Prokinetika

Prokinetika, or prokinetic agents, are drugs that enhance gastrointestinal motility by increasing the frequency or strength of peristaltic contractions or by coordinating movement through the GI tract. These drugs act at various sites, notably the stomach and proximal small intestine, to accelerate gastric emptying and improve lower esophageal sphincter tone.

Mechanistically, they include dopamine D2 receptor antagonists such as metoclopramide and domperidone, which increase acetylcholine release in the upper GI tract; 5-HT4 receptor agonists such as prucalopride (and historical tegaserod); and motilin receptor agonists such as erythromycin. Itopride combines D2 antagonism with acetylcholinesterase inhibition to enhance acetylcholine-mediated contraction.

Common indications include gastroparesis, functional dyspepsia, gastroesophageal reflux disease with impaired motility, and nausea or vomiting; they are sometimes used to improve postoperative ileus.

Safety and tolerance vary by drug. Metoclopramide can cause extrapyramidal symptoms and, with long-term use, tardive dyskinesia; domperidone carries a risk of QT interval prolongation and cardiac events; erythromycin can lead to tachyphylaxis and antibiotic resistance; cisapride was withdrawn due to QT prolongation risk. Prucalopride is generally better tolerated but may cause headache or GI upset; acotiamide or itopride are used in some regions for dyspepsia.

Regulatory status of prokinetika varies by country, with several older agents restricted or withdrawn and newer selective agents preferred where appropriate. Use typically requires evaluation of underlying causes of motility disturbance and careful monitoring.