tiotropium-bromide and oxitropium

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

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

The protective effect of inhaled anticholinergic drugs in the methacholine-induced bronchospasm is well-known. The objective of this study was to assess if any possible differences may be found among Ipratropium (IB), Oxitropium (OXI) and Tiotropium (TIO) pre-treatments to obtain the protective effect. Forty-four patients with intermittent bronchial asthma and PD(20)FEV(1) < 200 microg were selected (24 M, 20 F; mean age 32 +/- 8.8). On the baseline, they had mean FEV(1)%: 98.8 +/- 8.54 of theoretical and mean PD(15)FEV(1) 111.8 +/- 61.04 microg. After 72 hours, all patients underwent a second methacholine challenge and were given Ipratropium (40 microg by MDI in 14 pts) or Oxitropium (200 microg by MDI in 14 pts) or Tiotropium (18 microg by Handihaler in 16 pts) sixty minutes before the test. Sixty minutes after the bronchodilator inhalation, the FEV(1)% increase was higher (p < 0.05) in OXI (6.7 +/- 4.83%) and TIO groups (6.11 +/- 2.54%) than in the IB group (3.8 +/- 1.96%). In the IB group PD(15)FEV(1) and PD(20)FEV(1) were obtained in all patients, while in the OXI group they were obtained in 12 and 5 pts respectively and in the TIO group in 14 and 5 pts respectively. Normal hyperreactivity was obtained in 2 patients, in both OXI and TIO groups. In OXI and TIO, the PD(15) obtained after drug pre-medication, was similar (respectively 1628 +/- 955.7 and 1595.5 +/- 990 microg), but higher (p < 0.0001) in comparison to the PD(15) measured in the IB group (532.2 +/- 434.8 microg). Also, the dose-response slope (decline percentage of FEV(1)/cumulative methacholine dose) after PD(15) was similar in both OXI and TIO groups but different in the IB group. A significant relationship (p < 0.01) was found between PD(15)FEV(1) (obtained in 40 pts) and the increase in FEV(1)% obtained 60 minutes after bronchodilator inhalations (r = 0.53). In conclusion, with a standard dose, both Oxitropium and Tiotropium seem to have the same protective effect in bronchial asthma but higher than Ipratropium. It's probable that the best dose of Ipratropium should be a higher one than the usual dose taken.

Topics: Administration, Inhalation; Adult; Analysis of Variance; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Cholinergic Antagonists; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Forced Expiratory Volume; Humans; Ipratropium; Male; Methacholine Chloride; Premedication; Probability; Reference Values; Respiratory Function Tests; Scopolamine Derivatives; Sensitivity and Specificity; Severity of Illness Index; Tiotropium Bromide; Treatment Outcome

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

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