LORAZEPAM AND ALPRAZOLAM: PERFORMANCE EFFECTS IN ELDERLY

由于其广泛使用， 苯二氮卓类药物对人体的性能具有相当的实用价值 意义 对老年人（60至78岁）的影响如下： 特别令人担忧的是，这些人可能对某些 苯二氮卓类药物对中枢神经系统的不良影响 此外，正常 与年龄相关的认知功能下降可能会加重 药物引起的缺陷。 我们目前NIMH赞助的研究发现，地西泮，一种苯二氮卓类药物， 具有长的消除半衰期（t1/2），产生深刻的记忆， 急性给药后精神损害，第二天显著 老年人长期睡前服药后的记忆损害 科目 此外，只有部分耐受性发展到急性不利 长期服用后的效果。 虽然人们通常认为， 消除半衰期较短的苯二氮卓类药物长期治疗 （导致药物蓄积较少）通常与 对性能的不利影响较少， 系统研究这些药物对性能的影响， 老人 此外，还有更少的研究，其中包括非常 老年人，一个可能部分易受不良影响的群体 苯二氮卓类药物 这项研究的目的是评估急性 以及阿普唑仑和劳拉西泮对任务表现的慢性影响， 通常处方的苯二氮卓类药物，t1/2s相对较短。 更 具体而言，本研究旨在回答以下问题： 1.阿普唑仑和劳拉西泮的急性和慢性作用是什么？ 老年人的任务表现？ 这两种药物在以下方面是否不同 这些影响？ 2.在老年人群体中，年龄的增加是否与 对任务绩效的负面影响？ 3.药物诱导的程度与 损伤和药物血药浓度？

Because of their widespread use, the acute and chronic effects of benzodiazepines on human performance are of considerable practical significance. The effects on the elderly (aged 60 to 78 years) are of particular concern since these individuals may be more sensitive to some of the adverse central effects of benzodiazepines. Moreover, normal age-related decline in cognitive functions may accentuate the significance of drug-induced deficits. Our current NIMH-sponsored study has found that diazepam, a benzodiazepine with a long elimination half-life (t 1/2), produced profound memory and psychomotor impairment after acute administration, and significant next-day memory impairment following chronic bedtime administration in elderly subjects. Moreover, only partial tolerance developed to the acute adverse effects after chronic administration. While it is often assumed that chronic treatment with benzodiazepines with shorter elimination half-lives (which results in less drug accumulation) will, in general, be associated with a smaller number of adverse effects on performance, there are few systematic studies of the effects of these drugs on performance in the elderly. Additionally, there are even fewer studies which include the very elderly, a group which may be partially vulnerable to the adverse effects of benzodiazepines. The aim of the proposed study is to assess the acute and chronic effects on task performance of alprozolam and lorazepam, two commonly prescribed benzodiazepines with relatively short t 1/2s. More specifically, this study is designed to answer the following questions: 1. What are the acute and chronic effects of alprazolam and lorazepam on task performance in the elderly? Do the two drugs differ with respect to these effects? 2. Within the elderly group, is increasing age associated with increased adverse effects on task performance? 3. What is the relationship between the magnitude of drug-induced impairment and drug plasma concentration?