Central Nervous System Agents

中枢神经系统药剂
  • 文章类型: Journal Article
    本文对选定的药物组对牙科治疗结果和预后的影响提供了有价值的见解。这篇综述强调了全面病史的重要性,这可能会影响牙科治疗的预后。我们讨论作用于中枢神经系统的药物,胃肠道,呼吸道,内分泌系统,和骨骼代谢等。其他相关药物在本特刊的其他地方讨论。
    This article gives valuable insight into the effect of selected groups of medications on dental treatment outcome and prognosis. The review emphasizes the importance of thorough medical history, which may have an impact on the prognosis of dental treatment. We discuss drugs acting on the central nervous system, gastrointestinal tract, respiratory tract, endocrine system, and bone metabolism among others. Other pertinent drugs are discussed elsewhere in this special issue.
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  • 文章类型: Journal Article
    蓝斑神经变性后帕金森病(PD)的去甲肾上腺素能信号传导下降。流行病学研究表明,β作用药物可以减缓PD的进展。
    主要目的是比较3种β-肾上腺素受体(β-AR)作用药物在健康志愿者(HVs)中单剂量后对中枢神经系统(CNS)功能的安全性和作用,并评估多剂量β-AR作用药物在HVs和PD患者中的作用。
    在A部分中,HV接受单剂量32毫克沙丁胺醇,160μg克伦特罗,60毫克吲哚洛尔和安慰剂随机给药,4路交叉研究。在B部分(随机交叉)和C部分(平行,2:1随机),给予安慰剂和/或克伦特罗(第1天20μg,第2天40μg,第3-7天80μg)。使用NeuroCart测试电池评估CNS功能,包括瞳孔测量,自适应跟踪和召回测试。
    27例HV和12例PD患者完成了研究。克仑特罗改善,吲哚洛尔降低了自适应跟踪和即时言语回忆表现。克仑特罗和沙丁胺醇增加,吲哚洛尔降低了瞳孔与虹膜的比率。B部分和C部分选择克伦特罗。克伦特罗显着提高了自适应跟踪的性能,并倾向于改善即时和延迟口头回忆的性能。在C部分中,在PD患者中观察到了即时和延迟口头回忆表现改善的趋势。克仑特罗观察到典型的心血管外周β2-AR效应。
    这项研究证明了盐酸克伦特罗在PD患者中具有相似趋势的HVs中的促认知作用。作用机制可能是中枢神经系统中β2-ARs的激活。
    研究的目的和目的:本研究旨在探讨三种不同的药物如何影响脑功能。这些药物是沙丁胺醇,瘦肉精,和吲哚洛尔,并通过刺激特定的脑细胞在大脑中发挥作用,这些细胞可以改善记忆力和协调性等方面。主要的问题是看看这些药物有多安全,以及它们在健康人服用一剂后如何影响大脑功能,在健康人和帕金森病患者中多次服用后。研究背景:帕金森病是脑细胞开始死亡的一种疾病,影响大脑的不同区域,包括运动功能,以及记忆和注意力。这项研究很重要,因为找到影响大脑功能的药物可以改善帕金森病患者的生活。方法和研究设计:本研究分三个部分进行。在第一部分,健康志愿者服用三种药物中的每一种-沙丁胺醇,瘦肉精,和吲哚洛尔-以及安慰剂(一种没有效果的无害药丸)。研究人员使用各种任务测试参与者的大脑功能,包括记忆测试和眼睛反应测量。在第二和第三部分,健康的人和帕金森病患者服用了在健康志愿者中表现最好的药物7天。结果和重要性:在第一部分,单剂量的克伦特罗是安全的,并改善了健康人的记忆力和注意力任务,因此在第二和第三部分中选择了进一步的测试。在这些部分,多剂量克伦特罗是安全的,有助于改善健康人的记忆力和注意力任务,在帕金森病患者中也有类似的积极趋势。该研究表明,克伦特罗可能通过激活大脑中的特定受体来帮助改善大脑功能。这些结果很重要,因为它们表明克伦特罗可能是帮助改善帕金森病患者脑功能的潜在治疗方法。然而,需要更多的研究来充分了解其影响并确认这些发现。
    UNASSIGNED: Noradrenergic signaling declines in Parkinson\'s disease (PD) following locus coeruleus neurodegeneration. Epidemiologic studies demonstrate that β-acting drugs slow PD progression.
    UNASSIGNED: The primary objective was to compare the safety and effects of 3 β-adrenoceptor (β-AR) acting drugs on central nervous system (CNS) function after a single dose in healthy volunteers (HVs) and evaluate the effects of multiple doses of β-AR acting drugs in HVs and PD-patients.
    UNASSIGNED: In Part A, HVs received single doses of 32 mg salbutamol, 160μg clenbuterol, 60 mg pindolol and placebo administered in a randomized, 4-way cross-over study. In Part B (randomized cross-over) and Part C (parallel, 2:1 randomized), placebo and/or clenbuterol (20μg on Day 1, 40μg on Day 2, 80μg on Days 3-7) were administered. CNS functions were assessed using the NeuroCart test battery, including pupillometry, adaptive tracking and recall tests.
    UNASSIGNED: Twenty-seven HVs and 12 PD-patients completed the study. Clenbuterol improved and pindolol reduced the adaptive tracking and immediate verbal recall performance. Clenbuterol and salbutamol increased and pindolol decreased pupil-to-iris ratios. Clenbuterol was selected for Parts B and C. In Part B, clenbuterol significantly increased performance in adaptive tracking with a tendency toward improved performance in immediate and delayed verbal recall. In Part C trends toward improved performance in immediate and delayed verbal recall were observed in PD-patients. Typical cardiovascular peripheral β2-AR effects were observed with clenbuterol.
    UNASSIGNED: This study demonstrates the pro-cognitive effects of clenbuterol in HVs with similar trends in PD-patients. The mechanism of action is likely activation of β2-ARs in the CNS.
    Aims and Purpose of the Research:This research aimed to explore how three different drugs affect brain function. These drugs are salbutamol, clenbuterol, and pindolol and work in the brain by stimulating specific brain cells that can improve aspects like memory and coordination. The main question was to see how safe these drugs were and how they impact the brain function after one dose in healthy people, and after multiple doses in both healthy people and those with Parkinson’s disease.Background of the Research:Parkinson’s disease is a condition where brain cells start to die, which affects different areas of the brain, including movement function, as well as memory and attention. This research matters because finding drugs that affect the brain function could improve the lives of people with Parkinson’s disease.Methods and Research Design:The study was conducted in three parts. In the first part, healthy volunteers took one dose of each of the three drugs— salbutamol, clenbuterol, and pindolol— as well as a placebo (a harmless pill that has no effect). The researchers tested the participants’ brain functions using various tasks including memory tests and eye response measurements. In the second and third part, healthy people and people with Parkinson’s disease took the drug that performed best in healthy volunteers for seven days.Results and Importance:In the first part, a single dose of clenbuterol was safe and improved memory and attentions tasks in healthy people, and therefore was chosen for further testing in the second and third part. In these parts, multiple doses of clenbuterol were safe and helped improve memory and attention tasks in healthy people, with similar positive trends seen in people with Parkinson’s disease. The study suggests that clenbuterol might help improve brain function by activating specific receptors in the brain.These results are important because they suggest that clenbuterol could be a potential treatment to help improve brain function in people with Parkinson’s disease. However, more research is needed to fully understand its effects and to confirm these findings.
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  • 文章类型: Journal Article
    背景:辅助生活(AL)是痴呆症患者越来越普遍的居住环境;然而,由于AL的人员配备和服务水平较低,人们对该人群的次优护理存在担忧。我们的目标是(I)检查AL设置(痴呆症护理与其他),COVID-19大流行浪潮,和流行的抗精神病药,抗抑郁药,抗痴呆,苯二氮卓,和抗惊厥药物的使用在居民痴呆/认知障碍,(ii)探索居民和家庭特征与普遍药物使用之间的关联。
    方法:我们以人群为基础,使用关联的临床和健康管理数据库对艾伯塔省所有公共资助的AL家庭进行重复的横断面研究,加拿大,在2018年1月至2021年12月之间进行了检查。在每个环境和时期检查了分配研究药物的居民的季度比例(大流行与可比历史[2018/2019年合并])关注四个大流行浪潮(2020年3月-5月、2020年9月-2021年2月、2021年3月-5月、2021年9月-12月)。对数二项GEE模型估计的期间患病率比率(PR)(大流行与历史时期),设置(痴呆症护理与其他)和周期设定互动,调整为居民(年龄,性别)和家庭(COVID-19病例,卫生区域,所有权)特征。
    结果:2020年3月1日,有2,779名痴呆症患者和3,013名其他AL居民(平均年龄83岁,女性占69%)患有痴呆症/认知障碍。在两种情况下,抗精神病药的使用在第2-4波中增加,但在第3波和第4波期间,这在痴呆症护理中比其他AL更明显(例如,调整后的[调整]PR1.20,95%CI1.14-1.27与adjPR1.09,95%CI1.02-1.17,相互作用p=0.023,波3)。两种设置均显示出具有统计学意义但适度的抗抑郁药使用增加和苯二氮卓类药物使用减少。仅适用于痴呆症护理AL居民,在几波期间,加巴喷丁的使用在统计学上显着增加(例如,adjPR1.32,95%CI1.10-1.59,第3波)。在第2波中,除了两种情况下流行的抗痴呆药物的使用略有减少外,没有观察到其他明显的大流行效应。
    结论:大流行相关的抗精神病药和抗抑郁药在AL居民中的使用持续增加,再加上抗精神病药和加巴喷丁类药物在痴呆症护理环境中的使用增加,引起了对认知障碍居民随之而来的风险的担忧。
    BACKGROUND: Assisted living (AL) is an increasingly common residential setting for persons with dementia; yet concerns exist about sub-optimal care of this population in AL given its lower levels of staffing and services. Our objectives were to (i) examine associations between AL setting (dementia care vs. other), COVID-19 pandemic waves, and prevalent antipsychotic, antidepressant, anti-dementia, benzodiazepine, and anticonvulsant drug use among residents with dementia/cognitive impairment, and (ii) explore associations between resident and home characteristics and prevalent medication use.
    METHODS: We conducted a population-based, repeated cross-sectional study using linked clinical and health administrative databases for all publicly funded AL homes in Alberta, Canada, examined between January 2018 - December 2021. The quarterly proportion of residents dispensed a study medication was examined for each setting and period (pandemic vs. comparable historical [2018/2019 combined]) focusing on four pandemic waves (March-May 2020, September 2020-February 2021, March-May 2021, September-December 2021). Log-binomial GEE models estimated prevalence ratios (PR) for period (pandemic vs. historical periods), setting (dementia care vs. other) and period-setting interactions, adjusting for resident (age, sex) and home (COVID-19 cases, health region, ownership) characteristics.
    RESULTS: On March 1, 2020, there were 2,779 dementia care and 3,013 other AL residents (mean age 83, 69% female) with dementia/cognitive impairment. Antipsychotic use increased during waves 2-4 in both settings, but this was more pronounced in dementia care than other AL during waves 3 and 4 (e.g., adjusted [adj]PR 1.20, 95% CI 1.14-1.27 vs. adjPR 1.09, 95% CI 1.02-1.17, interaction p = 0.023, wave 3). Both settings showed a statistically significant but modest increase in antidepressant use and decrease in benzodiazepine use. For dementia care AL residents only, there was a statistically significant increase in gabapentinoid use during several waves (e.g., adjPR 1.32, 95% CI 1.10-1.59, wave 3). Other than a modest decrease in prevalent anti-dementia drug use for both settings in wave 2, no other significant pandemic effects were observed.
    CONCLUSIONS: The persistence of the pandemic-associated increase in antipsychotic and antidepressant use in AL residents coupled with a greater increase in antipsychotic and gabapentinoid use for dementia care settings raises concerns about the attendant risks for residents with cognitive impairment.
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  • 文章类型: Journal Article
    导致不良健康结果的高风险药物经常被处方给老年人。取消处方的干预措施减少了它们的使用,但研究的目的往往不是为了检查对患者相关健康结局的影响.
    为了测试针对老年人及其初级保健临床医生的医疗系统嵌入式处方干预措施的效果,以减少中枢神经系统活性药物的使用并防止药物治疗的跌倒。
    在这个随机分组中,平行组,临床试验,从2021年4月1日至2022年6月16日,从华盛顿州的综合医疗保健提供系统中招募了18个初级保健实践,以及他们符合条件的病人。随机化发生在临床水平。患者为60岁或以上的社区居住成年人,从5种靶向药物类别中的任何一种中开出至少1种药物(阿片类药物,镇静催眠药,骨骼肌松弛剂,三环抗抑郁药,和第一代抗组胺药)至少连续3个月。
    患者教育和临床医生决策支持。控制臂参与者接受常规护理。
    主要结果是药物治疗的跌倒。次要结果包括停药,持续停药,减少任何和每种目标药物的剂量。涉及阿片类药物或镇静催眠药的严重不良停药事件是主要的安全性结果。使用意向治疗分析进行分析。
    在2367名患者参与者中(平均[SD]年龄,70.6[7.6]岁;1488名妇女[63%]),干预组18个月时首次接受药物治疗的跌倒的校正累积发生率为0.33(95%CI,0.29-0.37),常规护理组为0.30(95%CI,0.27-0.34)(估计的校正风险比,1.11(95%CI,0.94-1.31)(P=.11)。干预组在停药方面存在显著差异,持续停药,并在6个月时减少三环抗抑郁药的剂量(停药调整率:干预组,0.23[95%CI,0.18-0.28]与常规护理组相比,0.13[95%CI,0.09-0.17];调整后相对风险,1.79[95%CI,1.29-2.50];P=.001)和次要时间点(9、12和15个月)。
    在这项针对社区居住的老年人的医疗系统嵌入处方干预的随机临床试验中,规定了中枢神经系统活性药物及其初级保健临床医生,在减少药物治疗的跌倒方面,干预没有比常规治疗更有效.对于将处方作为常规临床实践一部分的卫生系统,额外的干预措施可能会给处方带来适度的益处,而不会对临床结局产生可测量的影响.
    ClinicalTrials.gov标识符:NCT05689554。
    UNASSIGNED: High-risk medications that contribute to adverse health outcomes are frequently prescribed to older adults. Deprescribing interventions reduce their use, but studies are often not designed to examine effects on patient-relevant health outcomes.
    UNASSIGNED: To test the effect of a health system-embedded deprescribing intervention targeting older adults and their primary care clinicians for reducing the use of central nervous system-active drugs and preventing medically treated falls.
    UNASSIGNED: In this cluster randomized, parallel-group, clinical trial, 18 primary care practices from an integrated health care delivery system in Washington state were recruited from April 1, 2021, to June 16, 2022, to participate, along with their eligible patients. Randomization occurred at the clinic level. Patients were community-dwelling adults aged 60 years or older, prescribed at least 1 medication from any of 5 targeted medication classes (opioids, sedative-hypnotics, skeletal muscle relaxants, tricyclic antidepressants, and first-generation antihistamines) for at least 3 consecutive months.
    UNASSIGNED: Patient education and clinician decision support. Control arm participants received usual care.
    UNASSIGNED: The primary outcome was medically treated falls. Secondary outcomes included medication discontinuation, sustained medication discontinuation, and dose reduction of any and each target medication. Serious adverse drug withdrawal events involving opioids or sedative-hypnotics were the main safety outcome. Analyses were conducted using intent-to-treat analysis.
    UNASSIGNED: Among 2367 patient participants (mean [SD] age, 70.6 [7.6] years; 1488 women [63%]), the adjusted cumulative incidence rate of a first medically treated fall at 18 months was 0.33 (95% CI, 0.29-0.37) in the intervention group and 0.30 (95% CI, 0.27-0.34) in the usual care group (estimated adjusted hazard ratio, 1.11 (95% CI, 0.94-1.31) (P = .11). There were significant differences favoring the intervention group in discontinuation, sustained discontinuation, and dose reduction of tricyclic antidepressants at 6 months (discontinuation adjusted rate: intervention group, 0.23 [95% CI, 0.18-0.28] vs usual care group, 0.13 [95% CI, 0.09-0.17]; adjusted relative risk, 1.79 [95% CI, 1.29-2.50]; P = .001) and secondary time points (9, 12, and 15 months).
    UNASSIGNED: In this randomized clinical trial of a health system-embedded deprescribing intervention targeting community-dwelling older adults prescribed central nervous system-active medications and their primary care clinicians, the intervention was no more effective than usual care in reducing medically treated falls. For health systems that attend to deprescribing as part of routine clinical practice, additional interventions may confer modest benefits on prescribing without a measurable effect on clinical outcomes.
    UNASSIGNED: ClinicalTrials.gov Identifier: NCT05689554.
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  • 文章类型: Journal Article
    这项研究探讨了在患有阿尔茨海默病和相关痴呆症的Medicare死者中,临终关怀登记与中枢神经系统活性药物暴露相关的程度。
    This study explores the extent to which hospice enrollment is associated with CNS–active medication exposure among Medicare decedents with Alzheimer disease and related dementias.
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  • 文章类型: Journal Article
    母体中枢亲神经性药物暴露后新生儿发病率的评估。
    2018年至2021年CND后新生儿的回顾性单中心III级新生儿学队列分析。对照组在产科病房照顾没有CND的母亲所生的新生儿。
    CND新生儿需要更频繁的治疗[OR23(95%CI:7.8-62);RR14(95%CI:5.4-37);p<0.01]。CND后新生儿的Apgar评分较低,LM1[CND8.1;CG8.6;p<0.05];LM5[CND9;CG9.7;p<0.01];LM10[CND9.6;CG9.9;p<0.05]。24h内首发症状占95.35%(平均3.3h)。CND组显示早产明显更频繁[OR3.5;RR3.2;p<0.05],尤其是累积的多种症状[OR9.4;RR6.6;p<0.01],但与母亲多次用药无关(p=0.3)。
    暴露于CND的新生儿产后治疗的风险增加,通常是由于多种症状。应连续监测新生儿至少24小时。
    Evaluation of neonatal morbidity after maternal central neurotropic drug exposure.
    Retrospective single-center level-III neonatology cohort analysis of neonates after CND from 2018 to 2021. Control group of neonates born to mothers without CND cared for at the maternity ward.
    Significantly more frequent therapy need of neonates with CND [OR 23 (95% CI: 7.8-62); RR 14 (95% CI: 5.4-37); p < 0.01]. Neonates after CND had lower Apgar-scores LM 1 [CND 8.1; CG 8.6; p < 0.05]; LM 5 [CND 9; CG 9.7; p < 0.01]; LM 10 [CND 9.6; CG 9.9; p < 0.05]. The first symptom occurred in 95.35% within 24 h (mean: 3.3 h). CND group showed significantly more often preterm delivery [OR 3.5; RR 3.2; p < 0.05], and especially cumulative multiple symptoms [OR 9.4; RR 6.6; p < 0.01] but no correlation to multiple maternal medication use (p = 0.3).
    Neonates exposed to CND are at increased risk for postnatal therapy, often due to multiple symptoms. Neonates should be continuously monitored for at least 24 h.
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  • 文章类型: Journal Article
    背景:中枢神经系统(CNS)药物治疗与老年人的高发病率和高死亡率有关。住院治疗允许取消处方的机会。这项定性研究使用行为改变框架调查了临床医生和患者对住院期间中枢神经系统药物处方的看法。旨在告知干预措施并确定建议,以加强医院开处方流程。
    方法:这项定性研究的重点是住院医师,初级保健提供者,药剂师,和年龄≥60岁的患者在一般医学服务中住院,并开出了≥1种CNS药物。使用半结构化访谈和焦点小组,我们旨在评估患者的用药知识,以前的处方经验,和决策偏好,以及药物评估和取消处方的提供者流程和工具。应用能力的快速定性分析,机会,动机,和行为(COM-B)框架揭示了影响患者和提供者处方行为的主题。
    结果:共有52名参与者(20名患者和32名提供者)确定了去处方步骤的促进者和障碍,并提出了建议的策略来解决这些问题。临床医生和患者强调了住院期间中枢神经系统药物停用的机会,由多学科团队促进,提高临床医生改变药物的能力。两组还强调了强化患者参与的重要性,教育,以及住院期间的监测,承认开药的时间和程度方面的挑战,一些患者更愿意将决定推迟到门诊临床医生。医院和药剂师的建议集中在早期药剂师参与药物和解,扩大药学咨询和临床医生关于开处方的教育,而患者建议通过患者对药物不良反应的教育来加强共同决策,逐渐缩小的计划,和替代品。医院和PCP还强调标准化的出院指导和过渡护理呼吁,以改善护理过渡期间的药物审查和反馈。
    结论:临床医生和患者强调了医院干预中枢神经系统药物处方的潜在优势,强调解决沟通的必要性,教育,以及住院和门诊之间的协调挑战。
    BACKGROUND: Central nervous system (CNS) medications are linked to higher morbidity and mortality in older adults. Hospitalization allows for deprescribing opportunities. This qualitative study investigates clinician and patient perspectives on CNS medication deprescribing during hospitalization using a behavioral change framework, aiming to inform interventions and identify recommendations to enhance hospital deprescribing processes.
    METHODS: This qualitative study focused on hospitalists, primary care providers, pharmacists, and patients aged ≥60 years hospitalized on a general medicine service and prescribed ≥1 CNS medications. Using semi-structured interviews and focus groups, we aimed to evaluate patient medication knowledge, prior deprescribing experiences, and decision-making preferences, as well as provider processes and tools for medication evaluation and deprescribing. Rapid qualitative analysis applying the Capability, Opportunity, Motivation, and Behavior (COM-B) framework revealed themes influencing deprescribing behavior in patients and providers.
    RESULTS: A total of 52 participants (20 patients and 32 providers) identified facilitators and barriers across deprescribing steps and generated recommended strategies to address them. Clinicians and patients highlighted the opportunity for CNS medication deprescribing during hospitalizations, facilitated by multidisciplinary teams enhancing clinicians\' capability to make medication changes. Both groups also stressed the importance of intensive patient engagement, education, and monitoring during hospitalizations, acknowledging challenges in timing and extent of deprescribing, with some patients preferring decisions deferred to outpatient clinicians. Hospitalist and pharmacist recommendations centered on early pharmacist involvement for medication reconciliation, expanding pharmacy consultation and clinician education on deprescribing, whereas patients recommended enhancing shared decision-making through patient education on medication adverse effects, tapering plans, and alternatives. Hospitalists and PCPs also emphasized standardized discharge instructions and transitional care calls to improve medication review and feedback during care transitions.
    CONCLUSIONS: Clinicians and patients highlighted the potential advantages of hospital interventions for CNS medication deprescribing, emphasizing the necessity of addressing communication, education, and coordination challenges between inpatient and outpatient settings.
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  • 文章类型: Journal Article
    大多数药物尚未在老年人群中进行评估。认识到与药物处置变化和最终效果相关的生理变化,特别是在中枢神经系统作用的药物中,是根本的。在考虑药代动力学时,应该注意的是,大多数药物从胃肠道的吸收不会随着年龄的增长而改变。关于年龄对芬太尼等药物经皮吸收的影响只有很少的数据。在老年人中,肌肉注射的吸收可能与年轻患者相似。由于身体脂肪百分比的相对增加,亲脂性药物(例如地西泮)的分布增加,导致药物积累和停止后长期药物消除。I期药物生物转化在衰老过程中会不断减少,影响消除,在大多数研究的药物中,肝脏药物清除率已显示在老年人中降低10-40%。较低剂量的酚噻嗪,丁苯酮,非典型抗精神病药,抗抑郁药(西酞普兰,米氮平,和三环抗抑郁药),和苯二氮卓类药物(如地西泮)达到相同程度的暴露。对于没有先前代谢的肾清除药物(如加巴喷丁),肾小球滤过率可适当估计药物清除率.老年人的重要药效学变化包括苯二氮卓类药物在给定药物暴露时的镇静作用增加,和更高的敏感性μ阿片受体激动剂和阿片类药物的不良反应。人工智能,基于生理的药代动力学建模和模拟,和浓度效应模型能够区分衰老的药代动力学和药效学效应可能有助于缩小一些知识空白。
    Most drugs have not been evaluated in the older population. Recognizing physiological alterations associated with changes in drug disposition and with the ultimate effect, especially in central nervous system-acting drugs, is fundamental. While considering pharmacokinetics, it should be noted that the absorption of most drugs from the gastrointestinal tract does not change in advanced age. There are only few data about the effect of age on the transdermal absorption of medications such as fentanyl. Absorption from an intramuscular injection may be similar in older adults as in younger patients. The distribution of lipophilic drugs (such as diazepam) is increased owing to a relative increase in the percentage of body fat, causing drug accumulation and prolonged drug elimination following cessation. Phase I drug biotransformation is variably decreased in aging, impacting elimination, and hepatic drug clearance has been shown to decrease in older individuals by 10-40% for most drugs studied. Lower doses of phenothiazines, butyrophenones, atypical antipsychotics, antidepressants (citalopram, mirtazapine, and tricyclic antidepressants), and benzodiazepines (such as diazepam) achieve the same extent of exposure. For renally cleared drugs with no prior metabolism (such as gabapentin), the glomerular filtration rate appropriately estimates drug clearance. Important pharmacodynamic changes in older adults include an increased sedative effect of benzodiazepines at a given drug exposure, and a higher sensitivity to mu opiate receptor agonists and to opioid adverse effects. Artificial intelligence, physiologically based pharmacokinetic modeling and simulation, and concentration-effect modeling enabling a differentiation between the pharmacokinetic and the pharmacodynamic effects of aging might help to close some of the gaps in knowledge.
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