|
1
|
Visaggi P, Bertin L, Pasta A, Calabrese F, Ghisa M, Marabotto E, Ribolsi M, Savarino V, de Bortoli N, Savarino EV. Pharmacological management of gastro-esophageal reflux disease: state of the art in 2024. Expert Opin Pharmacother 2024; 25:2077-2088. [PMID: 39392340 DOI: 10.1080/14656566.2024.2416585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Revised: 10/03/2024] [Accepted: 10/10/2024] [Indexed: 10/12/2024]
Abstract
INTRODUCTION Gastroesophageal reflux disease (GERD) is a chronic disease of the esophagus characterized by the regurgitation of stomach contents into the esophagus, causing troublesome symptoms and/or complications. Among patients with GERD, around 30% of patients have visible mucosal damage, while 70% have normal esophageal mucosa. Accordingly, the optimal pharmacological treatment of GERD should address different disease manifestations, including symptoms, the mucosal damage when present, and possible chronic complications, including strictures, Barrett's esophagus, and esophageal adenocarcinoma. AREAS COVERED Available medical treatments for GERD include proton pump inhibitors (PPIs), potassium-competitive acid blockers (PCABs), histamine receptor antagonists (H2-RAs), prokinetics, and mucosal protectants, such as alginates, hyaluronic acid/chondroitin-sulfate, and poliprotect. Each compound has its own advantages and disadvantages, and knowledge of expected benefits and tips for their use is paramount for the success of treatment. In addition, the appropriateness of indications for initiating treatment is also crucial to achieve positive results when managing GERD patients. EXPERT OPINION PPIs, PCABs, H2-RAs, prokinetics, and mucosal protectants can all be used in patients with GERD, but careful assessment of patients' characteristics as well as advantages and disadvantages of each therapeutic compound is essential to ensure successful treatment of GERD.
Collapse
Affiliation(s)
- Pierfrancesco Visaggi
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Luisa Bertin
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Andrea Pasta
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | | | - Matteo Ghisa
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Elisa Marabotto
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Policlinico San Martino, Genoa, Italy
| | - Mentore Ribolsi
- Unit of Gastroenterology and Digestive Endoscopy, Campus Bio Medico University, Rome, Italy
| | | | - Nicola de Bortoli
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Edoardo Vincenzo Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| |
Collapse
|
|
2
|
Miyazaki H, Igarashi A, Takeuchi T, Teng L, Uda A, Deguchi H, Higuchi K, Tango T. Vonoprazan versus proton-pump inhibitors for healing gastroesophageal reflux disease: A systematic review. J Gastroenterol Hepatol 2019; 34:1316-1328. [PMID: 30883868 DOI: 10.1111/jgh.14664] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Revised: 03/08/2019] [Accepted: 03/10/2019] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND AIM Gastroesophageal reflux disease (GERD) is a common disease caused by reflux of gastric contents to the esophagus. Proton-pump inhibitors (PPIs) are recommended as a first-line therapy to treat GERD. Recently, a new potassium-competitive acid blocker, vonoprazan, was launched in Japan. We aimed to evaluate the comparative efficacy of vonoprazan and other PPIs in healing GERD. METHODS We used MEDLINE and the Cochrane Central Register of Controlled Trials to search the literature. Double-blind randomized controlled trials for PPIs and/or vonoprazan that were published in English or Japanese and assessed healing effects in adult GERD patients were included. To estimate the comparative efficacy of treatments, we performed a Bayesian network meta-analysis to assess the consistency assumption. RESULTS Of 4001 articles identified in the database, 42 studies were eligible. One study was hand-searched and added to the analysis. For the main analysis of healing effects at 8 weeks, odds ratios (ORs) of vonoprazan (20 mg daily) to esomeprazole (20 mg), rabeprazole (20 mg), lansoprazole (30 mg), and omeprazole (20 mg) were 2.29 (95% credible interval, 0.79-7.06), 3.94 (1.15-14.03), 2.40 (0.90-6.77), and 2.71 (0.98-7.90), respectively. Subgroup analysis for patients with severe esophagitis at baseline showed significantly higher ORs for vonoprazan versus most of the comparator PPIs. CONCLUSIONS This analysis shows that the GERD healing effect of vonoprazan is higher than that of rabeprazole (20 mg) but not higher than other PPIs. Subgroup analysis indicated that vonoprazan is more effective than most PPIs for patients with severe erosive esophagitis.
Collapse
Affiliation(s)
- Hirota Miyazaki
- Second Department of Internal Medicine, Osaka Medical College, Osaka, Japan
| | - Ataru Igarashi
- Department of Health Economics and Outcomes Research, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
| | - Toshihisa Takeuchi
- Second Department of Internal Medicine, Osaka Medical College, Osaka, Japan
| | - Lida Teng
- Department of Health Economics and Outcomes Research, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
| | - Akihito Uda
- Japan Medical Affairs, Takeda Pharmaceutical Company Ltd, Tokyo, Japan
| | - Hisato Deguchi
- Japan Medical Affairs, Takeda Pharmaceutical Company Ltd, Osaka, Japan
| | - Kazuhide Higuchi
- Second Department of Internal Medicine, Osaka Medical College, Osaka, Japan
| | - Toshiro Tango
- Director's Office, Center for Medical Statistics, Tokyo, Japan
| |
Collapse
|
|
3
|
Schmulson M, Frati-Munari A. Bowel symptoms in patients that receive proton pump inhibitors. Results of a multicenter survey in Mexico. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2019. [DOI: 10.1016/j.rgmxen.2018.05.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
|
|
4
|
Shim YK, Kim N. The Effect of H 2 Receptor Antagonist in Acid Inhibition and Its Clinical Efficacy. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2018; 70:4-12. [PMID: 28728310 DOI: 10.4166/kjg.2017.70.1.4] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
The first histamine H2 receptor antagonists (H2RAs) were developed in the early 1970s. They played a dominant role in treating peptic ulcer disease and gastroesophageal reflux disease (GERD). H2RAs block the production of acid by H+, K+-ATPase at the parietal cells and produce gastric luminal anacidity for varying periods. H2RAs are highly selective, and they do not affect H1 receptors. Moreover, they are not anticholinergic agents. Sequential development of H2RAs, proton pump inhibitors (PPIs), and discovery of Helicobacter pylori infection changed the paradigm of peptic ulcer disease with marked decrease of morbidity and mortality. PPIs are known to be the most effective drugs that are currently available for suppressing gastric acid secretion. Many studies have shown its superiority over H2RAs as a treatment for acid-related disorders, such as peptic ulcer disease, GERD, and Zollinger-Ellison syndrome. However, other studies have reported that PPIs may not be able to render stomach achlorhydric and have identified a phenomenon of increasing gastric acidity at night in individuals receiving a PPI twice daily. These nocturnal acid breakthrough episodes can be eliminated with an addition of H2RAs at night. The effectiveness of nighttime dose of H2RA suggests a major role of histamine in nocturnal acid secretion. H2RAs reduce secretion of gastric acid, and each H2RA also has specific effects. For instance, nizitidine alleviates not only symptoms of GERD, but also provokes gastric emptying, resulting in clinical symptom improvement of functional dyspepsia. The aim of this paper was to review the characteristics and role of H2RAs and assess the future strategy and treatment of upper gastrointestinal disease, including acid related disorders.
Collapse
Affiliation(s)
- Young Kwang Shim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| |
Collapse
|
|
5
|
Schmulson MJ, Frati-Munari AC. Bowel symptoms in patients that receive proton pump inhibitors. Results of a multicenter survey in Mexico. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2018; 84:44-51. [PMID: 29678362 DOI: 10.1016/j.rgmx.2018.02.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/17/2017] [Revised: 02/20/2018] [Accepted: 02/23/2018] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Proton pump inhibitors (PPIs) have been associated with small intestinal bacterial overgrowth (SIBO), which increases with prolonged PPI use, and SIBO has been associated with irritable bowel syndrome (IBS). OBJECTIVE The aim of the present study was to study the prevalence of bowel symptoms in patients treated with PPIs in Mexico. METHODS Gastroenterologists in 36 cities surveyed patients treated with PPIs, utilizing an ad hoc questionnaire to determine the presence of bowel symptoms and IBS. RESULTS Two hundred and fifteen physicians interviewed 1,851 patients. PPI indications were gastritis (48.8%), gastroesophageal reflux (38.5%), peptic ulcer (6.2%), and others (6.5%). A total of 77.5% of the patients received treatment for ≤6 months and 11.9% for ≥1 year. Symptoms were reported in 92.3% of the patients: abnormal bowel habits (90%), bloating (82%), abdominal pain (63%), flatulence (58%), and abdominal discomfort (53%). A total of 67.5% of the patients fit the Rome III criteria for IBS. Symptoms presented in 55.9% of the patients before PPI intake and in 44.1% of the patients after PPI use (P<.005). Constipation (63.8%) predominated in the former, and diarrhea (56.5%) in the latter (P<.0001). The treatments prescribed for managing those symptoms were antispasmodics, antibiotics, prokinetics, and antiflatulents, but patients stated greater satisfaction with antibiotics (mainly rifaximin) (P<.0001). CONCLUSION The association of PPIs with bowel symptoms and IBS is frequent in Mexico. Diarrhea and bloating predominate, and antibiotics produce the greatest treatment satisfaction, suggesting that SIBO or dysbiosis is the cause of the PPI-related bowel symptoms. However, that remains to be confirmed.
Collapse
Affiliation(s)
- M J Schmulson
- Laboratorio de Hígado, Páncreas y Motilidad (HIPAM)-Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Hospital General de México, Ciudad de México, México; Gastroenterología y Motilidad Gastrointestinal, Clínica Lomas Altas SC, Ciudad de México, México; Gastroenterología y Endoscopía en Práctica Médica-Centro Médico ABC, Ciudad de México, México.
| | - A C Frati-Munari
- Alfa Wassermann S.A. de C.V., Ciudad de México, México; Medicina interna, Hospital Médica Sur, Ciudad de México, México
| |
Collapse
|
|
6
|
Prospective Study of Gastroesophageal Reflux, Use of Proton Pump Inhibitors and H2-Receptor Antagonists, and Risk of Hearing Loss. Ear Hear 2018; 38:21-27. [PMID: 27556519 DOI: 10.1097/aud.0000000000000347] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
OBJECTIVES Gastroesophageal reflux disease (GERD) is common and often treated with proton pump inhibitors (PPIs) or H2-receptor antagonists (H2-RAs). GERD has been associated with exposure of the middle ear to gastric contents, which could cause hearing loss. Treatment of GERD with PPIs and H2-RAs may decrease exposure of the middle ear to gastric acid and decrease the risk of hearing loss. We prospectively investigated the relation between GERD, use of PPIs and H2-RAs, and the risk of hearing loss in 54,883 women in Nurses' Health Study II. DESIGN Eligible participants, aged 41 to 58 years in 2005, provided information on medication use and GERD symptoms in 2005, answered the question on hearing loss in 2009 or in 2013, and did not report hearing loss starting before the date of onset of GERD symptoms or medication use. The primary outcome was self-reported hearing loss. Cox proportional hazards regression was used to adjust for potential confounders. RESULTS During 361,872 person-years of follow-up, 9842 new cases of hearing loss were reported. Compared with no GERD symptoms, higher frequency of GERD symptoms was associated with higher risk of hearing loss (multivariable adjusted relative risks: <1 time/month 1.04 [0.97, 1.11], several times/week 1.17 [1.09, 1.25], daily 1.33 [1.19, 1.49]; p value for trend <0.001). After accounting for GERD symptoms, neither PPI nor H2-RA use was associated with the risk of hearing loss. CONCLUSIONS GERD symptoms are associated with higher risk of hearing loss in women, but use of PPIs and H2-RAs are not independently associated with the risk.
Collapse
|
|
7
|
Abstract
OBJECTIVES The aim of the study was to determine whether esophageal baseline impedance (BI) values in children could be predictive of esophagitis. MATERIALS AND METHODS Multichannel intraluminal impedance (MII) tracings of children 3 to 17 years of age suspected of having gastroesophageal reflux and esophagitis, who had also undergone upper endoscopy with multiple esophageal biopsies, were reviewed. Patients with eosinophilic esophagitis were excluded. Esophagitis was assessed by macroscopic and microscopic parameters. Esophageal histology was reported by 2 blinded independent pathologists unaware of the MII results. Mean BI was automatically calculated in the different MII channels (ch) by the specific software without removing any episode of increased/decreased BI. BI results were plotted against macroscopic and histological scores for each channel. RESULTS Tracings of 87 children, 53 boys, were evaluated. Mean age was 7.4 years: 45 had histologic esophagitis, 8 macroscopic. Histologic mild esophagitis (grade 1) was observed in 30, and 15 had moderate to severe esophagitis (grade 2-3). Ten had grade 3 esophagitis. Eight had macroscopic esophagitis as well. RESULTS in channel 6 of the MII, all 10 patients with grade 3 esophagitis and the 8 with macroscopic esophagitis had a BI <900 Ω/s (positive predictive value 100% and negative predictive value 100%), whereas none of those having a biopsy score of 0 to 2 or no endoscopic evidence of esophagitis had a mean BI below 2000 Ω/s. CONCLUSIONS The evaluation of the BI measured in channel 6 gave us 100% prediction of grade 3 and macroscopic esophagitis. BI on channel 6 may be useful to predict severe esophageal mucosa inflammation and could potentially be used for follow-up evaluation, rather than repeating an upper endoscopy. In addition, it would seem that grade 3 esophagitis even in the absence of macroscopic esophagitis affects the integrity of the esophageal epithelium.
Collapse
|
|
8
|
Boghossian TA, Rashid FJ, Thompson W, Welch V, Moayyedi P, Rojas‐Fernandez C, Pottie K, Farrell B. Deprescribing versus continuation of chronic proton pump inhibitor use in adults. Cochrane Database Syst Rev 2017; 3:CD011969. [PMID: 28301676 PMCID: PMC6464703 DOI: 10.1002/14651858.cd011969.pub2] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Proton pump inhibitors (PPIs) are a class of medications that reduce acid secretion and are used for treating many conditions such as gastroesophageal reflux disease (GERD), dyspepsia, reflux esophagitis, peptic ulcer disease, and hypersecretory conditions (e.g. Zollinger-Ellison syndrome), and as part of the eradication therapy for Helicobacter pylori bacteria. However, approximately 25% to 70% of people are prescribed a PPI inappropriately. Chronic PPI use without reassessment contributes to polypharmacy and puts people at risk of experiencing drug interactions and adverse events (e.g. Clostridium difficile infection, pneumonia, hypomagnesaemia, and fractures). OBJECTIVES To determine the effects (benefits and harms) associated with deprescribing long-term PPI therapy in adults, compared to chronic daily use (28 days or greater). SEARCH METHODS We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 10), MEDLINE, Embase, clinicaltrials.gov, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). The last date of search was November 2016. We handsearched the reference lists of relevant studies. We screened 2357 articles (2317 identified through search strategy, 40 through other resources). Of these articles, we assessed 89 for eligibility. SELECTION CRITERIA We included randomized controlled trials (RCTs) and quasi-randomized trials comparing at least one deprescribing modality (e.g. stopping PPI or reducing PPI) with a control consisting of no change in continuous daily PPI use in adult chronic users. Outcomes of interest were: change in gastrointestinal (GI) symptoms, drug burden/PPI use, cost/resource use, negative and positive drug withdrawal events, and participant satisfaction. DATA COLLECTION AND ANALYSIS Two review authors independently reviewed and extracted data and completed the risk of bias assessment. A third review author independently confirmed risk of bias assessment. We used Review Manager 5 software for data analysis. We contacted study authors if there was missing information. MAIN RESULTS The review included six trials (n = 1758). Trial participants were aged 48 to 57 years, except for one trial that had a mean age of 73 years. All participants were from the outpatient setting and had either nonerosive reflux disease or milder grades of esophagitis (LA grade A or B). Five trials investigated on-demand deprescribing and one trial examined abrupt discontinuation. There was low quality evidence that on-demand use of PPI may increase risk of 'lack of symptom control' compared with continuous PPI use (risk ratio (RR) 1.71, 95% confidence interval (CI) 1.31 to 2.21), thereby favoring continuous PPI use (five trials, n = 1653). There was a clinically significant reduction in 'drug burden', measured as PPI pill use per week with on-demand therapy (mean difference (MD) -3.79, 95% CI -4.73 to -2.84), favoring deprescribing based on moderate quality evidence (four trials, n = 1152). There was also low quality evidence that on-demand PPI use may be associated with reduced participant satisfaction compared with continuous PPI use. None of the included studies reported cost/resource use or positive drug withdrawal effects. AUTHORS' CONCLUSIONS In people with mild GERD, on-demand deprescribing may lead to an increase in GI symptoms (e.g. dyspepsia, regurgitation) and probably a reduction in pill burden. There was a decline in participant satisfaction, although heterogeneity was high. There were insufficient data to make a conclusion regarding long-term benefits and harms of PPI discontinuation, although two trials (one on-demand trial and one abrupt discontinuation trial) reported endoscopic findings in their intervention groups at study end.
Collapse
Affiliation(s)
- Taline A Boghossian
- The Ottawa HospitalDepartment of Pharmacy501 Smyth RoadOttawaONCanadaK1H 8L6
| | - Farah Joy Rashid
- The Ottawa HospitalDepartment of Pharmacy501 Smyth RoadOttawaONCanadaK1H 8L6
| | - Wade Thompson
- University of OttawaBruyère Research Institute43 rue Bruyere StRoom 730DOttawaONCanadaK1N 5C8
| | - Vivian Welch
- University of OttawaBruyère Research Institute43 rue Bruyere StRoom 730DOttawaONCanadaK1N 5C8
| | - Paul Moayyedi
- McMaster UniversityDepartment of Medicine, Division of Gastroenterology1200 Main Street WestRoom 4W8EHamiltonONCanadaL8N 3Z5
| | - Carlos Rojas‐Fernandez
- University of WaterlooSchool of Pharmacy10 Victoria St S.Room 7004KitchenerONCanadaN2G 1C5
| | - Kevin Pottie
- University of OttawaBruyère Research Institute43 rue Bruyere StRoom 730DOttawaONCanadaK1N 5C8
- University of OttawaFamily Medicine75 Bruyere StOttawaONCanadaK1N 5C8
| | - Barbara Farrell
- University of OttawaBruyère Research Institute43 rue Bruyere StRoom 730DOttawaONCanadaK1N 5C8
- University of WaterlooSchool of Pharmacy10 Victoria St S.Room 7004KitchenerONCanadaN2G 1C5
- University of OttawaFamily Medicine75 Bruyere StOttawaONCanadaK1N 5C8
| | | |
Collapse
|
|
9
|
Mössner J. The Indications, Applications, and Risks of Proton Pump Inhibitors. DEUTSCHES ARZTEBLATT INTERNATIONAL 2016; 113:477-83. [PMID: 27476707 PMCID: PMC4973002 DOI: 10.3238/arztebl.2016.0477] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/19/2015] [Revised: 03/17/2016] [Accepted: 03/17/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND Proton pump inhibitors (PPI) are the most effective drugs for inhibiting gastric acid secretion. They have been in clinical use for more than 25 years, In 2014, 3.475 billion daily defined doses (DDD) of PPI were prescribed in Germany. This high number alone calls for a critical analysis of the spectrum of indications for PPI and their potential adverse effects. METHODS This review is based on pertinent publications retrieved by a selective search in the PubMed and Cochrane Library databases, with particular emphasis on randomized, prospective multicenter trials, cohort studies, case-control studies, and meta-analyses. RESULTS The inhibition of gastric acid secretion with PPI is successfully used for the treatment of gastroesophageal reflux disease and of gastric and duodenal ulcers, for the secondary prevention of gastroduodenal lesions that have arisen under treatment with nonsteroidal anti-inflammatory drugs and acetylsalicylic acid, and for the prevention of recurrent hemorrhage from ulcers after successful endoscopic hemostasis. PPI are given along with practically all antibiotic regimens for the eradication of Helicobacter pylori infection. The number of prescriptions for PPI has risen linearly over the past 25 years. As there has been no broadening of indications, one may well ask whether the current, extensive use of PPI is justified. There is evidence that patients taking PPI are at greater risk for fractures. Moreover, the vitamin B12 level should be checked occasionally in all patients taking PPI. CONCLUSION PPI are among the more effective drugs for the treatment of diseases associated with gastric acid. In view of their cost and potential adverse effects, they should only be prescribed for scientifically validated indications.
Collapse
Affiliation(s)
- Joachim Mössner
- Division of Gastroenterology and Rheumatology, Department of Internal Medicine, Neurology and Dermatology, University Hospital of Leipzig, Germany: Mössner
| |
Collapse
|
|
10
|
|
|
11
|
Azizollahi HR, Rafeey M. Efficacy of proton pump inhibitors and H2 blocker in the treatment of symptomatic gastroesophageal reflux disease in infants. KOREAN JOURNAL OF PEDIATRICS 2016; 59:226-30. [PMID: 27279887 PMCID: PMC4897158 DOI: 10.3345/kjp.2016.59.5.226] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/18/2014] [Revised: 03/20/2015] [Accepted: 11/26/2015] [Indexed: 11/27/2022]
Abstract
Purpose Gastroesophageal reflux disease (GERD) occurs in pediatric patients when reflux of gastric contents presents with troublesome symptoms. The present study compared the effects of omeprazole and ranitidine for the treatment of symptomatic GERD in infants of 2-12 months. Methods This study was a clinical randomized double-blind trial and parallel-group comparison of omeprazole and ranitidine performed at Children Training Hospital in Tabriz, Iran. Patients received a standard treatment for 2 weeks. After 2 weeks, the patients with persistent symptoms were enrolled in this randomized study. Results We enrolled 76 patients in the present study and excluded 16 patients. Thirty patients each were included in group A (ranitidine) and in group B (omeprazole). GERD symptom score for groups A and B was 47.17±5.62 and 51.93±5.42, respectively, with a P value of 0.54, before the treatment and 2.47±0.58 and 2.43±1.15, respectively, after the treatment (P=0.98). No statistically significant differences were found between ranitidine and omeprazole in their efficacy for the treatment of GERD. Conclusion The safety and efficacy of ranitidine and omeprazole have been demonstrated in infants. Both groups of infants showed a statistically significant decrease in the score of clinical variables after the treatment.
Collapse
Affiliation(s)
- Hamid Reza Azizollahi
- Liver and Gastrointestinal Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mandana Rafeey
- Liver and Gastrointestinal Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| |
Collapse
|
|
12
|
Badillo R, Francis D. Diagnosis and treatment of gastroesophageal reflux disease. World J Gastrointest Pharmacol Ther 2014; 5:105-112. [PMID: 25133039 PMCID: PMC4133436 DOI: 10.4292/wjgpt.v5.i3.105] [Citation(s) in RCA: 110] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2014] [Revised: 02/21/2014] [Accepted: 06/20/2014] [Indexed: 02/07/2023] Open
Abstract
Gastroesophageal reflux disease (GERD) is a common disease with a prevalence as high as 10%-20% in the western world. The disease can manifest in various symptoms which can be grouped into typical, atypical and extra-esophageal symptoms. Those with the highest specificity for GERD are acid regurgitation and heartburn. In the absence of alarm symptoms, these symptoms can allow one to make a presumptive diagnosis and initiate empiric therapy. In certain situations, further diagnostic testing is needed to confirm the diagnosis as well as to assess for complications or alternate causes for the symptoms. GERD complications include erosive esophagitis, peptic stricture, Barrett’s esophagus, esophageal adenocarcinoma and pulmonary disease. Management of GERD may involve lifestyle modification, medical therapy and surgical therapy. Lifestyle modifications including weight loss and/or head of bed elevation have been shown to improve esophageal pH and/or GERD symptoms. Medical therapy involves acid suppression which can be achieved with antacids, histamine-receptor antagonists or proton-pump inhibitors. Whereas most patients can be effectively managed with medical therapy, others may go on to require anti-reflux surgery after undergoing a proper pre-operative evaluation. The purpose of this review is to discuss the current approach to the diagnosis and treatment of gastroesophageal reflux disease.
Collapse
|
|
13
|
Weijenborg PW, Cremonini F, Smout AJPM, Bredenoord AJ. PPI therapy is equally effective in well-defined non-erosive reflux disease and in reflux esophagitis: a meta-analysis. Neurogastroenterol Motil 2012; 24:747-57, e350. [PMID: 22309489 DOI: 10.1111/j.1365-2982.2012.01888.x] [Citation(s) in RCA: 107] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Symptomatic response to proton pump inhibitor (PPI) therapy in patients with non-erosive reflux disease (NERD) is often reported as lower than in patients with erosive reflux disease (ERD). However, the definition of NERD differs across clinical trials. This meta-analysis aims to estimate the rate of symptom relief in response to PPI in NERD patients. METHODS MEDLINE (1966-2010), Cochrane Comprehensive Trial Register (1997-2010) and EMBASE (1985-2010) databases were searched and manual searches from studies' references were performed. Randomized clinical trials were selected that included patients with heartburn, and analyzed the effect of short-term PPI treatment. The primary outcome of selected studies was defined as complete or partial heartburn relief. Two reviewers independently extracted data and assessed study quality of selected articles. Random effects models and meta-regression were used to combine and analyze results. KEY RESULTS The pooled estimate of complete relief of heartburn after 4 weeks of PPI therapy in patients with ERD was 0.72 (95% CI 0.69-0.74) (32 studies), vs 0.50 (0.43-0.57) (eight studies) in empirically treated patients, 0.49 (0.44-0.55) (12 studies) in patients defined as non-erosive by negative endoscopy, and 0.73 (0.69-0.77) (two studies) in patients defined as non-erosive by both negative endoscopy and a positive pH-test. CONCLUSIONS & INFERENCES In well-defined NERD patients, the estimated complete symptom response rate after PPI therapy is comparable to the response rate in patients with ERD. The previously reported low response rate in studies with patients classified as NERD is likely the result of inclusion of patients with upper gastrointestinal symptoms that do not have reflux disease.
Collapse
Affiliation(s)
- P W Weijenborg
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
| | | | | | | |
Collapse
|
|
14
|
Reid M, Keniston A, Heller JC, Miller M, Medvedev S, Albert RK. Inappropriate prescribing of proton pump inhibitors in hospitalized patients. J Hosp Med 2012; 7:421-5. [PMID: 22190465 DOI: 10.1002/jhm.1901] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2011] [Revised: 10/22/2011] [Accepted: 11/13/2011] [Indexed: 11/09/2022]
Abstract
BACKGROUND Proton pump inhibitors have numerous important side effects, yet they are prescribed for outpatients who do not have recognized indications. Less is known with respect to prescribing for inpatients. OBJECTIVE To determine the rate of inappropriate prescribing of protein pump inhibitors and to assess reasons why they are prescribed. DESIGN AND PARTICIPANTS The study was a retrospective review of administrative data for adult hospital patients discharged from the Medicine service of Denver Health (DH) and from the University HealthSystem Consortium (UHC) between January 1, 2008 and December 31, 2009. MEASUREMENTS Valid indications for proton pump inhibitors were sought from discharge diagnoses, prescription records, and, in a randomly selected group of patients from DH, from direct review of records. RESULTS Inclusion criteria were met by 9875 DH patients and 6,592,100 UHC patients; of patients receiving a proton pump inhibitor, 61% and 73%, respectively, did not have a valid indication. Increased rates of Clostridium difficile infection were found in both groups of patients receiving proton pump inhibitors. Chart reviews found valid indications for proton pump inhibitors in 19% of patients who did not have a valid indication on the basis of the administrative data, and "prophylaxis" was the justification for inappropriate prescribing in 56%. CONCLUSION Proton pump inhibitors are frequently inappropriately prescribed to Medicine inpatients who do not have a valid indication and this practice is associated with an increase in C. difficile infection. Interventions are needed to curtail this inappropriate prescribing practice.
Collapse
Affiliation(s)
- Mark Reid
- Department of Medicine, Denver Health Medical Center, Denver, Colorado 80204, USA.
| | | | | | | | | | | |
Collapse
|
|
15
|
Holtmann G, Bigard MA, Malfertheiner P, Pounder R. Guidance on the use of over-the-counter proton pump inhibitors for the treatment of GERD. Int J Clin Pharm 2011; 33:493-500. [PMID: 21472476 DOI: 10.1007/s11096-011-9489-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2010] [Accepted: 02/07/2011] [Indexed: 12/18/2022]
Abstract
OBJECTIVE The aim of this paper was to develop a guideline on the over-the-counter management of gastroesophageal reflux disease with proton pump inhibitors (i.e. omeprazole). SETTING A meeting of internationally renowned gastroenterologists in January 2009, in Berlin, Germany. METHODS An expert panel group of gastroenterologists convened to develop a consensus-based algorithm for pharmacists for over-the-counter (OTC) treatment with proton pump inhibitors (PPIs). Key considerations were the short-term safety and efficacy of PPIs, and the extent of the risk to the sufferer, owing to the treatment not being controlled by a physician. Main outcome measures A consensus-based treatment algorithm for the OTC management of gastroesophageal reflux disease and evidence-based guidance on the use of OTC PPIs. RESULTS As defined by the treatment algorithm, the pharmacist should first confirm the diagnosis based on the presence of typical symptoms and secondly, as a result, rule out general practitioner referral. The third step focuses on the nature, severity and frequency of the symptoms--the patients who might have the highest benefit from a short course (14 days) of OTC PPIs are those with less than three episodes of heartburn and/or acid regurgitation per week. Patients who have three or more episodes per week can use the OTC PPIs but should also be encouraged to visit a physician, and those who already have a diagnostic work-up can use proton pump inhibitors as rescue treatment if they are known responders. Guidance for pharmacists, in the form of questions and answers, summarises the current published clinical experience with PPIs in terms of their efficacy and safety, and optimal treatment schedule. Conclusions Gastroesophageal reflux disease imposes a considerable burden on sufferers. Owing to their accepted efficacy and safety, PPIs are becoming popular as OTC options for the treatment of gastroesophageal reflux disease symptoms such as heartburn and acid regurgitation. Effective self-management of gastroesophageal reflux disease with OTC PPIs, e.g. omeprazole, could lead to lasting freedom from symptoms and improved quality of life for sufferers.
Collapse
Affiliation(s)
- Gerald Holtmann
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, University of Adelaide, Adelaide, SA, Australia.
| | | | | | | |
Collapse
|
|
16
|
Efficacy and safety of pantoprazole delayed-release granules for oral suspension in a placebo-controlled treatment-withdrawal study in infants 1-11 months old with symptomatic GERD. J Pediatr Gastroenterol Nutr 2010; 50:609-18. [PMID: 20400912 DOI: 10.1097/mpg.0b013e3181c2bf41] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
OBJECTIVE The objective of this study was to assess the efficacy of pantoprazole in infants with gastroesophageal reflux disease (GERD). MATERIALS AND METHODS Infants ages 1 through 11 months with GERD symptoms after 2 weeks of conservative treatment received open-label (OL) pantoprazole 1.2 mg x kg(-1) x day(-1) for 4 weeks followed by a 4-week randomized, double-blind (DB), placebo-controlled, withdrawal phase. The primary endpoint was withdrawal due to lack of efficacy in the DB phase. Mean weekly GERD symptom scores (WGSSs) were calculated from daily assessments of 5 GERD symptoms. Safety was assessed. RESULTS One hundred twenty-eight patients entered OL treatment, and 106 made up the DB modified intent-to-treat population. Mean age was 5.1 months (82% full-term, 64% male). One third of patients had a GERD diagnostic test before OL study entry. WGSSs at week 4 were similar between groups. WGSSs decreased significantly from baseline during OL therapy (P < 0.001), when all patients received pantoprazole. The decrease in WGSSs was maintained during the DB phase in both treatment groups. There was no difference in withdrawal rates due to lack of efficacy (pantoprazole 6/52; placebo 6/54) or time to withdrawal during the DB phase. The greatest between-group difference in WGSS was slightly worse with placebo at week 5 (P = 0.09), mainly due to episodes of arching back (P = 0.028). No between-group differences in adverse event frequency were noted. Serious adverse events in 8 patients were considered unrelated to treatment. CONCLUSIONS Pantoprazole significantly improved GERD symptom scores and was well tolerated. However, during the DB treatment phase, there were no significant differences noted between pantoprazole and placebo in withdrawal rates due to lack of efficacy.
Collapse
|
|
17
|
Yaghoobi M, Padol S, Yuan Y, Hunt RH. Impact of oesophagitis classification in evaluating healing of erosive oesophagitis after therapy with proton pump inhibitors: a pooled analysis. Eur J Gastroenterol Hepatol 2010; 22:583-90. [PMID: 20061959 DOI: 10.1097/meg.0b013e328335d95d] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS The results of clinical trials with proton pump inhibitors (PPIs) are usually based on the Hetzel-Dent (HD), Savary-Miller (SM), or Los Angeles (LA) classifications to describe the severity and assess the healing of erosive oesophagitis. However, it is not known whether these classifications are comparable. The aim of this study was to review systematically the literature to compare the healing rates of erosive oesophagitis with PPIs in clinical trials assessed by the HD, SM, or LA classifications. METHODS A recursive, English language literature search in PubMed and Cochrane databases to December 2006 was performed. Double-blind randomized control trials comparing a PPI with another PPI, an H2-RA or placebo using endoscopic assessment of the healing of oesophagitis by the HD, SM or LA, or their modified classifications at 4 or 8 weeks, were included in the study. The healing rates on treatment with the same PPI(s), and same endoscopic grade(s) were pooled and compared between different classifications using Fisher's exact test or chi2 test where appropriate. RESULTS Forty-seven studies from 965 potential citations met inclusion criteria. Seventy-eight PPI arms were identified, with 27 using HD, 29 using SM, and 22 using LA for five marketed PPIs. There was insufficient data for rabeprazole and esomeprazole (week 4 only) to compare because they were evaluated by only one classification. When data from all PPIs were pooled, regardless of baseline oesophagitis grades, the LA healing rate was significantly higher than SM and HD at both 4 and 8 weeks (74, 71, and 68% at 4 weeks and 89, 84, and 83% at 8 weeks, respectively). The distribution of different grades in study population was available only for pantoprazole where it was not significantly different between LA and SM subgroups. When analyzing data for PPI and dose, the LA classification showed a higher healing rate for omeprazole 20 mg/day and pantoprazole 40 mg/day (significant at 8 weeks), whereas healing by SM classification was significantly higher for omeprazole 40 mg/day (no data for LA) and lansoprazole 30 mg/day at 4 and 8 weeks. The healing rate by individual oesophagitis grade was not always available or robust enough for meaningful analysis. However, a difference between classifications remained. CONCLUSION There is a significant, but not always consistent, difference in oesophagitis healing rates with the same PPI(s) reported by the LA, SM, or HD classifications. The possible difference between grading classifications should be considered when interpreting or comparing healing rates for oesophagitis from different studies.
Collapse
Affiliation(s)
- Mohammad Yaghoobi
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | | | | | | |
Collapse
|
|
18
|
Wang Y, Pan T, Wang Q, Guo Z. Additional bedtime H2-receptor antagonist for the control of nocturnal gastric acid breakthrough. Cochrane Database Syst Rev 2009:CD004275. [PMID: 19821323 DOI: 10.1002/14651858.cd004275.pub3] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND Nocturnal gastric acid breakthrough (NAB) is defined as intragastric pH<4 for more than one continuous hour overnight. Adding H(2)-receptor antagonists (H2RAs) at bedtime to high-dose proton pump inhibitors is likely to enhance nocturnal gastric pH control and decrease nocturnal gastric acid breakthrough. OBJECTIVES To assess the effectiveness of additional bedtime H2-receptor antagonists in suppressing nocturnal gastric acid breakthrough and the incidence of adverse effects. SEARCH STRATEGY We identified eligible trials by searching The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2008), MEDLINE (1966-August 2008), EMBASE (1980-August 2008) and CINAHL (1982-August 2008). We re-ran the search on CENTRAL (The Cochrane Library Issue 4, 2008), and in MEDLINE, EMBASE and CINAHL in June 2004, July 2005, August 2006 and August 2008. SELECTION CRITERIA All randomized controlled trials evaluating H2-receptor antagonists for the control of nocturnal gastric acid breakthrough were eligible for inclusion. DATA COLLECTION AND ANALYSIS Two reviewers have independently selected the trials to be included in the review according to the pre-stated eligibility criteria. Disagreements were resolved by a third reviewer. If the data could not be pooled for meta-analysis, a narrative description was provided. MAIN RESULTS 8 small randomized controlled trials were included for meta-analysis. The results show that additional bedtime H2RAs can decrease the prevalence rate of nocturnal gastric acid breakthrough. The results of the analyses for secondary outcomes show that additional bedtime H2RAs can decrease the percentage of time during which pH is less than 4.0 inside the stomach and promote median intragastric pH. AUTHORS' CONCLUSIONS We can conclude no implications for practice at this stage. Appropriately designed large-scale randomized controlled trials with long-term follow-up are needed to determine the effects of additional bedtime H2RAs in suppressing nocturnal gastric acid breakthrough.
Collapse
Affiliation(s)
- Yiping Wang
- Department of Digestive Disease, Huaxi Hospital of Sichuan University, Guoxuexiang 37#, Chengdu, Sichuan Province, China, 610041
| | | | | | | |
Collapse
|
|
19
|
Colin-Jones DG. The role and limitations of H2-receptor antagonists in the treatment of gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2008; 9 Suppl 1:9-14. [PMID: 7495945 DOI: 10.1111/j.1365-2036.1995.tb00778.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Gastro-oesophageal reflux disease (GERD) occurs in up to 44% of adults in the USA. Most individuals do not seek medical help, self-medicating with antacids. Manifestations of GERD range from symptoms without oesophagitis, which constitute the bulk of patients who self-medicate, to active oesophagitis and then to complications such as stricture and ulceration. It is the more severe cases who tend to come to the gastroenterologist, but it must be remembered that reflux symptoms are probably around 5-10 times more common than actual oesophagitis. Since acid in the refluxate is responsible for the bulk of the symptoms and mucosal damage, antacids are often used for quick relief--which of course may not be sustained. More prolonged suppression of acid secretion, such as by a histamine H2-receptor antagonist (H2RA) or a proton pump inhibitor (PPI), is required to give long-lasting symptomatic relief and heal any inflammatory change. H2-receptor antagonists inhibit acid secretion with an effect that lasts for 4-8 h with a single dose, decreasing stimulated acid secretion by around 70%. When treating oesophagitis, the H2RAs suffer from the disadvantage of their relatively short duration of action (compared with PPIs), development of tolerance, and incomplete inhibition of acid secretion in response to a meal. Therefore, it is not easy for the H2RAs to achieve optimum conditions for healing the more severe forms of oesophagitis--even very high doses may fail. In mild GERD the H2RAs have been shown to be effective in relieving symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)
Collapse
|
|
20
|
Abstract
UNLABELLED Efficacy (healing, symptom relief) and cost-effectiveness are the principal reasons for the rapidly increasing use of proton pump inhibitors (PPIs) for the management of gastro-oesophageal reflux disease. EFFICACY Mean healing rates pooled from clinical trials are as follows: on omeprazole (OME) 20 mg vs. H2-receptor antagonist. H2RA (cimetidine (CIM) 1.6 g or ranitidine (RAN) 300 mg) (eight studies) at 4 weeks, 67% vs. 37%: at 8 weeks, 81% vs. 49%: on lansoprazole (LAN) 30 mg vs. H2RA (three studies), 83% vs. 47% and 91% vs. 63% at 4 and 8 weeks, respectively. The benefit is greatest in severe disease because the H2RAs are disproportionately less effective. Heartburn is more rapidly relieved and in a higher proportion: at 4 weeks, on OME 20 mg vs. H2RA. 77% vs. 47% and on LAN 30 mg vs. H2RA, 81% vs. 46%. Both PPIs are effective in H2RA-refractory disease, approximately 80% healing occurring in 8 weeks. Relapse rates after healing vary from 25% to 85% at 6 months. Maintenance therapy sustains remissions: relapse at 1 year is, on OME 20 mg vs. RAN 300 mg (2 studies), 12% vs. 79%, and 28% vs. 55% (and 38% on OME 10 mg); on LAN 30 mg vs. 10 mg vs. RAN 600 mg, 20% vs. 31% vs. 68%. The effectiveness of the lower dose allows for dose titration. COST EFFECTIVENESS The higher drug costs for the PPIs are offset by their higher efficacy, making their use cost effective, particularly in severe disease. Efficacy and cost effectiveness are likely to further expand the use of PPIs at the expense of H2RAs as increasing numbers of patients with milder disease are treated.
Collapse
|
|
21
|
Hunt RH. The relationship between the control of pH and healing and symptom relief in gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2008; 9 Suppl 1:3-7. [PMID: 7495939 DOI: 10.1111/j.1365-2036.1995.tb00777.x] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Gastro-oesophageal reflux disease (GERD) is generally considered to be the result of a motility disorder which permits the abnormal and prolonged exposure of the lumen of the oesophagus to the acidic gastric contents. This view is supported by experimental data, intra-oesophageal pH measurement, and the dramatic results of symptom relief and healing seen with effective antisecretory treatment. Oesophageal mucosal injury is determined by the pH of the refluxate and duration of acid exposure. Most patients experience meal-stimulated reflux during the day and the more severe cases experience 24-h acid exposure. In contrast to the H2-receptor antagonists (H2RAs), the proton pump inhibitors (PPIs) are more effective at controlling meal-stimulated acid secretion when each is given in standard doses. Therefore, the degree and duration of acid suppression throughout 24 h is greater. Treatments which maintain intra-oesophageal pH > 4 for 96% or more of the 24 h normalize acid exposure and are associated with the highest healing rates. Peptic activity is minimized at or above pH 4. The time above pH 4 is significantly longer with the PPIs than with the H2RAs. Thus, the healing-time curves for GERD (grades II-IV) are shifted to the left for the PPIs which heal a significantly greater proportion of patients earlier than the H2RAs or sucralfate. Symptoms in GERD are related to the degree and duration of oesophageal acid exposure. Symptom relief is more rapid and complete with the PPIs than with the H2RAs or other treatments in standard doses.
Collapse
Affiliation(s)
- R H Hunt
- Department of Medicine, McMaster University Medical Centre, Hamilton, Ontario, Canada
| |
Collapse
|
|
22
|
Yamagishi H, Koike T, Ohara S, Horii T, Kikuchi R, Kobayashi S, Abe Y, Iijima K, Imatani A, Suzuki K, Hishinuma T, Goto J, Shimosegawa T. Stronger inhibition of gastric acid secretion by lafutidine, a novel H 2 receptor antagonist, than by the proton pump inhibitor lansoprazole. World J Gastroenterol 2008; 14:2406-10. [PMID: 18416470 PMCID: PMC2705098 DOI: 10.3748/wjg.14.2406] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To compare the antisecretory activity and plasma drug concentrations of a single oral dose of 10 mg lafutidine, a novel H2 receptor antagonist, with those of the proton pump inhibitor lansoprazole (LPZ) 30 mg.
METHODS: Ten volunteers without H pylori infection participated in this crossover study comparing lafutidine 10 mg with LPZ 30 mg. Intragastric pH was monitored for 6 h in all participants, and blood samples were collected from four randomly selected individuals after single-dose administration of each drug.
RESULTS: The median intragastric pH was significantly higher in individuals who received lafutidine 10 mg than in those who received LPZ 30 mg 2, 3, 4, 5, and 6 h after administration. Maximal plasma drug concentration was reached more promptly with lafutidine 10 mg than with LPZ 30 mg.
CONCLUSION: In H pylori-negative individuals, gastric acid secretion is more markedly inhibited by lafutidine than by LPZ.
Collapse
|
|
23
|
Shimatani T, Kuroiwa T, Moriwaki M, Xu J, Tazuma S, Inoue M. Acid-suppressive effects of various regimens of omeprazole in Helicobacter pylori-negative CYP2C19 homozygous extensive metabolizers: which regimen has the strongest effect? Dig Dis Sci 2007; 52:2826-32. [PMID: 17410461 DOI: 10.1007/s10620-006-9643-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2006] [Accepted: 10/09/2006] [Indexed: 01/15/2023]
Abstract
To achieve more potent and long-lasting acid suppression, omeprazole was administered for 7 days in 5 regimens: 10, 20, and 40 mg once daily (od), and 10 and 20 mg twice daily (bid), in 7 healthy Helicobacter pylori-negative CYP2C19 homozygous extensive metabolizers, and intragastric pH was continuously measured. The median intragastric pH and percent time pH > 4.0 for 24 hours increased dose dependently with 10, 20, and 40 mg od. Ten and 20 mg bid wre comparable to 20 and 40 mg od, respectively. Concerning percent time pH > 4.0 in the nighttime (20:00-8:00 hours), 20 mg bid was significantly superior to 40 mg od (P < .05). In 4 of the 5 regimens, all 7 subjects had nocturnal acid breakthrough, whereas with 20 mg bid it occurred in only 3. We concluded that, considering nighttime acid suppression, omeprazole 20 mg bid had the strongest effect.
Collapse
Affiliation(s)
- Tomohiko Shimatani
- Department of General Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | | | | | | | | | | |
Collapse
|
|
24
|
Diaz DM, Winter HS, Colletti RB, Ferry GD, Rudolph CD, Czinn SJ, Cochran W, Gold BD. Knowledge, attitudes and practice styles of North American pediatricians regarding gastroesophageal reflux disease. J Pediatr Gastroenterol Nutr 2007; 45:56-64. [PMID: 17592365 DOI: 10.1097/mpg.0b013e318054b0dd] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
BACKGROUND The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition launched a provider and public education campaign in 2002 to raise awareness of gastroesophageal reflux disease (GERD). To determine the effectiveness of campaign messages, we conducted a knowledge, attitudes, and practice styles (KAPS) survey of pediatric providers. Understanding the spectrum of management styles of GERD in children is critical to achieve better health outcomes and reduce health care costs. MATERIALS AND METHODS The KAPS questionnaire was administered to 6000 randomly selected members of the American Academy of Pediatrics. RESULTS A total of 1245 members responded; 82% worked in a primary care setting and 18% in subspecialty practices. Overall, 66% of the members order diagnostic testing in routine practice, 54% start testing for GERD in neonates, and 38% start testing after 1 month of age. The most common tests ordered were barium esophagram (45%) and esophageal pH monitoring (37%). GERD treatment with acid suppression before ordering diagnostic testing was a choice of 82% of the respondents. However, 19% believed acid suppression was best achieved by H2 blockers. If acid suppression was indicated, then only 36% followed guideline recommendations for therapy duration and 52% followed guideline recommendations for dosing. Antireflux surgery was recommended only as a last resort by 92%. Overall, 69% of providers believed the amount of GERD-related information available was not enough. Respondents who were not aware of available GERD practice guidelines ranged from 74% to 92%. CONCLUSIONS Pediatric providers appear to frequently order diagnostic testing and treatment for GERD, yet knowledge about evidence-based GERD management among this random sample appeared limited. Moreover, a significant number of providers were not aware of different guideline publications.
Collapse
Affiliation(s)
- Diego M Diaz
- Emory University School of Medicine, Atlanta, GA 30322, USA
| | | | | | | | | | | | | | | |
Collapse
|
|
25
|
Bardhan KD, Achim A, Riddermann T, Pfaffenberger B. A clinical trial comparing pantoprazole and esomeprazole to explore the concept of achieving 'complete remission' in gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2007; 25:1461-9. [PMID: 17539986 DOI: 10.1111/j.1365-2036.2007.03337.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM The outcome of gastro-oesophageal reflux disease treatment is traditionally assessed by measuring endoscopically confirmed healing and symptom relief separately. Both terms together, indicating complete remission, are intuitively a more realistic clinical endpoint but are assessed less often. AIM To explore this concept, we formally compared the efficacy of the proton pump inhibitors (PPIs) pantoprazole and esomeprazole using rates of complete remission judged against rates of healing and symptom relief separately. METHODS Five hundred and eighty-two patients with erosive gastro-oesophageal reflux disease were randomized to treatment for 4, 8, or 12 weeks with either pantoprazole or esomeprazole 40 mg daily. Symptom relief was assessed with the validated ReQuesttrade mark-GI subscale. RESULTS Approximately 75% of patients were free of symptoms or had no oesophageal lesions after 4 weeks' treatment, rising to about 93% and 96%, respectively, at 12 weeks. Complete remission rates were, however, lower at these time points; approximately 60% and about 90%, respectively. Both PPIs had similar efficacy. CONCLUSIONS Endoscopically confirmed healing and symptom relief assessed separately over-estimated the benefits of both drugs. In contrast, complete remission indicates that patients may be treated inadequately when given the standard 4- to 8-week treatment. We suggest that complete remission is a more reliable and clinically relevant endpoint of treatment.
Collapse
|
|
26
|
Shimatani T, Inoue M, Kuroiwa T, Moriwaki M, Xu J, Ikawa K, Morikawa N, Tazuma S. Which has superior acid-suppressive effect, 10 mg omeprazole once daily or 20 mg famotidine twice daily? Effects of single or repeated administration in Japanese Helicobacter pylori-negative CYP2C19 extensive metabolizers. Dig Dis Sci 2007; 52:390-5. [PMID: 17211705 DOI: 10.1007/s10620-006-9490-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2006] [Accepted: 06/14/2006] [Indexed: 12/29/2022]
Abstract
Low-dose omeprazole is superior to full-dose famotidine in maintenance therapy for gastroesophageal reflux disease, whereas "on-demand" famotidine is more effective for relief of episodes of heartburn. To explain this apparent discrepancy, intragastric pH was measured for 24-hr seven times in eight Japanese Helicobacter pylori-negative cytochrome P450 2C19 extensive metabolizers; on Days 1, 8, and 15 of repeated administration of 10 mg of omeprazole once daily and of 20 mg of famotidine twice daily and before medication. During repeated administration of omeprazole, mean intragastric pH and % time that intragastric pH > 4.0 were significantly higher and became greater. With famotidine, although these parameters were significantly higher, the degrees became smaller. Consequently, acid-suppressive effect was in the order; omeprazole < famotidine on Day 1, omeprazole approximately famotidine on Day 8, and omeprazole >famotidine on Day 15. This discrepancy possibly results from the "potentiation" of acid-suppressive effect of omeprazole and the "tolerance" phenomenon in respect to famotidine.
Collapse
Affiliation(s)
- Tomohiko Shimatani
- Department of General Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Hiroshima, Japan.
| | | | | | | | | | | | | | | |
Collapse
|
|
27
|
Pan T, Wang YP, Liu FC, Yang JL. Additional bedtime H2-receptor antagonist for the control of nocturnal gastric acid breakthrough: a Cochrane systematic review. ACTA ACUST UNITED AC 2006; 7:141-8. [PMID: 16808794 DOI: 10.1111/j.1443-9573.2006.00259.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
OBJECTIVES To assess the effectiveness and safety of additional bedtime H(2)-receptor antagonists (H(2)RAs) in suppressing nocturnal gastric acid breakthrough (NAB) via a systematic review. METHODS Eligible trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 2, 2004), MEDLINE (January 1966-June 2004), EMBASE (January 1980-June 2004) and CINAHL (January 1982-June 2004). Additional hand-searching was conducted on the proceedings of correlated conferences, eight important Chinese journals and references of all included trials. All randomized controlled trials evaluating H(2)RAs for the control of NAB were eligible for inclusion. The systematic review was conducted using methods recommended by The Cochrane Collaboration. RESULTS Only two randomized crossover studies, comprising 32 participants, met the inclusion criteria. Because the design, dosage and duration of the treatments were different between the studies, it was not possible to conduct meta-analysis. There were no consistent conclusions found between the two included studies in evaluating H(2)RAs for the control of NAB. CONCLUSIONS No implications for practice at this stage can be concluded. Appropriately designed large-scale randomized controlled trials with long-term follow up are needed to determine the effects of additional bedtime H(2)RAs in suppressing NAB.
Collapse
Affiliation(s)
- Tao Pan
- Department of Gastroenterology, The First People's Hospital of Chengdu, China
| | | | | | | |
Collapse
|
|
28
|
Mahmood Z, Byrne PJ, McMahon BP, Murphy EM, Arfin Q, Ravi N, Weir DG, Reynolds JV. Comparison of transesophageal endoscopic plication (TEP) with laparoscopic Nissen fundoplication (LNF) in the treatment of uncomplicated reflux disease. Am J Gastroenterol 2006; 101:431-6. [PMID: 16542276 DOI: 10.1111/j.1572-0241.2006.00534.x] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Transesophageal endoscopic plication (TEP) is a novel endotherapeutic approach in the management of gastroesophageal reflux disease (GERD). This non-randomized prospective study compares TEP with laparoscopic Nissen fundoplication (LNF). METHODS Twenty-four consecutive patients treated with LNF, and 27 managed by TEP were studied. Symptom severity scores, endoscopy, 24 h esophageal pH and esophageal manometry and quality-of-life assessments were obtained pre- and posttreatment. RESULTS In the LNF group the mean age was 36 yr (17-68) compared with 39 yr (22-62) in the TEP group. Symptom scoring, acid regurgitation score, reduction in the requirements of proton pump inhibitors (PPIs), and quality of life remained significantly improved in both groups at a median of 1 yr [10-18 months] follow-up post procedure. However, the improvement was significantly better in symptom score (p= 0.0383) and the control of acid reflux in the LNF group (p= 0.0007). Post-procedure dysphagia was more common in the LNF group. CONCLUSION Both techniques improved symptom score, acid regurgitation, quality of life, and reduced the requirements for PPIs. The control of heartburn and acid reflux was better for LNF. TEP, like LNF, is a safe and effective method of management of symptomatic GERD but further developments are necessary to ensure control of esophageal acid reflux.
Collapse
Affiliation(s)
- Zahid Mahmood
- Department of Surgery & Medicine, Trinity Centre for Health Sciences, St James's Hospital, Dublin 8, Ireland
| | | | | | | | | | | | | | | |
Collapse
|
|
29
|
Hongo M. Minimal changes in reflux esophagitis: red ones and white ones. J Gastroenterol 2006; 41:95-9. [PMID: 16568367 DOI: 10.1007/s00535-006-1775-4] [Citation(s) in RCA: 92] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2006] [Accepted: 01/23/2006] [Indexed: 02/08/2023]
Abstract
Minimal change esophagitis is commonly accepted as part of the spectrum of reflux esophagitis in Japan as well as in many reflux esophagitis classification systems. However, the Los Angeles system excludes minimal changes as a sign of reflux esophagitis because of low interobserver agreement. The high prevalence of minimal change esophagitis suggests that many endoscopists can recognize such findings in their patients' esophagi. However, we do not have a clear definition of minimal changes, which requires proven interobserver agreement, histological evidence, and response data to therapeutic intervention. Furthermore, erythematous changes (red ones) and acanthotic changes (white ones) are not distinguished in the definition of minimal change used in Japan. It is time to clarify such issues.
Collapse
Affiliation(s)
- Michio Hongo
- Department of Comprehensive Medicine, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba, Sendai 980-8574, Japan
| |
Collapse
|
|
30
|
Vieth M, Kulig M, Leodolter A, Nauclér E, Jaspersen D, Labenz J, Meyer-Sabellek W, Lind T, Willich S, Malfertheiner P, Stolte M. Histological effects of esomeprazole therapy on the squamous epithelium of the distal oesophagus. Aliment Pharmacol Ther 2006; 23:313-9. [PMID: 16393312 DOI: 10.1111/j.1365-2036.2006.02752.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
BACKGROUND Proton pump inhibitor therapy has been reported to reduce proliferative changes of the oesophagus significantly in gastro-oesophageal reflux disease (GERD). AIM To assess the histological effects of esomeprazole treatment on the oesophagus. METHODS Data were derived from a subgroup of patients participating in the proGERD study, who had either erosive reflux disease (n = 720) or non-erosive reflux disease (n = 35) and who had biopsy data from two sites [(i) 2 cm above the z-line and (ii) at the z-line], obtained at baseline and following treatment with esomeprazole. Proliferative changes of the squamous epithelium were assessed histologically by measuring thickness of the basal cell layer and elongation of the papillae as a percentage of the whole epithelial thickness. RESULTS In erosive reflux disease patients, the thickness of the basal cell layer and length of the papillae pretreatment were associated with the severity of oesophagitis (P < 0.05), at both biopsy sites. After esomeprazole treatment, baseline thickness and length of papillae were significantly reduced (P < 0.05) at both biopsy sites in non-erosive reflux disease and erosive reflux disease patients (particularly those with Los Angeles grades C and D). CONCLUSION This demonstrates a strong correlation between severity of GERD and histological parameters. Esomeprazole therapy resulted in clear reversal of proliferative changes observed prior to treatment in the squamous epithelium at both biopsy locations.
Collapse
Affiliation(s)
- M Vieth
- Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany.
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
31
|
Wada T, Sasaki M, Kataoka H, Tanida S, Itoh K, Ogasawara N, Oshima T, Togawa S, Kubota E, Yamada T, Mori Y, Fujita F, Ohara H, Nakao H, Sobue S, Joh T, Itoh M. Efficacy of famotidine and omeprazole in healing symptoms of non-erosive gastro-oesophageal reflux disease: randomized-controlled study of gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2005; 21 Suppl 2:2-9. [PMID: 15943840 DOI: 10.1111/j.1365-2036.2005.02467.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
BACKGROUND The epidemiology and pathophysiology of non-erosive gastro-oesophageal reflux disease differs from erosive gastro-oesophageal reflux disease. There is a possibility that non-erosive gastro-oesophageal reflux disease treatment requires a different regimen/approach but it is not yet acknowledged. AIM To investigate the efficacy of famotidine and omeprazole in the treatment of gastro-oesophageal reflux disease, especially non-erosive gastro-oesophageal reflux disease. PATIENTS AND METHODS A randomized, open-label trial was conducted. Fifty-four gastro-oesophageal reflux disease patients were assigned to treatment with famotidine at a dosage of 20 mg twice daily; or omeprazole, 20 mg once daily, for a period of 8 weeks. The Short Form-36 Health Survey and Gastrointestinal Symptom Rating Scale administered at baseline and after 8 weeks of treatment as well as a symptom questionnaire were conducted daily. RESULTS Short Form-36 revealed that gastro-oesophageal reflux disease has severe impact on health-related quality of life. Thirty-nine subjects (77%) were endoscopically diagnosed as non-erosive gastro-oesophageal reflux disease. The mean Gastrointestinal Symptom Rating Scale abdominal pain, and indigestion score of non-erosive gastro-oesophageal reflux disease significantly improved in famotidine-treated patients (P < 0.05), but not in the omeprazole. There was no significant change regarding improved heartburn symptoms of non-erosive gastro-oesophageal reflux disease between treatments in the daytime or night-time. CONCLUSION Famotidine and omeprazole were both effective in improving symptoms of gastro-oesophageal reflux disease, particularly non-erosive gastro-oesophageal reflux disease.
Collapse
Affiliation(s)
- T Wada
- Department of Internal Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
32
|
Hamamoto N, Hashimoto T, Adachi K, Hirakawa K, Ishihara S, Inoue H, Taniura H, Niigaki M, Sato S, Kushiyama Y, Suetsugu H, Miyake T, Kinoshita Y. Comparative study of nizatidine and famotidine for maintenance therapy of erosive esophagitis. J Gastroenterol Hepatol 2005; 20:281-6. [PMID: 15683433 DOI: 10.1111/j.1440-1746.2004.03546.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND The therapeutic effect of combined administration of prokinetics and histamine H2 receptor antagonists (H2RA) in gastroesophageal reflux disease is reported to be superior to that of monotherapy with H2RA alone. In addition to its acid-suppressing effect, the H2RA nizatidine also has a prokinetic action by suppressing acetylcholine esterase. The present multicenter, randomized controlled study was performed to investigate whether nizatidine is superior to famotidine, which does not suppress acetylcholine esterase activity, in maintenance therapy for erosive esophagitis. In addition, the question as to whether the grade of erosive esophagitis affects the non-recurrence rate during the maintenance therapy with H2RA was also investigated. METHODS Seventy-two patients with endoscopically healed erosive esophagitis after 8 weeks of initial treatment with proton pump inhibitors were randomly divided into two groups. Patients in the nizatidine group were treated with 150 mg nizatidine twice a day (b.i.d.), while patients in the famotidine group were treated with 20 mg famotidine b.i.d. for 6 months. At the end of therapy, and at the time when patients complained of symptoms, endoscopic investigations were repeated to find out whether the esophagitis had recurred. RESULTS Nizatidine produced a significantly higher non-recurrence rate than famotidine (P = 0.049 in intention-to-treat [ITT] analysis). This difference of remission rate between nizatidine and famotidine was observed mainly in grade B esophagitis (P = 0.016 in ITT analysis). CONCLUSION Nizatidine is a more effective H2RA than famotidine in the maintenance therapy of patients with reflux esophagitis.
Collapse
Affiliation(s)
- Naoharu Hamamoto
- Department of Gastroenterology and Hepatology, Shimane University, School of Medicine, 89-1 Enya-cho, Izumo-shi, Shimane 693-8501, Japan
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
33
|
Pan T, Wang Y, Guo Z, Wang Q. Additional bedtime H2-receptor antagonist for the control of nocturnal gastric acid breakthrough. Cochrane Database Syst Rev 2004:CD004275. [PMID: 15495095 DOI: 10.1002/14651858.cd004275.pub2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
BACKGROUND Nocturnal gastric acid breakthrough(NAB) is defined as intragastric pH<4 for more than one continuous hour overnight. Adding H2-receptor antagonists (H2RAs)at bedtime to high-dose proton pump inhibitors is likely to enhance nocturnal gastric pH control and decrease nocturnal gastric acid breakthrough. OBJECTIVES To assess the effectiveness of additional bedtime H2-receptor antagonists in suppressing nocturnal gastric acid breakthrough and the incidence of adverse effects. SEARCH STRATEGY We identified eligible trials by searching The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2003), MEDLINE (1966-July 2003), EMBASE (1980-July 2003) and CINAHL (1982-July 2003). We re-ran the search on CENTRAL (The Cochrane Library Issue 2, 2004), and in MEDLINE, EMBASE and CINAHL in June 2004. SELECTION CRITERIA All randomized controlled trials evaluating H2-receptor antagonists for the control of nocturnal gastric acid breakthrough were eligible for inclusion. DATA COLLECTION AND ANALYSIS We extracted data and recorded relevant information onto specially developed forms. One reviewer extracted data and a second reviewer checked data extraction. We have also double-checked data entry into RevMan. For binary outcomes, we expressed the impact of the intervention as relative risks, together with 95% confidence intervals. For scale-based outcomes, we used means and standard deviations to summarise the values in each group, provided the scale permitted sufficient values. We had intended to analyse such outcomes for the presence of skew, but the studies included were too limited to permit this. MAIN RESULTS Two randomized crossover studies including 32 participants met the inclusion criteria. Because the design, dosage and duration of the treatment were different between the studies, it was not possible to conduct meta-analysis. There is no consistent conclusion between the two included studies in evaluating H2RAs for the control of NAB. REVIEWERS' CONCLUSIONS We can conclude no implications for practice at this stage. Appropriately designed, large-scale randomized controlled trials with long-term follow-up are needed to determine the effects of additional bedtime H2RAs in suppressing nocturnal gastric acid breakthrough.
Collapse
|
|
34
|
Abstract
Gastroesophageal reflux disease (GERD) is one of the most common diagnoses in daily practice. Diagnosis can be made on symptom evaluation, on pH-monitoring or on endoscopic findings. In contrast to commonly held opinion there is no strong evidence that lifestyle factors are a dominant factor in the pathophysiology of GERD. The various agents currently used for treatment of GERD include mucoprotective substances, antacids, H(2)-blockers and proton pump inhibitors. This article gives an overview of the pharmacological management of GERD and focuses on the differential therapy of endoscopy-negative GERD, GERD with esophagitis and maintenance therapy.
Collapse
Affiliation(s)
- M Storr
- Department of Internal Medicine II - Standort Grosshadern, Ludwig-Maximilians University, Munich, Germany.
| | | |
Collapse
|
|
35
|
Adachi K, Furuta K, Katsube T, Fujisawa T, Azumi T, Fujishiro H, Ishihara S, Amano Y, Kinoshita Y. Nizatidine and cisapride increase salivary secretion in rats. Dig Dis Sci 2004; 49:399-403. [PMID: 15139487 DOI: 10.1023/b:ddas.0000020492.16088.28] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
Saliva is a neurally induced solution with buffering capacity against acidic solutions. Salivation therefore plays an important role in defending the esophageal mucosa against refluxed gastric acid and is evoked by cholinergic stimulation. Both nizatidine and cisapride are reported to increase acetylcholine concentrations in the postganglionic cholinergic synapses. We performed this study to clarify the effect of administration of nizatidine and cisapride on salivary secretion. Eight-week-old male Sprague-Dawley rats were used for the experiments. Histamine-stimulated gastric acid secretion was measured after intraduodenal administration of nizatidine or famotidine to determine the equipotent acid-suppressing doses. Salivary secretion was then measured for 3 hr after intraduodenal administration of nizatidine (30 mg/kg), famotidine (3 mg/kg), or cisapride (1 mg/kg). Both nizatidine and famotidine dose-dependently inhibited histamine-stimulated gastric acid secretion. Total salivary secretion was significantly increased by nizatidine (P = 0.02) and cisapride (P = 0.02) but not by famotidine (P = 0.50) compared with controls.
Collapse
Affiliation(s)
- Kyoichi Adachi
- Department of Gastroenterology and Hepatology, Shimane University, Shimane, Japan.
| | | | | | | | | | | | | | | | | |
Collapse
|
|
36
|
Shimatani T, Inoue M, Kuroiwa T, Horikawa Y, Mieno H, Nakamura M. Effect of omeprazole 10 mg on intragastric pH in three different CYP2C19 genotypes, compared with omeprazole 20 mg and lafutidine 20 mg, a new H2-receptor antagonist. Aliment Pharmacol Ther 2003; 18:1149-57. [PMID: 14653835 DOI: 10.1046/j.1365-2036.2003.01804.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
Abstract
BACKGROUND Omeprazole 10 mg is used as maintenance therapy for gastro-oesophageal reflux disease, but previous reports have not mentioned the potency of its acid suppression. AIM To evaluate the potency of acid suppression with omeprazole 10 mg, in relation to CYP2C19 genotypes. METHODS Eighteen healthy subjects without Helicobacter pylori participated. After a 7-day regimen of omeprazole 10 mg, 20 mg, lafutidine 20 mg (a novel H2-receptor antagonist) or water only (baseline data), intragastric pH was measured for 24 h. RESULTS With omeprazole 10 mg, greater differences were observed than 20 mg in median pH values and pH > 4 holding time ratios between poor metabolizers (PMs, n = 6) and the others [homozygous extensive metabolizers (homo-EMs, n = 6) and heterozygous extensive metabolizers (hetero-EMs, n = 6)]. With lafutidine 20 mg, these parameters were not influenced by the genotype. The potency of acid suppression was: omeprazole 20 mg approximately lafutidine 20 mg > omeprazole 10 mg in homo-EMs, omeprazole 20 mg > omeprazole 10 mg approximately lafutidine 20 mg in hetero-EMs, and omeprazole 20 mg approximately omeprazole 10 mg > lafutidine 20 mg in PMs. CONCLUSIONS Omeprazole 10 mg strongly suppresses acid secretion, but depending on the CYP2C19 genotypes shows greater interindividual variations in suppression than 20 mg.
Collapse
Affiliation(s)
- T Shimatani
- Department of General Medicine, Hiroshima University Hospital, Hiroshima, Japan.
| | | | | | | | | | | |
Collapse
|
|
37
|
Goeree R, O'Brien BJ, Blackhouse G, Marshall J, Briggs A, Lad R. Cost-effectiveness and cost-utility of long-term management strategies for heartburn. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2002; 5:312-328. [PMID: 12102694 DOI: 10.1046/j.1524-4733.2002.54145.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/23/2023]
Abstract
OBJECTIVES To compare the expected costs and outcomes of seven alternative long-term primary care strategies for the management of patients with moderate-to-severe heartburn over a 1-year period. METHODS A decision-analytic model was developed to estimate costs and effects (weeks with heartburn symptoms and quality adjusted life years [QALYs]) for each strategy. Meta-analyses were used to synthesize acute treatment and maintenance studies and physician surveys to collect information on patient management. The impact of uncertainty on the base case results was assessed using probabilistic sensitivity analysis. Probability distributions were defined for key model parameters and techniques of Monte Carlo simulation were used to draw values from these distributions. Cost-effectiveness acceptability curves (CEACs) conditional on the monetary value decision makers are willing to pay for a symptom-free day or QALY were created for each strategy. RESULTS In the base case, no strategy was strictly dominated by any other strategy. However, two strategies (maintenance H2-receptor antagonists H2RA] and step-down proton pump inhibitor PPI]) were dominated through principles of extended dominance. The least costly and least effective strategy was intermittent H2RA, while maintenance PPI was the most costly and most effective. CONCLUSIONS This analysis showed that the best way of managing patients with heartburn depends on how much society is willing to pay to achieve health improvements. Based on the commonly quoted threshold of US 50,000 dollars per QALY, the optimal primary care strategy for managing patients with moderate-to-severe heartburn symptoms is to treat the symptoms with a PPI followed by maintenance therapy with an H2RA to prevent symptomatic recurrence.
Collapse
Affiliation(s)
- Ron Goeree
- Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Ontario L8N 1G6, Canada.
| | | | | | | | | | | |
Collapse
|
|
38
|
Fackler WK, Ours TM, Vaezi MF, Richter JE. Long-term effect of H2RA therapy on nocturnal gastric acid breakthrough. Gastroenterology 2002; 122:625-32. [PMID: 11874994 DOI: 10.1053/gast.2002.31876] [Citation(s) in RCA: 197] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND & AIMS Adding histamine 2 receptor antagonists (H2RAs) to proton pump inhibitor (PPI) therapy is a common practice to block nocturnal acid breakthrough (NAB). Controversy exists over its efficacy because of H2RA intolerance. No prospective study has addressed this issue. METHODS Twenty-three healthy volunteers and 20 gastroesophageal reflux disease (GERD) patients were studied. Ambulatory pH monitoring was performed with one electrode in the gastric fundus and the other 5 cm above the lower esophageal sphincter. Baseline pH testing was performed and repeated after 2 weeks on PPI twice daily before meals (omeprazole 20 mg). All subjects then received 28 days of PPI plus H2RA Qhs (ranitidine 300 mg) with repeat pH testing on days 1, 7, and 28. RESULTS Eighteen controls and 16 GERD patients completed all 5 studies. Compared with baseline, all 4 medication regimens decreased supine % time pH < 4 (P = 0.001). The administration of PPI + 1 day of H2RA was the only therapy that significantly decreased % time gastric pH < 4 for the supine period compared with PPI twice daily alone (P < 0.001). There was no difference in % time supine gastric pH < 4 between 2 weeks of PPI twice daily alone and either 1 week or 1 month of PPI + bedtime H2RA. CONCLUSIONS The combination of H2RA and PPI therapy reduced NAB only with the introduction of therapy. Because of H2RA tolerance, there is no difference in acid suppression between PPI twice daily and PPI twice daily + H2RA after 1 week of combination therapy.
Collapse
Affiliation(s)
- William K Fackler
- Center for Swallowing and Esophageal Disorders, Department of Gastroenterology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
| | | | | | | |
Collapse
|
|
39
|
Mackenzie FD, Pillans PI, Radford JM, Claes MT, Flemin AM. Improving Concordance Between Use of Proton Pump Inhibitors and Prescribing Guidelines. JOURNAL OF PHARMACY PRACTICE AND RESEARCH 2002. [DOI: 10.1002/jppr200232131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
|
|
40
|
Abstract
Gastro-oesophageal reflux disease (GORD) is common in the elderly. The presenting symptoms of heartburn and regurgitation, so common in the young, are less frequent in the elderly. Common symptoms of GORD in the elderly are dysphagia, vomiting and respiratory problems. Because of the higher risk of associated pathological oesophageal lesions in the older person presenting with symptoms suggestive of GORD, oesophagogastroduodenoscopy must be performed earlier in their clinical course. There is only a poor correlation between the severity of the symptoms and the severity of the associated oesophagitis. Whereas lifestyle modifications are important in individuals with GORD, the use of proton pump inhibitors is recommended to heal the underlying pathology, to resolve the patient's symptoms, to prevent complications, and to improve the quality of life.
Collapse
|
|
41
|
Howden CW, Henning JM, Huang B, Lukasik N, Freston JW. Management of heartburn in a large, randomized, community-based study: comparison of four therapeutic strategies. Am J Gastroenterol 2001; 96:1704-10. [PMID: 11419818 DOI: 10.1111/j.1572-0241.2001.03861.x] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Our objective was to compare four management strategies for heartburn: therapy with an H2-receptor antagonist (ranitidine), therapy with a proton pump inhibitor (lansoprazole), crossover from ranitidine to lansoprazole ("step-up" therapy), and crossover from lansoprazole to ranitidine ("step-down" therapy). METHODS This was a controlled, double-blind, multicenter trial comprising 593 adults with heartburn, randomized to one of four groups for 20 wk. Subjects received either ranitidine 150 mg b.i.d. for 20 wk, or lansoprazole 30 mg once daily for 20 wk, or ranitidine 150 mg b.i.d. for 8 wk [corrected] followed by lansoprazole 30 mg once daily for 12 wk ("step-up"), or lansoprazole 30 mg once daily for 8 wk followed by ranitidine 150 mg b.i.d. for 12 wk ("step-down"). Outcome measures were based on self-reports in daily diaries of 24-h heartburn severity, measured by maximum daytime and nighttime severity, and percentage of 24-h heartburn-free days measured by absence of both daytime and nighttime heartburn. RESULTS Median heartburn severity was significantly lower (p < 0.05) for lansoprazole (0.25) than the other groups (0.46 ranitidine, 0.44 "step-up," 0.35 "step-down"). The lansoprazole group had a significantly higher percentage of 24-h heartburn-free days (median 81.4%, p < 0.01) than other groups (66.6, 66.9, and 73.6%, respectively). In the "step-up" and "step-down" groups, heartburn was less severe, and percentages of 24-h heartburn-free days were higher during lansoprazole treatment regardless of treatment sequence. CONCLUSION Proton pump inhibitor treatment provides more consistent heartburn relief than an H2-receptor antagonist, or "step-up" or "step-down" therapy.
Collapse
Affiliation(s)
- C W Howden
- Northwestern University Medical School, Chicago, Illinois, USA
| | | | | | | | | |
Collapse
|
|
42
|
Gerson LB, Robbins AS, Garber A, Hornberger J, Triadafilopoulos G. A cost-effectiveness analysis of prescribing strategies in the management of gastroesophageal reflux disease. Am J Gastroenterol 2000; 95:395-407. [PMID: 10685741 DOI: 10.1111/j.1572-0241.2000.01759.x] [Citation(s) in RCA: 83] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Patients who have uncomplicated gastroesophageal-reflux disease (GERD) typically present with heartburn and acid regurgitation. We sought to determine the cost-effectiveness of H2-receptor antagonists (H2RAs) and proton-pump inhibitors (PPIs) as first-line empiric therapy for patients with typical symptoms of GERD. METHODS Decision analysis comparing costs and benefits of empirical treatment with H2RAs and PPIs for patients presenting with typical GERD was employed. The six treatment arms in the model were: 1) Lifestyle therapy, including antacids; 2) H2RA therapy, with endoscopy performed if no response to H2RAs; 3) Step up (H2RA-PPI) Arm: H2RA followed by PPI therapy in the case of symptomatic failure; 4) Step down arm: PPI therapy followed by H2RA if symptomatic response to PPI, and antacid therapy if response to H2RA therapy; 5) PPI-on-demand therapy: 8 wk of treatment for symptomatic recurrence, with no more than three courses per year; and 6) PPI-continuous therapy. Measurements were lifetime costs, quality-adjusted life years (QALYs) gained, and incremental cost effectiveness. RESULTS Initial therapy with PPIs followed by on-demand therapy was the most cost-effective approach, with a cost-effectiveness ratio of $20,934 per QALY gained for patients with moderate to severe GERD symptoms, and $37,923 for patients with mild GERD symptoms. This therapy was also associated with the greatest gain in discounted QALYs. The PPI-on-demand strategy was more effective and less costly than the H2RA followed by PPI strategy or the other treatment arms. The results were not highly sensitive to cost of therapy, QALY adjustment from GERD symptoms, or the success rate of the lifestyle arm. However, when the success rate of the PPI-on-demand arm was < or =59%, the H2RA-PPI arm was the preferred strategy. CONCLUSION For patients with moderate to severe symptoms of GERD, initial treatment with PPIs followed by on-demand therapy is a cost-effective approach.
Collapse
Affiliation(s)
- L B Gerson
- Department of Medicine, Stanford University School of Medicine, California, USA
| | | | | | | | | |
Collapse
|
|
43
|
Goeree R, O'Brien B, Hunt R, Blackhouse G, Willan A, Watson J. Economic evaluation of long-term management strategies for erosive oesophagitis. PHARMACOECONOMICS 1999; 16:679-697. [PMID: 10724795 DOI: 10.2165/00019053-199916060-00007] [Citation(s) in RCA: 22] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/23/2023]
Abstract
OBJECTIVE To compare the expected costs and outcomes of alternative strategies for the management of patients with erosive oesophagitis. DESIGN There were 3 components to the overall analytic approach. First, a decision model was constructed to compare expected costs and outcomes of 6 management strategies. Second, principles of quantitative literature review and meta-analysis were used to determine probabilities of clinical events (i.e. oesophagitis healing and recurrence). Finally, principles of cost-effectiveness analysis were used to compare treatment alternatives in terms of dominance and incremental cost effectiveness. The viewpoint for the study was that of a provincial government payer for healthcare over a 1-year period. MAIN OUTCOME MEASURES AND RESULTS Healing rates were significantly higher for proton pump inhibitors (PPI) [p < 0.001]. Recurrence rates were significantly higher for intermittent therapy (placebo) and lower for regular dose PPI (p < 0.001). Maintenance prokinetic agent (PA) is dominated (i.e. more costly and less effective) and step-down maintenance PPI is dominated through principles of extended dominance. The 'efficient frontier' is represented by: maintenance H2-receptor antagonist (H2RA), intermittent PPI, step-down maintenance H2RA and maintenance PPI. CONCLUSIONS The price of H2RA is a key factor influencing whether step-down maintenance PPI forms part of, or is contained within, the 'efficient frontier' of long term management for erosive oesophagitis.
Collapse
Affiliation(s)
- R Goeree
- Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
| | | | | | | | | | | |
Collapse
|
|
44
|
Abstract
The management of dyspepsia has been radically altered by the discovery of the role of Helicobacter pylori and the advent of proton pump inhibitors (PPIs). The use of PPIs alone as antisecretory agents and as part of triple therapy regimens for H. pylori eradication accounts for a significant percentage of any healthcare system's drug budget. Thus, it is important to take into account a variety of factors when devising a formulary and considering which PPIs to include. Consideration of 3 factors are particularly crucial in this process, namely therapeutic efficacy, tolerability and cost but several other clinical and economic parameters should also be considered. The mechanisms of action of all 4 PPIs currently available (omeprazole, lansoprazole, pantoprazole and rabeprazole) are very similar, with any small differences in pharmacological properties unlikely to be of clinical significance. Therapeutic efficacy in patients with acute reflux oesophagitis is again very similar for all 4 PPIs at their standard dosages; all agents are superior to H2-antagonists. Data on maintenance therapy for reflux oesophagitis also suggest similar efficacy for omeprazole and lansoprazole; data on pantoprazole and rabeprazole are awaited. For the treatment of H. pylori-related ulcers, the consensus at present is for PPI-based triple therapy. Again, all PPIs seem equally efficacious for this indication but pantoprazole and rabeprazole have yet to receive licences for H. pylori eradication therapy (HPET) in most countries. Drug tolerability is another critical issue to consider in formulary inclusion decisions. As a class, the PPIs are well tolerated. Minor drug interactions are reported for omeprazole, lansoprazole and rabeprazole but not for pantoprazole. However, whether or not this is significant in clinical practice is open to debate. Most of the pharmacoeconomic data in these indicators, to date, relate to omeprazole and, to a lesser extent, lansoprazole. Certainly, the studies on these 2 drugs confirm the superior cost effectiveness of PPIs over H2-antagonists in the treatment of reflux oesophagitis and peptic ulceration in both the short and long-terms. Although data are awaited, there is no reason to suggest that this will be any different for pantoprazole and rabeprazole. PPI-based triple therapy for H. pylori eradication appears to be the most cost-effective treatment option for H. pylori-related peptic ulcer disease. It is clear that PPIs are superior in several regards to previously used medications in the treatment of dyspepsia. Which PPI(s) to include in a particular formulary is a more difficult decision. On review of many criteria involved in formulary decisions, differences between the individual PPIs appear minimal. The relative acquisition costs of the PPIs vary nationally and internationally and this may be a critical factor in formulary inclusion decisions. However, one should not ignore non-economic factors, as these should form the basis of any sound drug policies.
Collapse
Affiliation(s)
- M F Byrne
- Department of Gastroenterology, Beaumont Hospital, Dublin, Ireland.
| | | |
Collapse
|
|
45
|
Festen HP, Schenk E, Tan G, Snel P, Nelis F. Omeprazole versus high-dose ranitidine in mild gastroesophageal reflux disease: short- and long-term treatment. The Dutch Reflux Study Group. Am J Gastroenterol 1999; 94:931-6. [PMID: 10201459 DOI: 10.1111/j.1572-0241.1999.989_l.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Patients with reflux esophagitis suffer from a chronic condition that may cause considerable discomfort because of recurrent symptoms and diminished quality of life. This study was designed to evaluate acute and long-term treatment comparing standard doses of omeprazole and high-dose ranitidine. METHODS Patients with endoscopically verified symptomatic esophagitis grade I or II were initially treated with omeprazole 20 mg daily or ranitidine 300 mg twice daily for 4-8 wk. Patients who were symptom free were randomized to maintenance treatment with omeprazole 10 mg daily or ranitidine 150 mg twice daily. Patients were seen every 3 months or at symptomatic relapse. RESULTS The percentage of asymptomatic patients after 4 and 8 wk treatment were 61% and 74%, respectively, for omeprazole and 31% and 50%, respectively, for ranitidine. Of 446 patients treated initially, 277 were asymptomatic, of whom 263 entered the maintenance study. The estimated proportion of patients in remission after 12 months of maintenance treatment with omeprazole 10 mg daily (n = 134) and ranitidine 150 mg twice daily (n = 129) were 68% and 39%, respectively (p < 0.0001). CONCLUSIONS Omeprazole 20 mg daily is superior to high-dose ranitidine in the symptomatic treatment of reflux esophagitis grade I and II. Furthermore, omeprazole at half the standard dose is more effective than ranitidine in a standard dose in keeping patients in remission for a period of 12 months.
Collapse
Affiliation(s)
- H P Festen
- Department of Internal Medicine, Groot Ziekengasthuis, 's-Hertogenbosch, The Netherlands
| | | | | | | | | |
Collapse
|
|
46
|
Huang JQ, Hunt RH. pH, healing rate, and symptom relief in patients with GERD. THE YALE JOURNAL OF BIOLOGY AND MEDICINE 1999; 72:181-94. [PMID: 10780580 PMCID: PMC2579003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
Gastroesophageal reflux symptoms are common and occur in all of us from time to time. In others, reflux may be associated with ulcerative esophagitis. The symptoms may be aggravated by large meals, coffee, smoking and position. Physiological and pathological reflux can be separated by the frequency and duration of the exposure of the lower esophagus to acid. Pathological reflux results in symptoms and also esophagitis and ulceration in some patients. Although gastroesophageal reflux disease (GERD) is considered to result from a disorder of motility in the esophagus, gastric acid and peptic activity are deemed pivotal to the initiation and continuation of the esophageal damage and the development of symptoms. Acid exposure in the esophagus is normally less than 4 percent of the 24 hours with a pH below 4. An increase over 4 percent of the time with a pH less than 4 is considered pathological. Hence, antisecretory drugs have become the principle approach to the treatment of reflux symptoms and esophagitis since they reduce the acidity, of gastric juice and the activity of pepsin. Importantly, they also reduce the volume of gastric juice available for reflux into the esophagus. There is a clear relationship between the degree and duration of acid suppression and the relief of heartburn and healing of esophagitis. Pharmacodynamic studies with different dose regimens of the H2-receptor antagonists and the proton pump inhibitors show a difference in the degree and duration of the antisecretory effect, and this correlates closely with the results of clinical trials with respect to the healing of esophagitis and the relief of symptoms. Proton pump inhibitors achieve healing rates by week four, which are not achieved by H2-receptor antagonists even after 12 weeks of treatment. The advantage of proton pump inhibitors over H2-receptor antagonists is due to the greater degree, longer duration of effect and more complete inhibition of acid secretion that maintains intragastric pH above 4 for a maximal duration. Although there is no significant difference between proton pump inhibitors with respect to healing of esophagitis, symptom relief occurs earlier with lansoprazole than omeprazole, and this is probably due to the greater oral bioavailability and faster onset of action of lansoprazole when compared to omeprazole.
Collapse
Affiliation(s)
- J Q Huang
- Department of Medicine, McMaster University Medical Center, Hamilton, Ontario, Canada
| | | |
Collapse
|
|
47
|
Richardson P, Hawkey CJ, Stack WA. Proton pump inhibitors. Pharmacology and rationale for use in gastrointestinal disorders. Drugs 1998; 56:307-35. [PMID: 9777309 DOI: 10.2165/00003495-199856030-00002] [Citation(s) in RCA: 182] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Proton pump inhibitors (PPIs) are drugs which irreversibly inhibit proton pump (H+/K+ ATPase) function and are the most potent gastric acid-suppressing agents in clinical use. There is now a substantial body of evidence showing improved efficacy of PPIs over the histamine H2 receptor antagonists and other drugs in acid-related disorders. Omeprazole 20 mg/day, lansoprazole 30 mg/day, pantoprazole 40 mg/day or rabeprazole 20 mg/day for 2 to 4 weeks are more effective than standard doses of H2-receptor antagonists in healing duodenal and gastric ulcers. Patients with gastric ulcers should receive standard doses of PPIs as for duodenal ulcers but for a longer time period (4 to 8 weeks). There is no conclusive evidence to support the use of a particular PPI over another for either duodenal or gastric ulcer healing. For Helicobacter pylori-positive duodenal ulceration, a combination of a PPI and 2 antibacterials will eradicate H. pylori in over 90% of cases and significantly reduce ulcer recurrence. Patients with H. pylori-positive gastric ulcers should be managed similarly. PPIs also have efficacy advantages over ranitidine and misoprostol and are better tolerated than misoprostol in patients taking nonsteroidal anti-inflammatory drugs (NSAIDs). In endoscopically proven gastro-oesophageal reflux disease, standard daily doses of the PPIs are more effective than H2-receptor antagonists for healing, and patients should receive a 4 to 8 week course of treatment. For severe reflux, with ulceration and/or stricture formation, a higher dose regimen (omeprazole 40 mg, lansoprazole 60 mg, pantoprazole 80 mg or rabeprazole 40 mg daily) appears to yield better healing rates. There is little evidence that PPIs lead to resolution of Barrett's oesophagus or a reduction of subsequent adenocarcinoma development, but PPIs are indicated in healing of any associated ulceration. In Zollinger-Ellison syndrome, PPIs have become the treatment of choice for the management of gastric acid hypersecretion.
Collapse
Affiliation(s)
- P Richardson
- Division of Gastroenterology, University Hospital, Queens Medical Centre, Nottingham, England
| | | | | |
Collapse
|
|
48
|
Chabot I, Morin J, Bourbeau K, Moisan J. A Comparison of Retrospective and Concurrent Drug Utilization Review of Omeprazole. J Pharm Technol 1998. [DOI: 10.1177/875512259801400507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Objective: To compare the appropriateness of omeprazole prescriptions in a concurrent drug utilization review (DUR) with the assessed appropriateness of a retrospective DUR. Methods: A retrospective DUR of omeprazole was conducted on prescriptions written from August 23, 1993, to October 8, 1993, in a 340-bed university hospital. This DUR served as a baseline for a concurrent DUR that began on January 27, 1995, and ended on March 16, 1995. The concurrent DUR integrated three steps aimed at improving the quality of omeprazole use: Approval of the criteria by the pharmacology and therapeutics committee of the hospital, distribution of a drug bulletin to all physicians, and a pharmacist's verbal recommendations to physicians whose prescriptions did not meet explicit criteria. Results: Twenty-nine and 64 prescriptions were reviewed in the retrospective and concurrent DURs, respectively. During the concurrent DUR, the pharmacist made 34 verbal recommendations. Of these, 25 (74%) were agreed to by the prescribers. In comparison with the retrospective DUR, the percentage of prescriptions meeting the criteria of indication, combination therapy, and dosage went from 38% to 75% (p < 0.05), from 76% to 95% (p < 0.05), and from 83% to 100% (p > 0.05), respectively, during the concurrent DUR. Conclusions: The concurrent DUR appeared to successfully improve the quality of omeprazole utilization in the hospital.
Collapse
|
|
49
|
Kim KB, Chang MS, Chung YK, Sohn SK, Kim SG, Choi WS. Biochemical and pharmacological characteristics of 3-butyryl-8-methoxy-4-[(2-thiophenyl)amino]quinoline, a new proton-pump inhibitor, in rabbit gastric microsomes and in rats. J Pharm Pharmacol 1998; 50:521-9. [PMID: 9643446 DOI: 10.1111/j.2042-7158.1998.tb06194.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
We have investigated the properties of the newly synthesized proton-pump inhibitor, 3-butyryl-8-methoxy-4-[(2-thiophenyl)amino]quinoline (YJA20379-6), on gastric mucosal proton-pump (H+/K+-ATPase) activity, gastric acid secretion and gastroduodenal lesions in experimental rats. YJA20379-6 markedly inhibited H+/K+-ATPase activity in rabbit isolated gastric mucosal microsomes, confirming its classification as a proton-pump inhibitor. The inhibitory efficacy of YJA20379-6 on the proton pump was approximately 14-times higher than that of omeprazole at pH 7.4. YJA20379-6 given intraduodenally had a potent inhibitory effect on gastric secretion in pylorus-ligated rats (ED50 22.9 mg kg(-1)) but was less active than omeprazole. Pretreatment of rats with YJA20379-6 dose-dependently protected the gastric mucosa from damage induced by water-immersion stress, indomethacin and absolute ethanol, and the duodenal mucosa from damage induced by mepirizole. Repeated administration of YJA20379-6 also dose-dependently accelerated the spontaneous healing of acetic acid-induced gastric ulcers. These results suggest that YJA20379-6 has potent anti-secretory and anti-ulcer effects which are exerted by suppression of H+/K+-ATPase activity in gastric parietal cells. YJA20379-6 might be useful for the clinical treatment of peptic ulcer diseases.
Collapse
Affiliation(s)
- K B Kim
- Pharmacology and Toxicology Laboratory, Yung-Jin Pharmaceutical Co. Ltd, Kyunggi-Do, Korea
| | | | | | | | | | | |
Collapse
|
|
50
|
Abstract
Gastro-oesophageal reflux disease is common, with up to 10% of the general population experiencing heartburn on a daily basis. It is a chronic condition and follow-up studies indicate the presence of symptoms at least 20 years after initial diagnosis. In addition to lifestyle modifications, management usually involves the use of an acid suppressant from the H2-receptor antagonist or proton pump inhibitor groups or a prokinetic agent at some stage. In terms of initial symptom resolution and mucosal healing the proton pump inhibitors are consistently superior to the other available agents. However, while it is possible to keep the majority of patients in remission while taking medications, almost all patients have a recurrence of symptoms within six months of stopping medications. The introduction of laparoscopic fundoplication has produced promising initial results but the long-term benefits of this procedure remain to be established. The role of Helicobacter pylori eradication in the management of gastro-oesophageal reflux disease needs further evaluation.
Collapse
Affiliation(s)
- J M Lee
- Department of Gastroenterology, Meath Hospital, Trinity College, Dublin, Ireland
| | | |
Collapse
|