Abstract

Constipation, a condition characterized by heterogeneous symptoms, is common in Western society. It is associated with reduced physical health, mental health, and social functioning. Because constipation is rarely due to a life-threatening disease (for example, colon cancer), current guidelines recommend empiric therapy. Limited surveys suggest that fewer than half of treated individuals are satisfied with treatment, perhaps because the efficacy of drugs is limited, they are associated with undesirable side effects, or they may not target the underlying pathophysiology. For example, although a substantial proportion of constipated patients have a defecatory disorder that is more appropriately treated with pelvic floor biofeedback therapy than with laxatives, virtually no pharmacological trials formally assessed for anorectal dysfunction. Recent advances in investigational tools have improved our understanding of the physiology and pathophysiology of colonic and defecatory functions. In particular, colonic and anorectal high-resolution manometry are now available. High-resolution anorectal manometry, which is increasingly used in clinical practice, at least in the United States, provides a refined assessment of anorectal pressures and may uncover structural abnormalities. Advances in our understanding of colonic molecular physiology have led to the development of new therapeutic agents (such as secretagogues, pro-kinetics, inhibitors of bile acid transporters and ion exchangers). However, because clinical trials compare these newer agents with placebo, their efficacy relative to traditional laxatives is unknown. This article reviews these physiologic, diagnostic, and therapeutic advances and focuses particularly on newer therapeutic agents.

Highlights

  • Symptoms of constipation are reported by 10% to 20% of adults worldwide[1]

  • Initial studies of linaclotide demonstrated a dose-dependent increase in colonic transit with an associated increase in bowel motion frequency and consistency and reduced straining scores in patients with irritable bowel syndrome (IBS)-C89 and chronic constipation[90]

  • Animal models suggest that plecanatide, similar to linaclotide, reduces visceral sensitivity[101], and phase 3 trials in patients with IBS-C have demonstrated a significant improvement in bowel motion frequency, stool consistency, and abdominal pain above that seen with placebo[102]

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Summary

15 Oct 2018

F1000 Faculty Reviews are written by members of the prestigious F1000 Faculty. They are commissioned and are peer reviewed before publication to ensure that the final, published version is comprehensive and accessible. The reviewers who approved the final version are listed with their names and affiliations. Any comments on the article can be found at the end of the article. Keywords Constipation, diagnosis, management, lubiprostone, linaclotide, plecanatide, prucalopride, velusetrag, elobixibat, NGM282, tenapanor

Background
T here are insufficient criteria for irritable bowel syndrome
26. Bharucha AE
28. Rao SSC: Rectal Exam
53. Chey WD
PubMed Abstract
Findings
80. Renexxion Achieves Positive FDA Guidance for Phase 3-ready GI Drug
Full Text
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