Agonistas de receptores adrenérgicos α-2, Ácido Valproico y Carbamazepina como tratamiento adyuvante en la abstinencia alcohólica moderada-grave: Revisión Sistemática / α-2 adrenergic recipients, Valproic and Carbamazepine Acids as a adjuvant treatment in moderate-grave alcoholic abstinence: Systematic Review

La dependencia del alcohol se encuentra entre los principales factores de riesgo para la salud en la mayoría de los países desarrollados y en desarrollo.El éxito terapéutico en la abstinencia modera-grave podría incrementarse con tratamiento adyuvante a las benzodiacepinas. En nuestro medio los agonistas alfa2 (clonidina y dexmedetomidina), ácido valproico y carbamazepina son los de mayor uso. El objetivo de este trabajo fue realizar la búsqueda exhaustiva, análisis crítico y resumen de la evidencia para proporcionar una visión general de la efectividad de estos fármacos cuando son utilizado sin tiempo determinado de tratamiento comparados entre sí, contra ninguna intervención, placebo u otras intervenciones. Se realizó una búsqueda bibliográfica en bases de datos (Pubmed/MEDLINE, LILACs, EMBASE). Dos revisores seleccionaron, extrajeron los datos y evaluaron el riesgo de sesgo de los estudios incluidos de forma independiente mediante el software Covidence. Los desacuerdos fueron resueltos por consenso. Realizamos metanálisis utilizando RevMan 5. 3 y análisis de subgrupos por diseño de estudio. Se incluyeron 22 estudios donde ninguno de ellos presentó bajo riesgo de sesgo en todos los dominios, y la mayoría de los estudios presentaron al menos un dominio con alto riesgo de sesgo. Estudios con resultados estadísticamente bajos mostraron que la dexmedetomidina y el ácido valproico disminuyen los requerimientos de benzodiacepinas en pacientes que recibían placebo. Además, cuando se combinan ácido valproico con benzodiacepinas logran una disminución estable y continua de la abstinencia medido en escala CIWA-Ar. La clonidina fue la única descripta que presentaba disminución en la frecuencia cardiaca frente a placebo con alta significancia, situación clínica a tener presente frente al síndrome simpaticomimético que caracteriza al síndrome de abstinencia por alcohol.

Alcohol dependence is among the main risk factors for health in most developed and developing countries. Therapeutic success in moderate-Grave abstinence could be increased with adjuvant treatment to benzodiazepines. In our environment, agonists Alfa 2 (clonidine and dexmedetomidine), valproic acid and carbamazepine are the most used. The objective of this work was to carry out the thorough search, critical analysis and summary of the evidence to provide an overview of the effectiveness of these drugs when used without a certain time of treatment compared to each other, against any intervention, placebo or other interventions. A bibliographic search was carried out in databases (Pubmed/ Medline, Lilacs, Embase). Two reviewers selected, extracted the data and evaluated the bias risk of independently included studies using the COVIDENCE software. The disagreements were resolved by consensus. We perform meta-analysis using Revman 5. 3 and subgroup analysis by study design. 22 studies were included where none of them presented under a risk of bias in all domains, and most studies presented at least one domain with high bias risk. Studies with statistically low results showed that dexmedetomidine and valproic acid decrease the requirements of benzodiazepines in patients receiving placebo. In addition, when valproic acid is combined with benzodiazepines achieve a stable and continuous decrease in abstinence measured in CIWA-AR scale. Clonidine was the only one described that presented a decrease in heart rate against placebo with high significance, clinical situation to be in mind in front of the sympathomimetic syndrome that characterizes alcohol withdrawal syndrome

Perfil do consumo dos benzodiazepínicos nos anos de 2019 e 2020 no brasil e regiões / Profile of the benzodiazepines in the years 2019 e 2020 in Brazil and regions / Perfil de consume y hospitalizaciones de los benzodiacepinas en los años 2019 y 2020 enBrasil y regiones

Os benzodiazepínicos estão entre os medicamentos mais prescritos, principalmente em países ocidentais, onde estimativas mostram um consumo anual de 1% a 3% da população.Objetivo:Estudar o perfil do consumo dos benzodiazepínicosnos anos de 2019-2020. Metodologia:Foram estudadas a taxa de desocupação segundo o Instituto Brasileiro de Geografia e Estatística, consumo dos benzodiazepínicosa partir do Sistema Nacional de Gerenciamento de Produtos Controlados da Agencia de Vigilância Sanitáriae quantidade de internações por envenenamento com exposição (acidental ou proposital), auto-intoxicação e efeitos adversos aos anticonvulsivantes, sedativos, hipnóticos, antiparkinsonianos e psicotrópicos segundo o Departamento de Informática do Sistema Único de Saúde no Brasil. Resultados:A região Norte e Nordeste apresentou um aumento na taxa de desocupação. O rendimento nominal mensal domiciliar per capitada população residente nas regiões Norte e Nordeste se manteveabaixo de 01 salário-mínimo nos anos de 2019 e 2020. De 2019 para 2020, o princípio ativo mais utilizado dos benzodiazepínicos industrializados foi o Clonazepam com incremento de 9,81% no Brasil e 22,52% na região Nordeste. Todas as formas farmacêuticas manipuladas apresentaram umaredução no consumo de 2019 para 2020, com exceção da forma em mililitros que apresentou um incremento para o bromazepam (42,1%), clonazepam (8,76%) e diazepam (5,27%). De 2020 em relação a 2019, ocorreu um incrementode 119,05% e 25% nas regiões Nordeste e Centro-Oeste, respectivamente, nasinternações por envenenamento [intoxicação] por exposição, a anticonvulsivantes (antiepilépticos), sedativos, hipnóticos, antiparkinsonianos e psicotrópicos não classificados em outra parte, intenção não determinada. Conclusões:Ocorreu um aumento no consumo de benzodiazepínicosindustrial no ano de 2020 sendo o envenenamento [intoxicação] umadas principais causasde internação. Há necessidade de um controle do consumo e vigilância aos psicotrópicos visto que estes fármacos estão dentre aqueles com risco de internações devido àexposição acidental ou não, autointoxicaçãoou efeitos adversos (AU).

Benzodiazepines are among the most prescribed drugs, especially in Western countrieswhere estimates show an annual consumption of 1% to 3% of the population.Objective: To study the profile of benzodiazepinesconsumptionfrom the National Controlled Products Management System of the Sanitary Surveillance Agencyin the years 2019 and 2020.Methodology:The unemployment rate,according to theBrazilian Institute of Geography and Statistics,benzodiazepines consumptionfrom the National Controlled Products Management System of the Sanitary Surveillance Agency, and the number of hospitalizations due to poisoning with exposure (accidental or intentional), self-intoxication, and adverse effects to anticonvulsants, sedatives, hypnotics, antiparkinsonian drugs and psychotropic drugs according to the Department of Informatics of the Unified Health System in Brazil were studied.Results:The North and Northeast regions showed an increase in the unemployment rate. The nominal monthly household income per capita of the population residing in the North and Northeast regions remained below 01 minimum wage in the years 2019 and 2020. From 2019 to 2020, the most used active substanceof industrialized benzodiazepines was Clonazepam with an increase of 9.81% in Brazil and 22.52% in the Northeast region. All compounded pharmaceutical forms showed a reduction in consumption from 2019 to 2020, with the exception of the form in milliliters which showed an increase for bromazepam (42.1%), clonazepam (8.76%) and diazepam (5.27%). In 2020 compared to 2019, there was an increase of 119.05% and 25% in the Northeast and Midwest regions, respectively, in hospitalizations for poisoning[intoxication] due to exposure toanticonvulsants (antiepileptics), sedatives, hypnotics, antiparkinsonian drugs,and psychotropic drugs not elsewhere classified with intent undetermined.Conclusions:There was an increase in the consumption of industrial benzodiazepines in 2020, with poisoning [intoxication] being one of the main causes of hospitalization. There is a need to control the consumption andincrease the surveillance of psychotropic drugs becausethese drugs are among those that involverisk of hospitalization due to accidental or non-accidental exposure, self-intoxication or adverse effects (AU).

ntroducción: Las benzodiacepinas se encuentran entre los fármacos más recetados, especialmente en los países occidentales, donde se estima que de 1% al 3% de la poblaciónde estos países los consumen. Objetivo: Estudiar el perfil del consumo de benzodiacepinas en los años 2019-2020.Metodología: Se midieron la tasa de desempleo según elInstituto Brasileño de Geografía y Estadística, el consumo de benzodiacepinasdel Sistema Nacional de Gestión de Productos Controlados de la Agencia de Vigilancia Sanitariay el número de hospitalizaciones por intoxicación con exposición (accidental o intencional), además se estudiaron autointoxicaciones y efectos adversos a los anticonvulsivos, sedantes, hipnóticos, drogas contra el mal de Parkinsony psicotrópicossegún elDepartamento de Informática del Sistema Único de Salud de Brasil.Resultados: Las regiones Norte y Nordeste presentaron aumento de la tasa de desempleo. El ingreso nominal mensual de los hogares per cápita de la población residente en las regiones Norte y Nordeste se mantuvo por debajo de 01 salario mínimo en los años 2019-2020. De 2019 a 2020, el principio activo más utilizado de las benzodiacepinas industrializadas fue el clonazepam con un aumento de 9,81% en Brasil y de22,52% en la región Nordeste. Todas las formas farmacéuticas compuestas mostraron una reducción en su consumo de 2019-2020, a excepción de la forma en mililitros que mostró un aumento para bromazepam (42,1%), clonazepam (8,76%) y diazepam (5,27%). En 2020 respecto a 2019, hubo un aumento del 119,05% y 25% en las regiones Noreste y Medio Oeste, respectivamente, en las hospitalizaciones por intoxicación por exposición aanticonvulsivos (antiepilépticos), sedantes, hipnóticos, drogas contra el mal de Parkinsony psicofármacos no clasificados en otra parte conintención indeterminada.Conclusiones: Hubo un aumento en el consumo de benzodiacepinas industriales en 2020, siendo las intoxicaciones una de las principales causas de hospitalización. Existe la necesidad de controlar el consumo y vigilancia de los psicofármacos, ya que estos fármacos se encuentran entre los de riesgo de hospitalización por exposición accidental o no accidental, autointoxicación o efectos adversos (AU).

Impacto de la implementación de un protocolo de sedoanalgesia en una unidad de cuidados intensivos pediátricos / Impact of the implementation of a sedation and analgesia protocol in a pediatric intensive care unit

Introducción. La adecuada sedación y analgesia es fundamental en el tratamiento de pacientes que requieren asistencia ventilatoria mecánica (AVM). Se recomienda la utilización de protocolos y su monitoreo; son dispares los resultados reportados sobre adhesión e impacto. Objetivos. Evaluar el impacto de la implementación de un protocolo de sedoanalgesia sobre el uso de benzodiacepinas, opioides y evolución en la unidad de cuidados intensivos pediátricos (UCIP), en pacientes que requieren AVM mayor a 72 horas. Métodos. Estudio tipo antes-después, no controlado, en la UCIP de un hospital pediátrico. Se desarrolló en 3 etapas: preintervención de diagnóstico situacional (de abril a septiembre de 2019), intervención y posintervención de implementación del protocolo de sedoanalgesia, educación sobre uso y monitorización de adherencia y su impacto (de octubre de 2019 a octubre de 2021). Resultados. Ingresaron al estudio 99 y 92 pacientes en las etapas pre- y posintervención, respectivamente. Presentaron mayor gravedad, menor edad y peso en el período preintervención. En la comparación de grupos, luego de ajustar por gravedad y edad, en la etapa posintervención se reportó una reducción en los días de uso de opioides en infusión continua (6 ± 5,2 vs. 7,6 ± 5,8; p = 0,018) y los días de uso de benzodiacepinas en infusión continua (3,3 ± 3,5 vs. 7,6 ± 6,8; p = 0,001). No se observaron diferencias significativas en los días de AVM y en los días totales de uso de benzodiacepinas. Conclusión. La implementación de un protocolo de sedoanalgesia permitió reducir el uso de fármacos en infusión continua.

Introduction. Adequate sedation and analgesia is essential in the management of patients requiring mechanical ventilation (MV). The implementation of protocols and their monitoring is recommended; mixed results on adherence and impact have been reported. Objectives. To assess the impact of the implementation of a sedation and analgesia protocol on the use of benzodiazepines, opioids, and evolution in the pediatric intensive care unit (PICU) in patients requiring MV for more than 72 hours. Methods. Before-and-after, uncontrolled study in the PICU of a children's hospital. The study was developed in 3 stages: pre-intervention for situational diagnosis (from April to September 2019), intervention, and post-intervention for implementation of a sedation and analgesia protocol, education on use, and monitoring of adherence and impact (from October 2019 to October 2021). Results. A total of 99 and 92 patients were included in the study in the pre- and post-intervention stages, respectively. Patients had a more severe condition, were younger, and had a lower weight in the preintervention period. After adjusting for severity and age, the group comparison in the post-intervention stage showed a reduction in days of continuous infusion of opioids (6 ± 5.2 versus 7.6­5.8, p = 0.018) and days of continuous infusion of benzodiazepines (3.3 ± 3.5 versus 7.6 ± 6.8, p = 0.001). No significant  differences were observed in days of MV and total days of benzodiazepine use. Conclusion. The implementation of a sedation and analgesia protocol resulted in a reduction in the use of continuous infusion of drugs.

Detection of Carbamazepine and Its Metabolites in Blood Samples by LC-MS/MS / 法医学杂志

OBJECTIVES@#To establish a method for the detection of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS).@*METHODS@#The blood samples were treated with 1-butyl-3-methylimidazolium hexafluorophosphate as an extraction solvent. The samples were extracted by ultrasound-assisted extraction and separated by ZORBAX Eclipse Plus C18, 95Å column. The mobile phase A aqueous solution containing 0.1% formic acid and 10 mmol/L ammonium acetate, and mobile phase B mixed organic solvent containing acetonitrile/methanol (Vacetonitrile∶Vmethanol=2∶3) were used for gradient elution at the flow rate of 1.00 mL/min. An electrospray ion source in positive mode was used for detection in the multiple reaction monitoring.@*RESULTS@#The linearities of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples were good within the corresponding range, with correlation coefficients (r) greater than 0.995 6. The limits of detection were 3.00, 0.40 and 1.30 ng/mL, respectively. The limit of quantitation were 8.00, 1.00 and 5.00 ng/mL, respectively. The extraction recoveries ranged from 76.00% to 106.44%. The relative standard deviations of the intra-day and inter-day precisions were less than 16%. Carbamazepine and its main metabolite 10,11-dihydro-10,11-epoxycarbamazepine were detected in blood samples of death cases with a mass concentration of 2.71 μg/mL and 252.14 ng/mL, respectively.@*CONCLUSIONS@#This method has high sensitivity and good selectivity, which is suitable for the detection of carbamazepine and its metabolites in blood samples, and can be used for carbamazepine-related forensic identifications.

Sedative use and incidence of falls and hip fractures among older adults in an outpatient geriatric clinic / Perfil de uso de sedativos e ocorrência de quedas e fratura de fêmur entre idosos em um ambulatório de geriatria

OBJECTIVE: To investigate the use of sedatives by older adults attending a private outpatient geriatric clinic in Belo Horizonte (MG), Brazil, and its association with falls and hip fractures. METHODS: Using a longitudinal design, the prevalence of benzodiazepine and nonbenzodiazepine ("z-drugs") intake by older adults was described and their association with the incidence of falls and fractures (30 days after the initial visit) was evaluated through logistic regression. RESULTS: A total of 7821 older adults were included in the study, most of them women (72.50%), with a mean age of 77.5 years and a mean Clinical-Functional Vulnerability Index (IVCF-20) score of 16.5. The overall prevalence of sedative use (any sedative) was 6.19%, with 4.48% benzodiazepines and 1.98% z-drugs. The most widely used sedatives were clonazepam (29.04%), zolpidem (28.65%), and alprazolam (23.44%). Falls were reported for 182 patients (2.33%), with a higher incidence among users of any sedatives (4.34; p = 0.002; OR = 1.94, adjusted for sex, age, and IVCF-20) and benzodiazepines (5.14%; p < 0.001; OR = 2.28) than among non-users (2.19%). Hip fractures occurred in 33 patients (0.42%), and again were more frequent among users of sedatives (1.03%; p = 0.032; OR = 2.57) and benzodiazepines (1.43%; p = 0.003; OR = 3.45) than among non-users (0.38%). CONCLUSIONS: The use of sedatives, especially benzodiazepines, is associated with an increased incidence of falls and hip fractures in older adults

OBJETIVO: Investigar a utilização de sedativos entre idosos atendidos em ambulatório privado de geriatria em Belo Horizonte (MG), bem como sua associação com quedas e fraturas de fêmur. METODOLOGIA: Trata-se de estudo longitudinal, no qual foi descrita a prevalência de uso de benzodiazepínicos e drogas Z entre idosos (60 anos ou mais) e avaliada sua associação com a incidência de queda e fratura (30 dias após consulta inicial) por meio de regressão logística. RESULTADOS: Foram incluídos no estudo 7821 idosos, com maioria feminina (72,50%), idade média de 77,5 anos e Índice de Vulnerabilidade Clínico Funcional (IVCF-20) médio de 16,5 pontos. A prevalência de uso de sedativos em geral foi de 6,19%, sendo 4,48% de benzodiazepínicos e 1,98% de drogas Z. Os medicamentos sedativos mais utilizados foram clonazepam (29,04%), zolpidem (28,65%) e alprazolam (23,44%). Relatou-se queda para 182 idosos (2,33%), com incidência maior entre usuários de sedativos (4,34; p = 0,002; OR = 1,94 ajustada por sexo, idade e IVCF-20) e de benzodiazepínicos (5,14%; p < 0,001; OR = 2,28) do que entre não usuários (2,19%). Identificou-se fratura de fêmur em 33 idosos (0,42%), sendo mais frequente entre usuários de sedativos (1,03%; p = 0,032; OR = 2,57) e de benzodiazepínicos (1,43%; p = 0,003; OR = 3,45) do que entre não usuários (0,38%). CONCLUSÃO: Concluiu-se que a incidência de quedas e fraturas de fêmur em idosos possui associação com o uso de medicamentos sedativos, em especial os benzodiazepínicos

Prevalence of the Consumption of Tranquilizers without a Medical Prescription and Associated Factors in School-Based Adolescents in Colombia / Prevalencia del consumo de tranquilizantes sin prescripción médica y factores asociados en adolescentes escolarizados de Colombia / Prevalência do uso de tranquilizantes sem prescrição médica e fatores associados em adolescentes em idade escolar na Colômbia

Introduction: Non-prescription tranquilizers are a specific group of benzodiazepines, used as drugs that act on the central nervous system and have an extensive effect in patients with anxiety disorders and problems in sleep stages. Objective: To determine the prevalence of the year and month of consumption of tranquilizers without a medical prescription and the associated factors, in adolescents in school in Colombia. Methods: It is a cross-sec-tional study with an analytical scope. The universe of the study consisted of 3,243,377 students, from grades 7 to 11 (aged between 12 and 18 years), the valid surveys were 80,018. The adolescent who declared having used tranquilizers during the last 30 days and the last 12 months was considered a consumer. All variables were self-re-ported by adolescents. Results: The prevalence of tranquilizer use without medical prescription was 1.02% and 1.97% (month and year, respectively). Adolescents who presented disciplinary problems are the most predisposed to use during the last month with an OR 2.79 (95% CI: 2.20­3.53) and last year an OR of 2.77 (95 % CI: 2.34­3.27). Conclusions: There is a higher prevalence of the consumption of tranquilizers without medical prescription in women between 14 and 17 years of age, from mixed schools and it is associated with academic and disciplinary performance problems, in the last year. In addition, as age increases, the consumption of substances without a medical prescription increases

Introducción: Los tranquilizantes sin prescripción médica son un grupo específico de benzodiacepinas, usados como medicamentos que actúan sobre el sistema nervioso central y cuentan con un extenso efecto en pacientes con trastornos de ansiedad y problemas en las etapas del sueño. Objetivo: Determinar la prevalencia de año y mes de consumo de tranquilizantes sin prescripción médica y los factores asociados en adolescentes escolarizados de Colombia. Métodos: Estudio transversal con alcance analítico. El universo del estudio estuvo constituido por 3 243 377 estudiantes de los gados 7.º a 11.º (con edades entre 12 y 18 años). Las encuestas válidas fueron 80 018. Se consideró consumidor al adolescente que declaró haber consumido tranquilizantes durante los últimos 30 días y los últimos 12 meses. Todas las variables fueron autorreportadas por los adolescentes. Resultados: La prevalencia de consumo de tranquilizantes sin prescripción médica fue del 1,02 % y del 1,97 % (mes y año, respectivamente). Los adolescentes que presentaron problemas disciplinarios son los más predispuestos al consumo durante el último mes con un OR de 2,79 (IC95 %: 2,20-3,53) y último año un OR de 2,77 (IC95 %: 2,34-3,27). Conclusiones: Existe mayor prevalencia de consumo de tranquilizantes sin prescripción médica en mujeres entre los 14 y los 17 años, de colegios mixtos, y se encuentra asociada con problemas de rendimiento académico y disciplinarios, en el último año. Además, a medida que aumenta la edad, se incrementa el consumo de sustancias sin prescripción médica

Introdução: Os tranquilizantes isentos de prescrição são um grupo específico de benzodiazepínicos, usados como medicamentos que atuam no sistema nervoso central e têm um efeito extenso em pa-cientes com transtornos de ansiedade e problemas no estágio do sono. Objetivo: Determinar a prevalência anual e mensal do uso de tranquilizantes sem prescrição médica e os fatores associados em adolescentes em idade escolar na Colômbia. Métodos: Estudo transversal com escopo analítico. O universo do estudo consistiu em 3243377 alunos da 7ª à 11ª série (com idades entre 12 e 18 anos). Foram realizadas 80018 pesquisas válidas. Um adolescente foi considerado usuário, o qual relatou ter usado tranquilizantes nos últimos 30 dias e nos últimos 12 meses. Todas as variáveis foram autorrelatadas pelos adolescentes. Resultados: A prevalência do uso de tranquilizantes sem prescrição médica foi de 1,02% e 1,97% (mês e ano, respectivamente). Os adolescentes com problemas disciplinares apresentaram maior pro-babilidade de uso no último mês, com um OR de 2,79 (IC95%: 2,20-3,53) e no último ano, com um OR de 2,77 (IC95%: 2,34-3,27). Conclusões: Há uma maior prevalência de uso de tranquilizantes sem prescrição médica em mulheres de 14 a 17 anos, de escolas mistas, e isso está associado a problemas de desempenho acadêmico e disciplinar no último ano. Além disso, com o aumento da idade, aumenta o uso de substâncias sem prescrição médica.

Évaluation de la prescription et de l'utilisation des benzodiazépines dans la ville de Sidi Bel-Abbès / Evaluation of the prescription and use of benzodiazepines in Sidi Bel-Abbes city

Introduction :Une forte consommation des benzodiazépines (BZDs) a été remarquée en dehors parfois des règles de recommandations de prescription, ce qui rend leur consommation un problème majeur de santé publique. La présente étude a eu pour objectif d'évaluer la prescription et l'usage des BZDs dans la ville de Sidi Bel-Abbès. Méthodes-Il s'agissait d'une étude descriptive transversale réalisée du 01 Février 2018 au 30 Juin 2018 évaluant la prescription et l'usage des BZDs dans la ville de Sidi Bel-Abbès au moyen d'un questionnaire distribué aux patients de l'hôpital psychiatrique, du service de psychiatrie du CHU et aux pharmaciens d'officine.Le critère de jugement principal était l'évaluation de la prescription et de l'utilisation des BZDs dans cette ville. La saisie et l'analyse des données ont été réalisées par le logiciel SPSS. Résultats-Au total, 353 patients traités au moins par une BZD ont été inclus dont 178 hommes. Le taux de prescription des BZDs était de 1.10, des jeunes (59,77 %) et des personnes mariées (60,34%) constituaient les consommateurs privilégiés. La prescription était l'apanage des psychiatres, en monothérapie (07,42%), la molé cule la plus fréquemment prescrite était le Bromazépam (31,07%) et la prise noc turne était la plus importante (49,01%). Les BZDs étaient utilisées pour combattre l'insomnie (25,21%), l'anxiété (16,43%), pour une durée de plus d'une année (57,79 %). Conclusion-La prescription et l'utilisation des BZDs dans la ville de Sidi Bel-Abbès s'est avérée importante. L'insomnie et l'anxiété constituaient les principales raisons de leur utilisation, et le Bromazépam était la molécule la plus fréquemment utilisée .

Introduction-A high consumption of benzodiazepines (BZDs) has been noticed so metimes outside the rules of prescription recommendations, which makes their consumption a major public health problem. The present study aimed to evaluate the prescription and use of BZDs in Sidi Bel-Abbès city. Methods-: This was a descriptive cross-sectional study carried out from February 01st, 2018 to June 30th, 2018 evaluating the prescription and use of BZDs in of Sidi Bel-Abbès by means of a questionnaire distributed to patients from the psychiatric hospital, the CHU psychiatry department and community pharmacists. The primary endpoint was the assessment of the prescription and use of BZDs in this city. Data entry and analysis were performed using SPSS software. Results-A total of 353 patients treated with at least one BZD were included, including 178 men. The prescription rate of BZDs was 1.10, young people (59.77%) and married people (60.34%) were the privileged consumers. The prescription was the prerogative of psychiatrists, in monotherapy (07.42%), the molecule most frequent ly prescribed was Bromazepam (31.07%) and night intake was the most important (49.01%). BZDs were used to combat insomnia (25.21%), anxiety (16.43%), for a period of more than a year (57.79%). Conclusion-The prescription and use of BZDs in Sidi Bel-Abbès has proven to be important. Insomnia and anxiety were the main reasons for their use, and Bromazepam was the most molecule frequently used.

Automedicación y riesgo de abuso con benzodiacepinas en pacientes adultos Lima-Perú, 2019 / Self-medication and risk of abuse with benzodiazepines in adults patients Lima-Peru, 2019

RESUMEN: Introducción: Las benzodiacepinas tienen potencial para generar abuso, por lo que, un consumo indiscriminado, a través de la venta sin prescripción y la práctica de automedicación, significaría un alto riesgo, producto de su abuso. Objetivo: Establecer la relación entre la automedicación con benzodiacepinas y el riesgo de abuso en pacientes de un hospital de Lima-Perú. Metodología: Estudio transversal analítico. Se encuestó a 874 participantes, se usó una encuesta para determinar datos demográficos, uso de benzodiacepinas y preguntas de la prueba de detección de consumo de alcohol, tabaco y sustancias (ASSIST, por sus siglas en inglés); se obtuvo estadística descriptiva y analítica. Resultados: Hubo más encuestadas del sexo femenino (74,5%), la mediana de edades fue de 52 años (rango intercuartílico: 40-62 años). De los adultos estudiados, 485 fueron considerados como consumidores de benzodiacepinas con receta médica y 389 sin receta médica. Los consumidores con receta médica y sin receta médica que necesitaron tratamiento fueron 129 (26,6%) y 245 (63,0%), respectivamente (p<0.001). Conclusión: Hay una mayor prevalencia de personas que necesitan tratamiento por abuso en consumidores sin receta médica que en el grupo de consumidores con receta médica, por lo que, existe una relación significativa entre la automedicación con benzodiacepinas y el riesgo de abuso; lo que requiere tratamiento en la población estudiada.

ABSTRACT Introduction: Benzodiazepines have the potential to generate abuse, so an indiscriminate consumption, through the sale without prescription and the practice of self-medication, would mean a high risk due to their abuse. Objective: To establish the relationship between self-medication with benzodiazepines and the risk of abuse that requires treatment in adult patients of Hospital San Juan de Lurigancho, 2019. Methodology: It was an observational, correlational descriptive, transversal and prospective study. The sample size was 874 participants (95.0% confidence level; 80% power). Sampling was performed non-randomly. A survey was used to determine demographics, benzodiazepine use, and questions of Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). Results: Of the study population, the most prevalent demographic data were female sex (74.5%), the median age was 52 years (interquartile range: 40-62 years), the age range 50-59 years (26.43%), married marital status (31.6%), secondary education level (48.4%) and occupation as a housewife (47.3%). Of adults studied, 485 were considered as consumers of benzodiazepines with prescription and 389 consumers without a prescription. Prescription and non-prescription consumers needing treatment were 129 (26.60%) and 245 (62.98%), respectively (p <0.001). Conclusion: There is a higher prevalence of people who need treatment for abuse in consumers without a prescription than in the group of consumers with a prescription so there is a significant relationship between self-medication with benzodiazepines and the risk of abuse that requires treatment in study population.

Descripción de la disponibilidad y normas para el uso de las benzodiacepinas en algunos países de América Latina, 2022 / Description of benzodiazepines availability and regulation in several countries of Latin America, 2022 / Descrição da disponibilidade e regulamentação para o uso de benzodiazepínicos em alguns países da América Latina, 2022

Resumen: Introducción: las benzodiacepinas constituyen un grupo farmacológico de amplia prescripción a nivel mundial desde su aparición en la década de 1960. El objetivo del presente estudio fue identificar la disponibilidad, las modalidades de prescripción y dispensación de benzodiacepinas en diferentes países de América Latina, según reglamentación vigente en cada país participante del estudio. Materiales y métodos: estudio observacional, descriptivo y transversal, realizado con los datos disponibles al año 2022 de todos los países miembros de la Red de Centros de Información de Medicamentos de LatinoAmérica y el Caribe (Red CIMLAC) que fueron parte del estudio. Se utilizaron las bases de datos de las agencias regulatorias, la reglamentación vigente y otros documentos necesarios para obtener la información sobre la dispensación y prescripción en cada país. Resultados: doce de los 20 países de la Red CIMLAC completaron el estudio. El total de benzodiacepinas disponible en cada país varió entre 6 y 12 (media: 9). De ellas, en promedio 5 estaban incluidas en listados de medicamentos esenciales nacionales. La mayoría de los países cuentan con combinaciones a dosis fijas con benzodiacepinas. En todos los países se realiza la prescripción por receta especial. Más de la mitad de los países cuentan con recomendaciones nacionales. Conclusiones: la amplia disponibilidad de benzodiacepinas comercializadas, la existencia de combinaciones a dosis fijas y la falta de recomendaciones nacionales pueden ser factores que contribuyan al uso irracional de este grupo terapéutico.

Summary: Introduction: benzodiazepines constitute a widely prescribed group of drugs around the world, since they appeared in the sixties. This study aims to identify the availability, prescription modalities and dispensing of benzodiazepines in different countries around Latin America, as per the legal provisions in force in each of the countries participating in the study. Method: observational, descriptive, transversal study based on the information available in 2022 about all the member countries of the Network Medicines Information Centers of Latin America and the Caribbean (CIMLAC Network) that were part of the study. The databases of regulatory authorities were used and the legal provisions in force and relevant documents were consulted in order to obtain information on benzodiazepines dispensing and prescription in each country. Results: twelve out of the 20 CIMLAC Network member countries completed the study. The total number of benzodiazepines available in the study ranged from 6 to 12 (mean was 9), and 5 of them on average were included in the national essential medications lists. Most countries have benzodiazepines fixed dose combinations and in all countries a special medical prescription is needed. More than half of the countries have national recommendations. Conclusions: the wide availability of benzodiazepines in the market, the existence of fixed-dose combinations and the lack of national recommendations may constitute factors that contribute to the irrational use of this group of drugs.

Resumo: Introdução: os benzodiazepínicos constituem um grupo farmacológico amplamente prescrito em todo o mundo desde seu surgimento na década de 1960. O objetivo deste estudo foi identificar a disponibilidade, prescrição e modalidades de dispensação de benzodiazepínicos em diferentes países da América Latina, de acordo com as regulamentações vigentes em cada país participante do estudo. Materiais e métodos: estudo observacional, descritivo e transversal, realizado com os dados disponíveis até o ano de 2022 dos países membros da Rede de Centros de Informação sobre Medicamentos da América Latina e do Caribe (Red CIMLAC) que faziam parte do estudo. As bases de dados das agências reguladoras, normas vigentes e outros documentos necessários foram utilizados para obter informações sobre dispensação e prescrição em cada país. Resultados: doze dos 20 países da Rede CIMLAC completaram o estudo. O número total de benzodiazepínicos disponíveis em cada país variou entre 6 e 12 (média: 9). Destes, uma média de 5 foram incluídos nas listas nacionais de medicamentos essenciais. A maioria dos países tem combinações de dose fixa com benzodiazepínicos. Em todos os países é necessário prescrição especial. Mais da metade dos países têm recomendações nacionais. Conclusões: a ampla disponibilidade de benzodiazepínicos comercializados, a existência de combinações em doses fixas e a falta de recomendações nacionais podem ser fatores que contribuem para o uso irracional desse grupo terapêutico.

Segundo estudio de consumo de benzodiazepinas en una población uruguaya (2014-2018): el problema avanza / Second study on the use of benzodiazepines in a Uruguayan population (2014-2018): the problem advances / Segundo estudo de consumo de benzodiazepínicos em uma população uruguaia (2014-2018): o problema avança

Resumen: Introducción: las benzodiazepinas (BZD) constituyen uno de los grupos farmacológicos más prescritos. La forma de uso y el riesgo de aumento de efectos adversos evitables a partir del amplio uso, pueden representar en sí mismos problemas de salud pública. Objetivos: conocer el consumo de BZD en una población uruguaya en el período 2014-2018. Métodos: se realizó un estudio de utilización de medicamentos para evaluar el consumo de BZD por vía oral, a través del dato de dispensación de farmacias de instituciones de salud, mediante la variable DHD (dosis diaria definida/1.000 habitantes/día). Resultados: participaron siete instituciones, representando el 65% de la población uruguaya. Las DHD globales fueron 116,05, 114,36, 117,32, 131,17 y 124,4 DHD para los años 2014, 2015, 2016, 2017 y 2018 respectivamente, con un aumento de 7% en el período. Conclusiones: el consumo de BZD a nivel nacional entre 2014 y 2018 persiste elevado y superior al estudio previo realizado entre 2010 y 2012. Comparado con otros países, los valores para Uruguay se encuentran entre los más altos. Es necesario que todos los actores relevantes de la cadena del medicamento desarrollen estrategias para controlar la situación.

Summary: Introduction: benzodiazepines (BZD) constitute one of the most widely prescribed pharmacological groups. The use modality and the risk of increase of avoidable adverse effects resulting from wide consumption may represent a public health problem in itself. Objectives: to learn about the use of benzodiazepine in a Uruguayan population between 2014 and 2018. Method: a study was conducted on the use of medications to evaluate BZD consumption administered orally, by consulting dispensing of pharmacies in the health institutions, through the DHD variable (daily human doses/1.000 inhabitants/day). Results: 7 institutions participated in the study, representing 65% of the Uruguayan population. Global DHD were 116.05, 114.36, 117.32, 131.17 and 124.4 for 2014, 2015, 2016, 2017 and 2018 respectively, with a 7% increase in the period of study. Conclusions: the use of benzodiazepines was still high at the national level between 2014 and 2018 and greater than the figure found in the previous study, conducted between 2010 and 2012. Compared to other countries, Uruguayan figures are among the highest. All relevant actors in the drug chain need to develop strategies to control the situation.

Resumo: Introdução: os benzodiazepínicos (BZD) constituem um dos grupos farmacológicos mais prescritos. A forma de uso e o risco de aumento dos efeitos adversos evitáveis pelo uso extensivo podem representar, por si só, problemas de saúde pública. Objetivos: conhecer o consumo de BZD em uma população uruguaia no período 2014-2018. Métodos: foi realizado um estudo de uso de medicamentos para avaliar o consumo de BZD por via oral, utilizando dados da dispensação em farmácias de instituições de saúde, utilizando a variável DHD (dose diária definida/1000 habitantes/dia). Resultados: dados de sete instituições foram estudados, representando 65% da população uruguaia. Os DHDs globais foram 116,05, 114,36, 117,32, 131,17 e 124,4 DHDs para os anos de 2014, 2015, 2016, 2017 e 2018 respectivamente, com aumento de 7% no período. Conclusões: o consumo de BZD em nível nacional entre 2014 e 2018 continua alto e é superior aos resultados de um estudo anterior realizado entre 2010 e 2012. Quando comparados com outros países, os valores para o Uruguai estão entre os mais altos. É necessário que todos os atores relevantes da cadeia de medicamentos desenvolvam estratégias para controlar a situação.

Insomnio en tiempos de pandemia / Insomnia in pandemic times

El sueño es una función biológica de importancia para los seres vivos y su alteración más frecuente es el insomnio. Se define como la dificultad para conciliar o mantener el sueño, acompañada de una sensación de descanso no reparadora, a pesar de que las condiciones ambientales para ello son adecuadas, y que suele asociarse a fatiga y somnolencia durante el día. En los tiempos prepandemia ya se sabía que existía una alta prevalencia, pero durante la pandemia las cifras han aumentado y probablemente seguirán aumentando postpandemia, lo que conlleva a un incremento de las consultas en la atención primaria. Las medidas no farmacológicas son esenciales para incrementar la eficacia de las medidas terapéuticas. Las benzodiacepinas y los compuestos Z tienen bastantes efectos adversos y no son la primera opción, especialmente en los adultos mayores. La melatonina es mejor tolerada pero su eficacia no está comprobada.

Sleep is an important biological function for living beings and its most frequent alteration is insomnia. It is defined as difficulty in falling or staying asleep, accompanied by a feeling of non-restorative rest, despite adequate environmental conditions, and is usually associated with fatigue and sleepiness during the day. In pre-pandemic times, it was already known that there was a high prevalence, but during the pandemic, the figures have increased and will probably continue to increase post-pandemic, leading to an increase in consultations in primary care. Non-pharmacological measures are essential to increase the efficacy of therapeutic measures. Benzodiazepines and Z-compounds have quite a few adverse effects and are not the first choice, especially in older adults. Melatonin is better tolerated but its efficacy is not verified.

Benzodiazepines utilization in Brazilian older adults: a population-based study / Utilização de benzodiazepínicos em idosos brasileiros: um estudo de base populacional

ABSTRACT OBJECTIVE To evaluate the utilization of benzodiazepines (BZD) in Brazilian older adults, based on the Pesquisa Nacional de Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM - National Survey of Access, Use and Promotion of Rational Use of Medicines). METHODS The PNAUM is a cross-sectional study conducted between 2013 and 2014, representing the Brazilian urban population. In the present study, we included 60 years or older (n = 9,019) individuals. We calculated the prevalence of BZD utilization in the 15 days prior to survey data collection according to independent variables, using a hierarchical Poisson regression model. A semistructured interview performed empirical data collection (household interview). RESULTS The prevalence of BZD utilization in the older adults was 9.3% (95%CI: 8.3-10.4). After adjustments, BZD utilization was associated with female sex (PR = 1.88; 95%CI: 1.52-2.32), depression (PR = 5.31; 95%CI: 4.41-6, 38), multimorbidity (PR = 1.44; 95%CI: 1.20-1.73), emergency room visit or hospitalization in the last 12 months (PR = 1.42; 95%CI: 1.18-1.70 ), polypharmacy (PR = 1.26; 95%CI: 1.01-1.57) and poor or very poor self-rated health (PR = 4.16; 95%CI: 2.10-8.22). Utilization was lower in the North region (PR = 0.18; 95%CI: 0.13-0.27) and in individuals who reported abusive alcohol consumption in the last month (PR = 0.42; 95%CI: 0.19-0.94). CONCLUSION Despite contraindications, results showed a high prevalence of BZD utilization in older adults, particularly in those with depression, and wide regional and sex differences.

RESUMO OBJETIVO Avaliar a utilização de benzodiazepínicos (BZD) em idosos brasileiros,a partir de dados da Pesquisa Nacional de Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM). MÉTODOS A PNAUM é um estudo transversal, conduzido entre 2013 e 2014, com representatividade da população urbana brasileira. No presente estudo, foram incluídos indivíduos com 60 anos ou mais (n = 9.019). Foi calculada a prevalência de utilização de BZD nos 15 dias anteriores à coleta dos dados da pesquisa, geral e segundo as variáveis independentes, por meio de análise bruta e ajustada, utilizando modelo hierárquico de regressão de Poisson. A coleta de dados foi realizada por meio de entrevista domiciliar. RESULTADOS A prevalência de utilização de BZD em idosos foi de 9,3% (IC95%: 8,3-10,4). Após análise ajustada, foram associados à maior utilização de BZD: sexo feminino (RP = 1,88; IC95%: 1,52-2,32), depressão (RP = 5,31; IC95%: 4,41-6,38), multimorbidade (RP = 1,44; IC95%: 1,20-1,73), visita à emergência ou internação hospitalar nos últimos 12 meses (RP = 1,42; IC95%: 1,18-1,70), polifarmácia (RP = 1,26; IC95%: 1,01-1,57) e autopercepção de saúde ruim ou muito ruim (RP = 4,16; IC95%: 2,10-8,22). A utilização foi menor na região Norte (RP = 0,18; IC95%: 0,13-0,27) e em indivíduos que relataram consumo abusivo de álcool no último mês (RP = 0,42; IC95%: 0,19-0,94). CONCLUSÃO Apesar das recomendações contrárias ao uso, os resultados demonstraram elevada prevalência de utilização de BZD em idosos, particularmente naqueles que apresentam depressão, além de amplas diferenças em relação às regiões do país e ao sexo do indivíduo.

Cannabinoids for major neurocognitive disorder: case report and literature review / Uso de cannabinoides en trastorno neurocognitivo mayor: reporte de un caso y revisión de la literatura

ABSTRACT Introduction: Major neurocognitive disorder (MNCD) affects millions of people worldwide. However, the pharmacological options for its management are limited, ineffective and frequently associated with severe adverse reactions. Case report: An 85-year-old man with history of multiple chronic brain injuries (alcohol-use disorder, haemorrhagic stroke, brain trauma, chronic use of benzodiazepines) developed an MNCD, reaching 7 points on the Reisberg Global Deterioration Scale. He had minimal response to antidepressants, antipsychotics and anticholinergic medications. After the use of mother tincture of Indian hemp (cannabis), a significant improvement was found in his cognitive function, ability to carry out activities of daily living and independence. Discussion: The endocannabinoid system seems to be implicated in age-related cognitive decline. In addition, the evidence derived from in-vitro and animal models suggest that this system could play an important role in the management of MNCD of different causes. Conclusions: Cannabinoid treatment for MNCD emerges as a promising therapeutic approach that may benefit a growing number of patients who do not have other treatment options. It is therefore necessary to encourage more research efforts that will help to remove political and scientific barriers to its clinical use.

RESUMEN Introducción: El trastorno neurocognitivo mayor (TNM) afecta a millones de personas a nivel mundial. Sin embargo, las opciones farmacológicas para su manejo son limitadas, poco efectivas y se asocian a importantes reacciones adversas. Caso clínico: Se presenta el caso clínico de un hombre de 85 años, con antecedente de múltiples lesiones cerebrales crónicas (abuso de alcohol, enfermedad cerebrovascular, traumatismo cerebral, uso crónico de benzodiacepinas), quien desarrolló un TNM clasificado con 7 puntos en la Reisberg Global Deterioration Scale. Tuvo poca respuesta al manejo con antidepresivos, antipsicóticos y anticolinérgicos. Tras el uso de tintura madre de cáüamo índico (cannabis), se evidenció una mejoría en la función cognitiva, la capacidad de cuidado para las actividades de la vida diaria y la independencia. Discusión: El sistema endocanabinoide parece estar relacionado con los procesos de deterioro cognitivo asociados con la edad. Además, la evidencia derivada de modelos in vitro y animales sugiere que podría tener un papel importante en el manejo del TNM de diferentes etiologías. Conclusiones: El uso de cannabinoides en el TNM se presenta como una pista terapéutica prometedora. Por lo tanto, es necesario promover procesos de investigación que contribuyan a eliminar las barreras políticas y científicas para su uso clínico, beneficiando a un número creciente de pacientes que no poseen opciones terapéuticas eficaces.

Dilema terapéutico: síndrome de abstinencia alcohólica y encefalopatía hepática concurrentes. A propósito de un caso / Therapeutic dilemma: alcohol withdrawal syndrome and concurrent hepatic encephalopathy. A case report

RESUMEN El trastorno por consumo de alcohol es una de las principales causas de morbimortalidad en el mundo. La enfermedad hepática alcohólica es una complicación común de este trastorno y la encefalopatía hepática es una seria comorbilidad de la cirrosis alcohólica. Los factores precipitantes pueden relacionarse con infección, sangrado gastrointestinal, deshidratación o efectos de psicofármacos (p. ej., benzodiacepinas e hipnóticos no benzodiacepínicos). Se expone un caso del manejo hospitalario de un paciente con un trastorno severo por consumo de alcohol, cirrosis y encefalopatía hepática, quien desarrolla síntomas de abstinencia alcohólica durante su hospitalización y la complejidad del manejo antagónico de un delirium gabaérgico propio de la encefalopatía hepática en el contexto de un delirium glutamatérgico-noradrenérgico por abstinencia alcohólica.

ABSTRACT Alcohol use disorder is one of the main causes of morbidity and mortality in the world. Alcoholic liver disease is a common complication of this disorder, and hepatic encephalopathy is a serious complication of alcoholic cirrhosis. Precipitating factors may be related to infection, gastrointestinal bleeding, dehydration or the effects of psychotropic drugs (e.g. benzodiazepines and non-benzodiazepine hypnotics). We present a case of the hospital management of a patient with a severe alcohol use disorder, cirrhosis and hepatic encephalopathy who developed alcohol withdrawal symptoms while in hospital, and discuss the complexity of the antagonistic management of a GABAergic delirium characteristic of hepatic encephalopathy in the context of a glutamatergic-noradrenergic delirium due to alcohol withdrawal.

Supramolecular Solvent Extraction-Gas Chromatography-Tandem Mass Spectrometry for Detection of Benzodiazepines in Urines / 法医学杂志

Objective To establish a method using supramolecular solvent and gas chromatography-tandem mass spectrometry （GC-MS/MS） to analyze 9 benzodiazepines in urines. Methods Urine samples containing 9 benzodiazepines reference substance were subjected to liquid-liquid extractions with supramolecular solvent, which consisted of tetrahydrofuran and 1-hexanol. The solvent layer was evaporated to dryness by stream of nitrogen. The residue was reconstituted with methanol, and GC-MS/MS analysis was performed on it. The way of data collection was multiple reaction monitoring （MRM） mode; internal standard method was employed for quantification. Results In urine samples, when the range of mass concentration was 1-100 ng/mL for diazepam, midazolam, flunitrazepam and clozapine, 5-100 ng/mL for lorazepam and alprazolam, 2-100 ng/mL for nitrazepam and clonazepam, and 0.2-100 ng/mL for estazolam, respectively, good linearities were obtained, correlation coefficients were 0.999 1-0.999 9, the lower limits of the quantifications ranged from 0.2 to 5 ng/mL, the extraction recovery rates were 81.12%-99.52%. The intra-day precision ［relative standard deviation （RSD）］ and accuracy （bias） were lower than 9.86% and 9.51%, respectively; the inter-day precision （RSD） and accuracy （bias） were lower than 8.74% and 9.98%, respectively. Nine drugs in urine samples showed good stability at ambient temperature and -20 ℃ within 15 days. The mass concentrations of alprazolam in urine samples obtained from 8 volunteers who took alprazolam tablets orally within 8-72 h after ingestions ranged from 6.54 to 88.28 ng/mL. Conclusion The supramolecular solvent extraction GC-MS/MS method for analysis of 9 benzodiazepines in urines provided by this study is simple, fast, accurate and sensitive, which can provide technical support for monitoring of poisoning by benzodiazepines for clinical treatment and judicial identification.