Gamma band oscillations under influence of bromazepam during a sensorimotor integration task: An EEG coherence study

The goal of the present study was to explore the dynamics of the gamma band using the coherence of the quantitative electroencephalography (qEEG) in a sensorimotor integration task and the influence of the neuromodulator bromazepam on the band behavior. Our hypothesis is that the needs of the typewriting task will demand the coupling of different brain areas, and that the gamma band will promote the binding of information. It is also expected that the neuromodulator will modify this coupling. The sample was composed of 39 healthy subjects. We used a randomized double-blind design and divided subjects into three groups: placebo (n = 13), bromazepam 3 mg (n = 13) and bromazepam 6 mg (n = 13). The two-way ANOVA analysis demonstrated a main effect for the factors condition (i.e., C4-CZ electrode pair) and moment (i.e., C3-CZ, C3-C4 and C4-CZ pairs of electrodes). We propose that the gamma band plays an important role in the binding among several brain areas in complex motor tasks and that each hemisphere is influenced in a different manner by the neuromodulator. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

THE EFFECTS OF BROMAZEPAM ON THE PERFORMANCE OF A SENSORY-MOTOR ACTIVITY: AN ELECTROENCEPHALOGRAPHIC STUDY

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 would allow its to investigate the effects of bromazepam oil specific areas of the cortex. More, specifically, we expected to observe different patterns of powers in sensory-motor integration, attention and activation processes. Subjects and methods. The sample was 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 ill the typing task with a randomised double-blind model. Results. A three-way ANOVA and Scheffe test were used to analyse interactions between the factors condition and moment, and between condition and sector Conclusions. The doses used ill this study facilitated motor performance of the typing task. Ill 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 and specific aspects of typing. It also seemed to influence the rhythm and effectiveness of the operations performed during mechanisms related to the encoding and storage often, information. Likewise, a predominance of activity was observed in the left (dominant) frontal area in the 3 mg bromazepam group, which indicates that this close of the drug affords the subject a greater degree of directionality of cortical activity for planning and performing the task. [REV NEUROL 2009; 49: 295-9]

Effects of bromazepam in frontal theta activity on the performance of a sensorimotor integration task: A quantitative electroencephalography study

Our objective is to verify the modulatory effects of bromazepam on EEG theta absolute power when subjects were submitted to a visuomotor task (i.e., car driver task). Sample was composed of 14 students (9 males and 5 females), right handed, with ages varying between 23 and 42 years (mean = 32.5 +/- 9.5), absence of mental or physical impairments, no psychoactive or psychotropic substance use and no neuromuscular disorders (screened by a clinical examination). The results showed an interaction between condition and electrodes (p=0.034) in favor of F8 electrode compared with F7 in both experimental conditions (t-test; p=0.001). Additionally, main effects were observed for condition (p=0.001), period (p=0.001) and electrodes (p=0.031) in favor of F4 electrode compared with F3. In conclusion, Br 6 mg of bromazepam may interfere in sensorimotor processes in the task performance in an unpredictable scenario allowing that certain visuospatial factors were predominant. Therefore, the results may reflect that bromazepam effects influence the performance of the involved areas because of the acquisition and integration of sensory stimuli processes until the development of a motor behavior based on the same stimuli. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

The effects of bromazepam over the temporo-parietal areas during the performance of a visuomotor task: A qEEG study

This study investigated the effects of bromazepam on qEEG when 14 healthy subjects were asked to perform a visuomotor task (i.e., motor vehicle driving task). The subjects were exposed to two experimental conditions: the placebo (PL) and 6 mg of bromazepam (Br 6 mg), following a randomized, double-blind design on different days. Specifically, we observe absolute power extracted from qEEG data for theta band. We expected to see a decrease in absolute theta power in the temporal and parietal areas due to the influence of bromazepam for the experimental group when compared with the placebo group. We found a main effect for the condition factor for electrodes T3, T4, P3 and P4. We also observed a main effect for the period factor for electrodes P3 and P4. We observed that the ingestion of 6 mg of bromazepam induces different patterns in theta power at the temporal and parietal sites. We concluded that 6 mg of bromazepam was an important factor in the fluctuation of the activities in the temporal and parietal areas. We then hypothesize about the specific role of this drug during the execution of a visuomotor task and within the sensorimotor integration process. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Responsiveness of sensorimotor cortex during pharmacological intervention with bromazepam

The aim of this study was to investigate the influence of bromazepam on EEG and the motor learning process when healthy subjects were submitted to a typewriting task. We investigated bromazepam due to its abuse by various populations and its prevalent clinical use among older individuals which are more sensitive to the negative effects of long half-life benzodiazepines. A randomized double-blind design was used with subjects divided into three groups: placebo (n = 13), bromazepam 3 mg (n = 13) and bromazepam 6 mg (n = 13). EEG data comprising theta, alpha and beta bands was recorded before, during and after the motor task. Our results showed a lower relative power value in the theta band in the Br 6 mg group when compared with PL. We also observed a reduction in relative power in the beta band in the Br 3 mg and Br 6 mg when compared with PL group. These findings suggest that Br can contribute to a reduced working memory load in areas related to attention processes. On the other hand, it produces a higher cortical activation in areas associated with sensory integration. Such areas are responsible for accomplishing the motor learning task. The results are an example of the usefulness of integrating electrophysiological data, sensorimotor activity and a pharmacological approach to aid in our understanding of cerebral changes produced by external agents. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

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.

Eventos toxicológicos relacionados a medicamentos no Estado de São Paulo

OBJETIVO: Analisar as características epidemiológicas dos eventos toxicológicos relacionados a medicamentos. MÉTODOS: Realizou-se um estudo epidemiológico descritivo de série de casos. Utilizando a categoria "evento toxicológico relacionado a medicamentos", analisaram-se 6.673 casos registrados em centros de assistência toxicológica do Estado de São Paulo, no ano de 1998. As variáveis estudadas compreenderam características dos eventos, das pessoas afetadas, dos agentes tóxicos e das circunstâncias envolvidas. A análise dos agentes tóxicos considerou três níveis de desagregação: grupos terapêuticos, princípios ativos e nomes comerciais. RESULTADOS: Os medicamentos ocuparam o primeiro lugar entre todos os tipos de agentes tóxicos registrados pelos centros. Os eventos toxicológicos relacionados a medicamentos caracterizaram-se por serem registrados por telefone (78,5%), a partir de hospitais (86,6%); originaram-se de exposições agudas, pela via oral (90,2%), ocorridas em residência (85,7%) de área urbana (95%). Houve predomínio do sexo feminino (59%) e maior concentração na primeira década de vida (49,4%), sobretudo aos dois e três anos de idade. Os princípios ativos mais freqüentemente encontrados foram: fenobarbital, diazepam, haloperidol, carbamazepina e bromazepam. As principais circunstâncias foram as acidentais (38,8%) e tentativas de suicídio (36,5%). Entre os princípios ativos relacionados predominaram os dos grupos terapêuticos psiquiatria, analgesia/anestesia e respiratório. CONCLUSÕES: Aponta-se a necessidade de cumprimento da legislação quanto à venda de medicamentos sob receituário médico e de construção da toxicovigilância conforme diretrizes do Sistema Único de Saúde.

Quantification of chlordesmethyldiazepam by liquid chromatography-tandem mass spectrometry: application to a cloxazolam bioequivalence study

A rapid, sensitive and specific LC-MS/MS method was developed and validated for quantifying chlordesmethyldiazepam (CDDZ or delorazepam), the active metabolite of cloxazolam, in human plasma. In the analytical assay, bromazepam (internal standard) and CDDZ were extracted using a liquid-liquid extraction (diethyl-ether/hexane, 80/20, v/v) procedure. The LC-MS/MS method on a RP-C18 column had an overall run time of 5.0 min and was linear (1/x weighted) over the range 0.5-50 ng/mL (R > 0.999). The between-run precision was 8.0% (1.5 ng/mL), 7.6% (9 ng/mL), 7.4% (40 ng/mL), and 10.9% at the low limit of quantification-LLOQ (0.500 ng/mL). The between-run accuracies were 0.1, -1.5, -2.7 and 8.7% for the above mentioned concentrations, respectively. All current bioanalytical method validation requirements (FDA and ANVISA) were achieved and it was applied to the bioequivalence study (Cloxazolam-test, Eurofarma Lab. Ltda and Olcadil (R)-reference, Novartis Biociencias S/A). The relative bioavailability between both formulations was assessed by calculating individual test/reference ratios for Cmax, AUClast and AUCO-inf. The pharmacokinetic profiles indicated bioequivalence since all ratios were as proposed by FDA and ANVISA. Copyright (C) 2009 John Wiley & Sons, Ltd.

Farmacología en la tercera edad: Medicamentos de uso continuo y peligros de la interacción medicamentosa

Introduction: It was observed a considerable growth of elderly people. They are who use more medicines. The physiological changes associated with the age advancing can make pharmacokinetic and pharmacodynamic alterations. The cognitive decline, physical limitations and associate chronic pathology affect the medications appropriately use ability. Aims: Based in a literature review, appoint the main pharmacological groups prescribed to the elderly and the drug-drug interaction risks. Conclusion: The most of elderly use continually at least 3 medicines, the most prescribed are to cardiovascular and psychic diseases treatment.

Adverse drug reaction as cause of hospital admission of elderly people: a pilot study

The objective of this study was to estimate the prevalence of adverse drug reactions (ADR) related to hospital admission of elderly people, identifying the use of potentially inappropriate medication (PIM), the ADR and the risk factors associated with the hospitalization. A cross-sectional study was conducted in a private hospital of São Paulo State, Brazil. All patients aged ≥ 60 years, admitted in the general practice ward in May 2006 were interviewed about the drugs used and the symptoms/complaints that resulted in hospitalization. More than a half (54.5 %) of elderly hospitalizations were related with ADR. The therapeutic classes involved with ADR were: cardiovascular (37.7 %), central nervous (34.6 %) and respiratory (5.7 %). The ADR observed were disorders in circulatory (28.4 %), digestive (20.0 %) and respiratory (18.9 %) tracts. 27 elderly had made PIM and in 20 of them this was the cause of hospitalization. Polypharmacy was an ADR risk factor (p = 0.021).These data allows the healthcare professionals upgrade, qualifying them in pharmcovigilance.

Uso abusivo de benzodiazepínicos em idosos: revisão bibliográfica

Objetivos: identificar as consequências do abuso de benzodiazepínicos na população idosa, assim como, os benzodiazepínicos mais consumidos no Brasil. Metodologia: foi realizada uma revisão narrativa através de pesquisa bibliográfica utilizando o site Google acadêmico, através dos descritores DeCS "benzodiazepinas", "abuso" e "idoso", assim como suas combinações. Conclusão: entre os benzodiazepínicos mais utilizados foram encontrados diazepam, bromazepam, alprazolam, lorazepam, clonazepam e midazolam. Os principais efeitos colaterais do uso de benzodiazepínicos em idosos são sedação, lentificação psicomotora, comprometimento cognitivo (diminuição da atenção, amnésia, confusão mental), dependência, síndrome de ausência (insônia, irritabilidade e ansiedade). A toxicidade cerebelar pode gerar ataxia, disartria, incoordenação e instabilidade postural, o que aumenta o risco de quedas e fraturas.

Uso indiscriminado de Benzodiazepínicos: uma realidade da Estratégia de Saúde da Família de Bugre/MG

Os Benzodiazepínicos (BZD's), medicamentos psicotrópicos, mundialmente utilizados para o tratamento da ansiedade e da insônia, de baixo custo e de fácil acesso em saúde pública, são comumente prescritos pelos médicos generalistas, muitas vezes de maneira inadequada, levando ao risco de abuso desta medicação. Os usuários da equipe desse estudo relatam uso prolongado (entre 2 e 8 anos) com finalidades outras que não apenas a terapêutica. Enfatizam também a facilidade em adquirir a medicação e a falta de orientação médica sobre os cuidados necessários durante o tratamento. Este estudo objetivou elaborar uma proposta de intervenção capaz de otimizar o atendimento aos usuários da Unidade de Saúde Programa Saúde da Família da cidade de Bugre que vem fazendo uso indiscriminado desta medicação. A população alvo foi constituída por todos os usuários de Benzodiazepínicos (Clonazepam, Diazepam e Bromazepam) durante o ano de 2013. Antes, porém, fez-se pesquisa bibliográfica no SCIELO e LILACS, com os descritores: benzodiazepínicos, conhecimentos, atitudes, abuso. Os resultados deste estudo apontam que a ocorrência de uso indevido envolve não apenas o sistema de controle da dispensação, mas uma série de outros fatores, entre os quais as atitudes dos profissionais de saúde. Foi observado o predomínio do uso de benzodiazepínicos na idade adulta, com destaque para o sexo feminino. Diante dos dados obtidos, observa-se que a utilização de benzodiazepínicos é crescente e os estudos indicam que realmente esta classe de medicamentos vem sendo utilizada indiscriminadamente pela população. Conclui-se que, um conjunto de ações, como a organização da estratégia da família, incentivar a política nacional de medicamentos, orientar contra a automedicação, uma melhor assistência farmacêutica, a responsabilidade dos prescritores e o uso irracional das medicações, são pontos que devemos modificá-los, para assim mudarmos essa realidade.