RESUMO
INTRODUCTION: Benzodiazepine anxiolytics are believed to cause urination disorders due to their anticholinergic effects. OBJECTIVE: This study was carried out to investigate the potential inhibitory effects of 15 clinically available anxiolytics in Japan on acetylcholine (ACh)-induced contractions in rat detrusor smooth muscle (DSM) to predict whether these anxiolytics could induce urination disorders. METHODS: -Effects of anxiolytics on contractions induced by ACh and 80 mmol/L KCl solution in rat DSM and effects of anxiolytics on specific binding of [N-methyl-3H]scopolamine ([3H]NMS) in mouse cerebral cortex were investigated. RESULTS AND CONCLUSIONS: ACh-induced contractions in rat DSM were inhibited by clotiazepam and diazepam (benzodiazepine anxiolytics) at concentrations that were clinically relevant. These contractions were also significantly inhibited by paroxetine, escitalopram (selective serotonin reuptake inhibitors -[SSRIs]), and hydroxyzine (a histamine H1 receptor antagonist), albeit at concentrations that substantially exceeded clinically achievable blood levels. At a concentration of 10-5 mol/L, paroxetine, escitalopram, and hydroxyzine inhibited 80 mmol/L high-KCl solution-induced rat DSM contractions but not clotiazepam and diazepam. Paroxetine, escitalopram, and hydroxyzine also inhibited specific binding of [3H]NMS in mouse cerebral cortex but clotiazepam and diazepam did not. In contrast to the effects of the abovementioned anxiolytics, ACh-induced contractions were not significantly affected by tofisopam, alprazolam, lorazepam, bromazepam, oxazolam, chlordiazepoxide, clonazepam, ethyl loflazepate (benzodiazepine anxiolytics), fluvoxamine (an SSRI), or tandospirone (a serotonin 5-HT1A receptor agonist). These findings suggest that most clinically used anxiolytics are not likely to result in anticholinergic-induced urination disorders within their clinically achievable blood concentration ranges. However, clotiazepam and diazepam may induce urination disorders within their clinical dose ranges via nonanticholinergic inhibition of DSM contractility.
Assuntos
Acetilcolina/antagonistas & inibidores , Ansiolíticos/toxicidade , Benzodiazepinas/toxicidade , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Bexiga Urinária/efeitos dos fármacos , Animais , Masculino , Camundongos , Contração Muscular/fisiologia , Músculo Liso/fisiologia , Ratos , Ratos Wistar , Derivados da Escopolamina/metabolismo , Bexiga Urinária/fisiologia , Transtornos Urinários/induzido quimicamenteRESUMO
Antipsychotics are often the first-line treatment for behavioral and psychological symptoms of dementia. However, the potential anticholinergic effects of antipsychotics could counteract the therapeutic effects of cholinesterase inhibitors used to treat dementia. We investigated the inhibitory effects of 26 antipsychotics on [N-Methyl-3H]scopolamine specific binding in mouse cerebral cortex. At 10-5 M, chlorpromazine, levomepromazine, prochlorperazine, timiperone, zotepine, pimozide, blonanserin, olanzapine, quetiapine, and clozapine inhibited [N-Methyl-3H]scopolamine binding by > 45%. Furthermore, the pKi values of chlorpromazine, levomepromazine, zotepine, olanzapine, and clozapine overlapped with their clinically achievable blood concentrations. Therefore, the anticholinergic properties of these antipsychotics could attenuate the effects of cholinesterase inhibitors.
Assuntos
Antipsicóticos/metabolismo , Antipsicóticos/farmacologia , Córtex Cerebral/metabolismo , Antagonistas Colinérgicos/metabolismo , Inibidores da Colinesterase/metabolismo , Receptores Muscarínicos/metabolismo , Escopolamina/metabolismo , Animais , Clorpromazina/farmacologia , Depressão Química , Interações Medicamentosas , Masculino , Metotrimeprazina/farmacologia , Camundongos Endogâmicos , Proclorperazina/farmacologia , Ligação ProteicaRESUMO
Purpose: Although adolescent and young adult (AYA) cancer patients are digital natives and have high digital communication needs, previous studies of screening tools for AYAs have primarily used paper when measuring patient-reported outcomes (PROs). There are no reports on using an electronic PRO (ePRO) screening tool with AYAs. This study evaluated the feasibility of such a tool in clinical settings, and assessed the prevalence of AYAs' distress and supportive care needs. Methods: An ePRO tool based on the Distress Thermometer and Problem List (DTPL)-Japanese (DTPL-J) version for AYAs was implemented in a clinical setting for 3 months. To determine the prevalence of distress and need for supportive care, descriptive statistics were calculated for participant characteristics, selected items, and Distress Thermometer (DT) scores. Response rates, referral rates to an attending physician and other experts, and time required to complete PRO tools were assessed to evaluate feasibility. Results: From February to April 2022, 244 (93.8%) of 260 AYAs completed the ePRO tool based on the DTPL-J for AYAs. Based on a DT cutoff of ≥5, 65 of 244 patients (26.6%) had high distress. Worry (n = 81, 33.2%) was the most frequently selected item. Primary nurses referred 85 (32.7%) patients to an attending physician or other experts. The referral rate resulting from ePRO screening was significantly higher than that after PRO screening (χ2(1) = 17.99, p < 0.001). The average response time did not differ significantly between ePRO and PRO screening (p = 0.252). Conclusion: This study suggests the feasibility of an ePRO tool based on the DTPL-J for AYAs.
Assuntos
Detecção Precoce de Câncer , Neoplasias , Humanos , Adolescente , Adulto Jovem , Estudos de Viabilidade , Ansiedade , Medidas de Resultados Relatados pelo PacienteRESUMO
Cancer patients in adolescents and young adults (AYA) generation aged 15-39 years have various psychosocial needs during their treatment course such as school enrollment, finding employment, marriage, and fertility. It is difficult for medical professionals to gain experience related to providing medical care and consultation support to these kinds of AYA generation cancer patients. There is a need to provide information and establish both support and medical care systems that are able to meet the diverse needs unique to this generation. This review will explain how to launch an AYA support team (AST). We have worked and established the AST since 2016, which is medical care teams that provide support according to the life stage of each individual patient and build a multidisciplinary AYA generation patient support system. The team-building process consisted of two main projects: building and enlarging multidisciplinary team and establishing screening process of psychosocial needs of AYA generation patients. Multidisciplinary healthcare professionals got involved in the AST with already-existing patient support functions in our center: the patient support center, which is an outpatient department and the palliative care team, which is an inpatient interdepartmental team. The AST systematically finds patients in need of assistance and offers them support as a multidisciplinary team. The AST also established a procedure that systematically gathers information about the needs of patients by using a screening tool. In addition, the AST provides the following specialized services: reproductive medicine, supporting cancer patients with children, employment support, and peer support. The AST has been established and sophisticatedly worked. It can flexibly provide various psychosocial support services. This review will explain how to launch an AST.