New and Future Drug Development for Gastroesophageal Reflux Disease

Maradey–Romero, Carla; Fass, Ronnie

doi:10.5056/jnm.2014.20.1.6

Cited by 63 publications

(65 citation statements)

References 87 publications

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“…106 Therefore, patients with GERD are frequently treated with PPIs. 107,108 However, 17-32% of patients with GERD experienced persistent and troublesome heartburn or regurgitation despite standard-dose PPI treatment. In addition, the majority experienced refractory symptoms at higher doses.…”

Section: Sex/gender and Treatment Responsementioning

confidence: 99%

Sex and Gender Differences in Gastroesophageal Reflux Disease

Kim

2016

J Neurogastroenterol Motil

122

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It is important to understand sex and gender-related differences in gastroesophageal reflux disease (GERD) because gender-related biologic factors might lead to better prevention and therapy. Non-erosive reflux disease (NERD) affects more women than men. GERD symptoms are more frequent in patients with NERD than in those with reflux esophagitis. However, men suffer pathologic diseases such as reflux esophagitis, Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC) more frequently than women. The prevalence of reflux esophagitis is significantly increased with age in women, especially after their 50s. The mean age of EAC incidence in women is higher than in men, suggesting a role of estrogen in delaying the onset of BE and EAC. In a chronic rat reflux esophagitis model, nitric oxide was found to be an aggravating factor of esophageal injury in a male-predominant way. In addition, the expression of esophageal occludin, a tight junction protein that plays an important role in the esophageal defense mechanism, was up-regulated in women. This explains the male predominance of reflux esophagitis and delayed incidence of BE or EAC in women. Moreover, the symptoms such as heartburn, regurgitation, and extra-esophageal symptoms have been more frequently reported by women than by men, suggesting that sex and gender play a role in symptom perception. Differential sensitivity with augmented symptoms in women might have diagnostic and therapeutic influence. Furthermore, recent studies have suggested that hormone replacement therapy has a protective effect against esophageal cancer. However, an anti-inflammatory role of estrogen remains compelling, which means further study is necessary in this area.

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Section: Sex/gender and Treatment Responsementioning

confidence: 99%

Sex and Gender Differences in Gastroesophageal Reflux Disease

Kim

2016

J Neurogastroenterol Motil

122

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“…It could help physicians and patients to gain an insight into the symptoms possibly related to foods and reinsure avoidance of these foods. Regardless of the emergence of potent medicines (such as improved proton pump inhibitors, transient lower esophageal sphincter relaxation reducers, mucosal protectants, and esophageal-specific pain modulators), 31 correctable diet modifications should be emphasized.…”

Section: Discussionmentioning

confidence: 99%

Foods Inducing Typical Gastroesophageal Reflux Disease Symptoms in Korea

Choe

Joo

Kim

et al. 2017

J Neurogastroenterol Motil

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Background/AimsSeveral specific foods are known to precipitate gastroesophageal reflux disease (GERD) symptoms and GERD patients are usually advised to avoid such foods. However, foods consumed daily are quite variable according to regions, cultures, etc. This study was done to elucidate the food items which induce typical GERD symptoms in Korean patients. MethodsOne hundred and twenty-six Korean patients with weekly typical GERD symptoms were asked to mark all food items that induced typical GERD symptoms from a list containing 152 typical foods consumed daily in Korea. All patients underwent upper gastrointestinal endoscopy followed by 24-hour ambulatory esophageal pH monitoring. The definition of "GERD" was if either of the 2 studies revealed evidence of GERD, and "possible GERD" if both studies were negative. ResultsOne hundred and twenty-six cases (51 GERD and 75 possible GERD) were enrolled. In 19 (37.3%) of 51 GERD cases and in 17 (22.7%) of 75 possible GERD cases, foods inducing typical GERD symptoms were identified. In the GERD group (n = 19), frequent symptominducers were hot spicy stews, rice cakes, ramen noodles, fried foods, and topokki. In the possible GERD group (n = 17), frequent symptom-inducers were hot spicy stews, fried foods, doughnuts, breads, ramen noodles, coffee, pizza, topokki, rice cakes, champon noodles, and hotdogs. ConclusionsIn one-third of GERD patients, foods inducing typical symptoms were identified. Hot spicy stews, rice cakes, ramen noodles, fried foods, and topokki were the foods frequently inducing typical symptoms in Korea. The list of foods frequently inducing typical GERD symptoms needs to be modified based on their own local experiences.

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“…Finally, we await information on the effects of newer compounds with different mechanisms of action, including potassium-competitive acid blockers, inhibitors of transient lower esophageal sphincter relaxation, serotonergic agents/prokinetics, mucosal protectants, histamine H 3 receptor agonists, anti-gastrin agents, and esophageal pain modulators [29, 30]. …”

Section: Proton Pump Inhibitors: Harms and Questionsmentioning

confidence: 99%

Inhibiting the proton pump: mechanisms, benefits, harms, and questions

Aronson

2016

BMC Med

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Inhibition of the H+/K+-adenosine triphosphatase (the proton pump) is the final common mechanistic pathway in reducing gastric acid secretion pharmacologically. Proton pump inhibitors are widely used in upper gastrointestinal diseases, including gastric and duodenal ulcers, eradication of Helicobacter pylori in combination with antibiotics, gastroesophageal reflux disease, Zollinger–Ellison syndrome, eosinophilic esophagitis, and prevention of non-steroidal anti-inflammatory drug-induced peptic ulceration. Reviewing their benefits and harms in BMC Medicine, Scarpignato et al. report effectiveness in these conditions, and harms that are generally mild and uncommon (1–3 %). Serious adverse reactions, such as tubulointerstitial nephritis, are rare. However, the risks of gastric and pancreatic cancer are unclear. Drug–drug interactions can occur through effects on P glycoprotein and cytochrome P450 (CYP) isoenzymes. Several questions remain. Do all proton pump inhibitors carry the same risks of serious adverse reactions? Which individuals are most susceptible? What are the time courses of individual reactions? What monitoring strategies are best? New drugs for the same indications continue to emerge, including potassium-competitive acid blockers, inhibitors of transient lower esophageal sphincter relaxation, serotonergic agents/prokinetics, mucosal protectants, histamine H3 receptor agonists, anti-gastrin agents, and esophageal pain modulators. Their benefit to harm balance remains to be discovered.Please see related article: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0718-z

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New and Future Drug Development for Gastroesophageal Reflux Disease

Cited by 63 publications

References 87 publications

Sex and Gender Differences in Gastroesophageal Reflux Disease

Sex and Gender Differences in Gastroesophageal Reflux Disease

Foods Inducing Typical Gastroesophageal Reflux Disease Symptoms in Korea

Inhibiting the proton pump: mechanisms, benefits, harms, and questions

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