ABSTRACT
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.
Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Quinolines/adverse effects , Sulfides/adverse effects , Anti-Asthmatic Agents/adverse effects , Leukotriene Antagonists/adverse effects , Cyclopropanes/adverse effects , Acetates/adverse effects , Asthma/drug therapy , Sleep Wake Disorders/chemically induced , Retrospective StudiesABSTRACT
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 Reacciones adversas a montelukast: de la teoría a la práctica. Serie de casos Adverse drug reactions of montelukast: from theory to practice. Case report 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.
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.
Subject(s)
Anti-Asthmatic Agents , Drug-Related Side Effects and Adverse Reactions , Acetates/adverse effects , Cyclopropanes , Humans , Quinolines , Retrospective Studies , SulfidesABSTRACT
BACKGROUND: Leukotrienes (LTs) participate in the process of tissue damage in periodontal disease by leukocyte chemotaxis and osteoclastic activation. The activation of Cysteinyl-LT receptor is associated with increased expression of proinflammatory molecules and osteoclastogenesis. However, its implications on periodontal disease progression have not been studied. The present study evaluated the effect of the cysteinyl-LT receptor antagonist (montelukast [MT]) on ligature-induced experimental periodontitis (EP) in rats. METHODS: Adult male Wistar rats were subjected to bilateral ligature-induced periodontitis and orally treated with MT (at doses of 10 or 30 mg/kg/d, MT10, and MT30, respectively). Sham animals had the ligatures immediately removed and received placebo treatment. Sets of animals were euthanized 7, 14, or 21 days after ligature placement and the mandibles were removed for macroscopic evaluation of alveolar bone loss (ABL). In addition, histological analysis of periodontal tissues, myeloperoxidase (MPO) activity of gingival tissues, and periodontal tissue expression of collagen type I, RUNX2, RANK, RANKL, OPG, BLT1, Cys-LTR1, LTA4H, and LTC4S were also analyzed. RESULTS: MT significantly reduced ABL at 14 (MT10 and MT30) and 21 days (MT10) (P < 0.05), gingival MPO at 7 (MT10) and 14 days (MT30) (P < 0.05), LTA4H, BLT1 and LTC4S gene expression on day 14 day (MT30, P < 0.05) and increased RUNX2 expression on day 14 (MT30, P < 0.05). CONCLUSION: Systemic therapy with MT decreases periodontal inflammation and ABL in ligature-induced periodontitis in rats.
Subject(s)
Alveolar Bone Loss , Periodontitis , Alveolar Bone Loss/drug therapy , Alveolar Bone Loss/prevention & control , Animals , Inflammation , Leukotriene Antagonists , Male , Periodontitis/drug therapy , Rats , Rats, WistarABSTRACT
Resumen: En la última década se ha registrado un aumento en la prescripción de antileucotrienos, en particular montelukast. A partir del año 2007 comenzaron los primeros reportes efectos adversos de esfera neuropsiquiátrica en la edad pediátrica. Los efectos reportados incluían trastornos del sueño y del humor hasta una posible asociación con ideación suicida y suicidio consumado. En el presente trabajo se realiza una revisión de la seguridad de montelukast tema con objetivo de establecer o descartar una eventual asociación entes los fenómenos mencionados y la administración de antileucotrienos.
Summary: In the last decade there has been an increase in the prescription of antileukotrienes, specifically montelukast. The first pediatric reports discussing adverse neuropsychiatric effects go back to 2007. The reported effects included a range from sleep and mood disorders, to even a possible association with suicidal ideation and consummated suicide. In the present paper we carry out a review of the safety of using montelukast in order to confirm or rule out an eventual association between such adverse effects and the administration of antileukotrienes.
Resumo: Na última década, houve um aumento na prescrição de antileucotrienos, em particular do montelucaste. A partir de 2007, começaram a surgir os primeiros reportes relativos aos efeitos neuropsiquiátricos adversos na idade pediátrica. Os efeitos relatados incluíram desde distúrbios do sono e do humor até uma possível associação com ideação suicida e suicídio consumado. No presente paper realizamos uma revisão da segurança no uso do montelucaste com o objetivo de confirmar ou descartar uma eventual associação entre os seus efeitos adversos e a administração de antileucotrienos.
ABSTRACT
BACKGROUND: The clinical characteristics and physio-pathogenic mechanisms of asthma in patients older than 60 years appear to differ from the behavior described for other age groups. Therefore, the effectiveness of medications for elderly patients with asthma should not be extrapolated from studies conducted on teenagers or young adults. OBJECTIVE: The study aimed to establish the clinical effect of montelukast 10 mg in elderly patients with mild and moderate asthma compared to its effect on young adults. METHOD: A prospective cohort study was conducted during 12 weeks of follow-up, which consecutively included the total population of adult patients attended by a group of 21 general practitioners, between July and December 2016. Young adults (18-59 years) and older adults were included (60 years or older) with mild or moderate asthma, which, according to the criteria of his treating physician, had been prescribed montelukast 10 mg/day. The variables of interest were: use of inhaled corticosteroids during the last month, use of inhaled beta-2 adrenergic agonists as a rescue in the last month, having attended the emergency service during the last month due to an asthma attack, presence of wheezing in the physical examination, the number of attacks in the last month and the number of days without symptoms in the last month. RESULTS: A total of 126 patients entered the cohort and 104 completed the follow-up, of which 29% were older adults. On admission, 65.4% of patients (68/104) had used rescue inhaled beta2 in the last month and had been using schemes with corticosteroids. After 12 weeks of follow-up, 58.1% (43/74) of the young adults required treatment schedules with corticosteroids, while in the elderly, only 36.7% of the patients (11/30) required this treatment scheme (p-value: 0.047). Regarding the use of rescue inhaled beta-2 at 12 weeks, 55% of young adults reported using them, compared to 33.3% of older adults (p-value: 0.041). CONCLUSION: In this cohort of patients, treated with montelukast 10 mg/day for 12 weeks, there was a reduction of broncho-obstructive symptoms and exacerbations of the disease. In older adults compared to young adults, a greater reduction in the use of beta2 agonists rescue medications and in the concomitant use of inhaled corticosteroid schemes was documented.
ABSTRACT
Abstract Introduction: Inflammatory conditions of the nose and paranasal sinuses are very prevalent in the general population, resulting in marked loss of quality of life in affected patients, as well as significant work, leisure, and social activity losses. These patients require specific and specialized treatment. A wide range of oral medications are available. Objective: The present document is aimed to clarify, for professionals treating patients with inflammatory sinonasal diseases, both specialists and general practitioners, specific oral therapies in noninfectious nasal inflammatory conditions. Methods: The methodology used to create this article included the search for the key words: oral corticosteroids, antihistamines, antileukotrienes, rhinitis, rhinosinusitis in the MEDLINE and EMBASE databases in the last 5 years. Since no relevant article was found for the text on the subject of interest in the last 5 years, the search was extended for another 5 years, and so on, according to the authors’ needs. Results: Relevant literature was found regarding the use of antihistamines, antileukotrienes and oral corticosteroids in these conditions. The Brazilian Academy of Rhinology emphasizes, after extensive discussion by the collegiate, key points in the treatment with these drugs. Conclusion: There is support in the literature for the use of these drugs; however, final considerations about the role of each of them have been made.
Resumo Introdução: As afecções inflamatórias do nariz e dos seios paranasais são muito prevalentes na população geral, causam acentuada perda de qualidade de vida dos pacientes afetados, geram perdas significativas das atividades de trabalho, lazer e sociais. Esses pacientes necessitam de tratamento específico e especializado e uma ampla gama de medicações orais está disponível. Objetivo: O presente documento tem por objetivo esclarecer àqueles que tratam das doenças nasossinusais inflamatórias, tanto especialistas quanto generalistas, sobre as terapêuticas orais nas afecções inflamatórias nasais não infecciosas. Método: A metodologia usada para elaboração deste artigo incluiu a busca das palavras chave: corticosteroides orais, anti-histamínicos, antileucotrienos, rinite, rinossinusite nos bancos de dados Medline e Embase nos últimos 5 anos. Como não foi achado artigo relevante para o texto sobre o assunto de interesse nos últimos 5 anos, a busca foi estendida por mais 5 anos, e assim por diante, de acordo com a necessidade dos autores. Resultados: Literatura relevante foi encontrada com relação ao uso dos anti-histamínicos, antileucotrienos e corticosteroides orais nessas afecções. A Academia Brasileira de Rinologia ressalta, após amplo debate do colegiado, pontos-chave no tratamento com esses medicamentos. Conclusão: Há respaldo na literatura para o uso desses medicamentos, entretanto considerações finais acerca do papel de cada deles foram feitas.
Subject(s)
Humans , Sinusitis/drug therapy , Rhinitis/drug therapy , Adrenal Cortex Hormones/administration & dosage , Leukotriene Antagonists/administration & dosage , Histamine Antagonists/administration & dosage , Brazil , Acute Disease , Chronic Disease , Adrenal Cortex Hormones/adverse effects , Leukotriene Antagonists/adverse effects , Academies and Institutes , Histamine Antagonists/adverse effectsABSTRACT
INTRODUCTION: Inflammatory conditions of the nose and paranasal sinuses are very prevalent in the general population, resulting in marked loss of quality of life in affected patients, as well as significant work, leisure, and social activity losses. These patients require specific and specialized treatment. A wide range of oral medications are available. OBJECTIVE: The present document is aimed to clarify, for professionals treating patients with inflammatory sinonasal diseases, both specialists and general practitioners, specific oral therapies in noninfectious nasal inflammatory conditions. METHODS: The methodology used to create this article included the search for the key words: oral corticosteroids, antihistamines, antileukotrienes, rhinitis, rhinosinusitis in the MEDLINE and EMBASE databases in the last 5 years. Since no relevant article was found for the text on the subject of interest in the last 5 years, the search was extended for another 5 years, and so on, according to the authors' needs. RESULTS: Relevant literature was found regarding the use of antihistamines, antileukotrienes and oral corticosteroids in these conditions. The Brazilian Academy of Rhinology emphasizes, after extensive discussion by the collegiate, key points in the treatment with these drugs. CONCLUSION: There is support in the literature for the use of these drugs; however, final considerations about the role of each of them have been made.
Subject(s)
Adrenal Cortex Hormones/administration & dosage , Histamine Antagonists/administration & dosage , Leukotriene Antagonists/administration & dosage , Rhinitis/drug therapy , Sinusitis/drug therapy , Academies and Institutes , Acute Disease , Adrenal Cortex Hormones/adverse effects , Brazil , Chronic Disease , Histamine Antagonists/adverse effects , Humans , Leukotriene Antagonists/adverse effectsABSTRACT
PURPOSE:To determine the toxic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on reproductive system and the beneficial effects of Montelukast (ML) with histological and biochemical analysis.METHODS:Rats were randomly divided into four equal groups (control, TCDD, ML and TCDD+ML). Tissue samples were collected on day 60 and oxidative status and histological alterations were analyzed.RESULTS:The results showed a significant increase in oxidative and histological damage on uterine and ovarian tissues. Otherwise, the oxidative and histological damages caused by TCDD were prevented with ML treatment.CONCLUSION:The toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on female reproductive system were reversed with Montelukast treatment. Therefore, we claimed that ML treatment might be useful for TCDD toxicity.(AU)
Subject(s)
Animals , Female , Rats , Polychlorinated Dibenzodioxins/antagonists & inhibitors , Polychlorinated Dibenzodioxins/toxicity , Genitalia, Female/physiopathology , Leukotriene Antagonists/analysis , Leukotriene Antagonists/therapeutic use , Antioxidants , Dioxins/toxicity , Rats, WistarABSTRACT
ABSTRACT PURPOSE: To determine the toxic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on reproductive system and the beneficial effects of Montelukast (ML) with histological and biochemical analysis. METHODS: Rats were randomly divided into four equal groups (control, TCDD, ML and TCDD+ML). Tissue samples were collected on day 60 and oxidative status and histological alterations were analyzed. RESULTS: The results showed a significant increase in oxidative and histological damage on uterine and ovarian tissues. Otherwise, the oxidative and histological damages caused by TCDD were prevented with ML treatment. CONCLUSION: The toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on female reproductive system were reversed with Montelukast treatment. Therefore, we claimed that ML treatment might be useful for TCDD toxicity.
Subject(s)
Animals , Female , Rats , Ovary/drug effects , Quinolines/pharmacology , Oxidative Stress/drug effects , Polychlorinated Dibenzodioxins/toxicity , Acetates/pharmacology , Antioxidants/pharmacology , Ovary/pathology , Superoxide Dismutase/metabolism , Uterus/pathology , Catalase/metabolism , Random Allocation , Rats, Wistar , Glutathione/metabolism , Ovarian Follicle/drug effectsABSTRACT
Introducción. Aproximadamente el 50 % de los casos de urticaria crónica no mejoran adecuadamente con las dosis convencionales de antihistamínicos, por lo cual se han planteado múltiples opciones terapéuticas, entre las cuales el omalizumab es una herramienta novedosa que ahora cuenta con evidencia de alta calidad que soporta su uso en los casos difíciles, que mejora rápidamente el índice sintomático y el uso de medicamentos, y cuenta con un buen perfil de seguridad. Objetivo. Presentar tres casos de mujeres adultas con urticaria crónica espontánea de más de ocho años de evolución, que no mejoraron con el tratamiento con altas dosis de antihistamínicos, asociados a antileucotrienos e inmunomoduladores y en quienes se combinaban varios mecanismos fisiopatológicos: urticaria crónica espontánea con componente de autoinmunidad, componente de presión y urticaria vasculítica. Materiales y métodos. Se reportan los casos con sus respectivas evaluaciones clínicas y de laboratorio, los medicamentos usados y la respuesta después del inicio de omalizumab y se hace una revisión de la literatura científica sobre uso de este medicamento en la urticaria crónica. Resultados. En los tres casos presentados se obtuvo una mejoría completa de los síntomas tras el inicio del omalizumab. Conclusión. El omalizumab es una opción terapéutica exitosa en casos de urticaria crónica de difícil control con vasculitis asociada, cuando se han agotado las opciones propuestas por las guías internacionales.
Introduction: Approximately 50% of chronic urticaria cases do not respond adequately to conventional doses of antihistamines, so a number of other therapeutic options have been suggested. Among these, omalizumab is an innovative tool, which now has high-quality evidence that supports its use in difficult cases, rapidly improving the symptom index and the use of medications with a good safety profile. Objective: To report three cases of adult women with spontaneous chronic urticaria with an evolution of more than eight years, which did not improve with high doses of antihistamines and leukotriene receptor blockers, associated with immunomodulatory therapy in which several etiologic mechanisms were combined: chronic spontaneous urticaria with autoimmune and pressure components, and vasculitis. Materials and methods: We report the cases with their clinical and laboratory evaluations, used medication, the response after the start of omalizumab and we performed a review of the literature on the use of this drug in chronic urticaria. Results: In all the presented cases, we obtained complete improvement of symptoms after starting omalizumab. Conclusion: Omalizumab is a successful treatment option in cases of difficult to control chronic urticaria with associated vasculitis in which the options proposed by international guidelines have been exhausted.
Subject(s)
Adult , Female , Humans , Middle Aged , Anti-Allergic Agents/therapeutic use , Antibodies, Anti-Idiotypic/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Urticaria/complications , Urticaria/drug therapy , Vasculitis/complications , Chronic DiseaseABSTRACT
PURPOSE: To evaluate the effect of zafirlukast on capsular contracture around silicone implants by measuring the pressure within the implant, using a rat experimental model. METHODS: Forty adult female Wistar rats were used. Each one received two silicone implants, one with smooth-surface and the other with textured-surface. They were randomly divided into four groups (n=10). The rats of control group I were sacrificed after the implants. The remaining animals were subjected to a daily regimen of intra-peritoneal injection for a period of 90 days and they were distributed as follows: control group II received 0.9 percent physiological saline solution; experimental group I received zafirlukast 1.25 mg/kg; and experimental group II received zafirlukast 5 mg/kg. The measurement of intra-implant pressure of control group I was determined on the surgery day and in other groups on the ninetieth day, after being sacrificed. RESULTS: In the evaluation of textured implants there was an increase of internal pressure in the control group II, and there was no increase in the experimental groups. Compared to the controls there were not significant differences in smooth implants. CONCLUSION: Zafirlukast reduced the risk of developing capsular contracture around silicone implants with textured surface.(AU)
OBJETIVO: Avaliar o efeito do zafirlukast na contratura capsular ao redor de implantes de silicone, através da aferição da pressão intra-implante, utilizando-se um modelo experimental de ratos. MÉTODOS: Quarenta ratos fêmeas Wistar foram utilizados. Cada um recebeu dois implantes de silicone, sendo um com superfície lisa e outro texturizada. Foram divididos aleatoriamente em quatro grupos (n=10). Os ratos do grupo controle I foram sacrificados após o implante. O restante dos animais foi submetido a um regime diário de injeção intraperitoneal por um período de 90 dias e foram distribuídos: grupo controle II recebeu solução salina fisiológica 0,9 por cento, grupo experimental I recebeu zafirlukast 1,25 mg/kg, e grupo experimental II recebeu zafirlukast 5 mg/kg. O grupo controle II recebeu solução salina; grupo experimental I, 1,25 mg/kg/dia de zafirlukast; grupo experimental II, 5mg/kg/dia de zafirlukast. A aferição da pressão intra-implante do grupo controle I foi averiguada no dia do ato operatório, e nos outros grupos no nonagésimo dia, após serem sacrificados. RESULTADOS: Na avaliação dos implantes texturizados houve aumento da pressão interna no grupo controle II e, não se observou aumento nos grupos experimentais. Na comparação com os controles não foram observadas diferenças significativas nos implantes lisos. CONCLUSÃO: O Zafirlukast reduziu o risco de desenvolver contratura capsular em torno de implantes de silicone com superfície texturizada.(AU)
Subject(s)
Rats , Breast Implants/veterinary , Injections, Intraperitoneal , Contracture , Silicones/metabolism , Leukotrienes/chemistryABSTRACT
PURPOSE: To evaluate the effect of zafirlukast on capsular contracture around silicone implants by measuring the pressure within the implant, using a rat experimental model. METHODS: Forty adult female Wistar rats were used. Each one received two silicone implants, one with smooth-surface and the other with textured-surface. They were randomly divided into four groups (n=10). The rats of control group I were sacrificed after the implants. The remaining animals were subjected to a daily regimen of intra-peritoneal injection for a period of 90 days and they were distributed as follows: control group II received 0.9 percent physiological saline solution; experimental group I received zafirlukast 1.25 mg/kg; and experimental group II received zafirlukast 5 mg/kg. The measurement of intra-implant pressure of control group I was determined on the surgery day and in other groups on the ninetieth day, after being sacrificed. RESULTS: In the evaluation of textured implants there was an increase of internal pressure in the control group II, and there was no increase in the experimental groups. Compared to the controls there were not significant differences in smooth implants. CONCLUSION: Zafirlukast reduced the risk of developing capsular contracture around silicone implants with textured surface.
OBJETIVO: Avaliar o efeito do zafirlukast na contratura capsular ao redor de implantes de silicone, através da aferição da pressão intra-implante, utilizando-se um modelo experimental de ratos. MÉTODOS: Quarenta ratos fêmeas Wistar foram utilizados. Cada um recebeu dois implantes de silicone, sendo um com superfície lisa e outro texturizada. Foram divididos aleatoriamente em quatro grupos (n=10). Os ratos do grupo controle I foram sacrificados após o implante. O restante dos animais foi submetido a um regime diário de injeção intraperitoneal por um período de 90 dias e foram distribuídos: grupo controle II recebeu solução salina fisiológica 0,9 por cento, grupo experimental I recebeu zafirlukast 1,25 mg/kg, e grupo experimental II recebeu zafirlukast 5 mg/kg. O grupo controle II recebeu solução salina; grupo experimental I, 1,25 mg/kg/dia de zafirlukast; grupo experimental II, 5mg/kg/dia de zafirlukast. A aferição da pressão intra-implante do grupo controle I foi averiguada no dia do ato operatório, e nos outros grupos no nonagésimo dia, após serem sacrificados. RESULTADOS: Na avaliação dos implantes texturizados houve aumento da pressão interna no grupo controle II e, não se observou aumento nos grupos experimentais. Na comparação com os controles não foram observadas diferenças significativas nos implantes lisos. CONCLUSÃO: O Zafirlukast reduziu o risco de desenvolver contratura capsular em torno de implantes de silicone com superfície texturizada.