Irritable bowel syndrome constipation-predominant

Compare the features of chronic constipation with those of constipation-predominant irritable bowel syndrome (IBS). 

In the periphery, 5-HT4 receptor mRNA is found in vascular smooth muscle. Newly developed drugs that activate 5-HT4 receptors are of interest for their potential in treating cardiac arrhythmia. The 5-HT4 receptor is also located on neurons of the alimentary tract, for example the myenteric plexus of the ileum, and on smooth muscle cells and secretory cells of the gastrointestinal tract, where they evoke secretions and the peristaltic reflex. 5-HT4 receptor agonists (e.g. cisapride, prucalopride, tegaserod) are used therapeutically in the treatment of constipation-predominant irritable bowel syndrome and in functional motility disorders of the upper gastrointestinal tract. 

Caldarella MR Milano A, Laterza F et al. Visceral sensitivity and symptoms in patients with constipation- or diarrhea-predominant irritable bowel syndrome (IBS) effect of a low-fat intraduodenal infusion. Am J Gastroenterol 2005 100(2) 383-9. 

The standard pharmacokinetic parameters of the compound such as a half-life or bioavailability cannot be reliably calculated, because the concentrations in plasma are below lOpg/mL. As analogously expected from the results on the shift in keto-alcohol equilibrium of 16,16-difluoro-PGE2, it is rapidly metabolized by C-15 reduction mediated by the ubiquitously expressed carbonyl reductase. The metabolism followed by jS-oxidation and co-oxidation forms a mixture of a and fi epimers at the 15-hydroxy moiety as a sole measurable metabolite [46], In 2006, the US Food and Drug Administration approved the drug application for an oral treatment of chronic idiopathic constipation in adults, estimating that 4-5 million Americans are affected. Lubiprostone has also completed a phase II trial in constipation-predominant irritable bowel syndrome, and has been further evaluated for other bowel dysfunctions. 

Lubiprostone is a prostanoic acid derivative labeled for use in chronic constipation and irritable bowel syndrome (IBS) with predominant constipation. It acts by stimulating... 

A PGE related compound, lubiprostone (23) displays a quite different spectrum of activity. This compound has been recently approved for treatment of chronic constipation and is being investigated for its effect on constipation-predominant irritable bowel syndrome. It has been ascertained that the drug interacts with specific ion channels in the G1 tract causing increased fluid output into the lumen. Starting material for the synthesis (13) comprises yet another variant on the Corey lactone. Condensation... 

Women had significantly greater responses than men. Constipation was the most commonly reported adverse effect of alosetron (49% compared with 13% in the placebo group). In a randomized, double-blind, placebo-controlled trial in 626 women with diarrhea-predominant irritable bowel syndrome, alosetron 1 mg bd was significantly more effective than placebo in controlling symptoms... 

Irritable bowel syndrome presents as either diarrhea-predominant or constipation-predominant disease and can be defined as lower abdominal pain, disturbed defecation (constipation, diarrhea, or an alternating pattern of both), and bloating in the absence of structural or biochemical factors that might explain these symptoms (Table 36-10). 

FIGURE 36-3. A general stepwise approach to the management of both constipation- and diarrhea-predominant irritable bowel syndrome. 

Tougas G, Snape WJ, Otten MH, et al. Long-term safety of tegaserod in patients with constipation-predominant irritable bowel syndrome. AUment PUarmacol TUer 2002 16 1701-1708. 

Open-label studies An open-label extension study assessed the long-term safety, tolerability and efficacy of lubiprostone in 520 patients with constipation-predominant irritable bowel syndrome. Patients were orally administered lubiprostone (8 meg) twice daily for 36 weeks. The most common adverse events were diarrhoea (11%), nausea (11%), urinary tract infection (9%), sinusitis (9%) and abdominal distention (5.8%). No serious adverse events were considered as being treatment related. Seventeen patients discontinued lubiprostone due to a treatment-related adverse event, of which diarrhoea and nausea accoxmted for 1.2% and 0.6%, respectively [9. ... 

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