Open Channels for Functional Bowel Disorders: Guanylate Cyclase C Agonists in IBS and CC

Excerpt

Despite the high global prevalence and impact on the individual and society of irritable bowel syndrome and chronic idiopathic (functional) constipation (commonly referred to as chronic constipation or CC), new and effective therapies are remarkable by their paucity. Several factors have conspired to restrict the physician’s armamentarium in relation to functional bowel disorders, including the intrinsic heterogeneity of these entities, an absence of a unifying explanation for their pathophysiology, and a very low tolerance among regulatory agencies for any adverse events in the treatment of disorders so commonly, and inappropriately, regarded as nothing more than a nuisance. As a consequence, optimal therapeutic targets remain difficult to define, ideal outcome measures the subject of much debate, and the selection of the most appropriate study population a process that owes as much to art as science. Agents directed at the traditional targets, motility and visceral sensation, have in the past, been troubled, not only by marginal efficacy, but also by a prevalence of adverse events deemed unacceptable [1]. More recent refinements, such as the development of highly selective receptor agonists, seem to have overcome some of these hurdles, as exemplified by studies with the selective 5-HT₄ agonist, prucalopride, in chronic constipation [2]. Indeed, this drug has now been approved for the treatment of constipation in several jurisdictions. …