Faculdade de Medicina da Universidade de São Paulo, Departamento de Gastroenterologia, São Paulo, SP, Brasil.
Faculdade de Medicina da Universidade do Estado do Rio Janeiro, Departamento de Gastroenterologia, Rio de Janeiro, RJ, Brasil.
Arq Gastroenterol. 2022 Apr-Jun;59(2):219-225. doi: 10.1590/S0004-2803.202202000-40.
Proton pump inhibitors (PPIs) are one of the most prescribed drugs in the world. Frequent use and long-term maintenance of these drugs drew the attention of researchers for sporadic adverse effects reports.
The purpose of this narrative review is to discuss appropriate data and causality related to these adverse events and PPIs.
A narrative review was conducted by systematizing information about safety and adverse events on PPIs from 2015 to 2020. A structured search on Pubmed was performed to identify systematic reviews and meta-analysis investigating the following situations: a) gastric cancer; b) micronutrients deficiency; c) acid rebound; d) infections; e) fractures; f) dementia; g) kidney disease; and h) sudden death and cardiovascular changes.
Recent studies have potentially associated PPIs with some adverse events as osteoporosis-related fractures. There are also reports of intestinal infections, including Clostridium difficile, besides poor vitamins absorption and minerals such as vitamin B12, magnesium, and iron. Furthermore, there are some dementia, pneumonia, kidney disease, myocardial infarction, and stroke reports. For kidney diseases, studies consistently suggest that the use of PPI may be associated with an increased risk of adverse kidney events, especially in the elderly, with long-term PPI use and pre-existing kidney disease. Another additional question is whether chronic PPI use would also lead to the onset of gastric cancer. The abrupt discontinuation of PPIs is also related to increased gastric acid production above pre-PPI treatment levels; this phenomenon is called acid rebound.
The key to mitigate adverse effects is the rational use of PPIs at the lowest effective dose and in the shortest possible duration. Although these adverse effects have a potential clinical impact, their causal association is still subject to validation.
质子泵抑制剂（PPIs）是世界上使用最广泛的药物之一。这些药物的频繁使用和长期维持引起了研究人员的注意，因为它们会导致偶发的不良反应报告。
本文旨在讨论与这些不良反应和质子泵抑制剂相关的适当数据和因果关系。
通过系统整理 2015 年至 2020 年关于质子泵抑制剂安全性和不良反应的信息，进行叙述性综述。在 Pubmed 上进行了结构化搜索，以确定调查以下情况的系统评价和荟萃分析：a）胃癌；b）微量营养素缺乏；c）酸反弹；d）感染；e）骨折；f）痴呆；g）肾病；h）猝死和心血管变化。
最近的研究可能将质子泵抑制剂与一些不良反应相关联，如骨质疏松性骨折。也有报道称肠道感染，包括艰难梭菌，以及维生素 B12、镁和铁等矿物质吸收不良。此外，还有一些痴呆、肺炎、肾病、心肌梗死和中风的报告。对于肾脏疾病，研究一致表明，质子泵抑制剂的使用可能与不良肾脏事件的风险增加相关，特别是在长期使用质子泵抑制剂和存在肾脏疾病的老年人中。另一个额外的问题是，慢性质子泵抑制剂的使用是否也会导致胃癌的发生。质子泵抑制剂突然停药会导致胃酸分泌增加，超过治疗前水平；这种现象称为酸反弹。
减轻不良反应的关键是在最低有效剂量和最短可能时间内合理使用质子泵抑制剂。尽管这些不良反应具有潜在的临床影响，但它们的因果关系仍有待验证。
