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.

The impact of asthma and its treatment on growth: an evidence-based review / O impacto da asma e seu tratamento no crescimento: revisão baseada em evidências

Abstract Objectives: To assess the impact of asthma and its treatment (inhaled corticosteroids and other control medications) on growth. Data sources: The authors searched PubMed (up to August 24, 2018) and screened the reference lists of retrieved articles. Systematic reviews and meta-analysis were selected. If there was no such article, the authors selected either randomized clinical trials or observational studies. Data synthesis: A total of 37 articles were included in this review. The findings from 21 studies suggest that asthma per se, especially more severe and/or uncontrolled cases, can transitorily impair child's growth. Two Cochrane reviews of randomized clinical trials showed a small mean reduction in linear growth (-0.91 cm/year for beclomethasone, -0.59 cm/year for budesonide, and -0.39 cm/year for fluticasone) in the first year of treatment with inhaled corticosteroids in prepubertal children with persistent asthma. The effects were likely to be molecule- and dose-dependent. A recent review showed that most of "real-life" observational studies had not found significant effects of inhaled corticosteroids on growth in asthmatic children. Fifteen studies showed that the maintenance systemic corticosteroids could cause a dose-dependent growth suppression in children with severe asthma, but other controllers (cromones, montelukast, salmeterol, and theophylline) had no significant adverse effects no growth. Conclusions: Severe and/or uncontrolled asthma can transitorily impair child's growth. Regular use of inhaled corticosteroids may cause a small reduction in linear growth in children with asthma, but the well-established benefits of inhaled corticosteroids in controlling asthma outweigh the potential adverse effects on growth. Use of the minimally effective dose of inhaled corticosteroids and regular monitoring of child's height during inhaled corticosteroids therapy are recommended.

Resumo Objetivos: Avaliar o impacto da asma e seu tratamento (corticosteroides inalados e outros medicamentos de controle) no crescimento. Fontes de dados: Uma busca foi feita no PubMed (até 24 de agosto de 2018) e foram triadas as listas de referência dos artigos recuperados. Revisões sistemáticas e metanálises foram selecionadas. Se não houvesse tal artigo, ensaios clínicos randomizados ou estudos observacionais eram selecionados. Síntese dos dados: Trinta e sete artigos foram incluídos nesta revisão. Os achados de 21 estudos sugerem que a asma por si só, especialmente os casos mais graves e/ou descontrolados, podem prejudicar o crescimento da criança. Duas revisões Cochrane de ensaios clínicos randomizados mostraram uma pequena redução média no crescimento linear (−0,91 cm/ano para beclometasona, −0,59 cm/ano para budesonida e −0,39 cm/ano para fluticasona) no primeiro ano de tratamento com corticosteroides inalados em crianças pré-púberes com asma persistente. Os efeitos pareciam ter efeito dose- e molécula-dependente. Uma revisão recente mostrou que a maioria dos estudos observacionais da "vida real" não encontrou efeitos significativos dos corticosteroides inalados no crescimento de crianças asmáticas. Quinze estudos mostraram que a manutenção de corticosteroides sistêmicos poderia causar uma supressão do crescimento dose-dependente em crianças com asma grave, mas outros controladores (cromonas, montelucaste, salmeterol e teofilina) não tiveram efeitos adversos significativos no crescimento. Conclusões: A asma grave e/ou descontrolada pode prejudicar o crescimento da criança. O uso regular de corticosteroides inalados pode causar uma pequena redução no crescimento linear em crianças com asma, mas os benefícios bem estabelecidos dos corticosteroides inalados no controle da asma superam os potenciais efeitos adversos no crescimento. Recomenda-se o uso de doses minimamente eficazes de corticosteroides inalados e o monitoramento regular da altura da criança durante a terapia com corticosteroides inalados.

Risk factors for dental caries in children with developmental disabilities

Abstract The aim of the present study was to investigate risk factors for dental caries in children with developmental disabilities who were treated at a clinical reference service for patients with special needs in Belo Horizonte, MG, Brazil. This is a retrospective cohort study that evaluated 401 dental charts of individuals without dental caries or restorations in their first dental appointment. The dependent variable was the time of occurrence of new dental caries or restorations and was measured in months. Gender, age, International Code of Diseases (ICD), mother´s education, sugar consumption, use of fluoride toothpaste, oral hygiene, mouth breathing, reports of xerostomia, gingival status, use of psychotropic or asthma drugs, and history of asthma were covariates. The Cox proportional hazards regression model was used to estimate the raw and adjusted hazard ratios and their respective 95% confidence intervals. The average time that individuals remained free of dental caries/restoration was equal to 107.46 months (95%CI 95.41 to 119.51), with a median of caries-free children up to 94 months. For each point increase in the scale of sucrose consumption, the increase in caries risk was 1.07 (95%CI 1.01 to 1.15). Sucrose consumption was the only risk factor for dental caries found in this group of individuals with developmental disabilities.

Seguridad de los beta 2 agonistas (ß2a) en asma bronquial / [Safety of beta-agonists in asthma].

Beta 2 agonist bronchodilators (ß2A) are very important part in the pharmacotherapy of bronchial asthma, a disease that progresses in the world in an epidemic way. The ß2A are prescribed to millions of people around the world, therefore the safety aspects is of public interest. Short-Acting ß2 Agonists (SABAs), such as albuterol inhaler, according to current evidence, confirming its safety when used as a quick-relief or rescue medication. The long-acting ß2 agonists (LABAs) The long-acting bronchodilators ß2A (Long acting ß2 Agonists or LABAs) are used associated with inhaled corticosteroids as controller drugs for asthma exacerbationsaccess, for safety reasons LABAs are not recommended for use as monotherapy.

Local adverse effects associated with the use of inhaled corticosteroids in patients with moderate or severe asthma / Eventos adversos locais associados ao uso de corticosteroides inalatorios em pacientes com asma moderada ou grave

OBJECTIVE: To describe and characterize local adverse effects (in the oral cavity, pharynx, and larynx) associated with the use of inhaled corticosteroids (ICSs) in patients with moderate or severe asthma. METHODS: This was a cross-sectional study involving a convenience sample of 200 asthma patients followed in the Department of Pharmaceutical Care of the Bahia State Asthma and Allergic Rhinitis Control Program Referral Center, located in the city of Salvador, Brazil. The patients were ≥ 18 years of age and had been using ICSs regularly for at least 6 months. Local adverse effects (irritation, pain, dry throat, throat clearing, hoarseness, reduced vocal intensity, loss of voice, sensation of thirst, cough during ICS use, altered sense of taste, and presence of oral candidiasis) were assessed using a 30-day recall questionnaire. RESULTS: Of the 200 patients studied, 159 (79.5%) were women. The mean age was 50.7 ± 14.4 years. In this sample, 55 patients (27.5%) were using high doses of ICS, with a median treatment duration of 38 months. Regarding the symptoms, 163 patients (81.5%) reported at least one adverse effect, and 131 (65.5%) had a daily perception of at least one symptom. Vocal and pharyngeal symptoms were identified in 57 (28.5%) and 154 (77.0%) of the patients, respectively. The most commonly reported adverse effects were dry throat, throat clearing, sensation of thirst, and hoarseness. CONCLUSIONS: Self-reported adverse effects ...

OBJETIVO: Descrever e caracterizar os eventos adversos locais na orofaringe e laringe associados ao uso de corticosteroide inalatório (CI) em pacientes com asma moderada ou grave. MÉTODOS: Estudo de corte transversal, com amostra de conveniência composta por 200 pacientes acompanhados no Serviço de Assistência Farmacêutica da Central de Referência do Programa para Controle da Asma na Bahia, em Salvador (BA). Os pacientes tinham ≥ 18 anos e estavam em uso regular de CI por período ≥ 6 meses. Os eventos adversos locais (irritação, dor, garganta seca, pigarro, rouquidão, redução da potência da voz, perda de voz; sensação de sede, tosse durante inalação, alteração do paladar e presença de monilíase oral) foram avaliados por meio de um questionário com período recordatório de 30 dias. RESULTADOS: Dos 200 pacientes estudados, 159 (79,5%) eram mulheres. A média de idade foi de 50,7 ± 14,4 anos. Nesta amostra, 55 pacientes (27,5%) utilizavam altas doses de CI, com mediana de duração de tratamento de 38 meses. Em relação aos sintomas, 163 pacientes (81,5%) reportaram ao menos um evento adverso, e 131 (65,5%) tinham a percepção diária de pelo menos um sintoma. Os sintomas de voz e de faringe foram identificados em 57 (28,5%) e 154 (77,0%) pacientes, respectivamente. Os eventos adversos mais frequentemente relatados foram garganta seca, ...

Beta 2 agonistas de acción prolongada en el tratamiento del asma en niños / Long acting beta 2 agonists in the treatment in children with asthma

A pesar del uso de corticoides inhalados en el tratamiento del asma bronquial existe un número variable de pacientes que no logran el control de su enfermedad. En estos casos, una de las alternativas terapéuticas propuesta por diversas guías clínicas es la adición de beta 2 agonistas de acción prolongada. Este articulo, revisa las características farmacológicas, posibles efectos adversos y las indicaciones en niños.

Prevalence of dental erosion among asthmatic patients in India / Prevalência de erosão dentária em pacientes asmáticos na India

OBJETIVOS: O presente estudo foi realizado para investigar a associacao entre erosao dentaria e asma e estabelecer relacao com a historia medica, dieta e nivel de erosao dentaria. MATERIAL E METODO: O estudo transversal foi realizado entre 102 asmaticos e nao asmaticos, com idades entre 18 e 65 anos, em Udaipur, Rajasthan, India, em janeiro de 2009. A erosao dentaria foi determinada pelo uso de index de erosao utilizado em trabalho no Reino Unido em 1993. Os dados foram coletados por meio de questionarios. Os individuos foram examinados utilizando um procedimento do tipo III, por um unico examinador. A variacao intra examinadores foi testada estatisticamente, com acuracia de 90,3%. O teste qui-quadrado foi aplicado com utilizacao do programa SPSS, versao 11.0. RESULTADOS: Erosao dentaria estava presente em 76.5% de adultos com asma e em 66,7% de pacientes sem asma. 86% das drogas prescritas para asma tinham um pH abaixo de 5,5 %. Ocorreu tambem associacao entre erosao dentaria e consumo de refrigerantes, bebidas carbonatadas e frutas frescas. CONCLUSOES: Ha diferenca significativa na prevalencia de erosao, sendo que adultos com asma tem maior prevalencia do que nos grupos controle. Embora ocorra uma relacao entre niveis de erosao, ha tambem relacao dos niveis de erosao relacionadas com a historia medica e componentes acidos da dieta.

OBJECTIVE: This study was done to investigate association between tooth erosion and asthma and to find out the relationship between medical history, dietary practices and the level of dental erosion. MATERIAL AND METHOD: A cross sectional survey was conducted among 102 asthmatic and non asthmatic patient aged from 18 to 65 years old in Udaipur, Rajasthan, in January 2009. Tooth erosion was assessed using tooth erosion index employed in the childrenfs dental health in UK survey 1993. Data was collected by using self-prepared questionnaire. The subjects were examined using a type III examination procedure by single examiner. Intra examiner variability was tested by weighted kappa statistic which was 90.3%. Chi-square test was applied by using SPSS software (version 11.0). RESULTS: Tooth erosion was present in 76.5% of adults with asthma and in 66.7% asthma free subjects. 86% drugs which were prescribed for asthma had a pH below 5.5. There were also association between dental erosion and consumption of soft drinks, carbonated beverages and fresh fruits. CONCLUSION: There was significant difference in prevalence of erosion, adults with asthma having a higher prevalence than controlled group, although there is relationship between levels of erosion, medical history and acidic dietary components.

[Caries status in asthmatic children receiving anti-asthma inhalers]

Asthma is known as a probable risk factor for dental caries; however there is some controversy in this issue. Present study is designated to evaluate the caries status in asthmatics compared to non asthmatic controls. In addition probable factors and co-varieties associated with dental health were also investigated. Forty five asthmatics and 46 healthy controls aged 6 to 12, entered this case-control study. There was a history of asthmatic drugs for at least one year including inhalators of beta-agonist, Corticosteroid or both. DMFS Index recorded according to visual- tactile method. Stimulated saliva was obtained and microbial count performed as CFU/ml for S. Mutans and Lacto Bacilli. Data analysis performed according to t-test, Mann-Whitney, Kendall's Rank Correlation and Ridge Regression. Mean DMFS Index was 3.98 +/- 2.53 in asthmatics and 4.3 +/- 2.81 in healthy controls. The difference was not significant caries. Final Ridge Regression showed significant correlation between drug regimen and caries [P=0.001, r=0.76]. Those received beta agonist along with protective corticosteroid had significantly less caries compare to beta agonist alone [P<0.001]. S. Mutans count revealed significantly higher in controls. Lactobacilli count was not significantly different. DMFS index was not significantly different. Inhaled corticosteroids in asthmatics leads to better control of disease process, and reduce dental caries maybe because of reduced beta 2-agonist consumption as a potent xerostomic

Influence of obesity on bone mineral density in postmenopausal asthma patients undergoing treatment with inhaled corticosteroids

OBJECTIVES: The etiology of osteoporosis in asthma is complex as various factors contribute to its pathogenesis. The purpose of our study was to investigate the effects of obesity and inhaled steroids, as well as the severity and duration of asthma, on osteoporosis in postmenopausal asthma patients as compared to healthy controls. METHODS: A total of 46 patients with asthma and 60 healthy female controls, all postmenopausal, were enrolled in our study. Bone mineral density was assessed at the lumbar spine and hip using a Lunar DPX-L densitometer. RESULTS: Bone mineral density (BMD) scores were comparable between the asthmatic and control groups, with average scores of 0.95 ± 0.29 and 0.88 ± 0.14 g/cm², respectively. Likewise, osteoporosis was diagnosed in a similar percentage of patients in the asthmatic (39.1 percent) and control (43.3 percent) groups. Bone fracture was identified in four patients with asthma (8.6 percent) and in six patients from the control group (10 percent). We could not detect any relationship between BMD and duration of asthma, asthma severity, inhaled steroids or body mass index (BMI). There was no difference between the two groups with respect to age or years since menopause. Although asthma patients were more likely to be overweight and presented higher BMD scores on average than the control subjects, these differences were not statistically significant. CONCLUSIONS: There is a slight positive protective effect of high BMI against osteoporosis in asthma patients, but this effect is overcome by time and menopause status. Therefore, the protective effect of obesity against osteoporosis in asthma patients seems to not be significant.

Preditores da adesão ao tratamento em pacientes com asma grave atendidos em um centro de referência na Bahia / Predictors of adherence to treatment in patients with severe asthma treated at a referral center in Bahia, Brazil

OBJETIVO: Determinar a taxa de adesão ao tratamento padrão com corticóide inalatório em pacientes com asma grave, identificar seus fatores preditores e avaliar a relação entre adesão ao tratamento e os parâmetros de resposta clínica e funcional. MÉTODOS: Coorte prospectiva de pacientes atendidos no Programa de Controle da Asma e da Rinite Alérgica na Bahia, Brasil. O estudo incluiu 160 pacientes com asma grave, acompanhados por um período de 180 dias para medida da adesão (variável dependente) ao corticóide inalatório prescrito. As variáveis independentes foram determinadas na avaliação inicial e durante seis meses através de entrevistas e aplicação de questionário estruturado. Os pacientes registraram em um diário as doses não utilizadas. RESULTADOS: Do total de 160 pacientes, 158 completaram o estudo. A taxa de adesão ao tratamento foi de 83,8 por cento. Dos 158 pacientes, 112 (70,9 por cento) foram considerados aderentes ao tratamento (ponto de corte: 80 por cento de todas as doses administradas). Houve associação significante entre o controle da asma e adesão ao tratamento. Os fatores relacionados a uma baixa adesão foram efeitos adversos, local de residência distante do centro de referência, dificuldade de pagar pelo transporte e regime posológico. Outros fatores, como sintomas depressivos, religião e classe econômica, não tiveram relação com a adesão. CONCLUSÕES: A adesão ao tratamento foi considerada elevada, havendo relação com a resposta clínica ao tratamento em uma amostra de pacientes com asma grave atendidos em um programa público com fornecimento gratuito de medicamentos e atendimento multidisciplinar em unidade de referência.

OBJECTIVE: To determine the rate of adherence to treatment with inhaled corticosteroids in patients with severe asthma, to identify predictive factors for adherence and to evaluate the relationship between adherence to treatment and parameters of clinical and functional response. METHODS: Prospective cohort study of patients enrolled in the Program for the Control of Asthma and Allergic Rhinitis in the state of Bahia, Brazil. The study comprised 160 patients with severe asthma, monitored for 180 days in order to evaluate adherence (dependent variable) to the prescribed inhaled corticosteroid. Independent variables were assessed at baseline and for a six-month follow-up period by means of interviews and the completion of a standardized questionnaire.Patients recorded the missed doses in a diary. RESULTS: Of the 160 patients. 158 completed the study. Adherence rate was 83.8 percent. Of the 158 patients, 112 (70.9 percent) were considered adherent (cut-off point: 80 percent of prescribed doses administered). There was a significant association between asthma control and adherence to treatment.Predictors of poor adherence were adverse effects, living far from the referral center, limited resources to pay for transportation and dose schedule. Other factors, such as depressive symptoms, religion and economic status, were not associated with poor adherence. CONCLUSIONS: Adherence to asthma treatment was high and was associated with the clinical response to treatment, in a sample of patients with severe asthma enrolled in a public program that provides free medication and the assistance of a multiprofessional specialized team in a referral center

Inhaled corticosteroids in the treatment of respiratory allergy: safety vs. efficacy

OBJETIVO: Revisar os mecanismos moleculares de ação, eficácia e potenciais efeitos adversos relacionados aos corticosteróides inalados (CEI) em crianças com asma persistente. FONTES DOS DADOS: Artigos de língua inglesa da base de dados MEDLINE. Foram empregados os termos: corticosteroids, inhaled corticosteroids, asthma, children, beclomethasone, fluticasone, budesonide, ciclesonide, growth, adrenal insufficiency, bone mineral density, oral candidiasis. Foram selecionados guias de tratamento, artigos de revisão, estudos controlados, meta-análises e revisões sistemáticas que avaliaram a eficácia e os eventos adversos do tratamento com CEI. SíNTESE DOS DADOS: Estudos in vivo e in vitro mostram que os CEI disponíveis apresentam diferentes características farmacocinéticas e farmacodinâmicas que lhes conferem diferentes potenciais de ação. Os CEI também diferem quanto aos efeitos adversos sistêmicos e locais. Salienta-se a biodisponibilidade desses produtos como essencial para determinar a incidência de efeitos colaterais. Em linhas gerais, os CEI são capazes de controlar a asma, reduzindo o número de exacerbações, atendimentos médicos, hospitalizações e a necessidade de pulsos de corticosteróides orais. Também se observa melhora da função pulmonar, sobretudo nos pacientes com asma de início recente. O efeito adversos mais documentado é a desaceleração transitória do ritmo de crescimento. CONCLUSÕES: Os CEI são o principal agente antiinflamatório utilizado no tratamento da asma persistente. Quando administrados em doses baixas, mostram-se seguros e efetivos. O monitoramento dos pacientes permite a detecção precoce de eventuais efeitos adversos associados aos CEI.

OBJECTIVE: Review the molecular mechanisms of action, efficacy, and potential side effects associated with inhaled corticosteroids (ICS) in children with persistent asthma. SOURCES: Articles in English from MEDLINE. The following terms were used: corticosteroids, inhaled corticosteroids, asthma, children, beclomethasone, fluticasone, budesonide, ciclesonide, growth, adrenal insufficiency, bone mineral density, and oral candidiasis. Treatment guidelines, review articles, controlled trials, meta-analyses, and systematic reviews evaluating the efficacy and the adverse events of treatment with ICS were selected. SUMMARY OF THE FINDINGS: In vivo and in vitro studies show that the available ICS have different pharmacokinetic and pharmacodynamic properties that result in different action potentials. ICS also differ as to the systemic and local side effects. The bioavailability of these products is essential in order to determine the incidence of side effects. In general, ICS are capable of controlling asthma, reducing the number of exacerbations, medical consultations, hospitalizations, and the need of oral corticosteroid (applications) bursts. Improvement can also be seen in pulmonary function, especially in patients with recent onset asthma. The most documented adverse effect is transitory decrease of growth rate. CONCLUSIONS: ICS are the main anti-inflammatory agent used to treat persistent asthma. When administered in low doses, they seem to be safe and effective. Patient monitoring allows for early detection of possible side effects associated with ICS.

Clinical practice guidelines on bronchial asthma in adults.

Effective management of asthma requires a partnership between the patient and the health care provider. This depends on the patient having a good understanding of the disease and its management. As the level of literacy is widely variable in India, patient education methods may have to be tailored according to the patient's ability to understand. In any case, patients with asthma should be able to a) Understand that asthma is a chronic disease requiring prolonged treatment b) Understand that treatment for asthma should be continued even when symptoms have abated c) Understand that control of asthma needs to be assessed by using objective methods periodically e.g. PEFR measurement d) Recognise when asthma control is deteriorating e) Take appropriate steps when asthma control deteriorates f) Understand the basic nature of the drugs they need to take e.g. preventers, relievers, and protectors g) Recognise the advantages of the inhaled route over the oral route h) Take steps to avoid "triggers" which can aggravate or precipitate an asthma attack. Patients who are more literate can be instructed further on drug interactions, safety, efficacy and side effects of steroids as well as the influence of other diseases on asthma and its treatment.