Potentially Procholinergic Effects of Medications Commonly Used in Older Adults
Potentially Procholinergic Effects of Medications Commonly Used in Older Adults
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DOI：
10.1016/j.amjopharm.2011.02.003
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发表时间：
2011-02-01
期刊：
影响因子：
--
通讯作者：
Darvesh, Sultan
中科院分区：
文献类型：
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作者：
Rockwood, Kenneth;Walsh, Ryan;Darvesh, Sultan
背景：老年人易患多种疾病，其中许多疾病可以通过可能需要长期使用的药物治疗。人们对一些药物给予了相当的关注，这些药物除了具有预期的功能外，还可能具有抗胆碱能作用，从而导致不良的副作用，包括认知障碍。胆碱酯酶抑制剂被用作前胆碱能药物来改善阿尔茨海默病的认知功能障碍。我们假设，一些老年人常用的药物除了其预期功能外，还可能通过抑制胆碱酯酶而具有前胆碱能作用。目的：通过检测一些常用药物的胆碱酯酶抑制特性，确定其潜在的前胆碱能性质。方法：采用人乙酰胆碱酯酶和丁基胆碱酯酶的Ellman分光光度法，分别在无药和加药情况下测定。为了比较抑制效果，根据酶动力学数据，我们确定了每种药物对每种胆碱酯酶的一半最大抑制浓度（IC50值）。结果：在28种药物中，超过一半（17/28）抑制一种或两种人胆碱酯酶。抑制效力通常在目前用于治疗阿尔茨海默病的可逆胆碱酯酶抑制剂的1到2个数量级内。这些药物包括曲唑酮、喹硫平、利培酮、吲达帕胺和培哚普利。结论：许多老年人因其他原因使用的药物具有潜在的临床相关的前胆碱能作用。累积胆碱酯酶抑制的效果值得临床评价。(C) 2011 Elsevier HS Journals, Inc.；版权所有。
Background: Older adults are susceptible to a variety of illnesses, many of which can be treated with medications that may need to be used for the long term. Considerable attention has been paid to drugs that, in addition to their intended function, may have an anticholinergic effect that results in undesirable side effects, including impairment in cognition. Cholinesterase inhibitors are used as procholinergic drugs to improve cognitive dysfunction in Alzheimer's disease. We hypothesized that some of the drugs commonly used by older adults might, in addition to their intended function, also have procholinergic effects by virtue of inhibiting cholinesterases.Objective: To determine the potential procholinergic nature of some of the commonly used drugs by examining their cholinesterase inhibiting properties.Methods: The Ellman spectrophotometric method was used with human acetylcholinesterase and butyrylcholinesterase, in the absence and presence of increasing concentrations of each test drug. To compare inhibition potencies, from enzyme kinetic data, we determined half maximal inhibitory concentration (IC50 values) for each cholinesterase by each drug.Results: Of the 28 drugs examined, over half (17/28) inhibited one or both of the human cholinesterases. The inhibition potencies were often within 1 to 2 orders of magnitude of reversible cholinesterase inhibitors currently used to treat Alzheimer's disease. These included trazodone, quetiapine, risperidone, indapamide, and perindopril.Conclusions: Many drugs used by older adults for other reasons have potentially clinically relevant procholinergic effects. The effect of cumulative cholinesterase inhibition merits clinical evaluation. (Am J Geriatr Pbarmacother. 2011;9:80-87) (C) 2011 Elsevier HS Journals, Inc. All rights reserved.