Prokinetic

Prokinetic Agents

Prokinetic agents are a class of drugs 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 gastroparesis, gastroesophageal reflux disease (GERD), and other disorders characterized by impaired gastrointestinal motility.

Mechanism of Action

Prokinetic agents work by various mechanisms to enhance gastrointestinal motility:

• Dopamine Receptor Antagonism: Some prokinetic agents, such as Metoclopramide, act as antagonists to dopamine receptors. By blocking dopamine receptors, these drugs increase the release of acetylcholine in the gastrointestinal tract, which enhances motility.

• Serotonin Receptor Agonism: Agents like Cisapride act as agonists at serotonin receptors (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 gastrointestinal motility.

Clinical Uses

Prokinetic agents are used in the management of several gastrointestinal disorders:

• Gastroparesis: A condition characterized by delayed gastric emptying, often seen in diabetic patients. Prokinetic agents help in accelerating gastric emptying.

• Gastroesophageal Reflux Disease (GERD): By enhancing gastric emptying and increasing lower esophageal sphincter tone, prokinetic agents can help reduce reflux symptoms.

• Functional Dyspepsia: Prokinetic agents may be used to alleviate symptoms of bloating and early satiety.

Side Effects

While prokinetic agents are beneficial, they can have side effects, including:

• Extrapyramidal Symptoms: Due to dopamine antagonism, drugs like metoclopramide can cause movement disorders.

• Cardiac Arrhythmias: Some agents, particularly cisapride, have been associated with QT interval prolongation and arrhythmias.

• Diarrhea: Increased gastrointestinal motility can lead to diarrhea.

Examples of Prokinetic Agents

• Metoclopramide: A dopamine receptor antagonist used for gastroparesis and GERD.
• Domperidone: Similar to metoclopramide but with fewer central nervous system side effects.
• Cisapride: A serotonin receptor agonist, withdrawn in many countries due to cardiac side effects.
• Erythromycin: An antibiotic that acts as a motilin receptor agonist.

Also see

• Gastroesophageal Reflux Disease
• Gastroparesis
• Dopamine Receptor Antagonists
• Serotonin Receptor Agonists