Assistência pré-natal às usuárias de substâncias psicoativas: dificuldades elencadas pelos profissionais da saúde / Prenatal care for users of psychoactive substances: difficulties listed by health professionals / Atención prenatal a consumidoras de sustancias psicoactivas: dificultades mencionadas por los profesionales de la salud

Objetivo: conhecer as dificuldades elencadas pelos profissionais de saúde na assistência pré-natal às usuárias de substâncias psicoativas. Método: estudo qualitativo, exploratório-descritivo, realizado nas mídias sociais, com profissionais da área da saúde que realizam atendimento pré-natal. A coleta de dados ocorreu de novembro de 2022 a janeiro de 2023 por meio de questionário eletrônico. Os dados foram analisados por meio da análise temática. Protocolo aprovado pelo Comitê de Ética em Pesquisa. Resultados: os profissionais destacam o déficit de conhecimento para abordar este público em específico. A abordagem superficial e condenatória do uso de substâncias pelas políticas públicas corrobora para que os profissionais se sintam preparados em parte para atender essas gestantes. Considerações finais: a capacitação dos profissionais é necessária para superar práticas condenatórias e retrógradas de cuidado que focam unicamente a abstinência; como também, o investimento na capacitação acerca da rede de atenção à saúde, buscando ampliar sua visibilidade e utilização.

Objective: understanding the difficulties listed by health professionals in prenatal care for users of psychoactive substances. Method: this is a qualitative, exploratory-descriptive study carried out on social media with health professionals who provide prenatal care. Data was collected from November 2022 to January 2023 using an electronic questionnaire. The data was analyzed using thematic analysis. Protocol approved by the Research Ethics Committee. Results: the professionals highlight the lack of knowledge to deal with this specific public. The superficial and condemnatory approach to substance use by public policies contributes to making professionals feel partly prepared to deal with these pregnant women. Final considerations: the training of professionals is necessary to overcome condemnatory and retrograde care practices that focus solely on abstinence; and investment in training about the health care network, seeking to increase its visibility and use.

Objetivo: conocer las dificultades mencionadas por los profesionales de la salud en la atención prenatal de las consumidoras de sustancias psicoactivas. Método: estudio cualitativo, exploratorio-descriptivo, realizado en redes sociales, con profesionales de la salud que brindan atención prenatal. La recolección de datos se llevó a cabo de noviembre de 2022 a enero de 2023 a través de un cuestionario electrónico. Los datos se analizaron mediante análisis temático. El protocolo fue aprobado por el Comité de Ética en Investigación. Resultados: los profesionales destacan que les falta el conocimiento para atender a este público específico. El abordaje superficial y condenatorio del consumo de sustancias por parte de las políticas públicas contribuye a que los profesionales se sientan parcialmente preparados para atender a esas gestantes. Consideraciones finales: es necesario capacitar a los profesionales para superar las prácticas asistenciales condenatorias y retrógradas que se centran únicamente en evitar el consumo; e invertir en capacitación sobre la red de atención de salud, para ampliar su visibilidad y uso.

Usabilidade de um aplicativo móvel de apoio aos profissionaisde saúde para cálculos de doses de vancomicina / Usability of a mobile application supporting healthprofessionals on vancomycin dosing calculation

O aplicativo móvel CalcVAN foi desenvolvido para auxiliar os profissionais de saúde para otimizar as doses de vancomicina em pacientes hospitalizados. Porém, é imprescindível avaliar a sua usabilidade antes de disponibilizá-lo para prática clínica. Assim, o objetivo do estudo é avaliar a usabilidade do aplicativo móvel na perspectiva dos profissionais de saúde. Trata-se de um estudo descritivo, de avaliação heurística da usabilidade de um aplicativo móvel. Foram convidados profissionais da área de saúde com expertise no tema de gerenciamento de antimicrobianos e vancomicina. O instrumento validado Smartphone Usability questionnaiRE (SURE) foi utilizado para mensuração da usabilidade por meio de um questionário on-line. Vinte e um especialistas participaram do estudo, com média de idade de 32,6 anos, sendo a maioria de mulheres (n = 14, 66,7%), profissionais farmacêuticos (n = 13, 61,9%), com pós-graduação lato sensu (n = 10, 47,6%), que trabalhavam em hospitais públicos ou privados (n = 15, 71,4%) e com média de experiência em 9,7 anos. Com base na interpretação dos resultados obtidos pelo instrumento SURE, a média de usabilidade geral do CalcVAN foi de 83 pontos, com escore menor de 78 e maior de 90 pontos. O teste de usabilidade foi enquadrado nos dois últimos níveis, 70 e 80, onde os profissionais de saúde passaram a concordar fortemente e totalmente, indicando que o aplicativo móvel apresenta uma usabilidade satisfatória. O CalcVAN atingiu uma usabilidade satisfatória e atende as necessidades e exigências dos profissionais de saúde, mostrando--se eficiente para realizar as funções propostas.

The CalcVAN app was developed to assist healthcare professionals in optimizing vancomycin doses for hospitalized patients. However, the usability test before making it available for clinical practice is essential. Therefore, the study aims to evaluate the usability of the app from the perspective of health professionals. A descriptive study, a heuristic evaluation of the usability of a mobile application was conducted. Healthcare professionals with expertise in antimicrobial management and vancomycin were invited to participate. The validated Smartphone Usability questionnaiRE (SURE) was used to measure usability through an online questionnaire. Twenty-one experts participated in the study, with a mean age of 32.6 years, mostly of them women (n = 14, 66.7%), pharmacists (n = 13, 61.9%), with postgraduate education (n = 10, 47.6%), working in private or public hospitals (n = 15, 71.4%), and a mean experience of 9.7 years. Overall usability score for CalcVAN was 83 points, ranging from a minimum of 78 to a maximum of 90 points. The usability test registered within the last two levels, 70 and 80, with users expressing strongly and fully agreed, indicating that the app demonstrates satisfactory usability. CalcVAN achieved satisfactory usability, fulfilling the needs and requirements of health professionals, proving to be efficient in performing the intended functions.

Alterações sistêmicas e bucais em pacientes usuários de cocaína: uma revisão integrativa da literatura / Cambios sistémicos y orales em pacientes consumidores de cocaína: una revisión bibliográfica integradora / Systemic and oral changes in cocaína-using patients: an integrative literature review

Introdução: A utilização de cocaína é bastante associada ao surgimento de algumas manifestações sistêmicas e também de algumas alterações orais. Objetivo: Identificaras alterações sistêmicas e bucais mais comuns a pacientes usuários de cocaína. Metodologia: Trata-se de uma revisão sistemática da literatura, considerando artigos com texto completo, com restrição de idioma em Português ou Inglês e que tenham sido publicados entre os anos de 2017 a 2022. Usou-se as bases de dados LiLaCS, MedLine e BBO, por via portal Biblioteca Virtual de Saúde, e SciELO. Os artigos excluídosf oram aqueles que não apresentaram relação explícita do uso de cocaína com alguma manifestação sistêmica e/ou bucal. Resultados: Após o processo de triagem,10 artigos foram salvos para serem analisados e 111 foram descartados por não atenderem aos critérios de inclusão. Dos 10 artigosselecionados,40% deles (n=4) trouxeram informações identificando possíveis riscos de desenvolvimento de doenças cardiovasculares sofridas pelos usuários de cocaína, 10%(n=1) identificou problemas cognitivos associados ao uso da cocaína,30% dos artigos (n=3) mostrou as alterações bucais associadas à utilização abusiva de cocaína. Conclusões: Houve a predominância de algumas manifestações sistêmicas e bucais nos indivíduos usuários de cocaína, como doenças cardiovasculares, xerostomia, perfurações no palato, etc. A partir disso, há algumas alterações sistêmicas e bucais provocadas por esse uso. Mediante o risco considerável, faz-se necessário que o Cirurgião-Dentista se atualize sobre essas alterações em pacientes usuários de cocaína visando promover um trabalho transdisciplinare multiprofissional para atender adequadamente às suas necessidades (AU).

Introduction: The use of cocaine is closely associated with the appearance of some systemic manifestations and also some oral alterations.Objective: To identify the most common systemic and oral alterations in cocaine-using patients.Methodology:This is a systematic review of the literature, considering full-text articles, with a language restriction of "Portuguese" or "English" and published between 2017 and 2022. We used the LiLaCS, MedLine and BBO databases, via the Virtual Health Library (VHL) portal, and SciELO.The articles excluded were those that did not explicitly relate cocaine use to some systemic and/or oral manifestation.Results: After the screening process, 10 articles were saved for analysis and 111 were discarded because they did not meet the inclusion criteria. Of the 10 articles selected, 40% (n=4) provided information identifying possible risks of developing cardiovascular diseases suffered by cocaine users, 10% (n=1)identified cognitive problems associated with cocaine use, 30% of the articles (n=3) showed oral alterations associated with cocaine abuse.Conclusions: There has been a predominance of some systemic and oral manifestations in cocaine users, such as cardiovascular diseases, xerostomia, perforations in the palate, etc. Based on this, there are some systemic and oral alterations caused by this use. Given the considerable risk, it is necessary for dentists to be up-to-date on these alterations in cocaine-using patients in order to promote transdisciplinary and multi-professional work to adequately meet their needs (AU).

Introducción: El consumo de cocaína está estrechamente asociado a la aparición de algunas manifestaciones sistémicas y también de algunas alteraciones orales. Objetivo:Identificar las alteraciones sistémicas y bucales más frecuentes en los consumidores de cocaína. Metodología: Se trata de una revisión sistemática de la literatura, considerando artículos a texto completo, con restricción de idioma en "portugués" o "inglés" y publicados entre 2017 y 2022. Se utilizaron las bases de datos LiLaCS, MedLine y BBO, a través del portal Biblioteca Virtual en Salud (BVS) y SciELO. Los artículos excluidos fueron aquellos que no mostraban una relación explícita entre el consumo de cocaína y alguna manifestación sistémica y/o oral. Resultados: Tras el proceso de cribado, se guardaron10 artículos para el análisis y se descartaron 111 por no cumplir los criterios de inclusión. De los 10 artículos seleccionados, el 40% (n=4) proporcionaba información que identificaba posibles riesgos de desarrollar enfermedades cardiovasculares sufridaspor consumidores de cocaína, el 10% (n=1) identificaba problemas cognitivos asociados al consumo de cocaína, el 30% de los artículos (n=3) mostraban alteraciones orales asociadas al abuso de cocaína.Conclusiones:Ha habido un predominio de algunas manifestaciones sistémicas y orales en los consumidores de cocaína, como enfermedades cardiovasculares, xerostomía, perforaciones en el paladar, etc. De acuerdo con esto, existen algunas alteraciones sistémicas y orales causadas por este uso. Dado el considerable riesgo, es necesario que los odontólogos estén al día sobre estas alteraciones en los pacientes consumidores de cocaína, con el fin de promover el trabajo transdisciplinar y multiprofesional para atender adecuadamente sus necesidades (AU).

O uso de drogas e seus efeitos na cavidade oral

Objetivos: Descrever as principais manifestações bucais associadas ao uso das drogas lícitas e ilícitas mais utilizadas atualmente, bem como os cuidados que devem ser tomados durante o atendimento odontológico desses pacientes. Revisão de literatura: Na revisão foi abordada a classificação das substâncias químicas, as principais manifestações orais e os cuidados que o cirurgião-dentista deve ter durante o atendimento odontológico. As substâncias descritas foram álcool, tabaco, benzodiazepínicos, maconha, anfetaminas e cocaína/crack. As complicações de saúde bucal associadas ao abuso de drogas podem resultar da exposição direta dos tecidos orais às drogas durante o fumo ou ingestão, da interação biológica das drogas com a fisiologia normal da cavidade oral e dos efeitos das drogas na função cerebral que resultam em um espectro de comportamentos de dependência, como comportamento de risco, falta de higiene e descuido. Considerações finais: O consumo de substâncias psicoativas, seja a curto ou longo prazo, pode desencadear consequências, tanto na saúde geral como na saúde bucal do usuário. Sob essa perspectiva, o cirurgião-dentista deve estar ciente das manifestações orais e sistêmicas causadas pelas substâncias psicoativas e estar capacitado para diagnosticar, tratar ou também encaminhar o usuário, se necessário, visando um cuidado integral e multiprofissional.

Objective: to describe the main oral manifestations associated with the use of the most commonly used licit and illicit drugs today, as well as the care that should be taken during the dental care of these patients. Literature review: The review covered the classification of chemical substances, the main oral manifestations and the care that dentist should take during dental care. The substances described were alcohol, tobacco, benzodiazepines, marijuana, amphetamines and cocaine/crack. Oral health complications associated with drug abuse can result from direct exposure of oral tissues to drugs during smoking or ingestion, from the biological interaction of drugs with the normal physiology of the oral cavity, and from the effects of drugs on brain function that result in a spectrum of addictive behaviors, such as risk behavior, poor hygiene and carelessness. Final considerations: The consumption of psychoactive substances, whether in the short or long term, can have consequences for both the general health and the oral health of the user. From this perspective, the dentist must be aware of the oral and systemic manifestations caused by psychoactive substances and be able to diagnose, treat or also refer the user, if necessary, aiming for comprehensive, multi-professional care.

Aplicación de un modelo farmacocinético poblacional para el seguimiento de pacientes en tratamiento con dolutegravir: estudio piloto

Introducción: a pesar de los avances en tratamiento antirretroviral, existe la posibilidad de que personas que viven con el virus de la inmunodeficiencia humana (VIH) experimenten falla terapéutica vinculada a múltiples factores que impactan en la respuesta al fármaco. Objetivos: evaluar la utilidad de aplicar un modelo farmacocinético en pacientes con diagnóstico de VIH en tratamiento con dolutegravir para el análisis de las concentraciones plasmáticas experimentales. Adicionalmente, se pretende identificar potenciales interacciones farmacológicas, evaluar adherencia y fallo terapéutico. Material y método: se realizó un estudio piloto transversal y observacional en pacientes VIH tratados con dolutegravir que incluyó la dosificación de la concentración plasmática, evaluación de adherencia mediante el cuestionario simplificado de adherencia a la medicación (SMAQ) y retiro de medicación. Se utilizó un modelo poblacional referenciado en la bibliografía para la predicción de concentraciones de dolutegravir en cada paciente y se compararon con las concentraciones experimentales. Resultados: fueron incluidos en el estudio 21 pacientes. Al cotejar las concentraciones plasmáticas experimentales con la simulación farmacocinética se encontraron diferencias para 12 pacientes, las cuales se explican por posibles interacciones farmacológicas, mala adherencia u otros factores que afectan la farmacocinética. Se detectó 38% de no adherencia de acuerdo con SMAQ y 23% de acuerdo con el retiro de medicación. Conclusiones: se expone el rol potencial de los modelos farmacocinéticos para la interpretación de concentraciones plasmáticas y se genera la necesidad de avanzar en este tipo de estudios para el establecimiento de rango terapéutico y aplicabilidad clínica.

Introduction: Despite advances in antiretroviral treatment, there is a possibility that people living with HIV may experience treatment failure linked to multiple factors that impact drug response. Objective: To evaluate the usefulness of applying a pharmacokinetic model in patients diagnosed with HIV undergoing treatment with dolutegravir for the analysis of experimental plasma concentrations. Additionally, the aim is to identify potential drug interactions, assess adherence, and therapeutic failure. Method: A cross-sectional, observational pilot study was conducted in HIV patients treated with dolutegravir, which included plasma concentration dosing, assessment of adherence using the Simplified Medication Adherence Questionnaire (SMAQ), and medication withdrawal. A population-based model referenced in the literature was used to predict dolutegravir concentrations in each patient and these were compared with experimental concentrations. Results: Twenty-one patients were included in the study. When comparing experimental plasma concentrations with pharmacokinetic simulation, differences were found for 12 patients, which can be explained by possible drug interactions, poor adherence, or other factors affecting pharmacokinetics. Non-adherence was detected in 38% according to the SMAQ and 23% according to medication withdrawal. Conclusions: The potential role of pharmacokinetic models in the interpretation of plasma concentrations is highlighted, emphasizing the need to advance in this type of studies to establish therapeutic ranges and clinical applicability.

Introdução: Apesar dos avanços no tratamento antirretroviral, existe a possibilidade de que pessoas que vivem com HIV experimentem falha terapêutica ligada a múltiplos fatores que impactam na resposta ao medicamento. Objetivos: Avaliar a utilidade da aplicação de um modelo farmacocinético em pacientes com diagnóstico de HIV em tratamento com dolutegravir para análise de concentrações plasmáticas experimentais. Além disso, pretende-se identificar potenciais interações medicamentosas, avaliar a adesão e a falha terapêutica. Método: Um estudo piloto observacional transversal foi conduzido em pacientes HIV tratados com dolutegravir que incluiu dosagem de concentração plasmática, avaliação de adesão usando o questionário simplificado de adesão à medicação (SMAQ) e retirada da medicação. Um modelo populacional referenciado na literatura foi utilizado para prever as concentrações de dolutegravir em cada paciente e compará-las com as concentrações experimentais. Resultados: 21 pacientes foram incluídos no estudo. Ao comparar as concentrações plasmáticas experimentais com a simulação farmacocinética, foram encontradas diferenças em 12 pacientes, que são explicadas por possíveis interações medicamentosas, má adesão ou outros fatores que afetam a farmacocinética. Foram detectadas 38% de não adesão segundo o SMAQ e 23% segundo retirada da medicação. Conclusões: Fica exposto o papel potencial dos modelos farmacocinéticos para a interpretação das concentrações plasmáticas e gera-se a necessidade de avançar neste tipo de estudos para estabelecer a faixa terapêutica e a aplicabilidade clínica.

Percepção dos profissionais de enfermagem sobre manejo de reação infusional a antineoplásicos: estudo qualitativo / Perception of nursing professionals on the management of infusion reactions to antineoplastics: qualitative study

Identificar a percepção dos profissionais de enfermagem sobre o manejo de reação infusional imediata a antineoplásicos. Método: Trata-se de um estudo descritivo de caráter exploratório com abordagem qualitativa realizado em um hospital no Rio Grande do Sul. Resultados: Todos os participantes afirmaram saber identificar uma reação infusional. Após a identificação da reação, nota-se que a maioria obedeceu a uma ordem de condutas a serem realizadas. Quanto aos cuidados para prevenção das reações infusionais, a maioria dos participantes mencionou a administração de medicamentos pré-quimioterápicos, como antialérgicos e antieméticos. Conclusão: Os achados demonstram que a maioria dos profissionais sabe reconhecer e manejar, porém há a necessidade de treinamentos e padronização das ações.(AU)

To identify the perception of nursing professionals about the management of immediate infusion reactions to antineoplastic drugs. Method: This is a descriptive, exploratory study with a qualitative approach carried out in a hospital in Rio Grande do Sul. Results: All the participants said they knew how to identify an infusion reaction. After identifying the reaction, it was noted that the majority followed an order of conduct to be carried out. As for precautions to prevent infusion reactions, most of the participants mentioned the administration of pre-chemotherapy drugs, such as anti-allergic and anti-emetic drugs. Conclusion: The findings show that most professionals know how to recognize and manage them, but there is a need for training and standardization of actions.(AU)

Identificar la percepción de los profesionales de enfermería sobre el manejo de las reacciones infusionales inmediatas a medicamentos antineoplásicos. Método: Se trata de un estudio descriptivo, exploratorio, con abordaje cualitativo, realizado en un hospital de Rio Grande do Sul. Resultados: Todos los participantes afirmaron saber identificar una reacción a la infusión. Después de identificar la reacción, la mayoría siguió un orden de conducta. En cuanto a las precauciones para prevenir las reacciones a la infusión, la mayoría de los participantes mencionó la administración de fármacos prequimioterápicos, como antialérgicos y antieméticos. Conclusión: Los hallazgos muestran que la mayoría de los profesionales saben reconocerlas y manejarlas, pero es necesaria la formación y la estandarización de actuaciones.(AU)

Resistencia a los inhibidores de la integrasa en niños con el virus de la inmunodeficiencia humana por transmisión vertical: primeros casos en Uruguay / Resistance to integrase inhibitors in children with vertically-transmitted human immunodeficiency virus: First cases in Uruguay

La resistencia a los antirretrovirales (ARV) es un problema de salud pública. Con el uso de inhibidores de la integrasa (INSTI) en pediatría, también comienzan a aparecer resistencias. El objetivo de esta comunicación es describir 3 casos con resistencia a los INSTI. Se describen 3 pacientes pediátricos con transmisión vertical del virus de la inmunodeficiencia humana (VIH). Iniciaron ARV de lactantes y preescolares, con mala adherencia al tratamiento, cursaron con diferentes planes secundarios a comorbilidades asociadas y fallas virológicas por resistencia. Los 3 casos clínicos describen la rápida aparición de resistencia frente a la falla virológica y el compromiso de los INSTI. La adherencia debe ser supervisada para detectar precozmente el aumento de la viremia. La falla virológica en un paciente tratado con raltegravir obliga a un rápido cambio de esquema ARV, ya que continuar utilizándolo podría favorecer nuevas mutaciones y resistencia a los INSTI de segunda generación.

Antiretroviral (ARV) drug resistance is a public health issue. Resistance has also been observed in the case of integrase strand transfer inhibitors (INSTIs) used in pediatrics. The objective of this article is to describe 3 cases of INSTI resistance. These are the cases of 3 children with vertically-transmitted human immunodeficiency virus (HIV). They were started on ARVs as infants and preschoolers, with poor treatment adherence, and had different management plans due to associated comorbidities and virological failure due to resistance. In the 3 cases, resistance developed rapidly as a result of virological failure and INSTI involvement. Treatment adherence should be monitored so that any increase in viremia can be detected early. Virological failure in a patient treated with raltegravir forces to a rapid change in ARV therapy because its continued use may favor new mutations and resistance to second-generation INSTIs.

Interacciones potenciales entre productos herbolarios con fármacos hipoglucemiantes en adultos mayores con diabetes mellitus, en una zona rural mexicana / Potenciais interacções entre produtos à base de plantas e medicamentos hipoglicemiantes em adultos mais velhos com diabetes mellitus no Mexico rural / Potential interactions between herbal products with hypoglycemic drugs in older adults with diabetes mellitus in rural Mexico

Introducción: El 50% de la población mundial usa tratamientos alternativos como productos herbarios. El 20% los consume de manera simultánea con algún tratamiento farmacológico para el control la Diabetes Mellitus tipo 2; enfermedad prevalente en adultos mayores. Es escasa la información acerca de las interacciones medicamentosas que pudieran producirse, siendo responsables de más de 7,000 muertes al año. Objetivo: Identificar los productos herbarios de mayor consumo del Adulto Mayor con Diabetes Mellitus Tipo 2, en Chapulco, Puebla, México y describir las posibles interacciones medicamentosas entre fármaco hipoglucemiante ­ producto herbario reportados en la literatura científica. Metodología: Estudio observacional, prolectivo, transversal, descriptivo, en una población de 35 adultos mayores diabéticos, con edad promedio de 70±7 años. Para la identificación de los productos herbarios de uso común y sus aplicaciones terapéuticas se aplicó el cuestionario U-PLANMED. Resultados: Se identificaron 50 productos herbarios y 18 combinaciones entre estos a la vez. El 40% de los participantes consumen simultáneamente más de dos productos herbarios con uno o dos fármacos hipoglucemiantes. Entre los productos de mayor consumo se encuentran el nopal (Opuntia ficus-indica L.), la manzanilla (Matricaria chamomilla L.) y el zacate de limón (Cymbopogon citratus DC. Stapf.). Las interacciones medicamentosas potenciales identificadas, principalmente en estudios experimentales en animales, sugieren que, existe una acción hipoglucemiante del producto herbario al aumentar la capacidad orgánica sobre la secreción/liberación de insulina endógena. Conclusiones: Se ha evidenciado la presencia de interacciones medicamentosas ante el consumo simultaneo de fármacos prescritos para el control de la diabetes mellitus tipo 2 con productos herbarios. Es necesario que, los profesionales en atención a la salud identifiquen el uso de dichos productos y orienten a los adultos mayores sobre las posibles repercusiones en los niveles de glucosa ante el consumo.

Introduction: 50% of the world's population uses alternative treatments such as herbal products. Twenty percent use them in conjunction with some form of pharmacological treatment to control type 2 diabetes mellitus, a disease prevalent in older adults. There is little information on the drug interactions that may occur, which are responsible for more than 7,000 deaths per year. Objective: To identify the most consumed herbal products among older adults with type 2 diabetes mellitus in Chapulco, Puebla, Mexico, and to describe the possible drug-drug interactions between hypoglycemic drugs and herbal products reported in the scientific literature. Methodology: Observational, prospective, cross-sectional, descriptive study in a population of 35 diabetic older adults with a mean age of 70±7 years. The U-PLANMED questionnaire was used to identify commonly used herbal products and their therapeutic applications. Results: Fifty herbal products and 18 combinations of them were identified. Forty percent of the participants used more than two herbal products simultaneously with one or two hypoglycemic drugs. The most used products included prickly pear cactus (Opuntia ficus-indica L.), chamomile (Matricaria chamomilla L.), and lemon grass (Cymbopogon citratus DC. Stapf.). Potential drug-drug interactions identified mainly in experimental animal studies suggest that there is a hypoglycemic effect of the herbal product by increasing the organic capacity on endogenous insulin secretion/release. Conclusions: The presence of drug-drug interactions has been demonstrated with the simultaneous consumption of drugs prescribed for the control of type 2 diabetes mellitus with herbal products. It is necessary for health care professionals to recognize the use of such products and to inform older adults about the possible repercussions on glucose levels when consuming them.

Introdução: 50% da população mundial utiliza tratamentos alternativos como os produtos à base de plantas. Vinte por cento utilizam-nos em conjunto com algum tipo de tratamento farmacológico para controlar a diabetes mellitus tipo 2, uma doença prevalente em adultos mais velhos. Há pouca informação sobre as interacções medicamentosas que podem ocorrer e que são responsáveis por mais de 7.000 mortes por ano. Objetivos: Identificar os produtos fitoterápicos mais consumidos entre os idosos com diabetes mellitus tipo 2 em Chapulco, Puebla, México, e descrever as possíveis interações medicamentosas entre medicamentos hipoglicemiantes e produtos fitoterápicos relatados na literatura científica. Metodologia: Estudo observacional, prospetivo, transversal e descritivo numa população de 35 idosos diabéticos com uma idade média de 70±7 anos. O questionário U-PLANMED foi utilizado para identificar os produtos fitoterápicos mais utilizados e suas aplicações terapêuticas. Resultados: Foram identificados 50 produtos à base de plantas e 18 combinações dos mesmos. Quarenta por cento dos participantes utilizaram mais de dois produtos à base de plantas em simultâneo com um ou dois medicamentos hipoglicemiantes. Os produtos mais utilizados foram o cato de figo da Índia (Opuntia ficus-indica L.), a camomila (Matricaria chamomilla L.) e o capim-limão (Cymbopogon citratus DC. Stapf.). As potenciais interacções medicamentosas identificadas principalmente em estudos experimentais em animais sugerem que existe um efeito hipoglicémico do produto à base de plantas através do aumento da capacidade orgânica na secreção/libertação de insulina endógena. Conclusões: A presença de interacções medicamentosas foi demonstrada com o consumo simultâneo de medicamentos prescritos para o controlo da diabetes mellitus tipo 2 com produtos à base de plantas. É necessário que os profissionais de saúde reconheçam o uso de tais produtos e informem os idosos sobre as possíveis repercussões nos níveis de glicose ao consumi-los.

Perfil de seguridad y satisfacción con la combinación fija de memantina-donepezilo en pacientes con diagnóstico de Alzheimer moderado a severo / Safety and satisfaction profile with the fixed combination of memantine-donepezil in patients diagnosed with moderate to severe Alzheimer's disease

Introducción: La enfermedad de Alzheimer es un trastorno neurodegenerativo de inicio insidioso y progresión lenta. Epidemiológicamente representa 60% a 70% de los casos de demencia.Objetivo: Determinar el grado de satisfacción y seguridad con la combinación fija de memantina-donepezilo durante 6 meses.Material y métodos: Se llevó a cabo un estudio observacional, transversal y analítico con base a un diseño de Real World Evidence (RWE), para evaluar la satisfacción del tratamiento a través de preguntas con una escala de Likert para la valoración de la satisfacción de 31 pacientes que recibieron como parte de su tratamiento habitual la combinación fija de memantina + donepezilo una vez al día durante seis meses previos a la aplicación de la escala de satisfacción. La información se recopiló de febrero a noviembre del 2021. Resultados: 60% de los eventos adversos fueron leves, 40% moderados. La tolerabilidad luego de 3 meses fue percibida como muy buena o excelente por 81% de pacientes. A seis meses 87,1% calificó como muy bueno o excelente el tratamiento. Satisfacción con el tratamiento a 3 meses fue, "satisfecho en su mayoría" o "totalmente satisfecho" para el 87,1%. Discusión: Prevalencia en el género femenino de 77,4% mayor a la reportada para todo el país de 54,8%, comorbilidades reportadas similares a las descritas por la literatura. Tolerabilidad calificada como excelente en comparación con otros estudios que calificaron como buena tolerabilidad. Conclusión: La administración de la combinación fija de memantina 14 mg + donepezilo 10 mg o memantina 28 mg + donepezilo 10 mg, fue una opción segura y bien tolerada.

Introduction:Alzheimer's disease is a neurodegenerative disorder of insidious onset and slow progression. Epidemiologically it accounts for 60% to 70% of cases of dementia.Objective:Determine the degree of satisfaction and safety with the fixed combination of memantine-donepezil for 6 months.Materials and methods: A cross-sectional, observational, and analytical study was conducted based on a Real World Evidence (RWE) design to assess treatment satisfaction through Likert-scale questions of 31 patients who, as part of their regular treatment, received the fixed combination of memantine + donepezil once daily for six months before the administration of the satisfaction scale. Data collection took place from February to November 2021.Results: 60% of adverse events were mild, 40% moderate. Tolerability after 3 months was perceived as very good or excellent by 81% of patients. At six months 87,1% rated the treatment as very good or excellent. Satisfaction with treatment at 3 months was, "mostly satisfied" or "totally satisfied" for 87,1%. Discussion: Prevalence in the female gender of 77,4% higher than that reported for the whole country of 54,8%, reported comorbidities similar to those described in the literature. Tolerability rated as excellent compared to other studies which rated as good tolerability. Conclusions:Administration of the fixed combination of memantine 14 mg + donepezil 10 mg or memantine 28 mg + donepezil 10 mg was a safe and well-tolerated option.

Necrólisis epidérmica tóxica debido a un fármaco a base de caléndula más acetilcisteína: presentación de caso / Toxic Epidermal Necrolysis Induced by a Drug Combination of Calendula and Acetylcysteine: A Case Report / Necrólise epidermal tóxica por medicamento à base de calêndula mais acetilcisteína: relato de caso

Introducción: la hipersensibilidad por fármacos es inducida por una respuesta aberrante del sistema inmune; por lo general, impredecible, dosis independiente y amenazante para la vida del paciente. Las reacciones de hipersensibilidad por fármacos con compromiso mucocutáneo se dan en alrededor del 2 %-3 % de los pacientes hospitalizados. Objetivo: describir un caso de necrólisis tóxica epidérmica por un fármaco a base de caléndula y acetilcisteína como los presuntos desencadenantes. Presentación del caso: hombre de 39 años, quien asistió a emergencias, por malestar general, artralgias, mialgias, astenia y adinamia de un día de evolución. Tres días después refirió la aparición de lesiones purpúricas progre-sivas que se extendieron por cara, extremidades y glúteos; delimitadas; no dolorosas, y sin desaparecer a la digitopresión, asociado con disnea, inestabilidad hemodinámica y cardiovascular. Al sexto día de hos-pitalización, se interrogó al paciente, quien se había automedicado un fármaco de origen desconocido, presuntamente de extracto herbal a base de caléndula más acetilcisteína para artralgias, osteomialgias y disfagia. A la mañana siguiente, presentó lesiones purpúricas y ulcerativas extensas. Se observaron lesiones purpúricas progresivas y ulcerativas en cara extremidades y glúteos. Mediante la sospecha clínica y la evaluación histopatológica, se confirmó la necrólisis tóxica epidérmica. Conclusiones: las reacciones adversas medicamentosas severas que amenazan la vida del paciente son relativamente raras, pero representan un verdadero desafío diagnóstico y terapéutico. Es necesario profundizar en la investigación para esclarecer la causa de este tipo de reacción medicamentosa.

Introduction: Drug hypersensitivity is induced by an aberrant response from the immune system. It is usually unpredictable, dose-independent, and can be life-threatening to the patient. Drug-induced hypersensitivity reactions with mucocutaneous involvement occur in approximately 2­3% of hospitalized patients. However, Toxic Epidermal Necrolysis is a rare case. Aim: To describe a case of drug-induced toxic epidermal necrolysis triggered by Calendula officinalis and acetylcysteine. Case report: A 39-year-old male was pre-sented to the emergency room with malaise, arthralgia, myalgia, asthenia, and adynamia since day one. Three days later, he developed progressive purpuric lesions that spread to the face, extremities, and buttocks. These lesions were painless, not delineate, and did not blanch under pressure. They were asso-ciated with dyspnea and hemodynamic and cardiovascular instability. On the sixth day of hospitaliza-tion, the patient admitted to self-medicating with an unknown drug, presumably a herbal extract based on calendula and acetylcysteine, for arthralgia, myalgia, and dysphagia. The morning after the drug consumption, the patient developed extensive purpuric and ulcerative lesions. A diagnosis of toxic epi-dermal necrolysis was made based on clinical suspicion and histopathological confirmation. Conclusion:Severe adverse drug reactions that threaten a patient's life are relatively rare. However, they represent a real diagnostic and therapeutic challenge when they do occur

Introdução: a hipersensibilidade a drogas é induzida por uma resposta aberrante do sistema imunoló-gico; geralmente imprevisível, independente da dose e com risco de vida para o paciente. As reações de hipersensibilidade a drogas com comprometimento mucocutâneo estão em torno dos 2-3% dos pacien-tes hospitalizados. Objetivo: descrever um caso de necrólise epidérmica tóxica causada por uma droga à base de Calendula officinalis e acetilcisteína como os supostos desencadeantes. Apresentação do caso:homem, 39 anos, deu entrada no pronto-socorro manifestando mal-estar, artralgia, mialgia, astenia e adinamia há um dia. Posteriormente, três dias depois, relatou o aparecimento de lesões purpúricas pro-gressivas que se espalharam para a face, extremidades e nádegas; que são delimitadas, não dolorosas e não desaparecem com a acupressão associada a dispnéia, instabilidade hemodinâmica e cardiovascular. No sexto dia de internação, o paciente foi questionado, y disse que tinha se automedicado com uma droga de origem desconhecida, presumivelmente extrato de ervas à base de calêndula mais acetilcis-teína para artralgia, osteomialgia e disfagia. Na manhã seguinte, apresentou extensas lesões purpúricas e ulcerativas. Observam-se lesões purpúricas progressivas e ulcerativas que se estendem à face, extre-midades e nádegas. Pela suspeita clínica e confirmação histopatológica, confirma-se a necrólise epidér-mica tóxica. Conclusões: reações adversas graves a medicamentos que ameaçam a vida do paciente são relativamente raras, mas quando ocorrem representam um verdadeiro desafio a nível diagnóstico e terapêutico. São precisas mais pesquisas para esclarecer a causa desse tipo de reação medicamentosa.

Alteraciones genéticas asociadas a la enfermedad de Parkinson y Alzheimer: evolución y respuesta al tratamiento / Genetic Alterations Associated with Parkinson's and Alzheimer's Disease: Evolution and Response to Treatment

La enfermedad de Parkinson y Alzheimer son las enfermedades neurodegenerativas más frecuentes a nivel mundial. Tienen etiología multifactorial, entre ellas, la genética; y son motivo de interés en la investigación científica actual. Se realizó una revisión narrativa con el objetivo de determinar las alteraciones genéticas asociadas a estas patologías, además su influencia en la evolución y respuesta al tratamiento de ellas. Se consultaron artículos originales, revisiones bibliográficas, sistemáticas, metaanálisis en inglés y español, con fecha de publicación entre el 1 enero de 2018 y el 20 de mayo de 2023, en bases como PubMed y Medline. Se utilizaron los términos MeSH «Alzheimer Disease¼, «Parkinson Disease¼, «Drug Therapy¼ y «Mutations¼. El riesgo hereditario para la enfermedad de Parkinson suele ser poligenético, sin embargo, existen genes relacionados con mutaciones monogénicas. Se identifican alteraciones en genes de α-sinucleína, glucocerebrosidasa y quinasa 2 rica en leucina que se relacionan con mayor riesgo de desarrollar Parkinson, además de variaciones en el cuadro clínico y edad de inicio de síntomas. En cuanto a la enfermedad de Alzheimer, las alteraciones en los genes de la proteína precursora amiloide, presenilina 1 y 2 se relacionan con la forma familiar de la enfermedad; por otra parte, las de apolipoproteína E4 se han identificado en la forma esporádica, por lo que se consideran como el factor de riesgo genético más importante para su desarrollo

Parkinson's and Alzheimer's are the most frequent neurodegenerative diseases worldwide. They have a multifactorial etiology, including genetics, and are of interest in current scientific research. A narrative review was carried out with the aim of determining the genetic alterations associated with these pathologies, as well as their influence on their evolution and response to treatment. Original articles, literature reviews, systematic reviews, meta-analyses in English and Spanish, with publication date between January 1, 2018 and May 20, 2023, were consulted in databases such as PubMed and Medline. MeSH terms "Alzheimer Disease", "Parkinson Disease", "Drug Therapy" and "Mutation" were used. Hereditary risk for Parkinson's disease is usually polygenetic, however, there are genes related to monogenic mutations. Alterations in α-synuclein, glucocerebrosidase and leucine-rich kinase 2 genes have been identified that are related to an increased risk of developing Parkinson's disease, in addition to variations in the clinical picture and age of symptom onset. As for Alzheimer's disease, alterations in the genes of the amyloid precursor protein, presenilin 1 and 2 are related to the familial form of the disease; on the other hand, those of apolipoprotein E4 have been identified in the sporadic form, and are therefore considered to be the most important genetic risk factor for its development

Antifungal activity of 2-chloro-N-phenylacetamide: a new molecule with fungicidal and antibiofilm activity against fluconazole-resistant Candida spp / Atividade antifúngica de 2-cloro-N-fenilacetamida: uma nova molécula com atividade fungicida e anti-biofilme contra Candida spp. resistentes a fluconazol

In the current context of emerging drug-resistant fungal pathogens such as Candida albicans and Candida parapsilosis, discovery of new antifungal agents is an urgent matter. This research aimed to evaluate the antifungal potential of 2-chloro-N-phenylacetamide against fluconazole-resistant clinical strains of C. albicans and C. parapsilosis. The antifungal activity of 2-chloro-N-phenylacetamide was evaluated in vitro by the determination of the minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), inhibition of biofilm formation and its rupture, sorbitol and ergosterol assays, and association between this molecule and common antifungal drugs, amphotericin B and fluconazole. The test product inhibited all strains of C. albicans and C. parapsilosis, with a MIC ranging from 128 to 256 µg.mL-1, and a MFC of 512-1,024 µg.mL-1. It also inhibited up to 92% of biofilm formation and rupture of up to 87% of preformed biofilm. 2-chloro-N-phenylacetamide did not promote antifungal activity through binding to cellular membrane ergosterol nor it damages the fungal cell wall. Antagonism was observed when combining this substance with amphotericin B and fluconazole. The substance exhibited significant antifungal activity by inhibiting both planktonic cells and biofilm of fluconazole-resistant strains. Its combination with other antifungals should be avoided and its mechanism of action remains to be established.

No atual contexto de patógenos fúngicos resistentes emergentes tais como Candida albicans e Candida parapsilosis, a descoberta de novos agentes antifúngicos é uma questão urgente. Esta pesquisa teve como objetivo avaliar o potencial antifúngico da 2-cloro-N-fenilacetamida contra cepas clínicas de C. albicans e C. parapsilosis resistentes a fluconazol. A atividade antifúngica da substância foi avaliada in vitro através da determinação da concentração inibitória mínima (CIM), concentração fungicida mínima (CFM), ruptura e inibição da formação de biofilme, ensaios de sorbitol e ergosterol, e associação entre esta molécula e antifúngicos comuns, anfotericina B e fluconazol. O produto teste inibiu todas as cepas de C. albicans e C. parapsilosis, com uma CIM variando de 128 a 256 µg.mL-1, e uma CFM de 512-1,024 µg.mL-1. Também inibiu até 92% da formação de biofilme e causou a ruptura de até 87% de biofilme pré-formado. A 2-cloro-N-fenilacetamida não promoveu atividade antifúngica pela ligação ao ergosterol da membrana celular fúngica, tampouco danificou a parede celular. Antagonismo foi observado ao combinar esta substância com anfotericina B e fluconazol. A substância exibiu atividade antifúngica significativa ao inibir tanto as células planctônicas quanto o biofilme das cepas resistentes ao fluconazol. Sua combinação com outros antifúngicos deve ser evitada e seu mecanismo de ação deve ser estabelecido.

Mining and analysis of adverse drug event signals of cinacalcet and etelcalcetide / 中国药房

OBJECTIVE To explore and analyze the adverse drug event （ADE） signals of cinacalcet and etelcalcetide， to provide a reference for safe drug use in the clinic. METHODS ADE reports related to cinacalcet and etelcalcetide were extracted from the FDA Adverse Event Reporting System from January 1st， 2004 to June 30th， 2023 using the OpenVigil online tool. The Bayesian confidence propagation neural network method was adopted to detect the signals of ADE from the key organ systems. The signals were encoded according to the preferred term in the ADE terminology set of the Medical Dictionary for Regulatory Activities （26.0 edition）. RESULTS A total 41 709 and 1 710 ADE reports were extracted， and 29 and 45 safety signals were detected in key systems for cinacalcet and etelcalcetide， respectively； 20 and 36 positive signals were not included in the drug instructions. Hypocalcemia/decreased serum calcium， abnormal blood parathyroid hormone （PTH）/increased or decreased serum PTH were common ADEs of the two drugs， which were detected in the study. Among the signals not included in the drug instructions， new moderate and strong signals were detected， such as cinacalcet-induced calcification defense （metabolic and nutritional diseases）， bone starvation syndrome and high conversion bone diseases （musculoskeletal and connective tissue diseases） as well as etelcalcetide-induced sudden death， necrosis and treatment of non-responders （general disorders， administration site）， unstable angina pectoris， myocardial ischemia （cardiac diseases）， intestinal perforation， gastric antrum vasodilation and gastric ulcer （gastrointestinal diseases）. CONCLUSIONS In the clinical application of the two drugs， apart from the common ADEs such as hypocalcemia and abnormal blood PTH， the surveillance of some new potential ADEs should also be carried out， such as bone starvation syndrome， calcification defense， ventricular disease and other cinacalcet-induced ADEs， sudden death， myocardial ischemia， unstable angina pectoris， intestinal perforation， gastric ulcer and other etecalcetide-induced ADEs. If new ADEs appear， clinic should promptly assess the benefits and risks， and update the treatment plan and pharmacological monitoring plan to ensure the safety of patient medication.

Establishment and validation of nomogram prediction model of cefoperazone/sulbactam-induced thrombocytopenia / 中国药房

OBJECTIVE To explore the predictive factors of cefoperazone/sulbactam-induced thrombocytopenia in adult inpatients， and to establish and validate the nomogram prediction model. METHODS Data of adult inpatients treated with cefoperazone/sulbactam in Xi’an Central Hospital from Jun. 30th， 2021 to Jun. 30th， 2023 were retrospectively collected. The training set and internal validation set were randomly constructed in a 7∶3 ratio. Singler factor and multifactor Logistic regression analysis were used to screen the independent predictors of cefoperazone/sulbactam-induced thrombocytopenia. The nomogram was drawn by using “RMS” of R 4.0.3 software， and the predictive performance of the model was evaluated by the receiver operating characteristic curve and C-index curve. Hosmer-Lemeshow goodness-of-fit test was used to evaluate the calibration degree of the model. Using the same standard， the clinical data of hospitalized patients receiving cefoperazone/sulbactam in Xi’an First Hospital in the same period were collected for external validation of the nomogram prediction model. RESULTS A total of 1 045 patients in Xi’an Central Hospital were included in this study， among which 67 patients suffered from cefoperazone/sulbactam-induced thrombocytopenia， with an incidence of 6.41%. After the false positive patients were excluded， 473 patients were included finally， including 331 in the training set and 142 in theinternal validation set. Multifactor Logistic regression analysis showed that age [OR＝1.043， 95%CI （1.017， 1.070）]， estimated glomerular filtration rate （eGFR） [OR＝0.988，95%CI（0.977， 0.998）]， baseline platelet （PLT） [OR＝0.989， 95%CI（0.982， 0.996）]， nutritional risk [OR＝3.863， 95%CI（1.884， 7.921）] and cumulative defined daily doses （DDDs） [OR＝1.082， 95%CI（1.020， 1.147）] were independent predictors for cefoperazone/sulbactam-induced thrombocytopenia （P＜0.05）. The C-index values of the training set and the internal validation set were 0.824 [95%CI （0.759， 0.890）] and 0.828 [95%CI （0.749， 0.933）]， respectively. The results of the Hosmer-Lemeshow test showed that χ 2 values were 0.441 （P＝0.802） and 1.804 （P＝0.406）. In the external validation set， the C-index value was 0.808 [95%CI （0.672， 0.945）]， the χ 2 value of the Hosmer-Lemeshow test was 0.899 （P＝0.638）. CONCLUSIONS The independent predictors of cefoperazone/sulbactam-induced thrombocytopenia include age， baseline PLT， eGFR， nutritional risk and cumulative DDDs. The model has good predictive efficacy and extrapolation ability， which can help clinic identify the potential risk of cefoperazone/sulbactam-induced thrombocytopenia quickly and accurately.

Regulatory effect of autophagy on the resistance of human liver cancer cell Huh7 to lenvatinib / 中国药房

OBJECTIVE To investigate the regulatory effect of autophagy on the resistance of human liver cancer cell Huh7 to lenvatinib. METHODS Using human liver cancer cell Huh7 as subject， the lenvatinib-resist cell model （Huh7-LR） was generated by the low-dose gradient method combined with long-term administration. The sensitivity of parental cell Huh7 and drug-resistant cell Huh7-LR to lenvatinib was detected by using CCK-8 assay and flow cytometry. Western blot assay and GFP-mCherry-LC3 plasmid transfection were performed to detect the expression levels of autophagic protein Beclin-1， autophagic adapter protein sequestosome 1 （p62）， microtubule-associated protein 1 light chain 3 （LC3） and autophagic level. Furthermore， an autophagy activation model was constructed by cell starvation， the protein expression of p62 and autophagy level were detected by using Western blot assay and GFP-mCherry-LC3 plasmid transfection， and the effect of autophagy activation on the sensitivity of Huh7-LR cells to lenvatinib was detected by flow cytometry. RESULTS Compared with parental cells， the drug resistance index of Huh7-LR cells was 6.2； protein expression of p62 was increased significantly， while apoptotic rate， protein expression of Beclin-1 and LC3Ⅱ/ LC3Ⅰ ratio were all reduced significantly （P＜0.05 or P＜0.01）； the level of autophagy was decreased to some extent. Autophagy activation could significantly increase the protein expression of p62 in Huh7-LR cells （P＜0.05） and autophagy level， and significantly increase its apoptotic rate （P＜0.05）. CONCLUSIONS Autophagy is involved in lenvatinib resistance， and activating autophagy can reverse the resistance of liver cancer cells to lenvatinib to some extent.

Insights from Japan’s cost-effectiveness analysis policy on pricing for China’s NRDL access / 中国药房

The cost-effectiveness analysis policy for drugs was institutionalized in Japan since 2019， realizing quantitative adjustment of price across varieties. A hierarchical categorization approach was adopted to select medicines with high expected annual sales. For selected medicines， adjustments were made to the premium and profit components within the existing price structure based on a pre-defined incremental cost-effectiveness ratio （ICER） threshold， effectively resolving the issue of inconsistent criteria and magnitudes caused by subjective judgment. Meanwhile， incentive measures like evaluation exemption or threshold enhancement were granted for specific medicines. Besides， a price adjustment mechanism， which was allowed for upward and downward adjustments， involving tiered ICER threshold and quantified formulas， had been established for the premium and profit components of drug price. In China’s National Reimbursement Drug List （NRDL） access， certain issues remained to be addressed： insufficient clarity in the quantitative mechanism of price formation， incomplete price adjustment measures， and lagging in the communication channels. It is recommended that the following measures could be referred to when further improving the scientificity and fairness of drug pricing during China’s NRDL access， such as enhancing the ICER threshold for medicines catering to special populations， quantifying criteria and extents for price adjustment， granting preferential pricing policies to pharmaceutical companies that present high-quality evidence of effectiveness， preceding communication channels with pharmaceutical companies， as well as exploring a price floor mechanism for the drugs with excessive price reduction.

Novel antibacterial drug target against Gram-negative bacteria: lipopolysaccharide transport protein LptDE and its inhibitors / 药学学报

The outer membrane composed predominantly of lipopolysaccharide (LPS) is an essential biological barrier for most Gram-negative (G-) bacteria. Lipopolysaccharide transport protein (Lpt) complex LptDE is responsible for the critical final stage of LPS transport and outer membrane assembly. The structure and function of LptDE are highly conserved in most G- bacteria but absent in mammalian cells, and thus LptDE complex is regarded as an attractive antibacterial target. In recent 10 years, the deciphering of the three-dimensional structure of LptDE protein facilities the drug discovery based on such "non-enzyme" proteins. Murepavadin, a peptidomimetic compound, was reported to be the first compound able to target LptD, enlightening a new class of antibacterial molecules with novel mechanisms of action. This article is devoted to summarize the molecular characteristics, structure-function of LptDE protein complex and review the development of murepavadin and related peptidomimetic compounds, in order to provide references for relevant researches.

First-in-class small molecule drugs in 2023 / 药学学报

In 2023, drug discovery develops steadily, with improvement of small molecule drugs discovery keeps pace with biological drugs in this year. The Center for Drug Evaluation and Research of U.S. Food and Drug Administration has totally approved 55 kinds of new drugs which have significantly promotion compared to 37 new drugs approval in 2022, including 38 kinds of new molecular entities, 17 kinds of biological drugs, 5 kinds of gene therapeutics and 2 cell therapeutics. The proportion of first-in-class drugs increased steadily, with 13 small molecule first-in-class drugs and 7 biological first-in-class drugs approved this year, mostly in the fields of cancer and rare diseases. Among them, a plurality of first-initiated small molecule drugs exhibits breakthrough significance, such as the first neurokinin 3 (NK3) receptor antagonist fezolinetant, the first retinoic acid receptor (RIG-I) agonist palovarotene, the first protein kinase B (AKT) inhibitor capivasertib, the first complement factor B inhibitor iptacopan, etc. The pioneering drug has huge academic and commercial value, and has become the target of the academic and industrial circles. However, first-in-class drugs not only need new targets, new mechanisms and new molecules, but also need to comprehensively verify the causality between new targets and diseases, study the correlation between new mechanisms and drug efficacy, and explore the balance between new molecules and drug-manufacturing properties. This article analyzed the research background, development process and therapeutic application of three first-initiated small molecule drugs in this year, expecting to provide more research ideas and methods for more first-in-class drugs.

Anti-SARS-CoV-2 activity of small molecule inhibitors of cathepsin L / 药学学报

The coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to serious worldwide economic burden. Due to the continuous emergence of variants, vaccines and monoclonal antibodies are only partial effective against infections caused by distinct strains of SARS-CoV-2. Therefore, it is still of great importance to call for the development of broad-spectrum and effective small molecule drugs to combat both current and future outbreaks triggered by SARS-CoV-2. Cathepsin L (CatL) cleaves the spike glycoprotein (S) of SARS-CoV-2, playing an indispensable role in enhancing virus entry into host cells. Therefore CatL is one of the ideal targets for the development of pan-coronavirus inhibitor-based drugs. In this study, a CatL enzyme inhibitor screening model was established based on fluorescein labeled substrate. Two CatL inhibitors IMB 6290 and IMB 8014 with low cytotoxicity were obtained through high-throughput screening, the half inhibition concentrations (IC50) of which were 11.53 ± 0.68 and 1.56 ± 1.10 μmol·L-1, respectively. SDS-PAGE and cell-cell fusion experiments confirmed that the compounds inhibited the hydrolysis of S protein by CatL in a concentration-dependent manner. Surface plasmon resonance (SPR) detection showed that both compounds exhibited moderate binding affinity with CatL. Molecular docking revealed the binding mode between the compound and the CatL active pocket. The pseudovirus experiment further confirmed the inhibitory effects of IMB 8014 on the S protein mediated entry process. In vitro pharmacokinetic evaluation indicated that the compounds had relatively good drug-likeness properties. Our research suggested that these two compounds have the potential to be further developed as antiviral drugs for COVID-19 treatment.

The biotin synthesis pathway in Mycobacteria tuberculosis is a new target for the development of anti-tuberculosis drugs / 药学学报

italic>Mycobacterium tuberculosis, responsible for tuberculosis (TB), remains a major health problem worldwide and is one of the infectious diseases causing increased morbidity and mortality worldwide. Biotin, namely vitamin H, is an important cofactor necessary for fatty acid biosynthesis, gluconeogenesis and amino acid metabolism in organisms including Mycobacterium tuberculosis. Due to its inability to ingestion biotin from outside, Mycobacterium tuberculosis can only obtain biotin through biotin biosynthesis. Different from the classical BioC-BioH, BioI-BioW and non-classical BioZ pathways, Mycobacterium tuberculosis synthesized biotin by "BioC-BioH(2)" pathway in the early stage. This review focuses on the unique biotin synthesis pathway of Mycobacterium tuberculosis and its key genes, especially the response of this pathway and biotin-dependent carboxylase to tuberculosis first-and second-line drugs, as well as inhibitors and natural products targeting biotin synthesis.