Omer Anam, Quigley Eamonn M M
Lynda K. and David M. Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Department of Medicine, Houston Methodist Hospital, Houston, TX, USA.
Division of Gastroenterology and Hepatology, The Methodist Hospital, 6550 Fannin St, SM 1201, Houston, TX 77030, USA.
Therap Adv Gastroenterol. 2017 Nov;10(11):877-887. doi: 10.1177/1756283X17734809. Epub 2017 Oct 16.
Chronic constipation (CC) is a highly prevalent and often under-appreciated gastrointestinal disorder associated with significant impairment in quality of life. Symptoms of constipation are typically present for a number of years prior to a patient seeking help. Lifestyle modifications followed by, or coupled with, over-the-counter laxatives represent the initial treatment option; however, relief for many is limited and dissatisfaction rates for these approaches remain high. Over recent years, therefore, considerable effort has been exerted on the development of novel pharmacological approaches. Two major targets have emerged, motility and secretion. Research on the former led to the development of a number of prokinetic agents capable of stimulating colonic motility and, thus, accelerating colonic transit. Of these, earlier prototypes such as cisapride and tegaserod, though effective, were ultimately withdrawn due to cardiovascular adverse events due in part to receptor non-selectivity. Highly selective serotonergic receptor agonists have since emerged which appear to be equally effective in stimulating gut motility but are devoid of cardiac side effects. One such agent is prucalopride, which has now been approved for the management of chronic idiopathic constipation in several countries, but not in the United States. Multiple multicenter, randomized placebo-controlled clinical trials have demonstrated superiority for prucalopride compared to placebo in the short to medium term in relieving the major symptoms of constipation in both men and women across a broad spectrum of ages, ethnicities and geographic locations. To date, prucalopride has enjoyed a favorable safety profile and there have been no signals to suggest arrythmogenicity. Efficacy over longer periods of treatment remains to be confirmed. Evidence for efficacy in other forms of constipation, such as opioid-induced constipation and that related to Parkinson's disease is beginning to emerge; its status in the management of constipation-predominant irritable bowel syndrome or foregut motility disorders, such as gastroparesis, remains to be established.
慢性便秘（CC）是一种非常普遍但常被忽视的胃肠道疾病，会严重损害生活质量。便秘症状通常在患者寻求帮助前已持续数年。生活方式的改变，随后或同时使用非处方泻药是初始治疗选择；然而，对许多人来说缓解有限，这些方法的不满意率仍然很高。因此，近年来人们在开发新的药物治疗方法上付出了巨大努力。出现了两个主要靶点，即动力和分泌。对前者的研究导致了多种促动力剂的开发，这些促动力剂能够刺激结肠动力，从而加速结肠转运。其中，早期的原型药物如西沙必利和替加色罗，虽然有效，但最终因心血管不良事件而被撤市，部分原因是受体非选择性。此后出现了高度选择性的5-羟色胺能受体激动剂，它们在刺激肠道动力方面似乎同样有效，但没有心脏副作用。普芦卡必利就是这样一种药物，它现已在多个国家被批准用于治疗慢性特发性便秘，但在美国未获批准。多项多中心、随机、安慰剂对照临床试验表明，在短期至中期，普芦卡必利在缓解广泛年龄、种族和地理位置的男性和女性便秘主要症状方面优于安慰剂。迄今为止，普芦卡必利的安全性良好，没有迹象表明有致心律失常性。长期治疗的疗效仍有待证实。在其他形式的便秘，如阿片类药物引起的便秘和与帕金森病相关的便秘中的疗效证据也开始出现；其在以便秘为主的肠易激综合征或前肠动力障碍（如胃轻瘫）管理中的地位仍有待确定。
