Constipation tegaserod

Tegaserod maleate (Zelnorm) is a partial serotonin (5-HT4) receptor agonist that causes an increase in peristaltic activity and intestinal secretion and moderation of visceral sensitivity. It increases the frequency of bowel movements and reduces abdominal discomfort, bloating, and straining. It is indicated for the treatment of patients younger than 65 years of age who experience chronic idiopathic constipation. The most common adverse effects include headache, abdominal pain, diarrhea, and nausea. 

Slow-transit constipation can be treated with chronic administration of osmotic laxatives. Tegaserod maleate 6 mg orally twice daily is an acceptable treatment. Senna, bisacodyl, and other stimulants should be used only when the others fail to deliver the desired effect. 

Tegaserod maleate (Zelnorm) stimulates 5-HT4 receptors in the GI tract, thereby increasing intestinal secretion, peristalsis, and small bowel transit. It also reduces sensitivity related to abdominal distention. It has been shown to be more effective than placebo in improving global IBS symptoms and altered bowel habits in constipation-predominant IBS.21 Diarrhea is a possible adverse effect. 

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. 

Figure 1 Effects of tegaserod in a constipation model in conscious dogs. Tegaserod normalizes stool frequency, stool quantity and softens stool consistency. Mean SEM (n — 8) p < 0.05 versus Vehicle ftp < 0.05 versus Morphine. From Weber et al., Gastroenterology (2003), 124 A1806 (Please see Color Plate Section in the back of this book).

The clinical efficacy of tegaserod in female patients with constipation-predominant IBS was established in two prospective well-controlled studies,... 

The safety and efficacy of tegaserod in men with IBS with constipation have not been established. 

The efficacy of tegaserod for the treatment of IBS with constipation or chronic idiopathic constipation has not been studied beyond 12 weeks. 

Elderly Patients 65 years of age and older who received tegaserod for chronic idiopathic constipation experienced a higher incidence of diarrhea and discontinuations because of diarrhea than patients younger than 65 years of age. Pregnancy Category B. Use during pregnancy only if clearly needed. 

If drugs are used, the first choice should be a bulk laxative, e.g. isphagula or sterculia gum. Nonabsorbent carbohydrates with osmotic activity also work well but often cause flatulence. Salinic laxatives like polyethylene glycol and magnesium oxide are very effective but often cause stomach upsets like flatulence and abdominal pain. Tegaserod, a 5-HT4 partial agonist, appears to improve the frequency of bowel movements in those with chronic constipation (see Evans et ah, 2007). 

Evans BW, Clark WK, Moore DJ, Whorwell PJ. Tegaserod for the treatment of irritable bowel syndrome and chronic constipation. Cochrane Database Syst Rev 2007. 

Cisapride, a 5-HT4 agonist, was used in the treatment of gastroesophageal reflux and motility disorders. Because of toxicity, it is now available only for compassionate use in the USA. Tegaserod, a 5-HT4 partial agonist, is used for irritable bowel syndrome with constipation. These drugs are discussed in Chapter 62. 

The newer serotonin receptor agonists and antagonists tegaserod and alosetron act on Gl-specific serotonin receptors to treat constipation-predominant and diarrhea-predominant IBS, respectively. However, both drugs are currently only indicated for women. Efficacy and safety in men has not been established because the initial manufacturer s sponsored clinical trials contained insufficient numbers of men with IBS to provide the necessary statistical power to prove efficacy and safety. Ongoing studies should determine if these drugs are indicated in men. 

The 5-HT4 agonist tegaserod is the first therapy approved by the FDA specifically for the treatment of constipation-predominant... 

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. 

Muller-Lissner SA, EumagalU I, BardUan KD, et al. Tegaserod, a 5-HT4 receptor partial agonist, relieves symptoms in irritable bowel syndrome patients with abdominal pain, bloating and constipation. AUment Pharmacol Ther 2001 15 1655-1666. 

Tegaserod maleate is a GI agent that binds with high affinity to human 5-HT4 receptors, acting as an agonist at neuronal 5-HT4 receptors to trigger the release of neurotransmitters. Activation of 5-HT4 receptors in the GI tract stimulates peristaltic reflex and intestinal secretion, and inhibits visceral sensitivity. It is used for short-term treatment of women with irritable bowel syndrome (IBS) whose primary symptom is constipation and in treatment of patients younger than 65 years of age with chronic idiopathic constipation. 

Tegaserod is available for oral administration in 2-mg and 6-mg tablets and approved for use in women with constipation-dominant irritable bowel syndrome at a dose of 6 mg twice daily. Tegaserod also has been approved for the treatment of chronic constipation. Higher doses have been suggested for other prokinetic effects (e.g., stimula-... 

Tegaserod [9], a 5-HT4 agonist, was launched in the market in 2004 for the management of IBS and constipation. Three years later, the US Food and Drug Administration (FDA) requested that Novartis withdraw tegaserod from shelves due to concerns over increased risks of heart attack or stroke. However, tegaserod is stiU available in many countries across the world (see footnote 1). 

J.A. Di Palma, M.V. Cleveland, J. McGowan, J.L. Herrera, A randomized, multicenter cointarison of polyethylene glycol laxative and tegaserod in treatment of patients with chronic constipation. Am. J. Gastroenterol. 102 (2007) 1964—1971. 

Observational studies In two identical open studies (El, E2) of oral tegaserod (6 mg bd over 1 year) in 780 women with dysmotility-like functional dyspepsia, who had previously completed two 6-week, randomized, placebo-controlled trials with tegaserod at the same dosage, tegaserod was effective against dyspeptic symptoms. Most adverse events were reported within the first 6 months, and the most common included diarrhea, headache, nausea, abdominal pain, vomiting, and constipation. One patient developed severe bradycardia. 

Wagstaff AJ, Frampton JE, Croom KF. Tegaserod a review of its use in the management of irritable bowel syndrome with constipation in women. Drugs 2003 63 1101-20. 

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