Lacy Brian E, Loew Burr, Crowell Michael D
Division of Gastroenterology & Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756, USA.
Drugs Today (Barc). 2009 Dec;45(12):843-53. doi: 10.1358/dot.2009.45.12.1423115.
Chronic constipation is a frequently reported medical disorder that reduces patients' quality of life and imposes a significant economic burden on the health care system. Symptoms of constipation are diverse and include infrequent bowel movements, hard stool, straining at stool, sensations of anorectal obstruction and feelings of incomplete evacuation. Patients with chronic constipation can be categorized into one of three main groups based on their underlying pathophysiology: normal transit constipation; colonic inertia; and pelvic floor dyssynergia. Specialized tests (i.e., anorectal manometry, radio-opaque marker study) may be required in some patients to help distinguish the different subtypes of constipation and to guide appropriate therapy. Although the underlying mechanism of constipation differs among patients, serotonin (5-hydroxytryptamine (5-HT)) appears to have an important role in colonic motility in some patients. Previous research has demonstrated that stimulation of 5-HT4 receptors improves symptoms of chronic constipation in some patients. Prucalopride, a selective 5-HT4 agonist, relieved symptoms of constipation in phase II and phase III clinical trials. In this monograph, we review the pharmacology, mechanism of action, efficacy and safety of the selective 5-HT4 agonist prucalopride in patients with chronic constipation.
慢性便秘是一种经常被报道的医学病症，它会降低患者的生活质量，并给医疗保健系统带来巨大的经济负担。便秘的症状多种多样，包括排便次数减少、大便干结、排便时用力、肛门直肠梗阻感以及排便不尽感。根据潜在的病理生理学，慢性便秘患者可分为三大主要类型：正常传输型便秘；结肠无力型；盆底失协调型。在某些患者中可能需要进行专门的检查（如肛门直肠测压、不透X线标志物研究），以帮助区分便秘的不同亚型并指导适当的治疗。尽管不同患者便秘的潜在机制有所不同，但血清素（5-羟色胺（5-HT））在某些患者的结肠运动中似乎起着重要作用。先前的研究表明，刺激5-HT4受体可改善部分慢性便秘患者的症状。普芦卡必利是一种选择性5-HT4激动剂，在II期和III期临床试验中可缓解便秘症状。在本专题论文中，我们综述了选择性5-HT4激动剂普芦卡必利在慢性便秘患者中的药理学、作用机制、疗效和安全性。
