RESUMO
Urinary incontinence due to urethral sphincter mechanism incompetence (USMI) affects up to 20% of bitches that undergo spaying surgery. Amitriptyline is a tricyclic antidepressant whose urinary retention is a reported side effect. This study aimed to assess the efficacy and safety of amitriptyline when compared to estriol orally. Fifteen bitches with a clinical diagnosis of post-spaying UI were evaluated during 60 days in a non-blinded randomized clinical trial. All patients were enrolled after clinical evaluation consisting of anamnesis, physical examination, and complementary exams (complete blood count, biochemical parameters, urinalysis, and abdominal ultrasound). The amitriptyline (AMT) group consisted of 8 bitches, which received the initial dose of 1 mg/kg every 12 h, whereas the estriol (EST) group consisted of 7 bitches which were initially treated with 1 mg/animal every 24 h. Patients underwent clinical evaluation at 7 days, and then at 21 and 60 days of treatment to assess safety and efficacy, as well as adjustments of dose when necessary. A urinary incontinence scale was used to assess the level of incontinence and therapeutic response to treatment. During the period of the study, estriol was fully effective in 71% of cases and amitriptyline in 62%. Both drugs proved safe in the medical treatment of USMI, with adverse effects such as somnolence (AMT, n = 5/8) and male attraction (EST, n = 1/7). The results support the amitriptyline recommendation as a substitute for estriol in USMI treatment.
Assuntos
Doenças do Cão , Enurese , Incontinência Urinária , Feminino , Masculino , Animais , Cães , Amitriptilina/uso terapêutico , Ovariectomia/veterinária , Doenças do Cão/diagnóstico , Incontinência Urinária/tratamento farmacológico , Incontinência Urinária/veterinária , Incontinência Urinária/diagnóstico , Enurese/etiologia , Enurese/veterináriaRESUMO
There is a wealth of information on early pharmacological supportive treatment for early rehabilitation following acute ischemic stroke. This review aims to provide healthcare professionals involved in rehabilitating patients with a summary of the available evidence to assist with decision-making in their daily clinical practice. A search for randomized clinical trials and observational studies published between 1/1/2000 and 28/8/2022 was performed using PubMed, Cochrane and Epistemonikos as search engines with language restriction to english and spanish. The selected studies included patients older than 18 with acute ischemic stroke undergoing early rehabilitation. The outcomes considered for efficacy were: motor function, language, and central pain. The selected pharmacological interventions were: cerebrolysin, levodopa, selegiline, amphetamines, fluoxetine, citalopram, escitalopram, antipsychotics, memantine, pregabalin, amitriptyline and lamotrigine. Evidence synthesis and evaluation were performed using the GRADE methodology. This review provided a summary of the evidence on pharmacological supportive care in early rehabilitation of post-acute ischemic stroke patients. This will make it possible to improve current recommendations with the aim of collaborating with health decision-making for this population.
Existe una gran cantidad de información sobre el tratamiento de apoyo farmacológico temprano para la rehabilitación posterior a un accidente cerebrovascular isquémico agudo. El objetivo de esta revisión es ofrecer a los profesionales de la salud involucrados en la rehabilitación de los pacientes un resumen de la evidencia disponible que colabore con la toma de decisiones en su práctica clínica diaria. Se realizó una búsqueda de ensayos clínicos aleatorizados y estudios observacionales publicados entre el 1/1/2000 y el 28/8/2022 utilizando como motor de búsqueda PubMed, Cochrane y Epistemonikos con restricción de idioma a ingles y español. Los estudios seleccionados incluyeron pacientes mayores de 18 años con un accidente cerebrovascular isquémico agudo sometidos a rehabilitación temprana. Los desenlaces considerados para eficacia fueron: función motora, lenguaje y dolor. Las intervenciones farmacológicas seleccionadas fueron: cerebrolisina, levodopa, selegilina, anfetaminas, fluoxetina, citalopram, escitalopram, antipsicóticos, memantine, pregabalina, amitriptilina y lamotrigina. Se realizó síntesis y evaluación de la evidencia utilizando metodología GRADE. Esta revisión proporcionó un resumen de evidencia sobre el tratamiento de apoyo farmacológico en la neuro-rehabilitación temprana de pacientes post accidente cerebrovascular isquémico agudo. Esto permitirá mejorar las recomendaciones actuales con el objetivo de colaborar con la toma de decisiones en salud para esta población.
Assuntos
Antipsicóticos , AVC Isquêmico , Medicina , Humanos , Amitriptilina , CitalopramRESUMO
Beyond its actions on the nervous system, amitriptyline (AM) has been shown to lower inflammatory, angiogenic, and fibrogenic markers in a few pathological conditions in human and in experimental animal models. However, its effects on foreign body reaction (FBR), a complex adverse healing process, after biomedical material implantation are not known. We have evaluated the effects of AM on the angiogenic and fibrogenic components on a model of implant-induced FBR. Sponge disks were implanted subcutaneously in C57BL/6 mice, that were treated daily with oral administration of AM (5 mg/kg) for seven consecutive days in two protocols: treatment was started on the day of surgery and the implants were removed on the seventh day after implantation and treatment started 7 days after implantation and the implants removed 14 after implantation. None of the angiogenic (vessels, Vascular endothelial growth factor (VEGF), and interleukin-1ß (IL-1ß) or fibrogenic parameters (collagen, TGF-ß, and fibrous capsule) and giant cell numbers analyzed were attenuated by AM in 7-day-old implants. However, AM was able to downregulate angiogenesis and FBR in 14-day-old implants. The effects of AM described here expands its range of actions as a potential agent capable of attenuating fibroproliferative processes that may impair functionality of implantable devices.
Assuntos
Amitriptilina , Fator A de Crescimento do Endotélio Vascular , Camundongos , Animais , Humanos , Amitriptilina/farmacologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Camundongos Endogâmicos C57BL , Reação a Corpo Estranho/induzido quimicamente , Reação a Corpo Estranho/metabolismo , Reação a Corpo Estranho/patologia , Colágeno/metabolismoRESUMO
INTRODUCTION AND HYPOTHESIS: Women diagnosed with provoked vulvodynia frequently report a great deal of frustration in achieving symptomatic relief. Physical therapy and drug treatment are among the interventions most indicated by guidelines; however, whether those modalities are effective when combined remains unclear. The objective was to evaluate the effectiveness of adding a physical therapy modality compared with amitriptyline alone for the treatment of vulvodynia. METHODS: Eighty-six women with vulvodynia were randomized to (G1) 25 mg amitriptyline, once a day (n=27), (G2) amitriptyline + electrical stimulation therapy (n=29) or (G3) amitriptyline + kinesiotherapy (n=30). All treatment modalities were administered for 8 weeks. The primary endpoint was the reduction in vestibular pain. Secondary measurements focused on sexual pain, frequency of vaginal intercourse, Friedrich score, and overall sexual function. Data were analyzed using intention-to-treat. RESULTS: All treatment modalities resulted in a significant decrease in vestibular pain (p<0.001), sexual pain (p<0.05), Friedrich score (p<0.001), and an increase in the frequency of sexual intercourse (p<0.05). G3 was more effective than G1 at reducing sexual pain (G1: 5.3±3.3 vs G3: 3.2±2.7; p=0.01) and at improving sexual function (G1: 18.8±9.8 vs G3: 23.9±7.8; p=0.04). CONCLUSION: Kinesiotherapy and electrotherapy additions to amitriptyline administration as well as amitriptyline alone, were effective at improving vestibular pain in women with vulvodynia. Women receiving physical therapy had the greatest improvement in sexual function and frequency of intercourse at post-treatment and follow-up.
Assuntos
Vulvodinia , Feminino , Humanos , Vulvodinia/terapia , Amitriptilina/uso terapêutico , Medição da Dor , Dor , Estimulação ElétricaRESUMO
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.
Assuntos
Animais , Masculino , Ratos , Convulsões/induzido quimicamente , Consolidação da Memória/classificação , Amitriptilina/efeitos adversos , Pentilenotetrazol/agonistasRESUMO
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.
Assuntos
SARS-CoV-2 , COVID-19 , Antivirais , Cloroquina , Programas de Rastreamento , Fluoxetina , Amitriptilina , ImipraminaRESUMO
BACKGROUND: Rat isolated vas deferens releases 6-nitrodopamine (6-ND), and the spasmogenic activity of this novel catecholamine is significantly reduced by tricyclic compounds such as amitriptyline, desipramine, and carbamazepine and by antagonists of the α1 -adrenergic receptors such as doxazosin, tamsulosin, and prazosin. OBJECTIVES: To investigate the liberation of 6-ND by human epididymal vas deferens (HEVDs) and its pharmacological actions. METHODS: The in vitro liberation of 6-ND, dopamine, noradrenaline, and adrenaline from human vas deferens was evaluated by LC-MS/MS. The contractile effect of the catecholamines in HEVDs was investigated in vitro. The action of tricyclic antidepressants was evaluated on the spasmogenic activity ellicited by the catecholamines and by the electric-field stimulation (EFS). The tissue was also incubated with the inhibitor of nitric oxide (NO) synthase L-NAME and the release of catecholamines and the contractile response to EFS were assessed. RESULTS: 6-ND is the major catecholamine released from human vas deferens and its synthesis/release is inhibited by NO inhibition. The spasmogenic activity elicited by EFS in the human vas deferens was blocked by tricyclic antidepressants only at concentrations that selectively antagonize 6-ND induced contractions of the human vas deferens, without affecting the spasmogenic activity induced by dopamine, noradrenaline, and adrenaline in this tissue. Incubation of the vas deferens with L-NAME reduced both the 6-ND release and the contractions induced by EFS. DISCUSSION AND CONCLUSION: 6-ND should be considered a major endogenous modulator of human vas deferens contractility and possibly plays a pivotal role in the emission process of ejaculation. It offers a novel and shared mechanism of action for tricyclic antidepressants and α1 -adrenergic receptor antagonists.
Assuntos
Dopamina , Ducto Deferente , Antagonistas Adrenérgicos/farmacologia , Amitriptilina/farmacologia , Animais , Antidepressivos Tricíclicos/farmacologia , Carbamazepina/farmacologia , Cromatografia Líquida , Desipramina/farmacologia , Dopamina/análogos & derivados , Dopamina/farmacologia , Doxazossina/farmacologia , Epinefrina/farmacologia , Humanos , Masculino , Contração Muscular , Músculo Liso , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico , Norepinefrina/farmacologia , Prazosina/farmacologia , Ratos , Receptores Adrenérgicos , Tansulosina/farmacologia , Espectrometria de Massas em TandemRESUMO
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.
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.
Assuntos
Dor Crônica , Citalopram , Amitriptilina/uso terapêutico , Anticonvulsivantes/uso terapêutico , Antidepressivos/uso terapêutico , Antidepressivos Tricíclicos/uso terapêutico , Dor Crônica/tratamento farmacológico , Citalopram/uso terapêutico , Cloridrato de Duloxetina/uso terapêutico , Feminino , Gabapentina/uso terapêutico , Humanos , Imipramina/uso terapêutico , Norepinefrina/uso terapêutico , Nortriptilina/uso terapêutico , Dor Pélvica/tratamento farmacológico , Pregabalina/uso terapêutico , Serotonina/uso terapêutico , Sertralina/uso terapêutico , Cloridrato de Venlafaxina/uso terapêuticoRESUMO
Leishmaniases have a broad spectrum of clinical manifestations, ranging from a cutaneous to a progressive and fatal visceral disease. Chemotherapy is nowadays the almost exclusive way to fight the disease but limited by its scarce therapeutic arsenal, on its own compromised by adverse side effects and clinical resistance. Cyclobenzaprine (CBP), an FDA-approved oral muscle relaxant drug has previously demonstrated in vitro and in vivo activity against Leishmania sp., but its targets were not fully unveiled. This study aimed to define the role of energy metabolism as a target for the leishmanicidal mechanisms of CBP. Methodology to assess CBP leishmanicidal mechanism variation of intracellular ATP levels using living Leishmania transfected with a cytoplasmic luciferase. Induction of plasma membrane permeability by assessing depolarization with DiSBAC(2)3 and entrance of the vital dye SYTOX® Green. Mitochondrial depolarization by rhodamine 123 accumulation. Mapping target site within the respiratory chain by oxygen consumption rate. Reactive oxygen species (ROS) production using MitoSOX. Morphological changes by transmission electron microscopy. CBP caused on L. infantum promastigotes a decrease of intracellular ATP levels, with irreversible depolarization of plasma membrane, the collapse of the mitochondrial electrochemical potential, mild uncoupling of the respiratory chain, and ROS production, with ensuing intracellular Ca2+ imbalance and DNA fragmentation. Electron microscopy supported autophagic features but not a massive plasma membrane disruption. The severe and irreversible mitochondrial damage induced by CBP endorsed the bioenergetics metabolism as a relevant target within the lethal programme induced by CBP in Leishmania. This, together with the mild-side effects of this oral drug, endorses CBP as an appealing novel candidate as a leishmanicidal drug under a drug repurposing strategy.
Assuntos
Antiprotozoários , Leishmania infantum , Leishmaniose Visceral , Trifosfato de Adenosina/metabolismo , Amitriptilina/análogos & derivados , Animais , Antiprotozoários/metabolismo , Metabolismo Energético , Humanos , Leishmaniose Visceral/tratamento farmacológico , Camundongos , Camundongos Endogâmicos BALB C , Espécies Reativas de Oxigênio/metabolismoRESUMO
Background: Access to effective mental health services in low- and- middle income countries (LMICs) is limited, leading to a substantial global treatment gap. Amitriptyline, an anti-depressant, and diazepam, an anxiolytic drug, are classified as essential medications by the World Health Organization (WHO). They are the only psychotropic medications whose availability in health facilities is documented as part of Service Provision Assessment surveys. Our objective was to characterize the availability of these medicines in seven countries. Methods: We pooled nationally representative data from Service Provision Assessment surveys of health facilities conducted in Bangladesh, Democratic Republic of Congo (DRC), Haiti, Malawi, Nepal, Senegal, and Tanzania, from 2012 to 2018. We estimated the distribution and determinants of facility-level amitriptyline and diazepam availability in each country. Results: We analysed data from 7958 health facilities. An estimated 8.2% of facilities had amitriptyline and 46.1% had diazepam on the day of assessment. There was significant heterogeneity in both amitriptyline and diazepam availability across countries and within countries across facility characteristics. Multivariable models indicated that hospitals, faith-based and private-for-profit facilities, facilities with more staff, and facilities with more technological resources were more likely to have each medicine, relative to primary care facilities, public sector facilities, facilities with fewer staff, and facilities with fewer technological resources, respectively. Conclusion: Our results indicate limited availability of amitriptyline in health facilities in these seven LMICs. Diazepam is much more commonly available than amitriptyline. Efforts to narrow the global treatment gap for mental health - and especially to integrate mental health services into primary care in LMICs - will be limited without the availability of essential medicines like amitriptyline. Efforts to expand purchasing, distribution, and capacity-building in the appropriate use of essential mental health medicines in LMICs are warranted.