Lubiprostone

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Introduction Lubiprostone is an activator of chloride channels (ClC-2) in the intestine and is used for treatment of chronic constipation and irritable bowel syndrome.

Liver safety of Lubiprostone

Lubiprostone has not been linked to serum enzyme elevations during treatment or to episodes of clinically apparent liver injury.


Background Lubiprostone (loo” bi pros’ tone) is a fatty acid metabolite of prostaglandin E1 that activates the chloride channels in the intestine, which increase fluid secretion into the lumen and thus promote intestinal transport. Short term use of lubiprostone increases the number of spontaneous bowel movements and can alleviate symptoms of constipation in patients with irritable bowel syndrome.

FDA approval information for Lubiprostone

Lubiprostone was approved for use in the United States in 2006 for short term therapy of chronic constipation and indications were expanded in 2008 to management of patients with irritable bowel syndrome and constipation.

Brand name for Lubiprostone

Lubiprostone is available in capsules of 8 and 24 mcg under the brand name Amitiza.

Dosage and administration for Lubiprostone

The recommended dose for chronic constipation is 24 mcg twice daily and for irritable bowel syndrome with constipation 8 mcg twice daily.

Side effects of Lubiprostone

Systemic absorption is minimal, but may be greater in patients with liver disease. Side effects include nausea, diarrhea, abdominal pain and bloating, headache and chest tightness with shortness of breath.

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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