Faculty of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, UK.
Division of Biomedical Sciences, St George's University of London, London, UK.
Aliment Pharmacol Ther. 2023 May;57(9):962-978. doi: 10.1111/apt.17466. Epub 2023 Mar 14.
Drugs which can inhibit nausea/vomiting and/or increase gastric emptying are used to treat gastroparesis, mostly 'off-label'. Within each category, they act at different targets and modulate different physiological mechanisms.
Address the questions: In gastroparesis, why should blocking one pathway causing vomiting, be more appropriate than another? Why might increasing gastric emptying via one mechanism be more appropriate than another?
Drugs used clinically were identified via consensus opinions and reviews, excluding the poorly characterised. Their pharmacology was defined, mapped to mechanisms influencing vomiting and gastric emptying, and rationale developed for therapeutic use.
Vomiting: Rationale for 5-HT , D , H or muscarinic antagonists, and mirtazapine, amitriptyline, nortriptyline, are poor. Arguments for inhibiting central consequences of vagal afferent transmission by NK antagonism are complicated by doubts over effects on nausea. Gastric emptying: Confusion emerges because of side-effects of drugs increasing gastric emptying: Metoclopramide (5-HT agonist, D and 5-HT antagonist; also blocks some emetic stimuli and causes tardive dyskinesia) and Erythromycin (high-efficacy motilin agonist, requiring low doses to minimise side-effects). Limited trials with selective 5-HT agonists indicate variable efficacy.
Several drug classes inhibiting vomiting have no scientific rationale. NK antagonism has rationale but complicated by limited efficacy against nausea. Studies must resolve variable efficacy of selective 5-HT agonists and apparent superiority over motilin agonists. Overall, lack of robust activity indicates a need for novel approaches targeting nausea (e.g., modulating gastric pacemaker or vagal activity, use of receptor agonists or new targets such as GDF15) and objective assessments of nausea.
用于治疗胃轻瘫的止吐和/或促进胃排空药物大多为“超适应证”使用。在每个类别中，它们作用于不同的靶点，调节不同的生理机制。
解决以下问题：在胃轻瘫中，为什么阻断引起呕吐的一条途径比另一条途径更合适？为什么通过一种机制增加胃排空比另一种机制更合适？
通过共识意见和综述确定临床上使用的药物，不包括特征描述较差的药物。定义其药理学，将其映射到影响呕吐和胃排空的机制，并为治疗用途制定合理的方案。
呕吐：5-HT、D、H 或毒蕈碱拮抗剂以及米氮平、阿米替林、去甲替林的作用机制不合理。通过 NK 拮抗作用抑制迷走传入神经的中枢后果的论点因对恶心的影响存在疑问而变得复杂。胃排空：由于增加胃排空的药物的副作用，出现了混淆：甲氧氯普胺（5-HT 激动剂、D 和 5-HT 拮抗剂；也可阻断一些催吐刺激物并引起迟发性运动障碍）和红霉素（高效能胃动素激动剂，需要低剂量以最大限度减少副作用）。选择性 5-HT 激动剂的有限试验表明其疗效不同。
抑制呕吐的几种药物类别没有科学依据。NK 拮抗作用有一定的依据，但因对恶心的疗效有限而变得复杂。必须进行研究以解决选择性 5-HT 激动剂的疗效差异和明显优于胃动素激动剂的问题。总的来说，缺乏稳健的活性表明需要针对恶心的新方法（例如，调节胃起搏或迷走神经活动、使用受体激动剂或新的靶点，如 GDF15）和对恶心的客观评估。
