Prokinetics

Prokinetics

Prokinetics are a class of medications that enhance gastrointestinal motility by increasing the frequency or strength of contractions in the small intestine without disrupting their rhythm. These agents are primarily used to treat conditions such as gastroesophageal reflux disease (GERD), gastroparesis, and other disorders characterized by delayed gastric emptying.

Mechanism of Action

Prokinetic agents work through various mechanisms to stimulate gastrointestinal motility:

• Dopamine Receptor Antagonism: Some prokinetics, such as metoclopramide, act as antagonists at dopamine D2 receptors. By blocking these receptors, they enhance the release of acetylcholine in the enteric nervous system, which increases gastrointestinal motility.

• Serotonin Receptor Agonism: Agents like cisapride and prucalopride act as agonists at 5-HT4 receptors, promoting the release of acetylcholine and enhancing peristalsis.

• Motilin Receptor Agonism: Erythromycin, an antibiotic, can act as a motilin receptor agonist, stimulating gastric motility and accelerating gastric emptying.

Clinical Uses

Prokinetics are used in the management of several gastrointestinal disorders:

• Gastroesophageal Reflux Disease (GERD): By enhancing gastric emptying, prokinetics can reduce the frequency of reflux episodes.

• Gastroparesis: This condition, often seen in diabetic patients, is characterized by delayed gastric emptying. Prokinetics can help alleviate symptoms such as nausea, vomiting, and bloating.

• Functional Dyspepsia: Prokinetics may be used to relieve symptoms of indigestion by improving gastric motility.

Side Effects

While prokinetics can be effective, they are associated with several side effects:

• Central Nervous System Effects: Metoclopramide can cause drowsiness, fatigue, and, in some cases, extrapyramidal symptoms such as tardive dyskinesia.

• Cardiovascular Effects: Cisapride has been associated with QT interval prolongation, leading to serious cardiac arrhythmias.

• Gastrointestinal Effects: Some patients may experience diarrhea or abdominal cramping.

Examples of Prokinetic Agents

• Metoclopramide: A dopamine D2 receptor antagonist with antiemetic and prokinetic properties.

• Domperidone: Similar to metoclopramide but with fewer central nervous system side effects due to its limited ability to cross the blood-brain barrier.

• Cisapride: A 5-HT4 receptor agonist, withdrawn in many countries due to cardiac side effects.

• Prucalopride: A selective 5-HT4 receptor agonist used primarily for chronic constipation.

• Erythromycin: An antibiotic that acts as a motilin receptor agonist, used off-label for its prokinetic effects.

Also see

• Gastroesophageal reflux disease
• Gastroparesis
• Functional dyspepsia
• Motilin
• Serotonin