RESUMO
Background: Fexofenadine emerged as one of the most representative second generation histamine H1 antagonist drugs since the 1990s, with an outstanding efficacy and appreciable safety for the treatment of allergic patients. While allergic rhino-conjunctivitis represents the most frequent atopic disease globally, an update of fexofenadine efficacy and safety on this entity was proposed as a surrogate of allergic condition. Methods: Double blind, placebo controlled, randomized clinical trials investigating the efficacy and safety of fexofenadine for the treatment of Allergic Rhinitis were searched in 5 major global databases. Eligibility criteria and characteristics, risk of bias, and validity assessment, data extraction and heterogeneity evaluation are described. Primary outcome selected corresponded to 12-reflective and instantaneous total symptom scores (TSS), besides morning instantaneous TSS and the frequency of reported adverse events (AEs); analysis was planned on the intention-to-treat population.Standardized mean differences of scoring systems were analyzed, and Cochran's Q statistic test and the I2 test were assessed for heterogeneity. Results: From the initial 83 identified records, 12 eligible studies were selected. In the evaluated patients, individuals receiving fexofenadine (1910) showed a significant reduction of TSS compared with those who received placebo (1777), change from baseline: standardized mean difference (SMD) -0.33; 95% CI-0.47 to -0.18, p < 0.0001. Morning instantaneous TSS also demonstrated lower symptoms (change from baseline: SMS -1.42; 95% CI -2.22 to -0.62, p = 0.0005). Heterogeneity was found across selected studies.Frequency of AEs was similar compared to placebo (OR = 1.04; 0.88-1.21), with no detection of heterogeneity across these 12 studies. Conclusions: According to this new evidence, fexofenadine maintains its beneficial profile on signs and symptoms of patients with allergic conditions, as well as its attributes as one of the major candidates for an ideal antihistamine medication (including special conditions such as pregnancy and pre-school age), providing support to its over-the-counter condition in several countries.
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Leishmaniases are infectious diseases caused by protozoan parasites Leishmania and transmitted by sand flies. Drug repurposing is a therapeutic approach that has shown satisfactory results in their treatment. Analyses of antihistaminic drugs have revealed their in vitro and in vivo activity against trypanosomatids. In this way, this study evaluated the antileishmanial activity of H1-antihistamines and identified the cellular alterations in Leishmania (L.) infantum. Cinnarizine, cyproheptadine, and meclizine showed activity against promastigotes with 50% inhibitory concentration (IC50) values between 10-29 µM. These drugs also demonstrated activity and selectivity against intracellular amastigotes, with IC50 values between 20-35 µM. Fexofenadine and cetirizine lacked antileishmanial activity against both forms. Mammalian cytotoxicity studies revealed 50% cytotoxic concentration values between 52 - >200 µM. These drugs depolarized the mitochondria membrane of parasites and caused morphological alterations, including mitochondrial damage, disorganization of the intracellular content, and nuclear membrane detachment. In conclusion, the L. infantum death may be ascribed by the subcellular alterations followed by a pronounced decrease in the mitochondrial membrane potential, indicating dysfunction in the respiratory chain upon H1-antihistamine treatment. These H1-antihistamines could be used to explore new routes of cellular death in the parasite and the determination of the targets at a molecular level, would contribute to understanding the potential of these drugs as antileishmanial.
Assuntos
Antiprotozoários/farmacologia , Antagonistas dos Receptores Histamínicos H1/farmacologia , Leishmania infantum/efeitos dos fármacos , Animais , Feminino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Introducción La mastocitosis representa un grupo de enfermedades caracterizadas por una acumulación excesiva de mastocitos en uno o múltiples tejidos. Puede limitarse a la piel o tener un compromiso sistémico, siendo de baja prevalencia y pronóstico benigno en la infancia. Objetivo Reportar un caso de urticaria pigmentosa como subtipo de mastocitosis cutánea y hacer una revisión bibliográfica enfocada en los hallazgos clínicos, el diagnóstico y el manejo inicial básico. Caso clínico Lactante de 6 meses de edad con múltiples máculas y pápulas de color café claro localizadas en el tronco, los brazos y las piernas, cuadro compatible con una urticaria pigmentosa, confirmada mediante biopsia. Se solicitaron exámenes para descartar compromiso sistémico. La paciente fue tratada con medidas generales, educación y antihistamínicos, con excelente evolución. Conclusiones La mastocitosis cutánea es una enfermedad poco común, de buen pronóstico. En la infancia generalmente bastan las medidas generales y educación para obtener resultados favorables. La terapia farmacológica de primera línea son los antagonistas H1.
Introduction Mastocytosis represents a group of diseases characterised by an excesive accumulation of mastocytes in one or multiple tissues. It can affect only the skin, or have a systemic involvement. It has a low prevalence, and the prognosis is benign in children. Objective To report a case of urticaria pigmentosa as a subtype of cutaneous mastocytosis, and present a literature review focused on clinical findings, diagnosis and initial basic management. Clinical case A child of six months of age presenting with multiple blemishes and light brown papules located on the trunk, arms and legs. The symptoms were compatible with urticaria pigmentosa, and was confirmed by biopsy. Tests to rule out systemic involvement were requested. The patient was treated with general measures, education, and antihistamines, with favourable results. Conclusions Cutaneous mastocytosis is a rare disease with a good prognosis. In childhood general measures and education are usually enough to obtain favourable results. Histamine H1 antagonists are the first line drug treatment.
Assuntos
Humanos , Feminino , Lactente , Urticaria Pigmentosa/diagnóstico , Mastocitose Cutânea/diagnóstico , Prognóstico , Biópsia , Urticaria Pigmentosa/patologia , Urticaria Pigmentosa/terapia , Mastocitose Cutânea/patologia , Mastocitose Cutânea/terapia , Antagonistas dos Receptores Histamínicos H1/uso terapêuticoRESUMO
INTRODUCTION: Mastocytosis represents a group of diseases characterised by an excesive accumulation of mastocytes in one or multiple tissues. It can affect only the skin, or have a systemic involvement. It has a low prevalence, and the prognosis is benign in children. OBJECTIVE: To report a case of urticaria pigmentosa as a subtype of cutaneous mastocytosis, and present a literature review focused on clinical findings, diagnosis and initial basic management. CLINICAL CASE: A child of six months of age presenting with multiple blemishes and light brown papules located on the trunk, arms and legs. The symptoms were compatible with urticaria pigmentosa, and was confirmed by biopsy. Tests to rule out systemic involvement were requested. The patient was treated with general measures, education, and antihistamines, with favourable results. CONCLUSIONS: Cutaneous mastocytosis is a rare disease with a good prognosis. In childhood general measures and education are usually enough to obtain favourable results. Histamine H1 antagonists are the first line drug treatment.