medical treatment for GERD acid reflux

2Surface Protective Agents

 Surface protective agents usually contain alginate or sucralfate. Alginates are insoluble salts of alginic acid, a common anionic polysaccharide found in the cell walls of some algae. Alginate acts as a gumming agent and is typically combined with sodium bi-carbonate/potassium bicarbonate. When exposed to gastric acid, the bicarbonate is converted to carbon dioxide, which is then trapped by the alginate gel, forming a ‘foam raft’ that floats atop the gastric contents. In doing so, it acts as a buffering agent as well as a physical barrier to reflux of gastric contents into the esoph-agus. A systematic review of studies of alginates in children revealed variable efficacy with evidence that these preparations can marginally reduce the height of reflux episodes in the esoph-agus but may relieve symptoms temporarily.( Tighe MP, et al ,2009)

Sucralfate is a combination of sucrose, sulfate, and alumi-num. In an acidic environment, it forms a gel that binds to the exposed mucosa of peptic erosions. It has been shown to pro-mote healing of non-erosive esophagitis in adults but there is a paucity of safety and efficacy data in children and adoles-cents. Furthermore, there is the risk of aluminum toxicity with long-term use. The joint North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) guidelines do not recommend the sole use of these agents for treatment of severe symptoms or erosive esophagitis. .( Vandenplas Y, et al , 2009)

3Antacids

These products are acid buffers containing magnesium hy-droxide or aluminum hydroxide. On-demand, intermittent use may be helpful in providing symptom relief of heartburn in some children and adolescents with typical reflux syndrome, although it has not been formally studied in the pediatric population. Prolonged or high-dose use of aluminum-containing antacids has been associated with high plasma levels of aluminum and the potential for osteopenia, rickets, micro-cytic anemia, and neurotoxicity. Similarly, long-term, high-dose usage of calcium carbonate-based antacids is asso-ciated with the milk-alkali syndrome, a triad of hypercalcemia, alkalosis, and renal failure. Therefore, antacids should be utilized with caution in children, and prolonged use avoided in preference for safer and more superior treatments listed below. (Beall DP, et al , 2006)

4Histamine H2 Receptor Antagonists

Histamine H2 receptor antagonists (H2RAs) reduce gastric acidity by inhibiting secretion of gastric acid and pepsin from gastric parietal cells. Studies have shown superior efficacy of H2RAs (cimetidine, ranitidine, famotidine, and nizatidine) over placebo in improvement of symptoms as well as endoscopic features.( van Pinxteren B, et al , 2006)

Fewer studies have been conducted in pediatric populationsand there are no randomized controlled trials (RCTs) examining the efficacy of the most commonly prescribed H2RA in children, ranitidine, in the treatment of esophagitis. Extrapolation of large adult RCTs to older children and adolescents suggests that H2RAs may be an ef-fective short-term treatment in these patients for GERD symptoms and for healing of milder cases of esophagitis, al-though they are less effective than PPIs. Furthermore, the development of fairly rapid tachyphylaxis (diminution of the drug’s efficacy over time) limits its prolonged use.  Ranitidine is generally well tolerated in pediatric patients. The initial dose of ranitidine is usually 4–10 mg/kg/day ad-ministered in two to three divided doses orally. In general, dosing is twice daily, although there is evidence from infant studies that a 2 mg/kg/dose orally with three times daily dosing may achieve greater acid suppression. Some authors pro-mote an increase to 20 mg/kg/day if standard dosing does not control symptoms, although a change to a PPI is arguably safer and more efficacious. (Khan M,et al , 2007)

 

5Proton Pump Inhibitors

 PPIs suppress gastric acid by irreversibly inhibiting the parietal cell enzyme hydrogen-potassium stimulated ATPase (H+, K+-ATPase, also known as the ‘gastric proton pump’). As a class, they are the most potent inhibitors of gastric acid se-cretion available. The superior efficacy of PPIs over H2RAs has been well established in numerous RCTs in the adult pop-ulation. PPIs are superior in healing esophagitis as well as in maintaining remission. Unlike H2RAs, PPIs are able to inhibit meal-induced acid secretion, do not lose their potency over time, and, in adults, have been shown to be effective in treating H2RA non-responsive GERD.( Savarino V, et al ,2009)

Furthermore, PPIs have been shown to have superior acid-suppressing abil-ity, resulting in decreased 24-hour gastric secretion volumes, thereby facilitating gastric emptying and reducing residual gastric volumes. Several limitations of PPIs relate to their unique pharma-cologic properties. PPIs can only inhibit ‘activated’ proton pumps in the canalicular membrane, and the amount of proton pumps present in the parietal cell is maximal following a pro-longed fast. Thus, PPIs should be administered before the first meal of the day in order to achieve optimal control of daytime gastric acidity.( Kahrilas PJ et al ,2008)

As more enzyme is subsequently recruited into the canalicular membrane, it is made available for in-activation by accumulating drug. Time to maximal acid in-hibition is reported to take between 2 and 8 days, and, as such, PPIs do not reliably lend themselves to intermittent or occa-sional use as well as the rapid onset H2RAs. Although similar in structure, PPIs exhibit variable metab-olism by the hepatic cytochrome P450 (CYP) enzyme system, specifically CYP2C19 and CYP3A4 enzymes. Genetic CYP polymorphisms can affect the biotransformation of PPIs and their plasma clearance, potentially resulting in altered clinical response. This may underpin the reason for such variable dosing utilized in many pediatric studies. ( Kearns GL, et al , 2010)

Furthermore, variations in CYP activity may increase the potential for some metabolism-based drug-drug interactions in certain in-dividuals.[63,68] Compared with the adult literature, there is a paucity of safety and efficacy data for PPIs in children. More recently, there have been several pharmacokinetic and safetystudies in children published suggesting PPI usage to be safe and  efficacious,  although  children  may  require  a  higher  per kilogram dose for some PPIs than adults and adolescents in order to obtain a similar degree of acid suppression.( Orenstein SR, et al ,2007)

Side  effect  profiles  of  the  different  PPIs  are  fairly  com-parable   and  can   be  considered  in  four  main   categories: idiosyncratic  reactions;  drug-drug  interactions;  drug-induced hypergastrinemia; and drug-induced hypochlorhydria. Over-all,  PPIs  appear  well  tolerated  by  children  and  adolescents but side effects (mostly mild) have been reported to occur in up to 14% of children and adolescents on therapy. The most common reactions  include  headache,  diarrhea,  constipation  and  nau-sea. Other,  potentially  more  serious,  reactions  described mostly in the adult literature. (Williams C, et al ,2006)

It should be noted that these events are generally uncommon and have been only rarely reported in children and adolescents. One study ex-amining the outcomes of long-term PPI use (up to 11 years) in children showed that side effects were very few and were seldom indications for discontinuation of PPI therapy.  Commercially available PPIs for which safety and efficacy data exist for children include omeprazole, lansoprazole, pantoprazole, esomeprazole, and rabeprazole. Compounded PPI therapies, such as omeprazole and sodium bicarbonate, as well as novel PPI formulations, such as dexlansoprazole, the R-enantiomer of lan-soprazole, are emerging onto the commercial market but no pe-diatric safety or efficacy data have yet been published. Currently, no appropriate liquid formulation of PPI therapy is available for children who cannot (or will not) take a solid oral dosage form. In some countries, an oral dissolvable tablet form of lansoprazole is available.( Garcia Rodriguez LA, et al , 2007)

Similarly, esomeprazole is available as granules for delayed release oral suspension, but care must be taken not to chew or crush the pellets/granules. Unfortunately, these products are not licensed for use in children in all coun-tries. As a result, extemporaneous liquid formulations have been prepared with little research examining their stability and bioavailability. A number of PPIs are now available in a multiple-unit pellet form where each capsule contains numerous individually enteric-coated microspheres. These microspheres can be suspended in a mildly acidic medium such as apple, orange, or cranberry juice, and swallowed without chewing or crushing them. Appropriate administration of the drug is paramount to its effectiveness as the low pH environment of the stomach can render the non-enteric-coated drug inactive.  Dosing for each PPI can vary; therefore, reference should be made to the individual drug monographs before prescribing.( Canani RB, et al ,2006) 

6-Prokinetics Prokinetics include drugs such as erythromycin, domper-idone, metoclopramide, bethanecol, and cisapride. Currently, there is insufficient evidence to justify the use of prokinetics in the management of simple GERD and they should not be uti-lized as first-line therapies. Furthermore, their potential for serious side effects should limit their use to restricted programs with specialist supervision.( Pritchard DS, et al ,2005)