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At least 577 records · Page 32Linked to original sources
PubMed2004

Otilonium bromide inhibits calcium entry through L-type calcium channels in human intestinal smooth muscle.

Otilonium bromide (OB) is used as an intestinal antispasmodic. The mechanism of action of OB is not completely understood. As Ca(2+) entry into intestinal smooth muscle is required to trigger contractile activity, our hypothesis was that OB blocked Ca(2+) entry through L-type Ca(2+) channels. Our aim was to determine the effects of OB on Ca(2+), Na(+) and K(+) ion channels in human jejunal circular smooth muscle cells and on L-type Ca(2+) channels expressed heterologously in HEK293 cells. Whole cell currents were recorded using standard patch clamp techniques. Otilonium bromide (0.09-9 micromol L(-1)) was used as this reproduced clinical intracellular concentrations. In human circular smooth muscle cells, OB inhibited L-type Ca(2+) current by 25% at 0.9 micromol L(-1) and 90% at 9 micromol L(-1). Otilonium bromide had no effect on Na(+) or K(+) currents. In HEK293 cells, 1 micromol L(-1) OB significantly inhibited the expressed L-type Ca(2+) channels. Truncation of the alpha(1C) subunit C and N termini did not block the inhibitory effects of OB. Otilonium bromide inhibited Ca(2+) entry through L-type Ca(2+) at concentrations similar to intestinal tissue levels. This effect may underlie the observed muscle relaxant effects of the drug.

Calcium↗
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↗
PubMed1997

Involvement of a CCK-dependent capsaicin-sensitive afferent pathway in the inhibitory effect of pinaverium bromide on the colonic motor response to eating in rats.

The effects of pinaverium bromide on the stimulation of colonic motility induced by meal and cholecystokinin (CCK) were investigated in rats chronically fitted with intraparietal electrodes on the proximal colon and previously treated or not by capsaicin. Pinaverium bromide inhibited in a dose-related manner (2-50 mg/kg, per os) the increase in colonic spike burst frequency induced by a 3 g meal or CCK-8 (2 micrograms/kg, i.v.). The CCK-A and CCK-B antagonists, devazepide and L 365260 (100 micrograms/kg, i.p.), respectively, inhibited the postprandial colonic motor response while only L 365260 reduced the CCK-induced stimulation. The effects of pinaverium bromide and CCK antagonists were not observed in capsaicin-treated animals. Moreover, CCK-8 (2 micrograms/kg, i.v.) did not stimulate colonic motility after capsaicin treatment. The inhibition of postprandial colonic motility by pinaverium bromide, given orally at therapeutic doses, involves a CCK-dependent pathway which requires the integrity of capsaicin-sensitive afferents.

Action Potentials↗
PubMed1977

Effect of ethidium bromide on the oxidative metabolism and enzyme profiles of Crithidia fasciculata.

Changes in the metabolism of Crithidia fasciculata ATCC 11745 when grown in the presence of ethidium bromide were studied. Ethidium bromide-grown cells had decreased respiratory activity as measured by oxygen consumption. More than 50% of the organisms cultivated in a defined medium containing 1.0 mg/liter of ethidium bromide became dyskinetoplastic and had decreased activities of particulate succinate and NADH-linked dehydrogenases as well as of soluble isocitrate dehydrogenase. These cells also had increased activities of particulate alpha-glycerophosphate dehydrogenase, soluble alpha-glycerophosphate dehydrogenase, malic enzyme, hexokinase, and malate dehydrogenase. Ethidium bromide-grown cells had a lower level of ATP and contained less DNA than cells grown in its absence.

Adenosine Triphosphate↗
PubMed1995

Efficacy of ipratropium bromide in acute childhood asthma: a meta-analysis.

PURPOSE: To determine whether inhaled ipratropium bromide provides an additive, clinically important improvement in children with acute asthma who are being treated with beta 2-agonists. METHODS: An English-language literature search was conducted employing MEDLINE (1966 to 1992), Science Citation Index (1986 to 1992) using key citations, bibliographic reviews of primary research and review articles, and correspondence with authors of recent articles. After independent review by two observers, six studies were selected on the basis of prespecified selection criteria. Two observers independently assessed the selected papers by using explicit methodologic criteria for evaluating the quality of studies dealing with therapeutic intervention. RESULTS: None of the six studies found a significant difference in clinical rating score, admission rate, or length of stay in hospital between the ipratropium bromide and the control groups. The three studies with the highest methodologic validity measured the change in percentage predicted forced expiratory volume in 1 second (FEV1) from baseline to 60 minutes. The pooled effect size (95% CI) for these studies was 0.88 (0.42-1.34), which translates to an improvement in percentage predicted FEV1 over the control group of 12.5% (95% CI, 6.6-18.4). In a subset of 23 children who had severe airway obstruction, peak expiratory flow rate (PEFR) responded better to a beta 2-agonist alone (p = 0.007). CONCLUSION: The existing evidence reveals that the addition of ipratropium bromide to a beta 2-agonist offers a statistically significant improvement in percentage predicted FEV1 but no clinical improvement. As it may cause deterioration in PEFR in severely asthmatic children, ipratropium bromide should not be used universally for acute childhood asthma until further research determines the clinical significance of these spirometric changes.

Acute Disease↗
PubMed1997

Effects of administration of phentonium bromide on opioid withdrawal syndrome in rats.

This study has tested whether phentonium bromide, a quaternary ammonium anti-muscarinic agent, could reverse the signs of precipitated opioid withdrawal. Rats were treated with either saline or morphine for 4 days, after which half the rats received naloxone and half saline. Each animal also received one of four doses of phentonium bromide (0, 1, 3 and 9 mg kg(-1), i.p.). Administration of phentonium bromide in rats receiving naloxone after chronic morphine treatment reduced the intensity of withdrawal signs such as increased defecation or micturition, salivation and wet-dog shakes, and elevated the nociceptive threshold values. The effects of administration of phentonium bromide might result from its anti-muscarinic activity interfering peripherally with the mechanisms involved in the regulation of the withdrawal symptoms. The use of this drug is thus suggested as a possible means of controlling some of the signs observed during the acute phase of opioid withdrawal in heroin addicts.

Analgesics, Opioid↗
PubMed1973

Ethidium bromide-resistant mutant of Bacillus subtilis.

An ethidium bromide-resistant mutant (EB8) derived from a Marburg strain of Bacillus subtilis was found to be conditionally resistant to 10 mug of ethidium bromide per ml. Expression of resistance is complete only during vegetative growth at incubation temperatures above 30 C in complex medium or minimal medium supplemented with Casamino Acids. Strain EB8 is cross-resistant to acriflavine and proflavine. The ethidium bromide resistance marker is co-transduced with hisA1 at a frequency of 6% and is located to the right of hisA1 on the B. subtilis chromosome as it is usually represented on the map. Incorporation of [5-(3)H] uridine by strain EB8 showed that ribonucleic acid synthesis in both whole cells and protoplasts is ethidium bromide-resistant.

Acridines↗
PubMed1981

Ipratropium bromide in acute asthma.

Ipratropium bromide was given to patients admitted to hospital with acute asthma. A cumulative-dose-response technique in six patients showed that 500 micrograms given by nebuliser produced a maximal increase in peak expiratory flow rate. This dose of ipratropium bromide was included in a regimen in which it was given either two hours before or two hours after nebulised salbutamol to 22 patients. Ipratropium bromide given on admission was as effective as nebulised salbutamol. The two drugs in sequence produced greater bronchodilatation than either used alone, and the mean peak expiratory flow rate rose by 96% in four hours. Thus giving ipratropium bromide in addition to salbutamol in severe asthma enhances the bronchodilator effect. Further studies are needed to determine whether the same effect may be obtained by giving two maximal doses of salbutamol two hours apart.

Acute Disease↗
PubMed1982

Actual hazard of methyl bromide fumigation in soil disinfection.

Methyl bromide, a highly toxic and ready penetrating fumigant, is widely used against rodents, insects, mites, and a range of pathogenic organisms in soil, compost, and timber. To disinfect soil in greenhouses, methyl bromide is brought under pressure from outside by a vaporiser and blown on to ground under a polyethylene cover. The gas being three times heavier than air easily penetrates the ground. Depending on the local ventilation, a considerable amount of gas evaporates into the surrounding atmosphere, this emission being especially serious during the fumigation procedure and at the removal of the plastic cover. Previously, mechanical injection of methyl bromide on to the ground within closed areas was prohibited, since this technique exposed at least four disinfection workers at a time, who were provided with only a canister respirator, to gas concentrations of over 1000 ppm CH3Br. The present study established that fumigation with methyl bromide also carries risks for the well-protected worker inside, as well as for the one controlling the vaporiser. The concentration during application varies from 30 to 3000 ppm. Concentration in the air declines with time to 4 ppm CH3Br five days after application. Discarding the plastic sheet involves exposure to peak values as high as 200 ppm for a few seconds. On the ninth day after application, milling the soil can expose workers to up to 15 ppm; on the eleventh day no CH3Br concentration in the air could be found.

Agriculture↗
PubMed1984

Ipratropium bromide in patients with nocturnal asthma.

Fourteen patients with nocturnal asthma were recruited to a two period crossover trial which compared a run-in period on nightly salbutamol (200 micrograms) with a period on nightly ipratropium bromide (160 micrograms) and a period on nightly salbutamol plus ipratropium at night. Morning dipping, as assessed by the fall in peak flow overnight, was significantly reduced in the periods when ipratropium bromide was taken. Peak flow in the morning and also at night was improved when taking ipratropium bromide. Ipratropium bromide in adequate dosage appears to be effective in reducing morning dipping in asthma.

Adult↗
PubMed1986

Effect of four weeks' high dose ipratropium bromide treatment on lung mucociliary clearance.

In a randomised, double blind crossover study the effect of high dose ipratropium bromide (200 micrograms three times daily given by metered dose inhaler for four weeks) on lung mucociliary clearance and on the wet weight and mean apparent viscosity of sputum was compared with that of placebo. Six smokers, six ex-smokers, and three non-smokers (12 men and three women, median age 60 years) were studied. Eight subjects had chronic obstructive lung disease (median FEV1 46% predicted) and seven had asthma (FEV1 70% predicted). Seven subjects produced sputum regularly, two of whom had asthma. Clearance of secretions was measured by an inhaled radioaerosol technique. The number of coughs and the wet weight, radioactive content, and mean apparent viscosity of sputum produced during the six hour observation period were recorded, as was the mean wet weight of sputum produced during the last two 24 hour periods ending each treatment. Comparison with placebo showed that treatment with high dose ipratropium bromide was associated with a significant increase in the penetration index of inhaled particles, but there was no significant change in alveolar deposition of particles or in tracheobronchial clearance, uncorrected or corrected for sputum expectorated. The wet weight of sputum produced, its radioactive content, and mean apparent viscosity were similar after treatment with ipratropium bromide and placebo. These results show that high dose inhaled treatment with the synthetic anticholinergic bronchodilator ipratropium bromide for four weeks is not associated with detectable modification of the clearance of secretions from the lungs, or of sputum volume or viscosity.

Adult↗
PubMed1998

Effects of theophylline and ipratropium bromide on exercise performance in patients with stable chronic obstructive pulmonary disease.

BACKGROUND: The effects of theophylline or anticholinergic agents on exercise capacity in patients with chronic obstructive pulmonary disease (COPD) remain controversial. The aim of the present study was to compare the effect of an oral theophylline with an inhaled anticholinergic agent and to examine the effects of combined therapy on exercise performance using progressive cycle ergometry. METHODS: Twenty one men with stable COPD and a mean (SD) forced expiratory volume in one second (FEV1) of 1.00 (0.40) 1 were studied. Theophylline (600 or 800 mg daily), ipratropium bromide (160 micrograms), a combination of both drugs, and placebo were given in a randomised, double blind, four period crossover design study. Spirometric data, pulse rate, and blood pressure were assessed before and at 90 and 120 minutes after inhalation. Symptom limited progressive cycle ergometer exercise tests (20 watts/min) were performed 90 minutes after each inhalation, and dyspnoea was measured during exercise using the Borg scale. RESULTS: The mean (SD) serum theophylline concentration was 18.3 (6.3) micrograms/ml, and seven patients had side effects during treatment with theophylline. Theophylline and ipratropium bromide produced greater increases in FEV1, maximal oxygen consumption, maximal minute ventilation, and several dyspnoea ratios than placebo. There were no differences between theophylline and ipratropium bromide except in maximal heart rate. A combination of both drugs produced greater improvements in pulmonary function and exercise capacity than either drug alone. CONCLUSIONS: Both high dose theophylline and high dose ipratropium bromide improved exercise capacity in patients with stable COPD. Although data based on short term effects cannot be directly applied to long term therapy, theophylline added to an inhaled anticholinergic agent may have beneficial effects on exercise capacity in patients with COPD.

Aged↗
PubMed1989

Effect of four-week treatment with oxitropium bromide on lung mucociliary clearance in patients with chronic bronchitis or asthma.

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.

Aged↗
PubMed1990

[Effects of flutropium bromide, a new anti-asthma drug, alone or in combination with salbutamol, aminophylline and disodium cromoglycate on the acetylcholine induced bronchoconstriction].

Effects of flutropium bromide, a new bronchodilator with an anticholinergic action, alone or in combination with other antiasthma drugs were investigated in guinea pigs by using an index of inhibition of the acetylcholine (ACh)-induced bronchoconstriction. Single inhalation of flutropium bromide (0.0003%) into the airways of guinea pigs inhibited the ACh (i.v.)-induced bronchoconstriction without changing the fall in blood pressure induced by ACh. When salbutamol (3 micrograms/kg, i.v.), aminophylline (5 mg/kg, i.v.) or disodium cromoglycate (10 mg/kg, i.v.) was administered in combination with flutropium bromide (0.0003%), bronchodilation was enhanced as compared with single administration of the respective antiasthma drugs. From the above results, it is indicated that inhalation of flutropium bromide provides a more efficient bronchodilation in combination with other antiasthma drugs that possess different mechanisms of antiasthma effects.

Acetylcholine↗
PubMed1994

Effect of nebulized ipratropium bromide on intraocular pressures in children.

STUDY OBJECTIVE: To evaluate the effects of nebulized ipratropium bromide on intraocular pressures and pupillary responses in children with asthma. DESIGN: A double-blind, randomized, crossover study. SETTING: Children's Hospital of Winnipeg, University of Manitoba. PATIENTS OR PARTICIPANTS: Age 6 to 17 years with asthma. INTERVENTION: Nebulized ipratropium bromide added to albuterol sulfate, albuterol alone, or saline solution was given by face mask and nebulizer. Before and 0.5 h after nebulization, intraocular pressures (mm Hg), pupillary size (mm), and pupillary responses were measured. In a subsequent open study, patients who had been admitted to hospital with acute asthma who were treated with nebulized ipratropium bromide were recruited for measurement of intraocular pressures, pupillary size, and pupillary responses. MEASUREMENTS AND RESULTS: Twenty patients completed the double-blind study, and 26 patients completed the open study. There were no changes in intraocular pressures, pupillary size, or pupillary response after any treatment on any study day in either the double-blind or the open studies. CONCLUSION: In children with asthma, who have no pre-existing ocular abnormalities, the risk of an adverse reaction to nebulized ipratropium bromide delivered by face mask inadvertently absorbed in the eye is extremely small.

Adolescent↗
PubMed1994

Nebulized ipratropium bromide in ventilator-assisted patients with chronic bronchitis.

Whether nebulized ipratropium bromide is of benefit to mechanically ventilated patients with chronic bronchitis is not well defined. The objective of the study was to determine the effect of ipratropium bromide as a nebulized solution on ventilatory function in patients with severe airflow limitation and under ventilator treatment because of respiratory failure. The design was a randomized, double-blind, controlled trial. Forty-two ventilated patients (43 to 83 years old) with acute airflow obstruction and wheezing or coughing were chosen. The patients were randomly allocated to treatment every 6 h with either 500 micrograms of nebulized ipratropium bromide or 0.9 percent saline solution. Comparison was made between ipratropium bromide and placebo. Their responses were assessed in terms of arterial blood gas analysis, pulmonary mechanics, and respiratory symptoms. No significant differences in oxygenation, arterial CO2 tension, or static lung compliance attributable to ipratropium were found. However, a significant tendency to decreased mean airway resistance, peak inspiratory pressure, mean airway pressure, and improved symptom status 24 h after giving ipratropium was observed. We conclude that ventilated patients with obstructive lung disease could obtain incremental benefit from adding nebulized ipratropium to aminophylline. Their responses may be explained by the bronchodilating effect of ipratropium that resulted in a reduced airway resistance and a lower mean airway pressure.

Adult↗
PubMed1998

The effect of adding ipratropium bromide to salbutamol in the treatment of acute asthma: a pooled analysis of three trials.

OBJECTIVE: To assess the effect on FEV1 and clinical outcomes of adding ipratropium bromide to salbutamol in the treatment of acute asthma. METHODS: We conducted a pooled analysis of three randomized double-blinded clinical trials conducted in the United States, Canada, and New Zealand. The studies enrolled 1,064 patients aged 18 to 55 years who presented at the emergency department with acute asthma. Patients were randomized to treatment with a combination of nebulized 2.5 mg salbutamol plus 0.5 mg ipratropium bromide, or 2.5 mg salbutamol alone. Medications were administered at baseline and, in the US study, at 45 min. FEV1 was measured at baseline, 45 min, and 90 min. Patients were followed up for 48 h after hospital discharge for occurrence of asthma exacerbation and hospitalization. RESULTS: Treatment groups were comparable at baseline. Of the 1,064 patients randomized, 1,015 patients (95%) remained in the study for measurement at 45 min, and 961 patients (90%) completed the final measurement at 90 min. Comparison of overall improvement in FEV1 at 45 min indicated a better response for patients receiving combination therapy (mean difference=43 mL, 95% confidence interval [CI]=-20, 107). The distribution of change in FEV1 was skewed by a small number of patients with extreme values (38 of 1,064=3.6%) that may have been due to unreliable lung function testing. Removing these outliers produced a larger and more precise estimate of effect (mean difference=55 mL, 95% CI=2,107). Because the distribution was skewed, we performed nonparametric analyses that showed evidence of a beneficial effect of combination therapy. The difference between median values at 45 min is 40 mL (Wilcoxon p value=0.03). In addition, 4.9% (95% CI=-1%, 11%) more patients in the combination group achieved at least 20% of their potential improvement, as measured by the difference between their baseline FEV1 and their predicted FEV1. Patients receiving combination therapy had lower risk for each of three clinical outcomes: the need for additional treatment (relative risk [RR]=0.92, 95% CI=0.84, 1.0), risk of asthma exacerbation (RR=0.84, 95% CI=0.67, 1.04), and risk of hospitalization (RR=0.80, 95% CI=0.61, 1.06). CONCLUSION: Adding ipratropium bromide to salbutamol in the treatment of acute asthma produces a small improvement in lung function, and reduces the risk of the need for additional treatment, subsequent asthma exacerbations, and hospitalizations. These apparent benefits of adding ipratropium bromide were independent of the amount of beta-agonist that had been used earlier in the attack, and possibly related to a recent upper respiratory tract infection. Confirmatory studies are needed, especially for clinical outcomes.

Acute Disease↗
PubMed1999

Effect of ipratropium bromide treatment on oxygen saturation and sleep quality in COPD.

STUDY OBJECTIVES: Patients with COPD are at risk of experiencing a deterioration in arterial oxygen saturation (SaO2) during sleep, which is generally most pronounced during rapid eye movement (REM) sleep. Increased cholinergic tone has been suggested as a contributing factor to this decrease in SaO2. Therefore, we investigated whether 4-week treatment with ipratropium bromide inhalation solution 0.02% (qid) could improve sleep characteristics in COPD. DESIGN: Randomized, placebo-controlled, double-blind, two-arm parallel study of 4 weeks of treatment with ipratropium bromide solution or placebo. SETTING: Multicenter investigation. PATIENTS: Thirty-six patients with moderate-to-severe COPD (FEV1 < 65% of predicted). MEASUREMENTS AND RESULTS: Evaluation included polysomnographic, pulmonary function, and subjective quality of sleep (visual analog scale [VAS]) assessments. It was found that 4 week of treatment with ipratropium bromide solution in patients with COPD led to the following: (1) a significant (p = 0.05) improvement in mean nocturnal SaO2 with the more severe the nocturnal desaturation, the greater the improvement in SaO2; (2) significant (p = 0.03) improvement in perceived sleep quality (VAS: 5.5 +/- 0.5 after placebo; 7.2 +/- 0.5 after ipratropium); (3) a significant (p = 0.05) increase in REM sleep time (48.6 +/- 6.3 min after placebo; 66.5 +/- 6.4 min after ipratropium) with no effect on other sleep stages or total sleep time; and (4) a significant (p = 0.01) increase in pre-sleep FVC and flow rate at 50% of the vital capacity. CONCLUSIONS: These findings demonstrate that ipratropium bromide therapy can improve sleep SaO2 as well as sleep quality in patients with moderate-to-severe COPD.

Adult↗