RESUMEN
RATIONALE: Muscarinic receptor activity in the basolateral amygdala (BLA) is known to be involved in plasticity mechanisms that underlie emotional learning. The BLA is involved in the Attenuation of Neophobia, an incidental taste learning task in which a novel taste becomes familiar and recognized as safe. OBJECTIVE: Here we assessed the role of muscarinic receptor activity in the BLA in incidental taste learning. METHODS: Young adult male Wistar rats were bilaterally implanted with cannulas aimed at BLA. After recovery, rats were randomly assigned to either vehicle or muscarinic antagonist group, for each experiment. We tested the effect of specific and non-specific muscarinic antagonists administered either 1) 20 min before novel taste presentation; 2) immediately after novel taste presentation; 3) immediately after retrieval (the second taste presentation on Day 5 -S2-) or immediately after the fifth taste presentation on Day 8 (S5). RESULTS: Non-specific muscarinic receptor antagonist scopolamine infused prior to novel taste, while not affecting novel taste preference, abolished AN, i.e., the increased preference observed in control animals on the second presentation. When administered after taste consumption, intra-BLA scopolamine not only prevented AN but caused a steep decrease in the taste preference on the second presentation. This scopolamine-induced taste avoidance was not dependent on taste novelty, nor did it generalize to another novel taste. Targeting putative postsynaptic muscarinic receptors with specific M1 or M3 antagonists appeared to produce a partial taste avoidance, while M2 antagonism had no effect. CONCLUSION: These data suggest that if a salient gustatory experience is followed by muscarinic receptors antagonism in the BLA, it will be strongly and persistently avoided in the future. The study also shows that scopolamine is not just an amnesic drug, and its cognitive effects may be highly dependent on the task and the structure involved.
Asunto(s)
Reacción de Prevención , Complejo Nuclear Basolateral , Antagonistas Muscarínicos , Ratas Wistar , Sacarina , Escopolamina , Gusto , Animales , Escopolamina/farmacología , Escopolamina/administración & dosificación , Masculino , Antagonistas Muscarínicos/farmacología , Antagonistas Muscarínicos/administración & dosificación , Complejo Nuclear Basolateral/efectos de los fármacos , Complejo Nuclear Basolateral/metabolismo , Reacción de Prevención/efectos de los fármacos , Ratas , Sacarina/administración & dosificación , Gusto/efectos de los fármacos , Receptores Muscarínicos/metabolismoRESUMEN
BACKGROUND: Several studies have demonstrated that ACh modulates the dopaminergic circuit in the nucleus accumbens, and its blockade appears to be associated with the inhibition of the reinforced effect or the increase in dopamine caused by cocaine use. The objective of this study was to evaluate the effect of biperiden (a muscarinic receptor antagonist with a relatively higher affinity for the M1 receptor) on crack/cocaine use relapse compared to a control group that received placebo. METHODS: This study is a double-blind, randomized, placebo-controlled clinical trial. The intervention group received 2 mg of biperiden, 3 times a day, for a period of 3 months. The control group received identical placebo capsules, at the same frequency and over the same period. All participants were followed for a period of six months. RESULTS: The sample comprised 128 people, with 61 in the control group and 67 in the biperiden group. Lower substance consumption was observed in the group that received biperiden treatment two (bT2 = -2.2 [-3.3; -1.0], p < 0.001) and six months (bT4 = -6, 2 [-8.6; -3.9], p < 0.001) after the beginning of the intervention. The biperiden group had a higher latency until a possible first day of consumption, in the same evaluation periods (bT2 = 0.26 [0.080; 0.44], p = 0.004; bT4 = 0.63 [0.32; 0.93], p < 0.001). CONCLUSIONS: Despite the major limitations of the present study, the group that received biperiden reduced the number of days of cocaine/crack use and showed an increase in the latency time for relapse. More studies are needed to confirm the utility of this approach.
Asunto(s)
Biperideno , Trastornos Relacionados con Cocaína , Cocaína Crack , Humanos , Biperideno/uso terapéutico , Biperideno/farmacología , Trastornos Relacionados con Cocaína/tratamiento farmacológico , Cocaína Crack/efectos adversos , Método Doble Ciego , Antagonistas Muscarínicos/farmacología , Antagonistas Muscarínicos/uso terapéutico , Receptor Muscarínico M1RESUMEN
Purpose: Chronic obstructive pulmonary disease (COPD) affects approximately 174 million people worldwide. The objective was to determine the trends of COPD medication use in a group of Colombian patients. Patients and Methods: This was a retrospective study on prescription patterns of bronchodilators and other medications used in COPD from a population database with follow-up at 12 and 24 months. Patients older than 18 years of age of any sex with a COPD diagnostic code between 2017 and 2019 were included. Sociodemographic variables, medications, treatment schedules for COPD, comorbidities, comedications, and the specialty of the prescriber were considered. Results: Data from 9476 people with COPD was evaluated. The mean age was 75.9 ± 10.7 years, 50.1% were male, and 86.8% were prescribed by a general practitioner. A total of 57.9% had comorbidities, most often hypertension (44.4%). At the baseline measurement, on average, they received 1.6 medications/patient, mainly short-acting antimuscarinics (3784; 39.9%), followed by short-acting ß-agonists (2997, 31.6%) and inhaled corticosteroids (ICS) (2239, 23.6%); more than half (5083, 53.6%) received a long-acting bronchodilator. Prescription of triple therapy (antimuscarinic, ß-agonist, and ICS) went from 645 (6.8%) at baseline to 1388 (20.6%) at the 12-month mark. Conclusion: This group of patients with COPD treated in Colombia frequently received short-acting bronchodilators and ICS, but a growing proportion are undergoing controlled therapy with long-acting bronchodilators, a situation that can improve the indicators of morbidity, exacerbations, and hospitalization.
Asunto(s)
Broncodilatadores , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Masculino , Anciano , Anciano de 80 o más Años , Femenino , Broncodilatadores/efectos adversos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Colombia/epidemiología , Estudios Retrospectivos , Agonistas de Receptores Adrenérgicos beta 2/efectos adversos , Administración por Inhalación , Antagonistas Muscarínicos/efectos adversos , Corticoesteroides/efectos adversos , Quimioterapia CombinadaRESUMEN
bladder based on a systematic review and network meta-analysis approach. METHODS: Pubmed, Embase, Web of Science, and the Cochrane Register of Clinical Trials databases were systematically searched. The search time frame was from database creation to June 2, 2022. Randomized controlled double-blind trials of oral medication for overactive bladder were screened against the protocol's entry criteria. Trials were evaluated for quality using the Cochrane Risk of Bias Assessment Tool, and data were statistically analyzed using Stata 16.0 software. RESULT: A total of 60 randomized controlled double-blind clinical trials were included involving 50,333 subjects. Solifenacin 10mg was the most effective in mean daily micturitions and incontinence episodes, solifenacin 5/10mg in mean daily urinary urgency episodes and nocturia episodes, fesoterodine 8mg in urgency incontinence episodes/d and oxybutynin 5mg in voided volume/micturition. In terms of safety, solifenacin 5mg, ER-tolterodine 4mg, mirabegron, vibegron and ER-oxybutynin 10mg all showed a better incidence of dry mouth, fesoterodine 4mg, ER-oxybutynin 10mg, tolterodine 2mg, and vibegron in the incidence of constipation. Compared to placebo, imidafenacin 0.1mg showed a significantly increased incidence in hypertension, solifenacin 10mg in urinary tract infection, fesoterodine 4/8mg and darifenacin 15mg in headache. CONCLUSION: Solifenacin showed better efficacy. For safety, most anticholinergic drugs were more likely to cause dry mouth and constipation, lower doses were better tolerated. The choice of drugs should be tailored to the patient's specific situation to find the best balance between efficacy and safety.
Asunto(s)
Vejiga Urinaria Hiperactiva , Xerostomía , Humanos , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Succinato de Solifenacina/efectos adversos , Tartrato de Tolterodina/uso terapéutico , Metaanálisis en Red , Método Doble Ciego , Estreñimiento/tratamiento farmacológico , Xerostomía/tratamiento farmacológico , Resultado del Tratamiento , Antagonistas Muscarínicos/efectos adversos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVE: To compare the use of mirabegron with anticholinergics drugs for the treatment of overactive bladder (OB). DATA SOURCE: Systematic searches were conducted in EMBASE, PUBMED, Cochrane, and LILACS databases from inception to September 2021. We included RCTs, women with clinically proven OB symptoms, studies that compared mirabegron to antimuscarinic drugs, and that evaluated the efficacy, safety or adherence. DATA COLLECTION: RevMan 5.4 was used to combine results across studies. We derived risk ratios (RRs) and mean differences with 95% CIs using a random-effects meta-analytic model. Cochrane Collaboration Tool and GRADE was applied for risk of bias and quality of the evidence. DATA SYNTHESIS: We included 14 studies with a total of 10,774 patients. Fewer total adverse events was reported in mirabegron group than in antimuscarinics group [RR 0.93 (0.89-0.98)]. The risk of gastrointestinal tract disorders and dry mouth were lower with mirabegron [RR 0,58 (0.48-0.68); 9375 patients; RR 0.44 (0.35-0.56), 9375 patients, respectively]. No difference was reported between mirabegron and antimuscarinics drugs for efficacy. The adherence to treatment was 87.7% in both groups [RR 0.99 (0.98-1.00)]. CONCLUSION: Mirabegron and antimuscarinics have comparable efficacy and adherence rates; however, mirabegron showed fewer total and isolated adverse events.
OBJETIVO: Comparar o uso de mirabegrom com anticolinérgicos para o tratamento da bexiga hiperativa (BH). FONTE DE DADOS: Buscas sistemáticas foram realizadas nas bases de dados EMBASE, PUBMED, Cochrane e LILACS desde o início até setembro de 2021. Incluímos ECR, mulheres com sintomas de BH clinicamente comprovados, estudos que compararam mirabegrom a medicamentos antimuscarínicos e avaliaram a eficácia, segurança ou adesão. COLETA DE DADOS: RevMan 5.4 foi usado para combinar os resultados entre os estudos. Derivamos razões de risco (RRs) e diferenças médias com intervalo de confiança (IC) de 95% usando um modelo meta-analítico de efeitos aleatórios. Cochrane Collaboration Tool e GRADE foi aplicado para risco de viés e qualidade da evidência. SíNTESE DOS DADOS: Foram incluídos 14 estudos com um total de 10.774 pacientes. Menos eventos adversos totais foram relatados no grupo mirabegrom do que no grupo antimuscarínicos [RR: 0,93 (0,890,98)]. O risco de distúrbios do trato gastrointestinal e boca seca foram menores com mirabegrom [RR: 0,58 (0,480,68); 9.375 pacientes; RR: 0,44 (0,350,56), 9.375 pacientes, respectivamente]. Nenhuma diferença foi relatada entre mirabegrom e drogas antimuscarínicos para eficácia. A adesão ao tratamento foi de 87,7% em ambos os grupos [RR: 0,99 (0,981,00)]. CONCLUSãO: Mirabegrom e antimuscarínicos têm eficácia e taxas de adesão comparáveis, porém o mirabegrom apresentou menos eventos adversos totais e isolados.
Asunto(s)
Antagonistas Colinérgicos , Vejiga Urinaria Hiperactiva , Humanos , Femenino , Antagonistas Colinérgicos/uso terapéutico , Antagonistas Muscarínicos/uso terapéutico , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Vejiga Urinaria Hiperactiva/inducido químicamente , Acetanilidas/uso terapéutico , Resultado del TratamientoRESUMEN
Abstract Objective To compare the use of mirabegron with anticholinergics drugs for the treatment of overactive bladder (OB). Data Source Systematic searches were conducted in EMBASE, PUBMED, Cochrane, and LILACS databases from inception to September 2021. We included RCTs, women with clinically proven OB symptoms, studies that compared mirabegron to antimuscarinic drugs, and that evaluated the efficacy, safety or adherence. Data Collection RevMan 5.4 was used to combine results across studies. We derived risk ratios (RRs) and mean differences with 95% CIs using a random-effects meta-analytic model. Cochrane Collaboration Tool and GRADE was applied for risk of bias and quality of the evidence. Data Synthesis We included 14 studies with a total of 10,774 patients. Fewer total adverse events was reported in mirabegron group than in antimuscarinics group [RR 0.93 (0.89-0.98)]. The risk of gastrointestinal tract disorders and dry mouth were lower with mirabegron [RR 0,58 (0.48-0.68); 9375 patients; RR 0.44 (0.35-0.56), 9375 patients, respectively]. No difference was reported between mirabegron and antimuscarinics drugs for efficacy. The adherence to treatment was 87.7% in both groups [RR 0.99 (0.98-1.00)]. Conclusion Mirabegron and antimuscarinics have comparable efficacy and adherence rates; however, mirabegron showed fewer total and isolated adverse events.
Resumo Objetivo Comparar o uso de mirabegrom com anticolinérgicos para o tratamento da bexiga hiperativa (BH). Fonte de Dados Buscas sistemáticas foram realizadas nas bases de dados EMBASE, PUBMED, Cochrane e LILACS desde o início até setembro de 2021. Incluímos ECR, mulheres com sintomas de BH clinicamente comprovados, estudos que compararam mirabegrom a medicamentos antimuscarínicos e avaliaram a eficácia, segurança ou adesão. Coleta de Dados RevMan 5.4 foi usado para combinar os resultados entre os estudos. Derivamos razões de risco (RRs) e diferenças médias com intervalo de confiança (IC) de 95% usando um modelo meta-analítico de efeitos aleatórios. Cochrane Collaboration Tool e GRADE foi aplicado para risco de viés e qualidade da evidência. Síntese dos Dados Foram incluídos 14 estudos com um total de 10.774 pacientes. Menos eventos adversos totais foram relatados no grupo mirabegrom do que no grupo antimuscarínicos [RR: 0,93 (0,89-0,98)]. O risco de distúrbios do trato gastrointestinal e boca seca foram menores com mirabegrom [RR: 0,58 (0,48-0,68); 9.375 pacientes; RR: 0,44 (0,35-0,56), 9.375 pacientes, respectivamente]. Nenhuma diferença foi relatada entre mirabegrom e drogas antimuscarínicos para eficácia. A adesão ao tratamento foi de 87,7% em ambos os grupos [RR: 0,99 (0,98-1,00)]. Conclusão Mirabegrom e antimuscarínicos têm eficácia e taxas de adesão comparáveis, porém o mirabegrom apresentou menos eventos adversos totais e isolados.
Asunto(s)
Humanos , Antagonistas Muscarínicos , Vejiga Urinaria Hiperactiva/terapiaRESUMEN
INTRODUCTION: Hyoscine butyl bromide, better known as buscapine, widely used in medicine, is a muscarinic antagonist that shares properties with atropine. OBJECTIVE: To review the pharmacology, mechanism of action, systemic effects, interactions, toxicity, and side effects of hyoscine butyl bromide to understand why it may be useful in the management of perioperative bradycardia. MATERIALS AND METHODS: A bibliographic review was carried out in the main databases with the search of the scientific literature according to the key words defined. CONCLUSIONS: Butyl bromide hyoscine may be an option in the management of intraoperative bradyarrhythmias with a rapid onset of action, more controlled increased heart rate and low penetration to the central nervous system.
INTRODUCCIÓN: El butilbromuro de hioscina más conocido como buscapina, ampliamente utilizado en medicina, es un antagonista muscarínico que comparte propiedades con la atropina. OBJETIVO: Realizar una revisión de la farmacología, mecanismo de acción, efectos sistémicos, interacciones, toxicidad y efectos secundarios del butil bromuro de hioscina para poder entender por qué puede ser útil en el manejo de bradicardia perioperatoria. MATERIALES Y MÉTODOS: Se realizó una revisión bibliográfica en las principales bases de datos como PubMed, con la búsqueda de la literatura científica de acuerdo a las palabras claves definidas. CONCLUSIONES: El butil bromuro de hioscina puede ser una opción en el manejo de bradiarritmias intraoperatorias con un rápido inicio de acción, aumento de la frecuencia cardíaca más controlado y baja penetración al sistema nervioso central.
Asunto(s)
Humanos , Bradicardia/tratamiento farmacológico , Bromuro de Butilescopolamonio/uso terapéutico , Antagonistas Muscarínicos/uso terapéutico , Complicaciones Intraoperatorias/tratamiento farmacológico , Anestesia/métodos , Bromuro de Butilescopolamonio/efectos adversos , Bromuro de Butilescopolamonio/farmacología , Antagonistas Muscarínicos/efectos adversos , Antagonistas Muscarínicos/farmacologíaRESUMEN
Acetylcholine (ACh) may be involved in the regulation of ovarian functions. A previous systemic study in rats showed that a 4-week, intrabursal local delivery of the ACh-esterase blocker Huperzine-A increased intraovarian ACh levels and changed ovarian follicular development, as evidenced by increased healthy antral follicle numbers and corpora lutea, as well as enhanced fertility. To further characterize the ovarian cholinergic system in the rat, we studied whether innervation may contribute to intraovarian ACh. We explored the cellular distribution of three muscarinic receptors (MRs; M1, M3, and M5), analyzed the involvement of MRs in ovarian steroidogenesis, and examined their roles in ovarian follicular development in normal conditions and in animals exposed to stressful conditions by employing the muscarinic antagonist, atropine. Denervation studies decreased ovarian norepinephrine, but ovarian ACh was not affected, evidencing a local, nonneuronal source of ACh. M1 was located on granulosa cells (GCs), especially in large antral follicles. M5 was associated with the ovarian vascular system and only traces of M3 were found. Ex vivo ovary organo-typic incubations showed that the MR agonist Carbachol did not modify steroid production or expression of steroid biosynthetic enzymes. Intrabursal, in vivo application of atropine (an MR antagonist) for 4 weeks, however, increased atresia of the secondary follicles. The results support the existence of an intraovarian cholinergic system in the rat ovary, located mainly in follicular GCs, which is not involved in steroid production but rather via MRs exerts trophic functions and regulates follicular atresia.
Asunto(s)
Atresia Folicular , Ovario , Animales , Femenino , Ratas , Ovario/metabolismo , Receptores Muscarínicos/metabolismo , Acetilcolina/fisiología , Atropina/farmacología , Antagonistas Muscarínicos/farmacología , Esteroides/metabolismoRESUMEN
La difenhidramina tiene efectos antihistamínico anti-H1 específico y antimuscarínico que pueden ocasionar un desenlace fatal según la dosis total ingerida. Se reporta un caso de intoxicación por difenhidramina tratado de forma exitosa con emulsiones lipídicas a pesar de ingesta de dosis letal. Se presenta el caso de un paciente de 19 años que ingresó por intoxicación por difenhidramina a dosis de 25 mg/kg (1.5 g) después del tiempo de descontaminación, con toxidrome anticolinérgico, con neurotoxicidad, cardiotoxicidad (QRS y QT prolongados) y sin respuesta al enfoque inicial, se iniciaron emulsiones lipídicas y, a su vez, se logró alta temprana por evolución clínica favorable y resolución de la prolongación del intervalo QTc y del cuadro anticolinérgico. La emulsión lipídica es una opción terapéutica para disminuir la morbimortalidad y la estancia hospitalaria por contrarrestar la cardiotoxicidad y neurotoxicidad producidas por moléculas lipofílicas como la difenhidramina.
Diphenhydramine has specific anti-H1 antihistamine and antimuscarinic effects that can be fatal depending on the total dose ingested. A case of diphenhydramine poisoning successfully treated with lipid emulsions despite ingesting a lethal dose is presented. We present the case of a 19-year-old patient who was admitted for diphenhydramine intoxication at a dose of 25 mg/kg (1.5 g) after the decontamination time, with anticholinergic toxidrome, with neurotoxicity, cardiotoxicity (prolonged QRS and QT) and without response to initial approach. Lipid emulsions were started and, in turn, early discharge was achieved due to favorable clinical evolution and resolution of the prolongation of the QTc interval and the anticholinergic symptoms. Lipid emulsion is a therapeutic option to reduce morbidity and mortality and hospital stay by counteracting cardiotoxicity and neurotoxicity produced by lipophilic molecules such as diphenhydramine.
A difenidramina tem efeitos anti-histamínicos e antimuscarínicos anti-H1 específicos que podem ser fatais dependendo da dose total ingerida. Relata-se um caso de intoxicação por difenidramina tratada com sucesso com emulsões lipídicas apesar da ingestão de uma dose letal. Apresentamos o caso de uma paciente de 19 anos que foi internada por intoxicação por difenidramina na dose de 25 mg/kg (1,5 g) após o tempo de des-contaminação, com toxina anticolinérgica, neurotoxicidade, cardiotoxicidade (QS e QT prolongados) e sem resposta na abordagem inicial, iniciaram-se emulsões lipídicas e, por sua vez, obteve-se alta precoce devido à evolução clínica favorável e resolução do prolongamento do intervalo QTc e dos sintomas anticolinérgicos. A emulsão lipídica é uma opção terapêutica para reduzir a morbimortalidade e o tempo de internação por neutralizar a cardiotoxicidade e a neurotoxicidade produzidas por moléculas lipofílicas como a difenidramina.
Asunto(s)
Humanos , Difenhidramina , Intoxicación , Antagonistas Muscarínicos , Antagonistas Colinérgicos , Emulsiones , Antagonistas de los Receptores Histamínicos , LípidosRESUMEN
ABSTRACT Overactive bladder is a symptom complex consisting of bothersome storage urinary symptoms that is highly prevalent among both sexes and has a significant impact on quality of life. Various antimuscarinic agents and the beta-3 agonists mirabegron and vibegron are currently available for the treatment of OAB. Each drug has specific pharmacologic properties, dosing schedule and tolerability profile, making it essential to individualize the medical treatment for the patient's characteristics and expectations. In this manuscript, we review the most important factors involved in the contemporary pharmacological treatment of OAB.
Asunto(s)
Humanos , Masculino , Femenino , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Calidad de Vida , Resultado del Tratamiento , Antagonistas Muscarínicos/uso terapéutico , Agonistas de Receptores Adrenérgicos beta 3/uso terapéuticoRESUMEN
The spontaneous object recognition (SOR) task is one of the most widely used behavioral protocols to assess visual memory in animals. However, only recently was it shown that nonhuman primates also perform well on this task. Here we further characterized this new monkey recognition memory test by assessing the performance of adult marmosets after an acute systemic administration of two putative amnesic agents: the competitive muscarinic acetylcholine receptor antagonist scopolamine (SCP; 0.05 mg/kg) and the noncompetitive N-methyl-d-aspartate glutamate receptor antagonist MK-801 (0.015 mg/kg). We also determined whether the acetylcholinesterase inhibitor donepezil (DNP; 0.50 mg/kg), a clinically-used cognitive enhancer, reverses memory deficits caused by either drug. The subjects had an initial 10 min sample trial where two identical neutral objects could be explored. After a 6 h retention interval, recognition was based on an exploratory preference for a new rather than familiar object during a 10 min test trial. Both SCP and MK-801 impaired the marmosets' performance on the SOR task, as both objects were explored equivalently. Co-administration of 0.50 mg/kg of DNP reversed the SCP- but not the MK-801-induced memory deficit. These results indicate that cholinergic and glutamatergic pathways mediate object recognition memory in the monkey SOR task.
Asunto(s)
Maleato de Dizocilpina/farmacología , Prueba de Campo Abierto/efectos de los fármacos , Reconocimiento en Psicología/efectos de los fármacos , Escopolamina/farmacología , Acetilcolinesterasa/metabolismo , Animales , Callithrix/metabolismo , Donepezilo/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Femenino , Haplorrinos/metabolismo , Masculino , Memoria/efectos de los fármacos , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/metabolismo , Antagonistas Muscarínicos/farmacología , Nootrópicos/farmacología , Receptores Muscarínicos/metabolismoRESUMEN
OBJECTIVES: Studies have identified correlations between the psychological characteristics of individuals with primary hyperhidrosis (HH), the degree of sweating, and the quality of life (QoL). This study aimed to evaluate the prevalence of anxiety and depression symptoms in patients with HH before and after oxybutynin treatment. METHODS: Data were collected from 81 patients. Palmar or axillary HH was the most frequent complaint (84.0%). All patients were evaluated before the medication was prescribed and after five weeks of treatment. The Beck Depression Inventory and Beck Anxiety Inventory were used to evaluate depression and anxiety. RESULTS: Improvement in HH occurred in 58 patients (71.6%), but there was no improvement in 23 patients (28.4%). The QoL before treatment in all patients was either "poor" or "very poor." Patients who experienced improvement in sweating rates also experienced a greater improvement in QoL than patients who did not experience improvement in sweating at the main site (87.9% vs. 34.7%) (p<0.001). A total of 19.7% of patients showed an improvement in their level of depression, and a total of 46.9% of patients exhibited improvements in their level of anxiety. A significant correlation was observed between sweating and anxiety (p=0.015). CONCLUSION: Patients with HH who experienced improvements in sweating immediately after treatment with oxybutynin exhibited small improvements in their levels of depression and significant improvements in their levels of anxiety and QoL.
Asunto(s)
Hiperhidrosis , Calidad de Vida , Ansiedad , Depresión/tratamiento farmacológico , Depresión/epidemiología , Humanos , Hiperhidrosis/tratamiento farmacológico , Ácidos Mandélicos , Antagonistas Muscarínicos , Sudoración , Resultado del TratamientoRESUMEN
Overactive bladder is a symptom complex consisting of bothersome storage urinary symptoms that is highly prevalent among both sexes and has a significant impact on quality of life. Various antimuscarinic agents and the beta-3 agonists mirabegron and vibegron are currently available for the treatment of OAB. Each drug has specific pharmacologic properties, dosing schedule and tolerability profile, making it essential to individualize the medical treatment for the patient's characteristics and expectations. In this manuscript, we review the most important factors involved in the contemporary pharmacological treatment of OAB.
Asunto(s)
Vejiga Urinaria Hiperactiva , Agonistas de Receptores Adrenérgicos beta 3/uso terapéutico , Femenino , Humanos , Masculino , Antagonistas Muscarínicos/uso terapéutico , Calidad de Vida , Resultado del Tratamiento , Vejiga Urinaria Hiperactiva/tratamiento farmacológicoRESUMEN
This study evaluated the most common toxic agents affecting domestic cats, the clinical signs of toxicity, and the therapeutic approaches for recovery. A survey on poisoning in cats was conducted among small animal veterinary practitioners from 2017 to 2018. Of the 748 completed questionnaires, 543 (72.6%) were evaluated. Pesticides and household cleaning supplies were the most common causes of poisoning in cats. The toxicant groups included pesticides and household cleaning supplies (organophosphates), human drugs (acetaminophen), plants/plant derivatives (lily), and veterinary drugs (tramadol). The major clinical signs for these four groups of toxicants were (1) acetaminophen poisoning, which caused oxidative erythrocyte damage; (2) muscarinic and nicotinic cholinergic syndrome, which resulted from organophosphate poisoning; (3) acute kidney injury, which resulted from intoxication of lily; and (4) serotonin syndrome, which resulted from tramadol toxicosis. Interventions for treating poisoning in cats were based on the clinical presentation of animals. In the present study, the significant toxins identified to be dangerous for cats were characterized using the obtained data in Brazil as well as the main associated clinical signs and therapy recommended by veterinarians.(AU)
Objetiva-se com este trabalho caracterizar os principais toxicantes para gatos domésticos, bem como os prevalentes sinais clínicos e a terapêutica associada. Uma pesquisa sobre envenenamento em gatos foi realizada entre médicos veterinários no período de 2017 a 2018. Dos 748 questionários preenchidos, 543 (72,6%) foram avaliados. Pesticidas e domissanitários foram os principais causadores de intoxicação em gatos. Entre os grupos tóxicos, destacaram-se, na categoria pesticidas e domissanitários (organofosforados), medicamentos humanos (acetaminofeno), plantas e derivados de planta (lírio) e medicamentos veterinários (tramadol). Os principais sinais clínicos para os quatro grupos de substâncias tóxicas foram: (1) intoxicação por acetaminofeno, que causou dano eritrocitário oxidativo; (2) síndrome colinérgica muscarínica e nicotínica, resultante do envenenamento por organofosforado; (3) lesão renal aguda, causada pela intoxicação por lírio; e (4) síndrome serotoninérgica, resultante da exposição ao tramadol. As intervenções realizadas para o tratamento dos envenenamentos foram justificáveis mediante a apresentação clínica dos animais. Por meio dos dados obtidos, puderam-se caracterizar os principais tóxicos para gatos no Brasil, bem como os principais sinais clínicos associados e a terapêutica preconizada pelos médicos veterinários.(AU)
Asunto(s)
Animales , Gatos , Compuestos Organofosforados/toxicidad , Intoxicación/etiología , Intoxicación/veterinaria , Tramadol/toxicidad , Lilium/toxicidad , Acetaminofén/toxicidad , Serotoninérgicos/toxicidad , Estrés Oxidativo , Antagonistas Muscarínicos/toxicidad , Lesión Renal Aguda/inducido químicamenteRESUMEN
Over the years, experimental and clinical evidence has given support to the idea that acetylcholine (Ach) plays an essential role in mnemonic phenomena. On the other hand, the Hippocampus is already known to have a key role in learning and memory. What is yet unclear is how the Ach receptors may contribute to this brain region role during memory retrieval. The Ach receptors are divided into two broad subtypes: the ionotropic nicotinic acetylcholine receptors and the metabotropic muscarinic acetylcholine receptors. Back in 2010, we demonstrated for the first time the critical role of hippocampal α7 nicotinic acetylcholine receptors in memory reconsolidation process of an inhibitory avoidance response in mice. In the present work, we further investigate the possible implication of hippocampal muscarinic Ach receptors (mAchRs) in this process using a pharmacological approach. By specifically administrating agonists and antagonists of the different mAchRs subtypes in the hippocampus, we found that M1 and M2 but not M3 subtype may be involved in memory reconsolidation processes in mice.
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Hipocampo/fisiología , Consolidación de la Memoria/fisiología , Receptores Muscarínicos/fisiología , Animales , Reacción de Prevención/efectos de los fármacos , Reacción de Prevención/fisiología , Hipocampo/efectos de los fármacos , Masculino , Consolidación de la Memoria/efectos de los fármacos , Ratones , Agonistas Muscarínicos/farmacología , Antagonistas Muscarínicos/farmacología , Oxotremorina/análogos & derivados , Oxotremorina/farmacología , Pirenzepina/farmacología , Receptores Muscarínicos/efectos de los fármacos , Escopolamina/farmacología , Succinato de Solifenacina/farmacologíaRESUMEN
Atropine is an antimuscarinic alkaloid identified in Atropa belladonna. In pharmacopeias, percolation is standardized as an extraction method for A. belladonna leaves, along with liquid-liquid extraction as a cleanup procedure and titration as an analytical method for assaying the atropine in the leaves. In this study, a faster, solvent-saving, and more reliable method for quality control of A. belladonna samples was developed. Ultrasound-assisted extraction was proposed and optimized by fractional factorial design followed by Box-Behnken design. For modeling atropine content, the following optimal conditions were established: particle size, 180 µm; percentage methanol in water, 50%; volume of solvent, 15 ml; time of extraction, 60 min; and number of extractions, two. This led to a significant improvement in atropine extraction (P < 0.001). For cleanup, solid-phase extraction was used as an alternative to liquid-liquid extraction, giving similar results, with higher reproducibility. Finally, for the atropine assay, a UPLC method was validated as a substitute for the classic titration method. Taken together, the development of an ultrasound-assisted extraction-solid-phase extraction-UPLC approach allowed the determination of atropine content in A. belladonna leaves in a time- and solvent-saving manner, with high reliability.
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Atropa belladonna/química , Atropina/análisis , Cromatografía Líquida de Alta Presión/métodos , Extractos Vegetales/química , Hojas de la Planta/química , Extracción en Fase Sólida/métodos , Antagonistas Muscarínicos/análisis , Solventes/químicaRESUMEN
The sense of taste provides information regarding the nutrient content, safety or potential toxicity of an edible. This is accomplished via a combination of innate and learned taste preferences. In conditioned taste aversion (CTA), rats learn to avoid ingesting a taste that has previously been paired with gastric malaise. Recent evidence points to a role of cholinergic muscarinic signaling in the amygdala for the learning and storage of emotional memories. The present study tested the participation of muscarinic receptors in the amygdala during the formation of CTA by infusing the non-specific antagonist scopolamine into the basolateral or central subnuclei before or after conditioning, as well as before retrieval. Our data show that regardless of the site of infusion, pre-conditioning administration of scopolamine impaired CTA acquisition whereas post-conditioning infusion did not affect its storage. Also, infusions into the basolateral but not in the central amygdala before retrieval test partially reduced the expression of CTA. Our results indicate that muscarinic receptors activity is required for acquisition but not consolidation of CTA. In addition, our data add to recent evidence pointing to a role of cholinergic signaling in peri-hippocampal structures in the process of memory retrieval.
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Amígdala del Cerebelo/fisiología , Reacción de Prevención/fisiología , Receptores Muscarínicos/fisiología , Transducción de Señal/fisiología , Gusto/fisiología , Amígdala del Cerebelo/efectos de los fármacos , Animales , Reacción de Prevención/efectos de los fármacos , Emociones , Masculino , Consolidación de la Memoria/efectos de los fármacos , Recuerdo Mental/efectos de los fármacos , Microinyecciones , Antagonistas Muscarínicos/administración & dosificación , Antagonistas Muscarínicos/farmacología , Sistema Nervioso Parasimpático/efectos de los fármacos , Sistema Nervioso Parasimpático/fisiología , Ratas , Ratas Wistar , Receptores Muscarínicos/efectos de los fármacos , Escopolamina/administración & dosificación , Escopolamina/farmacología , Transducción de Señal/efectos de los fármacos , Gusto/efectos de los fármacosRESUMEN
BACKGROUND: Previous studies suggest that muscarinic cholinergic receptors might act upon the dopamine release in the mesolimbic system and alter drug-reinforcing values related to drug craving. AIMS: We examined the effects of systemic biperiden administration, a muscarinic cholinergic (M1/M4) receptor antagonist, on ethanol (dose of 2 g/Kg) conditioned place preference (CPP), neuronal activation, dopamine and its metabolites levels in the nucleus accumbens. METHODS: Thirty minutes before the ethanol-induced CPP test, mice received saline or biperiden at doses of 1.0, 5.0, or 10.0 mg/kg. The time spent in each compartment was recorded for 15 min. After the CPP protocol, animals were euthanized, and we investigated the activation of the nucleus accumbens by immunohistochemistry for Fos. We also quantified dopamine, homovanillic acid (HVA), and dihydroxyphenylacetic acid (DOPAC) levels in the nucleus accumbens by high-performance liquid chromatography (HPLC). Additionally, the rotarod was employed to evaluate the effects of biperiden on motor coordination. RESULTS: Biperiden at different doses (1.0, 5.0, and 10.0 mg/kg) blocked the expression of ethanol-induced CPP. These biperiden doses increased the number of Fos-positive cells and the dopamine turnover in the nucleus accumbens. None of the doses affected the motor coordination evaluated by the rotarod. CONCLUSIONS: Our results show that biperiden can modulate the effect of alcohol reward, and its mechanism of action may involve a change in dopamine and cholinergic mesolimbic neurotransmission.
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Biperideno/administración & dosificación , Condicionamiento Clásico/efectos de los fármacos , Etanol/administración & dosificación , Antagonistas Muscarínicos/administración & dosificación , Receptor Muscarínico M1/antagonistas & inhibidores , Receptor Muscarínico M4/antagonistas & inhibidores , Animales , Condicionamiento Clásico/fisiología , Dopamina/metabolismo , Relación Dosis-Respuesta a Droga , Ácido Homovanílico/metabolismo , Inyecciones Intraperitoneales , Masculino , Ratones , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/metabolismo , Receptor Muscarínico M1/metabolismo , Receptor Muscarínico M4/metabolismoRESUMEN
OBJECTIVES: Studies have identified correlations between the psychological characteristics of individuals with primary hyperhidrosis (HH), the degree of sweating, and the quality of life (QoL). This study aimed to evaluate the prevalence of anxiety and depression symptoms in patients with HH before and after oxybutynin treatment. METHODS: Data were collected from 81 patients. Palmar or axillary HH was the most frequent complaint (84.0%). All patients were evaluated before the medication was prescribed and after five weeks of treatment. The Beck Depression Inventory and Beck Anxiety Inventory were used to evaluate depression and anxiety. RESULTS: Improvement in HH occurred in 58 patients (71.6%), but there was no improvement in 23 patients (28.4%). The QoL before treatment in all patients was either "poor" or "very poor." Patients who experienced improvement in sweating rates also experienced a greater improvement in QoL than patients who did not experience improvement in sweating at the main site (87.9% vs. 34.7%) (p<0.001). A total of 19.7% of patients showed an improvement in their level of depression, and a total of 46.9% of patients exhibited improvements in their level of anxiety. A significant correlation was observed between sweating and anxiety (p=0.015). CONCLUSION: Patients with HH who experienced improvements in sweating immediately after treatment with oxybutynin exhibited small improvements in their levels of depression and significant improvements in their levels of anxiety and QoL.
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Humanos , Calidad de Vida , Hiperhidrosis/tratamiento farmacológico , Ansiedad , Sudoración , Resultado del Tratamiento , Antagonistas Muscarínicos , Depresión/tratamiento farmacológico , Depresión/epidemiología , Ácidos MandélicosRESUMEN
OBJECTIVES: The Brazilian public health system does not cover pharmacotherapy for urge urinary incontinence (UUI). The aim of this study was to estimate the cost-effectiveness and budget impact of providing tolterodine, solifenacin, oxybutynin (OXY), darifenacin, and mirabegron for the treatment of UUI in Brazilian public health system. METHODS: A cost-effectiveness analysis with budget impact was performed. Six scenarios were assessed: in one scenario, all 5 therapeutic alternatives approved for coverage, and in the remaining 5 scenarios, only 1 alternative is approved for adoption for all patients. Clinical data were derived from a rapid systematic review conducted in several databases. One-way sensitivity analysis was also performed. The time horizon was 12 months. RESULTS: The cost-effectiveness analysis showed that patients treated with OXY had the lowest incremental cost-effectiveness ratio (ICER) per outcomes assessed (change in urinary incontinence episodes (UIE): R$1180.08; change in urge incontinence episodes: R$757.85 and change in micturition frequency: R$907.75), corresponding to a budget impact of R$17.9 billion over 5 years. The change in effectiveness measures was the parameter that most influenced the results of the ICER per patient-year. CONCLUSION: The results of the study have shown that OXY and solifenacin had the lowest ICER per patient-year and the lowest budget impact when compared with other drugs.