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[胃肠功能障碍对帕金森病患者血浆左旋多巴浓度具有重要影响]

[Gastrointestinal dysfunction has important implications for plasma L-dopa concentrations in Parkinson's disease].

作者信息

Doi Hirokazu, Sakakibara Ryuji, Kishi Masahiko, Tsuyuzaki Yohei, Tateno Fuyuki, Hirai Shigekazu

机构信息

Pharmaceutical unit, Toho university Sakura medical center.

出版信息

Rinsho Shinkeigaku. 2013;53(11):1382-5. doi: 10.5692/clinicalneurol.53.1382.

Abstract

Gastrointestinal motility dysfunctions including anorexia, nausea, heartburn, bloating, etc. are common and frequent complication of Parkinson's disease (PD). Degeneration of enteric nerves system is supposed to be a pathogenesis of these symptoms. Impairment of gastric emptying (GE) leads to retardation of the drug delivery from stomach to jejunum, so that PD patients with GE impairment show the delayed elevation of plasma L-dopa concentration. Disturbance of L-dopa absorption will result in wearing-off and delayed-on, and these are called motor fluctuation. In our investigation, 69% of PD patients who exhibited delayed elevation of plasma L-dopa concentration complicated GE impairment, whereas only 22% of patients with normal L-dopa level showed GE retardation (p = 0.0044, χ(2)-test). Serotonin 5-HT4 agonist and dopamine D2 antagonist are useful to improve GE impairment in PD. These drugs stimulate the postganglionic cholinergic fiber to release acetylcholine amongst the enteric nerves system and facilitate the gastrointestinal tract. Rikkunshi-to, dietary herbal medicine, is also administered to ameliorate gastrointestinal symptoms in PD. Rikkunshi-to is reported to improve erratic GE and reduce the variation of plasma L-dopa level. Recently, intestinal continuous L-dopa administration is expected as the potential solution for L-dopa induced motor fluctuation in advanced PD.

摘要

胃肠动力功能障碍,包括厌食、恶心、烧心、腹胀等,是帕金森病(PD)常见且频发的并发症。肠神经系统变性被认为是这些症状的发病机制。胃排空(GE)受损会导致药物从胃到空肠的输送延迟,因此GE受损的PD患者血浆左旋多巴浓度升高延迟。左旋多巴吸收障碍会导致药效减退和起效延迟,这些被称为运动波动。在我们的研究中,血浆左旋多巴浓度升高延迟的PD患者中有69%并发GE受损,而左旋多巴水平正常的患者中只有22%出现GE延迟(p = 分)。血清素5-HT4激动剂和多巴胺D2拮抗剂有助于改善PD患者的GE受损。这些药物刺激节后胆碱能纤维在肠神经系统中释放乙酰胆碱,促进胃肠道蠕动。理气剂,一种膳食草药,也被用于改善PD患者的胃肠道症状。据报道,理气剂可改善不稳定的GE并减少血浆左旋多巴水平的波动。最近,肠道持续给予左旋多巴有望成为晚期PD患者左旋多巴诱发运动波动的潜在解决方案。

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