Tegaserod

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Information about Tegaserod

Tegaserod (teg” a ser’ od) is an aminoguanidine indole derivative of serotonin and a selective, partial 5-HT4 receptor agonist.

Mechanism of action of Tegaserod

It simulates the peristaltic reflex and increases intestinal and colonic motility resulting in hastened transit. It also reduces visceral sensation in response to distension. These features led to its development as therapy of irritable bowel syndrome and constipation.

FDA approval information for Tegaserod

It was approved for use in the United States in 2002 and was available in tablets of 2 or 6 mg under the brand name of Zelnorm.

Dosage and administration for Tegaserod

The typically recommended dose was 2 to 6 mg twice daily.

The drug Tegaserod was withdrawn from the US market

Tegaserod was withdrawn in 2007 because of adverse cardiovascular effects, postmarketing studies demonstrating an excess of severe adverse cardiovascular events in tegaserod treated patients (0.11%) compared to matched controls (0.01%).

The association of tegaserod with adverse cardiovascular events has been contested but, currently, tegaserod is available only on an emergency basis and with prior authorization from the FDA.

Antidiarrheal agents

Antidiarrheal agents include bulk forming agents, hydroscopic agents, bile acid resins, bismuth, inhibitors of intestinal motility, non-absorbed antibiotics and hormones. Bulk forming agents include methylcellulose; hydroscopic agents include pectin and kaolin; bile acid resins are cholestyramine, colestipol and colesevalam; inhibitors of intestinal motility include opioids such as diphenoxylate and loperamide. Antibiotics include rifamycin and rifaximin which are non-absorbed and are used for travelers' diarrhea. Hormones with antidiarrheal activity include octretide and somatostatin. Most antidiarrheal agents are active locally in the small intestine and colon and are largely not absorbed. Some, however, have been implicated in rare causes of liver injury (senna, cascara, cholestyramine). Telotristat is a relatively new agent that inhibits the synthesis of serotonin and is used specifically for the diarrhea of carcinoid syndrome.

Antiemetics are a diverse group of medications that act at different points in the pathways that regulate nausea and vomiting. These include antihistamines, anticholinergic agents, phenothiazines, serotonin type 3 receptor blockers, centrally acting benzamides, cannabinoid receptor agonists, substance P antagonists and miscellaneous.

Anticholinergic Agents

Antihistamines

Cannabinoid Receptor Agonists

Serotonin 5-HT3 Receptor Antagonists

Substance P/Neurokinin 1 Receptor Antagonists

Miscellaneous

Acid peptic disease/antiulcer agents that include antacids, the histamine type 2 receptor blockers (H2 blockers), and the proton pump inhibitors (PPIs). These agents are some of the most commonly taken medications and are very well tolerated, most being available both by prescription and over-the-counter. While many of these drugs are approved for use in duodenal and gastric ulcer disease, their major use is for acid reflux and indigestion.

Histamine H2 Receptor Antagonists (H2 Blockers) Cimetidine, Famotidine, Nizatidine, Ranitidine

Proton Pump Inhibitors

Cathartics, laxatives or agents for constipation include bulk forming agents, osmotic agents, stool wetting agents, nonspecific stimulants, prokinetic agents and agents that increase fluid secretion. Many of these therapies are not systemically absorbed and none are considered particularly hepatotoxic. Naldemedine and naloxegol are opioid antagonists and are used to treat the constipation associated with opioid use.

Inflammatory bowel disease encompasses several disorders, most commonly ulcerative colitis and Crohn colitis. Agents can be classified as 5-aminosalicyclic acid (5-ASA) based agents, immunosuppressive drugs, antitumor necrosis factor agents, corticosteroids, antibiotics and miscellaneous.

5-Aminosalicyclic Acid (5-ASA) Derivatives

Immunosuppressive Agents

Tumor Necrosis Factor Antagonists

Miscellaneous

Irritable Bowel Syndrome Agents Antimuscarinics/Antispasmodics [See Anticholinergic agents

Prokinetic Agents - See Serotonin 5-ht4 receptor agonists Alosetron, Cisapride, Domperidone, Linaclotide, Lubiprostone, Metoclopramide, Plecanatide, Prucalopride, Tegaserod

Other

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