Piper D W
University of Sydney, New South Wales, Australia.
Drug Saf. 1995 Feb;12(2):120-38. doi: 10.2165/00002018-199512020-00005.
During the past 2 decades, great advances have been made in the treatment of ulcer disease. This has involved the development of new drugs that are not only well tolerated, but are relatively inexpensive. The lack of significant adverse effects has revealed a degree of tolerability that, to write a review of the adverse effects, poses a difficult task. Most of the adverse effects are related to an excessive reaction to the relevant pharmacological characteristic that mediates the therapeutic response. The drug dosage can be reduced, freeing the patient of the adverse reaction, but leaving behind a background activity adequate to produce a therapeutically beneficial effect. The adverse effects of H2-antagonists fall into 2 groups. Firstly, there are poorly defined symptoms that have a prevalence similar to that in the community; these include headache, giddiness, dizziness, fatigue, constipation and diarrhoea. Secondly, they may delay the metabolism of drugs metabolised by the the cytochrome P450 system, and rarely be androgenic. Many antacids and the site-protective agent sucralfate contain aluminium, which can be absorbed, producing elevation of serum aluminium levels. In view of the possible association of aluminium with Alzheimer's disease, anxiety has arisen as to whether aluminium from these sources may, in those on prolonged treatment, cause Alzheimer's disease. However, the evidence so far indicates that aluminium is not a risk factor for Alzheimer's disease. The association of gastric cancer with achlorhydria has led to the fear that long term use of potent acid inhibitors may cause cancer. This fear has been accentuated by the observation that some rats, given omeprazole over their lifetime, developed carcinoid tumours of the stomach. However, enthusiastic research, both clinical and epidemiological, indicates that drug-induced achlorhydria is unlikely to be a problem in humans. Site protective agents have a role in certain conditions such as pregnancy where the systemic effect of a drug may produce adverse effects.
在过去20年里,溃疡病的治疗取得了巨大进展。这涉及到新药的研发,这些新药不仅耐受性良好,而且相对便宜。缺乏明显的不良反应显示出一定程度的耐受性,以至于撰写一篇关于不良反应的综述成为一项艰巨的任务。大多数不良反应与对介导治疗反应的相关药理学特性的过度反应有关。可以减少药物剂量,使患者摆脱不良反应,但仍保留足以产生治疗有益效果的背景活性。H2拮抗剂的不良反应分为两类。首先,有一些定义不明确的症状,其发生率与普通人群相似;这些症状包括头痛、眩晕、头晕、疲劳、便秘和腹泻。其次,它们可能会延迟由细胞色素P450系统代谢的药物的代谢,并且很少具有雄激素样作用。许多抗酸剂和黏膜保护剂硫糖铝含有铝,铝可以被吸收,导致血清铝水平升高。鉴于铝可能与阿尔茨海默病有关,人们担心这些来源的铝在长期治疗的患者中是否可能导致阿尔茨海默病。然而,迄今为止的证据表明铝不是阿尔茨海默病的危险因素。胃癌与胃酸缺乏的关联导致人们担心长期使用强效酸抑制剂可能会引发癌症。观察到一些终生服用奥美拉唑的大鼠发生了胃类癌肿瘤,这加剧了这种担忧。然而,临床和流行病学方面的积极研究表明,药物引起的胃酸缺乏在人类中不太可能成为问题。黏膜保护剂在某些情况下有作用,例如在怀孕期间,药物的全身作用可能会产生不良反应。