Primary Motility  Disorders of the  Esophagus
 The Esophageal
 Esophagogastric  Junction

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Volume: The Esophagogastric Junction
Chapter: Particular problems in medical therapy

What are the different groups of prokinetic agents, and their respective modes of action?

J. Behar (Providence)

They are defined as drugs that initiate or enhance peristalsis and facilitate bolus transport. These drugs act primarily through enteric neurons since peristalsis is based on neural reflexes. They also improve sphincteric function by increasing its resting pressures. Drugs that act directly on the smooth muscle such as bethanechol (cholinergic agent) do not initiate peristalsis and may facilitate bolus transport by increasing the force or amplitude of existing peristaltic contractions. For unknown reasons their therapeutic effects appear to be more effective on the motility of the esophagus and stomach than in the small intestine and colon. These prokinetic drugs stimulate esophageal clearance and gastric emptying and increase resting lower esophageal sphincter pressures.

There are three types of prokinetic drugs available:

1) Dopamine antagonists such as metoclopramide and domperidone. They are classified as such because they block the effects of dopamine in the central nervous system and at the chemoreceptor zone. Because of this last action they are effective anti-emetics. They stimulate peristalsis by releasing acetylcholine since their actions are antagonized by atropine, a muscarinic blocker. About 20% of patients, however, treated with metoclopramide complain of adverse effects and therefore its use is confined to patients with hypomotility disorders associated with nausea.

2) The substituted benzamides such as cisapride and mosapride seem to release acetylcholine by acting on 5HT4 receptors. Their actions are also blocked by atropine. They are being used in the treatment of mild to moderate gastroesophageal reflux, gastroparesis and some forms of pseudo-obstruction. Adverse effects are mild and relatively infrequent.

3) Motilides such as erythromycin which enhance peristalsis by acting on motilin receptors or by releasing motilin. Their actions appear to be mediated by acetylcholine since they are also blocked by atropine.

Thus effective treatment of gastrointestinal hypomotility disorders with these drugs requires the presence of some degree of neural and muscle function.

Publication date: May 1998 OESO©2015