Intestinal Motility Disorders Medication
- Author: Nafisa K Kuwajerwala, MD; Chief Editor: Julian Katz, MD more...
Drugs used in the management of intestinal motility disorders include cholinergic agonists, prokinetic agents, opioid antagonists, antidiarrheals, and antibiotics. The agents that are most useful in the treatment of these disorders are neostigmine, bethanechol, metoclopramide, cisapride, and loperamide. Neostigmine appears to increase antral and intestinal motor activity in patients with hypomotility, including intestinal dysmotility.
Excessive parasympathetic suppression appears to be involved in the genesis of intestinal pseudo-obstruction. Cholinergic agents may allow early resolution of pseudo-obstruction and obviate surgery.
Neostigmine inhibits destruction of acetylcholine by acetylcholinesterase, which facilitates transmission of impulses across myoneural junction.
Bethanechol is a synthetic muscarinic stimulant. It should never be administered intravenously (IV) or intramuscularly (IM).
Prokinetics are promotility agents, proposed for use with severe constipation-predominant symptoms.
Tegaserod was temporarily withdrawn from the US market in March 2007; however, as of July 27, 2007, restricted use of tegaserod is now permitted via a treatment investigational new drug (IND) protocol. This protocol allows tegaserod treatment of irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC) in women younger than 55 years who meet specific guidelines. Its use is further restricted to those in critical need who have no known or preexisting heart disease. (See the FDA MedWatch Product Safety Alert.)
Tegaserod is used for short-term treatment of women with IBS in which constipation is the predominant symptom. It is also indicated to treat CIC. Tegaserod is a serotonin type 4 receptor partial agonist with no affinity for 5-HT3 receptors. It may trigger peristaltic reflex via 5-HT4 activation, which enhances basal motor activity and normalizes impaired gastrointestinal (GI) motility. Research studies have shown inhibitory activity of the drug on visceral activity in the GI tract.
Metoclopramide is characterized by remarkable coordination of gastric and duodenal motility.
Cisapride indirectly improves GI motility by promoting acetylcholine release from postganglionic nerve endings in the myenteric plexus. It was withdrawn from the US market on July 14, 2000, but the manufacturer will make it available to certain patients meeting clinical eligibility criteria for a limited-access protocol only.
Opioid Reversal Agents
Consider using a peripherally selective opioid antagonist to treat constipation in patients who have advanced illness requiring chronic opioid analgesia and are unresponsive to laxatives.
Methylnaltrexone is a peripherally acting mu-opioid receptor antagonist. It selectively displaces opioids from mu-opioid receptors outside the central nervous system (CNS), including those located in the GI tract, thereby decreasing constipating effects. Methylnaltrexone is indicated for opioid-induced constipation in patients with advanced illness who are receiving palliative care and whose response to laxatives has not been sufficient. It is available as a 12-mg/0.6-mL injectable solution for subcutaneous use.
Antidiarrheal agents inhibit peristalsis and slow intestinal motility.
Loperamide inhibits peristalsis by acting directly on the muscles of the intestinal wall, thereby slowing intestinal motility. It prolongs movement of electrolytes and fluid through the bowel and increases viscosity and loss of fluids and electrolytes.
Diphenoxylate and atropine is an antidiarrheal drug combination wherein diphenoxylate is chemically related to the narcotic analgesic meperidine. It acts on intestinal muscles to inhibit peristalsis and slow intestinal motility. It prolongs the movement of electrolytes and fluid through the bowel and increases viscosity and loss of fluids and electrolytes. A subtherapeutic dose of anticholinergic atropine sulfate is added to discourage overdosage, in which case diphenoxylate may clinically mimic the effects of codeine.
Difenoxin and atropine is an antidiarrheal drug combination wherein diphenoxylate is chemically related to the narcotic analgesic meperidine. Difenoxin is the active metabolite of diphenoxylate, and it is active at one fifth the dose of diphenoxylate.
Erythromycin is a prokinetic agent for the stomach. It is indicated in patients with gastroparesis.
Erythromycin is a macrolide antibiotic that duplicates the action of motilin and is responsible for migrating motor complex activity by binding to and activating motilin receptors. IV administration enhances the emptying rate of liquids and solids. The effect can be seen with oral erythromycin. The enteric-coated form may be better tolerated.
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