gastroprokinetic

Gastroprokinetic refers to drugs that enhance motility of the upper gastrointestinal tract, especially the stomach, by increasing gastric emptying and advancing intestinal transit. They are used to treat conditions characterized by delayed gastric emptying, such as gastroparesis and certain functional dyspepsias, and can be considered in postoperative ileus or complex cases of GERD with impaired motility.

Gastroprokinetics work through different receptor pathways. Dopamine D2 antagonists, such as metoclopramide and domperidone, reduce inhibitory dopaminergic signaling to enhance acetylcholine-driven smooth muscle contractions, speeding gastric emptying and increasing lower esophageal sphincter tone. Serotonin 5-HT4 receptor agonists stimulate acetylcholine release to promote coordinated peristalsis. Macrolide antibiotics like erythromycin act as motilin receptor agonists, triggering migrating motor complexes that propel contents through the stomach and small intestine.

Common agents and uses include metoclopramide for gastroparesis and antiemetic effects, domperidone for nausea and vomiting and gastroparesis in some regions, and erythromycin as a short-term option for gastroparesis or postsurgical ileus. Cisapride, a historic 5-HT4 agonist, was widely used but withdrawn in many countries due to the risk of QT interval prolongation and torsades de pointes. Newer selective prokinetics continue to be studied, with limited approval for upper GI use in some jurisdictions.

Safety and limitations are important. Metoclopramide can cause extrapyramidal symptoms and tardive dyskinesia with prolonged use; domperidone carries a risk of QT prolongation and serious cardiac arrhythmias; erythromycin can lead to tachyphylaxis and antibiotic-related adverse effects. Prokinetics are contraindicated in mechanical obstruction, perforation, or GI bleeding and require careful monitoring and medical supervision.