Prokinetik

Prokinetik, or prokinetic agents, are substances that enhance gastrointestinal motility by promoting coordinated peristaltic activity and increasing the tone of the gastroesophageal sphincter. These drugs work through several mechanisms, including dopamine D2 receptor antagonism (which tends to boost upper GI motility), serotonin 5-HT4 receptor agonism (which increases acetylcholine release in the enteric nervous system), and activation of motilin receptors. Some agents combine multiple mechanisms, and certain macrolide antibiotics can act as short-term promotility agents via motilin receptor stimulation.

Common prokinetik include metoclopramide and domperidone (D2 antagonists that increase gastric motility and LES tone), prucalopride (a selective 5-HT4 agonist), and historically cisapride and erythromycin (motilin receptor agonists). Indications typically involve conditions characterized by delayed gastric emptying or impaired gut transit, such as gastroparesis (including diabetic and idiopathic forms), gastroesophageal reflux with delayed emptying, postoperative ileus, and sometimes functional dyspepsia. They may be used to facilitate enteral feeding or improve symptoms when motility is a limiting factor.

Safety and regulatory status vary by agent and region. Adverse effects reflect their mechanisms: dopamine antagonists can cause extrapyramidal symptoms, hyperprolactinemia, and, with chronic use, tardive dyskinesia; tardive risks limit long-term use of some drugs. Erythromycin and similar agents may cause tachyphylaxis and QT interval prolongation, with potential risk of arrhythmias. Cisapride was withdrawn in many markets because of serious cardiac risks. Availability of prokinetics is now often restricted to certain populations or requires careful monitoring, with newer agents like prucalopride used where approved.