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PubMed1988

Dose related effects of salbutamol and ipratropium bromide on airway calibre and reactivity in subjects with asthma.

The relationship between change in airway calibre and change in airway reactivity after administration of bronchodilator drugs has been investigated by comparing the effect of increasing doses of inhaled salbutamol and ipratropium bromide on the forced expiratory volume in one second (FEV1), specific airways conductance (sGaw), and the dose of histamine causing a 20% fall in FEV1 (PD20) in six subjects with mild asthma. On each of 10 occasions measurements were made of baseline FEV1, sGaw, and PD20 after 15 minutes' rest, and followed one hour later, when the FEV1 had returned to baseline, by a single nebulised dose of salbutamol (placebo, 5, 30, 200 and 1000 micrograms) or ipratropium (placebo, 5, 30, 200 and 1000 micrograms) given in random order. Measurements of FEV1, sGaw, and PD20 were repeated 15 minutes after salbutamol and 40 minutes after ipratropium. Salbutamol and ipratropium caused a similar dose related increase in FEV1 and sGaw, with a mean increase after the highest doses of 0.76 and 0.69 litres for FEV1 and 1.15 and 0.96 s-1 kPa-1 for sGaw. Salbutamol also caused a dose related increase in PD20 to a maximum of 2.87 (95% confidence interval 2.18-3.55) doubling doses of histamine after the 1000 micrograms dose, but ipratropium bromide caused no significant change in PD20 (maximum increase 0.24 doubling doses, 95% confidence interval -0.73 to 1.22). Thus bronchodilatation after salbutamol was associated with a significantly greater change in airway reactivity than a similar amount of bronchodilatation after ipratropium bromide. This study shows that the relation between change in airway reactivity and bronchodilatation is different for two drugs with different mechanisms of action, suggesting that change in airway calibre is not a major determinant of change in airway reactivity with bronchodilator drugs.

Administration, Inhalation↗
PubMed2002

Alternatives to methyl bromide treatments for stored-product and quarantine insects.

Methyl bromide is used to control insects as a space fumigant in flour and feed mills and ship holds, as a product fumigant for some fruit and cereals, and for general quarantine purposes. Methyl bromide acts rapidly, controlling insects in less than 48 h in space fumigations, and it has a wide spectrum of activity, controlling not only insects but also nematodes and plant-pathogenic microbes. This chemical will be banned in 2005 in developed countries, except for exceptional quarantine purposes, because it depletes ozone in the atmosphere. Many alternatives have been tested as replacements for methyl bromide, from physical control methods such as heat, cold, and sanitation to fumigant replacements such as phosphine, sulfuryl fluoride, and carbonyl sulfide, among others. Individual situations will require their own type of pest control techniques, but the most promising include integrated pest management tactics and combinations of treatments such as phosphine, carbon dioxide, and heat.

Animals↗
PubMed2005

Efficacy of nebulized flunisolide combined with salbutamol and ipratropium bromide in stable patients with moderate-to-severe chronic obstructive pulmonary disease.

BACKGROUND: The efficacy of nebulized corticosteroids in the prevention of exacerbation of chronic obstructive pulmonary disease (COPD) has been poorly studied. OBJECTIVE: To evaluate the efficacy and tolerability of nebulized flunisolide (1 mg) + salbutamol/ipratropium bromide (1,875/375 microg) b.i.d. in comparison with placebo + salbutamol/ipratropium bromide. METHODS: This was a randomized, parallel-group, double-blind study on 114 patients with COPD of moderate-to-severe degree. The main outcome was the frequency of severe exacerbations over a 6-month period. Before and after treatment, respiratory symptoms, forced expiratory volume in 1 s (FEV(1)), shuttle walking test distance and St. George's Respiratory Questionnaire scores were evaluated. RESULTS: The total number of exacerbations was slightly lower in the flunisolide group compared to the placebo group (19 vs. 34, p = 0.054); the number of patients experiencing at least one exacerbation during the study was also decreased (16 vs. 26, p = 0.059). In particular, type 3 Anthonisens's exacerbations were significantly reduced by flunisolide (p = 0.044). In the placebo group, scores were higher than in the flunisolide group but nonsignificant for dyspnea, cough, sputum amount and purulence. FEV(1) was significantly increased compared to baseline in both groups, and the area under the FEV(1)-time curve during the 6-month period was significantly greater in the flunisolide group (5.2 +/- 10.6 vs. 2.1 +/- 5.0, flunisolide vs. placebo, respectively; p = 0.047). For shuttle walking test distance and scores of the St. George's Respiratory Questionnaire, no significant difference between the baseline evaluation and the end of the study was observed in both groups. CONCLUSIONS: Nebulized flunisolide is a good alternative to other inhaled corticosteroids when added to nebulized salbutamol/ipratropium bromide in the long-term treatment of moderate-to-severe COPD patients.

Aged↗
PubMed1979

Immunological release of histamine from human lung. II. Studies on acetylcholine and the anticholinergic agent ipratropium bromide.

The experiments reported in this work have been performed to measure the effects of acetylcholine and the anticholinergic agent ipratropium bromide on the antigen-induced release of histamine from sensitized human lung in vitro. Primarily, ipratropium bromide did not have any effect, even at higher concentrations. Acetylcholine at a concentration of 1 x 10(-7)M increased the antigen-induced release of histamine by approximately 41%. When the lung tissue was treated with ipratropium bromide before acetylcholine, the competitive inhibition of the cholinergic receptor almost completely abolished this acetylcholine-induced increase of histamine release. Therefore, in our opinion, anticholinergic agents are primarily useful in vagus-controlled chronic obstructive ventilatory disorders; they are of secondary importance in allergic bronchial asthma.

Acetylcholine↗
PubMed1986

Prevention of fog-induced bronchospasm by Duovent and its components (fenoterol, ipratropium bromide) in asthmatics.

16 hyperreactive asthmatics were challenged with an ultrasonic mist of H2O at the same time of day on 4 usually consecutive days 2 h after premedication with placebo, fenoterol (200 micrograms), ipratropium bromide (80 micrograms) and Duovent (fenoterol 200 micrograms + ipratropium bromide 80 micrograms), given in random order and double-blind conditions. The challenge test consisted of 3 exposures of 30, 60 and 120 s with 4-min intervals. Specific airway resistance (sRaw) was measured under basal conditions and 1, 2 and 3 min after each exposure. FEV1 was measured under basal conditions and immediately after the last sRaw measurement. Fenoterol afforded a good protection; ipratropium bromide alone was ineffective but enhanced the protective effect of fenoterol when the two drugs were given in combination (Duovent). A similar effect was also observed after a second challenge performed 1 h (9 patients) or 3 h (6 patients) after the first one, which was performed 2 h after premedication.

Adolescent↗
PubMed1986

Effect of Duovent (ipratropium bromide and fenoterol) on non-specific bronchial hyperreactivity.

Beta 2-adrenergic and anticholinergic drugs have shown an action in modulating bronchial hyperreactivity to various stimuli (chemical, physical, immunological, pharmacological). The aim of our study was to compare the efficacy of a combination of ipratropium bromide and fenoterol (Duovent) with the activity of single drugs in the prevention of histamine-induced bronchospasm. Twenty-six atopic asthmatic subjects were examined in a double-blind trial, during an asymptomatic period, with a FEV1 value not lower than 20% of the predicted normal value. During 4 consecutive days all patients received 2 puffs, respectively, of Duovent (200 micrograms fenoterol + 40 micrograms ipratropium bromide), fenoterol (400 micrograms), ipratropium bromide (80 micrograms) and placebo in a randomized order. PD20 values were evaluated after each drug administration: after 2 h in 16 patients and after 5 h in the other 10 patients. The data were modified to log values, and statistical analysis was performed by two-way analysis of variance. This study showed that Duovent and fenoterol have a protective effect against histamine-induced bronchospasm with a significant increase in the PD20 values 2 h (p less than 0.01) and 5 h (p less than 0.05) after treatment when compared to placebo. Duovent inhalation determined a more protective effect than other drugs but not significantly when compared to fenoterol. Some advantages in the modulation of bronchial reactivity could be seen from using Duovent because with the lower dose of the beta 2-adrenergic drug the same results could be obtained without side-effects.

Adolescent↗
PubMed1992

Therapeutic equivalence of a fenoterol/ipratropium bromide combination (Berodual) inhaled as a dry powder and by metered dose inhaler in chronic obstructive airway disease.

A randomized double-blind cross-over study was performed to compare the bronchodilator effects of a fenoterol/ipratropium bromide combination (Berodual) when inhaled as a dry powder and by metered dose inhaler (MDI) in an equal doses (fenoterol 100 micrograms + ipratropium bromide 40 micrograms). Thirty-eight patients (29 male, 9 female, mean age 53 years) with reversible chronic obstructive airway disease were studied on 2 separate days by employing the double-dummy technique. The effects of the two modes of administration of the fixed combination were followed by pulmonary function tests [forced expiratory volume (FEV1), forced vital capacity (FVC)] from 15 min up to 6 h after administration. In addition, the pulse rate was recorded just before each pulmonary function test. The FEV1 and FVC time-response curves showed that the dry powder had an overall efficacy profile similar to MDI. Both formulations produced clinically significant improvements in FEV1 in approximately 10 min. Peak effects occurred in 1 h while at 6 h after test drug inhalation there was still an increase in FEV1 of 14%. No safety problems were observed after the use of the test drugs and no clinically significant changes in pulse rate were found. It is concluded that the dry powder of the fenoterol/ipratropium bromide combination provided effective bronchodilation of similar degree and duration to that achieved with the MDI. It would appear, therefore, to be a valuable alternative to MDI.

Administration, Inhalation↗
PubMed1976

Inhibition of transfer ribonucleic acid nucleotidyl transferase (EC 2.7.7.25) from Ehrlich tumor cells by proflavine sulfate and ethidium bromide.

Transfer RNA nucleotidyl transferase from Ehrlich tumor cells was inhibited by proflavine sulfate and ethidium bromide but not by actinomycin D, chromomycin, rifamycin SV, rifampin, daunomycin, or alpha-amanitin. Complete inhibition of nucleotidyl transferase activity was attained at a final concentration of 1 mmol/1 proflavine sulfate, while 2 mmol/1 ethidium bromide was required to completely inhibit the enzyme. CMP incorporation into tRNA was more sensitive to both proflavine sulfate and ethidium bromide than was AMP incorporation.

Acridines↗
PubMed1989

The effects of ipratropium bromide and fenoterol nebulizer solutions in children with asthma.

The effects of nebulized solutions of ipratropium bromide and fenoterol combined were compared with the response to either preparation alone in single dose and longer-term administration in children who had asthma. The combination produced a slightly greater response than either alone, especially in peak expiratory flow. Over a 1-month period, there were no significant differences in symptom scores or lung function parameters between the combination of ipratropium bromide and fenoterol and fenoterol alone in a group of children who had asthma. It is possible that the addition of ipratropium bromide to a sympathomimetic drug may be useful in a subgroup of asthmatics, particularly if there is a considerable large airway contribution to bronchial narrowing.

Adolescent↗
PubMedDate not supplied

Effect of terfenadine and ipratropium bromide on ultrasonically nebulized distilled water-induced asthma.

Inhalation of ultrasonically nebulized distilled water was used to evaluate non-specific bronchial reactivity and to investigate nonimmunologically mediated asthma. Release of histamine and other mediators from mast cells and stimulation of lung irritant receptors are mechanisms that may be involved in nebulized distilled water-induced bronchoconstriction. To investigate the contribution of these mechanisms the effect of terfenadine and ipratropium bromide on the bronchial response to this stimulus was assessed. A total of 30 asthmatics (mean 28.7 years) were submitted on three different days to distilled water challenge with or without prior treatment with oral terfenadine or inhaled aerosolized ipratropium bromide. The decrease in forced expiratory volume in 1 s induced by the same dose of distilled water was significantly (P less than 0.001) reduced from 35.6 +/- 15.8% to 19.5 +/- 16% with terfenadine and to 23.9 +/- 19.7% with ipratropium bromide. The results suggest that histamine release and reflex bronchoconstriction are mechanisms involved in asthma induced by ultrasonically nebulized distilled water.

Administration, Inhalation↗
PubMed1989

Effects of magnesium citrate and clidinium bromide on the excretion of activated charcoal in normal subjects.

The efficacy of cathartics in shortening the gastrointestinal transit time of activate charcoal (AC) in the presence of drugs that alter gastrointestinal motility has not been determined. We evaluated the effects of magnesium citrate (MC) on the excretion of activated charcoal in healthy volunteers alone and with concurrent administration of the anticholinergic drug clidinium bromide. Forty subjects were randomized to clidinium bromide 5 mg or placebo capsule (PC), followed by activated charcoal 15 g and magnesium citrate or a placebo liquid (PL). The onset and duration of excretion of activated charcoal were noted. Mean onset times for activated charcoal were: group I (CB, MC) 4.5 +/- 2.1 h; group II (CB, PL) 17.0 +/- 10.0 h; group III (PC, MC) 6.3 +/- 5.8 h; and group IV (PC, PL) 20.6 +/- 8.4 h. The onset of excretion of activated charcoal was statistically different in both magnesium citrate groups as compared with the placebo liquid groups. The duration of activated charcoal in the stool was similar among the groups. The addition of clidinium bromide did not appear to affect gastrointestinal transit time. These results support previous studies of the effects of cathartics on the excretion of activated charcoal, and suggest that cathartic efficacy is not inhibited by anticholinergic drugs when used in therapeutic doses.

Adult↗
PubMed2001

Antitrypanosomal properties of cis-platinum-pentamidine bromide, thiocyanate and seleniocyanate on Trypanosoma brucei brucei mouse and sheep models.

Three organometallic complexes derived from pentamidine were evaluated for their trypanocidal effect on in vivo Trypanosoma brucei brucei models in comparison to pentamidine isethionate as reference compound. On the T. b.brucei mouse model, the most active compound was cis-platinum-pentamidine bromide. This compound was active when subcutaneously administered at the single dose of 1.5 micromol/kg and its chemotherapeutic index was 200 whereas pentamidine isethionate was active at 6 micromol/kg with a chemotherapeutic index of 13, when administered in the same conditions. Cis-platinum-pentamidine bromide was active at 1 mg/kg (1.44 mmoles/kg), in a single dose by subcutaneous route against the early stage of the T. b.brucei Antat 1-9 sheep model. Platinum kinetics in serum showed a Cmax of 0.2 mg/l reached 80 h after the treatment at this dose. Cis-platinum-pentamidine bromide, cis-platinum-pentamidine seleniocyanate, and cis-platinum-pentamidine thiocyanate were distributed in the deep compartment according to a monocompartmental model. In all cases, platinum was eliminated from the serum 700 hours post-treatment. All data obtained from these models show activity on the early stage of the disease and justify further investigations on the late stage of the disease.

Animals↗
PubMed1982

A therapeutic comparison of ipratropium bromide and salbutamol in asthmatic patients.

A single-blind, crossover study was carried out in 43 asthmatic patients to compare the efficacy and tolerance of inhaled ipratropium bromide with inhaled salbutamol. One or other drug was given 3-times daily (0.04 mg ipratropium bromide or 0.2 mg salbutamol per dose) over a period of 4 weeks. Patients were then crossed over to the alternative medication for a further 4 weeks. The results of lung function tests performed at routine clinic visits and by the patients at home showed similar increases in peak flow and spirometry recordings, although more patients expressed a preference for salbutamol. Unwanted effects were minor with both drugs. It is suggested, therefore, that ipratropium bromide may be a useful alternative to beta-stimulants in some asthmatics.

Adult↗
PubMed1986

Effects of pinaverium bromide in the premedication of endoscopic retrograde cholangio-pancreatography and on motor activity of the sphincter of Oddi.

A double-blind study was carried out in 18 patients with biliary and pancreatic disease to assess the use of pinaverium bromide in premedication for endoscopic retrograde cholangio-pancreatography and its effects on motor activity of the sphincter of Oddi. Patients were divided at random into three groups. One group received 100 mg pinaverium bromide twice daily for 3 days before and then 100 mg 1 hour before the examination, the second group received placebo, and the third had no medication. All patients received 10 to 20 mg diazepam intravenously 10 minutes before endoscopy. Assessments were made of the transit time of various endoscopic phases and patients' tolerance of the procedure. The effects of treatment on the sphincter of Oddi were estimated by means of endoscopic manometry. The results showed that pinaverium bromide allowed transit time reduction in endoscopic procedure, a greater tolerance on the part of the patient and marked reduction in the amplitude and duration of the phasic activity of the sphincter.

Adult↗
PubMed1987

Effect of timepidium bromide on the motor activity of the sphincter of Oddi: manometric evaluation of intracholedochal pressure.

The intracholedochal pressure changes induced by timepidium bromide were studied in 12 patients who had undergone surgery because of gall bladder stones and were receiving transient external bile drainage by the Kehr method. Cholangiomanometric examination, carried out under basal conditions and after an intravenous dose of 15 mg timepidium bromide, revealed a statistically significant decrease in mean intracholedochal pressure in all 12 patients. It is concluded that timepidium bromide is likely to exert a direct action on the sphincter of Oddi, decreasing its basal tone and thus causing a decrease in intracholedochal pressure.

Aged↗
PubMed1980

The effect of chloramphenicol, ethidium bromide and cycloheximide on mortality and mitochondrial protein synthesis of adult blowflies.

The effects of cycloheximide, chloramphenicol and ethidium bromide on the blowfly Calliphora erythrocephala were studied. In the first set of experiments, toxic levels were determined by examining activity and mortality of flies after injection of various doses of each drug. In the second set of experiments, the effect of drug treatment on flight muscle mitochondrial protein synthesis was determined in relation to age by following the incorporation of radioactively labelled amino acid, [3H]leucine, into mitochondrial protein in vivo. To confirm the developmental changes in flight muscle mitochondria, mitochondrial protein content per fly was estimated from emergence to 30 days of age; the highest protein level was recorded between 6 and 10 days of age. Maximum incorporation of labelled amino acid was found in newly emerged flies, and this age group was also the most sensitive to drug treatment. By the time flies had reached 6--10 days of age, amino acid incorporation had declined to about two-thirds of the rate obtained with newly emerged flies. With 6--10-day old flies, however, the highest value for flight muscle mitochondrial protein per fly was recorded, and these flies also displayed the greatest resistance to drug treatment of any age group investigated. For example, inhibition of protein synthesis following injection of 300 micrograms/fly of chloramphenicol was only about 15% below the untreated control in 6-10-day-old flies, whereas in all other age groups investigated, inhibition ranged between 30 and 50% of the controls. At 15--20 days of age, protein synthesis decreased to a third of the newly emerged flies' rate and continued to decrease further in the 30--35-day-old group, where it was less than one sixth of the youngest age group. The effect of drug treatment on these older flies was also less than that observed with newly emerged flies, especially after chloramphenicol and ethidium bromide injections. The effect of cycloheximide however, was much the same in all age groups, with inhibition of protein synthesis being 80--90% of controls. Surprisingly, cycloheximide (1--10 micrograms/fly) had little initial effect on mortality of young flies, despite almost complete blockage in the synthesis of mitochondrial proteins at these concentrations. 95% mortality occurred only when doses of 20 micrograms/fly were given. In contrast, high doses of chloramphenicol (400 micrograms/fly) and ethidium bromide (15 micrograms/fly) caused almost total mortality a few hours after injection, although such doses never induced more than about 50% inhibition of mitochondrial protein synthesis. Each drug therefore has a different site of inhibition and induces different mortality effects. Possible explanations for these differences in mortality are discussed.

Aging↗
PubMed1980

The effects of spectinomycin and ethidium bromide on the synthesis of organelle rRNA and on ultrastructure in Ochromonas danica.

The effects of 24-h exposure to spectinomycin (100 microgram/ml) and ethidium bromide (1 microgram/ml) on the accumulation of chloroplast and mitochondrial rRNAs and on organelle ultrastructure were studied in greening cells of Ochromonas danica. Cells treated with ethidium bromide for 24 h divide at the same rate as controls but contain less than one third the normal amount of mitochondrial rRNA. Ultrastructural observations showed that these cells contain only 10% the number of mitochondrial ribosomes found in controls as well as fewer mitochondrial cristae. Ethidium bromide has no effect on chloroplast ultrastructure in Ochromonas. Greening cells treated with spectinomycin grow at close to control rates but contain 30-40% less chloroplast rRNA than do controls. Electron microscopy showed that spectinomycin disrupts the organization of chloroplast membranes and reduces the number of chloroplast ribosomes by 30%. Under these conditions, spectinomycin has no effect on mitochondrial rRNA or ultrastructure. Since spectinomycin is a specific inhibitor of translation on 70S ribosomes, these results are consistent with the possibility that at least some chloroplast ribosomal proteins are synthesized in the chloroplast of Ochromonas.

Cell Division↗
PubMed1989

[Determination of bromide ions in total blood, plasma and urine by ion chromatography with amperometric detection].

A direct injection method is described for the determination of bromide ions in plasma and urine by ion chromatography. After being diluted 10-20 times with eluent, the sample was directly injected into an ion chromatograph equipped with amperometric detection. Calibration curves were obtained in the range of 0.05 to 5 micrograms/ml of bromide ions. The coefficient of variation was calculated to be in the range of 1.3-9.4% for 10 repeated measurements and recovery was over 93%. The correlation between analytical results by the proposed method (Y) and those by a spectrophotometric method (X) of 169 urine samples in fumigators was expressed by the equation Y = 0.952 + 1.012X (correlation coefficient (r): 0.952). On the other hand, the correlation between analytical results by the proposed method (Y) and those by neutron activation analysis (X) of 47 total-blood samples in fumigators was expressed by the equation Y = 1.070 + 0.841 X (correlation coefficient (r): 0.931). The correlation between analytical results by the proposed method (Y) and those by neutron activation analysis (X) of 40 plasma samples in healthy workers was expressed by the equation Y = 0.633 + 0.871 X (correlation coefficient (r): 0.955). The proposed method is much more practical than other methods such as the spectrophotometric method and neutron activation analysis in epidemiological studies, because the proposed method is highly accurate and reproducible over longer periods. The proposed method is useful in biological fluid monitoring of bromide ions.

Bromine↗