Reacciones adversas a montelukast: de la teoría a la práctica. Serie de casos / Adverse drug reactions of montelukast: from theory to practice. Case report

El montelukast se utiliza ampliamente en el tratamiento de sibilancias recurrentes y/o asma. Están descritas numerosas reacciones adversas medicamentosas (RAM) en niños relacionadas con montelukast; se destacan las neuropsiquiátricas. Realizamos un estudio observacional, retrospectivo, descriptivo, sobre RAM relacionadas con montelukast. Entre enero de 2012 y diciembre de 2017, en la Unidad de Neumonología Pediátrica se trataron con Montelukast 348 pacientes; de ellos, 20 presentaron RAM. Los síntomas más frecuentes fueron insomnio (n = 7), hiperactividad (n = 4), pesadillas (n = 3), dolor abdominal (n = 2) y parestesias en extremidades (n = 2). Se presentaron desde días hasta meses tras iniciar el tratamiento, y desaparecieron tras su suspensión. Se destacan dos pacientes con parestesias en extremidades, síntoma no descrito antes en niños. El 5,7 % de los pacientes tratados con montelukast presentaron RAM que requirieron suspender el tratamiento. Los trastornos del sueño fueron los más frecuentes.

Montelukast is widely used in recurrent wheezing and/or asthma treatment. Several adverse drug reactions (ADRs) have been described in children related to montelukast. Neuropsychiatric reactions are one of the most important. We designed an observational, retrospective, descriptive study on ADRs related to montelukast in the Pediatric Pulmonology Unit, Hospital Universitario Miguel Servet, Zaragoza, Spain. Between January 2012 and December 2017, in the Pediatric Pulmonology Unit, 348 patients were treated with Montelukast; of them, 20 presented RAM. The main symptoms described were insomnia (n = 7), hyperactivity (n = 4), nightmares (n = 3), abdominal pain (n = 2) and paraesthesia in extremities (n = 2). They appeared from the first days to months after the start of treatment and disappeared after stopping it. Two patients presented limb paresthesia, not described previously in children. The 5.7 % of our patients treated with montelukast had ADRs that required treatment discontinuation. Sleep disorders were the most frequent.

Carbamazepine for prevention of chemotherapy-induced nausea and vomiting: a pilot study / Carbamazepina para prevenção de náusea e vômito induzidos por quimioterapia: um estudo piloto

CONTEXT AND OBJECTIVE: Nausea and vomiting are major inconveniences for patients undergoing chemotherapy. Despite standard preventive treatment, chemotherapy-induced nausea and vomiting (CINV) still occurs in approximately 50% of these patients. In an attempt to optimize this treatment, we evaluated the possible effects of carbamazepine for prevention of CINV. DESIGN AND LOCATION: Prospective nonrandomized open-label phase II study carried out at a Brazilian public oncology service. METHODS: Patients allocated for their first cycle of highly emetogenic chemotherapy were continuously recruited. In addition to standard antiemetic protocol that was made available, they received carbamazepine orally, with staggered doses, from the third day before until the fifth day after chemotherapy. Considering the sparseness of evidence about the efficacy of anticonvulsants for CINV prevention, we used Simon's two-stage design, in which 43 patients should be included unless overall complete prevention was not achieved in 9 out of the first 15 entries. The Functional Living Index-Emesis questionnaire was used to measure the impact on quality of life. RESULTS: None of the ten patients (0%) presented overall complete prevention. In three cases, carbamazepine therapy was withdrawn because of somnolence and vomiting before chemotherapy. Seven were able to take the medication for the entire period and none were responsive, so the study was closed. There was no impact on the patients' quality of life. CONCLUSION: Carbamazepine was not effective for prevention of CINV and also had a deleterious side-effect profile in this population. .

CONTEXTO E OBJETIVO: Náusea e vômito são inconvenientes importantes para pacientes submetidos a quimioterapia. A despeito do tratamento preventivo padrão, náuseas e vômitos induzidos por quimioterapia (NVIQ) ocorrem em aproximadamente 50% dos pacientes. Na tentativa de otimizar este tratamento, avaliamos os possíveis efeitos da carbamazepina na prevenção de náuseas e vômitos induzidos por quimioterapia. TIPO DE ESTUDO E LOCAL: Estudo fase II, prospectivo, não randomizado, aberto, realizado em um serviço público brasileiro de oncologia. MÉTODOS: Recrutaram-se continuamente pacientes alocados para o primeiro ciclo de quimioterapia altamente emetogênica. Além do protocolo anti-emético padrão disponibilizado, os pacientes receberam carbamazepina, por via oral, em doses escalonadas, a partir do terceiro dia anterior até o quinto dia após a quimioterapia. Dada a escassa evidência de eficácia dos anticonvulsivantes na prevenção de NVIQ, adotamos o desenho de Simon em duas fases, que deveria incluir 43 pacientes a não ser que prevenção completa global não fosse alcançada em 9 dos primeiros 15 participantes. O questionário "Functional Living Index-Emesis" foi usado para avaliar o impacto na qualidade da vida. RESULTADOS: Nenhum dos 10 pacientes (0%) apresentou prevenção completa global. Três tiveram a carbamazepina suspensa por sonolência e vômito antes da quimioterapia. Sete foram capazes de tomar a medicação por todo o período proposto e nenhum obteve resposta, sendo então interrompido o estudo. Não houve impacto na qualidade da vida. CONCLUSÃO: Carbamazepina não foi efetiva para prevenção de NVIQ e apresentou perfil deletério de efeitos adversos nesta população. .

Factors associated with sleep quality in the elderly receiving chemotherapy / Fatores associados à qualidade do sono de idosos submetidos à quimioterapia / Factores asociados a la calidad del sueño de mayores sometidos a la quimioterapia

OBJECTIVE: to evaluate the characteristics of sleep and the factors associated with the quality of sleep in elderly patients receiving outpatient chemotherapy treatment. METHOD: cross-sectional study with 140 elderly patients (51.2% female, average age 69.8 years) with stage III or stage IV cancer (67.9%), undertaken in a university hospital in the state of São Paulo in 2010. The following instruments were used: sociodemographic and clinical characterization questionnaire, validated by specialists; Pittsburgh Sleep Quality Index; Piper Fatigue Scale-reviewed; and a scale for the subjective measurement of pain. RESULTS: the majority of the elderly (62.9%) had a score compatible with poor sleep quality. On average, the duration of sleep was 388.0 minutes, latency was 44.6 minutes and efficiency of 83.8%. Through multiple logistic regression analysis, an increase of 21% in the probability of having poor sleep quality was observed for each single-point increase in the intensity of the pain. CONCLUSION: nursing interventions aiming to promote better sleep quality for elderly patients with cancer must include measures for pain control.

OBJETIVO: avaliar as características do sono e os fatores associados à qualidade do sono de pacientes idosos, submetidos ao tratamento quimioterápico ambulatorial. MÉTODO: estudo transversal, com 140 pacientes idosos (51,2% do sexo feminino, média de idade 69,8 anos), com câncer em estádio III ou IV (67,9%), conduzido em um hospital universitário do Estado de São Paulo, em 2010. Utilizaram-se os instrumentos: questionário de caracterização sociodemográfica e clínica, validado por especialistas; Índice de Qualidade do Sono de Pittsburgh; Escala de Fadiga de Piper-revisada; Escala de Mensuração Subjetiva de Dor. RESULTADOS: a maioria dos idosos (62,9%) apresentou pontuação compatível com má qualidade do sono. Em média, a duração do sono foi de 388,0 minutos, latência de 44,6 minutos e eficiência, 83,8%. À análise de regressão logística múltipla observou-se aumento de 21% da probabilidade de apresentar má qualidade do sono a cada acréscimo de um ponto na intensidade da dor. CONCLUSÃO: intervenções de enfermagem, visando promover melhor qualidade do sono aos pacientes idosos com câncer, devem agregar medidas para controle da dor.

OBJETIVO: evaluar las características del sueño y los factores asociados a la calidad del sueño de pacientes mayores sometidos al tratamiento de quimioterapia de ambulatorio. MÉTODO: estudio transversal con 140 pacientes mayores (51,2% del sexo femenino, media mayores 69,8 años) con cáncer en estadio III o IV (67,9%), acarreado en un hospital universitario de la provincia de São Paulo, en 2010. Se utilizaron los instrumentos: cuestionario de caracterización socio-demográfica y clínica, validado por expertos; Índice de Calidad del Sueño de Pittsburgh; Escala de Fatiga de Piper-revisada; Escala de mensuración subjetiva de dolor. RESULTADOS: la mayoría de los mayores (62,9%) presentó puntuación compatible con mala calidad del sueño. En media, la duración del sueño fue de 388,0 minutos, latencia de 44,6 minutos y eficiencia, 83,8%. Al análisis de regresión logística múltiple se observó aumento del 21% de la probabilidad de presentar mala calidad del sueño a cada añadidura de un punto en la intensidad del dolor. CONCLUSIÓN: intervenciones de enfermería objetivando promover mejor calidad del sueño a los pacientes mayores con cáncer deben agregar medidas para control del dolor.

Sedative antidepressants and insomnia / Antidepressivos sedativos e insônia

OBJECTIVE: The present review addresses the relationship between sleep and depression and how serotonergic transmission is implicated in both conditions. METHOD: Literature searches were performed in the PubMed and MedLine databases up to March 2010. The terms searched were "insomnia", "depression", "sedative antidepressants" and "serotonin". In order to pinpoint the sedative antidepressants most used to treat insomnia, 34 ISI articles, mainly reviews and placebo-controlled clinical trials, were selected from 317 articles found in our primary search. RESULTS: Sleep problems may appear months before the diagnosis of clinical depression and persist after the resolution of depression. Treatment of insomnia symptoms may improve this comorbid disease. Some antidepressant drugs can also result in insomnia or daytime sleepiness. Serotonin (5-HT) demonstrates a complex pattern with respect to sleep and wakefulness that is related to the array of 5-HT receptor subtypes involved in different physiological functions. It is now believed that 5HT2 receptor stimulation is subjacent to insomnia and changes in sleep organization related to the use of some antidepressants. CONCLUSION: Some drugs commonly prescribed for the treatment of depression may worsen insomnia and impair full recovery from depression. 5-HT2 receptor antagonists are promising drugs for treatment strategies since they can improve comorbid insomnia and depression.

OBJETIVO: Esta atualização aborda a relação entre sono e depressão e como a transmissão serotoninérgica está envolvida em ambas condições. MÉTODO: Foi realizada uma busca na literatura no PubMed e MedLine até março de 2010 com os termos "insônia", "depressão", "antidepressivos sedativos" e "serotonina". A fim de contemplar os antidepressivos sedativos mais utilizados no tratamento da insônia, 34 artigos ISI, principalmente revisões e estudos clínicos placebo-controlados, foram selecionados entre 317 artigos encontrados na busca inicial. RESULTADOS: Alterações de sono podem aparecer meses antes do diagnóstico clínico de depressão e persistir após a resolução da depressão. O tratamento dos sintomas de insônia pode melhorar essa doença associada. Alguns antidepressivos também podem levar à insônia ou sonolência diurna. A serotonina (5-HT) demonstra um padrão complexo no que diz respeito ao sono e vigília, o que está relacionado com a variedade de subtipos do receptor 5-HT envolvidos em diferentes funções fisiológicas. Acredita-se, atualmente, que a estimulação do receptor 5-HT2 esteja envolvida nas alterações da organização do sono e insônia relacionada a alguns antidepressivos. CONCLUSÃO: Alguns medicamentos normalmente prescritos para o tratamento de depressão podem piorar a insônia e dificultar a completa recuperação da depressão. Os antagonistas do receptor 5-HT2 são drogas promissoras para o tratamento, pois podem melhorar a insônia e depressão associadas.

Quality of life and sleep impairment in chronic cocaine dependents / Qualidade de vida e comprometimento do sono em dependentes crônicos de cocaína

OBJECTIVE: To evaluate quality of life (QL) and sleep quality impairment of cocaine chronic dependents in use of cocaine. METHOD: 40 patients, chronic cocaine dependents were evaluated (37 M; 3 F), with mean age of 28.92 years, along with 40 controls paired for gender and age. The following instruments were used: a) the semi-structured clinical interview; b) the Brazil Economic Classification; c) the Pittsburgh Sleep Quality Index; d) World Heath Organization Quality of Life-BREF (WHOQOL-BREF). RESULTS: The cocaine dependents showed QL impairment, with deficits in the physical, psychological and social relations domains. Impaired sleep quality was also observed in the cocaine dependents. However, the QL impairment was not directly due to sleep deficit. CONCLUSION: Chronic cocaine dependents showed impairment in QL and sleep impairment. However, for the cocaine dependent group, sleep impairment was not regarded as compromising QL probably because cocaine, rather than sleep, was the main factor negatively influencing QL.

OBJETIVO: Avaliar a qualidade de vida (QV) em dependentes de cocaína na fase de uso de droga e comprometimento da qualidade do sono. MÉTODO: Foram avaliados 40 pacientes dependentes de cocaína (37 M; 3 F), com média de idade de 29,92 anos; e 40 controles, equiparando-se as variáveis de gênero e idade e utilizando-se os seguintes instrumentos: a) Entrevista clínica semi-dirigida; b) Classificação Econômica Brasil; c) Índice de Qualidade do Sono de Pittsburgh; d) World Health Organization Quality of Life-BREF (WHOQOL-Breve). RESULTADOS: Os dependentes de cocaína apresentaram prejuízo na QV, com alterações nos domínios físico, psicológico e também das relações sociais. No grupo estudo não houve associação entre QV e qualidade do sono, ou seja, para os sujeitos desta amostra, a qualidade do sono não afetou a QV. CONCLUSÃO: No grupo estudo a QV foi considerada prejudicada, mas não devida de forma primordial ao comprometimento da qualidade do sono. Nestes pacientes a cocaína é provavelmente o fator primordial negativo sobre a QV e não o comprometimento do sono.

The effect of Galantamine on sleep quality in Thai Alzheimer's disease patients.

OBJECTIVE: To study the effect of Galantamine on sleep quality in Thai Alzheimer's disease (AD) patients with or without cerebrovascular disease. MATERIAL AND METHOD: A 6 month, multicenter open-label, uncontrolled trial was undertaken in 75 mild to moderate Alzheimer's disease patients with or without cerebrovascular disease. Eligible patients received a flexible-dose of Galantamine 16 or 24 mg/day for 24 weeks. The Pittsburgh Sleep Quality Index (PSQI) with self-analysis questionnaires were used to evaluate sleep quality. Analyses were based on the intent-to-treat population. RESULTS: Seventy-five eligible patients with mild to moderate Alzheimer's disease with or without cerebrovascular disease (male:female = 32:43, age range 74.5 +/- 0.9) were included and 58 patients (79%) completed the present study. The global PSQI scores showed some improvement over baseline (week 0 = 5.10 +/- 3.08, week 4 = 4.37 +/- 2.48, week 8 = 4.65 +/- 2.71, week 24 = 3.70 +/- 2.12) but were not yet statistical significant. In contrast, most of each component scores such as sleep quality, sleep latency, sleep duration, sleep disturbances, sleep medication, and daytime dysfunction except sleep efficiency, showed significant differences from baseline after week 8. Moreover, there were no significant differences in global PSQI and component scores between mild and moderate stages of Thai AD patients or between men and women patients. CONCLUSION: The result of the present study may be consistent with Galantamine being safe and can maintain good sleep quality for mild to moderate Thai AD patients with or without VaD. Galantamine doses of 16-24 mg/day were well tolerated.

Some consequences of ozone exposure on health

The reaction of ozone with polyunsaturated fatty acids from the surfactant factor and pulmonary epithelial cells produces different reaction products which can cross the alveolar-capillary barrier and reach distant structures. Although only a few papers claim extrapulmonary changes in animals exposed to this gas, some neurological deficits, such as complaints of fatigue, lethargy, headache in humans, as well as significant disarrangements in the sleep pattern related to biochemical changes int he brain have referred to in animals exposed to ozone. In the present review, the molecular configuration and the reaction of ozone at different lung levels are related to impairment at the respiratory and blood systems, in order to elucidate the mechanisms by which this gas or its reaction products, such as free radicals, prostaglandins and others can cross the alveolar-capillary and hemato-encephalic barriers, and to explain those neurological effects