrebnadzor.ru/activities/statistical-materials/statictic_details.php?ELEMENT_ ID=11277
  2. Геппе Н.А. и др. Острые инфекции дыхательных путей у детей. Диагностика, лечение, профилактика: клиническое руководство. 2-е изд. М., 2020. 254 с.
  3. Иванова Н.А. Рецидивирующая обструкция бронхов и бронхиальная астма у детей первых пяти лет жизни. Российский вестник перинатологии и педиатрии. 2016;61(5):64-9. doi: 10.21508/1027-4065-2016-61-5-64-69.
  4. Юренев Г.Л., Юренева-Тхоржевская Т.В. Бронхообструктивный синдром при острых респираторных вирусных инфекциях: причины и последствия. Практическая пульмонология. 2014;1:22-9.
  5. Harris M., Clark J., Coote N., et al. British Thoracic Society guidelines for the management of community acquired pneumonia in children: update 2011. Thorax. 2011;66(Suppl.):2-23. Doi: 10.1136/ thoraxjnl-2011-200598.
  6. Дронов И.А., Малахов А.Б. Антибактериальная терапия при острых респираторных инфекциях у детей. Педиатрия. Consilium Medicum. 2017;4:31-5.
  7. Morice A., Kardos P.Comprehensive evidence-based review on European antitussives. BMJ. Open Respir. Res. 2016;3(1):e000137. Doi: 10.1136/ bmjresp-2016-000137.
  8. Chang A.B., Oppenheimer J.J., Weinberger M.M., et al. CHEST Expert Cough Panel. Chest. 2017;151(4):884-90. Doi: 10.1016/j. chest.2017.01.025.
  9. Alyn H. Morice, Eva Millqvist, et al. ERS guidelines on the diagnosis and treatment of chronic cough in adults and children. Eur Respir J. 2020;55(1):1901136. doi: 10.1183/13993003.01136-2019.
  10. Thompson M., Vodicka T.A., Blair P.S., et al. TARGET Programme Team. Duration of symptoms of respiratory tract infections in children: systematic review. BMJ. 2013;347:f7027. doi: 10.1136/bmj.f7027.
  11. Kardos P, Schütt T., Mück T., et al. Pathophysiological Factors in The Relationship Between Chronological Age And Calculated Lung Age As Detected in A Screening Setting in Community-Dwelling Subjects. Front Med. 2016;3:2. doi: 10.3389/Fmed.2016.00002.
  12. Anderson-James S., Newcombe P.A., Marchant J.M., et al. An acute cough-specific quality-of-life questionnaire for children: development and validation. J Allergy Clin immunol. 2015;135:1179-85.E1174. doi: 10.1016/J.Jaci.2014.08.036
  13. Jiang B., Chen J.-L., Lou H.-G. et al. Pharmacokinetic and bioequivalence study of three oral formulations of Ambroxol 30 mg: a randomized, three-period crossover comparison in healthy volunteers.int J Clin Pharmacol Ther. 2014;52:920-26. Doi: 10.5414/ CP202156.
  14. Чучалин А.Г., Абросимов В.Н. Кашель. М., 2016. 160 с.
  15. Самсыгина Г.А. Кашель у детей. Клиническое руководство. М., 2016. 160 c.
  16. Jason L.P., Galeb A.A., Curtis H. The healthy human microbiome. Genome Med. 2016;8:51. Doi: 10.1186/ s13073-016-0307-y.
  17. Геппе Н.А., Озерская И.В., Малявина У.С. Цилиарный эпителий при респираторных вирусных инфекциях у детей. Влияние лекарственных препаратов. Русский медицинский журнал. 2012;20(24):1222-27.
  18. Seto W.H., Conly J.M., Pessoa-Silva C.L., et al. infection prevention and control measures for acute respiratory infections in health care settings: an update. East Mediterr Health J. 2013;19(Suppl. 1):39-47.
  19. Balsamo R., Lanata L., Egan C.G. Mucoactive drugs. Eur Respir Rev. 2010;19(116):127-33. doi: 10.1183/09059180.00003510.
  20. Старостина Л.С. Варианты муколитической терапии кашля у детей. Русский медицинский журнал. 2019;3:60-4
  21. Disse B.G. The pharmacology of ambroxol -review and newresults. Eur J Respir Dis. 1987;153(Suppl.): 255-62.
  22. Glowania A., Böhm M., Knopf A., Klimek L. The surfactant system - a new approach for treating the upper respiratory tract mucosa. Atemwegs Lungenkrankh. 2011;37:S1-5.
  23. European Medicine Agencies. Revised assessment report: Ambroxol and bromhexine containing medicinal products 2015. URL: https://www.ema.europa.eu/en/documents/referral/ambroxolbromhexine-article-31-referral-pracassessmentreport_en.pdf.
  24. Morgenroth K., Bolz J. Morphological features of the interaction between mucus and surfactant on the bronchial mucosa. Respiration. 1985;47:225-31. doi: 10.1159/000194774.
  25. Fois G., Hobi N., Felder E., et al. A new role for an old drug: Ambroxol triggers lysosomal exocytosis via pH-dependent Ca2+ release from acidic Ca2+ stores. Cell Calcium. 2015;58:628-37. Doi: 10.1016/j. ceca.2015.10.002.
  26. Kanie S., Yokohira M., Yamakawa K., et al. Suppressive effects of the expectorant drug ambroxol hydrochloride on quartz-induced lung inflammation in F344 rats. J Toxicol. 2017;30(2):153-15.
  27. Shui-juan Zhang, Juan-xia Jiang, Qian-qian Ren, et al. Ambroxol inhalation ameliorates LPS-induced airway inflammation and mucus secretion through the extracellular signal-regulated kinase 1/2 signaling pathway. Eur J Pharmacol. 2016;775:138-48. doi: 10.1016/j.ejphar. 2016.02.030.
  28. Seagrave J., Albrecht H.H., Hill D.B., et al. G. Effects of guaifenesin, N-acetylcysteine, and ambroxol on MUC5AC and mucociliary transport in primary differentiated human tracheal-bronchial cells. Respir Res. 2012;13(1):98. doi: 10.1186/14659921-13-98.
  29. Paleari D., Rossi G.A., Nicolini G., Olivieri D. Ambroxol: a multifaceted molecule with additional therapeutic potentials in respiratory disorders of childhood. Expert Opin Drug Discov. 2011;6:1203-14. doi: 10.1517/17460441.2011.629646.
  30. Olivieri D., Zavattini G., Tomasini G., et al. Ambroxol for the prevention of chronic bronchitis exacerbations: long-term multicenter trial. Respiration. 1987;51(Suppl. 1):42-51. doi: 10.1159/000195274.
  31. Cegla U.H. Long-term therapy over 2 years with Ambroxol (Mucosolvan) retard capsules in patients with chronic bronchitis. Prax Clin Pneumol. 1988;42:715-21.
  32. Matthys H., De Mey C., Carls C., et al. Efficacy and tolerability of Myrtol standardized in acute bronchitis. A multi-Centre, randomised, double-blind, placebocontrolled parallel group trial vs. cefuroxime and Ambroxol. Arzneimittelforschung. 2000;50:700-11. doi: 10.1055/s-0031-1300276.
  33. Du X., Zhao C., Liu S., Su S. Value of ambroxol in the treatment of asthmatic bronchitis. Pak J Med Sci. 2020;36 (3):501-4. Doi: 10.12669/ pjms.36.3.1607.
  34. Stetinova V., Herout V, Kvetina J. in vitro and in vivo antioxidant activity of ambroxol. Clin Exp Med. 2004;4(3):152-58. doi: 10.1007/s10238-004-0050-3.
  35. Moretti M., Marchioni C.F. An overview of erdosteine antioxidant activity in experimental re-search. Pharmacol Res. 2007;55(4):249-54. doi: 10.1016/j.phrs.2006.12.006.
  36. Takeda K., Miyahara N., Matsubara S., et al. Immunomodulatory effects of Ambroxol on airway Hyperresponsiveness and inflammation. immune New/. 2016;16:165-75. Doi: 10.4110/ In.2016.16.3.165.
  37. Deretic V, Timmins G.S. Enhancement of lung levels of antibiotics by ambroxol and bromhexine. Expert Opin Drug Metab Toxicol. 2019;15:213-18. doi: 10.1080/17425255.2019.1578748.
  38. Basabe-Burgos O., Zebialowicz J., Stichtenoth G., et al. Natural derived surfactant preparation as a carrier of polymyxin E for treatment of Pseudomonas aeruginosa pneumonia in a near-term rabbit model. J Aerosol Med Pulm Drug Deliv. 2019;32:110-18. doi: 10.1089/jamp.2018.1468.
  39. Абатуров А.Е., Крючко Т.А. Антибиопленочная терапия при лечении респираторных инфекционных заболеваний, вызванных бактериальными патогенами. Zdorov'e rebenka. 2018;13(7):704-09 doi: 10.22141/2224-0551.13.7.2018.148925.
  40. Cataldi M., Sblendorio V., Leo A., Piazza O. Biofilm-dependent airway infections: a role for ambroxol? Pulm Pharmacol Ther 2014;28:98-108. doi: 10.1016/j.pupt.2013.11.002.
  41. Principi N., Zavattini G., Daniotti S. Possibility of interaction among antibiotics and mucolytics in children.Int J Clin Pharmacol Res 1986;6:369-72.
  42. Chang C.C., Cheng A.C., Chang A.B. Over-the-counter medications to help reduce cough for children and adults on antibiotics for acute pneumonia. Cochrane Library Cochrane Database Syst. Rev. 2014 г. URL: https://www.cochrane.org/CD006088/ARI_over-the-counter-medications-to-help-reduce-cough-for-children-and-adults-on-antibiotics-for-acute-pneumonia.
  43. Zuqin Yang, et al. Effects and mechanisms of ambroxol inhalation (Mucosolvan®) in the treatment of neonatal pneumonia. Pharmazie. 2017;72(10):604-7. doi: 10.1691/ph.2017.7541.
  44. Yang B., Yao D.F., Ohuchi M., et al. Ambroxol suppresses influenza-virus proliferation in the mouse airway by increasing antiviral factor levels. Eur Respir J. 2002;19:952-58. doi: 10.1183/09031936.02.00253302.
  45. Li F., Yu J., Yang H., et al. Effects of ambroxol on alginate of mature Pseudomonas aeruginosa biofilms. Curr Microbiol. 2008;57:1-7. Doi: 10.1007/ s00284-008-9142-8.
  46. Yamaya M., Nishimura H., Lk N., et al. Ambroxol inhibits rhinovirus infection in primary cultures of human tracheal epithelial cells. Arch Pharm Res. 2014;37:520-29. doi: 10.1007/S12272-013-0210-7.
  47. Bradfute S.B., Ye C., Clarke E.C., et al. Ambroxol and Ciprofloxacin Show Activity Against SARS-CoV2 in Vero E6 Cells at Clinically-Relevant Concentrations. bioRxiv. 2020.08.11.245100. doi: 10.1101/2020.08.11.245100.
  48. Carpinteiro A., Gripp B., Hoffmann M., et al. Inhibition of acid sphingomyelinase by ambroxol prevents SARS-CoV-2 entry into epithelial cells. J Biol Chem. 2021;296:100701. Doi: 10.1016/j. jbc.2021.100701.
  49. 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;630:19-28. doi: 10.1016/J.Ejphar2009.12.027.
  50. De Mey C., Peil H., Kölsch S., et al. Efficacy and safety of Ambroxol lozenges in the treatment of acute uncomplicated sore throat. Arzneimittelforschung. 2008;58:557-68. d=doi: 10.1055/S-0031-1296557.
  51. Данные инструкций по медицинскому применению препаратов, содержащих амброксол. ГРЛС: (Электронный ресурс). URL: https://grls.rosminzdrav.ru/grls.aspx (дата доступа /access date 08.10.2020).
  52. Cazan D., Klimek L., Sperl A., et al. Safety of ambroxol in the treatment of airway diseases in adult patients. Expert Opin Drug Saf. 2018;17(12):1211-24. doi: 10.1080/14740338.2018.1533954.
  53. Малахов А.Б., Колосова Н.Г., Гребенева И.В. Выбор ингалятора (небулайзера) в клинической практике: вопросы и ответы. Педиатрия. Consilium Medicum. 2018;3:55-8. doi: 10.26442/2413-8460_2018.3.55-58.
  54. Шахназарова М.Д., Геппе Н.А., Озерская И.В. и др. Современные возможности небулайзерной терапии в лечении респираторной патологии у детей. Фарматека. 2021;28(1):20-26.
  55. Careddu P., Zavattini G. Mucosolvan (Ambroxol) in paediatric use - Controlled clinical trial vs. acetylcysteine. Asthma Bronch Emphys. 1984;4:23-6.
  56. Berni M., Collina A., Zavattini G. Ambroxol in bronchopulmonary pathology in children. [Article in Italian]. Clin Ter.1983;106:351-55.
  57. Baldini G., Gucci M., Tarô D., Memmini C. Controlled clinical study of a new ambroxol formulation in the treatment of infantile spastic bronchitis in children. [Article in Italian]. Min Ped. 1989;41:91-5.
  58. Malerba M., Ragnoli B. Ambroxol in the 21st century: pharmacological and clinical update. Expert Opin Drug Metab Toxicol. 2008;4:1119-29. doi: 10.1517/17425255.4.8.1119.
  59. Комитет по оценке рисков фармаконадзора (PRAC) Пересмотренный отчет об оценке: лекарственные средства, содержащие амброксол и бромгексин. URL: https://www.ema.europa.eu/en/medicines/human/referrals/ambroxol-bromhexine-containing-medicines

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