Effect of amitriptyline on learning and memory consolidation in the male Wistar rats with an experimental model of pentylenetetrazole-induced seizure

Abstract Amitriptyline (AMT) was developed for the treatment of chronic and neuropathic pain. There is also evidence it may be useful in the treatment of neurodegenerative disorders. In this regard, the effect of on the experimental model of seizures and memory impairment caused by seizures in rats is investigated in the present study. Seizures in Wistar rats (200-250 g) were induced by pentylenetetrazole (PTZ, 60 mg/kg, intraperitoneally (i.p.)). The anticonvulsant effect of AMT (10 and 20 mg/kg, i.p.) was evaluated in the seizure model. The effect on memory was assessed using passive avoidance (PA) learning and memory test. After behavioral tests, the animals underwent deep anesthesia and were put down painlessly. Animal serum was isolated for oxidant/antioxidant assays (malondialdehyde (MDA), and glutathione peroxidase (GPx)). Intraperitoneal injection of AMT decreased the mean number of myoclonic jerks and generalized tonic-clonic seizure (GTCS) duration and increased the mean latency of myoclonic jerk and GTCS compared to the PTZ group. Moreover, in the PA test, AMT caused a significant increase in retention latency (RL) and total time spent in the light compartment (TLC) compared to the PTZ group. Biochemical tests showed that AMT was able to significantly increase GPx serum levels and significantly reduce MDA serum levels compared to the PTZ group. Overall, this study suggests the potential neuroprotective effects of the AMT drug in a model of memory impairment caused by seizures via the mechanism of inhibition of the oxidative stress pathway.

Virtual screening based on molecular docking of lysosomotropic compounds as therapeutic agents for COVID-19 / Triagem virtual baseada no encaixe molecular de compostos lisossomotrópicos como agentes terapêuticos para COVID-19

Objective: Analyze lysosomotropic agents and their action on COVID-19 targets using the molecular docking technique. Methods: Molecular docking analyses of these lysosomotropic agents were performed, namely of fluoxetine, imipramine, chloroquine, verapamil, tamoxifen, amitriptyline, and chlorpromazine against important targets for the pathogenesis of SARS-CoV-2. Results: The results revealed that the inhibitors bind to distinct regions of Mpro COVID-19, with variations in RMSD values from 1.325 to 1.962 Å and binding free energy of -5.2 to -4.3 kcal/mol. Furthermore, the analysis of the second target showed that all inhibitors bonded at the same site as the enzyme, and the interaction resulted in an RMSD variation of 0.735 to 1.562 Å and binding free energy ranging from -6.0 to -8.7 kcal/mol. Conclusion: Therefore, this study allows proposing the use of these lysosomotropic compounds. However, these computer simulations are just an initial step toward conceiving new projects for the development of antiviral molecules.

Objetivo: aAnalisar agentes lisossomotrópicos e sua ação em alvos de COVID-19 usando a técnica de docking molecular. Métodos: Foram realizadas análises de docagem molecular destes agentes lisossomotrópicos, nomeadamente de fluoxetina, imipramina, cloroquina, verapamil, tamoxifeno, amitriptilina e clorpromazina contra alvos importantes para a patogenia do SARS-CoV-2. Resultados: Os resultados revelaram que os inibidores se ligam a regiões distintas do Mpro COVID-19, com variações nos valores de RMSD de 1.325 a 1.962 Å e energia livre de ligação de -5,2 a -4,3 kcal/mol. Além disso, a análise do segundo alvo mostrou que todos os inibidores se ligaram no mesmo sítio da enzima, e a interação resultante em uma variação de RMSD de 0,735 a 1.562 Å e energia livre de ligação variando de -6,0 a -8,7 kcal/mol. Conclusão: Portanto, este estudo permite propor o uso desses compostos lisossomotrópicos. No entanto, essas simulações em computador são apenas um passo inicial para a concepção de novos projetos para o desenvolvimento de moléculas antivirais.

Produção de fumo e insônia: relato de caso sobre os determinantes socioeconômicos para o uso contínuo de benzodiazepínicos em uma zona rural no Sul do Brasil / Tobacco production and insomnia: case report on socioeconomic determinants of the continuous use of benzodiazepines in a rural area in southern Brazil / Producción de tabaco e insomnio: Reporte de caso sobre determinantes socioeconómicos del uso continuo de benzodiacepinas en una zona rural del sur de Brasil

Introdução: A fumicultura concentra-se sobretudo em áreas rurais do Sul do país. Reconhecidamente, as áreas rurais apresentam disparidades socioeconômicas, desigualdades no acesso geográfico, bem como dificuldade de retenção de profissionais na Atenção Primária à Saúde (APS). Apresentação do caso: Descrevem-se, neste artigo, as intersecções de determinantes socioeconômicos de saúde ao se abordar um paciente masculino, de 57 anos, em uso crônico de benzodiazepínicos para o tratamento de insônia. Ao se aprofundar a anamnese, os determinantes socioeconômicos que levaram ao desenvolvimento da insônia foram identificados como: dificuldades financeiras na produção de tabaco, preocupações excessivas com o trabalho e presença de depressão como comorbidade. Nesse sentido, ser produtor de tabaco e a relação com a empresa podem ser considerados determinantes socioeconômicos da saúde para o desenvolvimento de insônia. Conclusões: No contexto deste caso, a rotatividade de profissionais e a falta de criação de vínculo fez com que o paciente permanecesse cronicamente a tratar a insônia como benzodiazepínico, o que é proscrito. Assim, revelam-se a fragmentação do cuidado e a alta rotatividade de profissionais como determinantes socioeconômicos da saúde.

Introduction: Tobacco production is mainly concentrated in rural areas of the southern region of the country. Rural areas present socioeconomic disparities, inequalities in geographic access, and difficulties in retaining professionals in primary care. Mental health problems, such as insomnia, are common in clinical practice. Case presentation: This article describes the intersections of the social determinants of health when approaching a patient with chronic use of benzodiazepines for treatment of insomnia. By delving deep into anamnesis, the socioeconomic determinants that led to the development of insomnia were identified as: financial trouble with tobacco production, excessive concern about work and presence of depression as comorbidity. Conclusions: In this context, the turnover of health professionals and lack of doctor-patient relationship meant that the patient continued using benzodiazepines, which are not recommended for long-term treatment. Therefore, fragmented care and high professional turnover stand out as socioeconomic determinants of health.

Introducción: La producción de tabaco se concentra principalmente en las zonas rurales del sur del país. Se reconoce que las zonas rurales presentan desigualdades socioeconómicas, desigualdades en el acceso geográfico, así como dificultad para retener profesionales en Atención Primaria de Salud (APS). Los problemas de salud mental como el insomnio son comunes en la práctica clínica. Presentación de caso: Este artículo describe las intersecciones de los determinantes socioeconómicos de la salud al abordar a un paciente uso crónico de benzodiazepinas para el tratamiento del insomnio. Al profundizar la anamnesis, se identificaron los determinantes socioeconómicos que llevaron al desarrollo del insomnio como: dificultades económicas en la producción de tabaco, excesiva preocupación por el trabajo y la presencia de depresión como comorbilidad. En este sentido, ser productor de tabaco y la relación con la empresa pueden considerarse determinantes socioeconómicos de la salud para el desarrollo del insomnio. Conclusiones: En el contexto de este caso, la rotación de profesionales y la falta de vinculación hicieron que el paciente continuara crónicamente tratando el insomnio como una benzodiazepina, lo que no es recomendable. Así, la fragmentación de la atención y la alta rotación profesional se evidencia como un determinante socioeconómico de la salud.

Eficácia e segurança de Duloxetina comparado a outros antidepressivos disponíveis no SUS para o tratamento de depressão maior: revisão rápida de evidências / Effectiveness and safety of Duloxetine compared to other antidepressant agents available in Brazilian Public Health for treatment of major depression: rapid response review of evidence

Tecnologia: Duloxetina e outros antidepressivos disponíveis no Sistema Único de Saúde (amitriptilina, nortriptilina, clomipramina, fluoxetina e bupropiona). Indicação: Tratamento do primeiro episódio depressivo no transtorno de depressão maior em adultos. Pergunta: A duloxetina é mais eficaz e tolerável que a amitriptilina, nortriptilina, clomipramina, fluoxetina e bupropiona para o tratamento do primeiro episódio de depressão maior em adultos? Métodos: Revisão rápida de evidências (overview) de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Resultados: Foi selecionada 1 revisão sistemática, que atendia aos critérios de inclusão. Conclusão: Os antidepressivos, comparados ao placebo, tinham maior taxa de resposta, taxa de remissão e taxa de descontinuação devido a efeitos colaterais, no tratamento de curto prazo. Duloxetina tinha taxa de resposta similar a amitriptilina, clomipramina, fluoxetina e bupropiona. Duloxetina e amitriptilina tinham maior taxa de remissão que fluoxetina. Comparando-se as taxas de abandono de tratamento devido a efeitos colaterais, clomipramina era menos seguro, amitriptilina, bupropiona e duloxetina eram parecidos entre si, e fluoxetina era o antidepressivo mais seguro

Technology: Duloxetine and other antidepressants available in the Brazilian Public Health System (amitriptyline, nortriptyline, clomipramine, fluoxetine and bupropion). Indication: Treatment of the first depressive episode in adult major depressive disorder. Question: Is duloxetine more effective and tolerable than amitriptyline, nortriptyline, clomipramine, fluoxetine and bupropion for the treatment of first episode of major depression in adults? Methods: Rapid response review of evidence (overview) from systematic reviews, with a bibliographic search in the PUBMED database, using a structured strategy. The methodological quality of systematic reviews was assessed with AMSTAR-2 (Methodological Quality Assessment of Systematic Reviews). Results: One systematic review was selected, which met the inclusion criteria. Conclusion: In short-term treatment, antidepressants, compared to placebo, had a higher rate of response, rate of remission and rate drop-out due to side effects. Duloxetine had a similar response rate to amitriptyline, clomipramine, fluoxetine and bupropion. Duloxetine and amitriptyline had higher remission rates than fluoxetine. Comparing rates of dropout due to side effects, clomipramine had the worst rates, amitriptyline, bupropion, and duloxetine were similar to each other, and fluoxetine had the better rates

Lisdexanfetamina comparada a Metilfenidato ou antidepressivos no tratamento de TDAH em crianças e adolescentes: revisão rápida de evidências / Lisdexamfetamine compared to Methylphenidate or antidepressants for treatment of ADHD: rapid response review of evidence

Lisdexanfetamina e drogas disponíveis no SUS (metilfenidato, bupropiona, amitriptilina, clomipramina, nortriptilina). Indicação: Transtorno do Déficit de Atenção e Hiperatividade (TDAH) em crianças e adolescentes. Pergunta: Lisdexanfetamina é eficaz e segura para melhoria de sintomática, comparada ao placebo e medicações disponíveis no SUS, no tratamento de crianças e adolescentes com TDAH? Métodos: Revisão rápida de evidências (overview) de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews). Resultados: Foram selecionadas 3 revisões sistemáticas, que atenderam aos critérios de inclusão. Conclusão: Lisdexanfetamina e metilfenidato são mais eficazes que placebo, e similares entre si, para reduzir sintomas em escalas de avaliação. Lisdexanfetamina e metilfenidato têm risco similar ao placebo de abandono do tratamento devido a efeitos adversos. Bupropiona não é mais eficaz que placebo para alívio sintomático. Lisdexanfetamina tem efeitos adversos de redução do apetite e insônia/ dificuldades do sono. Não foram encontradas evidências na literatura sobre os efeitos terapêuticos de amitriptilina, clomipramina e nortriptilina no tratamento de crianças e adolescentes com TDAH

Lisdexamfetamine and drugs available in the Brazilian Public Health System (BPHS) (methylphenidate, bupropion, amitriptyline, clomipramine, nortriptyline, bupropion). Indication: Children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD). Question: Lisdexamfetamine is effective and safe for symptomatic improvement, compared to placebo and drugs available in the BPHS, for treatment of children and adolescents with ADHD? Methods: Rapid response review of evidence (overview) of systematic reviews, with bibliographic search in the PUBMED database, using a structured strategy. The methodological quality of systematic reviews was assessed with AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews). Results: 3 systematic reviews met the inclusion criteria and were selected. Conclusion: Lisdexamfetamine and methylphenidate are more effective than placebo, and similar to each other, to reduce symptoms on rating scales. Lisdexamfetamine and methylphenidate are not different from placebo in the risk of treatment discontinuation due to adverse effects. Bupropion is no more effective than placebo for symptomatic relief. Lisdexamfetamine has adverse effects of decreased appetite and insomnia/sleep troubles. No evidence was found in the literature about therapeutic effects of amitriptyline, clomipramine and nortriptyline for treatment of children and adolescents with ADHD

Treatment of patients with neuropathic pain and provision of drug information by clinical pharmacists

Abstract Patient's satisfaction with healthcare services has an influence on pain management, which can be improved by patient education. Therefore, this study was aimed at identifying primary care health service opportunities in the treatment of neuropathic pain and assessing patients' satisfaction with the provision of drug information by clinical pharmacists. This was a cross- sectional, prospective study conducted at a pain unit during March-May 2017. Patients aged >18 years; diagnosed with neuropathic pain; and who used amitriptyline, gabapentin, pregabalin, or duloxetine were included. They were verbally informed about drug treatment by a clinical pharmacist, and their satisfaction was evaluated after 1 month. In all, 90 patients were included. The median duration for which the patients experienced pain until hospital admission was 3.6 years; furthermore, this duration was longer among women (p < 0.05). However, the median time to seeking advice from doctors was 3 months. The patients (15.6%) were less likely to admit pain unit initially and 46.7% had visited different units before being admitted to a pain unit. More than 95% of the patients indicated that they had received information from a pharmacist at a clinic and were satisfied with the provision of information (median duration, 8.5 min). Thus, the involvement of pharmacists in multidisciplinary pain management may help improve health- related outcomes at hospitals and/or in community care settings

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.

Eficácia e segurança de Pregabalina, Gabapentina, Memantina, Amitriptilina, treinamento físico com exercícios em solo ou aquáticos para tratamento de Fibromialgia: revisão rápida de evidências / Effectiveness and safety of Pregabalin, Gabapentin, Memantine, Amitriptyline, exercises on land or aquatic exercises for Fibromyalgia treatment: rapid evidence review

Tecnologia: Pregabalina, drogas não-opioides disponíveis no SUS, treinamento físico no solo ou em meio aquático. Indicação: Tratamento da fibromialgia. Pergunta: Há diferenças de eficácia e segurança entre a Pregabalina e as outras drogas não opioides ou terapias disponíveis no SUS para tratamento da dor crônica relacionada à fibromialgia? Métodos: Levantamento bibliográfico foi realizado nas bases eletrônicas PUBMED e Cochrane Database, seguindo estratégias de buscas predefinidas, com busca adicional na página eletrônica da Comissão Nacional de Incorporação de Tecnologias em Saúde. Avaliou-se a qualidade metodológica das revisões sistemáticas com Assessing the Methodological Quality of Systematic Reviews versão 2 (AMSTAR-II). Resultados: Foram selecionadas e incluídas 6 revisões sistemáticas. Conclusão: A afirmação de eficácia da Gabapentina, Amitriptilina e Memantina para tratamento da fibromialgia é pouco confiável, pois as evidências são de nível 3, provenientes de ensaios clínicos de baixa qualidade metodológica. Pregabalina é eficaz para reduzir a dor em curto prazo (risco absoluto é 50%, nível 1 de evidência), mas não em longo prazo. O treinamento físico, relatado como única estratégia eficaz para tratamento da fibromialgia nas diretrizes do SUS, não tem efeito clinicamente importante sobre a dor

Technology: Pregabalin, non-opioid drugs available in Brazilian Public Health System, aquatic exercise or exercise on land. Indication: Treatment of fibromyalgia. Question: Are there differences in efficacy and safety between Pregabalin and other non-opioid drugs or therapies available in the SUS for the treatment of chronic pain related to fibromyalgia? Methods: A bibliographic survey was carried out in the electronic databases PUBMED and Cochrane Database, following pre-defined search strategies, with an additional search on the website of the National Commission for the Incorporation of Health Technologies. The methodological quality of systematic reviews was evaluated with Assessing the Methodological Quality of Systematic Reviews version 2 (AMSTAR-II). Results: Six systematic reviews were selected and included. Conclusion: There is not confidence about effectiveness of Gabapentin, Amitriptyline and Memantine for fibromyalgia treatment (level 3 of evidence, from clinical trials of low methodological quality). Pregabalin, in the short term, is effective for reducing pain (absolut risk is 50%, level 1 of evidence), but not in the long term. Physical training, reported as the only effective strategy for treating fibromyalgia in Brazilian Public Health System guidelines, has no clinically important effect on pain.

Comparing the efficacy and safety of duloxetine and amitriptyline in the treatment of fibromyalgia: overview of systematic reviews

Abstract Background: Duloxetine and amitriptyline are antidepressants used in the treatment of fibromyalgia. In published systematic reviews, there is no agreement about which drug is more effective and safer. This study aimed to compare evidence of the efficacy and safety of duloxetine compared with amitriptyline in the treatment of adult patients with fibromyalgia. This work contributes to guiding clinicians on the use of duloxetine or amitriptyline for the treatment of fibromyalgia and provides information for public health decision-makers. Methods: Overview of systematic reviews of clinical trials comparing duloxetine and amitriptyline in the treatment of fibromyalgia. The reviews were screened in Cochrane, PubMed, EMBASE, and SRDR with no restrictions on language and year of publication, considering that the research was conducted in July 2018 and updated until May 2020. The selection was based on the following criteria: adult patients with a diagnosis of fibromyalgia treated with duloxetine or amitriptyline, comparing the efficacy and safety in pain, fatigue, sleep, and mood disorder symptoms and quality of life, in addition to the acceptability of these antidepressants. The methodological quality and strength of evidence were assessed using the AMSTAR and GRADE instruments. Results: Eight systematic reviews were selected. Amitriptyline had low evidence for pain, moderate evidence for sleep and fatigue, and high evidence for quality of life. Duloxetine had high quality of evidence in patients with mood disorders. With low evidence, duloxetine has higher acceptability, but is safer in older patients, while amitriptyline is safer for non-elderly individuals. Conclusion: Both antidepressants are effective in the treatment of fibromyalgia, differing according to the patient's symptoms and profile. Registration: PROSPERO: CRD42019116101.(AU)

Treatment data from the Brazilian fibromyalgia registry (EpiFibro)

Abstract Background: EpiFibro (Brazilian Epidemiological Study of Fibromyalgia) was created to study patients with fibromyalgia (FM). Patients were included since 2011 according to the classification criteria for FM of the American College of Rheumatology of 1990 (ACR1990). Objective: To analyze the therapeutic measures prescribed by Brazilian physicians. Materials and methods: Cross-sectional study of a multicenter cohort. The therapeutic measures were described using descriptive statistics. Results: We analyzed 456 patients who had complete data in the registry. The mean age was 54.0 ± 11.9 years; 448 were women (98.2%). Almost all patients (98.4%) used medications, 62.7% received health education, and less than half reported practicing physical exercise; these modalities were often used in combination. Most patients who practiced exercises practiced aerobic exercise only, and a significant portion of patients combined it with flexibility exercises. The most commonly used medication was amitriptyline, followed by cyclobenzaprine, and a minority used medication specifically approved for FM, such as duloxetine and pregabalin, either alone or in combination. Combinations of two or three medications were observed, with the combination of fluoxetine and amitriptyline being the most frequent (18.8%). Conclusion: In this evaluation of the care of patients with FM in Brazil, it was found that the majority of patients are treated with a combination of pharmacological measures. Non-pharmacological methods are underused, with aerobic exercise being the most commonly practiced exercise type. The most commonly prescribed single drug was amitriptyline, and the most commonly prescribed combination was fluoxetine and amitriptyline. Drugs specifically approved for FM are seldom prescribed.(AU)

Polifarmácia e cognição em pacientes com idade avançada / Polypharmacy and cognition in elderly patients

Objetivo: Avaliar a prevalência da polifarmácia e da prescrição de medicações inapropriadas, bem como suas associações com a capacidade cognitiva e funcional do idoso. Métodos: Estudo observacional transversal, no qual foram analisadas as medicações prescritas em 141 prontuários para pacientes acima de 50 anos, em associação com testes que quantificaram a capacidade funcional e cognitiva deles. Resultados: Observou-se média de 4,41 medicamentos por paciente, sendo que 0,41 deles foram considerados inapropriado, segundo o critério de Beers. Verificou-se também relação estatisticamente significativa quanto ao número de medicações e testes que mediam a capacidade funcional e cognitiva dos idosos. Conclusão: O aumento da polifarmácia e da prescrição de medicações potencialmente inadequadas acarretou significativa piora da capacidade cognitiva e funcional do idoso

Objective: To evaluate the prevalence of polypharmacy and of the prescription of inappropriate medications, as well as their associations with the cognitive and functional capacity of the elderly. Methods: Cross-sectional observational study which analyzed the drugs prescribed in 141 medical records for patients over 50 years of age, associated with tests that quantified their functional and cognitive capacity. Results: An average of 4.41 medications per patient was observed, and 0.41 were considered inappropriate according to the Beers criteria. There was also a statistically significant relation regarding the number of medications and tests that measure the functional and cognitive capacity of the elderly. Conclusion: The increase in polypharmacy and in the prescription of potentially inappropriate medications led to a significant impairment of the cognitive and functional capacity of the elderly

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)

Neuropathic pain and prognosis of a dog submitted to limb amputation after diagnosis of soft tissue sarcoma - case report / Dor neuropática e prognóstico de um cão submetido à amputação de membro após diagnóstico de sarcoma de tecidos moles - relato de caso

Neuropathic pain occurs when there is a lesion or a dysfunction of the nervous system. Humans and veterinary patients may develop neuropathic pain, but in veterinary it is not often reported probably because of its mistaken diagnosis. A canine patient was admitted to the Veterinary Hospital of UNESP-Jaboticabal-SP, Brazil with a nodule on the left thoracic limb. The nodule was surgically removed, and histopathological analysis demonstrated the tumor was a soft tissue sarcoma (STS) and the margins were not clean. Based on the patient's health condition and the lack of suitable equipment, the next procedure was limb amputation. The patient received analgesic medication in the post-surgery period; nevertheless, clinical signs of neuropathic pain were present, such as compulsive licking and other behavioral disorders. Medications were administered for forty days, but clinical signs ceased only when replaced with a tryciclic antidepressant drug, Amitriptyline. Therapeutic management of the patient in this report can be considered effective, since five years after the end of the treatment there was no recurrence or presence of metastasis.(AU)

A dor neuropática ocorre quando há uma lesão ou disfunção do sistema nervoso. Tanto pacientes humanos quanto veterinários podem desenvolver a dor neuropática, mas na medicina veterinária ela é pouco relatada provavelmente por não ser corretamente diagnosticada. Um paciente canino foi atendido no Hospital Veterinário da Unesp-Jaboticabal, SP, Brasil, com um nódulo em membro torácico esquerdo. O nódulo foi removido cirurgicamente, e o exame histopatológico evidenciou a presença de sarcoma de tecidos moles (STM) e de margens comprometidas. Baseando-se nas condições de saúde do paciente e na ausência de equipamentos adequados, o próximo procedimento foi a amputação do membro. No pós-cirúrgico, o animal recebeu medicações analgésicas, todavia, mesmo assim, apresentava sinais de dor neuropática, como lambedura compulsiva e outros distúrbios comportamentais. O tratamento para dor aguda se estendeu por 40 dias; no entanto, os sinais clínicos cessaram apenas quando os analgésicos comuns foram substituídos por um medicamento antidepressivo tricíclico, a amitriptilina. O manejo terapêutico do paciente do presente relato pode ser considerado satisfatório, uma vez que, após cinco anos do término do tratamento, não houve recidiva nem presença de metástase.(AU)

Effects of in vitro amitriptyline, fluoxetine, tranylcypromine and venlafaxine on saphenous vein grafts

Abstract Objective: In this study, we aimed to examine the effects of amitriptyline, fluoxetine, tranylcypromine and venlafaxine on saphenous vein grafts in coronary artery bypass graft surgeries. Methods: 59 patients (40 males and 19 females; mean age 65.1 years, distribution: 45-84 years) who had coronary artery bypass graft surgery between February 2014 and May 2016 were included in the study. After the saphenous vein grafts with intact and denuded endothelium were precontracted with 3×10-6M phenylephrine, amitriptyline, fluoxetine and tranylcypromine were cumulatively added to isolated organ baths in the range of 10-11-3x10-5M, while venlafaxine was added in the range of 10-9-3×10-5M. Then, the antidepressant-induced relaxation responses were recorded isometrically. Results: While the relaxation response of amitriptyline at -6.42 (Log M) was 74.6%, the response at -6.32 (Log M) was 75.5%. While the relaxation response at -6.46 (Log M) of fluoxetine was 68.02%, the response at -6.02 (Log M) was 72.12%. While the relaxation response of tranylcypromine at -7.53 (Log M) was 61.13%, the response at -7.23 (Log M) was 65.53%. While the relaxation response of venlafaxine at -6.21 (Log M) was 29.98%, the response at -5.90 (Log M) was 32.96%. Conclusion: The maximum relaxation at minimum and maximum therapeutic concentrations was obtained with amitriptyline, fluoxetine and tranylcypromine, and the minimum relaxation was obtained with venlafaxine. The relaxation responses were independent of the endothelium.

Amitriptyline inhibits the MAPK/ERK and CREB pathways and proinflammatory cytokines through A3AR activation in rat neuropathic pain models / 대한마취과학회지

BACKGROUND: The pain-relief properties of tricyclic antidepressants can be attributed to several actions. Recent observations suggest that adenosine is involved in the antinociceptive effect of amitriptyline. The A3 adenosine receptor (A3AR) is the only adenosine subtype overexpressed in inflammatory and cancer cells. This study was performed to investigate the role of A3AR in the anti-nociceptive effect of amitriptyline. METHODS: Spinal nerve-ligated neuropathic pain was induced by ligating the L5 and L6 spinal nerves of male Sprague-Dawley rats. The neuropathic rats were randomly assigned to one of the following three groups (8 per group): a neuropathic pain with normal saline group, a neuropathic pain with amitriptyline group, and a neuropathic pain with amitriptyline and 3-ethyl-5-benzyl- 2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS) group. Amitriptyline or saline was administered intraperitoneally and 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS-1191), an A3AR antagonist, was injected subcutaneously immediately before amitriptyline administration. The level of extracellular signal-regulated kinase P44/42 (ERK1/2), cyclic AMP response element-binding protein (CREB), and proinflammatory cytokines were assessed using immunoblotting or reverse-transciption polymerase chain reaction. RESULTS: Amitriptyline increased the mechanical withdrawal threshold of the neuropathic rats. The level of phospho-ERK1/2 and phospho-CREB proteins, and proinflammatory cytokines produced by spinal nerve ligation were significantly reduced by amitriptyline administration. However, the use of MRS-1191 before amitriptyline administration not only reduced the threshold of mechanical allodynia, but also increased the signaling protein and proinflammatory cytokine levels, which were reduced by amitriptyline. CONCLUSIONS: The results of this study suggest that the anti-nociceptive effect of amitriptyline involves the suppression of ERK1/2 and CREB signaling proteins, and A3AR activation also affects the alleviation of the inflammatory response.

Pain management in children with erythromelalgia: case report / Tratamento da dor em criança com eritromelalgia: relato de caso

Abstract Erythromelalgia is a neuropathic pain syndrome due to an autosomal dominant gene, characterized by erythema, increased skin temperature and burning pain in hands and feet, whose treatment is often unsatisfactory. In this paper, we report a case of a 9 years old female patient whose first episode of burning pain, erythema and edema of the hands, without triggering factors, had instant relief after immersion in cold water. She presented with systemic arterial hypertension and had seizures. The patient was treated with gabapentin (150 mg.8 h−1) and amitriptyline (12.5 mg) orally, intravenous lidocaine infusion (120 mg), without relieving pain complaints. Due to the lack of response to the proposed treatment, it was decided to gradually reduce these medications and to introduce carbamazepine (200 mg) orally and, after 4 days of treatment, there was complete relief of the manifestations.

Resumo Eritromelalgia é uma síndrome dolorosa neuropática decorrente de gene autossômico dominante, caracterizada por eritema, aumento da temperatura da pele e dor em queimação, em mãos e pés, e o tratamento é muitas vezes insatisfatório. Neste caso, está o relato de uma paciente do sexo feminino, com nove anos e primeiro episódio de dor em queimação, eritema e edema em mãos, sem fatores desencadeantes, com alívio instantâneo após imersão em água fria. Apresentava hipertensão arterial sistêmica e teve crises convulsivas. Foi tratada com gabapentina (150 mg.8 h-1) e amitriptilina (12,5 mg) via oral, lidocaína (120 mg) venosa em infusão, sem alívio das queixas álgicas. Devido à ausência de resposta ao tratamento proposto, decidiu-se redução gradativa dessas medicações e introdução de carbamazepina (200 mg) via oral e após quatro dias de tratamento houve alívio completo das manifestações.

Amitriptyline and intraoral devices for migraine prevention: a randomized comparative trial / Amitriptilina e dispositivos intraorais para a prevenção da migrânea: estudo randomizado e comparativo

ABSTRACT Objectives: Nonpharmacological treatments, such as the Nociceptive Trigeminal Inhibition Tension Suppression System (NTI-tss), are approved for migraine prophylaxis. We aimed at evaluating the effectiveness of the NTI-tss and to compare its efficacy with amitriptyline and with a sham intraoral device in the preventive treatment of migraine. Methods: Consecutive patients with migraine were randomized to receive 25 mg of amitriptyline/day (n = 34), NTI-tss (n = 33) and a non-occlusal splint (n = 30). The headache frequency was evaluated at six and 12 weeks. Results: The amitriptyline group showed, respectively, 60% and 64% reduction in attack frequency at six and 12 weeks (P = 0.000). In the NTI-tss and non-occlusal splint groups, reduction was 39% and 30%, respectively, at six weeks and 48% for both groups at 12 weeks. Conclusions: Amitriptyline proved superior to the NTI-tss and the non-occlusal splint. Despite its approval by the United States Food and Drug Administration, the NTI-tss was not superior to a sham device.

RESUMO Objetivo: Tratamentos não farmacológicos como o Nociceptive Trigeminal Inhibition Tension Suppression System (NTI-tss), são aprovados para a prevenção da migrânea. Avaliamos a eficácia do NTI-tss no tratamento preventivo da migrânea e comparamos sua eficácia com a de um medicamento tradicional (amitriptilina) e com um dispositivo intraoral que não interfere com a oclusão (placa palatina). Métodos: Pacientes consecutivos com migrânea foram randomizados e receberam 25mg de amitriptilina/dia (n = 34), NTI-tss (n = 33) ou placa palatina não oclusal (n = 30). A frequência da cefaleia foi comparada após seis e 12 semanas. Resultados: No grupo da amitriptilina houve redução de 60% em seis semanas e de 64% em 12 semanas (P = 0.000). Nos grupos do NTI-tss e da placa não oclusal a redução foi respectivamente de 39% e 30% após seis semanas, e de 48% para ambos em 12 semanas. Conclusões: Amitriptilina foi superior ao NTI-tss e à placa palatina no tratamento da migrânea sem aura. O NTI-tss obteve resultados similares aos da placa não oclusal.

Clinical manifestations of headache in children younger than 7 years / 소아과

PURPOSE: Headache is a common symptom during childhood. It is usually persistent and requires special care. This study aimed to identify the characteristics of headache in children < 7 years of age. METHODS: We reviewed 3 years of clinical files on children < 7 years of age with a chief complaint of headache. RESULTS: This study included 146 children (66 males, 80 females; mean age, 5.5±1.0 years). Mean symptom duration was 5.8±7.9 months. Attack durations were longer than 2 hours in 31 patients, shorter than 2 hours in 70 patients, and unchecked in 45 patients. Attack frequency was 15.1±10.6 times per month. Pain locations and characteristics were also variable. Mean pain severity score was 5.1±2.2 on the visual analog scale. Of 38 patients who underwent electroencephalography, 9 showed positive findings. Of 41 who underwent brain magnetic resonance imaging, 20 showed positive findings. The diagnoses were migraine (including probable migraine) in 34, tension-type headache in 5, and congenital malformations in 3. Medications were used in 29 patients: acetaminophen in 17, ibuprofen in 8, naproxen sodium in 1, and topiramate or amitriptyline in 3. CONCLUSION: In children aged < 7 years, headache has a relatively benign course, but detailed history taking is needed for more accurate diagnosis.