ASPECTOS RELEVANTES DO USO DO REMIMAZOLAN DURANTE A PRÁTICA ANESTÉSICA

RESUMO INTRODUCAO: Os sedativos mais frequentemente utilizados na pratica da anestesia sao o Midazolam, fentanil e propofol.These agents possess characteristics that have afforded various anesthetics to be delivered and produce relatively safe and effective outcomes. Tais agentes possuem caracteristicas farmacologicas que fornecem resultados relativamente seguros e efetivos. However, each agent has certain drawbacks in clinical practice. Por outro lado, os referidos agentes apresentam algumas desvantagens na pratica clinica. Em funcao disso, oRemimazolam, a novel benzodiazepine created out of so-called soft drug development, is an ultrashort-acting intravenous sedative-hypnotic currently being investigated in clinical trials. Remimazolam (CNS-7056), um novo membro da classe de drogas benzodiazepinicas, e um sedativo e hipnotico intravenoso que vem sendo investigado em ensaios clinicos. Este composto e um resultado de uma combinacao de propiedades de dois farmacos bem conhecidos: Midazolam e Remifentanil. O mesmo atua sobre os receptores GABA -alfa e sua via de metabolizacao ocorre a cargo das esterases tisulares. Sua primeira via de metabolizacao nao se realiza mediante citocromo P-450, visto que o mesmo nao esta sujeito a interacoes farmacologicas excessivas. Estudos pre-clinicos demonstraram que o remimazolan produziu um inicio de acao mais rapido e uma menor duracao da acao. Em um ensaio clinico de fase IIa que avaliou o remimazolan como sedativo para endoscopia gastrintestinal superior em pacientes, o tempo de recuperacao da sedacao foi menor e mais consistente com o remimazolan, em comparacao com o midazolan. Devido ao seu metabolismo independente e ao inicio e recuperacao rapidos e previsiveis, o remimazolan parece ter vantagens em relacao a outros sedativos de curta acao. METODOLOGIA: In this review, we evaluate the recent literature on the use of remimazolam in clinical practice as compared with current sedative agents, and we describe its potential roles for use in sedation.Nesta revisao, avaliamos a literatura recente sobre o uso de remimazolam em comparacao com os atuais agentes sedativos, e descrevemos suas potenciais funcoes para uso em sedacao. Para tal,A literature search of the Medline database (2012-May 2016) was performed. foi realizado um levantamento bibliografico no banco de dados Medline, sendoAdditional references were identified from a review of literature citations, manufacturer reports, and professional meeting abstracts.All premarket studies involving remimazolam as the primary study drug were evaluated. Avaliados estudos de pre-mercado envolvendo remimazolam como o principal farmaco. Literature describing the pharmacokinetics and pharmacodynamics of remimazolam, propofol, and midazolam was also included. Alem disso, foi incluida a literatura que descreve a sua farmacocinetica e a farmacodinâmica.Phase I and II studies in the United States have shown remimazolam to be a safe and effective option for procedural sedation. RESULTADOS E DISCUSSAO: Estudos de Fase I e II nos Estados Unidos mostraram remimazolam como uma opcao segura e efetiva para sedacao processual. Unlike midazolam and propofol, remimazolam undergoes organ-independent metabolism to an inactive metabolite. Ao contrario do midazolam e do propofol, o remimazolam sofre metabolismo independente de orgaos para um metabolito inativo. Em virtude do remimazolan seguir a farmacocinetica de primeira ordem, infusoes prolongadas ou doses mais elevadas provavelmente nao resultarao acumulo e efeito prolongado, tornado-o eficiente para o uso como anestesia intravenosa com efeito sedativo e hipnotico. CONCLUSAO: Com isso, acredita-se que os ensaios de fase III descrevam ainda mais o nicho que o remimazolam pode ocupar na pratica clinica. Postmarket cost-benefit analyses will need to be performed. E importante ressaltar a necessidade de realizacoes de analises custo-beneficio da referida droga. Espera-se que o surgimento desta nova droga, ainda nao disponivel no mercado, favoreca o paciente, pois os dois pilares da anestesia, hipnose e analgesia, estao contemplados neste farmaco. Palavras-chave: analgesia 1 , benzodiazepinico 2 , hipnotico 3 ABSTRACT INTRODUCTION: The sedatives most frequently used in the practice of anesthesia are Midazolam, Fentanyl and Propofol. Such agents have pharmacological characteristics that provide relatively safe and effective results. On the other hand, said agents have some disadvantages in clinical practice. Because of this, Remimazolam (CNS-7056), a new member of the benzodiazepine class of drugs, is an intravenous sedative and hypnotic that has been investigated in clinical trials. this compound is a result of a combination of properties of two well known drugs: midazolan and remifentanil. The same acts on GABA alpha receptors and its pathway of metabolization occurs through the tissue esterases. Its first route of metabolization is by cytochrome P-450, since it is not subject to excessive pharmacological interactions. Preclinical studies have shown that remimazolan produced a faster onset of action and shorter duration of action. In a phase IIa trial evaluating remimazolan as a sedative for upper gastrointestinal endoscopy in patients, the recovery time of sedation was lower and more consistent with remimazolan compared to midazolan. Because of its independent metabolism and rapid and predictable onset and recovery, remimazolan appears to have advantages over other short-acting sedatives. METHODOLOGY : In this review, we evaluated the recent literature on the use of remimazolam in comparison with current sedative agents, and described its potential roles for use in sedation. For this, a bibliographic survey was carried out in the Medline database, being evaluated premarket studies involving remimazolam as the main drug. In addition, the literature describing its pharmacokinetics and pharmacodynamics has been included. RESULTS AND DISCUSSION: Phase I and II studies in the United States have shown remimazolam as a safe and effective option for procedural sedation. Unlike midazolam and propofol, remimazolam undergoes organ-independent metabolism to an inactive metabolite. Because remimazolan follows first-order pharmacokinetics, prolonged infusions or higher doses are unlikely to result in accumulation and prolonged effect, making it effective for use as intravenous anesthesia with a sedative and hypnotic effect. CONCLUSION: Thus, it is believed that phase III trials further describe the niche that remimazolam may occupy in clinical practice. It is important to emphasize the need for cost-benefit analyzes of this drug. It is expected that the appearance of this new drug, not yet available in the market, favors the patient, since the two pillars of anesthesia, hypnosis and analgesia, are contemplated in this drug. Keywords: analgesia 1 ,benzodiazepine 2 , hypnotic 3