Role of NAC + Acebrophylline in OAD Management final.pptx

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1. Role of NAC and Acebrophylline in OAD management 1

2. Sr. No, Topic 1. Obstructive airway diseases (OADs): A brief overview Common risk factors for the development of obstructive airways disease A brief overview on asthma and COPD Management strategies for asthma and COPD 4. Acebrophylline and N-acetylcysteine in the management of OAD Acebrophylline : Drug overview Rationale for using acebrophylline as an add-on therapy in COPD Rationale for using acebrophylline in asthma as an add-on therapy Positioning N-acetylcysteine in COPD management Role of N- acetylcysteine in the management of COPD Role of N-acetylcysteine in asthma management Table of Contents 2

3. O bstructive airway diseases (OADs): A brief overview 1. Duke, J. (2011). Pulmonary Function Testing. Anesthesia Secrets, 68–74. 2. Zeki AA, Schivo M, Albertson TE, et al. The Asthma-COPD Overlap Syndrome: A Common Clinical Problem in the Elderly. Journal of Allergy Volume 2011, Article ID 861926, 10 pages doi:10.1155/2011/861926 Asthma, chronic bronchitis, emphysema, cystic fibrosis, and bronchiolitis are examples of obstructive airway diseases that cause decreased expiratory airflow and involve airways distal to the carina. 1

4. Common risk factors for the development of obstructive airways disease In utero or early life insults to: Increase risk of OADs Asthma COPD ± Emphysema Asthma-COPD overlap syndrome Zeki AA, Schivo M, Albertson TE, et al. The Asthma-COPD Overlap Syndrome: A Common Clinical Problem in the Elderly. Journal of Allergy Volume 2011, Article ID 861926, 10 pages doi:10.1155/2011/861926

5. 1. Weinberg H.N. (2003) Obstructive Airway Disease. In: Taylor R.B., David A.K., Fields S.A., Phillips D.M., Scherger J.E. (eds) Fundamentals of Family Medicine. Springer, New York, NY.  2. World Health organization. Asthma. 2021 [Internet]. [cited 2021 May 14]. Available from: https://www.who.int/news-room/fact-sheets/detail/asthma . 3. World Health organization. Chronic obstructive pulmonary disease (COPD). 2017 [Internet]. [cited 2021 May 14]. Available from: https://www.who.int/news-room/fact-sheets/detail/chronic-obstructive-pulmonary-disease-(copd) . 4. Barnes PJ. Pharmacol Rev. 2004;56:515–48. A brief overview on asthma and COPD The two entities in obstructive airway disease that share many common characteristics include asthma and chronic obstructive pulmonary disease (COPD). 1 4 4

6. Abbreviations: AECOPD: Acute exacerbation of chronic obstructive pulmonary disease; COPD: Chronic obstructive pulmonary disease; ICS: Inhaled corticosteroids; LABA: Long-acting b2 -agonists; LAMA: Long-acting antimuscarinic antagonists; LTRA: Leukotriene receptor antagonists; NIMV: Noninvasive mechanical ventilation; OCS: Oral corticosteroids; SMART: Single-inhaled maintenance and reliever therapy. Asthma COPD Ambrosino, N., & Paggiaro , P. (2012). The management of asthma and chronic obstructive pulmonary disease: current status and future perspectives. Expert Review of Respiratory Medicine, 6(1), 117–127. Management strategies for asthma and COPD

7. Personalized m anagement of asthma in adults Global Strategy for Asthma Management and Prevention (2021 update) [Internet]. [cited 2021 May 14]. Available from: https://ginasthma.org/wp-content/uploads/2021/04/GINA-2021-Main-Report_FINAL_21_04_28-WMS.pdf .

8. Global Initiative for Chronic Obstructive Lung Disease 2021 guidelines provide updated management approach for COPD Asthma and COPD may occur together in a person. If asthma is present simultaneously, pharmacotherapy should be given as per asthma guidelines, however, for COPD, both pharmacological and non-pharmacological approaches may also be required. GLOBAL strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (2021 report). [Internet]. [cited 2021 May 14]. Available from: https://goldcopd.org/wp-content/uploads/2020/11/GOLD-REPORT-2021-v1.1-25Nov20_WMV.pdf . Management of stable COPD

9. Acebrophylline and N-acetylcysteine in the management of OAD 9

10. Acebrophylline: Drug overview Pozzi E. Monaldi Arch Chest Dis. 2007; 67:106-15. Triple action 10 Abbreviations: OAD: obstructive airway disease

11. Acebrophylline : Mechanism of action Acebrophylline targets the OAD in multiple ways 1. Synthesis and release of pulmonary surfactant Action on phosphocholine-cytidyl-transferase Action on choline-kinase 3. Mucosecretory action Activity of acebrophylline on mucus higher than ambroxol alone Pozzi E. Monaldi Arch Chest Dis. 2007; 67:106-15. 11 Abbreviations: OAD: obstructive airway disease

12. 4 . Mucokinetic activity (mucociliary clearance) 5. Effects on mucus and anti-inflammatory action Blockade at phospholipase A leaves a residue of phosphatidylcholine that can be used by type II pneumocytes to re-synthesize surfactant Acebrophylline : Mechanism of action (Cont.) Pozzi E. Monaldi Arch Chest Dis. 2007; 67:106-15. 12

13. Acebrophylline : An effective treatment option for OAD Pozzi E. Monaldi Arch Chest Dis. 2007; 67:106-15. Acebrophylline 13 Abbreviations: OAD: obstructive airway disease

14. Tapadar SR, et al. J Clin Diagn Res . 2014;8(9):MC11-4. Rationale for using acebrophylline as an add-on therapy in COPD 14 Abbreviations: COPD: Chronic obstructive pulmonary disease; ; LAMA: Long-acting muscarinic antagonist

15. Objective A comparison between acebrophylline and theophylline SR to compare the effectiveness and tolerance at recommended doses as compared to theophylline SR Conclusion For COPD patients with cardiovascular co-morbidity, acebrophylline is a better option than theophylline . Acebrophylline was also considerably effective as add-on therapy with LAMA for COPD management. p=0.0001* p=0.0001* p=0.0001* p=0.01* Tapadar SR, et al. J Clin Diagn Res . 2014;8:MC11-4. SR: Sustained release; PFT: Pulmonary function test; FEV1: Forced expiratory volume in one second; FVC: Forced vital capacity; FEF: Forced expiratory flow; PEFR: Peak expiratory flow rate; LAMA: Long-acting muscarinic antagonist; COPD: Chronic obstructive pulmonary disease Acebrophylline , a valuable add-on therapy in COPD management 15

16. Gain R, et al. J Evolution Med Dent Sci. 2020;9:191-4. Objective To compare the effectiveness and safety of theophylline, doxophylline and acebrophylline as add-on in the management of COPD p=0.002* Conclusion Distinct positive effect on lung function (FEV1) with the use of acebrophylline as add-on was observed. No cardiovascular side effects were noted in doxophylline and acebrophylline groups. COPD: Chronic obstructive pulmonary disease; FEV1: Forced expiratory volume in one second Acebrophylline as an add-on therapy over standard therapy 16

17. Sharma A, et al. J Clin Diagn Res. 2014;8:HC13-HC15. Rationale for using acebrophylline in asthma as an add-on therapy 17 COPD: Chronic obstructive pulmonary disease; ICS: inhaled corticosteroids; LABA: long acting β2- agonists

18. Objective A comparison between formoterol, montelukast and acebrophylline , in combination with budesonide, for their effectiveness in bronchial asthma and evaluation of their role in improving the quality of life Conclusion Acebrophylline in combination with ICS appears as a logical treatment approach due to its different mode of action in relieving asthma. Similar effects on the quality of life of patients by all drugs are also seen. p<0.01* p<0.01* Sharma A, et al. J Clin Diagn Res. 2014;8:HC13-HC15. FEV1: Forced expiratory volume in one second; PEFR: Peak expiratory flow rate; ICS: Inhaled corticosteroid Role of acebrophylline in asthma as an add-on therapy 18

19. Thus, NAC can be used as an add-on therapy to the standard treatment of COPD Kale SB, et al. Int J Basic Clin Pharmacol . 2016;5:775-81. Positioning N-acetylcysteine in COPD management 19 COPD: Chronic obstructive pulmonary disease; GSH: Glutathione; NAC: N-acetylcysteine;

20. Role of N-acetyl cysteine in the management of COPD: Guideline recommendations Gold guideline mentions that in COPD patients not receiving inhaled corticosteroids, regular treatment with mucolytics such as carbocysteine and N-acetylcysteine (NAC) may reduce exacerbations and modestly improve health status.

21. Objective Can NAC promote the improvement of clinical symptoms and lung function in patients with AECOPD Jiang C, Zou J, Lv Q, Yang Y. Ann Palliat Med. 2021;10(6):6564-6576. 21 COPD: Chronic obstructive pulmonary disease; NAC: N- acetylcysteine ; AECOPD: Acute exacerbation of chronic obstructive pulmonary disease Role of NAC in COPD

22. Objective Can NAC promote the improvement of clinical symptoms and lung function in patients with AECOPD Jiang C, Zou J, Lv Q, Yang Y. Ann Palliat Med. 2021;10(6):6564-6576. 22 COPD: Chronic obstructive pulmonary disease; NAC: N- acetylcysteine ; AECOPD: Acute exacerbation of chronic obstructive pulmonary disease Long term use of NAC in COPD

23. Thus, NAC can be used as an add on therapy in asthma management Aliyali M, Poorhasan Amiri A, Sharifpoor A, Zalli F. Effects of N-Acetylcysteine on Asthma Exacerbation. Iran J Allergy Asthma Immunol. 9(2):103-109. Role of N-acetylcysteine in asthma management 23 NAC: N-acetylcysteine;

24. Objective Drugs with antioxidant and anti-inflammatory properties, such as NAC, might provide a useful therapeutic approach for COPD and this study assessed whether NAC could reduce the rate of exacerbations in COPD Conclusion In patients with moderate-to-severe COPD, long-term use of NAC 600 mg twice daily can prevent exacerbations. This study showed a 22% reduction in the risk of exacerbations with NAC. NAC: N-acetylcysteine; COPD: Chronic obstructive pulmonary disease; CABG: Coronary artery bypass graft; FEV1: Forced expiratory volume in one second At 1-year NAC group: 497 acute exacerbations in 482 patients Placebo group: 641 acute exacerbations in 482 patients Risk ratio 0·78, 95% CI 0·67-0·90; p=0·0011) Zheng JP, et al.; PANTHEON study group Lancet Respir Med. 2014;2(3):187-9d. NAC in patients with asthma exacerbations 24

25. Conclusion In a patient with moderate COPD add on therapy with Acebrophylline 100 mg + NAC 600 mg NAC, along with non-pharmacological measures, helped improve lung function and the quality of life of the patient. This therapy was continued over the long-term and reduced exacerbations by half. NAC: N-acetylcysteine; COPD: Chronic obstructive pulmonary disease; CABG: Coronary artery bypass graft; FEV1: Forced expiratory volume in one second A case with moderate COPD 25 The case A patient with a history of COPD had increasing dyspnea

26. Combination therapy: NAC + Acebrophylline 26 COPD Mucoregulator Antioxidant Bronchodilator Mucocilliary Clearance Breaking up mucus Acebrophylline NAC GSH PDE Inflammation ASTHMA BRONCHITIS NAC: N-acetylcysteine; PDE: phosphodiesterase; GSH: glutathione; COPD: Chronic obstructive pulmonary disease; Pozzi E. Monaldi Arch Chest Dis. 2007; 67:106-15; Aliyali M, Poorhasan Amiri A, Sharifpoor A, Zalli F. Effects of N-Acetylcysteine on Asthma Exacerbation. Iran J Allergy Asthma Immunol. 9(2):103-109.