化痰藥(Mucolytic agents)是療效未明之藥物?!

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MK
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化痰藥(Mucolytic agents)是療效未明之藥物?!

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相關討論:

Gascon是療效未明之藥物?!

http://forum.doctorvoice.org/viewtopic.php?f=81&t=36391
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Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease.
http://www.ncbi.nlm.nih.gov/pubmed/1685 ... d_RVDocSum

Cochrane Database Syst Rev. 2006 Jul 19;3:CD001287

Poole PJ, Black PN.
University of Auckland, Private Bag 92019, Auckland, New Zealand. p.poole@auckland.ac.nz

BACKGROUND: Individuals with chronic bronchitis or chronic obstructive pulmonary disease (COPD) may suffer recurrent exacerbations with an increase in volume and/or purulence of sputum. Because of the personal and healthcare costs associated with exacerbations, any therapy that reduces the number of exacerbations is useful. There is a marked difference between countries in terms of prescribing of mucolytics depending on whether or not they are perceived to be effective.

OBJECTIVES: To assess the effects of oral mucolytics in adults with stable chronic bronchitis or COPD.

SEARCH STRATEGY: We have searched the Cochrane Airways Group Specialised Register and reference lists of articles on four separate occasions, the most recent being in June 2005. This is the third major update.

SELECTION CRITERIA: Randomised trials that compared oral mucolytic therapy with placebo for at least two months in adults with chronic bronchitis or COPD. Studies of people with asthma and cystic fibrosis were excluded.

DATA COLLECTION AND ANALYSIS: One reviewer extracted data. Study authors and drug companies were contacted for missing information.

MAIN RESULTS: Twenty six trials were included (7335 participants). Compared with placebo, there was a significant reduction in the number of exacerbations per patient with oral mucolytics (weighted mean difference (WMD) -0.05 per month, 95% confidence interval -0.05, -0.04). Using the annualised rate of exacerbations in the control patients of 2.6 per year, this is a 20% reduction. The number of days of disability also fell (WMD -0.56, 95% confidence interval -0.77, -0.35). A recent study has shown that the benefit may apply only to those patients not already receiving inhaled corticosteroids. The number of patients who remained exacerbation-free was greater in the mucolytic group (OR 2.13 (95% CI 1.86 to 2.42)). There was no difference in lung function or in adverse effects reported between the treatments.

AUTHORS' CONCLUSIONS: In subjects with chronic bronchitis or COPD, treatment with mucolytics was associated with a small reduction in acute exacerbations and a reduction in total number of days of disability. Benefit may be greater in individuals who have frequent or prolonged exacerbations, or those who are repeatedly admitted to hospital with exacerbations with COPD. They should be considered for use, through the winter months at least, in patients with moderate or severe COPD in whom inhaled corticosteroids (ICS) are not prescribed.
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Role of N-acetylcysteine in the management of COPD.

http://www.pubmedcentral.nih.gov/articl ... d=18044098

Sadowska AM, Verbraecken J, Darquennes K, De Backer WA.
Department of Pulmonary Medicine, University of Antwerp, Antwerp, Belgium. anna.sadowska@ua.ac.be

The importance of the underlying local and systemic oxidative stress and inflammation in chronic obstructive pulmonary disease (COPD) has long been established. In view of the lack of therapy that might inhibit the progress of the disease, there is an urgent need for a successful therapeutic approach that, through affecting the pathological processes, will influence the subsequent issues in COPD management such as lung function, airway clearance, dyspnoea, exacerbation, and quality of life. N-acetylcysteine (NAC) is a mucolytic and antioxidant drug that may also influence several inflammatory pathways. It provides the sulfhydryl groups and acts both as a precursor of reduced glutathione and as a direct reactive oxygen species (ROS) scavenger, hence regulating the redox status in the cells. The changed redox status may, in turn, influence the inflammation-controlling pathways. Moreover, as a mucolytic drug, it may, by means of decreasing viscosity of the sputum, clean the bronchi leading to a decrease in dyspnoea and improved lung function. Nevertheless, as successful as it is in the in vitro studies and in vivo studies with high dosage, its actions at the dosages used in COPD management are debatable. It seems to influence exacerbation rate and limit the number of hospitalization days, however, with little or no influence on the lung function parameters. Despite these considerations and in view of the present lack of effective therapies to inhibit disease progression in COPD, NAC and its derivatives with their multiple molecular modes of action remain promising medication once doses and route of administration are optimized.
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Re: 化痰藥(Mucolytic agents)是療效未明之藥物?!

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The pharmacologic approach to airway clearance: mucoactive agents.

http://www.ncbi.nlm.nih.gov/pubmed/1208 ... d_RVDocSum

Respir Care. 2002 Jul;47(7):818-22

Rubin BK.
Department of Pediatrics, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1081, USA. brubin@wfubmc.edu

The airway mucosa responds to infection and inflammation in a variety of ways. This response often includes surface mucous (goblet) cell and submucosal gland hyperplasia and hypertrophy, with mucus hypersecretion. Products of inflammation, including neutrophil-derived deoxyribonucleic acid (DNA) and filamentous actin (F-actin), effete cells, bacteria, and cell debris, all contribute to mucus purulence and, when this mucus is expectorated it is called sputum. Mucoactive medications are intended to serve one of 2 purposes; either to increase the ability to expectorate sputum or to decrease mucus hypersecretion. Mucoactive medications have been classified according to their proposed mechanisms of action. Increased knowledge of the properties of mucus has given us tools to better understand the mechanisms of airway disease and mucoactive therapy. Expectorants are thought to increase the volume or hydration of airway secretions. Systemic hydration and classic expectorants have not been demonstrated to be clinically effective. Modifiers of airway water transport are being clinically investigated as expectorants. Mucolytics degrade polymers in secretions. The classic mucolytics have free thiol groups to degrade mucin. Peptide mucolytics break pathologic filaments of neutrophil-derived DNA and actin in sputum. Nondestructive mucolysis includes mucin dispersion by means of charge shielding. Mucokinetics are medications that increase mucociliary efficiency or cough efficiency. Cough flow can be increased by bronchodilators in patients with airway hyperreactivity. Abhesives such as surfactants decrease mucus attachment to the cilia and epithelium, augmenting both cough and mucociliary clearance. Mucoregulatory agents reduce the volume of airway mucus secretion and appear to be especially effective in hypersecretory states such as bronchorrhea, diffuse panbronchiolitis, and some forms of asthma. Mucoregulatory agents include anti-inflammatory agents (indomethacin, glucocorticosteroids), anticholinergic agents, and some macrolide antibiotics. Classifying mucoactive agents should help us to develop and evaluate new types of therapy and to better direct therapy toward the patients who are most likely to benefit.
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Re: 化痰藥(Mucolytic agents)是療效未明之藥物?!

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High-dose N-acetylcysteine in patients with exacerbations of chronic obstructive pulmonary disease

Clin Drug Investig. 2005;25(6):401-8.

Zuin R, Palamidese A, Negrin R, Catozzo L, Scarda A, Balbinot M.
Department of Clinical and Experimental Medicine, Section of Respiratory Diseases, University of Padova, Padova, Italy.

OBJECTIVE: To investigate the efficacy and tolerability of high-dose N-acetylcysteine (NAC) in the treatment of patients with exacerbations of chronic obstructive pulmonary disease (COPD).

DESIGN and patients: Randomised, double-blind, double-dummy, placebo-controlled study in 123 patients experiencing an acute exacerbation of COPD.

INTERVENTIONS: NAC 1200 mg/day, 600 mg/day or placebo administered once daily for 10 days. MAIN OUTCOME MEASURES: The primary objective was to assess the proportion of patients with normalised C-reactive protein (CRP) levels. Also assessed were effects on interleukin (IL)-8 levels, lung function and symptoms.

RESULTS: Both NAC 600 and 1200 mg/day were associated with a significantly higher proportion of patients achieving normalised CRP levels compared with placebo (52% and 90% vs 19% of patients; p </= 0.01); however, NAC 1200 mg/day was superior to NAC 600 mg/day (p = 0.002). Furthermore, treatment with NAC 1200 mg/day was more efficacious than NAC 600 mg/day in reducing IL-8 levels and difficulty of expectoration, while the two active regimens had similar beneficial effects on lung function and other clinical outcomes (cough intensity and frequency, and lung auscultation). Treatments were well tolerated with one adverse event reported in NAC 1200 mg/day recipients and two reported in placebo recipients.

CONCLUSION: Treatment with NAC 1200 mg/day improved biological markers and clinical outcomes in patients with COPD exacerbations. It is speculated that the effect of NAC on inflammatory markers may be due to both mucolytic and antioxidant properties.
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Re: 化痰藥(Mucolytic agents)是療效未明之藥物?!

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MK 寫:High-dose N-acetylcysteine in patients with exacerbations of chronic obstructive pulmonary disease

Clin Drug Investig. 2005;25(6):401-8.

Zuin R, Palamidese A, Negrin R, Catozzo L, Scarda A, Balbinot M.
Department of Clinical and Experimental Medicine, Section of Respiratory Diseases, University of Padova, Padova, Italy.

OBJECTIVE: To investigate the efficacy and tolerability of high-dose N-acetylcysteine (NAC) in the treatment of patients with exacerbations of chronic obstructive pulmonary disease (COPD).

DESIGN and patients: Randomised, double-blind, double-dummy, placebo-controlled study in 123 patients experiencing an acute exacerbation of COPD.

INTERVENTIONS: NAC 1200 mg/day, 600 mg/day or placebo administered once daily for 10 days. MAIN OUTCOME MEASURES: The primary objective was to assess the proportion of patients with normalised C-reactive protein (CRP) levels. Also assessed were effects on interleukin (IL)-8 levels, lung function and symptoms.

RESULTS: Both NAC 600 and 1200 mg/day were associated with a significantly higher proportion of patients achieving normalised CRP levels compared with placebo (52% and 90% vs 19% of patients; p </= 0.01); however, NAC 1200 mg/day was superior to NAC 600 mg/day (p = 0.002). Furthermore, treatment with NAC 1200 mg/day was more efficacious than NAC 600 mg/day in reducing IL-8 levels and difficulty of expectoration, while the two active regimens had similar beneficial effects on lung function and other clinical outcomes (cough intensity and frequency, and lung auscultation). Treatments were well tolerated with one adverse event reported in NAC 1200 mg/day recipients and two reported in placebo recipients.

CONCLUSION: Treatment with NAC 1200 mg/day improved biological markers and clinical outcomes in patients with COPD exacerbations. It is speculated that the effect of NAC on inflammatory markers may be due to both mucolytic and antioxidant properties.
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順便請教lysozyme 這類的藥
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hi54turtlela
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Re: 化痰藥(Mucolytic agents)是療效未明之藥物?!

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只能說用藥要很小心
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http://www.ncbi.nlm.nih.gov/pubmed/1926 ... dinalpos=1


The cleaning system of the airways: physiology, pathophysiology and effects of ambroxol
[Article in German]

Wunderer H, Morgenroth K, Weis G.

The human airways are faced by a mucous membrane that keeps the airways humid and protects them. One of the main factors of this protection system is the secretion that covers the surface of the membrane. Like an escalator, secretion is moved steadily, day and night in order to eliminate germs and pollutants from the airways. Healthy people normally do not notice this transport. Infection of the airways accompanied by cough disturbs the transport. The aim of the therapy should be the reconstitution of the transport, not the unsighted suppression of mucus production. Therefore adequate rheological properties of the secretion are needed as well as the balance of its components. Ambroxol affects this system at several sites.
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Antiinflammatory properties of ambroxol

http://www.ncbi.nlm.nih.gov/pubmed/1907 ... dinalpos=4

Eur J Med Res. 2008 Dec 3;13(12):557-62

Beeh KM, Beier J, Esperester A, Paul LD.

insaf Respiratory Research Institute, 65187 Wiesbaden, Germany. k.beeh@insaf-wi.de

Ambroxol is frequently used as mucolytic agent in respiratory diseases associated with increased mucus production like acute or chronic bronchitis. Further, ambroxol is used topically (lozenges) for the treatment of sore throat and pharyngitis associated with common cold. In addition to the effects of ambroxol on mucus regulation and local anaesthetic effects, a wide range of pharmacological antiinflammatory properties of ambroxol have been described in vitro and in vivo, including inhibition or scavenging of oxidative and nitro?sative stress, increase of local defense molecules involved in respiratory virus replication, reduction of proinflammatory cytokines and arachidonic acid meta?bolites, inflammatory cell chemotaxis, and lipid peroxidation of tissues. The present review summarizes the antiinflammatory effects of ambroxol and relates these properties to results from controlled clinical trials in targeted diseases such as chronic bronchitis, chronic obstructive pulmonary disease and sore throat.

PMID: 19073395 [PubMed - indexed for MEDLINE]
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Ambroxol in the 21st century: pharmacological and clinical update.

http://www.ncbi.nlm.nih.gov/pubmed/1868 ... dinalpos=7


Malerba M, Ragnoli B.

University of Brescia, Department of Internal Medicine, 1 degrees Divisione di Medicina, Spedali Civili di Brescia, Pzza Spedali Civili 1, 25100 Brescia, Italy. malerba@med.unibs.it

BACKGROUND: Belonging to the group of expectorants, ambroxol is an active substance with a long history that influences parameters considered to be the basis for the physiological production and the transport of the bronchial mucus. Therefore, ambroxol's indication is 'secretolytic therapy in acute and chronic bronchopulmonary diseases associated with abnormal mucus secretion and impaired mucus transport'.

OBJECTIVE: The aim of this review is to evaluate the pharmacological and clinical data on the mucokinetic compound ambroxol.

METHODS: The existing database that covers >40 years of pharmacological research and clinical development was analysed. Only studies with adequate study design were evaluated.

CONCLUSION: Ambroxol is shown to exert several activities: i) secretolytic activity (i.e., promotes mucus clearance, facilitates expectoration, and eases productive cough); ii) anti-inflammatory and antioxidant activity; and iii) a local anaesthetic effect through sodium channel blocking at the level of the cell membrane. The reduction on chronic obstructive pulmonary disease exacerbations is consistent and clinically relevant. The anaesthetic effect is a new pharmacological action that could be beneficial in the management of acute respiratory tract infections. The efficacy and safety of ambroxol is well established.
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Re: 化痰藥(Mucolytic agents)是療效未明之藥物?!

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Mucolytics in acute and chronic respiratory tract disorders. I. Pathophysiology and mechanisms of action

http://www.ncbi.nlm.nih.gov/pubmed/1205 ... inalpos=19

[Article in Polish]

Kupczyk M, Kuna P.

Klinika Pneumonologii i Alergologii Instytutu Medycyny Wewnetrznej Akademii Medycznej w Łodzi.

Mucus hypersecretion is a cardinal sign of both acute and chronic pulmonary diseases. Normally, mucus protects respiratory tract, but its overproduction leads to airway obstruction and promotes bacterial colonization. In the first part of our review we outlined the possible factors responsible for mucus hypersecretion and clinical consequences of this process. Mucolytic agents such as Ambroxol and N-acetylcysteine are able to alter the secretion of mucus and its physical properties which results in improvement of mucociliary clearance. Mechanisms of action and indications for use of mucolytics are presented. Mucolytics have been shown to have a role in improving lung functions and patients' quality of life. Undoubtedly they are useful as an adjunctive therapy of respiratory tract disorders.
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Re: 化痰藥(Mucolytic agents)是療效未明之藥物?!

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Mucolytics in acute and chronic respiratory tract disorders. II. Uses for treatment and antioxidant properties

[Article in Polish]

http://www.ncbi.nlm.nih.gov/pubmed/1205 ... inalpos=18

Kupczyk M, Kuna P.

Klinika Pneumonologii i Alergologii Instytutu Medycyny Wewnetrznej Akademii Medycznej w Łodzi.

In the first part of our editorial we reviewed the possible factors responsible for mucus hypersecretion in acute and chronic pulmonary diseases. The present paper presents the results of studies proving, that mucolytics are useful in adjunctive therapy of respiratory tract disorders. Mucolytic agents such as Ambroxol and N-acetylcysteine are able to alter the secretion of mucus and its physical properties which results in improvement of mucociliary clearance. Current evidence indicate, that these drugs are effective, especially in chronic obstructive pulmonary disease, asthma and acute bronchitis. They produce a modest improvement in symptom control and lung function. It has been demonstrated that there is a synergism between mucolytics and antibiotics in the treatment of exacerbation of chronic bronchitis. Moreover, they act as scavengers of reactive oxygen species. Ambroxol is able to inhibit mediator release involved in the pathogenesis of allergic inflammation. As mucolytics are cheap and well-tolerated they are beneficial in the therapy of patients suffering from respiratory tract disorders.
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