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PubMed1990

Bronchodilator responses to salbutamol followed by ipratropium bromide in partially reversible airflow obstruction.

We have performed a retrospective survey on 296 patients, who attended the Respiratory Function Unit at Guy's Hospital to have their bronchodilator responses (BR) tested. The aim of the study was to see the effect of ipratropium bromide (IB) in a group of patients with incomplete reversibility after salbutamol (S). Patients were routinely given salbutamol and ipratropium bromide sequentially by inhalation, and spirometric changes were recorded after each drug. We identified two groups: Group A, 95 patients with FEV1 response greater than or equal to 0.2 l after either drug and FEV1 less than 80% predicted after salbutamol; and, Group B, 49 with change in FEV1 less than 0.02 l, FVC less than 80% predicted after salbutamol and an improvement in FVC greater than or equal to 0.33 l. Seventy-nine of the 95 patients in Group A also had an FVC response. In Group A, age was negatively correlated with response to salbutamol (r = -0.41, P less than 0.0001), and within Group B baseline FVC was negatively correlated with response to ipratropium bromide (r = -0.30, P = 0.03). There were no differences in age, sex, or doses given to each group (median dose: salbutamol, 800 micrograms, ipratropium bromide 120 micrograms). Baseline FEV1 and FVC (% predicted) were significantly higher in FEV1 responders. Mean (SD) FEV1 were 43% (14) in Group A vs. 29% (14) in Group B, while FVC were 62% (16) vs. 47% (13), P less than 0.001. Responses to ipratropium bromide were more frequent in Group B; in Group A 87% improved after salbutamol and 26% after ipratropium bromide, while in Group B 68% responded to salbutamol and 47% to ipratropium bromide (P = 0.03). Most patients responded to salbutamol, but in 33% ipratropium bromide had an additional effect. The FEV1 response to salbutamol declined with age. Isolated volume responders had more severe airflow obstruction, had less responses to salbutamol and were more likely to show a response to ipratropium bromide. These results support a trial of ipratropium bromide in patients with inadequate beta responsiveness, especially in those with severe airflow obstruction.

Administration, Inhalation↗
PubMed2002

Randomized, double-blind, placebo-controlled trial of intravenous salbutamol and nebulized ipratropium bromide in early management of severe acute asthma in children presenting to an emergency department.

BACKGROUND: In acute severe asthma, treatment must be initiated early to reverse the pathophysiology that may render airways less responsive to bronchodilation. The addition of nebulized ipratropium bromide to initial emergency department therapy improves pulmonary function, but it is unclear whether this approach results in earlier hospital discharge. The early use of bolus intravenous salbutamol has also been shown to improve outcome, including earlier discharge. We therefore assessed the relative benefits of intravenous salbutamol and nebulized ipratropium bromide in the early management of acute severe asthma in children by a double-blind, randomized, controlled trial. METHODS: This study was undertaken at a tertiary children's hospital, The Children's Hospital at Westmead, The Royal Alexandra Hospital for Children, Westmead, Sydney, Australia. Only children with severe acute asthma as determined by the National Asthma Campaign guidelines criteria and pulmonary index were included. All children received initial nebulized salbutamol therapy (2.5-5 mg salbutamol in 4 mL of normal saline depending on age) at initial emergency department presentation. If asthma remained severe 20 mins later, an intravenous cannula was inserted and intravenous methylprednisolone (1 mg/kg) was administered to all children receiving nebulized salbutamol every 20 mins. Children were then randomized to one of three groups: intravenous salbutamol (15 microg/kg as a single bolus over 10 mins), ipratropium bromide (250 microg), or intravenous salbutamol plus ipratropium bromide. All observers were blinded to treatment groups. Children were randomly assigned to receive a single-dose intravenous bolus of either saline or salbutamol and either nebulized saline or ipratropium bromide determined by a number generated randomly in the hospital pharmacy. The primary outcomes were recovery time and discharge time of each group. Respiratory and hemodynamic monitoring were continuous during the first 2 hrs of the study and then children were monitored clinically for 24 hrs. RESULTS: A total of 55 children with acute severe asthma were entered into the study over an 18-month period. The three groups were similar demographically, with a mean age of 5.9 yrs, and mean duration of attack of 19.6 hrs. No side effects or treatment intolerance were reported. Children in the groups that received intravenous salbutamol had a significant reduction in recovery time to achieving second hourly inhaled salbutamol (p =.008) compared with those administered inhaled bronchodilator alone. The addition of ipratropium bromide to intravenous salbutamol provided no significant further benefit in terms of nebulizer therapy (intravenous salbutamol compared with intravenous salbutamol plus ipratropium bromide). Children administered intravenous salbutamol ceased supplemental oxygen therapy earlier than those administered ipratropium alone at 12 hrs post-randomization (p =.0003). Children administered intravenous salbutamol could be discharged from the hospital 28 hrs earlier than those administered ipratropium bromide (p =.013). CONCLUSION: Children administered intravenous salbutamol for severe acute asthma showed a more rapid recovery time, which resulted in earlier discharge from the hospital than those administered inhaled ipratropium bromide. There was no additional benefit obtained by combining ipratropium bromide and intravenous salbutamol administration.

Adolescent↗
PubMed2006

Bromide as a marker to measure adherence to drug therapy.

OBJECTIVE: Several methods have been described to measure adherence to prescribed drug therapy. However, most of these have been shown to be inaccurate. Bromide is an anion that is readily absorbed in the gut and has an elimination half-life of about 12 days. In the present study, we investigated the pharmacokinetic properties of bromide with the objective to use it as a measure of drug adherence. METHODS: Three groups of each 8 healthy volunteers took 15, 24 or 30 mg potassium bromide, respectively, daily for 20 weeks. Serum concentrations of bromide were measured every two weeks. RESULTS: There was a linear relationship between the daily dosage taken and the mean increase of bromide concentration. In every group considerable inter-individual variability was seen. Correction for body weight resulted in an improved correlation between daily bromide dose and increase in concentration (r=0.78, p<0.01). CONCLUSIONS: Unfortunately, the inter-individual variability in clearance of bromide was considerable. This limits the use of bromide to primarily measuring adherence in individual patients during long term follow-up. Bromide appears to be a potentially useful marker to be added to drugs for assessment of individual adherence to long term drug therapy. This needs to be investigated in various patients, particularly for patients with relatively asymptomatic diseases (e.g. hypertension).

Bromides↗
PubMed1982

A study of the actions of bromide on frog sympathetic ganglion.

The effects of sodium bromide on the bullfrog sympathetic ganglion were studied by extracellular and intracellular recording techniques. Equimolar replacement of sodium chloride (112 mM) by sodium bromide in Ringer's solution caused hyperpolarization (means = 7.4 mV) of ganglion cells, and antidromically evoked spikes showed increased rates of rise as well as prolonged post-spike positivity. These effects, rapid in onset, returned to control values after approximately 30 min of continued exposure to bromide Ringer. Orthodromic synaptic transmission was not impaired by bromide (84-112 mM); instead it produced increased post-spike negativity and occasionally, stimulus-bound repetitive postganglionic responses (SBR) to each single preganglionic stimulus. This synaptic enhancement persisted as long as exposure to bromide continued. Since ethanol also causes responses, its interaction with bromide was tested and pronounced synergism was found in which 95% of ganglion cells displayed repetitive orthodromic responses to each single preganglionic stimulus. The present and previous studies suggest that bromide and ethanol act at the unmyelinated presynaptic nerve terminal to generate stimulus-bound repetitive responses. The transient nature of the hyperpolarization produced by bromide argues against a mechanistic role in its anticonvulsant action. The persistent synaptic excitatory effects of bromide, however, may have implications for the role of chloride channels in anticonvulsant mechanisms or in epileptogenesis.

Animals↗
PubMed2006

Interaction of pyridostigmine bromide and N,N-diethyl-m-toluamide alone and in combination with P-glycoprotein expressed in Escherichia coli leaky mutant.

P-glycoprotein (P-gp), the most extensively studied ATP-binding transporter, functions as a biological barrier by extruding toxic substances and xenobiotics out of the cell. This study was carried out to determine the effect of N,N-diethyl-m-toluamide (DEET) and pyridostigmine bromide (PB), alone and in combination, on P-gp expression using Escherichia coli leaky mutant transformed with Mdr1 gene (pT5-7/mdr1), which codes for P-gp or lactose permease (pT5-7/lacY) as negative control. Also, daunomycin (a known P-gp sustrate) was used as a positive control and reserpine (a known P-gp inhibitor) served as a negative control. An in vitro cell-resistant assay was used to monitor the potential of test compounds to interact with P-gp. Following exposure of the cells to pyridostigmine bromide or daunomycin, P-gp conferred significant resistance against both compounds, while reserpine and DEET significantly inhibited the glycoprotein. Cells were grown in the presence of noncytotoxic concentrations of daunomycin, pyridostigmine bromide, reserpine, or DEET, and membrane fractions were examined by Western immunoblotting for expression of P-gp. Daunomycin induced P-gp expression quantitatively more than pyridostigmine bromide, while reserpine and DEET significantly inhibited P-gp expression in cells harboring mdr1. Photoaffinity labeling experiment performed with the P-gp ligand [125I]iodoarylazidoprazosin demonstrated that compounds that induced or inhibited P-gp transport activity also bound to P-gp. DEET was also found to be a potent inhibitor of P-gp-mediated ATPase activity, whereas pyridostigmine bromide increased P-gp ATPase activity. Cells expressing P-gp or lac permease were exposed to pyridostigmine bromide and DEET, alone and in combination. Noncytotoxic concentrations of DEET significantly inhibited P-gp-mediated resistance against pyridostigmine bromide, resulting in a reduction of the number of effective drug interactions with biological targets. An explanation of these results might be that DEET is a third-generation inhibitor of P-gp; it has high potency and specificity for P-gp, it inhibits hydrolysis of ATP, it exerts no appreciable impact on cytochrome P-450 3A4, and it prevents transport of xenobiotics, such as pyridostigmine bromide, out of the cell. This conclusion explains, at least in part, the increased toxicity and bioavailability of pyridostigmine bromide following combined administration with DEET. This study improves our understanding of the basis of chemical interactions with DEET by defining the ability of drugs to interact with P-gp either as inhibitors or substrates, which may in turn lead to altered efficacy or toxicity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Pharmacokinetics and clinical utility of sodium bromide (NaBr) as an estimator of extracellular fluid volume in horses.

The purpose of this study was to describe the pharmacokinetics of bromide in horses and to evaluate the corrected bromide space as an indicator of extracellular fluid volume (ECFV) in horses after the administration of a single dose of bromide by intravenous infusion. Sodium bromide (30 mg/kg of body weight, IV) was administered to 6 clinically healthy mares over a period of 3 minutes. Blood samples were collected before infusion and at intervals between 0.5 hours and 53 days after infusion. Mean elimination half-life (harmonic mean) was 126 hours (5.2 days), clearance was 1.4 +/- 0.09 mL/(kg x h), area under the curve was 17,520 +/- 1,100 microg x h/mL. and volume of distribution (steady state) was 0.255 +/- 0.015 L/kg. The mean corrected bromide space was determined from the volume of distribution (steady state) and the serum concentrations of bromide at equilibration. Corrected bromide space, an estimate of ECFV, was 0.218 +/- 0.01 L/kg. The conclusion was made that ECFV of horses can be estimated by measuring bromide concentrations in a preinfusion serum sample and a sample obtained 5 hours after the administration of bromide.

Animals↗
PubMed2005

The role of tiotropium bromide, a long-acting anticholinergic bronchodilator, in the management of COPD.

Bronchodilator therapy forms the mainstay of treatment for symptomatic patients with COPD. Long-acting bronchodilators, which maintain sustained airway patency over a 24-hour period, represent an advance in therapy. Tiotropium bromide is a new long-acting inhaled anticholinergic agent with superior pharmacodynamic properties compared with the short-acting anticholinergic, ipratropium bromide. Tiotropium bromide has been consistently shown to have a greater impact than ipratropium bromide on clinically important outcome measures such as health status. The mechanisms of clinical benefit with tiotropium bromide are multifactorial, but improved airway function, which enhances lung emptying and allows sustained deflation of over-inflated lungs, appears to explain improvements in dyspnea and exercise endurance in COPD. Inhaled tiotropium bromide therapy has also been associated with reduction in acute exacerbations of COPD as well as reduced hospitalizations. The safety profile of tiotropium bromide is impressive: dry mouth is the most common adverse event and rarely necessitates termination of the drug. No tachyphylaxis to tiotropium bromide has been demonstrated in clinical trials lasting up to 1 year. There is preliminary information that the combination of long-acting anticholinergics and long-acting beta2-adrenoceptor agonists provides additive physiological and clinical benefits. According to recent international guidelines, long-acting bronchodilators should be considered early in the management of symptomatic patients with COPD in order to achieve effective symptom alleviation and reduction in activity limitation. Tiotropium bromide, because of its once-daily administration and its established efficacy and tolerability profile, has emerged as an attractive therapeutic option for this condition.

Bronchodilator Agents↗
PubMed1997

Clinical efficacy of propantheline bromide in neurocardiogenic syncope: pharmacodynamic implications.

The pharmacological response with tilt-table testing predicts long-term efficacy in neurocardiogenic syncope. However, beta-blockers for neurocardiogenic syncope are often not tolerated or are ineffective. Since cholinergic tone is important in the efferent part of the neurocardiogenic reflex, we investigated the pharmacodynamics and efficacy of propantheline bromide in preventing neurocardiogenic syncope. We studied 16 patients (11 males) with a mean age of 48.8 (+/- 15.1) years with presyncope or syncope and who had positive baseline tilt-table studies at a mean of 15.8 (+/- 10.3) minutes into the upright 60 degrees tilt. They were given propantheline bromide orally, an anticholinergic agent, at a dose of 64.3 (+/- 21.8) mg/day for 7 days, and tilt-table testing was repeated 1 hour after readministration of propantheline bromide, 30 mg orally. After propantheline bromide treatment, 13 of 16 patients (81%) had no inducible presyncope or syncope on repeat tilt-table testing. In this group of responders, the mean minimum heart rate during upright tilt-table testing increased from 43.2 (+/- 77.3) beats/min to 77.3 (+/- 17.2) beats/min after propantheline bromide (p < 0.005). More significantly, the minimum mean arterial blood pressure increased from 42.2 (+/- 25) mmHg to 81.3 (+/- 16.7) mmHg (p < 0.0005) during upright tilt. At a follow-up of 15.2 (+/- 7.4) months, in the responder group (12 patients with long-term follow-up), the average dose of propantheline bromide was 32.5 (+/- 23.8) mg/day, which was significantly reduced from the initial dose (p < 0.05). A clinical recurrence of symptoms occurred in only 4 out of 12 patients on propantheline bromide (33%), none of which were directly attributable to drug failure. It was concluded from this study that propantheline bromide is highly effective in preventing neurocardiogenic syncope. In addition, propantheline bromide's effectiveness is more than would be expected by prevention of cardioinhibition in neurocardiogenic syncope and would support a role for direct cholinergic control of vascular tone.

Adolescent↗
PubMed1999

Antimuscarinic, calcium channel blocker and tachykinin NK2 receptor antagonist actions of otilonium bromide in the circular muscle of guinea-pig colon.

We have analyzed, by the sucrose gap method, the action of otilonium bromide, a quaternary ammonium derivative in use for the symptomatic therapy of irritable bowel syndrome, on the electrical and mechanical responses initiated by different stimuli in the circular muscle of the guinea-pig proximal colon. Otilonium bromide produced a concentration-dependent inhibition of membrane depolarization (IC50 4.1 microM), action potentials (APs) and contraction (IC50 3.7 microM) produced by the muscarinic receptor agonist, methacholine. It also produced a concentration-dependent inhibition of APs and accompanying contraction (IC50 31 microM) produced by KCl (30 mM), and had a biphasic effect on the cholinergic excitatory junction potential (e.j.p.) produced by single pulse electrical field stimulation: at low concentrations (0.1-0.3 microM) otilonium bromide enhanced the e.j.p. and, at higher concentrations (IC50 22 microM and 16 microM toward depolarization and contraction), produced a concentration-dependent inhibition. Otilonium bromide eliminated the APs superimposed on the depolarization induced by the tachykinin NK1 receptor agonist, [Sar9]substance P-sulphone and suppressed the corresponding contraction (IC50 43 microM) but had little effect on the sustained membrane depolarization induced by this agonist. On the other hand, otilonium bromide produced a similar inhibitory effect on both membrane depolarization and contraction (IC50 38 microM and 45 microM, respectively) induced by the tachykinin NK2 receptor agonist [betaAla8]neurokinin A (4-10). When tested in the presence of nifedipine (1 microM), otilonium bromide had no effect on the membrane depolarization induced by [Sar9]substance P-sulphone but inhibited in a concentration-dependent manner the depolarization induced by [betaAla8]neurokinin A (4-10) (IC50 41 microM). In contrast, the blocker of receptor-operated cation channels, SKF 96365, inhibited with similar potency the depolarization induced by both [Sar9]substance P-sulphone and [betaAla8]neurokinin A (4-10) (IC50 60 microM and 54 microM, respectively). In radioligand binding experiments otilonium bromide produced a concentration-dependent inhibition of the binding of both an agonist ([125I]neurokinin A, Ki 7.2 microM) and an antagonist ([3H]SR 48968, Ki 2.2 microM) to membranes of Chinese hamster ovary cells transfected with the human tachykinin NK2 receptor. In conclusion, the present findings demonstrate that, in the microM range of concentrations, otilonium bromide acts as a muscarinic and tachykinin NK2 receptor antagonist and as a calcium channel blocker. The latter property is likely to account for its ability to suppress contraction initiated by the tachykinin NK1 receptor agonist. Therefore multiple mechanisms of action account for the ability of otilonium bromide to reduce stimulated motility of intestinal smooth muscle.

Animals↗
PubMed1998

Genotoxicity in workers exposed to methyl bromide.

To address the genotoxicity of in vivo methyl bromide (CAS 74-83-9) exposure in humans, we collected blood and oropharyngeal cells as part of a cross-sectional morbidity study of methyl bromide-exposed fumigation workers and their referents. Micronuclei were measured in lymphocytes and oropharyngeal cells, and hypoxanthine-guanine phosphoribosyl transferase gene (hprt) mutations were measured in lymphocytes. A total of 32 workers and 28 referents provided specimens. Among current non-smokers, mean hprt variant frequencies (Vfs) were found to be elevated among workers compared to referents (geometric mean: workers=4.49x10(-6), referents=2.96x10-(6); two-sided p=0.22); this difference was more pronounced among workers with 4 h or more of recent methyl bromide exposure compared to referents (geometric mean: workers=6.56x10(-6), referents=2.96x10(-6); two-sided p=0.06). Mean oropharyngeal cell micronuclei were higher among workers compared to referents (mean: workers=2.00, referents=1.31; two-sided p=0.08); the results were similar when workers with 4 h or more of recent methyl bromide exposure were compared to referents (mean: workers=2.07, referents=1.31; two-sided p=0.13). No consistent differences between workers and referents were observed for frequencies of kinetochore-negative lymphocyte micronuclei, or kinetochore-positive lymphocyte micronuclei. The study was limited by a sample size sufficient only for detecting relatively large differences, absence of a reliable method to measure the intensity of workplace methyl bromide exposures, and relatively infrequent methyl bromide exposure (e.g., the median length of exposure to methyl bromide during the 2 weeks preceding the survey was 4 h). In conclusion, our findings provide some evidence that methyl bromide exposure may be associated with genotoxic effects in lymphocytes and oropharyngeal cells. Further study on the genotoxicity of methyl bromide exposure in humans is warranted.

Adult↗
PubMed2000

Mechanistic role of benzylic bromides in the catalytic autoxidation of methylarenes.

Different pathways for benzylic bromide transformations were examined under conditions of cobalt-bromide catalysis in acetic acid. It has been shown that benzylic bromides participate in the catalytic cycle through their catalyzed and noncatalyzed oxidation, through their reaction with Co(III), and through cobalt(II)-catalyzed solvolysis. The rates of the direct reduction of Co(III) by several benzylic bromides were measured under an argon atmosphere; the reaction occurs by a mechanism involving two forms of Co(III). The same reaction under an oxygen atmosphere initiates the cobalt-bromide-catalyzed oxidation of benzyl bromide, thus leading to the regeneration of inorganic bromide and the fast reduction of Co(III). Solvolysis of benzylic bromides plays only a minor role in the regeneration of inorganic bromide in glacial acetic acid.

Journal Article↗
PubMed1994

Behavioral evidence for modified receptor sensitivity in rat brain induced by methyl bromide exposure.

To clarify the neurochemical basis of methyl bromide toxicity in rats, we measured changes in the sensitivity of cerebral monoamine, dopamine (DA) and norepinephrine (NE) receptors, using abnormal behavior and locomotor activity as indicators of receptor sensitivity. Apomorphine and clonidine were used as specific agonists of DA (D1 and D2) and NE (alpha 2) receptors, respectively. In the first experiment, rats were exposed to methyl bromide gas at 25-200 ppm for 8hr once or to methyl bromide at 5-50 ppm 8hr a day for 7 days. The intensity of stereotyped oral (STO) behavior produced by an injection of apomorphine, 0.5 mg/kg i.p., was rated over the following 28 days. The STO behavior of rats exposed to methyl bromide (MB rats) was much more intense than in air-exposed (control) rats. This finding strongly suggests that the sensitivity of striatal DA, D1 and D2, receptors to apomorphine was increased by methyl bromide exposure. In the second experiment, rats were exposed to 50 ppm methyl bromide for 8hr once or to 10-50 ppm methyl bromide 8hr a day for 7 days. Seven days after the final exposure, rats were injected with a small dose of apomorphine, 0.3 mg/kg i.p., and the counts of apomorphine-induced locomotor activity (ALA) were recorded. The ALA counts of MB rats were markedly higher than in the control rats. This finding suggests that the DA receptors in the nucleus accumbens of MB rats are more sensitive to apomorphine than those of control rats. In the third experiment, rats were exposed to 50 ppm methyl bromide, 8hr a day for one day or 7 consecutive days, and the degree of attenuation of locomotor activity following clonidine injection (CLA) was rated. CLA counting was performed 7 days after the final exposure. CLA counts in MB rats were not attenuated as much as in the control rats. This indicates that the cerebral NE receptors, i.e., alpha 2-adrenoceptors, of MB rats may be less sensitive to clonidine than those of control rats. Increased behavioral sensitivity to apomorphine was observed in rats even when exposed to 5 ppm (TLV) methyl bromide.

Animals↗
PubMed1988

Use of ipratropium bromide in obstructive lung disease.

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of ipratropium bromide are reviewed. Ipratropium bromide, a synthetic quaternary isopropyl derivative of atropine, interrupts vagally mediated bronchoconstriction by inhibiting the cyclic guanosine 3',5'-monophosphate system at parasympathetic nerve endings. Ipratropium bromide is poorly absorbed after oral and inhaled administration but diffuses rapidly into tissue after i.v. or i.m. administration. The elimination half-life is 3.2-3.8 hours. After inhalation, the drug is eliminated in the urine and feces. The bronchodilatory effect of ipratropium bromide in stable chronic obstructive pulmonary disease appears to be comparable, and may be superior, to that of the beta-sympathomimetic agents. In acute exacerbations, ipratropium bromide is useful but may not be the preferred agent because of a delayed onset of action (within 15 minutes; mean dose-dependent duration of effect, three to five hours). Combination therapy with other bronchodilating drugs has proved useful. Ipratropium bromide may be a useful adjunctive agent in the treatment of asthma. Since the onset of action is delayed, ipratropium bromide should not be used as single-drug therapy in an acute asthmatic exacerbation. Reported adverse effects, including cough, nausea, palpitations, dry mouth, nervousness, gastrointestinal distress, and dizziness, have been mild. The usual dosage is two inhalations (36 micrograms) four times daily, and the maximum number of doses per day should not exceed 12. Although ipratropium bromide is currently indicated only for maintenance therapy in stable chronic bronchitis and emphysema, it may be useful as adjunctive therapy in asthma and in the management of acute exacerbations of chronic bronchitis and asthma. Additional experience in a variety of chronic obstructive pulmonary disorders will help to clarify the role of ipratropium bromide in the treatment of obstructive pulmonary disease.

Asthma↗
PubMed1980

Pharmacological study of a new competitive neuromuscular blocking steroid, pipecurium bromide.

2 beta, 16 beta-Bis-(4'-dimethyl-1'-piperazino)-3 alpha, 17 beta-diacetoxy-5 alpha-androstane dibromide (pipecurium bromide, RGH-1106, Arduan), a newly synthetized bisquaternary steroid, produces competitive neuromuscular blockade in chicks, rats, cats, rabbits and dogs. The onset of paralysis is rapid. Pipecurium bromide is 2-4 times as potent as pancuronium bromide. The duration of action is about twice as long as that of pancuronium bromide in equiactive doses. Neostigmine rapidly and completely antagonises the neuromuscular blockade caused by pipecurium bromide. Even one hundred times higher dose than the effective blocking dose (2-6 microgram/kg) does not influence the cardiovascular system. Higher doses (1-2 mg/kg) cause transient decrease in blood pressure, in 10-20 mg/kg doses pipecurium bromide has ganglion blocking effect. In 1 mg/kg dose pipecurium bromide does not release histamine. Many times higher doses than the effective dose administered for 20 days, do not cause any toxic damage to respirated beagle dogs. According to examinations in rats, the placentary transfer of pipecurium bromide is lower than 0.1%. According to preliminary clinical examinations pipecurium bromide is free from side effects, and elicits as well controllable muscle relaxation.

Action Potentials↗
PubMed1983

Mechanism of gastric antisecretory effects of nolinium bromide.

Nolinium bromide [2-(3,4-dichlorophenyl amino)-quinolizium bromide] inhibits histamine-stimulated gastric acid secretion by bullfrog gastric mucosa in vitro. Nolinium bromide was effective from both the secretory and the nutrient sides of the chambered mucosa. The inhibitory effects of secretory but not the nutrient nolinium bromide could be largely reversed by elevating the concentration of K+ of the secretory solution. The mechanisms of the inhibitory effects of nutrient nolinium bromide appeared to be different than those from the secretory side. Gastric microsomes highly enriched in H+, K+-ATPase activity (which has been identified as the proton pump) were used to elucidate the mechanism of nolinium bromide action. Nolinium bromide inhibits in a dose-dependent manner both the gastric H+, K+-ATPase activity and H+ uptake ability of the microsomes. Increasing concentrations of K+ could reverse the nolinium bromide inhibition of both the H+, K+-ATPase activity and vesicular H+ transport. The data strongly suggest that nolinium bromide interferes primarily with the K+-dependent phosphatase step and thereby reduces the turnover of the enzyme. The data have been discussed in the light of our present day knowledge on gastric H+ transport.

4-Nitrophenylphosphatase↗
PubMed1981

[Pharmacological studies of antispasmodics. III. Antispasmodic activity of 3-(di-2-thienylmethylene)-5-methyl-trans-quino-lizidinium bromide (HRS-902) on smooth muscle organs and its organ selectivity (author's transl)].

Pharmacological activities of HSR-902, a new antispasmodic agent, in gastrointestinal tract, biliary and urinary systems were compared with those of atropine, butylscopolamine bromide, timepidium bromide, prifinium bromide and diphemanil methylsulfate. In isolated smooth muscle organs (stomach, duodenum, ileum, colon, gall bladder and urinary bladder), anti-acetylcholine activities of HSR-902 were the most potent among these agents but its activity in urinary bladder, similar to findings in the cases of atropine and diphemanil methylsulfate, was relatively less potent than that of prifinium bromide, timepidium bromide and butylscopolamine bromide. Regarding the contractions of stomach, jejunum and ileum, which were induced by vagus nerve stimulation or acetylcholine, and on the ileum spontaneous motility, antispasmodic activities of HSR-902 were almost equal to or somewhat more potent than those of atropine, and its activities were more potent than those of prifinium bromide, timepidium bromide, diphemanil methylsulfate and butylscopolamine bromide. On the gall bladder pressure and the counts of perfusion through Oddi's Sphincter, these agents exhibited a similar inhibition and enhancement, respectively. In the case of urinary bladder contractions induced by pelvic nerve stimulation, these agents exhibited a weak inhibition. The inhibitory effect of HSR-902 was relatively less potent than that of other agents except atropine, which had little effect. HSR-902 was similar to atropine in this so-called "atropine-resistance".

Acetylcholine↗
PubMed1980

[The new anticholinergic bronchospasmolytic oxitropium bromide. Is long lasting protective effect through the night].

Oxitropium bromide (Ba 253, Boehringer, Ingelheim) is a scopolamine-like atropine derivate with a mode of action approximating to that of ipratropium bromide (Atrovent, Sch 1000). The peak effect and duration of bronchodilatation with oxitropium bromide appears to be better than that of ipratropium bromide. Fifteen patients with a stable chronic bronchial obstruction were investigated in a double blind cross-over study. The obstruction was partially reversible by beta-stimulation. The patients inhaled 0.2 mg oxitropium bromide or placebo at 9.30 p.m. after two controls of FEV1 at 9 p.m. and 9.15 p.m. We re-examined the patients at 7 a.m. and 7.15 a.m. the following day and observed a significant parasympathetic additional obstruction under placebo, whereas, under the medication with oxitropium bromide overnight, significant bronchodilation was observable. When 0.2 mg oxitropium bromide was given at 7.30 a.m. to all patients, those pretreated with placebo showed significantly better bronchodilation than those pretreated with oxitropium bromide. It is concluded that oxitropium bromide is a long-acting (10 hours) overnight bronchodilator. The bronchodilation is probably due to prolonged parasympathicolysis in the airways.

Adult↗
PubMed1994

Bromide pharmacokinetics in cystic fibrosis.

OBJECTIVE: Individuals with cystic fibrosis (CF) have altered kinetics for a number of drugs, most often an increased volume of distribution (Vd) per body weight and increased clearance per body weight. To further evaluate those differences, we studied bromide kinetics (Vd, elimination rate constant, and clearance) and body mass index in eight adults with mild-to-moderate forms of CF, 21 obligate carriers of the CF gene, and 21 healthy controls. Bromide distribution approximates the extracellular fluid volume and bromide is excreted unchanged by the kidney. DESIGN: Individuals were given a single oral dose of bromide (50 mg/kg), and serum bromide concentrations were measured over 4 weeks. Bromide pharmacokinetics (Vd, elimination rate constant, and clearance) were determined using a one-compartment model with first-order kinetics. Body mass index was determined for each individual. RESULTS: Individuals with CF had a significantly greater lean body mass per kilogram as estimated by body mass index compared with individuals in the obligate carrier and control groups. The mean (+/- SD) Vd per kilogram for the CF group (311 +/- 29 mL/kg) was significantly greater than that of the obligate carrier group (261 +/- 26 mL/kg) and the control group (274 +/- 30 mL/kg). However, the mean (+/- SD) Vd per square meter for the three groups was similar. The mean elimination rate constant for the CF group (3.55 +/- 0.98 x 10(-3)/h) was significantly greater compared with the mean elimination rate constant for the obligate carrier group (2.55 +/- 0.36 x 10(-3)/h) and the control group (2.58 +/- 0.49 x 10(-3)/h). The mean (+/- SD) clearance per kilogram was also significantly greater for the CF group (1095 +/- 283 microL/kg per hour) compared with the obligate carrier group (664 +/- 100 microL/kg per hour) and the control group (700 +/- 115 microL/kg per hour). CONCLUSIONS: These findings indicate that individuals with CF have a greater Vd per kilogram for bromide and drugs that distribute in the extracellular fluid volume because of their greater lean body mass per kilogram. The findings also suggest that individuals with CF have a greater renal clearance of bromide and presumably of other anionic drugs excreted by the kidney. The results emphasize the importance of body composition in drug disposition.

Adolescent↗