Gastroesophageal Reflux and Prokinetics
Prokinetic agents have been widely employed in pediatric patients in order to reduce the symptoms of GERD. These drugs seem to enhance lower esophageal sphincter (LES) tone, to improve esophageal clearance, and to increase gastric motility thus increasing emptying of gastric contents.
Cisapride was probably the best studied prokinetic agent in children; however, it was taken off the market in the 2000s by the European and American authorities owing to its cardiac side effects. Other agents such as metoclopramide and domperidone have been evaluated, but a high incidence of adverse effects including drowsiness, restlessness, and extrapyramidal reactions has been reported. Bethanechol, a direct-acting cholinergic agonist, has been evaluated in a few studies and also has uncertain efficacy and a high incidence of adverse effects in children with GERD. Other prokinetic molecules including mosapride, itopride, and prucalopride have not been studied or have been insufficiently tested in children. Baclofen, used to treat patients with neurological impairment, is a γ-aminobutyric acid receptor agonist that was shown to be effective in reducing the number of transient lower esophageal sphincter relaxations (TLSERs) and acid GER as well as to accelerate gastric emptying. However, data on baclofen in pediatric GERD are very limited, and the high incidence of adverse events does not justify its widespread use. Other agents acting on TLSERs such as arbaclofen and lesogaberan have been evaluated in adult patients, but studies in children are lacking.
Overall, although the prokinetic concept is attractive, no effective and safe drug is currently available. Furthermore, all agents have a high incidence of adverse effects that outweigh the benefits achieved with their use.
KeywordsGastroesophageal reflux disease Children Pediatrics Drug therapy Prokinetic Cisapride Domperidone Metoclopramide Bethanechol Baclofen
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