Antimicrobial activity of selective serotonin reuptake inhibitors in bacteria and fungi: a systematic review / Atividade antimicrobiana de inibidores seletivos de recaptação de serotonina em bactérias e fungos: uma revisão sistemática

Objective: this systematic review aims to compile literature data on the antimicrobial action of Selective Serotonin Reuptake Inhibitors (SSRI). Methods: To this end, the articles in this review were searched in the PubMed database between the years 2010 to 2020, using terms found in MESH as descriptors. The PRISMA flow diagram was used to analyze the process flow of the research. Later, inclusion and exclusion criteria and eligibility for data extraction and statistical analysis were applied. Results: Thus, of 252 articles found, 13 were used for this systematic review. The period in which there were more publications was in 2016-2017. All articles demonstrated the antimicrobial activity of ISRS, such as sertraline, fluoxetine, and paroxetine, in addition to their synergistic activity with some antifungals and antibacterial. Conclusion: With this, it could be concluded that the repositioning of non-antibiotic drugs that have antimicrobial activity is a promising alternative for the scientific community and, in the future, in clinical practice

Objetivo: compilar dados da literatura sobre a ação antimicrobiana dos Inibidores Seletivos de Recaptação de Serotonina (ISRS). Métodos: os artigos desta revisão foram pesquisados na base de dados PubMed, entre os anos de 2010 a 2020, utilizando, como descritores, termos encontrados no MESH. O fluxograma PRISMA foi utilizado para analisar o fluxo do processo da pesquisa. Posteriormente, foram aplicados os critérios de inclusão e exclusão e de elegibilidade para extração de dados e análise estatística. Resultados: dos 252 artigos encontrados, 13 foram utilizados para esta revisão sistemática. O período em que houve mais publicações foi em 2016-2017. Todos os artigos demonstraram a atividade antimicrobiana do ISRS, como sertralina, fluoxetina e paroxetina, além de sua atividade sinérgica com alguns antifúngicos e antibacterianos. Conclusão: o reposicionamento de medicamentos não antibióticos que possuam atividade antimicrobiana é uma alternativa promissora para a comunidade científica e, futuramente, na prática clínica.

The Effect of Neuromodulatory Drugs on the Intensity of Chronic Pelvic Pain in Women: A Systematic Review / Efeito de neuromoduladores na intensidade da dor pélvica crônica em mulheres: Revisão sistemática

Abstract Objective: To evaluate the effect of neuromodulatory drugs on the intensity of chronic pelvic pain (CPP) in women. Data sources: Searches were carried out in the PubMed, Cochrane Central, Embase, Lilacs, OpenGrey, and Clinical Trials databases. Selection of studies: The searches were carried out by two of the authors, not delimiting publication date or original language. The following descriptors were used: chronic pelvic pain in women OR endometriosis, associated with MESH/ENTREE/DeCS: gabapentinoids, gabapentin, amitriptyline, antidepressant, pregabalin, anticonvulsant, sertraline, duloxetine, nortriptyline, citalopram, imipramine, venlafaxine, neuromodulation drugs, acyclic pelvic pain, serotonin, noradrenaline reuptake inhibitors, and tricyclic antidepressants, with the Boolean operator OR. Case reports and systematic reviews were excluded. Data collection: The following data were extracted: author, year of publication, setting, type of study, sample size, intervention details, follow-up time, and results. Data synthesis: A total of 218 articles were found, with 79 being excluded because they were repeated, leaving 139 articles for analysis: 90 were excluded in the analysis of the titles, 37 after reading the abstract, and 4 after reading the articles in full, and 1 could not be found, therefore, leaving 7 articles that were included in the review. Conclusion: Most of the studies analyzed have shown pain improvement with the help of neuromodulators for chronic pain. However, no improvement was found in the study with the highest statistical power. There is still not enough evidence that neuromodulatory drugs reduce the intensity of pain in women with CPP.

Resumo Objetivo: Avaliar o efeito de drogas neuromoduladoras na intensidade da dor pélvica crônica em mulheres. Fontes de dados: As buscas foram realizadas nas bases de dados PubMed, Cochrane Central, Embase, Lilacs, OpenGrey e Clinical Trials. Seleção dos estudos: As buscas foram realizadas por dois dos autores, não delimitando data de publicação ou idioma de publicação. Foram usados os seguintes descritores: chronic pelvic pain in women OR endometriosis, associated with MESH/ENTREE/DeCS: gabapentinoids, gabapentin, amitriptyline, antidepressant, pregabalin, anticonvulsant, sertraline, duloxetine, nortriptyline, citalopram, imipramine, venlafaxine, neuromodulation drugs, acyclic pelvic pain, serotonin, noradrenaline reuptake inhibitors e tricyclic antidepressants, com o operador booleano OR. Relatos de caso e revisões sistemáticas foram excluídos. Coleta de dados: Foram extraídos os seguintes dados: autor, ano de publicação, local de origem, tipo de estudo, tamanho da amostra, detalhes da intervenção, tempo de seguimento e resultados. Síntese dos dados: Foram encontrados 218 artigos, sendo 79 deles excluídos por serem repetidos, restando 139 artigos para análise, dos quais 90 foram excluídos na análise dos títulos, 37 após a leitura do resumo e 4 após a leitura dos artigos na íntegra, e 1 não foi encontrado, restando, então, 7 artigos que foram incluídos na revisão. Conclusão: A maioria dos estudos analisados mostrou melhora da dor crônica com auxílio de neuromoduladores. No entanto, nenhuma melhora foi encontrada no artigo com maior poder estatístico. Ainda não há evidências suficientes de que drogas neuromoduladoras reduzam a intensidade da dor pélvica crônica em mulheres.

Development and optimization of cosolvent-based blended Sertraline orodispersible films - A step to personalized medicine

Abstract Personalized medicine is gaining importance in pharmacotherapeutics as it allows tailoring the drug treatment to achieve the best patient response. Orodispersible film (ODF) is easy to formulate in hospitals, produces dose flexibility to suit an individual needs, particularly for patients suffer from swallowing issues or prohibited to take fluids. Sertraline Hydrochloride (SRT) was solubilized in several cosolvents, then different SRT ODFs based on five hydrophilic polymers namely; polyvinyl alcohol (PVA), hydroxylethyl cellulose (HEC), hydroxypropyl methylcellulose E5 LV (HPMC E5 LV), sodium alginate (NaAlg) and gelatin at two concentrations (2% and 4%) were developed and characterized. The outcomes were exposed to response surface analysis to obtain the desirability results to obtain the optimized formulation. Blended ODFs were developed from 4% PVA and 2% HEC in different blends and then potassium chloride (KCl) as a pore-forming agent was added to the best formulation to investigate its dissolution enhancement effect. F14 containing 4% PVA: 2% HEC 2:1 with 5% KCl showed best physicochemical properties of suitable pH (5.6), disintegration time (6 sec), good folding endurance which released 91 % SRT after 15 min. SRT ODF is an encouraging delivery system in the course of personalized medicine for the management of depression.

Analysis of potential drug interactions in medical clinic sector in a Hospital of João Pessoa - PB

Abstract The objective of this study was to evaluate drug interactions based on medical records of patients hospitalized in University Hospital Lauro Wanderley (UHLW) in João Pessoa-PB, Brazil. This was a quantitative, descriptive study with a cross-sectional design. This research was conducted in the medical clinic of the above hospital by analyzing pharmaceutical intervention in medical records. The investigated samples consisted of all medical profiles with drug interaction information of patients hospitalized from June 2016 to June 2017. Most of these drug interactions were determined and classified by Micromedex® Solutions database. This research was approved by the Ethics Committee in Institutional Human Research, protocol number 2.460.206. In total, 331 drug interactions were found in 131 medical profiles. Dipyrone, enoxaparin, sertraline, ondansetron, quetiapine, tramadol, bromopride, amitriptyline, and simvastatin were medications that showed highest interactions. According to Anatomical Therapy Classification (ATC), drugs that act on the central nervous system result in more interactions. The most prevalent interaction was between dipyrone and enoxaparin. Some limitations of this study are the lack of notifications and data on drug interactions.

Suspensión de la lactancia materna durante el tratamiento de la depresión postparto con sertralina: una revisión bibliográfica / Suspension of breastfeeding during treatment of postpartum depression with sertraline: a literature review

La Organización Mundial de la Salud recomienda amamantar a los recién nacidos, pero resulta contraproducente si la madre presenta una enfermedad que afecte este proceso natural, como la depresión postparto (DPP), una complicación psiquiátrica frecuente en el puerperio que influye en la salud de la madre y del lactante. El tratamiento farmacológico consiste en la administración de antidepresivos, considerándose los riesgos y ventajas, algunos ISRS se destacan por su menor detección en la leche materna; por ello la Sertralina puede ser el más seguro, el lactante ingiere cantidades pequeñas y generalmente no se detectan en el plasma. También se requiere de consejería por la incertidumbre de continuar o no amamantando.

The World Health Organization recommends breastfeeding newborns,but it is counterproductive if the mother presents a disease that affects this natural process, such as possible acute or chronic pathologies in the life cycle of pregnancy, as well as in lactation; one of them is postpartum depression (PPD), a frequent psychiatric complication in the puerperium that influences the health of the mother and the infant, such as early interruption or continued breastfeeding. Pharmacological treatment consists of the administration of antidepressants, considering the risks and advantages, some SSRIs stand out for their lower detection in breast milk; for this reason Sertraline may be the safest, the infant ingests small amounts and is generally not detected in the plasma. It is also the most used during lactation according to most researchers. Mothers may need breastfeeding counseling due to the uncertainty of continuing or not breastfeeding

Hepatotoxicidad grave inducida por sertralina / Sertraline-induced severe hepatotoxicity

We report the case of a 19-year-old patient, with a history of traumatic liver damage, but with a normal liver profile at her first discharge; 1 month after the event, with post-traumatic stress disorder, treatment with 25 mg of sertraline was started every day; one month later, she develops severe hepatotoxicity without a specific etiology. According to the Naranjo algorithm, it is attributed as a probable case of sertraline hepatotoxicity. Management is carried out with support measures and suspension of the medication, and the patient recovers until she is asymptomatic, currently has normal liver tests

Reportamos el caso de una paciente de 19 años, con antecedentes de daño hepático traumático, pero con un perfil hepático normal en su primer alta; después de 1 mes del evento, con trastorno de estrés postraumático se inició tratamiento con 25 mg diarios de sertralina; un mes después, desarrolla una hepatotoxicidad severa sin etiología determinada. De acuerdo con el algoritmo de Naranjo, se atribuye como caso probable de hepatotoxicidad por sertralina. El manejo se realiza con medidas de apoyo y suspensión del medicamento, y la paciente se recupera hasta que se encuentra asintomática, actualmente tiene pruebas hepáticas normales

Effects of sertraline in the prevention of low blood pressure in patients undergoing hemodialysis / Efeitos da sertralina na prevenção de hipotensão arterial em pacientes submetidos à hemodiálise

Abstract Introduction: Intradialytic hypotension (IDH) is a major complication of hemodialysis, with a prevalence of about 25% during hemodialysis sessions, causing increased morbidity and mortality. Objective: To study the effects of sertraline to prevent IDH in hemodialysis patients. Methods: This was a double-blind, crossover clinical trial comparing the use of sertraline versus placebo to reduce intradialytic hypotension. Results: Sixteen patients completed the two phases of the study during a 12-week period. The IDH prevalence was 32%. A comparison between intradialytic interventions, intradialytic symptoms, and IDH episodes revealed no statistical difference in the reduction of IDH episodes (p = 0.207) between the two intervention groups. However, the risk of IDH interventions was 60% higher in the placebo group compared to the sertraline group, and the risk of IDH symptoms was 40% higher in the placebo group compared to the sertraline group. Survival analysis using Kaplan-Meier estimator supported the results of this study. Sertraline presented a number needed to treat (NNT) of 16.3 patients to prevent an episode from IDH intervention and 14.2 patients to prevent an episode from intradialytic symptoms. Conclusion: This study suggests that the use of sertraline may be beneficial to reduce the number of symptoms and ID interventions, although there was no statistically significant difference in the blood pressure levels.

Resumo Introdução: A hipotensão intradialítica (HID) é uma das principais complicações da hemodiálise, com uma prevalência de cerca de 25% durante as sessões de hemodiálise, causando aumento da morbimortalidade. Objetivo: Estudar os efeitos da sertralina na prevenção da HID em pacientes em hemodiálise. Métodos: Este foi um ensaio clínico duplo-cego, cruzado, comparando o uso de sertralina versus placebo para reduzir a hipotensão intradialítica. Resultados: Dezesseis pacientes completaram as duas fases do estudo durante um período de 12 semanas. A prevalência de HID foi de 32%. Uma comparação entre intervenções intradialíticas, sintomas intradialíticos (ID) e episódios de HID não revelou diferença estatística na redução dos episódios de HID (p = 0,207) entre os dois grupos de intervenção. No entanto, o risco de intervenções para HID foi 60% maior no grupo placebo em comparação com o grupo Sertralina, e o risco de sintomas ID foi 40% maior no grupo placebo em comparação com o grupo Sertralina. A análise de sobrevida utilizando o estimador de Kaplan-Meier corroborou os resultados deste estudo. A sertralina apresentou um número necessário para tratar (NNT) de 16,3 pacientes para prevenir um episódio de intervenção de HID e 14,2 pacientes para prevenir um episódio de sintomas intradialíticos. Conclusão: Este estudo sugere que o uso de sertralina pode ser benéfico para reduzir o número de sintomas e intervenções de HID, embora não tenha havido diferença estatisticamente significante nos níveis pressóricos.

La depresión: un desafío en la práctica médica general / La depresión: un desafío en la práctica médica general

Asociada o no a una enfermedad orgánica, la depresión tiene gran prevalencia en la práctica médica pero es subdiagnosticada. El trastorno del ánimo suele coexistir con variadas quejas somáticas y dolores crónicos, configurando síndromes mixtos con un diagnóstico diferencial complejo. En este artículo se describen distintas presentaciones clínicas de la depresión en medicina general, con énfasis en los estados depresivos atípicos, depresiones enmascaradas muy relevantes por su frecuencia y consecuencias: depresión posquirúrgica, cuadros dolorosos crónicos como cefaleas o lumbago, la fatiga crónica y la fibromialgia. Solo el reconocimiento y diagnóstico de la depresión subyacente posibilitará la implementación de las adecuadas intervenciones terapéuticas. Se revisan también algunas recomendaciones para el uso de antidepresivos en atención primaria y la eventual consulta psiquiátrica. (AU)

Associated or not with an organic disease, depression has a high prevalence in medical practice but is underdiagnosed. The mood disorder usually coexists with varied somatic complaints and chronic pain, forming mixed syndromes with a complex differential diagnosis. This article describes different clinical presentations of depression in general medicine, with emphasis on atypical depressive states, masked depressions very relevant for their frequency and consequences: post-surgical depression, chronic painful conditions such as headaches or lumbago, chronic fatigue and fibromyalgia. Only the recognition and diagnosis of the underlying depression will enable the implementation of appropriate therapeutic interventions. Some recommendations for the use of antidepressant drugs in primary care and the eventual psychiatric consultation are also reviewed. (AU)

Which of available selective serotonin reuptake inhibitors (SSRIs) is more effective in treatment of premature ejaculation? A randomized clinical trial

ABSTRACT Purpose: To compare the efficacy and safety of available selective serotonin reuptake inhibitors (SSRIs) in order to find the most effective drug with the least number of side effects in treatment of premature ejaculation (PE). Materials and Methods: This study was a randomized clinical trial. Four hundred and eighty patients with PE in the 4 groups referred to Imam Reza hospital Tehran, Iran from July 2018 to February 2019 were enrolled in the study. The patients received sertraline 50mg, fluoxetine 20mg, paroxetine 20mg and citalopram 20mg, every 12 hours daily. The intravaginal ejaculatory latency time (IELT) before treatment, fourth and eighth weeks after treatment was recorded by the patient's wife with a stopwatch. Results: Mean IELT before, 4 and 8 weeks after treatment in four groups were: sertraline 69.4±54.3, 353.5±190.4, 376.3±143.5; fluoxetine 75.5±64.3, 255.4±168.2, 314.8±190.4; paroxetine 71.5±69.1, 320.7±198.3, 379.9±154.3; citalopram 90.39±79.3, 279.9±192.1, 282.5±171.1 seconds, respectively. The ejaculation time significantly increased in all groups (p <0.05), but there was no significant difference between the groups (P=0.75). Also, there was no significant difference in drugs side effects between groups (p >0.05). The most common side effects were drowsiness and dyspepsia, which were not severe enough to cause discontinuation of the drug. Conclusions: All available SSRIs were effective and usually had no serious complications. In patients who did not respond to any of these drugs, other SSRI drugs could be used as a salvage therapy.

Mareo postural perceptual persistente: la causa más frecuente de mareo crónico es fácil de tratar / Persistent postural-perceptual dizziness: the most frequent cause of chronic dizziness is easy to manage

RESUMEN Los trastornos vestibulares funcionales se constituyen como una de las causas más frecuentes de consulta por vértigo y trastornos del equilibrio. El mareo postural perceptual persistente (MPPP) es un síndrome recientemente definido, enmarcado en la categoría de síndromes vestibulares crónicos, que agrupa trastornos vestibulares funcionales crónicos como el vértigo postural fóbico, el malestar con el movimiento espacial, el vértigo visual y el mareo subjetivo crónico. El MPPP se manifiesta por síntomas de mareo, inestabilidad y/o vértigo no rotatorio, persistentes, exacerbados por cambios posturales, movimientos y exposición a distintos estímulos visuales. El tratamiento de este cuadro es más sencillo de lo que parece, basado en psicoeducación efectiva respecto a la patología como primer abordaje, adicionando o no rehabilitación vestibular, uso de inhibidores selectivos de la recaptación de serotonina y/o terapia cognitivo conductual. Se presentan dos casos clínicos de pacientes diagnosticados con MPPP y su respuesta a tratamiento.

ABSTRACT Functional vestibular disorders are one of the most frequent causes of consultation due to vertigo and balance disorders. Persistent postural-perceptual dizziness (PPPD) is a recently defined syndrome, categorized as a chronic vestibular syndrome, that includes functional vestibular disorders such as phobic postural vertigo, space-motion discomfort, visual vertigo and chronic subjective dizziness. PPPD manifests with dizziness, unsteadiness and/or non-spinning vertigo, which are persistent, exacerbated by postural changes, movements and exposure to various visual stimuli. PPPD treatment is simpler than it may seem initially. It is based on effective psychoeducation related to the pathology in the first place, followed, or not, by vestibular rehabilitation, use of selective serotonin reuptake inhibitors and/or cognitive behavioral therapy. We present two clinical cases of patients diagnosed with PPPD and their response to treatment.

Paciente con cansancio / Tired patient

El médico de familia está capacitado para resolver la mayoría de los problemas de salud de sus pacientes. Dentro del consultorio, el cansancio constituye un motivo de consulta muy frecuente. Su abordaje debe incluir la evaluación del contexto del paciente y un enfoque sistémico que incluya otros niveles diagnósticos y terapéuticos. Se presenta el caso de una paciente que, a partir de este motivo de consulta tan frecuente y junto a intervenciones de su médico de cabecera, logró modificar el foco del problema y comenzar un tratamiento acorde. (AU)

Family physicians are able to solve the majority of their patients' health issues. In the office, fatigue is a common complaint. Its approach should include the evaluation of the context of the patient and a systemic approach that includes other diagnostic and therapeutic levels. We present the case of a patient who went to his doctor with a common complaint and was able to change the focus of the problem and begin a consistent treatment. (AU)

Drug administration adjustments for elderly patients with dysphagia: A case report / Ajustes da administração de medicamentos para pacientes idosos com disfagia: um relato de caso

ABSTRACT An elderly patient, aged 76 years, diagnosed with dysphagia, depression, hypothyroidism, Alzheimer's disease and mild cognitive deficit, was identified with sertraline and levothyroxine- drug-related problems. Medication Therapy Management (MTM) was used to adjust therapy to the patient's needs by macerating sertraline tablets and solubilizing them in 10-30 mL of orange juice. The patient was advised to take levothyroxine after fasting. Six months later, pharmaceutical follow-up identified an increase in the Mini-Mental State Exam score from 22 to 26 and a decrease in the Clinical Dementia Rating (CDR) scale score from 1.0 to 0.5 in conjunction with mood and physical improvements, as well as a significant decrease in aggressiveness and agitation. Cognitive deficit may be a result of poor drug administration procedures, leading to drug ineffectiveness. Optimizing levothyroxine and sertraline administration, based on knowledge of their physicochemical properties, improves their clinical effectiveness, including the cognition of patients with Alzheimer's disease and dysphagia.

RESUMO Paciente idosa, 76 anos, diagnosticada com disfagia, depressão, hipotireoidismo, doença de Alzheimer e déficit cognitivo leve, foram identificados problemas relacionados com a sertralina e levotiroxina. O Gerenciamento da Terapia Medicamentosa foi usado para ajustar a terapia às necessidades da paciente, macerando comprimidos de sertralina e solubilizando-os em 10-30 mL de suco de laranja. Foi recomendado a paciente tomar levotiroxina após o jejum. Seis meses depois, o seguimento farmacêutico identificou um aumento no score da escala Mini-Mental de 22 para 26 e Avaliação Clínica da Demência (CDR) de 1,0 para 0,5 em conjunto com melhorias físicas e de humor, bem como uma diminuição significativa na agressividade e agitação. O déficit cognitivo pode ser o resultado de procedimentos de administração inadequada de fármacos, levando à ineficácia do fármaco. A otimização da administração de levotiroxina e sertralina, com conhecimento de suas propriedades físico-químicas, melhora sua efetividade clínica, incluindo a cognição do paciente com a doença de Alzheimer e disfagia.

Development of self-nanoemulsifying tablet (SNET) for bioavailability enhancement of sertraline

The purpose of the study was to combine the advantages of self-nanoemulsifying drug delivery systems and tablets as a conventional dosage form. Self-nanoemulsifying drug delivery system (SNEDDS) was prepared to enhance the solubility and thus oral bioavailability of sertraline. Aqueous titration method was used to prepare the liquid SNEDDS; ternary phase diagrams were constructed and based on smaller droplet size (24.8 nm), minimum viscosity (153.63 cP) and polydispersity index (0.182), higher percentage transmittance (95%) and in vitro drug release (97%), an optimum system was designated. Liquid SNEDDS was transformed into free-flowing powder by solid adsorption technique followed by compression into tablets. In vitro release of sertraline from liquid and solid SNEDDS was found to be highly significant compared to plain sertraline (p<0.01). Pharmacokinetic studies after oral administration of liquid and solid SNEDDS in rats showed about 6-and 5-fold increased absorption of sertraline compared to the aqueous suspension of sertraline. These studies demonstrate that the solid SNEDDS are promising strategies for successful delivery of poorly water-soluble drug like sertraline

Estudo pré-clínico da sertralina nanolipossomal na leishmaniose visceral / Preclinical study of nanoliposomal sertraline in visceral leishmaniasis

A leishmaniose visceral (LV) é uma protozoose negligenciada fatal se não tratada, afetando 1,5 milhões de pessoas em todo o mundo. Na América Latina, o Brasil é responsável por 90% dos casos de LV, sendo seu tratamento um grande desafio, por apresentar alta toxicidade. Desta forma, a busca por alternativas terapêuticas é uma necessidade iminente. O reposicionamento de fármacos vem sendo uma abordagem importante na redução do custo e do tempo nas pesquisas. Além disso, sistemas de entrega de fármacos (Drug Delivery) como lipossomos, têm contribuído para a redução de dose terapêutica e consequentemente, dos efeitos adversos dos fármacos. Sendo assim, neste trabalho, foi avaliado o potencial anti-Leishmania do antidepressivo sertralina (SERT) em modelos in vitro e in vivo, utilizando tanto o fármaco livre (SERT), como encapsulado em nanolipossomos (SERT-LP). A SERT apresentou atividade contra formas promastigotas e amastigotas intracelulares com valores de Concentração Efetiva 50% (CE50) de 0,7 µM e 4 µM, respectivamente. A associação in vitro da SERT com miltefosina demonstrou valores da média das somatórias das Concentrações Inibitórias Fracionárias (X∑CIF) de 0,64 e 1,32 em promastigotas e amastigotas, respectivamente, resultando em uma associação aditiva. Visando verificar a eficácia in vivo, foi realizado um estudo farmacocinético da SERT em modelo murino, resultando em uma meia vida plasmática (T1/2) de aproximadamente 8 horas. O estudo in vivo da eficácia da SERT demonstrou falha terapêutica, tanto na administração pela via oral, como subcutânea. Porém, quando encapsulada em lipossomos (125 nm) de carga negativa, resultou em uma significativa redução (89%) da carga parasitária no fígado de camundongos tratados, pela via de administração subcutânea, por 10 dias a 1 mg/kg/dia. Inesperadamente, em uma dose 15 vezes maior, foi observado um aumento de 100% da carga parasitária, valor este, correlacionado ao aumento dos níveis séricos da citocina IL-6 e da quimiocina MCP-1. Estudos de biodistribuição da SERT-LP, demonstraram a presença da formulação no fígado e baço - 12 a 48 horas após administração subcutânea. Estudos histopatológicos dos animais tratados a 1 e 15 mg/kg/dia por 10 dias demonstraram a presença de múltiplos 6 focos de infiltrado inflamatório linfohistiocitário, formando esboços granulomatosos, em parênquima hepático. No baço, foi observado a presença de hiperplasia linfóide reativa, não diferindo do grupo controle. Os dados obtidos no estudo histopatológico corroboram os níveis de citocinas observados por citometria de fluxo, resultando em um infiltrado inflamatório. O presente estudo demonstra a eficácia da sertralina encapsulada em lipossomos na LV experimental, e sugere pela primeira vez, uma correlação entre o aumento da carga parasitária com a imunomodulação dose-dependente do fármaco. (AU)

Visceral leishmaniasis (VL) is a fatal neglected protozoan, affecting 1.5 million people in all the world. In Latin America, Brazil is responsible for 90% of cases of VL, and its treatment is a challenge once it shows high toxicity. Thats why it's important to search for therapeutic alternatives. Drug repositioning has been an important approach in reducing cost and time for the research. In addition, controlled drug delivery systems such as liposomes have contributed to the reduction of the therapeutic dose and, consequently, to the adverse effects of the drugs. In this study, the anti-Leishmania potential of sertraline antidepressant (SERT) was evaluated in in vitro and in vivo models, using the free drug (SERT) and the encapsulated in nanoliposomes (SERT-LP). SERT showed a potent activity against promastigotes and intracellular amastigotes with concentrations of 50% Effective Concentration (EC50) of 0.7 µM and 4 µM, respectively. The in vitro association of SERT with miltefosine demonstrated mean values of the sum of Fractional Inhibitory Concentrations (XΣCIF) of 0.64 and 1.32 in promastigotes and amastigotes, respectively, resulting in an additive association. Aiming for in vivo efficacy studies, a pharmacokinetic study of free sertraline in the murine model was performed, resulting in a plasma halflife (T1/2) of approximately 8 hours. In vivo study of the efficacy of SERT demonstrated therapeutic failure, in oral and subcutaneous administration. However, when encapsulated in nanoliposomes (125 nm) charge negativelly (SERT-LP), it resulted in a significant reduction (89%) of the parasite burden in the liver of mice treated for 10 days at 1 mg/kg. Unexpectedly, at a dose 15 times higher, showed 100% of increase in the parasite burden, which was correlated with increased of cytokine IL-6 and chemokine MCP-1 levels. Studies of biodistribution of SERT-LP, demonstrated the presence of the formulation in liver and spleen - 12 to 48 hours after subcutaneous administration. Histopathological studies of animals treated at 1 and 15 mg/kg for 10 days showed the presence of multiple foci of inflammatory lymphohistiocytic infiltrate, forming granulomatous sketches in hepatic parenchyma. In the spleen, the presence of reactive lymphoid hyperplasia was observed, not differing from the control group. The data obtained in the histopathological study corroborate with 8 the levels of cytokines observed in the flow cytometry, resulting in an inflammatory infiltrate. The present study demonstrates the potential of this new sertraline nanoformulation in experimental LV and suggests for the first time a correlation between increased parasite burden with dose-dependent immunomodulation of the drug. (AU)

Efficacy of sertraline against Trypanosoma cruzi: an in vitro and in silico study

Drug repurposing has been an interesting and cost-effective approach, especially for neglected diseases, such as Chagas disease. Methods: In this work, we studied the activity of the antidepressant drug sertraline against Trypanosoma cruzi trypomastigotes and intracellular amastigotes of the Y and Tulahuen strains, and investigated its action mode using cell biology and in silico approaches. Results: Sertraline demonstrated in vitro efficacy against intracellular amastigotes of both T. cruzi strains inside different host cells, including cardiomyocytes, with IC50 values between 1 to 10 µM, and activity against bloodstream trypomastigotes, with IC50 of 14 µM. Considering the mammalian cytotoxicity, the drug resulted in a selectivity index of 17.8. Sertraline induced a change in the mitochondrial integrity of T. cruzi, resulting in a decrease in ATP levels, but not affecting reactive oxygen levels or plasma membrane permeability. In silico approaches using chemogenomic target fishing, homology modeling and molecular docking suggested the enzyme isocitrate dehydrogenase 2 of T. cruzi (TcIDH2) as a potential target for sertraline. Conclusions: The present study demonstrated that sertraline had a lethal effect on different forms and strains of T. cruzi, by affecting the bioenergetic metabolism of the parasite. These findings provide a starting point for future experimental assays and may contribute to the development of new compounds.(AU)

TeleCondutas: ansiedade / TeleGuides: anxiety

A ansiedade pode ser vista como sintoma psiquiátrico e/ou como reação emocional não patológica associada a diversos contextos de vida. Ela representa um sinal de alarme a determinado estímulo percebido pelo indivíduo como perigoso. Em geral, é composta por uma combinação variável de sintomas físicos, pensamentos catastróficos e alterações de comportamento. A ansiedade pode ser compreendida como mecanismo evolutivo, isto é, uma ferramenta que nos ajuda a detectar o perigo e adotar as medidas necessárias para lidar com ele. No entanto, esse recurso adaptativo muitas vezes encontra-se desregulado, causando sofrimento e prejuízo ao desempenho social e/ou profissional. A ansiedade se torna um transtorno psiquiátrico quando representa emoção desconfortável e inconveniente, surgindo na ausência de um estímulo externo claro ou com magnitude suficiente para justificá-la, e apresenta intensidade, persistência e frequência desproporcionais. Estudos epidemiológicos indicam os transtornos de ansiedade como os mais prevalentes dentre os transtornos psiquiátricos. Na grande maioria dos casos, não há como estabelecer uma causa específica aos transtornos aqui tratados. A interação entre fatores genéticos e ambientais resume a etiologia atualmente proposta e aceita. Esta guia apresenta informação que orienta a conduta para casos de ansiedade no contexto da Atenção Primária à Saúde, incluindo: Diagnóstico, Diagramas diagnósticos, Condições de saúde associadas aos sintomas, Fármacos associados aos sintomas, Abordagem psicoeducativa/psicossocial, Tratamento conforme diagnóstico, Medicamentos e dose, Quando encaminhar.

Uso de antidepressivos em um município do Rio Grande do Sul / Use of antidepressants in a city of Rio Grande do Sul

Estudo transversal, realizado na Unidade Básica de Saúde (UBS) do município de São José do Inhacorá/RS com o objetivo de realizar um levantamento quanto ao uso de medicamentos antidepressivos e os fatores associados ao seu uso. A amostragem e o tempo de coleta foi do tipo intencional, entre os meses de dezembro de 2013 a janeiro de 2014 foram identificados os pacientes que retiraram antidepressivos no município no ano de 2013 e entre janeiro a julho de 2014, os quais foram entrevistados nas residências. O projeto foi aprovado pelo Comitê de Ética em Pesquisa da Unijuí sob parecer consubstanciado nº 508.920/2013.9. Dos 88 pacientes elegíveis para amostra, pode-se observar maior consumo de antidepressivos por mulheres (75%), e entre idosos. Os clínicos gerais realizaram a maioria das prescrições de antidepressivos, o que justifica-se pelo fato do município não apresentar serviço especializado e a classe farmacológica mais frequente foi ISRS (69,6%) e o antidepressivo mais prescrito foi a sertralina (31,8%). Apenas 18,2% dos usuários relataram efeitos adversos, conforme autorrelato. Não houve diferença significativa com: estado civil (p = 0,193; p > 0,005; ANOVA/Tuckey) e escolaridade (p = 0,543; p > 0,005; ANOVA/Tuckey), mas foi verificada quanto a idade (p = 0,0032; p > 0,005; ANOVA/Tuckey) e com sexo dos entrevistados (p = 0,0045; p > 0,005; Qui-quadrado), sendo mais utilizado por mulheres. Observou-se que em relação aos medicamentos antidepressivos utilizados pelos usuários apenas a Fluoxetina, Amitriptilina, Nortriptilina, Bupropiona estão incluídos na RENAME (BRASIL, 2013). Dos 12 medicamentos antidepressivos utilizados, oito não pertencem a RENAME (BRASIL, 2013), sendo estes sertralina, citalopram, imipramina, paroxetina, trazodona, venlafaxina, mirtazapina e escitalopram. O que se pode observar dos três antidepressivos mais utilizados apenas a fluoxetina encontra-se na RENAME (BRASIL, 2013), e o mais utilizado, a sertralina, não está presente nesta relação, mostrando a importância da reavaliação dos critérios de prescrição, criação da Relação de Medicamentos Municipais (REMUME) e elaboração de protocolos clínicos que amparem o uso destes medicamentos. Os dados mostram que a amostra usou antidepressivos distintos, sendo em sua maioria idosos e usuários de politerapia, sendo que estes dados mostram a necessidade de acompanhamento destes pacientes. Quanto ao relato de eventos adversos verifica-se que é necessário o desenvolvimento da cultura da farmacovigilância. Destaca-se, que este trabalho serviu de subsídio para a formação de grupo de saúde mental na UBS de São José do Inhacorá/RS, com objetivo potencializar as trocas dialógicas, compartilhar experiências e melhorar a adaptação individual e do convívio coletivo, buscando mais segurança no uso de medicamentos e indivíduos com mais qualidade de vida.

In order to research the use of antidepressant medications and factors associated with their use in the public health service of a municipality in the northwestern region of the state of Rio Grande do Sul, a cross-sectional study was performed in the Basic Health Unit (BHU) in the city of São José do Inhacorá/RS. The sampling and collection time were intentional, with patients who withdrew antidepressants being identified in the period from December 2013 to January 2014, and between January and July 2014, these patients were interviewed in their homes. The project was approved by the Research Ethics Committee of Unijuí under substantiated opinion No. 508 920/2013.9. From the 88 patients eligible for the sample, a higher consumption of antidepressants could be observed by women (75%), and the elderly. General practitioners performed most of the antidepressant prescriptions, which is justified by the fact that the municipality does not provide specialized service. The most common pharmacological drug class was SSRI (69.6%) and the most frequently prescribed antidepressant was sertraline (31.8 %). Only 18.2% of users reported adverse effects, according to their self-report. There were no significant differences in marital status (p = 0.193; p> 0.005; ANOVA/Tukey) and education (p = 0.543; p> 0.005; ANOVA/Tukey) but significant differences were observed for age (p = 0.0032; p> 0.005; ANOVA/Tukey) and gender of respondents (p = 0.0045; p> 0.005; Chi-squared), being more frequently used by women. It was observed that compared to antidepressant medications used by users, only fluoxetine, amitriptyline, nortriptyline and bupropion are included in RENAME (BRAZIL, 2013). Among the 12 antidepressant drugs used, eight do not belong to RENAME (BRAZIL, 2013), namely sertraline, citalopram, imipramine, paroxetine, trazodone, venlafaxine, mirtazapine and escitalopram. It can be observed that among the three most widely used antidepressants, only fluoxetine is in RENAME (BRAZIL, 2013), and the most commonly used one ­ sertraline - is not present in this list, showing the importance of reassessment of prescription criteria, as well as the creation of List of Municipal Drugs (REMUME) and preparation of clinical protocols that support the use of these drugs. These data show that the sample used different antidepressants, being composed mostly of elderly and poly-therapy users, as well as showing the need to monitor these patients. Regarding the report of adverse events, it could be noted that the development of a Pharmacovigilance culture is needed. It is noteworthy that this work served as a subsidy for the mental health training group at UBS São José do Inhacorá/RS, in order to enhance the dialogic exchanges, share experiences and enhance their individual and collective living adaptation, seeking more security in the use of medication and individuals, providing a better quality of life.

Análisis de costo-efectividad de escitalopram comparado con paroxetina, sertralina y venlafaxina como terapia de mantenimiento para pacientes con trastorno de ansiedad generalizada en Colombia / Cost-effectiveness analysis of escitalopram compared to paroxetine, sertraline and venlafaxine as maintenance therapy for patients with generalized anxiety disorder in Colombia

Problema de investigación: Describir los costos y la efectividad de escitalopram comparado con paroxetina, sertralina y venlafaxina como terapia de mantenimiento en adultos con diagnóstico de trastorno de ansiedad generalizada en Colombia. Tipo de evaluación económica: Análisis de costo-utilidad. Población objetivo: Adultos colombianos con diagnóstico de trastorno de ansiedad generalizada. Intervención y comparadores: Intervención: escitalopram, Comparadores: paroxetina, sertralina y venlafaxina. Horizonte temporal: 32 semanas. Perspectiva: SGSSS. Tasa de descuento: No aplica. Estructura del modelo: Se estructuró un árbol de decisión, teniendo en cuenta modelos publicados en la literatura. Fuentes de datos de efectividad y seguridad: Reporte de efectividad y seguridad elaborado en diciembre de 2014 en el IETS, Ensayos clínicos aleatorizados. Desenlaces y valoración: AVAC, Tasa de respuesta al medicamento, Tasa de recaídas con el medicamento. Costos incluidos: Costo de los medicamentos, Costo de procedimientos, Costo de los eventos adversos. Fuentes de datos de costos: SISMED, Manual tarifario ISS 2001. Resultados del caso base: Para el caso base, escitalopram es la alternativa cost-efectiva con un costo esperado de $39.127.045 respecto a sertralina. La RICE de paroxetina fue superior al umbral de costo-efectividad de 3 veces el PIB per cápita. Venlafaxina fue dominada por todos los demás medicamentos. Se encuentra gran incertidumbre en la decisión y una e fectividad esperada muy similar entre todas las alternativas, por lo que estos resultados deben analizarse con precaución. Análisis de sensibilidad: Los análisis de sensibilidad y el diagrama de tornado mostraron que las variables con mayor impacto sobre las estimaciones de costo-utilidad del escitalopram son la probabilidad de respuesta, ponderaciones de utilidad, las dosis de los medicamentos y el desenlace utilizado. Conclusiones y discusión: Escitalopram parece ofrecer una mejorrelación entre costos y efectividad respecto a sus comparadores. No obstante, es necesario tener en cuenta que sertralina y paroxetina pueden llegar a ser costo-efectivas bajo escenarios plausibles. Venlafaxina obtuvo una peor relación de costos y beneficios comparativos. La principal limitación de este estudio se centra en la ausencia de ensayos clínicos de no inferioridad con un horizonte de largo plazo.(AU)