Pharmacological Options Beyond Proton Pump Inhibitors in Children with Gastroesophageal Reflux Disease Armano C, Fumagalli LA, Ripepi A, Moretti A, Macchi F, Scolari A and Salvatore S * Pediatric Department, Ospedale “F. Del Ponte”, Università dell’Insubria, Varese, Italy * Corresponding author: Salvatore S, Pediatric Department, Ospedale “F. Del Ponte”, Università dell’Insubria, Varese, Italy, Tel: 0039-0-332 299247; E-mail: silvia.salvatore@uninsubria.it Received date: August 29, 2016; Accepted date: October 10, 2016; Published date: October 18, 2016 Copyright: © 2016 Armano C, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Pharmacological treatment of gastroesophageal reflux (GER) disease is mostly based on acid control. However, different molecules have been proposed both for patients with persisting symptoms and to limit adverse effects of proton pump inhibitors (PPI). This paper focuses on other acid inhibitors, alginate, prokinetics, drug acting on lower esophageal sphincter and esophageal hypersensitivity. Mechanism of action, indications, efficacy, limits and recent advances are reported. Pediatric data and possible adverse effects are also considered. Keywords: Refux; Ranitidine; Alginate; Prokinetics; Baclofen Abbreviations: ASIC: Acid-sensitive ion channels; ESPGHAN: European Society for Paediatric Gastroenterology, Hepatology and Nutrition; GABA: γ aminobutyric acid; GER: Gastroesophageal refux; GERD: Gastroesophageal refux disease; NASPGHAN: North American Society for Pediatric Gastroenterology, Hepatology and Nutrition; NICE: National Institute for Health and Care Excellence; PPI: Proton pump inhibitors; PCABs: Acid-inhibitor acting on potassium; SSRIs: Serotonine selective re-uptake inhibitors; TLESRs: Transient lower esophageal sphincter relaxation; TRPV: Transient receptor potential vanilloid. Introduction Proton pump inhibitors (PPI) are the treatment of choice both for children and adolescents with heartburn, refux esophagitis, pathological acid exposure or signifcant association with symptoms related to acid gastroesophageal refux (GER) detected by (impedance) pH-monitoring [1]. Persisting symptoms on PPI may be related to several factors such as: insufcient drug dosage (e.g., in neurological patients), incorrect intake (e.g., not before the frst meal of the day), major efect of the non-acid component (or currently classifed as weakly acid refux with pH>4) or of the volume of refux (esophageal distention) in the generation of symptoms, esophageal hypersensitivity, primary motor disorders or other diagnosis (non GER disorder). Te pathogenesis of GER disease (GERD) is complex and include several contributing factors such as inappropriate lower esophageal sphincter (LES) relaxations, abnormal esophageal motility and clearance, delayed gastric emptying, increased both acid and non-acid GER, impaired esophageal resistance and esophageal hypersensitivity. Physiologic GER and infantile regurgitation do not need medical treatment although they frequently cause parental distress and anxiousness [1]. Management in these patients should be based on parental education and reassurance, dietary and, eventually, positional treatment. Pharmacological therapy used to treat GERD encompass antisecretory agents, antacids, surface barrier agents, prokinetics, agents reducing LES relaxations and, more recently in adult patients, anti-depressant drugs. From the pathophysiologic point of view, prokinetic drugs are the most logic therapeutic approach to treat GERD because they improve the motility of both esophagus and stomach, reducing the time of the esophageal contact with refuxate and accelerating gastric emptying. However, there is no efective and safe prokinetic agent on the market. Appropriate treatment of GERD is important to reduce GER related symptoms and possible esophageal (e.g., esophagitis) and extra- esophageal (e.g., respiratory manifestations, sleeping or feeding disturbances) complications and to improve quality of life of the patients. Tis article focuses on current therapeutic pharmacological options beyond PPI in GERD and updates the current pediatric data of other acid-inhibitors, “barrier agents”, prokinetics, and drugs that act on the inferior esophageal sphincter or on the “symptomatic sensitivity” (Table 1). Neither non-pharmacological therapies (e.g., postural, dietetic ones) nor endoscopic and surgical treatments will be herein discussed. Other acid-inhibitors except PPI Ranitidine is ofen (too much) administered, especially in infants, on clinical basis without a proven diagnosis of GERD. Te preference towards ranitidine compared to PPI is mostly related to its availability as a syrup and of-label use of PPI in the frst year of life. Ranitidine (at an oral dose of 5-10 mg/kg/die divided in 2-3 doses) suppresses the gastric acid secretion less (partially) and for a shorter period (about 4-8 hours) of time compared to PPI, and is ofen associated with tachyphylaxis, which cannot be solved with an increase of the dosage. In 2006 Pfeferkorn evaluated the possible beneft of ranitidine (4 mg/kg), as add-on therapy to PPI, to cover the night-time acid secretion (nocturnal acid breakthrough) in children with refux esophagitis. Tere was no evidence of any decrease in the symptomatic score, in the acid exposure detected by pH-monitoring or in the esophageal mucosal lesions compared to placebo [2]. Armano et al., J Dev Drugs 2016, 5:3 DOI: 10.4172/2329-6631.1000161 Review Article Open Access J Dev Drugs, an open access journal ISSN: 2329-6631 Volume 5 • Issue 3 • 1000161 Journal of Developing Drugs J o u r n a l o f D e v e l o p i n g D r u g s ISSN: 2329-6631