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Comparative evaluation of neuromuscular blockade and reversibility of AH 8165 and pancuronium bromide in man.

The neuromuscular properties of AH 8165 were compared to those of pancuronium bromide in 66 patients during analgesic anesthesia procedures. Administration of 0.5 mg/kg AH 8165 and 0.04 mg/kg pancuronium bromide produced very similar degrees of non-depolarizing block. AH 8165 acted quicker and therefore gave better conditions for intubation. Spontaneous recovery of muscle twitch tension was slightly shorter for AH 8165 than for pancuronium bromide, whether small or larger amounts of drugs were used. Administration of neostigmine caused rapid and complete return of muscle twitch tension, well-maintained tetanus and insignificant posttetanic potentiation within 20 minutes, with a similar efficiency of competitive neuromuscular block reversal for both drugs.

Adult↗

Effect of inhalation of salbutamol, beclomethasone dipropionate & ipratropium bromide on mucociliary clearance in some patients with chronic stable bronchial asthma.

BACKGROUND & OBJECTIVES: Asthma is now regarded as an inflammatory disease and bronchial inflammation may disrupt mucociliary function. Inhaled drugs may act by improving mucociliary function. The aim of the study was to investigate the effect of salbutamol, ipratropium bromide and beclomethasone on mucociliary clearance in patients with chronic stable asthma and to compare the efficacy of these drugs on mucociliary clearance. METHODS: Ten patients with chronic stable asthma were enrolled in the study, but two patients did not complete the study. Patients with bronchial asthma were chosen on clinical grounds. (99m)Tc phytate radioaerosol generated through a nebulizer, was given to each patient on four days. After each administration the radioactivity over the thorax was constantly measured in sequential frame mode for 120 min. Radioactivity in the thorax was also measured after 24 h. A base-line pulmonary function test with reversibility was obtained. Salbutamol, ipratropium bromide, beclomethasone dipropionate and placebo inhalation were given randomly to each patient on four days. RESULTS: The mean age of patients (n = 8) was 36 +/- 9.3 yr and mean duration of symptoms was 5 +/- 6.6 yr. There was no visual impression that mucociliary clearance was enhanced with any of the drugs. The time activity curves did not show any visually recognisable change in slope. In only one patient the curve tended to show a steeper slope with ipratropium inhalation. In the rest of the patients the curves showed no difference at all with medication when compared with placebo. All the quantitative indices analyzed by two-way ANOVA at the end of one and two hours were comparable for the three test drugs and placebo. None of the three test drugs demonstrated statistically significant mucociliary clearance effect compared with placebo. However, the temporal difference in airways clearance efficiency (ACE) was significant with beclomethasone and ipratropium bromide. INTERPRETATION & CONCLUSION: Inhalation of any of the three drugs tested did not produce any immediate improvement in mucociliary clearance as compared to placebo in patients with stable bronchial asthma suggesting the need for further studies using higher doses of drugs for longer duration in a large sample.

Administration, Inhalation↗

[Extraction-spectrophotometric determination of carbethopendecinium-bromide in drug preparations].

The paper elaborated the conditions for the determination of carbethopendecinium bromide with bromthymol blue and methyl orange (concentration of the drug and the colouring agent, pH of the aqueous phase, period of extraction with chloroform). Within a carbethopendecinium bromide concentration range of 1.10(-5) to 6.10(-5) mol/l, the linear dependence of absorbance of the ion-associate with the colouring agent on concentration was confirmed. At pH 3 and pH 10, the above-described procedure was used to determine the content of carbethopendecinium bromide in medicinal preparations (eye and nasal drops) using the calibration curve and comparison with one standard. The results were reproducible and the found deviations from the declared content ranged within a tolerance of +/- 10%.

Ophthalmic Solutions↗

Bronchial spasmolytic action of terbutaline and fenoterol compared with that of ipratropium bromide in the anaesthetized dog.

Continuous recordings of heart rate, respiration rate, minute volume and bronchial resistance were made over a period of altogether three hours in spontaneously breathing dogs anaesthetized with chloralose. At hourly intervals, before and 1 and 2 hr after the administration of bronchodilators, bronchial spasm was induced by inhalation of an acetylcholine solution. Two beta2-stimulants, terbutaline and fenoterol, were administered by inhalation in doses of 0.5, 0.16 and 0.05 mg/kg and 0.1, 0.3 and 0.01 mg/kg respectively. For comparison, an atropine derivative, ipratropium bromide, was also given by the same route in doses of 0.04 and 0.01 mg/kg. Controls received normal saline. Terbutaline and fenoterol caused an increase in heart rate, respiration rate and minute volume. Acetylcholine-induced bronchial spasm was inhibited to the extent of 10--70% for 2 hr after the administration of terbutaline, and by 15--70% after fenoterol. The acetylcholine antagonist ipratropium bromide caused only transient changes in heart rate, respiration rate and minute volume. Acetylcholine-induced bronchial spasm was inhibited by 95% and 80% for 2 hr after doses of 0.04 and 0.01 mg/kg, respectively. Fenoterol had a slightly greater central stimulant effect than terbutaline; ipratropium bromide displayed no stimulant activity.

Acetylcholine↗

Protective effects of inhaled ipratropium bromide on bronchoconstriction induced by adenosine and methacholine in asthma.

Although adenosine-induced bronchoconstriction is mainly due to mast cell mediator release, vagal reflexes have also been implicated in this response. We have investigated the effect of a specific muscarinic-receptor antagonist, ipratropium bromide, on methacholine- and adenosine-induced bronchoconstriction in a randomized, placebo-controlled, double-blind study of 12 asthmatic subjects. Airway response was evaluated as forced expiratory volume in one second (FEV1). Inhaled ipratropium bromide (40 micrograms), administered 20 min prior to bronchoprovocation, increased the provocation dose of inhaled methacholine and adenosine required to reduce FEV1 by 20% from baseline (PD20) from 0.11 to 0.79 mg (p less than 0.01) and from 0.57 to 1.27 mg (p less than 0.01), respectively. The mean baseline FEV1 values after administration of ipratropium bromide were significantly higher than after placebo administration (p less than 0.05). However, there was no correlation between the degree of bronchodilatation and dose-ratios for methacholine and adenosine. The findings of the present study implicate vagal reflexes in the bronchospastic response induced by inhaled adenosine in asthma.

Adenosine↗

The influence of ipratropium bromide in the recovery phase of methacholine induced-bronchospasm.

BACKGROUND: The protective effect of Ipratropium Bromide (IB) in the methacholine-induced bronchospasm is well known from some time. The objective of the present study was to assess whether a pretreatment with IB may influence the subsequent phase of methacholine-induced bronchospasm relief. METHODS: Sixteen patients with bronchial hyper-reactivity (PD20 FEV1 < 200 microg) were randomly assigned to three methacholine challenge tests at a 48 to 72 hours interval apart. In the first test IB was inhaled before the challenge (pre-IB), in the second IB was administered soon after the PD20 FEV1 (post-IB), and in the third no treatment was given (control). RESULTS: The pre-IB PD20 FEV1 (695 +/- 587.6 microg) was significantly greater (p < 0.0001) than that of post-IB (82.2 +/- 49.18 microg) and of control (73.9 +/- 41.8 microg). The dose response slope (DRS) (decline percentage of FEV1/cumulative methacholine dose), in pre-IB was greatly lower (p < 0.0001) than that in post-IB and in control. During the bronchospasm relief phase, the increase of FEV1 measured after 5, 10, 15, 30 and 60 minutes from the PD20 FEV1 was significantly greater in post-IB (p < 0.05) compared with the other two conditions. Conversely, the recovery slope (RS) (increase percentage of FEV1 at 60 minutes after PD20 FEV1 x cumulative methacholine dose) was significantly more efficient (p < 0.001) in pre-IB than in post-IB and in control. CONCLUSION: In conclusion, ipratropium bromide confirmed to have a good protective activity against methacholine-induced bronchospasm; the pre-administration of ipratropium bromide showed also a positive effect on the recovery phase.

Administration, Inhalation↗

A case of fatal methyl bromide poisoning.

A case of preventable fatality and a nearly greater disaster as a result of methyl bromide fumigation of a restaurant is presented. Methyl bromide is a nearly odorless, volatile hydrocarbon used as a fumigant in the food industry. As a result of this episode, recommendations are made for worker and community notification of the hazards involved whenever fumigation takes place. Addition of a mucosal irritant or olfactory stimulant is recommended to provide warning for methyl bromide exposure.

Fumigation↗

[Distigmine bromide induced Parkinsonism. A case report].

A 74-year-old man became unable to walk two days following the initiation of administration of oral distigmine bromide, 10 mg per day, for his constipation. Neurological examination revealed bradykinesia, rigidity and fine postural tremor without laterality. T2 weighted MRI showed mild front-temporal atrophy and multiple hyperintensities in both deep white matters. His symptoms fully improved one week after discontinuance of distigmine bromide. This is the first case report of distigmine bromide induced Parkinsonism.

Aged↗

[A study of the peripheral quaternary ligand binding site of cholinesterase with the use of ethidium bromide].

The peripheral binding site of horse serum cholinesterase (EC 3.1.1.7) for quaternary ligands was investigated by fluorescent probing with the use of ethidium bromide. Spectral evidence for the participation of the tryptophan indole group of the peripheral site of horse serum cholinesterase in the formation of a cholinesterase complex with ethidium bromide is presented. The mechanism of cholinesterase effect on ethidium bromide fluorescence is proposed.

Animals↗

Inhaled formoterol versus ipratropium bromide in chronic obstructive pulmonary disease.

BACKGROUND: Short-acting anticholinergic bronchodilator, ipratropium bromide has been recommended as first-line drug in chronic obstructive pulmonary disease (COPD). More recently, long acting beta2-agonist (LABA) bronchodilators such as formoterol have been shown to be useful in COPD. Limited information is available on the relative efficacy of these two drugs in COPD. METHODOLOGY: A randomised, double-blind, cross-over, placebo-controlled study was carried out. Forty-four stable patients with COPD received single doses of formoterol (12 microg), ipratropium bromide (40 microg) or placebo, administered through a metered-dose inhaler on three consecutive days in a random order. Spirometry, static lung volumes, pulse rate and blood pressure, and assessment of sensation of dyspnoea at rest using a visual analog scale (Borg Scale) were recorded at baseline. Subsequently, these were repeated for assessment of response: spirometry at 5, 30 and 60 minutes and static lung volumes, pulse rate, blood pressure and dyspnoea measurement at 60 minute. RESULTS: Formoterol resulted in greater immediate improvement in lung function, with the change in FEV1 at 5 min being greater than that observed with ipratropium. The changes in static lung volumes were similar between the two but superior to placebo. Both the drugs reduced dyspnoea. Formoterol produced a significantly greater increase in heart rate and systolic blood pressure as compared to ipratropium, although the magnitude of these changes was small and clinically unimportant. CONCLUSIONS: Single therapeutic doses of formoterol and ipratropium bromide are equally effective in improving lung function and reducing dyspnoea. However, formoterol appears to be a better bronchodilator producing a faster improvement in lung function.

Administration, Inhalation↗

Increase in mitochondrial DNA quantity and impairment of oxidative phosphorylation in bovine fibroblast cells treated with ethidium bromide for 15 passages in culture.

Bovine fetal fibroblast cells were treated with ethidium bromide at a low concentration for 15 passages in culture to determine its effect on mitochondrial DNA copy number and on cell metabolism. Mitochondrial membrane potential and lactate production were estimated in order to characterize cell metabolism. In addition, mitochondrial DNA ND5 in proportion to a nuclear gene (luteinizing hormone receptor) was determined at the 1st, 2nd, 3rd, 10th, and 15th passages using semi-quantitative PCR amplification. Treated cells showed a lower mitochondrial membrane potential and higher levels of lactate production compared with control cells. However, the mitochondrial DNA/nuclear DNA ratio was higher in treated cells compared with control cells at the 10th and 15th passages. This ratio changed between the 3rd and 10th passages. Despite a clear impairment in mitochondrial function, ethidium bromide treatment did not lead to mitochondrial DNA depletion. It is possible that in response to a lower synthesis of ATP, due to an impairment in oxidative phosphorylation, treated cells develop a mechanism to resist the ethidium bromide effect on mtDNA replication, resulting in an increase in mitochondrial DNA copy number.

Animals↗

[Effects of salbutamo and ipraopium bromide inhalation on pulmonary function in young children with asthmatoid bronchitis].

OBJECTIVE: The efficacy of bronchodilator in asthmatoid bronchitis remains controversial. This study was designed to investigate the effects of bronchodilators, salbutamo and ipraopium bromide, on the pulmonary function in young children with this disease. METHODS: Pulmonary function tests were performed in 20 children with asthmatoid bronchitis (2 months-2.5 years of age) before and 30, 60, and 120 minutes after salbutamo and ipratropium bromide inhalation. The indexes of pulmonary function measured included tidal breathing flow volume (TBFV) loop, percent of tidal volume to peak tidal expiratory flow (%V-PF), terminal flows per peak expiratory flow (25/PF), peak tidal expiratory flow (PTEF), rate of mid-expiratory to mid-inspiratory flow (ME/MI), respiratory rate (RR) and tidal volume per kilogram (TV/kg). RESULTS: Before drug inhalation, the descending branch of the TBFV loop was depressed. The PTEF shifted forward and %V-PF (0.19 +/- 0.04) and 25/PF (0.42 +/- 0.11) decreased. These changes did not improve and the remaining indexes, RR, ME/MI and TV/kg, 30, 60, and 120 minutes after drug inhalation also remained similar to before inhalation. CONCLUSIONS: Salbutamo and ipratropium bromide inhalation did not improve the airway resistance and ventilation function in children with asthmatoid bronchitis. This suggests that the efficacy of bronchodilator in the treatment of this disease is doubtful.

Administration, Inhalation↗

[Inhalation bronchodilators in infancy--comparative study between salbutamol and ipratropium bromide].

The effectiveness of bronchodilators in infancy still remains uncertain. The objective of the present study was, on the basis of clinical scores, to determine the effect of salbutamol and ipratropium bromide in the treatment of acute airways obstruction in infants. For this purpose, we investigated a total of 22 infants whose ages ranged between 1 and 12 months and who were randomized to three different treatment groups. Infants in group 1 were given 0.9% NaCl to inhale, those in group 2 received ipratropium bromide, and those in group 3 salbutamol. The response to treatment was assessed on the basis of a decrease in the clinical score. A statistically significant decrease in the score was found only for those infants given ipratropium to inhale. None of the infants in this group failed to respond to treatment. Ipratropium bromide proved to be more effective than salbutamol in the treatment of infants with acute airways obstruction.

Airway Obstruction↗

Localization of bronchial response to ipratropium bromide by respiratory impedance measurement in asthmatics.

In 10 asthmatic subjects, the influence of 0.040 mg ipratropium bromide on impedance (Z) of the respiratory system (rs) was determined after cold air challenge. Cold air inhalation caused a significant increase of respiratory resistance (Rrs) at frequencies between 8 and 32 Hz. This increase of Rrs was more pronounced at lower frequencies and, therefore, Rrs became frequency dependent. Respiratory reactance (Xrs) decreased at all frequencies, resulting in an increase of resonant frequency. These changes were compatible with a peripheral airway obstruction and a decrease of airway compliance, according to Mead's analog of the respiratory system. Five min after inhalation of ipratropium bromide, a significant decrease of Rrs between 8 and 28 Hz and a significant increase of Xrs at all frequencies were observed, resulting in a decrease of resonant frequency. Ipratropium bromide significantly reversed the peripheral broncho-constriction induced by cold air challenge.

Adolescent↗

Mutagenic effects of lead (II) bromide.

The mutagenicity of lead (II) bromide (a combustion product of the gasoline additives lead (IV) tetraethyl and 1,2-dibromoethane) was investigated using various strains of bacteria. Taking prodigiosin (the red pigment) production as a marker, lead (II) bromide was found to be mutagenic in S. marcescens, leading to the appearance of white mutant colonies that are unable to produce such a pigment. This compound was also found to be mutagenic in E. coli KMBL1851, resulting in the appearance of rifampicin-resistant mutants in addition to Met+ and His+ revertants. Some of the S. marcescens mutants were found to be reversible, able to resynthesize prodigiosin. Differences in the sensitivity to antibiotics as well as in the biochemical properties were detected between the mutants and their corresponding wild types. Lead (II) bromide gave positive results in the Ames test performed with strain TA 1535.

Anti-Bacterial Agents↗

[The toxicity of sanguinarine compared to a number of other DNA-tropic compounds for ethidium bromide-sensitive and -resistant transformed murine fibroblasts in culture].

A natural DNA-intercalator plant benzo-c-phenanthridine alkaloid sanguinarine is more toxic for mouse transformed fibroblast L-cells in culture than synthetic DNA-intercalator ethidium bromide (EtB) and alkaloid berberine. Dimidium bromide is also an inhibitor of the L-cell growth. In assay conditions, growth of L-cells is stopped by 1.5 x 10(-5) M of sanguinarine. Lebr-625 cells, resistant to 25 micrograms/ml of EtB, have sanguinarine sensitivity close to that of L-cells, but Lebr-625 cells are resistant to dimidium bromide. Sanguinarine is more toxic for L-cells in culture than the anticancer drug cis-PtNH3)2Cl2. Trans-Pt(NH3)2Cl2 is less toxic for these cells. The strong toxicity of sanguinarine for L- and Lebr-625 cells in culture, as compared to other DNA-complexing drugs, seems to be associated with the wide range of potential cell targets for sanguinarine influence. Besides the inhibition of nucleic acid metabolism reactions, characteristic of DNA-intercalators, and disruption the mitochondrial ATP synthesis, also characteristic of organic heterocyclic cationic molecules of DNA-intercalators, sanguinarine can modify the thiol groups of enzymes including SH-sensitive membrane-bound Na+, K(+)-ATPase of cerebral cortex and Ca2(+)-ATPase of skeletal muscle sarcoplasmic reticulum fragments.

Alkaloids↗

Effect of cimetropium bromide and other antispasmodic compounds on in vitro guinea-pig gallbladder.

The effect of cimetropium bromide, a new antimuscarinic compound, on bethanechol- and electrically-induced contractions was studied on isolated guinea-pig gallbladder. Atropine and two other widely employed antispasmodics (i.e., rociverine and octylonium bromide) were employed as reference compounds. Cimetropium and atropine proved to be competitive antimuscarinics, their pA2 being 7.77 +/- 0.14 and 8.31 +/- 0.14, respectively. On the contrary, rociverine displayed a dual effect being a competitive antagonist at low (up to 10(-5) mol/l) and a mixed one at high (greater than 10(-5) mol/l) concentrations. When tested against bethanechol- and electrically-induced contractions, all the compounds, with the exception of octylonium bromide, showed a concentration-dependent relaxant effect. In both experimental conditions, the potency of cimetropium was of the same order of magnitude as that of atropine and 150-200 times higher than that of rociverine. These data, together with the reported activity on human gallbladder in vivo and the well known involvement of cholinergic system in the control of gallbladder motility, could represent the rationale for the clinical use of cimetropium in the treatment of biliary colics as well as spasms of biliary tree.

Animals↗

Treatment of irritable bowel syndrome with prifinium bromide.

Prifinium bromide, an anticholinergic agent, was given to patients with irritable bowel syndrome in an open trial to evaluate the drug's clinical efficacy. The trial lasted four weeks, although two of the 40 patients were treated for only two weeks. Prifinium bromide was judged beneficial in 28 patients (70%), slightly beneficial in six (15%), and not beneficial in six (15%). One case of moderate constipation was the only side effect encountered. In conclusion, prifinium bromide is considered a valuable drug for the management of irritable bowel syndrome.

Adolescent↗