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PubMed1986

Pharmacology of the anticholinergic bronchospasmolytic agent flutropium bromide.

The anticholinergic agent (8r)-8-(2-fluoroethyl)-3 alpha-hydroxy-1 alpha H,tropanium bromide benzilic acid ester (flutropium bromide, Ba 598 BR) is a classic competitive antagonist of acetylcholine. In in vitro experiments it is more effective than atropine. In addition there are indications, that flutropium bromide may interfere with the anaphylactic reaction in a certain dose range in vitro. In in vivo experiments for the characterization of the anticholinergic properties flutropium bromide is also somewhat more effective than atropine after parenteral administration. Because of its quaternary structure no central anticholinergic effect is detectable. Furthermore, a poor enteral absorption is to be expected; this can be concluded from the low relative effectiveness after oral administration. After systemic administration, flutropium bromide is only slightly more effective than atropine. The duration of action is longer. After local administration as an aerosol it is superior to atropine with regard to both effectiveness and duration of action. Since in aerosol administration the ratio of the main effect to the most sensitive side effects, inhibition of salivary secretion, is 1:100, no side effects are to be expected even after high inhalational overdoses. Flutropium bromide can therefore be described as a preparation which is free of side effects. When used prophylactically it represents a therapeutic alternative to beta-mimetics and xanthine derivatives for most cases of obstructive airway diseases.

Animals↗
PubMed1988

Evaluation of the systemic anticholinergic activity of nasally administered ipratropium bromide.

Plasma concentrations of nasally inhaled ipratropium bromide were analyzed in eight healthy volunteers by using a sensitive radioreceptor assay (RRA). The rate of saliva secretion, heart rate and changes in visual accommodation were quantitated in order to measure possible systemic anticholinergic drug effects. 240 micrograms of ipratropium bromide (40 micrograms each nostril, repeated twice at 15 min intervals) were inhaled nasally in a double blind, randomized, placebo-controlled experiment. Ipratropium bromide absorbed fast, and peak plasma concentrations of the drug (257 +/- 55 pg/ml) were detected as soon as 5 min after the last inhalation (at 35 min from the beginning). The plasma levels of ipratropium bromide decreased rapidly, being only 86 +/- 7 pg/ml one hour after the last inhalation. These low concentrations of ipratropium bromide indicate that only a small portion of it absorbs after nasal application, which is consistent with the lack of any systemic anticholinergic drug effects in our subjects. It is concluded that nasally applied ipratropium bromide is not likely to cause systemic anticholinergic side-effects, even in doses exceeding the therapeutic recommendations.

Absorption↗
PubMed1981

[Pharmacological studies on antispasmodics. IV. Ganglion blocking activity of 3-(di-2-thienylmethylene)-5-methyl-trans-quinolizidinium bromide (HSR-902) and the correlation between its blocking activity and its inhibitory activity towards urinary bladder contraction (author's transl)].

The ganglion blocking activity of HSR-902, a new antispasmodic agent, was compared with those of atropine sulfate, butylscopolamine bromide, timepidium bromide, prifinium bromide and hexamethonium chloride. These agents inhibited the postganglionic action potential induced by preganglionic cervical sympathetic nerve stimulation in cat and the order of potency was as follows: hexamethonium chloride much greater than timepidium bromide in equilibrium with butylscopolamine bromide greater than prifinium bromide greater than HSR-902 much greater than atropine sulfate. Moreover, the inhibitory activities were correlated with the inhibitory activities of these agents on urinary bladder contraction induced by pelvic nerve stimulation in cat which had been demonstrated in a previous report. On the nictitating membrane contraction induced by postganglionic cervical sympathetic nerve stimulation in cat, HSR-902 alone exhibited a slight inhibition. HSR-902, as well as tolazoline hydrochloride, an alpha-blocking agent, shifted the dose-response curve of noradrenaline-contraction in parallel to the right without decreasing maximal response in the isolated aorta of guinea pig, and the plots of Schild were found to be linear. These results suggested that the weak inhibitory activity of HSR-902 on urinary bladder contraction would be due to the weakness of its ganglion blocking activity and that it is a new antispasmodic agent with a slight alpha-blocking activity.

Action Potentials↗
PubMed1980

Comparison of three sample preparation techniques for determination of organic bromide and chloride in halogenated lipids by x-ray fluorescence spectroscopy.

Three sample preparation techniques--thin-film, solution, and cellulose pellet--were applied to the determination of bromide in brominated lipids by X-ray fluorescence spectroscopy. Using brominated vegetable oils of known bromide content it was demonstrated that the thin-film technique could result in erroneously high bromide contents, which could also vary with the amount of oil applied, depending on the solvent used. As solutions in hexane, slightly high bromide contents were observed at high concentrations. With the cellulose pellets, bromide contents similar to known values were observed. It was concluded that the cellulose pellet procedure, although more time consuming, and less convenient for ready recovery of sample, was the most suitable for organic bromide determination. Similar results were indicated for chlorinated oils.

Fats↗
PubMedDate not supplied

[Study of complex formation of ethidium bromide with the self-complementary deoxytetranucleotide 5'-d(ApGpCpT) by unidimensional and two- dimensional 1H NMR spectroscopy].

Complex formation of ethidium bromide (3,8-diamino-6-phenyl-5-ethyl-phenanthridine) with the self-complementary desoxytetraribonucleosidetriphosphate d(ApGpCpT) was studied in aqueous solution by uni- and two-dimensional 1H NMR spectroscopy (500 and 600 MHz). The concentration dependence of the chemical shifts of protons of the complex at a fixed temperature (T = 308 K) were measured. The schemes of complexing of the dye with the tetranucleotide which take into account eventual molecular associates in solution are discussed. Equilibrium constants of the reactions and the limiting values for the chemical shifts of the protons of ethidium bromide incorporating into the complex were calculated. Relative contents of different complex types were analyzed. The relationship between the dynamic equilibrium and dye/tetranucleotide concentration ratio was examined. The conclusion is made that, as with the complex of proflavine with the d(AGCT) examined earlier, ethidium bromide is intercalated essentially into the G-C site of the tetranucleotide being in the duplex form. The difference in intercalation between ethidium bromide and proflavine lies in the fact that ethidium bromide incorporate on the side of the narrow groove, whereas proflavine is built in on the side of the large groove. Based on the calculated values of the induced chemical shift of ethidium bromide protons and 2-d NOE spectal data, an adequate model (1:2) of the complex of the dye with tetranucleotide in solution was constructed.

Ethidium↗
PubMed1997

[Assessment of neurotoxic effects of methyl bromide in exposed workers].

BACKGROUND: Methyl bromide is an aliphatic hydrocarbon derivative used as a pesticide that causes skin, kidney, respiratory, liver and neurological damage. AIM: To assess the neurological and psychiatric damage caused by methyl bromide in exposed workers of seed and fruit export industries in a rural area near Santiago. SUBJECTS AND METHODS: We studied prospectively 15 male middle age workers before and after a fumigation period with methyl bromide, that lasted two to four weeks. According to the initial assessment, 5 of these subjects had a chronic exposure to the chemical. As controls, 10 non exposed workers matched for age, sex and working conditions were studied in two occasions. The evaluation included the WHO Neuro Behavior Core Test Battery, dynamometric and vibrator assessment of peripheral nerve function, the Nothingham test for psychological functioning and Titmus test for visual acuity. Methyl bromide levels were measured in blood and urine. RESULTS: Blood methyl bromide levels increased from 13.3 to 30 mg/dl after exposure. Symptoms that appeared with a higher frequency in exposed workers were insomnia, headache, paresthesiae, mood changes and loss of memory and concentration. In these subjects, the threshold for the Vibraton test increased from 2.4 to 2.85 sec, dynamometry showed a strength reduction in the right side from 51.4 to 47.2 kg and there was an increase in the score for negative auto-perception in the Nothingham test from 11.2 to 13.6. No deterioration in these tests were observed in unexposed workers. CONCLUSIONS: Acute and chronic methyl bromide exposure causes important psychological and neurological derangement.

Adult↗
PubMed1985

Secretion of bromide by the canine prostate.

Four dogs with surgically produced prostatic fistulas were given single oral doses of 1.13 gm of sodium bromide daily for five consecutive days. Two days later the mean (+/- SE) serum level of bromide was 28.0 +/- 4.0 meq/L and the serum chloride level had decreased from a pretreatment value of 112.5 +/- 1.0 meq/L to 86.5 +/- 3.7 meq/L; in the basal prostatic secretion, the mean prostatic fluid to serum (PF/S) ratios for bromide and chloride were 0.56 +/- 0.15 and 0.53 +/- 0.11, respectively, and were not different (P greater than 0.05, paired t-test); at higher rates of secretion provoked by intravenous pilocarpine the corresponding PF/S ratios of 1.48 +/- 0.04 and 1.32 +/- 0.01 were significantly different (P less than 0.05, paired t-test). It is concluded that the processes involved in forming the basal and pilocarpine-induced prostatic secretions must differ and that the ability of the chloride-transporting system to transport bromide is slightly greater than that for chloride. Because it may impair sperm motility, bromide secreted in prostatic fluid potentially could adversely affect reproduction.

Animals↗
PubMed1979

Accelerated fall in serum bromide level after administration of perchlorate to man.

Five patients intoxicated with bromoureide showed accelerated elimination of bromide from serum after a single dose of perchlorate. It was probably due to increased renal excretion of bromide. Perchlorate has been reported to increase the renal clearance of other monovalent anions by inhibiting their tubular reabsorption and a similar interaction between perchlorate and bromide is suggested. Although perchlorate effectively eliminates bromide it should not replace chloride in the treatment of bromide intoxication, because of the side effects of its repeated administration.

Adult↗
PubMed1990

An unbiased estimation of the total number of synapses in the superior cervical ganglion of adult rats established by the disector method. Lack of change after long-lasting sodium bromide administration.

Previous physiological and morphological studies suggested that sodium bromide promotes synaptogenesis of implanted cholinergic nerves in the superior cervical ganglion of adult rats. To check whether sodium bromide also modifies synaptic numbers in the intact ganglion, quantitative electron microscopy was used to determine the total number of synaptic junctions in the superior cervical ganglion of adult rats. Untreated controls were compared with animals which drank water containing 280 mg ml-1 sodium bromide for 7 days. The disector method, an unbiased estimator of volume density of certain particles, has been adapted to this particular case. To accomplish the task, an on-line counting procedure was developed, which permitted the efficient adaptation of the disector method for the superior cervical ganglion, in which the synapses are known to be distributed sparsely. Three pairs of (control and treated) ganglia have been completely processed by three independent examiners. The estimated number of synapses in the ganglia ranged from 4 to 8 million while the volumes of the ganglia varied from 0.65 to 0.90 mm3. Evaluation of the results showed that variations in the total number of synapses were in each case proportional to differences in ganglionic volumes. This suggests that: (1) sodium bromide does not lead to changes in density of intrinsic synapses; and (2) the morphogenetic action of sodium bromide on principal ganglion cells previously described is essentially postsynaptic and requires additional presynaptic elements to increase the number of synapses.

Animals↗
PubMed1990

Elevated serum bromide concentrations following repeated halothane anaesthesia in a child.

A 20-month-old child received 25 brief halothane general anaesthetics over a five-week period to allow cranial irradiation treatments for a posterior fossa ependymoma. Personality change during the last week of the treatment protocol raised the question of possible bromide intoxication. Serum bromide concentrations, using a gold chloride assay technique, were monitored at that time, and at four- and six-week intervals thereafter. Serum bromide concentrations demonstrated a four-fold change during this period ranging from peak levels of 2.2 mEq.L-1 (176 micrograms.kg-1) during the fifth week of treatment decreasing to less than 0.5 mEq.L-1 (less than 40 micrograms.ml-1) six weeks following the end of treatments. This demonstrates the possibility for repetitive, short halothane exposures to result in elevations of serum bromide and the potential of bromide intoxication in paediatric neuro-oncology patients.

Anesthesia, Inhalation↗
PubMed1994

An improved bromide assay for the estimation of extracellular water volume by capillary gas chromatography.

A sensitive bromide determination has been developed that consists of the following steps: isolation (purification) of bromide; oxidation of bromide to bromine with potassium permanganate and subsequent reaction with acetone, to give the volatile bromoacetone; quantification of bromoacetone by capillary gas chromatography. The method can also be used with small sample volumes appropriate for paediatric applications. Thermodynamic arguments are used to calculate the equilibria involved. The accuracy and reproducibility of the method have been determined. Finally, the bromide space of six volunteers was determined and the clearance of the bromide by the kidneys was investigated.

Bromides↗
PubMed1982

Modification of the serum bromide assay for the measurement of extracellular fluid volume in small subjects.

Serum bromide has been used in the past to measure extracellular fluid volume in infants. In this report, a modification and refinement of a previously described spectrophotometric assay suitable for determining bromide levels in blood is presented. The assay involves sample deproteinization with perchloric acid followed by spectrophotometric analysis of the complexes formed by the reaction between sodium bromide and gold chloride. Linear standard curves were obtained by diluting 1:2 with pooled serum at the following bromide concentrations: 10, 20, 30 and 40 mg%. Intra- and interassay variation using this technique was extremely small (n = 6, correlation coefficient, 0.995, and n = 5, correlation coefficient, 0.988, respectively). For toxicological analysis, a linear standard curve was derived from sodium bromide standards at the following concentrations: 40, 60, 80, and 100 mg%. The reproducibility and reliability of this assay have been excellent and the correlation with neutron activation analysis was excellent. The assay is easily adapted for the analysis of large numbers of samples, is easy to perform, and requires only small sample volumes.

Age Factors↗
PubMed1985

Cyanogen bromide cleaves Fc fragments of pooled human IgG at both methionine and tryptophan residues.

An attempt was made to obtain fragments containing the C gamma 2 region by selectively cleaving human Fc fragments prepared from pooled IgG at Met residues using cyanogen bromide. Based on the known locations of Met residues in the Fc regions of human IgG subclasses, fragments between Met 252 and 358, comprising the C gamma 2 domains, were expected from IgGl Gm -1, IgG2, IgG3 and IgG4. Greater fragmentation of the Fc fragments occurred, however, than was predicted. Automated N-terminal sequencing identified five major points (Trp 381, 313 and 277, and Met 397 and 252) and two minor points of cleavage (Met 428 and Trp 417). The majority of cleavage points occurred at Trp rather than Met. Furthermore, cleavage at Met 358, necessary to produce C gamma 2 domains, was not detected. Control experiments verified the integrity of the Fc fragments handled in exactly the same manner without cyanogen bromide exposure and the ability of the same cyanogen bromide preparation to produce the expected cleavages at Met of sperm whale apomyoglobin without fragmentation at Trp. Cleavage at Met 358 did not occur presumably because of the difficulty associated with cyanogen bromide cleavage at Met-Thr peptide bonds. Cleavage at Trp probably occurred by way of halogen promoted oxidation of the indole nucleus with resultant peptide bond fissure. These observations show that cyanogen bromide cleavage of pooled human Fc fragments is not selective for Met, but also cleaves at Trp residues. The resultant fragmentation of the C gamma 2 region coupled with the inability to make the required cleavage at the 358-359 Met-Thr bond resulted in the inability to produce fragments comprising the C gamma 2 domains. The reasons for the selective cleavage at Met in some proteins and the cleavage at both Trp and Met in others are not known.

Chemical Phenomena↗
PubMed1990

Two-year oral chronic toxicity and carcinogenicity study in rats of diets fumigated with methyl bromide.

A chronic toxicity and carcinogenicity study was conducted by feeding diets containing 80, 200 or 500 ppm total bromine following fumigation with methyl bromide, a diet containing 500 ppm potassium bromide, or a basal diet alone to groups of 60 male and 60 female Fischer (F344) rats for up to 2 yr. Ten males and ten females from each group were killed after wk 52 and 104 for urinalysis, haematology, blood biochemistry and pathology. Rats that were killed in extremis or found dead during the study and all rats that survived to the end of the study were also subjected to pathological examinations. In rats fed the diets fumigated with methyl bromide there were no marked toxic changes, except for a slight depression of body-weight gain from wk 60 onwards in males of the 500-ppm group, and tumour incidence was unaffected. Rats given a diet containing potassium bromide did not show any treatment-related changes. It was concluded that residues of up to 500 ppm total bromine in diets fumigated with methyl bromide are not carcinogenic in F344 rats of either sex and that the maximum no-effect level is 200 ppm (6.77 mg total bromine/kg body weight/day) in males. The maximum no-effect level could not be determined in females.

Animals↗
PubMed1991

Optimum doses of deuterium oxide and sodium bromide for the determination of total body water and extracellular fluid.

A practical approach for determining optimum tracer doses is described for measurements of total body water (TBW) and extracellular water (ECW) based on dilution of deuterium oxide and sodium bromide with respective analyses by nuclear magnetic resonance and anion-exchange chromatography. Using these techniques and plasma concentrations corresponding to adult doses up to 1.5 g kg-1 body weight of deuterium oxide and 0.05 g kg-1 of sodium bromide, the variations of analyses of these tracers, at these respective doses, were calculated. TBW determination with an RSD of less than 2% was found to require administration of 0.4 g kg-1 of deuterium oxide. Because basal concentrations of bromide are quantifiable, the accuracy of the extracellular water determination depends upon the magnitude of the increase in plasma bromide concentration; a sodium bromide dose of 0.01 g kg-1 provides a deviation in the determined ECW volume of approximately 1%.

Body Water↗
PubMed2005

Bromination and chlorination reactions of myeloperoxidase at physiological concentrations of bromide and chloride.

Myeloperoxidase and eosinophil peroxidase use hydrogen peroxide to oxidize halides and thiocyanate to their respective hypohalous acids. Myeloperoxidase produces mainly hypochlorous acid and hypothiocyanite. Hypobromous acid and hypothiocyanite are the major products of eosinophil peroxidase. We have investigated the ability of myeloperoxidase to produce hypobromous acid in the presence of physiological concentrations of chloride and bromide. In accord with previous studies, between pH 5 and 7, myeloperoxidase converted about 90% of available hydrogen peroxide to hypochlorous acid and the remainder to hypobromous acid. Above pH 7, there was an abrupt rise in the yield of hypobromous acid. At pH 7.8, it accounted for 40% of the hydrogen peroxide. Bromide, at physiological concentrations, promoted a dramatic increase in bromination of human serum albumin catalyzed by myeloperoxidase. The level of 3-bromotyrosine increased to 16-fold greater than that for 3-chlorotyrosine. Chlorination of tyrosyl residues was not affected by bromide. With reagent hypohalous acids, bromination of tyrosyl residues was considerably more facile than chlorination. Hypochlorous acid promoted bromination to only a limited extent, which ruled out transhalogenation as a substantive route to 3-bromotyrosine. Chloramines and bromamines were also formed on albumin. Bromamines decayed much faster than chloramines and rapidly gave rise to protein carbonyls. We conclude that at physiological concentrations of chloride and bromide, hypobromous acid can be a major oxidant produced by myeloperoxidase. Its production in vivo will depend on pH and the concentration of bromide. Once produced, hypobromous acid will react with proteins to form bromamines, carbonyls, and brominated tyrosine residues. Consequently, 3-bromotyrosine should be considered as an oxidative product of myeloperoxidase and cannot be used as a specific biomarker for eosinophil peroxidase.

Body Fluids↗
PubMed2005

Morphine, haloperidol and hyoscine N-butyl bromide combined in s.c. infusion solutions: compatibility and stability. Evaluation in terminal oncology patients.

The administration of drugs by subcutaneous infusion is routinely practiced in palliative medicine for the management of patients who are no longer able to take oral medication. It is common for two or more drugs to be combined in subcutaneous solutions. The combination of an opioid with other drugs (haloperiol lactate and hyoscine N-butyl bromide) can be very valuable. Unfortunately, the compatibility and stability of morphine hydrochloride, haloperidol lactate and hyoscine N-butyl bromide combined in the same solution has not yet been determined. Therefore, this study examined the stability of ternary solutions containing morphine HCl, haloperidol lactate and hyoscine N-butyl bromide at different dose ranges. Twelve different solutions were assessed for 15 days after preparation in polypropylene syringes using 0.9% saline as diluent. Triplicate syringes were stored at 25 degrees C. HPLC was the analytical technique used to measure morphine HCl, haloperidol lactate and hyoscine N-butyl bromide. Initial concentration ranges were 1.67-10.0 mg/ml for morphine HCl, 0.417-0.625 mg/ml for haloperidol lactate and, 5.0-6.67 mg/ml for hyoscine N-butyl bromide. All three drugs were very stable (>92.5%) when stored at 25 degrees C. The clinical performance of the admixture was retrospectively assessed in 21 terminal oncology patients. Total symptom control was achieved in 17 out of 21 patients with very good local tolerance.

Aged↗
PubMed2006

A case of sudden death after intramuscular injection of butylscopolamine bromide.

A 40-year-old man experienced cardiopulmonary arrest after intramuscular injection of 20 mg of butylscopolamine bromide. No pathological changes were found at autopsy, and 1.19 microg/mL of butylscopolamine bromide was detected in his serum. Since he had taken no other drugs, his severe symptoms were thought to have been caused by an anaphylactic reaction to butylscopolamine bromide. Butylscopolamine bromide has been used for many years worldwide, and is considered to be a safe drug, with no reports of severe side effects following intramuscular injection. Since an anaphylactic reaction may not be related to a particular medication, the possibility of such a severe reaction must be considered, even during administration of an ostensibly safe drug such as butylscopolamine bromide.

Adult↗