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PubMed2000

Bromide-free TEMPO-mediated oxidation of primary alcohol groups in starch and methyl alpha-D-glucopyranoside.

TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl)-mediated oxidation of potato starch and methyl alpha-D-glucopyranoside (MGP) was performed in the absence of sodium bromide (NaBr) as co-catalyst, solely using sodium hypochlorite (NaOCl) as the primary oxidant. The low reaction rate associated with a bromide-free process was increased by performing the oxidation at increased temperatures. The reaction proceeded stoichiometrically and with high selectivity and with only minor depolymerisation, provided that temperature and pH were kept < or = 20 degrees C and < 9.0, respectively. At 20 degrees C and pH 8.5, the reaction rate was comparable to that of a corresponding oxidation catalysed by NaBr at 2 degrees C. Consequently, this is a simple approach to raise the TEMPO/NaOCl reaction rate under bromide-free conditions while still maintaining good product properties. At higher oxidation temperatures (> or = 25 degrees C) and under more alkaline conditions (pH > or = 9.0) degradation of the starch skeleton occurred. Simultaneously, side-reactions of the nitrosonium ion lowered the yield of the oxidation. Despite the absence of the NaBr catalyst, the reaction rate-controlling step was found to be the oxidation of the primary hydroxyl groups with the nitrosonium ion. The reaction was first-order in MGP and in TEMPO.

Alcohols↗
PubMed2001

Drotaverine hydrochloride vs. valethamate bromide in acceleration of labor.

OBJECTIVES: To compare the efficacy and safety of drotaverine hydrochloride and valethamate bromide in shortening the duration of labor. METHODS: In a randomized controlled trial of 150 nulliparous women in established labor with cervical dilation of 4 cm, 50 women were given drotaverine (group I), 50 women were given valethamate (group II) and another 50 women were not given any medication (group III). Duration of labor, mode of delivery, side effects, and neonatal outcome were measured in all cases. Appropriate non-parametric tests and chi(2) tests were used for assessment of statistical significance. RESULTS: In the three groups, 100%, 96% and 46% women delivered within 6 h, respectively. The injection-to-delivery interval was significantly reduced in the drotaverine group (193.96 min) in contrast to the valethamate group (220.68 min) and control group (412.84 min). The rate of cervical dilation was highest in the drotaverine group (2.04 cm/h) compared with the valethamate bromide group (1.86 cm/h) and control group (1.01 cm/h). There were no major maternal or fetal adverse effects in any group, but minor side effects were more common in the valethamate group. CONCLUSION: Both intramuscular drotaverine hydrochloride and valethamate bromide are effective in acceleration of labor; however, drotaverine accelerates labor more rapidly and is associated with less side effects.

Cervix Uteri↗
PubMed1985

Determination of demecarium bromide and related compounds by high-performance liquid chromatography.

A high-performance liquid chromatographic method for the determination of demecarium bromide and related process intermediate and companion products is described. The compounds of interest are separated by isocratic reversed-phase chromatography on a mu Bondapak CN column using UV detection. The reproducibility of the method and stability of demecarium bromide is demonstrated. Applications presented for the method include quantitation of demecarium bromide in aqueous solutions and control of the raw material.

Benzalkonium Compounds↗
PubMed1998

Randomized controlled trial of ipratropium bromide and frequent low doses of salbutamol in the management of mild and moderate acute pediatric asthma.

OBJECTIVES: To compare the effectiveness and safety of alternative nebulized drug protocols in children with mild or moderate asthma exacerbations. METHODS: We conducted a blinded, randomized, controlled trial with a 2 x 2 factorial design. Two interventions, nebulized salbutamol in frequent low doses (0.075 mg/kg every 30 minutes) and the addition of ipratropium bromide (250 micrograms), were compared with salbutamol in hourly high doses (0.15 mg/kg every 60 minutes) in children with mild or moderate acute asthma. The primary end point was the improvement in respiratory resistance. Secondary end points included oxygen saturation, corticosteroid use, patient disposition, and relapse status. RESULTS: A total of 298 participants aged 3 to 17 years were studied, and 15% were admitted to the hospital; 14% of the children had relapses. No increased bronchodilation was associated with frequent low doses versus hourly high doses of salbutamol (RR = 0.9 [95% confidence interval 0.7, 1.3]) or the addition of ipratropium bromide versus placebo (RR = 1.0 [0.8, 1.3]). No group differences were observed in secondary end points. Salbutamol in frequent low doses was associated with increased vomiting (RR = 2.5 [1.1, 6.0]). CONCLUSION: Our results do not support the use of frequent low doses of nebulized salbutamol or the addition of ipratropium bromide compared with hourly high doses of salbutamol in children with mild or moderate asthma.

Acute Disease↗
PubMed1995

A clinical trial of ipratropium bromide nasal spray in patients with perennial nonallergic rhinitis.

Intranasal ipratropium bromide has been shown to significantly reduce rhinorrhea. Use of a freon-propelled intranasal preparation has resulted in side effects associated with the drying properties of the propellant. The purpose of the present trial was to study the safety and efficacy of a new isotonic aqueous ipratropium bromide nasal spray pump, specifically in patients with perennial nonallergic rhinitis. Two hundred thirty-three patients participated in an 8-week double-blind parallel comparison of ipratropium bromide nasal spray with its vehicle, a saline solution. Treatment with the ipratropium spray resulted in a 30% reduction in rhinorrhea; this reduction was significantly greater than that seen with the saline vehicle. There was a modest reduction in postnasal drip, sneezing, and congestion with both treatments, which may be attributable to the salutary effects of the saline solution. Patients also perceived a significant reduction in the degree to which rhinorrhea interfered with their daily activities and moods. Treatment was well tolerated, with no drug-related systemic adverse events and no evidence of nasal rebound on discontinuation of treatment. Minor, infrequent episodes of nasal dryness and epistaxis were the only significant adverse events reported; these did not limit treatment.

Adult↗
PubMed1977

A second look at emepronium bromide in urinary incontinence.

Response to oral and intramuscular emepronium bromide was assessed cystometrically in nine patients with urinary incontinence caused by an uninhibited bladder. Oral therapy had no effect, whereas intramuscular administration increased bladder capacity and significantly delayed the onset of bladder spasm and the desire to void. Plasma-propranolol response was delayed and concentrations were reduced after an oral 40 mg dose of propranolol in 3 patients who had received oral emepronium bromide. These results indicate that although oral emepronium bromide had some anticholinergic effect--i.e., in reducing gastrointestinal motility--absorption of an oral dose was not sufficient for the bladder to be affected.

Administration, Oral↗
PubMed1994

Acute angle-closure glaucoma as a complication of combined beta-agonist and ipratropium bromide therapy in the emergency department.

Acute angle-closure glaucoma is an uncommon complication of inhaled ipratropium bromide therapy for asthma. All previously reported cases have occurred in hospitalized patients receiving continuing nebulized therapy. A 66-year-old woman with asthma returned to the emergency department with bilateral acute angle-closure glaucoma less than 48 hours after successful treatment with nebulized albuterol sulfate and ipratropium bromide given by metered-dose inhaler. Acute angle-closure glaucoma occurring after ipratropium bromide use is believed to result from local ophthalmic effects attributable to topical absorption instead of systemic action. Greater awareness of this complication and suggested preventive measures may lessen morbidity.

Acute Disease↗
PubMed1998

Oral teratogenicity studies of methyl bromide in rats and rabbits.

Teratogenicity studies of methyl bromide, a widely used fumigant, were conducted in rats and rabbits. Methyl bromide was dissolved in corn oil and administered orally to groups of 24 copulated female Crj:CD (SD) rats at dose levels of 0 (corn oil), 3, 10 or 30 mg/kg/day on days 6-15 of gestation and to groups of 18 artificially inseminated female Kbl:JW rabbits at 0, 1, 3 or 10 mg/kg/day on days 6-18 of gestation. Maternal rats and rabbits were euthanized on respective days 20 and 27 of gestation. Foetuses were examined for survival, growth and teratological alterations. Maternal toxicity was evident in the high-dose groups for both species. In these groups, maternal body weight gains and food consumption were significantly decreased during the dosing and post-dosing periods. Necropsy of maternal rats also revealed erosive lesions in the stomach and the surrounding organs. However, no treatment-related adverse effects were found in foetuses of the treated groups for both rat and rabbit studies. These results led to the conclusion that methyl bromide was not foetotoxic or teratogenic to rat and rabbit foetuses up to dose levels of 30 and 10 mg/kg/day, respectively, at which maternal toxicity was evident for both species.

Abnormalities, Drug-Induced↗
PubMed1999

Simultaneous determination of chlordiazepoxide and clidinium bromide in pharmaceutical formulations by derivative spectrophotometry.

A direct and simple first derivative spectrophotometric method has been developed for the simultaneous determination of clidinium bromide and chlordiazepoxide in pharmaceutical formulations. Acetonitrile was used as solvent for extracting the drugs from the formulations and subsequently the samples were evaluated directly by derivative spectrophotometry. Simultaneous determination of the drugs can be carried out using the zero-crossing method for clidinium bromide at 220.8 nm and the graphical method for chlordiazepoxide at 283.6 nm. The calibration graphs were linear in the ranges from 0.983 to 21.62 mg/l of clidinium bromide and from 0. 740 to 12.0 mg/l of chlordiazepoxide. The ingredients commonly found in commercial pharmaceutical formulations do not interfere. The proposed method was applied to the determination of these drugs in tablets.

Acetonitriles↗
PubMed1997

The determination of a degradation product in clidinium bromide drug substance by capillary electrophoresis with indirect UV detection.

A capillary electrophoresis (CE) method utilizing indirect ultraviolet (UV) detection was developed for the determination of a non-UV absorbing degradation product, Ro 5-5172, in clidinium bromide drug substance. The electrophoresis buffer consisted of sodium phosphate and benzyltrimethylammonium bromide. Rinsing the capillary with sodium hydroxide followed by water then fresh capillary electrophoresis buffer was found to significantly improve the reproducibility of the migration times of the analytes. To further improve run-to-run reproducibility, an internal marker was used to account for differences in injection volumes and migration times between runs. The precision of the method was found to be less than 1% relative standard deviation for the migration time ratio and peak area ratio of Ro 5-5172 to the internal standard. The method was found to be linear for 0.05-1% Ro 5-5172 with respect to a 10 mg ml-1 sample preparation. The limit of detection was found to be less than 0.01% Ro 5-5172. Results obtained for the analysis of a clidinium bromide drug substance lot using this CE method and a thin layer chromatography method were compared and found to be in agreement.

Drug Stability↗
PubMed2000

Effects of oral pinaverium bromide on colonic response to food in irritable bowel syndrome patients.

We have recently developed a simple method to investigate the colonic response to food (CRF). This study describes the modifications of CRF induced by treatment with oral pinaverium bromide in irritable bowel syndrome (IBS) patients. Thirty healthy subjects and 43 patients suffering from IBS were studied. Colonic transit time (CTT) was measured in fasting conditions and after eating a standard test meal. Colonic response to food was quantified by calculating the variation in number of markers in each zone of interest of the large bowel between the X-ray films of the abdomen taken before and after eating. CRF is characterized by caudal propulsion of colonic contents in the two groups. In controls, there is emptying of the caecum-ascending colon region and filling of the rectosigmoid. In IBS patients, only the left transverse colon and the splenic flexure empty. Pinaverium bromide exerts no effect in controls but reverses the CRF of the right colon in IBS patients by inhibiting right colon emptying. These results suggest that the inhibitory action of pinaverium bromide on CRF may support the clinical efficacy of this calcium channel blocker in the treatment of IBS.

Adult↗
PubMed2002

[Benefits of ipratropium bromide in the management of asthmatic crises in the emergency department].

BACKGROUND: To determine if the addition of ipratropium bromide in the emergency department (ED) for the treatment of childhood asthma reduces rates of hospitalization and relapses for moderate and severe exacerbations. METHODS: Patients were given an oral corticosteroid treatment (2 mg/kg) and received every 20 minutes either three nebulizations with albuterol (0.15 mg/kg) and ipratropium bromide (250 micrograms) or six nebulizations with albuterol alone (control group). The primary end point was the need for hospitalization, additional nebulizations or a relapse during the following week. Secondary end point included the effect of age. RESULTS: One hundred and forty three children, two to 15 years old, were randomized to ipratropium or control groups and 121 were evaluated on day seven. As a whole, the control group was less often hospitalized or in relapse than those treated with three nebulizations of albuterol and ipratropium (17.5% vs 37.9%, p < 0.02). The ipratropium group reached the same result after three additional albuterol nebulizations. The benefit of anticholinergic therapy was observed for children less than six years of age who had a similar rate of success (73.5 vs 75.7%). CONCLUSION: The association of ipratropium bromide to the first three doses of the albuterol protocol for acute asthma did not act as well as six nebulizations of albuterol alone. The effect was age dependent and two to six years old children needed more attention. Nevertheless the hospitalization rate did not support the use of ipratropium compared with repeated albuterol nebulizations.

Adolescent↗
PubMed1992

Chronic persistent cough: use of ipratropium bromide in undiagnosed cases following upper respiratory tract infection.

The clinical effects of inhaled ipratropium bromide were studied in 14 non-smoking patients with persistent post-viral infective cough employing a controlled double-blind, cross-over trial. Patients were selected if they demonstrated no apparent underlying cause for their persistent cough after appropriate radiological and respiratory function tests including methacholine reactivity and bronchoscopic examination. Inhaled ipratropium bromide (320 micrograms day-1) produced significantly less day and night time cough (P < 0.05) with overall clinical improvement in 12 cases, five of whom had total resolution of their cough. We conclude that ipratropium bromide is an effective treatment in non-smoking adults with protracted cough following clinical upper respiratory tract infection.

Administration, Inhalation↗
PubMed1997

Effects of high-dose ipratropium bromide and oral aminophylline on spirometry and exercise tolerance in COPD.

Exercise tolerance in chronic obstructive pulmonary disease (COPD) patients treated with oral aminophylline may be different from those treated with high-dose inhaled ipratropium bromide. The purpose of this study was to compare the effects of therapeutic doses of oral aminophylline with high-dose ipratropium bromide on spirometry and exercise tolerance. The study was conducted on three consecutive days in a double-blind, randomized, crossover fashion. Baseline studies obtained on each study day included vital signs, simple spirometry and a symptom-limited maximal cardiopulmonary stress test, after which patients received one of the following treatments on each day: Treatment 1, inhaled ipratropium (total dose of 144 micrograms) with placebo tablets; Treatment 2, inhaled placebo with oral aminophylline (400 mg); Treatment 3, inhaled placebo and placebo tablets. Simple spirometry was repeated at 60 and 120 min after baseline. Vital signs and cardiopulmonary stress testing was repeated at 120 min. Eighteen patients were enrolled in the study, and 17 of these completed the study. There was a significant (P < 0.05) increase in both forced expiratory volume in 1 s (FEV1), from 0.75 (0.21) to 0.92 (0.3), and forced vital capacity (FVC), from 1.8 (0.79) to 2.11 (0.84), with high-dose ipratropium despite prior beta-agonist therapy. Lack of improvement in exercise capacity was noted with ipratropium despite improvement in spirometry. These results suggest that elderly patients with severe COPD may have exercise limitation that is not directly dependent on severity of airflow obstruction. Ipratropium bromide and aminophylline demonstrated no acute effects on exercise capacity.

Administration, Oral↗
PubMed2002

2-O-substituted cyclodextrins as reversal agents for the neuromuscular blocker rocuronium bromide.

A series of secondary face modified cyclodextrins (CDs) were synthesised with the aim of constructing host molecules capable of forming host-guest complexes with neuromuscular blockers, especially with rocuronium bromide. Perfacial 2-O-substitution of gamma-CD with 4-carboxybenzyl resulted in a CD host molecule 1 that forms a 1:1 binary complex with rocuronium bromide (K(a) 6.2 x 10(5) M(-1)). The biological activities of this compound and other derivatives as reversal agents of rocuronium bromide were examined in vitro (mouse hemi-diaphragm) and in vivo (anaesthetized guinea pigs). The host molecule 1 was found to exert potent reversal activity (ED(50) 0.21 micromol/kg, iv) against rocuronium-induced neuromuscular block, and thus proved the viability of using host molecules as antidotes of a biologically active compound.

Androstanols↗
PubMed2006

Comparison of nebulized ipratropium bromide with salbutamol vs salbutamol alone in acute asthma exacerbation in children.

BACKGROUND: Despite multiple doses of beta2-agonists in the treatment of acute asthma exacerbation, significant residual airways obstruction often remains. OBJECTIVE: To determine whether the addition of inhaled ipratropium bromide to salbutamol provides improvement in lung function and clinical asthma symptoms in young children with acute asthma exacerbation. METHODS: This study was a prospective, double-blind randomized control trial of children aged 3 to 15 years who presented with an acute asthma exacerbation at the emergency department or outpatient clinic of Thammasat University Hospital, Pathumthani, Thailand, between September 2001 and February 2003. Subjects were randomized to receive 3 doses of nebulized salbutamol mixed with isotonic sodium chloride solution (control) or ipratropium bromide (treatment) every 20 minutes. Additional doses of salbutamol were given every 30 minutes as needed. Asthma outcome measures were evaluated 40, 70, 100, and 120 minutes after baseline. Primary outcomes were the differences in percent change in asthma clinical score and percent change in peak expiratory flow rate (PEFR) from baseline. Secondary outcomes included change in percent predicted PEFR. RESULTS: Of 74 children randomized and enrolled in the trial, 71 had complete data for analysis. Thirty-three children were in the control group and 38 were in the treatment group. Both the percent change in PEFR and the change in percent predicted PEFR at any time were higher in the treatment group, but these findings were not statistically significantly different. The number of subjects with at least a 100% percent predicted PEFR at any time point was greater in the treatment group. CONCLUSION: Although this study did not demonstrate a significant advantage in clinical score and PEFR, the trend toward additional effect of ipratropium bromide was consistent with previous studies.

Administration, Inhalation↗
PubMed1999

Comparison of ipratropium bromide 0.03% with beclomethasone dipropionate in the treatment of perennial rhinitis in children.

OBJECTIVE: To compare the safety and efficacy of ipratropium bromide 0.03% (IB) with beclomethasone dipropionate 0.042% (BDP) in the treatment of perennial rhinitis in children. METHODS: Thirty-three children with nonallergic perennial rhinitis (NAPR) and 113 with allergic perennial rhinitis (APR) were randomly assigned to either IB or BDP for 6 months in a single-blind, multicenter protocol in which the physician was blinded to treatment. At each visit, patients and physicians rated symptom control of rhinorrhea, nasal congestion, and sneezing. Patients also completed quality of life questionnaires at baseline and after 6 months of therapy. RESULTS: Both treatments showed a significant improvement in control of rhinorrhea, congestion, and sneezing compared with baseline over the 6 months of treatment (P < .05). Only for the control of sneezing was BDP consistently better than IB (P < .05). Among the patients given IB, 61% to 73% assessed the control of rhinorrhea as good or excellent on different study visit days, 43% to 60% similarly rated the control of nasal congestion, and 39% to 43% the control of sneezing. The results for BDP were 68% to 78% for the control of rhinorrhea, 55% to 72% for the control of nasal congestion, and 54% to 68% for the control of sneezing. Quality of life assessment documented that both drugs significantly reduced interference with daily activities and disturbance of mood due to rhinorrhea compared with baseline (P < .05). Both treatments were well tolerated with IB causing less nasal bleeding and irritation than BDP. CONCLUSIONS: Ipratropium bromide was safe and effective in controlling rhinorrhea and diminishing the interference by rhinorrhea in school attendance, concentration on school work, and sleep. Ipratropium bromide was as effective as BDP in the control of rhinorrhea and showed a relatively good effect on congestion. Patient and physician assessment favored BDP in the control of sneezing.

Adolescent↗
PubMed1994

Sequential 1H NMR assignment of the complex of aponeocarzinostatin with ethidium bromide and investigation of protein-drug interactions in the chromophore binding site.

Two-dimensional 1H NMR spectroscopy has been used to investigate the binding site, binding interactions, and the conformation of a 1:1 complex of aponeocarzinostatin (apo-NCS) with ethidium bromide in solution. The protein component in the complex has been sequence-specifically assigned using information derived from coherence transfer and two-dimensional homonuclear 1H NOESY experiments. The conformation of the protein in the complex has been found to be similar to the free form of the apoprotein, and intermolecular NOEs between the residues of the protein to protons on the ethidium bromide suggest that the ethidium bromide is bound to the protein in the same cleft in which the neocarzinostatin chromophore binds. Protons on ethidium show NOE interactions to the following protein residues: Trp-39, Leu-45, Cys-47, and Gln-94 which interact with the phenanthridine ring system of ethidium, Gly-102 and Asn-103 which interact with the alkyl chain of ethidium, and Phe-52 which interacts with the phenyl ring of ethidium. The orientation of ethidium in the cleft of apo-NCS is compared and contrasted to orientation of the chromophore as determined by high-resolution NMR and X-ray diffraction studies.

Amino Acid Sequence↗