Characteristics of Refractory Gastroesophageal Reflux Disease (GERD) Symptoms -Is Switching Proton Pump Inhibitors Based on the Patient's CYP2C19 Genotype an Effective Management Strategy?

Takeuchi, Toshihisa; Oota, Kazuhiro; Harada, Satoshi; Edogawa, Shoko; Kojima, Yuichi; Sanomura, Makoto; Sakaguchi, Masahiro; Hayashi, Katsuyoshi; Hongoh, Yasushi; Itabashi, Takeshi; Kitae, Hidehiro; Hoshimoto, Masahiro; Takeuchi, Nozomi; Higuchi, Kazuhide

doi:10.2169/internalmedicine.54.3412

Cited by 8 publications

(8 citation statements)

References 23 publications

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“…65 Future studies utilizing such strategies are needed as the only study utilizing this strategy was significantly limited by its small sample size. 27 It is important to note that these studies are almost exclusively limited to patients with EE, and the impact of CYP genotypes on PPI response in NERD is not well described.…”

Section: Discussionmentioning

confidence: 99%

“…26 Switching PPINR from OME 20mg to RBZ 20mg daily was not an effective strategy as there were similar response rates between homoEM/heteroEM and PM (14% vs 67%), though the study was limited by the small number of PPINR (n=17). 27 In regards to ESO, patients treated with ESO 40mg daily for 8 weeks, homoEM, hetero EM and PM had similar rates of persistent EE (43%, 50%, and 35%, respectively) and symptom relapse (65%, 52%, and 69%). 28 Likewise, EE healing rates in patients treated with ESO 40mg daily were similar regardless of CYP polymorphism.…”

Section: Ppi Metabolizer Genotypesmentioning

confidence: 92%

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A review of medical therapy for proton pump inhibitor nonresponsive gastroesophageal reflux disease

Hillman

Yadlapati

Thuluvath

et al. 2017

Diseases of the Esophagus

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Introduction Up to 40% of patients report persistent gastroesophageal reflux disease (GERD) symptoms despite proton pump inhibitor (PPI) therapy. This review outlines the evidence for medical therapy for PPI non-responsive GERD. Materials and Methods A literature search for GERD therapies from 2005–2015 in PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews identified unique 2928 citations. Of those, 40 unique articles specific to the impact of PPI metabolizer genotype on PPI response and the use adjunctive medical therapies were identified. Results Thirteen articles reported impacts on CYP genotypes on PPI metabolism demonstrating lower endoscopic healing rates in extensive metabolizers; however, outcomes across genotypes were more uniform with more CYP independent PPIs rabeprazole and esomeprazole. Twenty-seven publications on 11 adjunctive medications showed mixed results for adjunctive therapies including nocturnal histamine-2 receptor antagonists, promotility agents, transient lower esophageal sphincter relaxation inhibitors, and mucosal protective agents. Discussion Utilizing PPI metabolizer genotype or switching to a CYP2C19 independent PPI is a simple and conservative measure that may be useful in the setting of incomplete acid suppression. The use of adjunctive medications can be considered particularly when the physiologic mechanism for PPI non-response is suspected. Future studies using adjunctive medications with improved study design and patient enrollment are needed to better delineate medical management options before proceeding to anti-reflux interventions.

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Section: Discussionmentioning

confidence: 99%

Section: Ppi Metabolizer Genotypesmentioning

confidence: 92%

A review of medical therapy for proton pump inhibitor nonresponsive gastroesophageal reflux disease

Hillman

Yadlapati

Thuluvath

et al. 2017

Diseases of the Esophagus

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“…Also, Giannikoulis et al found no improvement in cardiopulmonary exercise test after 12 weeks of the treatment with a double dose of omeprazole (21). The different results may be due to the long usage and refractory period of omeprazole (22). In the present study, we used a single dose of omeprazole, just for eight weeks.…”

Section: Discussionmentioning

confidence: 74%

The Effects of Diaphragmatic Breathing and Omeprazole on Respiratory Indices and Diaphragmatic Excursion in Patients with Gastroesophageal Reflux Disease

Ahmadi¹,

Amiri²,

Rezaeian³

et al. 2020

Iran Red Crescent Med J

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Background: Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal disorders that can disturb patients’ respiratory indices. Proton pump inhibitors (PPIs) such as omeprazole are currently the most common treatment in the patients. PPI-refractory GERD is a clinical problem constituting around 30% of patients with GERD. Objectives: The aim of this study was to investigate the effects of diaphragmatic breathing (DB) and omeprazole on respiratory indices (RI) and diaphragmatic excursion (DEX) in patients with GERD. Methods: This is a clinical trial conducted for eight weeks among 40 patients with severe GERD in Tehran in 2018. The block randomization method was designed to randomize 40 patients into two groups (DB and control) that resulted in equal sample sizes. The control group received omeprazole 20 mg once daily, and the DB group, in addition to omeprazole, performed DB. Respiratory indices, including (Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 second (FEV1), Peak Expiratory Flow (PEF)), and DEX were evaluated before, immediately, and six weeks after the end of intervention by spirometry and ultrasonography; respectively. Results: There was no significant difference in the RI and DEX before the intervention between groups. FVC (P = 0.04) and PEF (P = 0.02) significantly changed in the control group, but FEV1 (P = 0.001), FVC (P = 0.002), PEF (P = 0.001) and DEX (0.001) significantly changed after DB. There was a significant difference in terms of RI between before and followed up in DB. Conclusions: Diaphragmatic breathing with omeprazole had more effects on RI and DEX than omeprazole alone. The positive effects of DB remain at least six weeks after the end of the intervention.

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“…No significant differences in resolution of symptoms between rabeprazole 20 mg, esomeprazole 20 mg and 40 mg esomeprazole were identified (75). Regarding the refractory GERD, a recent study evaluates the effect of the change of PPI, noting that 28.4% of patients had no improvement after administration of omeprazole 20 mg daily for 8 weeks and when in this group of patients omeprazole was replaced by rabeprazole 20 mg daily, clinical improvement was observed in only 23.5% (77).…”

Section: Clinical Differences Between Ppismentioning

confidence: 99%

Practical considerations in the management of proton-pump inhibitors

Aguilera¹,

Martín-de-Argila-dePrados²,

Albillos-Martínez³

2015

Rev Esp Enferm Dig

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Proton-pump inhibitors (PPIs) are one of the most active ingredients prescribed in Spain. In recent decades there has been an overuse of these drugs in both outpatient clinics and hospitals that has lead to a significant increase in healthcare spending and to an increase in the risk of possible side effects. It is important for health professionals to know the accepted indications and the correct doses for the use of these drugs. On the market there are different types of PPI: omeprazole, pantoprazole, lansoprazole, rabeprazole and esomeprazole. Omeprazole is the oldest and most used PPI, being also the cheapest. Although there are no important differences between PPIs in curing diseases, esomeprazole, a newgeneration PPI, has proved to be more effective in eradicating H. pylori and in healing severe esophagitis compared to other PPIs. In recent years the use of generic drugs has spread; these drugs have the same bioavailability than the original drugs. In the case of PPIs, the few comparative studies available in the literature between original and generic drugs have shown no significant differences in clinical efficacy.Key words: Proton-pump inhibitor. PPI. Omeprazole. Pantoprazole. Lansoprazole. Rabeprazole. Esomeprazole. INTRODUCTIONProton-pump inhibitors (PPIs) represent a family of drugs widely used in our country. The advent in the nineties of PPIs was a great revolution in the treatment of ulcer disease and gastroesophageal reflux. The main problems of PPIs at present time are its overuse and the errors in the therapeutic indication. This fact leads to a considerable health economic cost and the risk of long-term side effects. In this review the main problems of PPIs prescription, their indications, the differences between PPIs and tips on their use are discussed. Brief historical memory: since alkaline diets until PPIsThe treatment of ulcer disease and gastroesophageal reflux disease (GERD) in the early twentieth century was the prescription of alkaline foods like milk, eggs and puree (1). Later, there were products as sodium bicarbonate that improved symptoms but did not prevent complications. Surgical treatment consisted of different types of gastric surgeries for peptic ulcer disease and Nissen fundoplication for GERD (2).In the mid twentieth century the use of muscarinic antagonists was introduced, atropine being its main active ingredient. Acids secretion was partially inhibited by blocking the muscarinic receptor of the parietal cell. However, these drugs had little effectiveness and numerous adverse effects due to the amount of muscarinic receptors distributed throughout the body. E-type prostaglandin was discovered later, but, again, the limitations of these substances were their short half life and side effects. An important progress in gastric antisecretory therapy was the appearance of H 2 receptors antagonists (H 2 blockers) (3). The most used were ranitidine and famotidine. These drugs established a substantial change by blocking the action of histamine receptor in gastric parietal ...

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Characteristics of Refractory Gastroesophageal Reflux Disease (GERD) Symptoms -Is Switching Proton Pump Inhibitors Based on the Patient's CYP2C19 Genotype an Effective Management Strategy?

Cited by 8 publications

References 23 publications

A review of medical therapy for proton pump inhibitor nonresponsive gastroesophageal reflux disease

A review of medical therapy for proton pump inhibitor nonresponsive gastroesophageal reflux disease

The Effects of Diaphragmatic Breathing and Omeprazole on Respiratory Indices and Diaphragmatic Excursion in Patients with Gastroesophageal Reflux Disease

Practical considerations in the management of proton-pump inhibitors

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