Siegert Fritzi, Nieber Karen
Institut für Pharmazie, Lehrstuhl Pharmakologie für Naturwissenschaftler, Leipzig.
Med Monatsschr Pharm. 2010 Aug;33(8):285-92; quiz 293-4.
Irritable bowel syndrome is a common functional disorder of the gut. The cause is not known. Symptoms can be quite variable and include abdominal pain, bloating, and sometimes bouts of diarrhea and/or constipation. It causes a great deal of discomfort and distress, but it does not permanently harm the intestine and does not lead to a serious disease, such as cancer. There are numerous treatment options in functional gastrointestinal disorders acting peripherally by influencing motility and visceral sensitivity. However, older 5-HT4 receptor agonists had limited clinical success because they were associated with changes in the cardiac function. New generation 5-HT4 receptor agonists, 5-HT, antagonists or partial antagonists are promising approaches to treat gastrointestinal dysmotility, particularly colonic diseases. A further new approach is the activation of chloride cannels within the gastrointestinal wall by the prostaglandin E metabolite lubiprostone. In patients with chronic constipation, lubiprostone produced a bowel movement, with sustained improvement in frequency as well as other constipation symptoms. Ongoing clinical trials suggest that linaclotide, a first-in-class, 14-amino acid peptide guanylate cyclase C (GC-C) receptor agonist and intestinal secretagogue is also an effective treatment for chronic constipation. The pharmacological profile suggests that orally administered linaclotide may be capable of improving the abdominal symptoms and bowel habits of patients suffering from of constipation-predominant irritable bowel syndrome and chronic constipation. Data are emerging, but the efficacy and safety profile of these agents in the treatment irritable bowel disease appears encouraging. Further randomized controlled trials are warranted.
肠易激综合征是一种常见的肠道功能性疾病。病因不明。症状可能差异很大,包括腹痛、腹胀,有时还伴有腹泻和/或便秘发作。它会引起极大的不适和痛苦,但不会对肠道造成永久性损害,也不会导致严重疾病,如癌症。在功能性胃肠疾病中,有许多通过影响运动性和内脏敏感性而在外周起作用的治疗选择。然而, older 5-HT4受体激动剂临床成功率有限,因为它们与心脏功能变化有关。新一代5-HT4受体激动剂、5-HT拮抗剂或部分拮抗剂是治疗胃肠动力障碍,特别是结肠疾病的有前景的方法。另一种新方法是前列腺素E代谢物鲁比前列酮激活胃肠壁内的氯离子通道。在慢性便秘患者中,鲁比前列酮可促进排便,频率及其他便秘症状持续改善。正在进行的临床试验表明,利那洛肽,一种一流的14氨基酸肽鸟苷酸环化酶C(GC-C)受体激动剂和肠道促分泌剂,也是慢性便秘的有效治疗方法。药理学特征表明,口服利那洛肽可能能够改善以便秘为主的肠易激综合征和慢性便秘患者的腹部症状和排便习惯。数据正在不断涌现,但这些药物在治疗肠易激疾病方面的疗效和安全性似乎令人鼓舞。有必要进行进一步的随机对照试验。