oxitropium and Pulmonary-Disease--Chronic-Obstructive

Anticholinergics have been used to treat obstructive respiratory disease for many years from historical preparations of the deadly nightshade genus, to the more recent developments ofipratropium, oxitropium, and tiotropium. The medical treatment of airways obstruction has focused on achieving maximal airway function through bronchodilators. Of the two main bronchodilators, beta2-agonists are often the first treatment choice although there is evidence of equivalence and some suggestions of the superiority of anticholinergics in chronic obstructive pulmonary disease (COPD). The following review looks at the background of anticholinergics, their pharmacological properties, and the evidence for use with suggestions for their place in the treatment of COPD.

Topics: Cholinergic Antagonists; Exercise Tolerance; Humans; Ipratropium; Pulmonary Disease, Chronic Obstructive; Quality of Life; Receptor, Muscarinic M1; Receptor, Muscarinic M2; Receptor, Muscarinic M3; Scopolamine Derivatives; Tiotropium Bromide

Anticholinergic agents have important uses as bronchodilators for the treatment of obstructive airway diseases, both asthma and, more particularly, chronic obstructive pulmonary disease (COPD). Those in approved clinical use are synthetic quaternary ammonium congeners of atropine, and include ipratropium bromide, oxitropium bromide, and tiotropium bromide, each of which is very poorly absorbed when given by inhalation. Ipratropium and oxitropium have relatively short durations of action (4-8 h). They have been widely used for many years, either alone or in combination with short-acting beta-adrenergic agents such as albuterol and fenoterol, for both maintenance treatment of stable disease and for acute exacerbations of airway obstruction. Tiotropium, which was introduced in the early 2000s, has a duration of action of at least 1-2 days making it suitable for once-daily maintenance treatment of COPD. All of the above agents have a wide therapeutic margin and are safe and well tolerated by patients.

Topics: Asthma; Bronchodilator Agents; Cholinergic Antagonists; Clinical Trials as Topic; Humans; Ipratropium; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality in the world. In the majority of cases, the disease is the result of years of cigarette smoking. Contributing factors leading to bronchial obstruction in COPD include mucus hypersecretion and an increase in bronchial muscle tone, which is triggered mainly by cholinergic mechanisms. Anticholinergic bronchodilators reduce vagal cholinergic tone, the main reversible component of COPD; hence they are the first-line treatment for bronchial obstruction in COPD. In addition to improving lung function, anticholinergics improve dyspnea, quality of life and exercise tolerance, and they reduce exacerbations. When compared with other bronchodilators, anticholinergics show at least equivalent bronchodilator potency, but with fewer side effects. In addition, due to their unique site of action, anticholinergics can be effectively combined with other bronchodilators. The introduction of new, long-acting anticholinergics is a promising addition to the treatment of COPD and is expected to lead to improved treatment outcomes and improved patient compliance.

Topics: Adrenergic beta-Agonists; Cholinergic Antagonists; Humans; Ipratropium; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide

Inhaled bronchodilators form the mainstay of treatment for acute exacerbations of COPD. Two types of agent are used routinely, either singly or in combination: anticholinergic agents and beta2-sympathomimetic agonists.. To assess the effect of anti-cholinergic agents on lung function and dyspnea in patients with acute exacerbations of COPD, compared with placebo or short-acting beta-2 agonists.. A comprehensive search of the literature was carried out on MEDLINE, EMBASE, CINAHL and the Cochrane COPD Trials Register, using the terms: bronchodilator* OR ipratropium OR oxitropium. References listed in each included trial were searched for additional trial reports.. Studies were included if the participants were adult patients with a known diagnosis of COPD and had symptoms consistent with criteria for acute exacerbation of COPD. All randomized controlled trials that compared inhaled ipratropium bromide or oxitropium bromide to appropriate controls were considered. Appropriate control treatments included placebo, other bronchodilating agents, or combination therapies. Studies of acute asthma or ventilated patients were excluded.. All trials that appeared to be relevant were assessed by two reviewers who independently selected trials for inclusion. Differences were resolved by consensus.. Four trials compared the short-term effects of ipratropium bromide vs. a beta2-agonist. Short-term changes in FEV1 (up to 90 minutes) showed no significant difference between beta2-agonist and ipratropium bromide treated patients. The differences were similar among the studies and when combined: Weighted Mean Difference (WMD) 0.0 liters (95% Confidence Interval (95% CI) -0.19, 0.19). There was no significant additional increase in change in FEV1 on adding ipratropium to beta2-agonist: WMD 0.02 liter (95% CI -0.08, 0.12). Long-term effects (24 hours) of the ipratropium bromide and beta2-agonist treatment combination were similar: WMD 0.05 liters (95%CI -0.14, 0.05). Neither of two studies found significant changes in PaO2, either short- or long-term, with ipratropium vs. beta-agonist, although one showed an increase in PaO2 in subjects receiving ipratropium bromide at 60 minutes. Adverse drug reactions included dry mouth and tremor.. There was no evidence that the degree of bronchodilation achieved with ipratropium bromide was greater than that using a short-acting beta2-agonist. The combination of a beta2-agonist and ipratropium did not appear to increase the effect on FEV1 more than either used alone.

Topics: Bronchodilator Agents; Cholinergic Antagonists; Humans; Ipratropium; Parasympatholytics; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Scopolamine Derivatives

Tiotropium partially relieves exertional dyspnea and reduces the risk of congestive heart failure in chronic obstructive pulmonary disease (COPD) patients. However, its effect on the sympathetic activation response to exercise is unknown.. This study aimed to determine whether tiotropium use results in a sustained reduction in sympathetic activation during exercise.. We conducted a 12-week, open-label (treatments: tiotropium 18 μg or oxitropium 0.2 mg × 3 mg), crossover study in 17 COPD patients. Treatment order was randomized across subjects. The subjects underwent a pulmonary function test and two modes of cardiopulmonary exercise (constant work rate and incremental exercise) testing using a cycle ergometer, with measurement of arterial catecholamines after each treatment period.. Forced expiratory volume in 1 second and forced vital capacity were significantly larger in the tiotropium treatment group. In constant exercise testing, exercise endurance time was longer, with improvement in dyspnea during exercise and reduction in dynamic hyperinflation in the tiotropium treatment group. Similarly, in incremental exercise testing, exercise time, carbon dioxide production, and minute ventilation at peak exercise were significantly higher in the tiotropium treatment group. Plasma norepinephrine concentrations and dyspnea intensity were also lower during submaximal isotime exercise and throughout the incremental workload exercise in the tiotropium treatment group.. Tiotropium suppressed the increase of sympathetic activation during exercise at the end of the 6-week treatment, as compared with the effect of oxipropium. This effect might be attributed to improvement in lung function and exercise capacity and reduction in exertional dyspnea, which were associated with decreases in respiratory frequency and heart rate and reduced progression of arterial acidosis.

Topics: Aged; Cholinergic Agents; Cholinergic Antagonists; Cross-Over Studies; Dyspnea; Exercise Tolerance; Female; Heart Failure; Heart Function Tests; Humans; Male; Physical Exertion; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

No consistent data are available regarding the effect of inhaled corticosteroids (ICS) in alpha(1)-antitrypsin-deficiency (AATD)-related COPD. Recent data report inflammatory effects of the polymers of alpha(1)-antitrypsin on the peripheral lung.. The aim of this study was to assess the effectiveness of an extra-fine ICS, hydrofluoroalkane-134a beclometasone dipropionate (HFA-BDP) with a mass median aerodynamic diameter of 1.1 microm, on lung function and exercise tolerance in COPD patients with AATD when added to long-acting bronchodilators (LABAs).. After a 1-week washout, 8 steroid-naïve COPD patients with AATD (ZZ genotype), within a double-blind randomized cross-over study, were assigned to one of the following 16-week treatments: (1) HFA-BDP 400 microg b.i.d., salmeterol 50 microg b.i.d. and oxitropium bromide 200 microg t.i.d. or (2) placebo, salmeterol 50 microg b.i.d. and oxitropium bromide 200 microg t.i.d; after a 2-week washout period they received the other treatment. In weeks 1, 17, 19 and 35, patients took a spirometry assessment (breathing air and heliox) and a shuttle walking test (SWT) with dyspnea assessed by the modified Borg scale.. Significant differences in improvement were found in FEV(1), FVC, IC, distance covered and dyspnea perceived during SWT between the 2 treatments and baseline values (p < 0.05; Friedman's test). However, further analysis showed that only the LABAs + ICS condition showed significant increases in the FEV(1), FVC, IC, DeltaMEF(50%) and distance covered during SWT along with a reduction in maximum isostep exertional dyspnea (p < 0.05; Wilcoxon test). A greater distance was walked at the end of the SWT with LABA + ICS than LABAs alone (301 +/- 105 vs. 270 +/- 112 m; p < 0.05).. In AATD-related COPD patients (ZZ genotype) the addition of extra-fine ICS to LABAs decreases airway narrowing, mostly in the small airways, further reducing dynamic hyperinflation with a marked improvement in exercise tolerance and dyspnea, suggesting that a peripheral inflammatory process contributes to airflow obstruction in these patients.

Topics: Administration, Inhalation; Aged; Albuterol; alpha 1-Antitrypsin Deficiency; Beclomethasone; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Dyspnea; Exercise Tolerance; Female; Glucocorticoids; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Salmeterol Xinafoate; Scopolamine Derivatives

The present study was undertaken to evaluate the long-term effect of procaterol hydrochloride (CAS 62929-91-3, Meptin), a third generation beta2-receptor agonist on lung function, exercise capacity, health-related quality of life (HRQOL) and activities of daily living (ALDs) in patients with stable chronic obstructive pulmonary disease (COPD). Twenty patients were randomly assigned to the procaterol group or to the control group, who received oxitropium bromide (CAS 30286-75-0), an anticholinergic agent. Procaterol was inhaled three times a day at a dose of 20 pg, while oxitropium was inhaled three times a day at a dose of 200 microg. The subjects were evaluated based on spirometry, exercise capacity, the Borg Scale, HRQOL, and ADLs before and after 12, 24 and 52 weeks of therapy. The values of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), functional residual capacity (FRC), residual volume (RV), maximal inspiratory pressure (PImax), and maximal expiratory pressure (PEmax) were significantly improved at 12, 24 and 52 weeks compared with baseline values in the procaterol group (p < 0.05, p < 0.01), while these values did not differ from baseline values at any point in the oxitropium group (p > 0.05). Additionally, 6-min walking distances and Borg Scale values showed significant improvement at 12, 24 and 52 weeks compared with baseline values in the procaterol group (p < 0.05, p < 0.01), but did not significantly differ from baseline values in the oxitropium group at any point (p > 0.05). Likewise, the scores for dyspnea, fatigue, emotional function, mastery, total scores and ADLs were significantly higher at 12, 24 and 52 weeks compared with the baseline values in the procaterol group (p < 0.05, p < 0.01), but did not differ at any point in the oxitropium group (p > 0.05). These results suggest the effectiveness of long-term regular bronchodilator therapy with the beta2-receptor agonist procaterol in patients with stable COPD.

Topics: Activities of Daily Living; Adrenergic beta-Agonists; Aged; Exercise; Exercise Test; Female; Forced Expiratory Volume; Humans; Male; Parasympatholytics; Procaterol; Pulmonary Disease, Chronic Obstructive; Quality of Life; Respiratory Function Tests; Scopolamine Derivatives; Spirometry; Surveys and Questionnaires

Inhaled bronchodilators are first line drugs in the treatment of chronic obstructive pulmonary disease (COPD). Tiotropium bromide is a recently introduced long-acting anticholinergic agent able to reduce dyspnoea and COPD exacerbations and to improve pulmonary function and quality of life. We designed a study to compare the short-term efficacy of tiotropium bromide with that of oxitropium bromide in improving pulmonary function in patients with COPD.. Eighty patients were randomized either to continue oxitropium 800 mcg/day or to receive tiotropium 18 mcg/day. Seventy-six (39 in the tiotropium and 37 in the oxitropium group) completed the study. Plethysmography was performed at baseline and after 72 h in all patients. The changes in functional parameters in the two groups were compared by the Mann-Whitney U-test.. There were no differences between the two groups regarding age (72.5 vs. 74.2 years), male/female ratio (25/14 vs. 23/14) and pulmonary function at baseline. The changes in spirometric parameters were significantly greater in tiotropium- than in oxitropium-treated patients: mean forced expiratory volume in 1s (FEV(1)) increased significantly by 15% vs. 3% (P=0.017), mean FVC by 10.5% vs. 2.2% (P=0.044), and FEF 25, 50, and 75 by 34% vs. 14% (P<0.05), 33% vs. 7% (P<0.05), and 50% vs. 6% (P<0.0001), respectively; mean FRC and RV decreased nonsignificantly by 7.5% and 10% with tiotropium vs. 4.3% and 6.5% with oxitropium, respectively.. The replacement of oxitropium with tiotropium significantly increases pulmonary function in patients with COPD. The improvement involves also small airways that have not been investigated thus far.

Topics: Aged; Bronchodilator Agents; Cholinergic Antagonists; Female; Humans; Lung; Male; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Scopolamine Derivatives; Tiotropium Bromide

It has been shown that patients with chronic obstructive pulmonary disease (COPD) develop dynamic hyperinflation (DH), which contributes to dyspnoea and exercise intolerance. Formoterol, salmeterol and oxitropium have been recommended for maintenance therapy in COPD patients, but their effect on DH has only been assessed for salmeterol. The aim of the present study was to compare the acute effect of four inhaled bronchodilators (salbutamol, formoterol, salmeterol and oxitropium) and placebo on forced expiratory volume in one second, inspiratory capacity, forced vital capacity and dyspnoea in COPD patients. A cross-over, randomised, double-blind, placebo-controlled study was carried out on 20 COPD patients. Patients underwent pulmonary function testing and dyspnoea evaluation, in basal condition and 5, 15, 30, 60 and 120 min after bronchodilator or placebo administration. The results indicate that in chronic obstructive pulmonary disease patients with decreased baseline inspiratory capacity, there was a much greater increase of inspiratory capacity after bronchodilator administration, which correlated closely with the improvement of dyspnoea sensation at rest. For all bronchodilators used, inspiratory capacity reversibility should be tested at 30 min following the bronchodilator. On average, formoterol elicited the greatest increase in inspiratory capacity than the other bronchodilators used, though the difference was significant only with salmeterol and oxitropium. The potential advantage of formoterol needs to be tested in a larger patient population.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Aged; Albuterol; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Dyspnea; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate; Scopolamine Derivatives; Time Factors; Vital Capacity

The aim of the present study was to assess the reproducibility of changes in forced inspiratory volumes after bronchodilator inhalation. Thirteen patients with chronic obstructive pulmonary disease (COPD) (FEV1, 32-75%pred) and 10 patients with asthma (FEV1, 43-75%pred) inhaled either 200 microg fenoterol or 200 microg oxitropium bromide or placebo, each of them on three occasions, on nine different days in a randomised, cross-over, double-blind fashion. Forced expiratory (FEV1) and inspiratory (FIV1) volumes were measured before and 30 min after inhalation. In patients with COPD, the increase in FEV1 (coefficient of variation) was 221 ml (43%) after fenoterol and 235 ml (33%) after oxitropium; changes in FIV1 were 301 ml (45%) and 360 ml (29%). In patients with asthma, FEV1 improved by 618 ml (26%) and 482 ml (25%), FIV1 by 553 ml (41%) and 475 ml (23%). In less severe COPD or asthma, the reduction in dyspnoea was associated with the improvements in both FIV1 and FEV1, but in severe COPD with the improvement in FIV1 only. The data demonstrate that, at least in terms of relative changes, the reproducibility of bronchodilator responses in terms of FIV1 is similar to that of FEV1 and they underline the assertion of FIV1 being a sensible parameter particularly in severe COPD.

Topics: Adrenergic beta-Agonists; Aged; Asthma; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Female; Fenoterol; Forced Expiratory Volume; Humans; Inspiratory Capacity; Male; Middle Aged; Parasympatholytics; Pulmonary Disease, Chronic Obstructive; Reproducibility of Results; Scopolamine Derivatives

Anti-cholinergic agents are considered the bronchodilator therapy of first-choice in the treatment of patients with stable chronic obstructive pulmonary disease (COPD) associated with heart disease since they may be as effective or more effective than inhaled beta2-agonists and, moreover, they do not interact with cardiac beta-adrenoceptors. The aim of our study was to evaluate the bronchodilator activity of oxitropium bromide in outpatients suffering from exacerbations of COPD associated with heart diseases (ischaemic heart disease and/or arrhythmias). We recruited 50 consecutive outpatients (33 males and 17 females, mean age 68.6 years, 15 current smokers and 35 ex-smokers). Each patient performed body plethismography in basal condition and 30 min after inhalation of 200 microg metered dose inhaler (MDI) oxitropium bromide administered by a device (Fluspacer). FEV1, FVC, MMEF25-75, sRaw and tRaw were evaluated. Thirty minutes after 200 microg oxitropium bromide administration, we observed a significant improvement in FEV1 11.6% +/- 1 (mean +/- SEM) (P<0.01); FVC, MMEF25-75 sRaw variation was respectively: 9.2% +/- 0.6, 31.4 +/- 2.9, -19.9 +/- 1.1. Placebo did not significantly change pulmonary function. Our data suggest that oxitropium bromide bronchodilator activity is effective in exacerbations of COPD.

Topics: Acute Disease; Aged; Arrhythmias, Cardiac; Bronchodilator Agents; Cholinergic Antagonists; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Myocardial Ischemia; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Smoking; Vital Capacity

Acute bronchodilator response (BDR) is a potential phenotypic characteristic of COPD. However, the clinical factors associated with BDR in patients with COPD remain unclear, particularly for BDR to anticholinergic agents.. We aimed to clarify the clinical factors associated with BDR to β2-agonist and/or anticholinergic agent, considering time-associated variations of BDR. We also evaluated the association between BDR and clinical course of COPD.. We analyzed 152 subjects who participated in the Hokkaido COPD cohort study. We repeatedly measured BDR to salbutamol (400 μg) or oxitropium (400 μg) three times for each every 6 months alternately over 3 years. Reversibility was defined by ≥ 12% and ≥200 mL increase in FEV. For either agent, the mean blood eosinophil count was significantly higher in those with consistently reversible than those with consistently irreversible (p < 0.05). The subjects with consistently reversible to oxitropium (p < 0.05), but not to salbutamol (p = 0.56), showed increased risk of exacerbation compared with the other two groups.. We identified the distinct clinical characteristics of COPD associated with acute BDR status. Increased cholinergic airway tone, which is reflected in the higher BDR only to anticholinergic agent, but not to β2-agonist, may be associated with exacerbation in COPD.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Aged; Aged, 80 and over; Albuterol; Bronchodilator Agents; Cholinergic Antagonists; Cohort Studies; Disease Progression; Eosinophils; Female; Forced Expiratory Volume; Humans; Japan; Male; Phenotype; Pulmonary Disease, Chronic Obstructive; Risk Assessment; Scopolamine Derivatives

Previous studies have shown that polymorphisms in the β2-adrenergic receptor gene (ADRB2) may influence bronchodilator response (BDR) to both β2-agonists and anticholinergics, possibly by intracellular cross-talk, but in opposite ways, in the Japanese population. We hypothesized that the preferential response to either class of bronchodilators might be determined by ADRB2 polymorphisms in patients with chronic obstructive pulmonary disease (COPD).. To examine the association of ADRB2 polymorphisms and preferential BDR to β2-agonists and anticholinergics in patients with COPD.. The participants had been enrolled in the Hokkaido COPD cohort study. BDR to either class of bronchodilators (salbutamol or oxytropium, 0.4 mg) was measured every 6 months for 2 years. Considering the variation of BDR within and between days, mean values of postbronchodilator increases in forced expiratory volume in 1 s (ΔFEV₁) for the two agents measured at two different visits were initially used for the primary analysis (N=189). To confirm the results of the primary analysis, ΔFEV₁ measured at a single visit was also used for secondary analyses.. Although a significant correlation between BDRs to salbutamol and to oxytropium was observed (P<0.001, r=0.36), there were individuals who responded preferentially to one of the two agents. When the participants were classified into two groups based on the bronchodilator causing the better response (salbutamol-dominant group and oxytropium-dominant group), Arg allele was significantly more common in the oxytropium-dominant group than in the salbutamol-dominant group (0.001

Topics: Adrenergic beta-2 Receptor Agonists; Aged; Albuterol; Asian People; Bronchodilator Agents; Cholinergic Antagonists; Cohort Studies; Female; Genetic Predisposition to Disease; Humans; Male; Polymorphism, Genetic; Pulmonary Disease, Chronic Obstructive; Receptors, Adrenergic, beta-2; Scopolamine Derivatives; Treatment Outcome

Chronic obstructive pulmonary disease (COPD), which ranks fifth in terms of the global burden of diseases, is one of the major risk factors of post-operative pulmonary complications. Tiotropium bromide is a new inhaled bronchodilator for COPD patients with a sustained duration of action; it has superior efficacy compared to other bronchodilators. However, little is known regarding its clinical value as a preoperative treatment for COPD patients. In this study, we compared the incidence of post-operative complications between COPD patients who received with tiotropium bromide and those who did not.. Retrospective study.. For 1 month before surgery we examined 84 and 82 patients treated with tiotropium bromide (tiotropium group) and oxitropium bromide (oxitropium group), respectively, in combination with other medications. We performed a statistical comparison of clinical features, pulmonary functions, and postoperative complications between the 2 groups.. The improvements in clinical symptoms and forced expiratory volume in 1 second were better in the tiotropium group than in the oxitropium group. The incidence of post-operative pulmonary complications (refractory bronchospasm, pulmonary infection, and acute respiratory failure) was significantly lower in the tiotropium group than in the oxitropium group. Three patients in the tiotropium group complained of dry mouth; however, the symptoms could be controlled. The incidence of post-operative non-pulmonary complications was not significantly different between the 2 groups.. We propose that tiotropium bromide might be a safe and useful drug for pre-operative treatment of COPD patients.

Topics: Adult; Aged; Aged, 80 and over; Bronchodilator Agents; Female; Humans; Male; Middle Aged; Preoperative Care; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Scopolamine Derivatives; Tiotropium Bromide