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Eluxadoline

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Information about Eluxadoline

Eluxadoline is a mixed opioid receptor agonist (mu) and antagonist (delta) that is used to treat diarrhea-predominant irritable bowel disease.

Mechanism of action of Eluxadoline

Eluxadoline is associated with a low rate of serum aminotransferase elevations that appear to be due to isolated instances of sphincter of Oddi spasm and/or pancreatitis that occurs most frequently in persons without a gallbladder.

Mechanism of action of Eluxadoline

Eluxadoline (el" ux ad' oh leen) is mixed opioid receptor agonist and antagonist, having agonist activity for the mu (µ) receptor and antagonist activity for the delta (δ) receptor. This combination of activities leads to its activity in reducing bowel transit and decreasing pain without the side effects that occur with mu receptor agonism alone. Eluxadoline is also minimally absorbed and thus does not have the central nervous system effects of typical opiates and does not require DEA restrictions.

FDA approval information for Eluxadoline

Several prospective controlled trials have shown that eluxadoline decreases gastrointestinal discomfort and symptoms in patients with diarrhea-predominant irritable bowel syndrome and it was approved for this use in the United States in 2015.

Dosage and administration for Eluxadoline

Eluxadoline is available in tablets of 75 and 100 mg under the brand name Viberzi.

Dosage and administration for Eluxadoline

The recommended dose is 100 mg twice daily with dose reduction based upon tolerance.

Side effects of Eluxadoline

Side effects include constipation, nausea, and abdominal pain. Uncommon, but potentially severe adverse reactions include severe abdominal pain due to spasm of the sphincter of Oddi or pancreatitis, complications that occur mostly in patients without a gallbladder or with preexisting pancreatic or hepatobiliary disease.

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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