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Prucalopride
Information about Prucalopride
Prucalopride is a serotonin type 4 (5-HT4) receptor agonist that has potent prokinetic activity and is used as therapy for chronic idiopathic constipation.
Liver safety of Prucalopride
Prucalopride has been associated with a minimal rate of transient serum enzyme elevations during therapy and has not been implicated in cases of clinically apparent liver injury with jaundice.
Mechanism of action of Prucalopride
Prucalopride (proo kal' oh pride) is a highly selective serotonin type 4 (5-HT4) receptor agonist that increases the release of serotonin by the specialized enterochromaffin cells in the mucosa of the gut and stimulates intestinal peristalsis and tone. Serotonin (5-HT) is released in response to chemical and mechanical stimulation and acts through the type 4 receptors that are common in the intestinal mucosa to increase peristalsis and intestinal tone. 5-HT4 receptors are also found in the central nervous system, urinary bladder and atria of the heart, which may explain some of the adverse effects of 5-HT4 receptor agonists. Prucalopride was found to improve symptoms of bloating and gastric distension in patients with gastroparesis and to decrease symptoms of reflux in patients with GERD.
FDA approval information for Prucalopride
Prucalopride was approved in the United States in 2018 for treatment of idiopathic chronic constipation. Prucalopride is available in tablets of 1 and 2 mg under the brand name Motegrity. The recommended dose in adults is 2 mg once daily with a lower dose recommended for patients with renal impairment (creatinine clearance less than 30 mL/min).
Side effects of Prucalopride
Adverse events include headache, abdominal pain, nausea, diarrhea, abdominal bloating, dizziness, flatulence and fatigue. Uncommon but potentially severe adverse events include depression, suicidal ideation and behavior and hypersensitivity reactions. Two 5-HT4 receptor agonists were approved for treatment of chronic constipation in the past (cisapride in 1993, tegaserod in 2002), both of which were subsequently withdrawn from general use because of serious adverse events including cardiac arrhythmias and prolongation of the QTc interval. Prucalopride is a more highly selective 5HT4 receptor agonist and has not been linked to an increased rate of these cardiac adverse events.
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.
- Cholestyramine
- Colesevelam
- Colestipol
- Crofelemer
- Difenoxin
- Diphenoxylate
- Kaolin
- Loperamide
- Methylcellulose
- Octreotide
- Pectin
- Rifamycin
- Rifaximin
- Somatostatin
- Telotristat
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
- Dronabinol, Nabilone, Tetrahydrocannabinol
- Phenothiazines [See Antipsychotic Agents]
- Chlorpromazine, Prochlorperazine
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
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.
- Bisacodyl
- Cascara Sagrada
- Castor Oil
- Docusate
- Fiber, Bran
- Lactulose
- Magnesium Sulfate
- Methylcellulose
- Naldemedine (Opioid Antagonist)
- Naloxegol (Opioid Antagonist)
- Plecanatide (for Chronic Idiopathic Constipation)
- Prucalopride (for Chronic Idiopathic Constipation)
- Senna
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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