Katz I R, Sands L P, Bilker W, DiFilippo S, Boyce A, D'Angelo K
Section of Geriatric Psychiatry, University of Pennsylvania Philadelphia 19104, USA.
J Am Geriatr Soc. 1998 Jan;46(1):8-13. doi: 10.1111/j.1532-5415.1998.tb01006.x.
To evaluate the cognitive effects of acute challenges with the antispasmodic agent oxybutynin hydrochloride in normal older volunteers and to compare these effects with those attributable to diphenhydramine, another commonly used medication with anticholinergic (muscarinic-blocking) activity.
A double-blind, placebo-controlled cross-over study.
Laboratory evaluations of community subjects.
A convenience sample of 12 volunteers, average age 69.17 years.
Baseline assessment was followed by randomized administration of a placebo, oxybutynin hydrochloride (5 and 10 mg), and diphenhydramine hydrochloride (50 mg) in test sessions separated by 1 week.
Evaluation of cognitive performance with a 1-hour battery of pencil and paper, interviewer-administered, and computer-administered tests beginning 90 minutes after drug (or placebo) administration.
Random regression analyses demonstrated that oxybutynin caused significant cognitive decrements on seven of 15 cognitive measures, and diphenhydramine caused decrements on five measures. The most sensitive measures for detecting the effects of oxybutynin hydrochloride were the Buschke Selective Reminding Test and Reaction Time.
These findings demonstrate that oxybutynin can cause cognitive impairment and suggest that physicians prescribing it should monitor their patients to facilitate the early recognition of those who experience drug-related cognitive deficits. More generally, the findings demonstrate that systematic research with normal volunteers can identify cognitive toxicity not recognized during the process of drug development or postmarketing surveillance.
评估抗痉挛药物盐酸奥昔布宁急性激发试验对正常老年志愿者认知功能的影响，并将这些影响与另一种常用的具有抗胆碱能（毒蕈碱阻断）活性的药物苯海拉明的影响进行比较。
双盲、安慰剂对照交叉研究。
对社区受试者进行实验室评估。
12名志愿者的便利样本，平均年龄69.17岁。
在基线评估之后，在相隔1周的测试环节中随机给予安慰剂、盐酸奥昔布宁（5毫克和10毫克）和盐酸苯海拉明（50毫克）。
在药物（或安慰剂）给药90分钟后开始，通过为期1小时的一系列笔试、由面试官实施以及计算机实施的测试来评估认知表现。
随机回归分析表明，奥昔布宁在15项认知测量中的7项上导致了显著的认知功能减退，苯海拉明在5项测量上导致了减退。检测盐酸奥昔布宁效果最敏感的测量方法是布施克选择性提醒测试和反应时间。
这些发现表明奥昔布宁可导致认知障碍，并提示开具该药物的医生应监测患者，以便于早期识别那些出现与药物相关认知缺陷的患者。更普遍地说，这些发现表明，对正常志愿者进行的系统研究可以识别在药物开发或上市后监测过程中未被认识到的认知毒性。
