Whorwell Peter, Lange Robert, Scarpignato Carmelo
Neurogastroenterology Unit, Wythenshawe Hospital, Southmoor Road, Wythenshawe, Manchester M23 9LT, UK.
Sanofi, Frankfurt am Main, Germany.
Therap Adv Gastroenterol. 2024 Jun 16;17:17562848241249664. doi: 10.1177/17562848241249664. eCollection 2024.
Stimulant laxatives are well established as first- or second-line treatments for constipation and although they have a reliable therapeutic effect, alleged safety concerns still exist, particularly with long-term use. The potential harmful effects on the gastrointestinal system (including carcinogenicity) of the long-term use of diphenylmethane [bisacodyl, sodium picosulfate (SPS)] and senna stimulant laxatives were assessed in a comprehensive review of the publications identified in literature searches performed in PubMed and Embase up to and including June 2023. We identified and reviewed 43 publications of interest. While stimulant laxatives at supratherapeutic doses have been shown to cause structural alterations to surface absorptive cells in animals and humans, these effects are reversible and not considered clinically relevant. No formal long-term studies have demonstrated morphological changes in enteric neural elements or intestinal smooth muscle with bisacodyl or SPS in humans. Furthermore, there is no convincing evidence that stimulant laxatives are associated with the development of colon cancer, and in fact, chronic constipation itself has been reported to potentially increase the risk of colon cancer, therefore, the use of stimulant laxatives might reduce this risk. Many studies suggesting a possible harmful effect from laxatives were limited by their failure to consider confounding factors such as concomitant neurological disease, metabolic disorders, and age. These findings highlight the lack of evidence for the harmful effects of laxatives on the colon, and thus, the benefits of treatment with stimulant laxatives, even in the long-term, should be reconsidered for the management of patients with constipation.
刺激性泻药作为便秘的一线或二线治疗药物已被广泛认可,尽管它们具有可靠的治疗效果,但所谓的安全问题仍然存在,尤其是长期使用时。通过对截至2023年6月在PubMed和Embase上进行文献检索所确定的出版物进行全面综述,评估了长期使用二苯甲烷类(比沙可啶、匹可硫酸钠)和番泻叶刺激性泻药对胃肠道系统的潜在有害影响(包括致癌性)。我们识别并综述了43篇相关的感兴趣的出版物。虽然超治疗剂量的刺激性泻药已被证明会在动物和人类中引起表面吸收细胞的结构改变,但这些影响是可逆的,且不被认为具有临床相关性。尚无正式的长期研究表明,在人类中,比沙可啶或匹可硫酸钠会导致肠神经元或肠道平滑肌出现形态学变化。此外,没有令人信服的证据表明刺激性泻药与结肠癌的发生有关,事实上,据报道慢性便秘本身可能会增加患结肠癌的风险,因此,使用刺激性泻药可能会降低这种风险。许多表明泻药可能有有害影响的研究,因未考虑诸如伴随的神经系统疾病、代谢紊乱和年龄等混杂因素而受到限制。这些发现凸显了缺乏证据支持泻药对结肠有有害影响,因此,即使是长期使用,对于便秘患者的治疗,刺激性泻药的益处也应重新审视。