Effect of Evening Bromazepam Administration on Blood Pressure and Heart Rate in Mild Hypertensive Patients.

AIM: To assess the effects of chronic evening oral administration of bromazepam alone or in combination with propranolol on ambulatory blood pressure (BP) and heart rate (HR) in mild hypertensive subjects. METHODS: Thirty-seven mild hypertensive patients after a 2-week placebo period were randomized to bromazepam 3 mg, propranolol 40 mg, bromazepam 3 mg plus propranolol 40 mg or placebo for 2 weeks according to a double-blind, double dummy, cross-over design. After each treatment period, 24-h BP and HR ambulatory monitoring was performed by using a non-invasive device. RESULTS: Ambulatory monitoring showed that during night-time SBP and DBP values were unaffected by bromazepam as compared to placebo, whereas SBP was significantly reduced by propranolol both when taken alone and in combination with bromazepam. HR nocturnal values were significantly reduced by propranolol, whereas they were significantly increased by bromazepan both when taken alone (+11.5%, p < 0.05 vs. placebo) and in combination with propranolol (+12.8%, p < 0.05 vs. propranolol). No significant difference in day-time values of SBP, DBP and HR was observed among the 4 treatment groups. CONCLUSIONS: In mild hypertensive patients, evening consumption of bromazepam for a 2-week period did not affect BP, while it increased nocturnal HR. Such an increase was observed both when bromazepam was taken alone and in combination with propranolol, which suggests that it depends on a bromazepam mediated decrease in vagal tone. Whatever the mechanism, the HR nocturnal increase might be of clinical relevance, due to the role of high HR as cardiovascular risk factor, particularly in already at risk hypertensive subjects.

Activation of Anxiogenic Circuits Instigates Resistance to Diet-Induced Obesity via Increased Energy Expenditure.

Anxiety disorders are associated with body weight changes in humans. However, the mechanisms underlying anxiety-induced weight changes remain poorly understood. Using Emx1Cre/+ mice, we deleted the gene for brain-derived neurotrophic factor (BDNF) in the cortex, hippocampus, and some amygdalar subregions. The resulting mutant mice displayed impaired GABAergic transmission and elevated anxiety. They were leaner when fed either a chow diet or a high-fat diet, owing to higher sympathetic activity, basal metabolic rate, brown adipocyte thermogenesis, and beige adipocyte formation, compared to control mice. BDNF re-expression in the amygdala rescued the anxiety and metabolic phenotypes in mutant mice. Conversely, anxiety induced by amygdala-specific Bdnf deletion or administration of an inverse GABAA receptor agonist increased energy expenditure. These results reveal that increased activities in anxiogenic circuits can reduce body weight by promoting adaptive thermogenesis and basal metabolism via the sympathetic nervous system and suggest that amygdalar GABAergic neurons are a link between anxiety and metabolic dysfunction.

Efectividad y seguridad del escitalopram o bromazepam comparado con fluoxetina, sertralina, fluvoxamina, paroxetina y psicoterapia en pacientes con Trastorno de Ansiedad Generalizada o Trastorno de Fobia Social / Effectiveness and safety of escitalopram or bromazepam compared to fluoxetine, sertraline, fluvoxamine, paroxetine and psychotherapy in patients with Generalized Anxiety Disorder or Social Phobia Disorder

Introducción: En la actualidad el Trastorno de Ansiedad Generalizada y el Trastorno de Fobia Social, son los trastornos de ansiedad de mayor incidencia a nivel mundial; se encuentra que un 12% de la población con trastornos mentales corresponde a TFS y un 6% a TAG En la Encuesta Nacional de Salud Mental realizada en el año 2003, las mujeres presentan una mayor prevalencia global, presentando una edad de inicio más temprana el TFS (14 años) comparado con el TAG (18 años) (1). Objetivo: Examinar los beneficios y riesgos del uso del escitalopram o bromazepam en el Trastorno de Ansiedad Generalizada o Fobia Social, como uno de los criterios para informar la toma de decisiones relacionada con la posible inclusión de tecnologías en el Plan Obligatorio de Salud, en el marco de su actualización integral para el año 2015. Metodología: A partir de la pregunta PICO se establecieron los criterios de elegibilidad para la realización de la búsqueda de la evidencia científica (a ensayos clínicos, revisiones sistemáticas de estudios observacionales y estudios de cohortes analíticas), se realizó la tamización y selección de la evidencia evaluando su calidad y posteriormente se realizó la extracción de datos y la síntesis de la evidencia. Resultados: El escitalopram y el eromazepan es efectivo en el manejo del Trastorno de Ansiedad Generalizada y Fobia Social, pero no muestra ser superior comparado con otros Inhibidores Selectivos de Recaptación de Serotonina. En cuanto a seguridad el escitalopram presentó menos efectos adversos comparados con los otros medicamentos, pero en los niños se documentó el aumento en el riesgo de suicidio e ideación suicida. El bromazepam genera adicción, somnolencia y no es recomendado su uso a largo plazo. Conclusiones: El escitalopram y el bromazepam pueden ser usados en el manejo del Trastorno de Ansiedad Generalizada y Fobia social teniendo en cuenta la evidencia de los estudios reportados.(AU)

Benzodiazepines increase the reward effects of buprenorphine in a conditioned place preference test in the mouse.

Buprenorphine (BPN) is widely used as a substitution treatment for opioid addiction. Some cases of abuse and misuse, especially associated with various benzodiazepines (BZDs), have been described, and a previous study has shown that BZDs increase the sedative effect of BPN and decrease its anxiogenic properties. To investigate the reward effect that may lead to the abusive combination of BPN and BZD, we studied the influence of different doses of three BZDs extensively used with BPN by drug addicts on conditioned place preference behavior in mice. BPN (0.3, 1, 3 mg/kg) was injected subcutaneously into male mice alone or in combination with a BZD administered intraperitoneally: dipotassium clorazepate (CRZ; 1, 4, 16 mg/kg), diazepam (DAZ; 0.5, 1, 5 mg/kg), or bromazepam (BMZ; 0.5, 1, 3 mg/kg). Amphetamine (8 mg/kg) was used as a reference drug. Reward effects of BPN alone or in combination were measured in a conditioned place preference paradigm using an unbiased procedure. Our results showed that groups treated with BPN associated with different doses of diazepam and clorazepate, but not bromazepam, spent significantly more time in the drug-paired compartment compared to the group treated with BPN alone. Our study shows that joint consumption of diazepam and clorazepate, but not bromazepam, can increase the reward properties of BPN alone in mice. These results could help to explain the use of this type of drug combination in the drug addict population.

Efectos del bromacepam en el desarrollo de una actividad sensoriomotora: un estudio electroencefalográfico / The effects of bromazepan on the performance of a sensory-motor activity: an electroencephalographic study

Objetivos. Investigar los efectos del uso del bromacepam en la potencia relativa en alfa durante la realización de unatarea de mecanografía. Teniendo en cuenta las particularidades de cada hemisferio cerebral, nuestra hipótesis era que a travésde la medida de la potencia relativa sería posible investigar el efecto del bromacepam sobre áreas corticales específicas. Concretamente,se esperaba observar diferentes patrones de potencias en los procesos de atención, activación e integración sensoriomotora.Sujetos y métodos. La muestra estaba formada por 39 sujetos (15 hombres y 24 mujeres) con una media de edad de30 ± 10 años. Los grupos control (placebo) y experimental (bromacepam de 3 mg y 6 mg) fueron entrenados en la tarea de mecanografíacon un modelo doble ciego aleatorizado. Resultados. Mediante el ANOVA de tres vías y el test de Scheffé se comprobaroninteracciones entre los factores condición y momento y entre condición y sector. Conclusión. Las dosis empleadas en esteestudio facilitaron el desarrollo motor de la tarea de mecanografía. En este estudio, el uso del fármaco no impidió el aprendizajede la tarea, pero parece ser que concentró el esfuerzo mental sobre aspectos más restringidos y específicos de la mecanografía.Tuvo lugar una influencia sobre el ritmo y la eficacia de las operaciones ejecutadas durante mecanismos de codificacióny almacenamiento de nuevas informaciones. Asimismo, se comprobó un predominio de actividad en el área frontal izquierda(dominante) en el grupo bromacepam 3 mg, lo cual indica que esta dosis del fármaco permite al sujeto un mayor direccionamientode la actividad cortical para la planificación y la ejecución de la tarea(AU)

Aims. To investigate the effects of using bromazepam on the relative power in alpha while performing a typing task.Bearing in mind the particularities of each brain hemisphere, our hypothesis was that measuring the relative power wouldallow us to investigate the effects of bromazepam on specific areas of the cortex. More specifically, we expected to observedifferent patterns of powers in sensory-motor integration, attention and activation processes. Subjects and methods. The samplewas made up of 39 subjects (15 males and 24 females) with a mean age of 30 ± 10 years. The control (placebo) and experimental(3 mg and 6 mg of bromazepam) groups were trained in the typing task with a randomised double-blind model. Results. A threewayANOVA and Scheffé test were used to analyse interactions between the factors condition and moment, and betweencondition and sector. Conclusions. The doses used in this study facilitated motor performance of the typing task. In this study,the use of the drug did not prevent learning of the task, but it did appear to concentrate mental effort on more restricted andspecific aspects of typing. It also seemed to influence the rhythm and effectiveness of the operations performed duringmechanisms related to the encoding and storage of new information. Likewise, a predominance of activity was observed in theleft (dominant) frontal area in the 3 mg bromazepam group, which indicates that this dose of the drug affords the subject agreater degree of directionality of cortical activity for planning and performing the task(AU)

Effects of a cognitive modulator in the theta and alpha asymmetry during a typewriting task: a sensorimotor integration perspective.

This study aimed to elucidate cortical mechanisms and to identify the areas where occur such mechanisms due to interaction between bromazepam and motor learning. The sample was composed of 45 healthy subjects randomly distributed in 3 groups: placebo (n=15), bromazepam 3 mg (n=15) or bromazepam 6 mg (n=15). To perform the experimental task, subjects sat comfortably at a distance of approximately 20 cm from the typewriter. The typewriter keyboard was covered with a wooden box to avoid visual information about the hands' position. The typewriting task was performed concomitantly with EEG recording. ANOVA two-way results indicated a decreased asymmetry in sensorimotor areas in the experimental groups. Our interpretation is that moderate doses of bromazepam may improve performance on tasks with predictable elements to promote stability of psychomotor functions, but may also impair performance on tasks executed in unpredictable environments.

Effects of a cognitive modulator in the theta and alpha asymmetry during a typewriting task: a sensorimotor integration perspective / Efeitos de um modulador cognitivo na assimetria de teta e alfa durante uma tarefa de datilografia: uma perspectiva da integração sensório-motora

This study aimed to elucidate cortical mechanisms and to identify the areas where occur such mechanisms due to interaction between bromazepam and motor learning. The sample was composed of 45 healthy subjects randomly distributed in 3 groups: placebo (n=15), bromazepam 3 mg (n=15) or bromazepam 6 mg (n=15). To perform the experimental task, subjects sat comfortably at a distance of approximately 20 cm from the typewriter. The typewriter keyboard was covered with a wooden box to avoid visual information about the hands' position. The typewriting task was performed concomitantly with EEG recording. ANOVA two-way results indicated a decreased asymmetry in sensorimotor areas in the experimental groups. Our interpretation is that moderate doses of bromazepam may improve performance on tasks with predictable elements to promote stability of psychomotor functions, but may also impair performance on tasks executed in unpredictable environments.

O objetivo do estudo foi elucidar mecanismos corticais e identificar as áreas onde estas ocorrem tais mecanismos devido à interação entre bromazepam e aprendizagem motora. A amostra compreendeu 45 sujeitos hígidos distribuídos randomicamente em 3 grupos: placebo (n=15), bromazepam 3 mg (n=15) ou bromazepam 6 mg (n=15). Para a realização da tarefa experimental, sujeitos sentaram-se confortavelmente a uma distância de aproximadamente 20 cm da máquina de escrever. O teclado da máquina foi coberto com uma caixa de madeira para evitar informações visuais sobre a posição das mãos. O registro do EEGq ocorreu simultaneamente à tarefa de datilografia. Os resultados da ANOVA two-way indicaram menor assimetria em áreas sensório-motoras nos grupos experimentais. Nossa interpretação é que doses moderadas de bromazepam podem melhorar o desempenho em tarefas previsíveis por promover estabilidade das funções psicomotoras, mas pode prejudicar o desempenho em tarefas realizadas em ambientes imprevisíveis.

The bioavailability of bromazepam, omeprazole and paracetamol given by nasogastric feeding tube.

AIMS: To characterize and compare the pharmacokinetic profiles of bromazepam, omeprazole and paracetamol when administered by the oral and nasogastric routes to the same healthy cohort of volunteers. METHODS: In a prospective, monocentric, randomized crossover study, eight healthy volunteers received the three drugs by the oral (OR) and nasogastric routes (NT). Sequential plasma samples were analyzed by high-performance liquid chromatography-UV, pharmacokinetic parameters (Cmax, AUC(0-infinity), t(1/2), k(e), tmax) were compared statistically, and Cmax, AUC(0-infinity) and t(max) were analyzed for bioequivalence. RESULTS: A statistically significant difference was seen in the AUC(0-infinity) of bromazepam, with nasogastric administration decreasing availability by about 25%: AUC(OR) = 2501 ng mL(-1) h; AUC(NT) = 1855 ng mL(-1) h (p < 0.05); ratio (geometric mean) = 0.74 [90% confidence interval (CI) 0.64-0.87]. However, this does not appear to be clinically relevant given the usual dosage range and the drug's half-life (approx. 30 h). A large interindividual variability in omeprazole parameters prevented any statistical conclusion from being drawn in terms of both modes of administration despite their similar average profile: AUC(OR) = 579 ng mL(-1) h; AUC(NT) = 587 ng mL(-1) h (p > 0.05); ratio (geometric mean) = 1.01 (90% CI 0.64-1.61). An extended study with a larger number of subjects may possibly provide clearer answers. The narrow 90% confidence limits of paracetamol indicate bioequivalence: AUC(OR) = 37 microg mL(-1) h; AUC(NT) = 41 microg mL(-1) h(p > 0.05); ratio (geometric mean) = 1.12 (90% CI 0.98-1.28). CONCLUSION: The results of this study show that the nasogastric route of administration does not appear to cause marked, clinically unsuitable alterations in the bioavailability of the tested drugs.

Efecto del bromacepam sobre el aprendizaje motor: análisis electroencefalográfico a partir del ritmo beta / Effects of bromazepan on motor learning: an electroencephalogram analysis based on the beta rythm

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[Electroencephalography measures in motor skill learning and effects of bromazepam]. / Medidas eletrencefalográficas durante a aprendizagem de tarefa motora sob efeito do bromazepam.

Neuromodulators change brain's neural circuitry. Bromazepam is often been used in the pharmacological treatment of anxiety disorders. Few papers links this anxiolytic to motor tasks. The purpose of this study was to examine motor and electrophysiological changes produced by administration of bromazepam in differents doses (3 and 6 mg). The sample consisted of 39 healthy individuals, of both sexes, between 20 and 30 years of age. The control (placebo) and experimental (bromazepam 3mg and bromazepam 6 mg) groups were submitted to a typewriting task, in a randomized, double-blind design. The results did not reveal differences on score and time of the attention test. In the comportamental analysis was noticed blocks as main effect to behavioral variables (time and mistakes in the task). Electrophysiological data showed significants interactions to: laterally/condition/moment; laterally/condition; laterally/moment; condition/moment; condition/site.

Medidas eletrencefalográficas durante a aprendizagem de tarefa motora sob efeito do bromazepam / Electroencephalography measures in motor skill learning and effects of bromazepam

Neuromoduladores alteram constantemente as relações neurais pré-existentes no sistema nervoso. O bromazepam é utilizado com freqüência na prática clínica para diminuir padrões de ansiedade. Poucos são os experimentos correlacionando este ansiolítico às tarefas motoras. Neste contexto, o presente experimento visa analisar as alterações motoras e eletrocorticais decorrentes da administração de diferentes doses de bromazepam mediante a prática motora, e relacionar o efeito da droga a performance motora mão-dominante versus não dominante. Sujeitos saudáveis (39), de ambos os sexos, entre 20 a 30 anos compuseram a amostra. Os grupos controle (placebo) e experimental (bromazepam de 3mg e 6mg) foram treinados na tarefa de datilografia num modelo duplo-cego randomizado. Resultados do teste Stroop (atenção) não demonstraram diferenças no escore bruto e no tempo de execução do mesmo. Em contrapartida, nos resultados comportamentais foram observados um efeito principal entre blocos nas variáveis tempo de execução e erros cometidos durante a pratica motora. Os dados eletrofisiológicos evidenciaram interações significantes para: lateralidade/condição/momento; lateralidade/condição; lateralidade/momento; condição/momento; condição/setor.

Efficacy of antiepileptic drugs in patients with benign convulsions with mild gastroenteritis.

The aim of this study was to clarify the efficacy of antiepileptic drugs during a cluster of seizures in patients with convulsions with mild gastroenteritis (CwG). We retrospectively investigated the details of antiepileptic treatment in 110 consecutive episodes in 103 patients with CwG. The temporal course of the seizures and the use of antiepileptic drugs were investigated in each episode. Drugs were judged as effective when seizure cessation was achieved after administration of the drug. As the first drug, diazepam (DZP)/bromazepam (BZP) was effective in 38%, phenobarbital (PB) in 40%, and lidocaine (LD) in 100%. As the second drug, DZP/BZP was effective in 42%, PB in 69%, and LD in 100%. As the third drug, PB was effective in 70%. When the efficacy of the first doses of PB and LD were compared, the efficacy rate was significantly higher for LD than for PB (P = 0.047). In conclusion, LD was effective for the cessation of seizures in patients with CwG.

[Chemical submission]. / Soumission chimique.

INTRODUCTION: The clinical submission syndrome is well known by the general population, but too frequently ignored by physicians. OBSERVATION: A 23 year-old woman was drugged by a third person wishing to sexually abuse of her. The diagnosis was proved biologically after the judicial enquiry. COMMENTS: The diagnosis of clinical submission is difficult to make because of the frequent delays in emergency consultations and the difficulties in biological assays, since the doses of drugs administered are often very low and infra-therapeutic. Over a period of one year, we evoked the diagnosis four times and it was confirmed only once. It sometimes leads to diagnostic peregrinations. Close cooperation between the physicians and the police is required so that a judicial enquiry can be rapidly set-up.

Valores máximos e mínimos de pressão arterial, freqüência cardíaca e saturação de oxigênio durante as exodontias de terceiros molares inclusos sob anestesia local e sedação prévia / Values maximum and minimun of the blood pressure, cardiac frequency and oxygen saturation included 3rd molar extractions under local anesthesia and previous conscious sedation

Neste trabalho avaliou-se os valores máximos e mínimos da saturação de oxigênio, freqüência cardíaca e pressão arterial de 120 pacientes submetidos à exodontia dos terceiros molares inclusos. Os pacientes da amostra foram divididos em quatro grupos onde foram administrados diazepam 10 mg (Grupo I), bromazepam 6 mg (Grupo II), Midazolam 15 mg (Grupo III). Os pacientes do grupo IV (Controle) não receberam medicamentos. Os resultados mostram que as melhores taxas obtidas se enquadram no Grupo III (Midazolam), e na análise da freqüência cardíaca não foi constatada diferença estatística entre os grupos testados

Effect of fluconazole on the pharmacokinetics and pharmacodynamics of oral and rectal bromazepam: an application of electroencephalography as the pharmacodynamic method.

Quantitative analysis of electroencephalography (EEG) is used increasingly to evaluate the pharmacodynamics of benzodiazepines. The present study aimed to apply the EEG method as well as more traditional approaches to an interaction study of bromazepam and fluconazole. Twelve healthy male volunteers participated in a randomized, double-blind, four-way crossover study. The subjects received single oral or rectal doses of bromazepam (3 mg) after 4-day pretreatment of oral fluconazole (100 mg daily) or its placebo. Plasma bromazepam concentrations were measured before and 0.5, 1, 2, 3, 4, 6, 12, 22, 46, and 70 hours after bromazepam administration. Pharmacodynamic effects of bromazepam were assessed using self-rated drowsiness, continuous number addition test, and EEG. Fluconazole caused no significant changes in pharmacokinetics and pharmacodynamics of oral or rectal bromazepam. Rectal administration significantly increased AUC (1.7-fold, p < 0.0001) and Cmax (1.6-fold, p < 0.0001) of bromazepam. These changes following rectal dose may be due to avoidance of degradation occurring in the gastrointestinal tract. Rectal bromazepam also increased the area under the effect curves assessed by EEG (p < 0.05) and subjective drowsiness (p < 0.05). EEG effects were closely correlated with mean plasma bromazepam concentrations (r = 0.92, p < 0.001 for placebo; r = 0.89, p < 0.0001 for fluconazole). Thus, the EEG method provided pharmacodynamic data that clearly reflected the pharmacokinetics of bromazepam.

[Benzodiazepine consumption: survey of community pharmacies in Aquitaine]. / Consommation de benzodiazépines: enquête auprès de pharmaciens d'officine en aquitaine.

For many years, the use of benzodiazepines has been particularly high in France. This use can be described through pharmacy delivery. A cross-sectional one-day survey was conducted in June 1999, within a randomly selected network of community pharmacies in Aquitaine. Pharmacists were asked to interview each patient presenting with a prescription form including at least one benzodiazepine. A total of 58 pharmacies participated in this study; 328 patients were included representing 356 benzodiazepines prescribed. Among the 20 different benzodiazepines concerned, bromazepam, lorazepam and alprazolam represented more than half (54 per cent) of the prescriptions. The mean age of the patients was 62 years (median: 64) and 70 per cent of them were women. Most patients (93 per cent) were known to the pharmacist and 86 per cent had benzodiazepines prescribed by a single physician. In most cases (77 per cent), the prescribed benzodiazepine had been used for more than one year and in one quarter for more than five years. For 81 per cent of chronic users, no dose increase was observed. This study confirmed that long-term use of benzodiazepines is frequent, particularly in the elderly. This use is commonly accepted by health professionals as well as by patients, although it clearly reflects the dependence potential of benzodiazepines.

Comparative bioavailability of two oral formulations of bromazepam in healthy volunteers.

The aim of this study was to assess the pharmacokinetic profile of two bromazepam (CAS 1812-30-2) formulations in 24 healthy volunteers. An open, randomised clinical trial designed as two-period crossover with 14-day washout between doses was employed. Plasma samples for assessments of their bromazepam concentration by HPLC-UV were obtained over 96 h after administration. No adverse effect was reported for any of the formulations administered. The following pharmacokinetics parameters were calculated: AUC(0-96 h), AUCinf, Cmax, Tmax, Ke and T1/2. The 90% confidence intervals (CI) for the mean test/reference individual ratios were 81-109 for AUC and 84-116 for Cmax. Since the 90% CI for both, AUC and Cmax ratios were within the 80-125% interval proposed by the Food and Drug Administration, it is concluded that the new bromazepam slow-release formulation is therapeutic equivalent to the conventional formulation for both, the extent and the rate of absorption after single dose administration in healthy volunteers.