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PubMed2003

A comparison of the effects of salbutamol and ipratropium bromide on exercise endurance in patients with COPD.

STUDY OBJECTIVE: Inhaled bronchodilators are the first-line pharmacotherapy against COPD. The purpose of the present study was to investigate the effects of beta(2)-agonists and anticholinergic agents on the exercise capacity of patients with COPD. METHODS: A total of 67 stable patients with COPD were recruited at the Kyoto University Hospital. After inhaling 400 micro g salbutamol, 80 micro g ipratropium bromide, or an identical placebo in a randomized, double-blind, crossover fashion, the patients performed cycle endurance tests at a constant workload of 80% of the maximum work rate reached on progressive cycle ergometry, and the endurance time was recorded. RESULTS: Both salbutamol and ipratropium bromide significantly improved the endurance time by 29 s (15%; p < 0.001) and 27 s (14%; p < 0.001), respectively, in comparison with the placebo. However, there was no statistically significant difference between them (p = 0.71). The dyspnea ratios were also similarly reduced by both bronchodilators. The difference in the endurance time between therapy with salbutamol and placebo was significantly, but moderately, related to the difference between therapy with ipratropium bromide and placebo. In addition, there were no relationships, or only weakly significant relationships, between the change in FEV(1) and the change in the endurance time, the highest oxygen uptake, and the highest minute ventilation for both salbutamol and ipratropium bromide. CONCLUSIONS: Therapy with both salbutamol and ipratropium bromide improved exercise capacity, as evaluated by the endurance time, and reduced dyspnea similarly in patients with COPD. In addition, the effects of the different bronchodilators on exercise capacity varied within individuals, and a complex mechanism may be responsible for the different effects of these two bronchodilators on exercise capacity vs airflow limitation. These results support the conclusion that both types of inhaled bronchodilators can be used as first-line drugs for the treatment of stable patients with COPD.

Adrenergic beta-Agonists↗
PubMed1989

Effect of salbutamol, ipratropium bromide and cromolyn sodium on prostaglandin F2 alpha-induced bronchospasm.

We studied the effects of salbutamol, ipratropium bromide and cromolyn sodium on PGF2 alpha-induced bronchospasm in ten patients with asthma. Initially, the bronchial reactivity to IC-PGF2 alpha and the DP20-PGF2 alpha were determined. Recalculations were made two days later and again 1 h after administration of various drugs given on different days. Salbutamol and ipratropium bromide induced significant bronchodilation and of similar magnitude 1 h after administration. On the day salbutamol was given, surface area under the dose-response curve to PGF2 alpha was significantly higher and the final drop of FEV1 significantly lower than those observed on days when placebo, ipratropium bromide and cromolyn sodium were given. No differences among these values were found for placebo, ipratropium bromide and cromolyn sodium. Thus, beta 2 stimulants attenuate significantly PGF2 alpha-induced bronchospasm, while ipratropium bromide and cromolyn sodium do not have protective effect.

Adolescent↗
PubMed1990

Airways responses to ipratropium bromide do not vary with time in asthmatic subjects. Studies of interindividual and intraindividual variation of bronchodilatation and protection against histamine-induced bronchoconstriction.

Bronchial histamine provocation tests were performed in nine patients with nonallergic asthma on four consecutive days 45 minutes after inhalation of placebo or ipratropium bromide in a dose-response manner (40 micrograms, 200 micrograms, and 800 micrograms). The drugs were administered double-blind, one dose on each day. This procedure was repeated identically after three to nine months to investigate whether the bronchial responses to ipratropium bromide are constant or change with time. Ipratropium bromide induced a significantly better bronchodilation and protection against histamine-induced bronchoconstriction than placebo with no differences between the three doses. No correlation between bronchodilatation and protection was found. In six asthmatic patients ("responders") ipratropium bromide induced a significant protective effect against histamine-induced bronchoconstriction but no dose-response relationship was found. In three patients none or a very poor protective effect was found at all dose levels ("nonresponders"). The protective effect of ipratropium bromide against histamine-induced bronchoconstriction did not differ between the first and second occasion. Thus, the bronchoprotection differed between different asthmatic subjects but did not vary with time (three to nine months) within the same subject. This finding seems to be of clinical importance since it implicates that the effect of anticholinergic agents on the airways is predictable.

Administration, Inhalation↗
PubMed1988

[Cases of severe methyl bromide poisoning residing above a warehouse].

Methyl bromide has been widely used in Japan to fumigate grains and wood. One death and 3 cases of hospitalization resulted from exposure to methyl bromide at place of residence. These 4 cases were not employed and were members of one family living above a warehouse, the ground level of this building was a warehouse where herbs were stored and the second floor was their living area. On the 13th of May 1978 at 7:00 p.m., the herbs were fumigated with methyl bromide gas. The fumigator used 15 kg of methyl bromide (2 cylinders), a quantity far greater than usual. It is assumed that the concentration in the warehouse was between 10,000-15,000 ppm. Early in the morning on the 16th of May (3 days later), one of the family members, a 12-year-old girl, developed severe convulsions, and later 2 others also had severe convulsions, while the other suffered from marked mental confusion. The serum or plasma bromide ion level ranged from 280 to 600 ppm. The results of the clinical laboratory test showed that GOT exceeded the normal level in 3 out of the 4 cases. Moreover, LDH activity was above the normal range in 3 cases and CPK activity was increased in all the cases.

Adult↗
PubMed1978

Treatment of urgency by instillation of emepronium bromide in the urinary bladder.

The possibility of a purely local action of intravesically instilled emepronium bromide (Cetiprin) was investigated. Subjective reports and simultaneous urethrocystometry were used to assess such effect. In order to ascertain the purely local nature of effect, the serum was analyzed for freely circulating emepronium ion at increasing intravesical concentrations. No adverse effects were found at the highest dosage (100 mg in 100 ml saline solution), and the concentrations in serum were very low or were not detectable. The seemingly promising influence on micturition frequency and urge prompted a double-blind study of 20 patients with chronic urgency. In ten of them 100 mg emepronium bromide in 100 ml saline solution was instilled intravesically, while the other ten received only the same volume of saline solution. The symptoms were relieved in eight of the ten patients given emepronium bromide. The observation time was one week. The therapeutic possibilities were further evaluated in 24 women with frequency and urgency with or without urge incontinence. Emepronium bromide was intravesically instilled in the mentioned concentration and, if the symptoms were not totally relieved, this was repeated at weekly intervals. The maximum number of instillations was four and the observation time after the final treatment was at least three weeks. Frequency and urgency disappeared in approximately 70% of the affected women, nocturia in 60%, but urge incontinence in only 30%. Both frequency and urgency therefore were therapeutically influenced by intravesical instillation of emepronium bromide.

Administration, Topical↗
PubMed1998

An unusual exposure to methyl bromide leading to fatality.

INTRODUCTION: Methyl bromide has been responsible for deaths that usually occur from its accidental inhalation during fumigation. CASE REPORT: We report an accidental fatality that occurred after methyl bromide seeped through underground conduits from a fumigated building to an adjacent guest house on the same property. The patient developed refractory seizures, intermittent fever, and multiorgan system failure before dying 19 days after exposure. The initial serum bromide was 27 mg/dL. Postmortem analysis detected methyl bromide concentrations of 2.9 mg/dL in the blood, 1.7 mg/dL in the bile, 24 micrograms/g in the liver, and 28 micrograms/g in the adipose tissue. CONCLUSION: Methyl bromide, although applied under acceptable safety standards, led to the inadvertent death of a young woman. Extreme care must be used when fumigating to insure no unsuspected seepage routes exist.

Adult↗
PubMed1992

A new methyl bromide gas generator for inhalation toxicity studies.

A simple generator for methyl bromide gas has been newly developed by us. For inhalation toxicity studies, until now, there have been few generators capable of producing a constant and stable concentration of methyl bromide gas easily because of its high volatility. The principle of this new generator is based on gas-liquid equilibrium. The gas is generated from the surface of liquid methyl bromide in an evaporator made of a Teflon tube. The generator can produce up to 10,000 ppm of methyl bromide gas in a 0.1 m3 exposure chamber, and the concentration of this generated gas is able to be kept within +/- 0.8% over a long period of time. The generator has proved to be useful for investigating the effects of methyl bromide on health in inhalation toxicity studies.

Administration, Inhalation↗
PubMed1999

[Effectiveness of pinaverium bromide therapy on colonic motility disorders in irritable bowel syndrome].

The special patterns of the slow wave activity in irrittable bowel syndrome by means of surface electromyography were examined and the effect of pinaverium bromide on the symptoms and on the colonic motility in this disease was estimated. Twenty two patients with irritable bowel syndrome and 7 healthy controls were selected to the study. The clinical symptoms were abdominal pain and bloating in all patients, constipation in 9, and diarrhoea in 6 cases. Surface electromyography was carried out before and on the 14th day of the treatment with pinaverium bromide (50 mg t. i. d). The colonic motility was analysed in a 2 hour fasting and a 2 hour postprandial period following a standard (800 kCal) meal. The slow wave frequency of 0.01-0.04 Hz were selected and analysed. The mean frequency of activity peaks (n/10 min) and power-index (area under curve, microV 10 min) were measured. For statistical analysis Student's t-test was applied. Electromyogram of patients with irritable bowel syndrome showed a significant increase of the measured colonic motility parameters both in fasting and postprandial states. Fourteen days of pinaverium bromide treatment was able to significantly reduce the intensity of the colonic motor activity. Administration of pinaverium bromide completely released in 6 and significantly improved the abdominal pain in other 12 patients, while the bloating disappeared in 12 and was significantly improved in 5 from 22 patients. Pinaverium bromide was able to normalise the stool frequency: the weekly number of stools was decreased from 16 to 7 in the patients complaining diarrhoea ant it was increased from 2 to 6 in the patients with constipation.

Calcium Channel Blockers↗
PubMedDate not supplied

Stability-indicating methods for determining omeprazole and octylonium bromide in the presence of their degradation products.

Four stability-indicating assays were developed for determining omeprazole and octylonium bromide. Omeprazole is photodegraded and estimated in the presence of its degradation products sulphenamide (I) and benzimidazole sulphide (II) by 2 methods. The first method depends on use of first-, second-, and third-derivative spectrophotometry at 290.4, 320.6, and 311.6 nm, respectively. The second method is based on applying the charge-transfer technique with chloranil as pi acceptor to form a complex with omeprazole, the absorbance of which is measured at 377 nm. These methods determine omeprazole in concentration ranges of 5-20 micrograms/mL by first-, second-, and third-derivative spectrophotometry and 10-50 micrograms/mL by charge-transfer complexation with mean accuracies of 99.92 +/- 0.73, 99.71 +/- 1.02, 99.64 +/- 0.66, and 100.24 +/- 0.81%, respectively. Octylonium bromide is determined by a densitometric method using thin-layer chromatography in the presence of its degradation products p-[2-(n-octyoxy)benzoyl]-aminobenzoic acid (III) and diethyl-(2-hydroxyethyl)-methyl ammonium bromide (IV) without any interferences. Alternatively, octylonium bromide is evaluated by a colorimetric method using the acid dye rose bengal. The ion pair formed is extracted in chloroform at pH 4, and its absorbance is measured at 562 nm. These methods determine octylonium bromide in the presence of its degradation products in concentration ranges of 0.1-0.5 microgram/microL by densitometry and 4.5-22.5 micrograms/mL by colorimetry, with mean accuracies of 100.21 +/- 0.93 and 99.73 +/- 0.89%, respectively. The suggested methods were used to determine drugs in bulk powder, laboratory-prepared mixtures, and pharmaceutical dosage forms. Results were compared statistically with those obtained with reference methods.

Anti-Ulcer Agents↗
PubMed1975

Ethidium bromide mutagenesis in yeast: protection by anaerobiosis.

The mutagenesis by ethidium bromide, an intercalating dye, which induces the mutation from wild type (rho+) to the cytoplasmic respiratory deficient petite (rho-) in Saccharomyces cerevisiae, was studied under aerobic and anaerobic conditions. During growth of anaerobic cells at pH 6.5, ethidium bromide at a concentration of 2 mug/ml is unable to induce rho- mutants whereas under aerobic conditions the entire population is converted into rho- cells within 1 generation at the same drug concentration. With ethidium bromide 10 mug/ml 98% of the anaerobic cells are transformed into rho- in 5.5 h (more than 2 generations). In non-growing conditions, ethidium bromide 10 mug/ml has no effect in anaerobic cells. 3 h adapted cells used as control, are converted into rho- in 8 h. Increasing the ethidium bromide concentration to 20 mug/ml resulted in the appearance of some rho- mutants in the anaerobic population but marked at the same time the onset of a detectable toxic effect of the drug.

Aerobiosis↗
PubMed2001

Late confirmation of acute methyl bromide poisoning using S-methylcysteine adduct testing.

Methyl bromide poisoning is difficult to confirm because routine laboratory testing has not been reliable. Measurable levels of the parent agent are rapidly reduced, probably as a result of direct tissue chemical reaction. Serum bromide levels have been used as an indirect measure of exposure and/or toxicity but are inconsistent. Recently special testing has shown that protein adducts formed after exposure to methyl bromide may be a better measure of significant exposure. The S-methylcysteine adduct was used to confirm acute methyl bromide toxicity 10 weeks after an exposure. Additionally, genotyping of the glutathione-S-transferase TI enzyme in erthyrocytes from this case characterized a predisposition to the neurotoxic effects of methyl bromide.

Adult↗
PubMed1998

[Comparing the bronchodilating effects of ipratropium bromide and theophylline].

OBJECTIVE: To compare the bronchodilating effects of ipratropium bromide and theophylline in chronic obstructive pulmonary disease(COPD). METHOD: In 26 patients, mean peak forced expiratory volume in 1 second(FEV1) were measured at the time before and 30 minute, 1, 2, 3, 4, 5, 6 hours after the drugs were administered in a double-blind, placebo-controlled crossover method. RESULT: The mean peak of FEV1, increased over baseline were 34% and 19% respectively, for ipratropium bromide and theophylline (P < 0.01), and the reaching duration were 1-2 hours and 2-3 hours, the proportion of patients attaining at least a 15% (P < 0.01) increase in the FEV1, responders were 19% and 50% (P < 0.01) respectively, for ipratropium bromide and theophylline. The average FEV1, increased during the 6-hours observation period were 18% for ipratropium bromide and 8% for theophylline (P < 0.01). The mean duration of FEV1 > 15% was 3.6 and 1.6 hours respectively. CONCLUSION: Ipratropium bromide nebulized is a more potent bronchodilator than the oral theophylline in patients with chronic airflow obstruction.

Adult↗
PubMed2001

A stability-indicating proton nuclear magnetic resonance spectroscopic method for the analysis of propantheline bromide in pharmaceutical samples.

A rapid, specific and accurate proton nuclear magnetic resonance (1H NMR) spectroscopic method was developed for the simultaneous quantitative analysis of propantheline bromide and its degradation product, xanthanoic acid, in bulk materials and tablets. 1,3,5-Trinitrobenzene served as an internal standard and deuterochloroform was used as the solvent for the analytical samples. The quantities of propantheline bromide and xanthanoic acid were calculated on the basis of the integrals for signals of the methine proton of propantheline at 5.09 ppm, the methine proton of xanthanoic acid at 4.99 ppm, and the aromatic protons of the internal standard at 9.39 ppm. The accuracy of the method was established through the analysis of synthetic mixtures containing the parent compound, its degradation product and the internal standard. An excellent agreement was verified between the assay results and the quantities of the various compounds in the mixtures. The mean +/- SD recovery values for propantheline bromide and xanthanoic acid from a set of 10 synthetic mixtures were 99.6 +/- 0.8% and 98.9 +/- 1.8%, respectively. The assay of 10 lots of commercial propantheline bromide tablets by 1H NMR spectroscopy indicated drug and degradate contents in the ranges 97.1-99.8% and 0.1-0.9%, respectively. In addition, the proposed analytical method was found suitable for detecting the formation of xanthanoic acid from propantheline bromide in aqueous media in concentrations below 0.1% of that of the parent compound.

Drug Stability↗
PubMed1992

Octylonium bromide in the treatment of the irritable bowel syndrome: a clinical-functional study.

We investigated the effect of octylonium bromide on a number of symptoms and functional aspects of the irritable bowel syndrome. Seventy-two patients complaining mainly of abdominal pain were studied in a double-blind trial (octylonium bromide 40 mg tid for 4 weeks or placebo). Clinical parameters were: abdominal pain, bloating and bowel frequency. Sigmoid manometry with simultaneous recording of the thresholds for distension and/or pain upon graded inflation of an endoluminal balloon was performed before and at the end of treatment. In contrast to placebo, octylonium bromide significantly reduced pain and bloating, and significantly increased (p < 0.02) the pain threshold throughout the treatment period. However, comparison with the placebo group failed to show any relevant differences. Neither treatment influenced the frequency of bowel movement. Sigmoid motility during distension was significantly reduced after octylonium bromide (p < 0.05), but it did not change after placebo. In conclusion, octylonium bromide is capable of reducing symptoms and motor reactivity of the sigmoid in patients with irritable bowel syndrome.

Abdominal Pain↗
PubMed2003

Chemical alternatives for soil fumigation with methyl bromide on tobacco seedbeds in nematode and weed control.

The proposed phase out of methyl bromide necessitated the evaluation of a number of chemical alternatives to replace it. The recommended rate of application for methyl bromide, 50 g/m2 was evaluated over three years against various rates of 65% 1,3-Dichloropropene mixed with 35% chloropicrin (1,3-D/C-35); a combination of metham sodium and ethylene dibromide (EDB) and 65% 1,3-Dichloropropene (1,3-D) alone. Chloropicrin and 1,3-D have long been registered and used in Zimbabwe as individual chemicals and their combination as a single product had never been tested. 1,3-D/C-35 at 36.9 ml/m2 was as effective as methyl bromide in nematode and weed control and led to similar seed germination and seedling growth rate. A combination of EDB at 21 ml/m2 and metham sodium at 35 ml/m2 was also equally effective. The use of 1,3-D alone at 35 ml/m2 gave unsatisfactory weed control and led to a reduced seedling growth rate. Metham sodium alone at 35 ml/m2 gave comparable weed control, seed germination and seedling growth comparable with methyl bromide. However nematode control evaluated using a gall rating scale was reduced. 1,3-D/C-35 at 36.9 ml/m2 and metham sodium at 35 ml/m2 used in combination with EDB at 21 ml/m2 are therefore, possible replacements for methyl bromide soil fumigation in tobacco seedbeds.

Animals↗
PubMed1990

Determination of methyl bromide traces in some food products by HS-GC/MS.

A simple and rapid method has been developed for fast selective determination of residues of methyl bromide in food products. The method is based on the use of a GC/MS computer-aided system equipped with a headspace. Analysis of methyl bromide was carried out directly on the food products without preliminary extraction of fumigant. An MSD quadrupole mass spectrometer with data processing allowed rapid identification of the separated volatile compound in the samples. The technique of focusing on characteristic single ion monitoring for quantification of methyl bromide, compared with chromatographic peak area measurement, turned out to have a good degree of accuracy and sensitivity. The use of known amount of added methyl bromide allowed better evaluation of traces of this compound. The proposed method was applied to the analysis of methyl bromide residues in alimentary pastes, white flour, rice, hazelnuts, peanuts and dried mushrooms (boletus).

Food Analysis↗
PubMed1985

Influence of ethidium bromide on hyperthermic modification of bleomycin-DNA interaction.

The effect of hyperthermic treatment on the binding of 59Fe-labeled bleomycin to DNA has been studied. Enhanced binding was observed at elevated temperatures. The influence of the DNA-intercalating agent, ethidium bromide, on bleomycin-DNA interaction was also studied and revealed a considerable decrease in this interaction at ethidium bromide levels below 1 microgram/ml. Ethidium bromide was observed to remove the enhanced bleomycin-DNA interaction recorded previously following incubation at hyperthermic temperatures. Synergistic action of bleomycin and hyperthermia on loss of clonogenic ability of HT29R cells is reported. Incubation of cells under hyperthermic conditions with bleomycin in the presence of ethidium bromide removes this synergism, producing a less than additive effect for the action of bleomycin and heat after ethidium bromide effects are taken into account.

Adenocarcinoma↗
PubMed1989

Ipratropium bromide (Atrovent) in childhood asthma: a cumulative dose-response study.

Thirteen children with perennial bronchial asthma, with a mean age of 11.2 years, were studied concerning the bronchodilatory effect of ipratropium bromide in cumulative doses. All the children had reduced basal forced expiratory flow (FEV1) and bronchial reversibility of at least 20% after inhalation of salbutamol. The study had a double-blind design with a crossover technique. The inhaled dose of ipratropium bromide solution was increased stepwise from 25 micrograms to 500 micrograms and saline was used as the placebo. FEV1 was recorded 20, 40, and 60 minutes after inhalation of the test solution. At the lower ipratropium bromide dose levels no bronchodilatory effect was seen, but 60 minutes after the inhalation of 500 micrograms ipratropium bromide the increase in the FEV1 was significantly greater than that after placebo. Additional inhalation of salbutamol caused no further rise in FEV1. At the 500-micrograms level a fall in the heart rate was noted. No side effects occurred. We concluded that ipratropium bromide has bronchodilatory properties in childhood asthma when given in sufficiently high doses.

Adolescent↗