RESUMO
A urticária aquagênica é uma forma rara de urticária crônica induzida (UCInd) desencadeada por um estímulo específico. A patogênese não é totalmente compreendida, mas os sintomas se iniciam minutos após a exposição cutânea à água, independentemente de sua temperatura, e as urticas têm o padrão foliculocêntricas. O diagnóstico é confirmado através do teste de provocação, e o tratamento de primeira linha são os anti-histamínicos de segunda geração. Neste artigo, relatamos um caso de urticária aquagênica e fazemos uma breve revisão da literatura sobre o tema.
Aquagenic urticaria is a rare form of chronic inducible urticaria (CIndU) triggered by a specific stimulus. Pathogenesis is not fully understood, but symptoms appear minutes after cutaneous exposure to water, regardless of temperature, and wheals have a folliculocentric pattern. The diagnosis of CIndU is confirmed by provocation testing using established protocols, and first-line treatment is second-generation antihistamines. In this article, we report a case of aquagenic urticaria and provide a brief review of the relevant literature.
Assuntos
Humanos , Feminino , Adulto Jovem , Água , Antagonistas não Sedativos dos Receptores H1 da Histamina , Urticária Crônica , Sinais e Sintomas , Terapêutica , Testes Cutâneos , Diagnóstico , Antagonistas dos Receptores HistamínicosRESUMO
A síndrome DRESS é uma entidade rara e distinta, caracterizada por acometimento cutâneo e envolvimento de órgãos internos, com risco potencial de morte. O diagnóstico e o tratamento pre- coces são de vital importância. Relatos de DRESS por paraceta- mol são raros na literatura, razão pela qual apresentamos este caso. Paciente do sexo masculino, 56 anos, com surgimento de rash maculopapular, febre, linfadenopatia e hipereosinofilia 3 semanas após suspensão de paracetamol, associados ao ante- cedente familiar de reação a fármaco. Evoluiu bem após pulso- terapia com metilprednisolona.
DRESS syndrome is a rare and distinct entity characterized by cutaneous manifestations and internal organs involvement with a potential risk of death. Early diagnosis and treatment are vi- tally important. Reported cases of DRESS syndrome due to ace- taminophen are rare in the literature, and that is the reason for this case report. A 56-year-old male patient with maculopapular rash, fever, lymphadenopathy, and hypereosinophilia three we- eks after suspension of acetaminophen, associated with a family history of drug reaction. It progressed well after pulse therapy with methylprednisolone.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Antipiréticos/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Acetaminofen/efeitos adversos , Prednisona/uso terapêutico , Loratadina/uso terapêutico , Corticosteroides/uso terapêutico , Artralgia/etiologia , Antagonistas não Sedativos dos Receptores H1 da Histamina/uso terapêutico , Exantema/etiologia , Febre/etiologia , Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Linfadenopatia/etiologiaRESUMO
PURPOSE: Fexofenadine is a well-identified in vivo probe substrate of P-glycoprotein (P-gp) and/or organic anion transporting polypeptide (OATP). This work aimed to investigate the transplacental pharmacokinetics of fexofenadine enantiomers with and without the selective P-gp inhibitor fluoxetine. METHODS: The chiral transplacental pharmacokinetics of fexofenadine-fluoxetine interaction was determined using the ex vivo human placenta perfusion model (n = 4). In the Control period, racemic fexofenadine (75 ng of each enantiomer/ml) was added in the maternal circuit. In the Interaction period, racemic fluoxetine (50 ng of each enantiomer/mL) and racemic fexofenadine (75 ng of each enantiomer/mL) were added to the maternal circulation. In both periods, maternal and fetal perfusate samples were taken over 90 min. RESULTS: The (S)-(-)- and (R)-(+)-fexofenadine fetal-to-maternal ratio values in Control and Interaction periods were similar (~0.18). The placental transfer rates were similar between (S)-(-)- and (R)-(+)-fexofenadine in both Control (0.0024 vs 0.0019 min-1) and Interaction (0.0019 vs 0.0021 min-1) periods. In both Control and Interaction periods, the enantiomeric fexofenadine ratios [R-(+)/S-(-)] were approximately 1. CONCLUSIONS: Our study showed a low extent, slow rate of non-enantioselective placental transfer of fexofenadine enantiomers, indicating a limited fetal fexofenadine exposure mediated by placental P-gp and/or OATP2B1. The fluoxetine interaction did not affect the non-enantioselective transplacental transfer of fexofenadine. The ex vivo placental perfusion model accurately predicts in vivo placental transfer of fexofenadine enantiomers with remarkably similar values (~0.17), and thus estimates the limited fetal exposure.
Assuntos
Antagonistas não Sedativos dos Receptores H1 da Histamina/farmacocinética , Troca Materno-Fetal/efeitos dos fármacos , Placenta/metabolismo , Terfenadina/análogos & derivados , Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Área Sob a Curva , Interações Medicamentosas , Feminino , Fluoxetina/administração & dosagem , Fluoxetina/farmacocinética , Antagonistas não Sedativos dos Receptores H1 da Histamina/administração & dosagem , Humanos , Perfusão/instrumentação , Perfusão/métodos , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/imunologia , Estereoisomerismo , Terfenadina/administração & dosagem , Terfenadina/farmacocinéticaRESUMO
BACKGROUND AND OBJECTIVE: Fluoxetine, antidepressant widely-used during pregnancy, is a selective inhibitor for P-glycoprotein (P-gp). Fexofenadine, an in vivo P-gp probe, is an antihistamine drug for seasonal allergic rhinitis and chronic urticaria treatment during pregnancy and it is available as a racemic mixture. This study evaluated the chiral discrimination of P-gp investigating the effect of fluoxetine on maternal-fetal pharmacokinetics of fexofenadine. METHODS: Healthy parturient women received either a single oral dose of 60 mg racemic fexofenadine (Control group; n = 8) or a single oral dose of 40 mg racemic fluoxetine 3 h before a single oral dose of 60 mg racemic fexofenadine (Interaction group; n = 8). Maternal blood and urine samples were collected up to 48 h after fexofenadine administration. At delivery, maternal-placental-fetal blood samples were collected. RESULTS: The maternal pharmacokinetics of fexofenadine was enantioselective (AUC0-∞R-(+)/S-(-) ~ 1.5) in both control and interaction groups. Fluoxetine increased AUC0-∞ (267.7 vs 376.1 ng.h/mL) and decreased oral total clearance (105.1 vs 74.4 L/h) only of S-(-)-fexofenadine, whereas the renal clearance were reduced for both enantiomers, suggesting that the intestinal P-gp-mediated transport of S-(-)-fexofenadine is influenced by fluoxetine to a greater extent that the R-(+)-fexofenadine. However, the transplacental transfer of fexofenadine is low (~16%), non-enantioselective and non-influenced by fluoxetine. CONCLUSIONS: A single oral dose of 40 mg fluoxetine inhibited the intestinal P-gp mediated transport of S-(-)-fexofenadine to a greater extent than R-(+)-fexofenadine in parturient women. However, the placental P-gp did not discriminate fexofenadine enantiomers and was not inhibited by fluoxetine.
Assuntos
Antidepressivos de Segunda Geração/administração & dosagem , Fluoxetina/administração & dosagem , Antagonistas não Sedativos dos Receptores H1 da Histamina/farmacocinética , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Parto , Terfenadina/análogos & derivados , Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Adulto , Antidepressivos de Segunda Geração/efeitos adversos , Estudos de Casos e Controles , Interações Medicamentosas , Feminino , Sangue Fetal/metabolismo , Fluoxetina/efeitos adversos , Antagonistas não Sedativos dos Receptores H1 da Histamina/administração & dosagem , Antagonistas não Sedativos dos Receptores H1 da Histamina/sangue , Humanos , Mucosa Intestinal/metabolismo , Troca Materno-Fetal , Circulação Placentária , Gravidez , Terfenadina/administração & dosagem , Terfenadina/sangue , Terfenadina/farmacocinética , Adulto JovemRESUMO
PURPOSE OF REVIEW: This article presents an update on the clinical pharmacology, mechanisms of action, and safety of second generation antihistamines (SGAHs). RECENT FINDINGS: Recent research has shown the efficacy and good tolerance of SGAHs supporting its indication as first line medications for the treatment of allergic rhinoconjunctivitis and urticaria. SUMMARY: The information contained in this review is relevant for the correct utilization of SGAHs by practicing physicians who take care of these highly prevalent clinical disorders.
Assuntos
Antialérgicos/uso terapêutico , Conjuntivite Alérgica/tratamento farmacológico , Antagonistas não Sedativos dos Receptores H1 da Histamina/uso terapêutico , Rinite Alérgica/tratamento farmacológico , Animais , Conjuntivite Alérgica/epidemiologia , Uso de Medicamentos , Humanos , Guias de Prática Clínica como Assunto , Padrões de Prática Médica , Rinite Alérgica/epidemiologia , Espanha/epidemiologiaRESUMO
BACKGROUND: Urticarias are frequent diseases, with 15% to 20% of the population presenting at least one acute episode in their lifetime. Urticaria are classified in acute ( ≤ 6 weeks) or chronic (> 6 weeks). They may be induced or spontaneous. OBJECTIVES: To verify the diagnostic and therapeutic recommendations in chronic spontaneous urticaria (CSU), according to the experience of Brazilian experts, regarding the available guidelines (international and US). METHODS: A questionnaire was sent to Brazilian experts, with questions concerning diagnostic and therapeutic recommendations for CSU in adults. RESULTS: Sixteen Brazilian experts answered the questionnaire related to diagnosis and therapy of CSU in adults and data were analyzed. Final text was written, considering the available guidelines (International and US), adapted to the medical practices in Brazil. Diagnostic work up in CSU is rarely necessary. Biopsy of skin lesion and histopathology may be indicated to rule out other diseases, such as, urticarial vasculitis. Other laboratory tests, such as complete blood count, CRP, ESR and thyroid screening. Treatment of CSU includes second-generation anti-histamines (sgAH) at licensed doses, sgAH two, three to fourfold doses (non-licensed) and omalizumab. Other drugs, such as, cyclosporine, immunomodulatory drugs and immunosuppressants may be indicated (non-licensed and with limited scientific evidence). CONCLUSIONS: Most of the Brazilian experts in this study partially agreed with the diagnostic and therapeutic recommendations of the International and US guidelines. They agreed with the use of sgAH at licensed doses. Increase in the dose to fourfold of sgAH may be suggested with restrictions, due to its non-licensed dose. Sedating anti-histamines, as suggested by the US guideline, are indicated by some of the Brazilian experts, due to its availability. Adaptations are mandatory in the treatment of CSU, due to scarce or lack of other therapeutic resources in the public health system in Brazil, such as omalizumab or cyclosporine.
Assuntos
Consenso , Urticária/diagnóstico , Urticária/tratamento farmacológico , Adulto , Antialérgicos/uso terapêutico , Brasil , Doença Crônica , Ciclosporinas/uso terapêutico , Dermatologia , Antagonistas não Sedativos dos Receptores H1 da Histamina/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Omalizumab/uso terapêutico , Índice de Gravidade de Doença , Sociedades Médicas , Urticária/prevenção & controleRESUMO
Abstract: Background: Urticarias are frequent diseases, with 15% to 20% of the population presenting at least one acute episode in their lifetime. Urticaria are classified in acute ( ≤ 6 weeks) or chronic (> 6 weeks). They may be induced or spontaneous. Objectives: To verify the diagnostic and therapeutic recommendations in chronic spontaneous urticaria (CSU), according to the experience of Brazilian experts, regarding the available guidelines (international and US). Methods: A questionnaire was sent to Brazilian experts, with questions concerning diagnostic and therapeutic recommendations for CSU in adults. Results: Sixteen Brazilian experts answered the questionnaire related to diagnosis and therapy of CSU in adults and data were analyzed. Final text was written, considering the available guidelines (International and US), adapted to the medical practices in Brazil. Diagnostic work up in CSU is rarely necessary. Biopsy of skin lesion and histopathology may be indicated to rule out other diseases, such as, urticarial vasculitis. Other laboratory tests, such as complete blood count, CRP, ESR and thyroid screening. Treatment of CSU includes second-generation anti-histamines (sgAH) at licensed doses, sgAH two, three to fourfold doses (non-licensed) and omalizumab. Other drugs, such as, cyclosporine, immunomodulatory drugs and immunosuppressants may be indicated (non-licensed and with limited scientific evidence). Conclusions: Most of the Brazilian experts in this study partially agreed with the diagnostic and therapeutic recommendations of the International and US guidelines. They agreed with the use of sgAH at licensed doses. Increase in the dose to fourfold of sgAH may be suggested with restrictions, due to its non-licensed dose. Sedating anti-histamines, as suggested by the US guideline, are indicated by some of the Brazilian experts, due to its availability. Adaptations are mandatory in the treatment of CSU, due to scarce or lack of other therapeutic resources in the public health system in Brazil, such as omalizumab or cyclosporine.
Assuntos
Humanos , Adulto , Urticária/diagnóstico , Urticária/tratamento farmacológico , Consenso , Sociedades Médicas , Urticária/prevenção & controle , Índice de Gravidade de Doença , Brasil , Doença Crônica , Antialérgicos/uso terapêutico , Ciclosporinas/uso terapêutico , Antagonistas não Sedativos dos Receptores H1 da Histamina/uso terapêutico , Dermatologia , Omalizumab/uso terapêutico , Imunossupressores/uso terapêuticoRESUMO
Chronic urticaria (CU) is characterized by itchy wheals, angioedema or both lasting six weeks or more. It is classified as spontaneous (CSU) and inducible urticaria (CIndU), depending whether there is an identifiable trigger or not. CSU is the predominant form, affecting more than 75% of patients, although overlaps often occur. The prevalence of CSU throughout life is around 1.8% and predominates in women at a ratio of 2:1. The higher incidence of CSU is between 20 and 40 years of age and lasts between one to five years. However, in up to 20% of patients the disease may last longer. CSU not only hampers quality of life, but also affect performance at work and school. The diagnosis of CSU is mainly clinical, and laboratory tests are required depending on the clinical history of the patient. Extensive laboratory tests are usually unnecessary. Second generation anti-histamines are used as first line treatment for CSU treatment. In refractory patients, systemic treatments, such as cyclosporine or omalizumab are suggested. We herein report the first Chilean CSU guidelines.
Assuntos
Humanos , Urticária/patologia , Urticária/tratamento farmacológico , Guias de Prática Clínica como Assunto , Urticária/diagnóstico , Chile , Doença Crônica , Antagonistas não Sedativos dos Receptores H1 da Histamina/uso terapêuticoRESUMO
BACKGROUND: Despite the current knowledge of UV, there is a lack of consensus among diagnostic criteria and management. In general, antihistamine therapy is regularly used for the symptomatic management of pruritus but does not control inflammation or alter the course of the disease. Monoclonal antibodies such as omalizumab (anti-IgE) have been proposed as a potential treatment for urticarial vasculitis. A few studies have reported the benefits of omalizumab in patient-reported outcome measures (PROMs). Herein we describe a female patient with urticarial vasculitis who was treated with omalizumab. We discuss the response to treatment and possible implications of PROMs in guiding the management of the disease. CASE PRESENTATION: We describe the case of a 57-year-old woman with a diagnosis of urticarial vasculitis. Due to lack of response to first-line treatment and the severity of the disease, treatment with omalizumab was initiated. Omalizumab 150 mg was administered every four weeks for three months. Second-generation antihistamines were used as needed. Both CU-Q2oL and UAS 7 improved. After three-month therapy with omalizumab, disease severity improved from moderate severity (UAS7 = 19) to well controlled (UAS7 = 6). However, 5 months after the last administration of omalizumab, the patient complained of worsening symptoms and active disease with quality of life impairment. A single dose of omalizumab (150 mg) was prescribed with corticosteroids. Thereafter, the patient presented a disease activity and quality of life with a fluctuating pattern that was controlled with additional doses of omalizumab. CONCLUSION: In chronic urticaria, patient-reported outcome measures (PROMs) are important for assessing disease status and the impact of symptoms on patients' lives. However, to our knowledge, there is no validated tool to measure such outcomes in UV patients. Although UAS7 and CU-Q2oL were not designed for UV assessment, they might be useful in the clinical setting as objective measures to determine treatment efficacy. However, some domains in the CU-Q2oL questionnaires do not correlate well with UAS7, which might serve as a relative indication to continue treatment despite disease severity improvement. Based on our observations, we believe omalizumab 150 mg might be a feasible therapeutic alternative when first-line treatment is unsuccessful.
Assuntos
Antialérgicos/uso terapêutico , Omalizumab/uso terapêutico , Medidas de Resultados Relatados pelo Paciente , Urticária/tratamento farmacológico , Vasculite Leucocitoclástica Cutânea/tratamento farmacológico , Doença Crônica , Feminino , Antagonistas não Sedativos dos Receptores H1 da Histamina/uso terapêutico , Humanos , Pessoa de Meia-Idade , Prurido/tratamento farmacológico , Prurido/etiologia , Recidiva , Urticária/etiologia , Vasculite Leucocitoclástica Cutânea/complicaçõesRESUMO
Abstract Introduction: A combination of antihistamines and oral corticosteroids is often used to treat acute symptoms of allergic rhinitis. Objective: To evaluate safety and efficacy of desloratadine plus prednisolone in the treatment of acute symptoms of children (2-12 years) with allergic rhinitis, and to compare it to dexchlorpheniramine plus betamethasone. Methods: Children with moderate/severe persistent allergic rhinitis and symptomatic (nasal symptoms score [0-12] ≥ 6) were allocated in a double-blind, randomized fashion to receive dexchlorpheniramine plus betamethasone (n = 105; three daily doses) or desloratadine plus prednisolone (n = 105; single dose followed by two of placebo) for 7 days. At the beginning and end of the evaluation, the following were obtained: nasal symptoms score, extra nasal symptoms score, peak nasal inspiratory flow, blood biochemistry, and electrocardiogram. Ninety-six children of the dexchlorpheniramine plus betamethasone group and 98 of the desloratadine plus prednisolone group completed the protocol. Results: The two groups were similar regarding initial and final nasal symptoms scores, extra nasal symptoms scores and peak nasal inspiratory flow. A drop of 76.4% and 79.1% for nasal symptoms score, 86.0% and 79.2% for extra nasal symptoms score, as well as an increase of 25.2% and 24.3% for peak nasal inspiratory flow occurred for those treated with desloratadine plus prednisolone and dexchlorpheniramine plus betamethasone, respectively. There were no significant changes in blood chemistry. Sinus tachycardia was the most frequent electrocardiogram change, but with no clinical significance. Drowsiness was reported significantly more often among those of dexchlorpheniramine plus betamethasone group (17.14% × 8.57%, respectively). Conclusion: The desloratadine plus prednisolone combination was able to effectively control acute symptoms of rhinitis in children, improving symptoms and nasal function. Compared to the dexchlorpheniramine plus betamethasone combination, it showed similar clinical action, but with a lower incidence of adverse events and higher dosing convenience.
Resumo Introdução: A associação entre anti-histamínicos e corticosteroides orais é frequentemente empregada no tratamento de sintomas agudos de rinite alérgica. Objetivo: Avaliar a segurança e eficácia da associação desloratadina + prednisolona no tratamento de sintomas agudos de crianças (2-12 anos) com rinite alérgica e compará-las com as da associação dexclorfeniramina + betametasona. Método: Crianças com rinite alérgica persistente moderada/grave e sintomáticas (escore de sintomas nasais [0-12] ≥ 6) foram alocadas de modo duplo-cego e randômico para receber dexclorfeniramina + betametasona (n = 105; três doses diárias) ou desloratadina + prednisolona (n = 105; dose única seguida por duas de placebo) por 7 dias. No início e no fim da avaliação foram obtidos: escore de sintomas nasais, escore de sintomas extranasais, pico de fluxo inspiratório nasal, bioquímica sanguínea e eletrocardiograma. Do total, 96 crianças do grupo dexclorfeniramina + betametasona e 98 do grupo desloratadina + prednisolona concluíram o protocolo. Resultados: Os dois grupos foram iguais com relação ao escore de sintomas nasais, escore de sintomas nasais extranasais e pico de fluxo inspiratório nasal iniciais e finais. Observou-se queda de 76,4% e 79,1% nos escores para escore de sintomas nasais, de 86,0% e 79,2% para escore de sintomas extranasais, assim como incremento de 25,2% e de 24,3% para o pico de fluxo inspiratório nasal para os grupos desloratadina + prednisolona e dexclorfeniramina + betametasona, respectivamente. Não houve alterações significativas da bioquímica sanguínea. Taquicardia sinusal foi a alteração do eletrocardiograma mais encontrada, mas sem significância clínica. Sonolência foi significantemente mais referida entre os tratados com dexclorfeniramina + betametasona do que entre os desloratadina + prednisolona (8,57% × 17,14%, respectivamente). Conclusão: A associação desloratadina + prednisolona foi capaz de controlar efetivamente os sintomas agudos de rinite em crianças, melhorou sintomas e a função nasal. Na comparação com a associação dexclorfeniramina + betametasona, demonstrou ação clínica semelhante, mas com menor incidência de eventos adversos e maior comodidade posológica.
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Prednisolona/administração & dosagem , Loratadina/análogos & derivados , Rinite Alérgica/tratamento farmacológico , Glucocorticoides/administração & dosagem , Fatores de Tempo , Índice de Gravidade de Doença , Betametasona/administração & dosagem , Betametasona/efeitos adversos , Prednisolona/efeitos adversos , Pico do Fluxo Expiratório , Método Duplo-Cego , Reprodutibilidade dos Testes , Resultado do Tratamento , Loratadina/administração & dosagem , Loratadina/efeitos adversos , Estatísticas não Paramétricas , Antagonistas não Sedativos dos Receptores H1 da Histamina/administração & dosagem , Antagonistas não Sedativos dos Receptores H1 da Histamina/efeitos adversos , Combinação de Medicamentos , Glucocorticoides/efeitos adversosRESUMO
BACKGROUND: Solar urticaria is a rare type of inducible urticaria characterized by wheal and erythema formation shortly after exposure to sunlight or to an artificial light source; its pathophysiology is not yet entirely understood. The treatment of choice, in addition to exposure avoidance, consists in antihistamine administration. CLINICAL CASE: This is the case of a 27-year-old woman with no personal history of allergic diseases and with a 2-year history of erythema and wheals in photo-exposed areas associated with sunlight exposure for periods longer than 10 minutes. A provocation test was carried out; she was started on fexofenadine at 4-fold the standard dose (720 mg/day). Six weeks later, a new challenge was carried out without the antihistamine being discontinued; the reaction was less severe, but she continued with erythema for the first 60 minutes post-exposure. After 3 months on high-dose antihistamines, she referred marked improvement in her quality of life and tolerance to brief sunlight exposure (for less than 15 minutes). CONCLUSIONS: Solar urticaria is a rare process but with a high impact on the patient. The use of antihistamines partially relieves symptoms and allows better tolerance to lighting expositions.
Antecedentes: La urticaria solar es un tipo infrecuente de urticaria inducible que se manifiesta con erupciones y eritema poco después de la exposición a la luz del sol o de una fuente de luz artificial; su fisiopatología aún no se comprende del todo. El tratamiento de elección, además de evitar la exposición, consiste en la administración de antihistamínicos. Caso clínico: Mujer de 27 años, sin antecedente personal de enfermedades alérgicas, con cuadro clínico de 2 años de evolución consistente en eritema y erupciones en áreas fotoexpuestas asociados con exposición a la luz del sol durante más de 10 minutos. Se realizó prueba de reto. Se decidió continuar con una dosis de fexofenadina 4 veces mayor a la convencional (720 mg/día). Seis semanas después se efectuó nuevo reto sin suspender el antihistamínico; la reacción fue menos severa, pero la paciente continuó con eritema durante los primeros 60 minutos posteriores a la exposición. Después de 3 meses con dosis altas de antihistamínicos, la paciente refirió notable mejoría en su calidad de vida y tolerancia a exposiciones cortas a luz solar (menos de 15 minutos). Conclusiones: La urticaria solar es un proceso raro pero con alto impacto en el paciente. El uso de antihistamínicos alivia parcialmente los síntomas y permite una mejor tolerancia a las exposiciones lumínicas.
Assuntos
Transtornos de Fotossensibilidade/etiologia , Luz Solar/efeitos adversos , Urticária/etiologia , Adulto , Fármacos Dermatológicos/uso terapêutico , Feminino , Antagonistas não Sedativos dos Receptores H1 da Histamina/uso terapêutico , Humanos , Transtornos de Fotossensibilidade/tratamento farmacológico , Terfenadina/análogos & derivados , Terfenadina/uso terapêutico , Urticária/tratamento farmacológicoRESUMO
Neurotensin is known to inhibit neuronal Na+ , K+ -ATPase, an effect that is rescued by nitric oxide (NO) synthase inhibition. However, whether the neurotensinergic and the nitrergic systems are independent pathways, or are mechanistically linked, remains unknown. Here, we addressed this issue and found that the administration of low affinity neurotensin receptor (NTS2) antagonist, levocabastine (50 µg/kg, i.p.) inhibited NO synthase (NOS) activity by 74 and 42% after 18 h in synaptosomal and mitochondrial fractions isolated from the Wistar rat cerebral cortex, respectively; these effects disappeared 36 h after levocabastine treatment. Intriguingly, whereas neuronal NOS protein abundance decreased (by 56%) in synaptosomes membranes, it was enhanced (by 86%) in mitochondria 18 h after levocabastine administration. Levocabastine enhanced the respiratory rate of synaptosomes in the presence of oligomycin, but it failed to alter the spare respiratory capacity; furthermore, the mitochondrial respiratory chain (MRC) complexes I-IV activities were severely diminished by levocabastine administration. The inhibition of NOS and MRC complexes activities were also observed after incubation of synaptosomes and mitochondria with levocabastine (1 µM) in vitro. These data indicate that the NTS2 antagonist levocabastine regulates NOS expression and activity at the synapse, suggesting an interrelationship between the neurotensinergic and the nitrergic systems. However, the bioenergetics effects of NTS2 activity inhibition are likely to be independent from the regulation of NO synthesis.
Assuntos
Encéfalo/efeitos dos fármacos , Antagonistas não Sedativos dos Receptores H1 da Histamina/farmacologia , Mitocôndrias/efeitos dos fármacos , Óxido Nítrico/biossíntese , Piperidinas/farmacologia , Animais , Encéfalo/metabolismo , Masculino , Óxido Nítrico Sintase/metabolismo , Ratos , Ratos Wistar , Receptores de Neurotensina/antagonistas & inibidoresRESUMO
INTRODUCTION: A combination of antihistamines and oral corticosteroids is often used to treat acute symptoms of allergic rhinitis. OBJECTIVE: To evaluate safety and efficacy of desloratadine plus prednisolone in the treatment of acute symptoms of children (2-12 years) with allergic rhinitis, and to compare it to dexchlorpheniramine plus betamethasone. METHODS: Children with moderate/severe persistent allergic rhinitis and symptomatic (nasal symptoms score [0-12]≥6) were allocated in a double-blind, randomized fashion to receive dexchlorpheniramine plus betamethasone (n=105; three daily doses) or desloratadine plus prednisolone (n=105; single dose followed by two of placebo) for 7 days. At the beginning and end of the evaluation, the following were obtained: nasal symptoms score, extra nasal symptoms score, peak nasal inspiratory flow, blood biochemistry, and electrocardiogram. Ninety-six children of the dexchlorpheniramine plus betamethasone group and 98 of the desloratadine plus prednisolone group completed the protocol. RESULTS: The two groups were similar regarding initial and final nasal symptoms scores, extra nasal symptoms scores and peak nasal inspiratory flow. A drop of 76.4% and 79.1% for nasal symptoms score, 86.0% and 79.2% for extra nasal symptoms score, as well as an increase of 25.2% and 24.3% for peak nasal inspiratory flow occurred for those treated with desloratadine plus prednisolone and dexchlorpheniramine plus betamethasone, respectively. There were no significant changes in blood chemistry. Sinus tachycardia was the most frequent electrocardiogram change, but with no clinical significance. Drowsiness was reported significantly more often among those of dexchlorpheniramine plus betamethasone group (17.14%×8.57%, respectively). CONCLUSION: The desloratadine plus prednisolone combination was able to effectively control acute symptoms of rhinitis in children, improving symptoms and nasal function. Compared to the dexchlorpheniramine plus betamethasone combination, it showed similar clinical action, but with a lower incidence of adverse events and higher dosing convenience.
Assuntos
Glucocorticoides/administração & dosagem , Antagonistas não Sedativos dos Receptores H1 da Histamina/administração & dosagem , Loratadina/análogos & derivados , Prednisolona/administração & dosagem , Rinite Alérgica/tratamento farmacológico , Betametasona/administração & dosagem , Betametasona/efeitos adversos , Criança , Pré-Escolar , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Glucocorticoides/efeitos adversos , Antagonistas não Sedativos dos Receptores H1 da Histamina/efeitos adversos , Humanos , Loratadina/administração & dosagem , Loratadina/efeitos adversos , Masculino , Pico do Fluxo Expiratório , Prednisolona/efeitos adversos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Histamine receptors are known to participate in spinal cord nociceptive transmission, and previous studies have suggested that histaminergic receptors are involved in the analgesic effects of morphine. Herein, we investigated the effect of intrathecal injection of histaminergic agonists and antagonists in a model of acute articular inflammation and their interaction with morphine. METHODS: After carrageenan injection in the right knee joint, articular incapacitation was measured hourly, for up to 6 hours, by the paw elevation time during 1-minute periods of stimulated walking. Inflammatory edema was also assessed hourly by determining an increase in articular diameter. Spinal treatments were administered 20 minutes before knee-joint carrageenan injection and were compared with the saline-treated control group. RESULTS: Intrathecally injected histamine increased incapacitation and articular edema, whereas the H1R antagonist, cetirizine, decreased both parameters. The H3R agonist, immepip, decreased both incapacitation and edema, but the H3R antagonist, thioperamide, increased both incapacitation and edema. Morphine inhibited both incapacitation and edema. Furthermore, combining a subeffective dose of morphine with cetirizine or immepip potentiated the analgesic and antiedematogenic effect. CONCLUSIONS: Histamine seems to act at the spinal level via H1 and H3 receptors to modulate acute arthritis in rats. An H1R antagonist and H3R agonist were found to potentiate the analgesic and antiedematogenic effects of morphine, suggesting that histaminergic and opioid spinal systems may be explored for means of improving analgesia, as well as peripheral anti-inflammatory effects.
Assuntos
Analgésicos Opioides/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Edema/tratamento farmacológico , Agonistas dos Receptores Histamínicos/farmacologia , Antagonistas dos Receptores Histamínicos/farmacologia , Histamina/metabolismo , Articulações/inervação , Morfina/administração & dosagem , Osteoartrite/tratamento farmacológico , Medula Espinal/efeitos dos fármacos , Animais , Carragenina , Cetirizina/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/metabolismo , Edema/fisiopatologia , Antagonistas não Sedativos dos Receptores H1 da Histamina/farmacologia , Antagonistas dos Receptores Histamínicos H3/farmacologia , Imidazóis/farmacologia , Injeções Espinhais , Masculino , Osteoartrite/induzido quimicamente , Osteoartrite/metabolismo , Osteoartrite/fisiopatologia , Piperidinas/farmacologia , Ratos Wistar , Receptores Histamínicos H1/efeitos dos fármacos , Receptores Histamínicos H1/metabolismo , Receptores Histamínicos H3/efeitos dos fármacos , Receptores Histamínicos H3/metabolismo , Medula Espinal/metabolismo , Medula Espinal/fisiopatologiaRESUMO
Nonsedating antihistamines are the first-choice treatment for all forms of urticaria. In patients with recalcitrant urticaria who do not respond to conventional doses of antihistamines, current guidelines recommend increasing doses by up to 4 times in order to obtain better control of the disease. Although few studies have been conducted, there are convincing data from controlled trials for cetirizine, levocetirizine, and desloratadine that support the use of increased doses of such drugs in unresponsive patients. The use of higher doses of antihistamines has not been associated with increased adverse effects or somnolence. More studies with other second-generation antihistamines are required in order to improve the treatment of patients with severe, recalcitrant urticaria.
Assuntos
Antagonistas não Sedativos dos Receptores H1 da Histamina/administração & dosagem , Urticária/tratamento farmacológico , Doença Crônica , HumanosRESUMO
BACKGROUND: Allergic rhinitis (AR) is one of the most common chronic diseases in childhood. No large, multicentre clinical trials in children with persistent allergic rhinitis (PER) have previously been performed. Rupatadine, a newer second-generation antihistamine, effective and safe in adults, is a promising treatment for children with AR. The aim of the present study was to evaluate the efficacy and safety of a new rupatadine oral solution in children aged 6-11 yr with PER. METHODS: A multicenter, randomized, double-blind, placebo-controlled study was carried out worldwide. Patients between 6 and 11 yr with a diagnosis of PER according to ARIA criteria were randomized to receive either rupatadine oral solution (1 mg/ml) or placebo over 6 wk. The primary efficacy end-point was the change from baseline of the total nasal symptoms score (T4SS) after 4 wk of treatment. RESULTS: A total of 360 patients were randomized to rupatadine (n = 180) or placebo (n = 180) treatment. Rupatadine showed statistically significant differences vs. placebo for the T4SS reduction both at 4 (-2.5 ± 1.9 vs. -3.1 ± 2.1; p = 0.018) and 6 wk (-2.7 ± 1.9 vs. -3.3 ± 2.1; p = 0.048). Rupatadine also showed a statistically better improvement in the children's quality of life compared with placebo. Adverse reactions were rare and non-serious in both treatment groups. No QTc or laboratory test abnormalities were reported. CONCLUSIONS: Rupatadine oral solution (1 mg/ml) was significantly more effective than placebo in reducing nasal symptoms at 4 and 6 wk and was well tolerated overall. This is the first large clinical report on the efficacy of an H1 receptor antagonist in children with PER in both symptoms and quality of life.
Assuntos
Antialérgicos/administração & dosagem , Ciproeptadina/análogos & derivados , Antagonistas não Sedativos dos Receptores H1 da Histamina/administração & dosagem , Rinite Alérgica Perene/tratamento farmacológico , Rinite Alérgica Sazonal/tratamento farmacológico , Administração Oral , Análise de Variância , Antialérgicos/efeitos adversos , Argentina , Criança , Ciproeptadina/administração & dosagem , Ciproeptadina/efeitos adversos , Método Duplo-Cego , Europa (Continente) , Feminino , Antagonistas não Sedativos dos Receptores H1 da Histamina/efeitos adversos , Humanos , Masculino , Qualidade de Vida , Rinite Alérgica , Rinite Alérgica Perene/diagnóstico , Rinite Alérgica Perene/psicologia , Rinite Alérgica Sazonal/diagnóstico , Rinite Alérgica Sazonal/psicologia , África do Sul , Fatores de Tempo , Resultado do TratamentoRESUMO
AIM: This study aimed to investigate the in vitro effects of three paediatric liquid oral medicines on bovine dental enamel subsurfaces under pH cycling conditions. METHODS: Bovine enamel blocks were evaluated for surface hardness at baseline for sample selection. 52 intact bovine enamel blocks (16mm(2)) were randomly divided into four groups (n=13) according to the immersion treatments: G1: antibiotic (Klaricid®), G2: antihistamine (Claritin®), G3: antihistamine (Dimetapp®) and G4: control (de-ionised water). The blocks were submitted to pH cycling treatments twice a day for 12 days. The medicines were evaluated for pH, viscosity, and concentration of calcium, phosphate and fluoride. After the treatment period, cross-sectional microhardness (CSMH) measurements of the enamel blocks were taken and the data, expressed in Knoop hardness number (kg/mm(2)) was used to calculate the ΔS. STATISTICS: ANOVA followed by the Tukey test were used for statistical analyses (p<0.05). RESULTS: The antibiotic Klaricid® showed the highest concentration of fluoride, calcium and phosphate. Considering pH and viscosity, the following pattern was observed according to the treatment group: G4>G1>G2>G3 and G1>G2>G3>G4 respectively. Regarding the demineralisation pattern, the following results were observed: G4>G3>G2>G1. Compared to the control, the antibiotic and both the antihistamines provoked less demineralisation of the enamel blocks (p<0.05). CONCLUSIONS: Antibiotic G1 (Klaricid®) presented an in vitro protective effect against acid attacks probably due to its mineral content and viscosity.
Assuntos
Esmalte Dentário/efeitos dos fármacos , Excipientes Farmacêuticos/efeitos adversos , Anatomia Transversal , Animais , Antibacterianos/efeitos adversos , Antibacterianos/química , Bromofeniramina/efeitos adversos , Bromofeniramina/química , Cálcio/análise , Bovinos , Claritromicina/efeitos adversos , Claritromicina/química , Solubilidade do Esmalte Dentário/efeitos dos fármacos , Combinação de Medicamentos , Fluoretos/análise , Dureza , Antagonistas não Sedativos dos Receptores H1 da Histamina/efeitos adversos , Antagonistas não Sedativos dos Receptores H1 da Histamina/química , Concentração de Íons de Hidrogênio , Loratadina/efeitos adversos , Loratadina/química , Descongestionantes Nasais/efeitos adversos , Descongestionantes Nasais/química , Excipientes Farmacêuticos/química , Fosfatos/análise , Pseudoefedrina/efeitos adversos , Pseudoefedrina/química , Distribuição Aleatória , Soluções , Desmineralização do Dente/induzido quimicamente , ViscosidadeRESUMO
INTRODUCTION: Uremic pruritus is common among dialysis patients. Effective treatments are not readily available. Early evidence with antihistamines and gabapentin indicate variable effects. OBJECTIVE: To compare the efficacy and side effects of gabapentin and desloratadine in patients with dialysis pruritus. METHODS: Prospective, open-label, cross-over clinical trial in 22 patients on chronic hemodialysis with sustained pruritus over a period of at least 60 days. After a one-week run-in period, we assigned patients to three weeks of either gabapentin 300 mg thrice weekly or desloratadine 5 mg thrice weekly. After a one-week washout period, each patient crossed-over to the alternate regimen for three more weeks. The primary endpoint of the study was the change in the visual analogue pruritus score (VAS). RESULTS: Nineteen subjects completed the two treatment blocks and were available for analysis. VAS scores decreased with both treatments (5.95 to 4.6 with gabapentin, p = 0.07; 5.89 to 3.4 with desloratadine, p = 0.004), but only desloratadine reached statistical significance. There were no differences when comparing the final pruritus score with gabapentin and desloratadine (4.6 versus 3.4, p = 0.16) Excessive sedation was common with gabapentin. Desloratadine was well tolerated. CONCLUSION: Desloratadine provides significant relief of uremic pruritus compared with no therapy. gabapentin has marginal efficacy. Desloratadine is better tolerated than gabapentin.