oxitropium and Chronic-Disease

Anticholinergic medications have been accepted as an important treatment modality in chronic bronchitis and chronic asthma, but their use in acute asthma is more controversial. A brief historical context of anticholinergics is given. The innervations of the lung that govern bronchoconstriction and bronchodilatation are reviewed. The pharmacological and neurological properties of anticholinergics make them excellent modalities for treatment of asthma. The benefits of anticholinergics in acute asthma, exercise-induced asthma, nocturnal asthma, and psychogenic asthma are reviewed. The use of anticholinergics in anaphylaxis with beta-blockade is examined.

Topics: Adrenergic beta-Antagonists; Adult; Anaphylaxis; Asthma; Asthma, Exercise-Induced; Bronchitis; Bronchoconstriction; Child; Child, Preschool; Cholinergic Antagonists; Chronic Disease; Glycopyrrolate; Humans; Lung; Parasympatholytics; Scopolamine Derivatives; Status Asthmaticus

The purpose of this study was to evaluate the usefulness of ultrasonically nebulized distilled water (UNDW) inhalation for assessing cough receptor sensitivity and also the effects of inhaled anticholinergic agents and beta 2-agonists on the number of coughs induced by the UNDW inhalation in patients with chronic cough. All patients were non-smokers and had neither bronchial hyperreactivity nor atopic status. We studied the effects of inhaled oxitropium bromide (300 micrograms) and fenoterol hydrobromide (600 micrograms) on the number of coughs induced by UNDW inhalation for 3 minutes in 9 patients with chronic cough and the effects of inhaled fenoterol hydrobromide (400 micrograms) on the number of coughs induced by UNDW inhalation for 1 minute in 8 patients with chronic cough using a randomized, double-blind, cross-over method. There was no significant difference in pulmonary function test results before and after UNDW inhalation. In both the 3-minute and 1-minute UNDW inhalation studies, the number of coughs was greater in the patients than in normal subjects. Patients with chronic cough may have a high level of cough sensitivity, inhaled fenoterol significantly reduced the number of coughs in the patients in both the 3-minute and 1-minute UNDW inhalation studies (p < 0.05). However, compared with control, inhaled oxitropium did not reduce the number of coughs caused by the 3-minute UNDW inhalation in the patients. Tachyphylaxis was observed in normal subjects in the 3-minute UNDW inhalation study when repeated at a 30-minute interval. We conclude that 1-minute UNDW inhalation method may be safe and useful for measuring cough receptor sensitivity of patients with chronic cough and that inhaled beta 2-agonists may have an inhibitory effect on cough induced by irritation of cough receptors through unknown mechanisms other than the bronchodilator effect.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Bronchial Provocation Tests; Chronic Disease; Cough; Cross-Over Studies; Double-Blind Method; Female; Fenoterol; Humans; Male; Middle Aged; Parasympatholytics; Scopolamine Derivatives; Sensory Receptor Cells; Water

The aim of this study was to compare the bronchodilator response of patients with either stable asthma or stable chronic bronchitis to the acute administration of oxitropium bromide and a beta agonist (fenoterol) when given both separately and together in order to determine the responses of these two groups of patients and the optimal doses of these agents when given in combination. The responses of 23 patients with asthma and 25 patients with chronic bronchitis to 400 micrograms of fenoterol, and 200 micrograms of oxitropium given either alone or together with 100, 200 or 400 micrograms of fenoterol was studied. The peak bronchodilator response to oxitropium bromide of the patients with chronic bronchitis was equivalent to the fenoterol response while, in the patients with asthma, the response to oxitropium bromide was approximately 30% of the response to fenoterol. In both groups of subjects the addition of oxitropium bromide to fenoterol significantly increased both the magnitude and the duration of the bronchodilator response without a significant increase in side effects. In both groups of subjects 200 micrograms of oxitropium bromide and 200 micrograms or more of fenoterol gave the optimal response.

Topics: Adult; Asthma; Bronchitis; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Fenoterol; Humans; Middle Aged; Parasympatholytics; Scopolamine Derivatives

The aim of this study was to compare the effects of beta-2 stimulant adrenergic bronchodilators, salbutamol (S) and atropinic bronchodilators, oxitropium bromide (O). The drugs were administered by aerosol, alone or in combination. 20 patients with stable chronic bronchitis were randomised into two groups G1 and G2 and respiratory function tests were done on each group in two sequences, S1 and S2 with 24 hours between. The sequence S1 consisted of three spirometric measurements; an initial control measurement (C) preceding the inhalation of two puffs of 100 mcg of S with a repeat spirometry 15 minutes later followed by the inhalation of two puffs of 100 mcg of O followed by a final spirometry 45 minutes later, one hour after beginning the test. The protocol S2 was similar but the order of drugs was reversed (O then S). The subjects were subjected successively to regimes S1 and S2 for group 1 and inversely for group 2 according to the standard procedure for a crossover trial. The forced expired volume (FEV1) was expected as a percentage of the predicted values and absolute values. Thus only the first dose of inhaled bronchodilator increased slightly but significantly the FEV1. In effect, the administration of the second product led to no supplementary bronchodilator effect. The patients were classified as responders or non-responders for different thresholds of improvement of FEV1 of 10, 15 and 20%. The number of non-responders to the 2 classes of drugs was much greater when the threshold of improvement was raised to 20%. Some patients responded to bronchodilators, others uniquely to one of the two products and finally some to neither. Without reversibility tests it is not possible to predict the response to atropine from the response to beta-2-mimetics.

Topics: Aerosols; Airway Obstruction; Albuterol; Bronchi; Bronchitis; Bronchodilator Agents; Chronic Disease; Drug Combinations; Female; Humans; Male; Maximal Expiratory Flow-Volume Curves; Middle Aged; Parasympatholytics; Scopolamine Derivatives; Spirometry

The effect of oxitropium bromide on lung mucociliary clearance, pulmonary function and viscoelastic properties of sputum was investigated in 10 asthmatics and 10 chronic bronchitics. A controlled, double-blind, crossover study was performed. Following a baseline (B) measurement the patients were, in a random order, allocated placebo (P) or oxitropium bromide (O; 0.1 mg/puff), administered from metered dose inhalers, which they used for 4 weeks at a dose of 2 puffs t.d.s. This test medication was used in conjunction with their normal medication. At the end of the treatment period the patients were assessed, the treatments were then crossed over and a final assessment made 4 weeks later. The administration of oxitropium bromide resulted in (1) small but statistically significant increases in pulmonary function (less than 10% vs. placebo); (2) increased penetrance of radioaerosol into the lungs (mean +/- SEM alveolar deposition: 35 +/- 3, 26 +/- 3 and 24 +/- 3% for the O, P and B runs respectively; p less than 0.025); (3) no significant change in particle clearance rate from the lungs despite their deeper penetration (mean +/- SEM area under the tracheobronchial clearance curves between 0 and 6 h: 317 +/- 26, 324 +/- 25 and 287 +/- 25%.h for the O, P and B runs respectively; p greater than 0.1); (4) no alteration in sputum production, and (5) no significant changes in apparent viscosity (mean +/- SEM: 640 +/- 162, 446 +/- 79 and 557 +/- 115 mPa.s for the O, P and B runs, respectively; p greater than 0.1) and elasticity (mean +/- SEM: 3,682 +/- 1,383, 1,779 +/- 353 and 2,061 +/- 366 mPa for the O, P and B runs, respectively; p greater than 0.1) of sputum. When the two groups, i.e. the chronic bronchitics and asthmatics, were studied separately, no significant differences in any parameter measured (other than radioaerosol penetrance which was significantly enhanced on oxitropium bromide in chronic bronchitics) were noted between the three assessments.

Topics: Aged; Asthma; Bronchitis; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Humans; Middle Aged; Mucociliary Clearance; Parasympatholytics; Random Allocation; Scopolamine Derivatives

Oxitropium bromide (OB) is a quaternary ammonium congener of hyoscine with anticholinergic properties. We studied its bronchodilating properties in 14 patients with chronic obstructive lung disease without features of asthma in whom theophylline and other bronchodilators were withheld. Five doses of OB(20, 40, 100, 200, and 400 micrograms) as well as 150 micrograms of isoproterenol (ISO) and placebo were administered by metered-dose inhaler on separate occasions in a double-blind fashion. Pulmonary function (flow volume loops and airways resistance), blood pressure, and pulse rate were measured at baseline and periodically for eight hours after drug administration. Onset of bronchodilator effect was within five minutes for OB (P less than .025). Duration of action of OB was at least eight hours (P less than .025). The dose response characteristics of OB were examined by correlating the log dose with the areas under the time-FEV1 curve (r = .97, P less than .01), the time-forced vital capacity curve (r = .98, P less than .01), and the time-SGAW curve (r = .83, P less than 0.1). For FEV1, doses of 40 to 400 micrograms were significantly better than placebo and 100 to 400 micrograms were better than ISO (P less than .01). For forced vital capacity, all doses of OB were better than placebo (P less than .05). For SGAW, the response to the 100- and 400-micrograms doses were significantly better than placebo and isoproterenol (P less than .05). There were no significant effects of OB on pulse, blood pressure, or electrocardiogram. No side effects were noted from the use of OB.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Pressure; Bronchodilator Agents; Chronic Disease; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Heart Rate; Humans; Lung Diseases, Obstructive; Male; Parasympatholytics; Plethysmography; Pulse; Random Allocation; Respiration; Scopolamine Derivatives; Spirometry; Theophylline; Time Factors

In a dose response study 12 patients with chronic bronchitis and airflow obstruction received inhaled placebo and incremental doses of oxitropium bromide. Significant improvements in peak expiratory flow rate, forced expiratory volume in one second, and forced vital capacity were recorded at all times up to 10 hours after all doses of oxitropium bromide. Oxitropium bromide is an effective bronchodilator in chronic bronchitis with an optimal dose of 400-600 micrograms.

Topics: Aged; Bronchitis; Chronic Disease; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Parasympatholytics; Peak Expiratory Flow Rate; Scopolamine Derivatives; Vital Capacity

Topics: Aged; Cholinergic Antagonists; Chronic Disease; Humans; Muscle Relaxation; Muscle, Smooth; Pulmonary Emphysema; Respiratory Function Tests; Scopolamine Derivatives; Trachea

19 consecutive patients (18 men, one woman, mean age 61.4 [49-73]years) with chronic obstructive airways disease (bronchitis and emphysema) together with angiographically confirmed coronary heart disease were studied to investigate their cardiopulmonary exercise tolerance and the effects of bronchodilators on their myocardial ischaemia. Because they were receiving drug therapy for angina or because they had previously undergone aortocoronary bypass operation or balloon dilatation, the patients were symptom-free. In three cases slight ischaemia was demonstrable during maximal exertion. Aerobic and anaerobic exercise capacity was determined by spiroergometry after inhalation of salbutamol (S, 0.2 mg) alone or in combination with oxitropium bromide (O, 0.2 mg). The supplementary effect of oral theophylline (T, 15 mg/kg.day) was studied in 13 patients. In terms of maximal aerobic exercise tolerance the following improvements were noted: energy output (watts): S: + 6.3%; S and O: + 12.3% (P < 0.05); S, O and T: + 14.0% (P < 0.01). Oxygen uptake (ml/min): S: + 8.2% (P < 0.05); S and O: + 18.2% (P < 0.01); S, O and T: + 35.4% (P < 0.01). Maximum exercise capacity was not significantly improved, although maximum oxygen uptake was significantly increased by the two-drug combination by 16.9% (P < 0.05) and by the three-drug combination by 19.2% (P < 0.05). Maximum minute volume and tidal volume rose significantly, though respiratory rate was unchanged. Heart rate and blood pressure remained practically unaffected by the treatment, both at rest and during exertion. There was no evidence of significant aggravation of ventricular arrhythmias or of ischaemia during ergometric testing.

Topics: Albuterol; Bronchitis; Chronic Disease; Coronary Disease; Delayed-Action Preparations; Drug Therapy, Combination; Female; Hemodynamics; Humans; Male; Middle Aged; Parasympatholytics; Physical Endurance; Pulmonary Emphysema; Respiratory Function Tests; Scopolamine Derivatives; Theophylline