Reposicionamento de fármacos: um estudo sobre o ambroxol
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Publicado
Feb 7, 2023
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Resumo
Objetivo: Reunir evidências e identificar abordagens científicas que justifiquem o uso do ambroxol para outras finalidades terapêuticas. Métodos: Tratou-se de revisão da literatura do tipo integrativa e teve como base de dados a Medical Literature Analysis and Retrieval System Online (MEDLINE) e Science Direct e Scientific Eletronic Library Online (SCIELO) e foram incluídos estudos identificados por busca manual. Resultados: Preliminarmente 162 trabalhos foram recuperados sendo 20 artigos incluídos. Foi identificado mecanismos de ação ao ambroxol relacionados a interação com proteínas de entrada viral; com etapas de reparo de enzimas com função chaperona; modulação de canais iônicos; antioxidante; anti-inflamatório; analgésico; anestésico e imunomoduladora. As pesquisas associaram o uso de altas doses de ambroxol como possibilidade segura para tratamento, prevenção e/ou como adjuvante em doenças como COVID-19, Parkinson, Gaucher, alívio da dor e como novas perspectivas de uso para o Sistema Respiratório. Considerações finais: O reposicionamento do ambroxol é uma possibilidade vantajosa e se qualifica como uma alternativa de sucesso a novas abordagens de tratamento terapêuticos, onde os diferentes mecanismos de ação explorados do ABX o capacitam como uma alternativa de uso combinado com outras terapias.
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Como Citar
BarbosaS. R., SilvaR. I., BorgesR. dos S., & QueirozA. N. (2023). Reposicionamento de fármacos: um estudo sobre o ambroxol. Revista Eletrônica Acervo Saúde, 23(2), e11700. https://doi.org/10.25248/reas.e11700.2023
Seção
Revisão Bibliográfica
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Referências
1. ALKOTAJI M. Azithromycin and ambroxol as potential pharmacotherapy for SARS-CoV-2. International journal of antimicrobial agents, 2020; 56(6):106192.
2. ARMSTRONG MJ, OKUN MS. Diagnosis and Treatment of Parkinson Disease: A Review. JAMA, 2020; 323(6):548-560.
3. BAR BI, et al. Ambroxol as a pharmacological chaperone for mutant glucocerebrosidase. Blood Cells Mol Dis.,2013; 50(2):141-5
4. BARAKA AM, EL-HADIDY F. Role of ambroxol as a prophylactic agent against COVID-19. Universal Journal of Pharmaceutical Research., 2021; 6(1):61-65
5. BOUSCARY A. Drug repositioning in neurodegeneration: An overview of the use of ambroxol in neurodegenerative diseases. European Journal of Pharmacology, 2020; 884:173446.
6. CAI L, et al. Drug repositioning based on the heterogeneous information fusion graph convolutional network. Brief Bioinform, 2021; 22(6):bbab319.
7. CAZAN D, et al. Safety of ambroxol in the treatment of airway diseases in adult patients. Expert opinion on drug safety, 2018; 17(12):1211-1224.
8. CHENOT JF, et al. Efficacy of Ambroxol lozenges for pharyngitis: a meta-analysis. BMC Family Practice, 2014; 13; 15:45.
9. DE MEY C, et al. Efficacy and Safety of Ambroxol Lozenges in the Treatment of Acute Uncomplicated Sore Throat–a Pooled Analysis. Drug Research, 2016; 66(7):384-92.
10. FATIMA S, et al. Repurposing Immunomodulatory Drugs to Combat Tuberculosis. Frontier Immunology, 2021; 13; 12:645485.
11. GAIDA W, et al. Ambroxol, a Nav1.8-preferring Na (+) channel blocker, effectively suppresses pain symptoms in animal models of chronic, neuropathic and inflammatory pain. Neuropharmacology, 2005; 49(8):1220-7.
12. KEHINDE I A, et al. Inhibitory mechanism of Ambroxol and Bromhexine Hydrochlorides as potent blockers of molecular interaction between SARS-CoV-2 spike protein and human angiotensin-converting Enzyme-2. Journal of Molecular Graphics and Modelling, 2022; 114:108201
13. KERN KU, WEISER T. Topical ambroxol for the treatment of neuropathic pain. An initial clinical observation. Der Schmerz, 2015; 29 Suppl 3(Suppl 3):S89-96.
14. KHOURY T, et al. A synergistic effect of Ambroxol and Beta-Glucosylceramide in alleviating immune-mediated hepatitis: A novel immunomodulatory non-immunosuppressive formulation for treatment of immune-mediated disorders. Biomed Pharmacother, 2020; 132:110890.
15. KIM YM, et al. Pharmacologic properties of high-dose ambroxol in four patients with Gaucher disease and myoclonic epilepsy. J Med Genet, 2020; 57(2):124-131.
16. LIPPI G, et al. COVID-19: unravelling the clinical progression of nature’s virtually perfect biological weapon. Annals of translational medicine, 2020; eight (11):693.
17. MCNEILL a et al. Ambroxol improves lysosomal biochemistry in glucocerebrosidase mutation-linked Parkinson disease cells. Brain, 2014; 137(Pt 5):1481-95.
18. MITINI-NKHOMA SC. et al. Ion Transport Modulators Differentially Modulate Inflammatory Responses in THP-1-Derived Macrophages. Journal of immunology research., 2021; 2021: 8832586
19. MULLIN S, et al. Ambroxol for the Treatment of Patients with Parkinson Disease with and Without Glucocerebrosidase Gene Mutations: A Nonrandomized, Noncontrolled Trial. JAMA Neurol., 2020; 1; 77(4):427-434.
20. OLALEYE OA, et al. Ambroxol hydrochloride inhibits the interaction between severe acute respiratory syndrome coronavirus 2 spike protein’s receptor binding domain and recombinant human ACE2. BioRxiv, 2020; 14:2020.09.13.295691.
21. PFEIFER S, et al. Reduction of cytokine release of blood and bronchoalveolar mononuclear cells by ambroxol. European journal of medical research,1997; 24; 2(3): 129-32
22. PINHEIRO DCSN, et al. Atividade imunomoduladora das plantas medicinais: perspectivas em medicina veterinária, Ciência animal, 2003; 13(1): 23-32.
23. PITCAIRN C, et al. Dysregulation of the autophagic-lysosomal pathway in Gaucher and Parkinson's disease. Neurobiology of disease, 2019; 122: 72-82.
24. PUSHPAKOM S, et al. Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov., 2019; 18(1): 41-58.
25. RATJEN F, et al. A double-blind placebo controlled trial with oral ambroxol and N-acetylcysteine for mucolytic treatment in cystic fibrosis. European journal of pediatrics.1985; 374-378
26. REFAI M, et al. Short-term perioperative treatment with ambroxol reduces pulmonary complications and hospital costs after pulmonary lobectomy: a randomized trial. European journal of cardio-thoracic surgery, 2009; 35(3):469-73.
27. SILVEIRA CRA, et al. Ambroxol as a novel disease-modifying treatment for Parkinson's disease dementia: protocol for a single-centre, randomized, double blind, placebo-controlled trial. BMC Neurol., 2019; 9; 19(1): 20.
28. TANG H, et al. The application of ambroxol hydrochloride combined with fiberoptic bronchoscopy in elderly patients with severe pneumonia: A meta-analysis and systematic review. Medicine, 2022; 28-101(4): e28535.
29. VAN DRIEL ML, et al. Are sore throat patients who hope for antibiotics actually asking for pain relief?.The Annals of Family Medicine, 2006; 4(6):494-9.
30. WANG Yu, et al. Sputum characteristics and airway clearance methods in patients with severe COVID-19. Medicine, 2020; 13; 99(46): e23257.
31. WAUER RR, et al. Randomized double blind trial of Ambroxol for the treatment of respiratory distress syndrome. European journal of pediatrics, 1992; 151(5):357-63
32. WU X, et al. Meta‐analysis of high doses of ambroxol treatment for acute lung injury/acute respiratory distress syndrome based on randomized controlled trials. The Journal of Clinical Pharmacology, 2014; 54(11):1199-206.
33. XIA DH, et al. The protective effects of ambroxol on radiation lung injury and influence on production of transforming growth factor β1 and tumor necrosis factor α. Medical Oncology, 2010; 27(3): 697-701.
34. ZHANG H, et al. Antenatal maternal medication administration in preventing respiratory distress syndrome of premature infants: A network meta‐analysis. The Clinical Respiratory Journal, 2018; 12(10): 2480-2490.
35. ZHANG ZQ, et al. Prevention of respiratory distress syndrome in preterm infants by antenatal ambroxol: a meta-analysis of randomized controlled trials. American journal of perinatology, 2013; 30(7): 529-36.
36. ZIMRAN A, et al. Pilot study using ambroxol as a pharmacological chaperone in type 1 Gaucher disease. Blood Cells, Molecules, and Diseases, 2013; 50(2): 134-7.
2. ARMSTRONG MJ, OKUN MS. Diagnosis and Treatment of Parkinson Disease: A Review. JAMA, 2020; 323(6):548-560.
3. BAR BI, et al. Ambroxol as a pharmacological chaperone for mutant glucocerebrosidase. Blood Cells Mol Dis.,2013; 50(2):141-5
4. BARAKA AM, EL-HADIDY F. Role of ambroxol as a prophylactic agent against COVID-19. Universal Journal of Pharmaceutical Research., 2021; 6(1):61-65
5. BOUSCARY A. Drug repositioning in neurodegeneration: An overview of the use of ambroxol in neurodegenerative diseases. European Journal of Pharmacology, 2020; 884:173446.
6. CAI L, et al. Drug repositioning based on the heterogeneous information fusion graph convolutional network. Brief Bioinform, 2021; 22(6):bbab319.
7. CAZAN D, et al. Safety of ambroxol in the treatment of airway diseases in adult patients. Expert opinion on drug safety, 2018; 17(12):1211-1224.
8. CHENOT JF, et al. Efficacy of Ambroxol lozenges for pharyngitis: a meta-analysis. BMC Family Practice, 2014; 13; 15:45.
9. DE MEY C, et al. Efficacy and Safety of Ambroxol Lozenges in the Treatment of Acute Uncomplicated Sore Throat–a Pooled Analysis. Drug Research, 2016; 66(7):384-92.
10. FATIMA S, et al. Repurposing Immunomodulatory Drugs to Combat Tuberculosis. Frontier Immunology, 2021; 13; 12:645485.
11. GAIDA W, et al. Ambroxol, a Nav1.8-preferring Na (+) channel blocker, effectively suppresses pain symptoms in animal models of chronic, neuropathic and inflammatory pain. Neuropharmacology, 2005; 49(8):1220-7.
12. KEHINDE I A, et al. Inhibitory mechanism of Ambroxol and Bromhexine Hydrochlorides as potent blockers of molecular interaction between SARS-CoV-2 spike protein and human angiotensin-converting Enzyme-2. Journal of Molecular Graphics and Modelling, 2022; 114:108201
13. KERN KU, WEISER T. Topical ambroxol for the treatment of neuropathic pain. An initial clinical observation. Der Schmerz, 2015; 29 Suppl 3(Suppl 3):S89-96.
14. KHOURY T, et al. A synergistic effect of Ambroxol and Beta-Glucosylceramide in alleviating immune-mediated hepatitis: A novel immunomodulatory non-immunosuppressive formulation for treatment of immune-mediated disorders. Biomed Pharmacother, 2020; 132:110890.
15. KIM YM, et al. Pharmacologic properties of high-dose ambroxol in four patients with Gaucher disease and myoclonic epilepsy. J Med Genet, 2020; 57(2):124-131.
16. LIPPI G, et al. COVID-19: unravelling the clinical progression of nature’s virtually perfect biological weapon. Annals of translational medicine, 2020; eight (11):693.
17. MCNEILL a et al. Ambroxol improves lysosomal biochemistry in glucocerebrosidase mutation-linked Parkinson disease cells. Brain, 2014; 137(Pt 5):1481-95.
18. MITINI-NKHOMA SC. et al. Ion Transport Modulators Differentially Modulate Inflammatory Responses in THP-1-Derived Macrophages. Journal of immunology research., 2021; 2021: 8832586
19. MULLIN S, et al. Ambroxol for the Treatment of Patients with Parkinson Disease with and Without Glucocerebrosidase Gene Mutations: A Nonrandomized, Noncontrolled Trial. JAMA Neurol., 2020; 1; 77(4):427-434.
20. OLALEYE OA, et al. Ambroxol hydrochloride inhibits the interaction between severe acute respiratory syndrome coronavirus 2 spike protein’s receptor binding domain and recombinant human ACE2. BioRxiv, 2020; 14:2020.09.13.295691.
21. PFEIFER S, et al. Reduction of cytokine release of blood and bronchoalveolar mononuclear cells by ambroxol. European journal of medical research,1997; 24; 2(3): 129-32
22. PINHEIRO DCSN, et al. Atividade imunomoduladora das plantas medicinais: perspectivas em medicina veterinária, Ciência animal, 2003; 13(1): 23-32.
23. PITCAIRN C, et al. Dysregulation of the autophagic-lysosomal pathway in Gaucher and Parkinson's disease. Neurobiology of disease, 2019; 122: 72-82.
24. PUSHPAKOM S, et al. Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov., 2019; 18(1): 41-58.
25. RATJEN F, et al. A double-blind placebo controlled trial with oral ambroxol and N-acetylcysteine for mucolytic treatment in cystic fibrosis. European journal of pediatrics.1985; 374-378
26. REFAI M, et al. Short-term perioperative treatment with ambroxol reduces pulmonary complications and hospital costs after pulmonary lobectomy: a randomized trial. European journal of cardio-thoracic surgery, 2009; 35(3):469-73.
27. SILVEIRA CRA, et al. Ambroxol as a novel disease-modifying treatment for Parkinson's disease dementia: protocol for a single-centre, randomized, double blind, placebo-controlled trial. BMC Neurol., 2019; 9; 19(1): 20.
28. TANG H, et al. The application of ambroxol hydrochloride combined with fiberoptic bronchoscopy in elderly patients with severe pneumonia: A meta-analysis and systematic review. Medicine, 2022; 28-101(4): e28535.
29. VAN DRIEL ML, et al. Are sore throat patients who hope for antibiotics actually asking for pain relief?.The Annals of Family Medicine, 2006; 4(6):494-9.
30. WANG Yu, et al. Sputum characteristics and airway clearance methods in patients with severe COVID-19. Medicine, 2020; 13; 99(46): e23257.
31. WAUER RR, et al. Randomized double blind trial of Ambroxol for the treatment of respiratory distress syndrome. European journal of pediatrics, 1992; 151(5):357-63
32. WU X, et al. Meta‐analysis of high doses of ambroxol treatment for acute lung injury/acute respiratory distress syndrome based on randomized controlled trials. The Journal of Clinical Pharmacology, 2014; 54(11):1199-206.
33. XIA DH, et al. The protective effects of ambroxol on radiation lung injury and influence on production of transforming growth factor β1 and tumor necrosis factor α. Medical Oncology, 2010; 27(3): 697-701.
34. ZHANG H, et al. Antenatal maternal medication administration in preventing respiratory distress syndrome of premature infants: A network meta‐analysis. The Clinical Respiratory Journal, 2018; 12(10): 2480-2490.
35. ZHANG ZQ, et al. Prevention of respiratory distress syndrome in preterm infants by antenatal ambroxol: a meta-analysis of randomized controlled trials. American journal of perinatology, 2013; 30(7): 529-36.
36. ZIMRAN A, et al. Pilot study using ambroxol as a pharmacological chaperone in type 1 Gaucher disease. Blood Cells, Molecules, and Diseases, 2013; 50(2): 134-7.