LORAZEPAM AND ALPRAZOLAM: PERFORMANCE EFFECTS IN ELDERLY

由于它们的广泛使用，急性和慢性影响 苯二氮卓类药物对人体功能有相当大的实用价值 意义。对老年人(60岁至78岁)的影响包括 尤其令人担忧，因为这些人可能对某些 苯二氮类药物的不良中枢作用。此外，正常的 与年龄相关的认知功能下降可能会突出这一意义 药物引起的缺陷。 我们目前由NIMH赞助的研究发现，苯二氮卓类药物地西潘 具有较长的消除半衰期(t 1/2)，产生了深刻的记忆和 急性给药后精神运动障碍，第二天显著 老年人慢性睡前用药后的记忆损害 研究对象。此外，只有部分耐受性发展为急性不良反应。 慢性给药后的影响。虽然人们通常认为 消除半衰期较短的苯二氮卓类药物慢性治疗 (这导致药物积累减少)通常将与 由于对性能的负面影响数量较少，因此很少 这些药物对运动成绩影响的系统研究 老年人。此外，更少的研究包括非常 老年人，一个可能在一定程度上容易受到不利影响的群体 苯二氮卓类药物。拟议研究的目的是评估急性 阿普唑仑和劳拉西潘对任务绩效的慢性影响，两种 常用的苯二氮卓类药物，其t1/2s相对较短。更多 具体地说，这项研究旨在回答以下问题： 1.阿普唑仑和劳拉西潘对患者的急性和慢性影响是什么 老年人的任务表现如何？这两种药物在以下方面有区别吗？ 这些影响？ 2.在老年群体中，年龄的增加与年龄的增加有关 对任务绩效有负面影响吗？ 3.药物所致精神障碍的大小 损害和药物血浆浓度？

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?