Metoclopramide

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Information about Metoclopramide

Metoclopramide is an oral prokinetic and antiemetic agent used in the therapy of gastroesophageal reflux disease, gastroparesis and severe or chemotherapy induced nausea

Liver safety of Metoclopramide

Metoclopramide has been reported to cause rare instances of clinically apparent liver injury, but the clinical features have not been well described.  

Mechanism of action of Metoclopramide

Metoclopramide is a benzamide (a para-aminobenzoic acid derivative) which acts as a prokinetic agent on the gastrointestinal tract and an antiemetic, particularly in persons with gastrointestinal dysmotility.  Its mechanism of action is uncertain; it is a serotonin type 4 (5-HT4) receptor agonist, but also has antagonist activity against vagal and central 5HT3 receptors and dopamine type 2 (D2) receptors.  It increases the tone and amplitude of gastric contractions, relaxes the pyloric sphincter and increases peristalsis in the duodenum and jejunum, resulting in improved gastrointestinal motility and accelerated gastric emptying. 

FDA approval information for Metoclopramide

Metoclopramide was approved for use in the United States in 2005 and is widely used in therapy of nausea, vomiting and gastrointestinal motility disorders including gastroparesis, with more than 6 million prescriptions being filled yearly. 

Dosage and administration for Metoclopramide

Metoclopramide is available as 5 and 10 mg tablets in generic forms and under the brand name Reglan.  It is also available as a liquid solution for oral use and in injectable forms.  The typical oral dose for gastroesophageal reflux and gastroparesis in adults is 10 to 15 mg taken 30 minutes before meals.  Intravenous and intramuscular formulations are used for therapy of postoperative or chemotherapy induced nausea and vomiting

Side effects of Metoclopramide

Common side effects include restlessness, drowsiness, dizziness, headache, fatigue, diarrhea and polyuria.  Chronic therapy has been associated with episodes of dystonia, oculogyric crises and extrapyramidal syndromes including tardive dyskinesia and Parkinson like symptoms for which it has a “black box” warning.

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

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