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PubMed1995

Bronchodilating effects of combined therapy with clinical dosages of ipratropium bromide and salbutamol for stable COPD: comparison with ipratropium bromide alone.

Several studies have suggested that anticholinergics are at least equal to or may be superior to beta agonists in the treatment of stable COPD. However, since most previous studies have been performed to evaluate the bronchodilating effects of these two agents at relatively high doses, the clinical value of combining these two agents still is under debate. The purpose of this study was to determine if combination therapy with ipratropium bromide and salbutamol, in clinically available dosages, is superior in bronchodilation to ipratropium bromide alone. Twenty-six male patients (mean age, 67.5 +/- 5.9 years; FEV1, 0.87 +/- 0.32 L) with stable COPD were studied in randomized, double-blind, placebo-controlled experiments. On five separate days, all the patients received one of the following: (1) 40 micrograms ipratropium bromide, (2) 80 micrograms ipratropium bromide, (3) 40 micrograms ipratropium bromide plus 200 micrograms salbutamol, (4) 80 micrograms ipratropium bromide plus 400 micrograms salbutamol, or (5) placebo, using metered-dose inhalers (MDIs). Spirometry was assessed before and 15, 30, 60, 90, and 120 min after inhalation. Positive FEV1 responses to combined dosages of 80 micrograms ipratropium bromide and 400 micrograms salbutamol were significantly greater than responses to any other treatment regimen. Significantly greater responses also were achieved by combining 200 micrograms salbutamol with 40 micrograms ipratropium bromide compared with 40 micrograms ipratropium bromide alone. Combination therapy with 200 micrograms salbutamol and 40 micrograms ipratropium bromide produced a significantly greater effect on forced vital capacity than therapy with 80 micrograms ipratropium bromide alone. No significant differences were found between the responses induced by therapy with 80 and 40 micrograms ipratropium bromide. No adverse reactions to any regimen were noted throughout the study. In conclusion, combining the standard dosages of ipratropium bromide and salbutamol may provide greater bronchodilation than doubling the standard dosage of ipratropium bromide in patients with COPD.

Aged↗
PubMed1986

Ipratropium bromide (Atrovent) as inhalation powder. A double-blind study of comparison with ipratropium as a pressure aerosol in patients with reversible airways obstruction.

The bronchospasmolytic effects of 40 micrograms ipratropium bromide (Atrovent) given either as an aerosol (2 puffs of 20 micrograms) or as a powder inhalation were compared in a double-blind cross-over study. Following a randomisation list the drug was given on 2 successive days to 20 patients with stable bronchospasm in whom it had previously been shown that the bronchial obstruction was reversible after administration of 40 micrograms ipratropium bromide as an aerosol (with an increase over the baseline value of the FEV1 of at least 15% 1 h after drug administration). The effects of the two presentations of ipratropium bromide were followed by respiratory function tests from 15 min to 6 h after administration of the drug. With both formulations excellent bronchospasmolytic effects were noted in each of the parameters measured. The peak of the effects was noted approximately 1 h after the inhalations. Six hours later there was still a significant improvement in comparison with the baseline values. There was no significant difference between the results with the two different formulations. Inhalation powder of ipratropium bromide was well tolerated and there were no complaints of irritation or coughing. It would appear, therefore, to be a valuable alternative to the pressure aerosol.

Administration, Intranasal↗
PubMed1989

Standard and double dose ipratropium bromide and combined ipratropium bromide and inhaled metaproterenol in COPD.

Inhaled ipratropium bromide (IPR) is effective in the management of COPD. The purpose of this study was to determine if doubling the standard dose of IPR resulted in greater bronchodilation and if the addition of an inhaled beta-agonist was superior to standard dose IPR alone. Twelve male patients with stable COPD completed a double blind, randomized trial. On each of three consecutive days, following baseline spirometry, all patients inhaled two puffs of IPR. This was followed by either two additional puffs of IPR, two puffs of metaproterenol (META), or two puffs of placebo. All inhalants were delivered by an InspirEase spacer. Spirometry was repeated at 30, 60, 120, and 180 minutes. The group mean percentage increases in the FEV1 and FVC from baseline were similar at all times tested for the three protocols. In conclusion, for the group, there was no objective benefit to doubling the standard dose of IPR or combining IPR with META. Two of 12 patients benefited from combining the two bronchodilators. A potential sequence for bronchodilator testing is suggested.

Administration, Inhalation↗
PubMed1976

[Ipratropium Bromide, an Anticholinergic Bronchodilator/Behavior of airways resistance in patients with reversible respiratory obstruction following inhalation of various doses of ipratropium bromide].

A dose- and time-response study using different doses of an inhaled derivative of atropine, (8r)-3alpha-hydroxy-8-isopropyl-1 aH, 5aH-tropaniumbromide-(+/-)-tropate (Sch 1000, ipratropium bromide, Atrovent) was performed in 12 patients with reversible chronic obstructuve airways disease. The drug was shown to be an effective bronchodilator with the typical action of reducing airways resistance with 2 puffs (0.02 mg per puff). Increasing the dose to 4 and 8 puffs did not produce any relevant difference in time response. The onset of action was rapid and reached a maximum between 30 and 60 min after inhalation. The duration of bronchodilation was maintained during the observation period of 3 h. 30 min after inhalation the results corresponded to those following the inhalation of 2 puffs of orciprenaline (0.75 mg per puff). Isolated side-effects were independent of the dosage.

Adult↗
PubMed1976

[Ipratropium bromide in controlled clinical trials. Short communication (II): Time-response measurements of pulmonary function after ipratropium bromide and isoprenaline].

(8R)-3alpha-Hydroxy-8-isopropyl-1alphaH, 5alphaH, 5alphaH-tropaniumbromide (+/-)-tropate (ipratropiumbromide, Sch 1000, Atrovent) was compared with isoprenaline in a cross-over study with randomized selection in 12 stable asthmatics, using total airways resistance (Rt) measured by whole-body plethysmography, peak expiratory flow (PEF) and pulse rate as parameters. 2 puffs ipratropiumbromide (0.02 mg per puff) or isoprenaline (0.1 mg per puff) were administered by metered dose inhaler and measurements taken at 5, 20, 35, 50, 90 min, 2, 3, 4, and 6 h later. Drugs were given on alternate days. Rt decreased significantly (p less than 0.001) for 4 h to 53% of the initial value after ipratropiumbromide and to 70% of the initial value after isoprenaline, but only for about 2 h after the latter. The maximum 20-min effect on Rt was almost the same for both drugs. The difference in the time course of the bronchodilation was also significant. The rise in PEF after 4 h following ipratropiumbromide was similarly highly significant (p less than 0.001); as for Rt the time course for both drugs ran nearly parallel. Neither substance caused a significant rise in pulse rate at the dosages used.

Airway Resistance↗
PubMed1995

A comparison of the bronchodilating effects of salmeterol, salbutamol and ipratropium bromide in patients with chronic obstructive pulmonary disease.

Bronchodilator efficacy of salbutamol (200 micrograms), salmeterol (50 micrograms) and ipratropium bromide (40 micrograms) aerosols has been compared in 16 patients with stable chronic obstructive pulmonary disease (COPD) using a double-blind placebo controlled cross-over design. When absolute changes in FEV1 were used as the response criterion, efficacy of the three drugs was significantly better than placebo (P < 0.05). The onset of bronchodilatation after ipratropium bromide was slower than after salbutamol, but ipratropium induced more and longer-lasting bronchodilatation than the adrenergic drug. Salmeterol was slower but its duration was longer than salbutamol. The onset of the effect of salmeterol was slower than ipratropium bromide, but salmeterol showed, on average, superior bronchodilator efficacy compared with the anticholinergic agent, sustaining bronchodilation longer than ipratropium bromide (responses to salmeterol were significantly (P < 0.05) greater than those to ipratropium bromide from 4-12 h time period, but from 15 min to 1 h time periods response to ipratropium bromide exceeded salmeterol). The mean FEV1 area under the curve was significantly (P < 0.05) larger after salmeterol when compared to ipratropium bromide and salbutamol. Moreover, the mean FEV1 area under the curve after ipratropium bromide was significantly (P < 0.05) higher than that after salbutamol. In any case, our data showed individual differences in patient response. We conclude that salmeterol compares favourably with ipratropium bromide in terms of effects on lung function at clinically recommended doses because it has a longer duration of action than ipratropium bromide. The longer dosing intervals, which may enhance compliance, encourage its administration in patients with COPD.

Administration, Inhalation↗
PubMed1997

Efficacy of nebulized ipratropium in severely asthmatic children.

STUDY OBJECTIVE: To determine the effect of adding the nebulized anticholinergic drug ipratropium bromide to standard therapy compared with standard therapy alone for acute severe asthma (peak expiratory flow rate [PEFR] < 50% of predicted) in children presenting to the emergency department. METHODS: Ninety children aged 6 to 18 years were randomly assigned to two groups in a prospective, double-blind, placebo-controlled study performed in the ED of an urban children's hospital. All children received nebulized albuterol solution (.15 mg/kg) every 30 minutes, and all received oral steroids with the second dose of albuterol. Children in group 1 received ipratropium bromide (500 micrograms/dose) with the first and third dose of albuterol those in group 2 received saline placebo instead of ipratropium. Pulmonary functions (PEFR and 1-second forced expiratory volume [FEV1]) and physiologic measurements were assessed every 30 minutes up to 120 minutes. By chance, the baseline values for percent of predicted PEFR and FEV1 differed between the two groups. Therefore a multivariate model accounting for both time and baseline effects was used to compare the response between groups. RESULTS: On average, and adjusting for baseline measures, children in the ipratropium group had a significantly greater improvement in percent of predicted PEFR than did children in the placebo group at 60 minutes (P = .02), 90 minutes (P = .002), and 120 minutes (P < .0001). The improvement in percent predicted FEV1 was significantly greater for children in the ipratropium group only at 120 minutes (P = .013). Nine children (20%) from the ipratropium group and 14 (31.1%) from the control group were admitted (P = .33, chi 2). There were no significant adverse effects attributable to the ipratropium, and there was no relation between ipratropium use and changes in pulse, respiratory rate, blood pressure, or oxygen saturation. CONCLUSION: We detected significant improvement in pulmonary function studies over 120 minutes in children with severe asthma who were given nebulized ipratropium combined with albuterol and oral steroids, compared with children who received the standard therapy. Further study is needed to determine whether early use of ipratropium decreases the need for hospitalization.

Adolescent↗
PubMed1990

Bronchodilator responses to salbutamol followed by ipratropium bromide in partially reversible airflow obstruction.

We have performed a retrospective survey on 296 patients, who attended the Respiratory Function Unit at Guy's Hospital to have their bronchodilator responses (BR) tested. The aim of the study was to see the effect of ipratropium bromide (IB) in a group of patients with incomplete reversibility after salbutamol (S). Patients were routinely given salbutamol and ipratropium bromide sequentially by inhalation, and spirometric changes were recorded after each drug. We identified two groups: Group A, 95 patients with FEV1 response greater than or equal to 0.2 l after either drug and FEV1 less than 80% predicted after salbutamol; and, Group B, 49 with change in FEV1 less than 0.02 l, FVC less than 80% predicted after salbutamol and an improvement in FVC greater than or equal to 0.33 l. Seventy-nine of the 95 patients in Group A also had an FVC response. In Group A, age was negatively correlated with response to salbutamol (r = -0.41, P less than 0.0001), and within Group B baseline FVC was negatively correlated with response to ipratropium bromide (r = -0.30, P = 0.03). There were no differences in age, sex, or doses given to each group (median dose: salbutamol, 800 micrograms, ipratropium bromide 120 micrograms). Baseline FEV1 and FVC (% predicted) were significantly higher in FEV1 responders. Mean (SD) FEV1 were 43% (14) in Group A vs. 29% (14) in Group B, while FVC were 62% (16) vs. 47% (13), P less than 0.001. Responses to ipratropium bromide were more frequent in Group B; in Group A 87% improved after salbutamol and 26% after ipratropium bromide, while in Group B 68% responded to salbutamol and 47% to ipratropium bromide (P = 0.03). Most patients responded to salbutamol, but in 33% ipratropium bromide had an additional effect. The FEV1 response to salbutamol declined with age. Isolated volume responders had more severe airflow obstruction, had less responses to salbutamol and were more likely to show a response to ipratropium bromide. These results support a trial of ipratropium bromide in patients with inadequate beta responsiveness, especially in those with severe airflow obstruction.

Administration, Inhalation↗
PubMed1997

Airway response of horses with COPD to dry powder inhalation of ipratropium bromide.

To determine the effects of the dry powder inhalation (DPI) of ipratropium bromide (ipratropium) on the airways of health horses and the dose-response curve in horses suffering from chronic obstructive pulmonary disease (COPD) by means of pulmonary function tests, five healthy horses were first studied. Ipratropium (2400 micrograms ipratropium horse-1) was contained in gelatine capsules and administered using a dry powder device connected to an adapted face mask. Pulmonary function tests were recorded before inhalation and 15 and 60 min after inhalation. No modification of pulmonary function was observed. The airway response to ipratropium DPI was then determined in six horses suffering from COPD. To induce airway obstruction, the horses were bedded on straw and fed hay. When the maximal change in pleural pressure during tidal breathing exceeded 1.96 kPa, pulmonary function tests were recorded before DPI, and 15 and 60 min post-inhalation. Placebo (six capsules horse-1) or ipratropium (600, 1200 and 2400 micrograms horse-1) was administered in a randomized order to each horse using the dry powder device and the adapted face mask. Neither ipratropium nor placebo DPI affected respiratory frequency (f) or tidal volume (VT). Inhalation of 600 micrograms ipratropium horse-1 resulted in a delayed decrease of total pulmonary resistance (RL) whereas dynamic compliance (Cdyn) was improved (although not significantly) at both times of measurement when compared with values following placebo inhalation. Simultaneous decreased RL and increased Cdyn, was observed within 15 min after DPI of 1200 micrograms ipratropium horse-1 and persisted for the 1 h duration of the experiment. Doubling the dose also improved pulmonary function but not significantly more than following inhalation of 1200 micrograms ipratropium. No systemic side effects were observed in either group of horses.

Administration, Inhalation↗
PubMed1992

Effects of ipratropium bromide nebulizer solution with and without preservatives in the treatment of acute and stable asthma.

In a recent study, it was suggested that the preservatives in ipratropium bromide nebulizer solution may cause a paradoxic bronchoconstrictor response in 20 percent or more of patients with stable asthma. The frequency of this response in patients with acute asthma is unknown. The aim of this study was to examine the acute effects of the usual dose of nebulized ipratropium bromide (0.25 mg) in patients with either stable or acute asthma using formulations with and without added preservatives. Twenty-five patients with stable asthma and 25 patients with acute asthma were studied. Each subject was given preservative-containing ipratropium bromide, preservative-free ipratropium bromide, pH 7 preservative-free ipratropium bromide, and saline solution in random order using a double-blind crossover technique with at least 4 h between drug administrations. Very frequent measurements of FEV1 were made for 30 min after each drug administration and then 5 mg of albuterol was nebulized and the FEV1 was measured again after another 30 min. Changes in FEV1 were expressed as a percentage of the predicted FEV1. Paradoxic bronchoconstriction to ipratropium was detected in only one patient with acute asthma (12 percent fall in FEV1) but in none of the patients with stable asthma. A 6 percent fall in FEV1 change occurred with the saline solution in this subject suggesting that the response may have been a nonspecific one due to increased bronchial responsiveness. The mean response (+/- 1 SD) to albuterol plus either preservative-containing ipratropium, preservative-free ipratropium, or pH7 preservative-free ipratropium was significantly greater (p less than 0.05) than the response to albuterol alone both in the patients with acute asthma (25 +/- 12 percent, 27 +/- 15 percent, 26 +/- 15 percent, and 20 +/- 15 percent, respectively) and stable asthma (26 +/- 7 percent, 25 +/- 8 percent, 24 +/- 6 percent, and 22 +/- 9 percent) supporting the use of ipratropium bromide as an additional bronchodilator in patients with asthma who do not show a satisfactory response to nebulized beta-adrenergic agonist.

Aerosols↗
PubMed1996

Effectiveness and safety of intranasal ipratropium bromide in common colds. A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To determine the tolerability and clinical effectiveness of intranasal ipratropium bromide for the treatment of symptoms of common colds. DESIGN: Multicenter, double-blind, randomized trial. SETTING: 3 university student health services. PATIENTS: 411 previously healthy persons 14 to 56 years of age who had cold symptoms that had lasted for no more than 36 hours, rhinorrhea subjectively judged to be of at least moderate severity, and documented nasal discharge of at least 1.5 g over a 1-hour observation period. INTERVENTION: Either 1) ipratropium bromide nasal spray 0.06% in buffered salt solution, two 42-micrograms sprays per nostril administered by metered pump spray; 2) control nasal spray, which consisted of buffered salt solution; or 3) no treatment. Treatments were self-administered three or four times daily during waking hours for 4 days. After receiving their morning dose, patients stayed at the study center for 6 hours on study day 1 and 3 hours on study day 2; symptom severity was recorded and nasal mucus discharges were collected and weighed hourly during these periods. RESULTS: Ipratropium recipients had 26% less nasal discharge than controls (P = 0.0024) and 34% less nasal discharge than untreated patients (P = 0.0001). Severity of rhinorrhea as judged subjectively was reduced in ipratropium recipients by 31% compared with controls and by 78% compared with untreated patients (P = 0.0001 for both comparisons). In addition to being associated with reductions in daily assessments of the severity of rhinorrhea (P < or = 0.003), ipratropium was associated with reduced sneezing on study days 2 (20% difference; P = 0.03) and 4 (30% difference; P = 0.02) but not with reduced nasal congestion compared with the control spray. Ipratropium was generally well tolerated but was associated with higher rates of blood-tinged mucus (16.8% in the ipratropium group compared with 3.6% in the control group; P = 0.01) and nasal dryness (11.7% in the ipratropium group compared with 3.6% in the control group; P = 0.021) than the control spray. Patient assessments of the overall effectiveness of treatment were more favorable for ipratropium than for the control spray (P < or = 0.026) or for no treatment (P < or = 0.002) on each day of inquiry (study days 1, 2, and 5). CONCLUSIONS: Intranasal ipratropium bromide provides specific relief of rhinorrhea and sneezing associated with common colds.

Administration, Intranasal↗
PubMed1990

Severe exacerbations of COPD and asthma. Incremental benefit of adding ipratropium to usual therapy.

Single dose studies have assessed the utility of ipratropium bromide alone or with beta agonists in the short- and long-term management of chronic obstructive lung disease and asthma. We performed a randomized, double-blind trial to assess the incremental benefit over 24 hours of adding ipratropium vs placebo to a standardized regimen of medications commonly used in the acute and subsequent hospital management of COPD and asthma. Sixty-eight subjects received nebulized salbutamol, intravenous methylprednisolone, intravenous aminophylline, and antibiotics and were randomized to receive either 80 micrograms of ipratropium or placebo via metered dose inhaler and spacing device with each salbutamol treatment (6 to 8 times per day). Among the 50 patients who completed the study, there were no significant differences between ipratropium and placebo groups with respect to baseline FEV1, FVC, and PaCO2. The improvement of FEV1 from baseline to 24 hours was 294 (SD = 568) ml in the ipratropium group vs 393 (SD = 622) ml in placebo group. Adjusting FEV1 by age, gender, and smoking did not significantly alter the findings. Those with an admission diagnosis of asthma showed larger 24 hour FEV1 responses (487 ml in ipratropium vs 801 ml in placebo) than those with COPD (149 ml ipratropium vs 102 ml in placebo). However, within these two strata, there were no significant differences in FEV1 improvement between ipratropium and placebo groups. This study suggests that if ipratropium is used in the initial emergency treatment of COPD or asthma, it could safely be discontinued by 24 hours in order to reduce the cost and complexity of therapy.

Administration, Inhalation↗
PubMed1988

Use of ipratropium bromide in obstructive lung disease.

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of ipratropium bromide are reviewed. Ipratropium bromide, a synthetic quaternary isopropyl derivative of atropine, interrupts vagally mediated bronchoconstriction by inhibiting the cyclic guanosine 3',5'-monophosphate system at parasympathetic nerve endings. Ipratropium bromide is poorly absorbed after oral and inhaled administration but diffuses rapidly into tissue after i.v. or i.m. administration. The elimination half-life is 3.2-3.8 hours. After inhalation, the drug is eliminated in the urine and feces. The bronchodilatory effect of ipratropium bromide in stable chronic obstructive pulmonary disease appears to be comparable, and may be superior, to that of the beta-sympathomimetic agents. In acute exacerbations, ipratropium bromide is useful but may not be the preferred agent because of a delayed onset of action (within 15 minutes; mean dose-dependent duration of effect, three to five hours). Combination therapy with other bronchodilating drugs has proved useful. Ipratropium bromide may be a useful adjunctive agent in the treatment of asthma. Since the onset of action is delayed, ipratropium bromide should not be used as single-drug therapy in an acute asthmatic exacerbation. Reported adverse effects, including cough, nausea, palpitations, dry mouth, nervousness, gastrointestinal distress, and dizziness, have been mild. The usual dosage is two inhalations (36 micrograms) four times daily, and the maximum number of doses per day should not exceed 12. Although ipratropium bromide is currently indicated only for maintenance therapy in stable chronic bronchitis and emphysema, it may be useful as adjunctive therapy in asthma and in the management of acute exacerbations of chronic bronchitis and asthma. Additional experience in a variety of chronic obstructive pulmonary disorders will help to clarify the role of ipratropium bromide in the treatment of obstructive pulmonary disease.

Asthma↗
PubMed1995

[Use of ipratropium bromide by inhalation in the treatment of acute asthma in children. Clinical experience].

Clinical experience. Anticholinergic drugs, notably atropine, have long been known to be potent bronchodilators, but their use was limited by systemic absorption and significant side effects. Ipratropium bromide has no systemic anticholinergic action, but maintains the local anticholinergic action on the tracheobronchial tree. In 1984, we observed that in children with acute asthma, treated aggressively with frequent doses of nebulized beta 2 adrenergics, a significant degree of airway obstruction remained, and did not improve with further doses of beta 2 agonists. We postulated that vagal bronchomotor tone might contribute to this problem and that further improvement could be obtained with the use of ipratropium bromide. Ipratropium was shown to be useful in pediatric asthma in the early 1980s. There appeared to be an age difference in the response to the medication. A dose-response curve for nebulized ipratropium was determined. The optimal dose was found to be > 75 micrograms. Repeated studies and extensive experience demonstrated safety and few side effects. In 1984 we studied the effect of adding ipratropium after one hour of treatment with a regimen of frequent nebulized salbutamol in children with acute asthma. We found a slight but significant further improvement in FEV1, beginning one hour after administration of ipratropium. Further studies confirmed these findings, when using two doses of combined ipratropium/fenoterol an hour apart or every 40 minutes for three doses. One study using ipratropium every eight hours failed to show a change, confirming the need to use the medication more frequently. For the past six years, we have been using a protocol that incorporates ipratropium in the treatment of acute asthma in children. (ABSTRACT TRINCATED AT 250 WORDS)

Acute Disease↗
PubMed1996

Ipratropium decreases airway size in dogs by preferential M2 muscarinic receptor blockade in vivo.

BACKGROUND: Two major groups of drugs are available to prevent bronchoconstriction: beta-agonists and muscarinic blocking agents. Ipratropium is the most commonly used anticholinergic agent to treat chronic obstructive pulmonary disease. The authors studied anti-muscarinic agents to determine if they are as effective bronchodilators as beta-adrenergic agents and if not to identify the mechanism of their reduced effectiveness. METHODS: Six anesthetized dogs were studied using high-resolution computed tomography to measure changes in the cross-sectional area of conducting airways induced by cumulative doses of ipratropium with and without gallamine, a selective M2 muscarinic receptor blocker, and after metaproterenol. RESULTS: Metaproterenol dilated the airways and ipratropium constricted the airways. Ipratropium in concentrations of 0.01 and 0.1 mg/ml constricted the airways to 22 +/- 2% and 20 +/- 3% of control, respectively (P < 0.01), whereas larger concentrations caused bronchodilation. After complete blockade of the M2 receptors by pretreatment with intravenous gallamine, the bronchoconstrictor effect of ipratropium was abolished, and ipratropium dilated the airways by 16 +/- 8% and 27 +/- 10% of pre-gallamine baseline after doses of 0.01 and 0.1 mg/ml, respectively (P < 0.01). CONCLUSION: Low-dose ipratropium can decrease airway size by the initial, preferential blockade of neuronal M2 muscarinic receptors, whereas a larger dose of ipratropium blocks M3 muscarinic receptors on airway smooth muscle, resulting in bronchodilation.

Adrenergic beta-Agonists↗
PubMed1982

Use of ipratropium bromide in patients with severe airways obstruction.

In ten adult patients with severe, partially reversible airflow obstruction due to asthma, with or without co-existent chronic bronchitis, the acute bronchodilator responses of ipratropium bromide (40 micrograms) and terbutaline (500 micrograms) from metered-dose inhalers, atropine methonitrate (2 mg) as a wet aerosol and placebo were compared in a double blind trial. Also the combination of ipratropium bromide and terbutaline aerosols was compared with both ipratropium and terbutaline alone in short-term and long-term studies. In the short-term study, all the drugs produced significant bronchodilatation compared with placebo. The responses to ipratropium bromide and terbutaline alone were not significantly different. The combination of ipratropium bromide with terbutaline did not produce significantly greater changes in the FEV1, SGaw or static lung volume than terbutaline alone. Atropine methonitrate however, produced significantly greater changes of the airway conductance (SGaw) and static lung volumes (TLC and RV) but not FEV1, when compared to ipratropium bromide. When administered over randomised periods of one month each there were no significant differences between the combination of ipratropium bromide and terbutaline and each drug alone in daily airflometer recordings, daily symptom scores or fortnightly spirometry and clinical assessment. It is concluded that ipratropium bromide, in the conventional dose of 40 microgramm by metered-dose inhaler produces safe, effective bronchodilatation. Its effect, however, did not significantly augment that of the beta adrenergic stimulant, terbutaline and was less than that of atropine methonitrate 2 mg by wet aerosol.

Aerosols↗
PubMed1996

Dose response study of ipratropium bromide aerosol on maximum exercise performance in stable patients with chronic obstructive pulmonary disease.

BACKGROUND: Although the bronchodilating effect of inhaled anticholinergics has been established in patients with chronic obstructive pulmonary disease (COPD), their effects on exercise capacity are still controversial. Previous studies have suggested that the standard dosage hardly affects exercise tolerance, whereas higher doses might elicit an improvement. The aim of the present study was to determine the dose of ipratropium bromide aerosol that improves exercise performance using progressive cycle ergometry in patients with stable COPD. METHODS: Twenty men with stable COPD of mean (SD) age 69.2 (4.6) years and forced expiratory volume in one second (FEV1) 1.00 (0.37) 1 were studied in a randomised double blind manner. Each patient received ipratropium bromide in doses of 240 micrograms, 160 micrograms, 80 micrograms, 40 micrograms, and placebo from a metered dose inhaler (MDI) with an InspirEase spacer on five separate days. Spirometric parameters were assessed before and at 30, 60, 90, and 120 minutes after each inhalation, and pulse rate and blood pressure were also measured immediately before each spirometric measurement. Symptom limited progressive (20 watts/min) cycle ergometer exercise tests were performed 90 minutes after each inhalation. RESULTS: Ipratropium bromide in doses of 160 micrograms and 240 micrograms produced a greater increase in FEV1 than 40 micrograms or 80 micrograms ipratropium bromide at all time points. Doses of 160 micrograms and 240 micrograms ipratropium bromide also produced greater increases in maximal work load and maximal oxygen consumption than placebo, whereas 40 micrograms and 80 micrograms ipratropium bromide did not. There was a weak correlation between the change in FEV1 and the change in maximal work load (r = 0.45). No differences were found in pulse rate or blood pressure between the treatment and placebo groups, and no side effects were noted throughout the study. CONCLUSIONS: A dose of at least four times the standard dose of ipratropium bromide from an MDI with a spacer device was necessary to improve maximal cycle exercise capacity in patients with stable COPD. Although the data from cycle ergometry cannot be directly applied to exercise performed during day to day activities, it is conceivable that the recommended doses of ipratropium bromide do not elicit the optimal clinical benefits.

Aerosols↗