Letter to the editor: Donepezil-induced parkinsonism in end-stage renal disease
Letter to the editor: Donepezil-induced parkinsonism in end-stage renal disease
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致编辑的信：终末期肾病中多奈哌齐诱发的帕金森病
DOI：
10.1007/s10072-021-05522-6
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发表时间：
2021
影响因子：
3.3
通讯作者：
Hsiu
中科院分区：
文献类型：
--
作者：
Hsin;L. Liou;Chung;Hsiu
讨论和结论据我们所知，这是第一份描述标准剂量多奈哌齐在终末期肾病患者中出现帕金森副作用的报告。尽管多奈哌齐是治疗 AD 的安全有效的药物，但临床研究中发现，多奈哌齐剂量为 10 mg/天时的不良事件发生率高于 5 mg/天时的不良事件发生率 [4]。我们的 ESRD 患者在多奈哌齐剂量增加至 10 毫克/天，持续 4 天后出现帕金森病。这些帕金森症状在停药后消失。临床过程强烈表明多奈哌齐与帕金森病之间存在直接因果关系。考虑到这一点，在 ESRD 患者中增加多奈哌齐剂量时应考虑副作用。证明多奈哌齐可诱发或加重帕金森病的病例报告有限[5-9]。根据刘等人的研究[7]和Arai等人[5]，在标准剂量的多奈哌齐（5毫克/天）下，痴呆患者与抗精神病药物（包括利培酮[7]和泰必利[5]）同时使用后，可能会突然出现帕金森病特征。布尔克等人。还报告称，多奈哌齐可能会加重患有帕金森病和痴呆症的患者的帕金森病症状，每天服用 5 毫克，持续 14 天[6]。奥诺弗吉等人。报道了一个案例，一名护理人员误解了多奈哌齐的治疗方案，并在 15 小时内给一名可能患有路易体痴呆 (DLB) 的患者服用了 5 剂 5 mg 多奈哌齐，该患者之前接受过常规左旋多巴和喹硫平治疗 [8]。注意到帕金森病急性恶化并伴有严重的弯曲皮炎，这些症状从停用多奈哌齐后第五天开始逐渐改善[8]。除了高剂量的多奈哌齐能够急性加重帕金森病症状之外，Rozzini 等人。强调长期使用高剂量多奈哌齐治疗也可能与 DLB 患者的帕金森症状相关[9]。这些报告表明，高剂量多奈哌齐诱发帕金森病的原因可能是药物的急性或慢性蓄积，这会干扰黑质纹状体区域的多巴胺能-胆碱能系统的平衡。表 1 提供了这些病例报告的比较。多奈哌齐是乙酰胆碱酯酶 (AChE) 的可逆胆碱酯酶抑制剂，可延迟乙酰胆碱的分解并增强大脑中的胆碱能传递。检测到了几种球状形式的 AChE，包括 G1 和 G4 亚型 [10]。在 AD 大脑中，特别是在皮质和基底神经节中，观察到 G4 形式的 AChE 水平降低，而 G1 形式的 AChE 水平升高或不变[11]。
Discussion and conclusionsTo the best of our knowledge, this is the first report to describe a parkinsonian side effect of donepezil with standard dosage in this end-stage renal disease patient. Although donepezil is a safe and effective drug in the management of AD, a higher rate of adverse events was noted in clinical studies when the donepezil dosage was 10 mg/day than when it was 5 mg/day [4]. Our patient with ESRD developed parkinsonism after the donepezil dosage was enhanced to 10 mg/day for 4 days. These parkinsonian symptoms disappeared after the drug was discontinued. The clinical course strongly suggests a direct causation between donepezil and parkinsonism. With this in mind, the adverse effect should be considered when the donepezil dosage is being titrated up in patients with ESRD. Case reports demonstrating that donepezil can induce or aggravate parkinsonism are limited [5–9]. According to Liu et al.[7] and Arai et al.[5], parkinsonian features could be noted abruptly after concomitant use with antipsychotics, including risperidone [7] and tiapride [5], in patients with dementia under a standard dosage of donepezil (5 mg/day). Bourke et al. also reported that donepezil could have worsened parkinsonian symptoms in a patient with Parkinson’s disease and dementia at a dose of 5 mg once per day for 14 days [6]. Onofrj et al. reported the case of a caregiver misunderstanding the regimen of donepezil and giving five doses of 5 mg of donepezil within 15 h to a patient with probable dementia with Lewy bodies (DLB) who had formerly received regular l-dopa and quetiapine treatment [8]. Acute worsening of parkinsonism with severe camptocormia was noted, and these symptoms were gradually improved from the fifth day after donepezil was discontinued [8]. In addition to the ability of a high dosage of donepezil to acutely aggravate parkinsonian symptoms, Rozzini et al. highlighted that long-term treatment with a high dosage of donepezil could also be associated with parkinsonian symptoms in patients with DLB [9]. These reports suggest that the reason for high doses of donepezil inducing parkinsonism might be acute or chronic accumulation of the drug, which would interfere with the balance of the dopaminergic–cholinergic system in the nigrostriatal area. A comparison of these case reports is provided in Table 1.Donepezil is a reversible cholinesterase inhibitor of acetylcholinesterase (AChE) that delays the breakdown of acetylcholine and enhances cholinergic transmission in the brain. Several globular forms of AChE, including the G1 and G4 isoforms, were detected [10]. A reduction level of the G4 form of AChE and an increased or unchanged level of the G1 form of AChE were observed in the AD brain, particularly in the cortex and basal ganglion [11].