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International Journal of Molecular... Sep 2022Proton pump inhibitors (PPIs) are an antacid drug often used in acid-related disorders. They decrease acid secretion in the stomach by blocking an enzyme called H+/K+... (Review)
Review
Proton pump inhibitors (PPIs) are an antacid drug often used in acid-related disorders. They decrease acid secretion in the stomach by blocking an enzyme called H+/K+ ATPase which controls acid production. Introduced to the market in 1989, their use has increased rapidly worldwide and they are now among the top 10 most prescribed drugs in the United States. As of 2015, the FDA has already approved six drugs of this class (omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole and rabeprazole). Recently, the risks and benefits of long-term PPI use were questioned and many studies indicated that their use should be carefully considered, especially in young patients, whose treatment with these drugs could last many years. Even greater concerns have been raised about a potential positive association between PPIs and osteoporotic fracture risk including the hip, spine and wrist. Although based on observational studies, there is substantial evidence associating the long-term use of PPIs and fracture. This relationship is only partially admitted due to the lack of consistent effects of PPIs on bone mineral density loss. Therefore, this narrative review aimed to discuss the recent findings pertaining to the risk of osteoporotic fracture associated with PPIs, in particular prolonged use, and to call for further research to elucidate the mechanisms associated with this bone fragility.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adenosine Triphosphatases; Antacids; Bone Density; Dexlansoprazole; Esomeprazole; Humans; Lansoprazole; Omeprazole; Osteoporotic Fractures; Pantoprazole; Proton Pump Inhibitors; Rabeprazole; United States
PubMed: 36142643
DOI: 10.3390/ijms231810733 -
Veterinary Journal (London, England :... 2022Many domesticated horses have gastric ulcers which can be diagnosed and graded during gastroscopy. A distinction should be made between equine squamous gastric disease... (Review)
Review
Many domesticated horses have gastric ulcers which can be diagnosed and graded during gastroscopy. A distinction should be made between equine squamous gastric disease (ESGD), which is caused by exposure of the mucosa to acid, and equine glandular gastric disease (EGGD), thought to occur when mucosal defence mechanisms are compromised. Horses with gastric ulcers may, but do not always, show clinical signs such as poor appetite, mild colic, discomfort during girthing, behavioural changes and reduced performance. The mainstay of treatment is blocking acid production using the proton pump inhibitor omeprazole. Treatment is usually successful in cases of ESGD, but less so for EGGD, where treatment duration is longer and for which sucralfate may be added or alternatives necessary, such as misoprostol, a prostaglandin analogue. To prevent recurrence of ulcers known risk factors, such as high concentrate diets, intense exercise and stress should be avoided or minimized.
Topics: Animals; Gastric Mucosa; Gastroscopy; Horse Diseases; Horses; Omeprazole; Stomach Ulcer
PubMed: 35472513
DOI: 10.1016/j.tvjl.2022.105830 -
Expert Opinion on Drug Metabolism &... May 2022Proton pump inhibitors (PPIs) block the gastric H/K-ATPase, therefore inhibiting acid gastric secretion, leading to an increased pH (>4). They account for an extremely... (Review)
Review
INTRODUCTION
Proton pump inhibitors (PPIs) block the gastric H/K-ATPase, therefore inhibiting acid gastric secretion, leading to an increased pH (>4). They account for an extremely high number of prescriptions worldwide. Numerous drug-drug interactions have been described with PPIs, but all the described interactions do not have clinical significance.
AREAS COVERED
This review will discuss the latest updates on drug-drug interactions with PPIs, focusing on the last 10-year publications in the following areas: anti-infective agents, anticancer drugs, antiplatelet agents and anticoagulants, and antidiabetics.
EXPERT OPINION
Although pharmacokinetic interactions of PPIs have been described with many drugs, their clinical relevance remains controversial. However, given the extremely high number of people being treated with PPIs, clinicians should remain vigilant for interactions that may be clinically significant and require dose adjustment or therapeutic monitoring. Interestingly, not all PPIs have the same pharmacokinetic and pharmacodynamic profile, with some having a strong potential to inhibit CYP2C19, such as omeprazole, esomeprazole, and lansoprazole, while others, pantoprazole, rabeprazole, and dexlansoprazole, are weak CYP2C19 inhibitors. These may be preferred depending on co-prescribed treatments.In addition, new formulations have been developed to prevent some of the gastric pH-dependent drug interactions and should be evaluated in further large-scale prospective comparative studies.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Drug Interactions; Enzyme Inhibitors; Esomeprazole; Humans; Omeprazole; Prospective Studies; Proton Pump Inhibitors
PubMed: 35787720
DOI: 10.1080/17425255.2022.2098107 -
BMJ Evidence-based Medicine Nov 2023To compare the efficacy of curcumin versus omeprazole in improving patient reported outcomes in people with dyspepsia. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To compare the efficacy of curcumin versus omeprazole in improving patient reported outcomes in people with dyspepsia.
DESIGN
Randomised, double blind controlled trial, with central randomisation.
SETTING
Thai traditional medicine hospital, district hospital, and university hospitals in Thailand.
PARTICIPANTS
Participants with a diagnosis of functional dyspepsia.
INTERVENTIONS
The interventions were curcumin alone (C), omeprazole alone (O), or curcumin plus omeprazole (C+O). Patients in the combination group received two capsules of 250 mg curcumin, four times daily, and one capsule of 20 mg omeprazole once daily for 28 days.
MAIN OUTCOME MEASURES
Functional dyspepsia symptoms on days 28 and 56 were assessed using the Severity of Dyspepsia Assessment (SODA) score. Secondary outcomes were the occurrence of adverse events and serious adverse events.
RESULTS
206 patients were enrolled in the study and randomly assigned to one of the three groups; 151 patients completed the study. Demographic data (age 49.7±11.9 years; women 73.4%), clinical characteristics and baseline dyspepsia scores were comparable between the three groups. Significant improvements were observed in SODA scores on day 28 in the pain (-4.83, -5.46 and -6.22), non-pain (-2.22, -2.32 and -2.31) and satisfaction (0.39, 0.79 and 0.60) categories for the C+O, C, and O groups, respectively. These improvements were enhanced on day 56 in the pain (-7.19, -8.07 and -8.85), non-pain (-4.09, -4.12 and -3.71) and satisfaction (0.78, 1.07, and 0.81) categories in the C+O, C, and O groups, respectively. No significant differences were observed among the three groups and no serious adverse events occurred.
CONCLUSION
Curcumin and omeprazole had comparable efficacy for functional dyspepsia with no obvious synergistic effect.
TRIAL REGISTRATION NUMBER
TCTR20221208003.
Topics: Humans; Female; Adult; Middle Aged; Proton Pump Inhibitors; Curcumin; Dyspepsia; Omeprazole; Pain
PubMed: 37696679
DOI: 10.1136/bmjebm-2022-112231 -
The Cochrane Database of Systematic... Aug 2023Gastro-oesophageal reflux (GOR) is characterised by the regurgitation of gastric contents into the oesophagus. GOR is a common presentation in infancy, both in primary... (Review)
Review
BACKGROUND
Gastro-oesophageal reflux (GOR) is characterised by the regurgitation of gastric contents into the oesophagus. GOR is a common presentation in infancy, both in primary and secondary care, affecting approximately 50% of infants under three months old. The natural history of GOR in infancy is generally of a self-limiting condition that improves with age, but older children and children with co-existing medical conditions can have more protracted symptoms. The distinction between gastro-oesophageal reflux disease (GORD) and GOR is debated. Current National Institute of Health and Care Excellence (NICE) guidelines define GORD as GOR causing symptoms severe enough to merit treatment. This is an update of a review first published in 2014.
OBJECTIVES
To assess the effects of pharmacological treatments for GOR in infants and children.
SEARCH METHODS
For this update, we searched CENTRAL, MEDLINE, Embase, and Web of Science up to 17 September 2022. We also searched for ongoing trials in clinical trials registries, contacted experts in the field, and searched the reference lists of trials and reviews for any additional trials.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared any currently-available pharmacological treatment for GOR in children with placebo or another medication. We excluded studies assessing dietary management of GORD and studies of thickened feeds. We included studies in infants and children up to 16 years old.
DATA COLLECTION AND ANALYSIS
We used standard methodology expected by Cochrane.
MAIN RESULTS
We included 36 RCTs involving 2251 children and infants. We were able to extract summary data from 14 RCTs; the remaining trials had insufficient data for extraction. We were unable to pool results in a meta-analysis due to methodological differences in the included studies (including heterogeneous outcomes, study populations, and study design). We present the results in two groups by age: infants up to 12 months old, and children aged 12 months to 16 years old. Infants Omeprazole versus placebo: there is no clear effect on symptoms from omeprazole. One study (30 infants; very low-certainty evidence) showed cry/fuss time in infants aged three to 12 months had altered from 246 ± 105 minutes/day at baseline (mean +/- standard deviation (SD)) to 191 ± 120 minutes/day in the omeprazole group and from 287 ± 132 minutes/day to 201 ± 100 minutes/day in the placebo group (mean difference (MD) 10 minutes/day lower (95% confidence interval (CI) -89.1 to 69.1)). The reflux index changed in the omeprazole group from 9.9 ± 5.8% in 24 hours to 1.0 ± 1.3% and in the placebo group from 7.2 ± 6.0% to 5.3 ± 4.9% in 24 hours (MD 7% lower, 95% CI -4.7 to -9.3). Omeprazole versus ranitidine: one study (76 infants; very low-certainty evidence) showed omeprazole may or may not provide symptomatic benefit equivalent to ranitidine. Symptom scores in the omeprazole group changed from 51.9 ± 5.4 to 2.4 ± 1.2, and in the ranitidine group from 47 ± 5.6 to 2.5 ± 0.6 after two weeks: MD -4.97 (95% CI -7.33 to -2.61). Esomeprazole versus placebo: esomeprazole appeared to show no additional reduction in the number of GORD symptoms compared to placebo (1 study, 52 neonates; very low-certainty evidence): both the esomeprazole group (184.7 ± 78.5 to 156.7 ± 75.1) and placebo group (183.1 ± 77.5 to 158.3 ± 75.9) improved: MD -3.2 (95% CI -4.6 to -1.8). Children Proton pump inhibitors (PPIs) at different doses may provide little to no symptomatic and endoscopic benefit. Rabeprazole given at different doses (0.5 mg/kg and 1 mg/kg) may provide similar symptom improvement (127 children in total; very low-certainty evidence). In the lower-dose group (0.5 mg/kg), symptom scores improved in both a low-weight group of children (< 15 kg) (mean -10.6 ± SD 11.13) and a high-weight group of children (> 15 kg) (mean -13.6 ± 13.1). In the higher-dose groups (1 mg/kg), scores improved in the low-weight (-9 ± 11.2) and higher-weight groups (-8.3 ± 9.2). For the higher-weight group, symptom score mean difference between the two different dosing regimens was 2.3 (95% CI -2 to 6.6), and for the lower-weight group, symptom score MD was 4.6 (95% CI -2.9 to 12). Pantoprazole: pantoprazole may or may not improve symptom scores at 0.3 mg/kg, 0.6 mg/kg, and 1.2 mg/kg pantoprazole in children aged one to five years by week eight, with no difference between 0.3 mg/kg and 1.2 mg/kg dosing (0.3 mg/kg mean -2.4 ± 1.7; 1.2 mg/kg -1.7 ± 1.2: MD 0.7 (95% CI -0.4 to 1.8)) (one study, 60 children; very low-certainty evidence). There were insufficient summary data to assess other medications.
AUTHORS' CONCLUSIONS
There is very low-certainty evidence about symptom improvements and changes in pH indices for infants. There are no summary data for endoscopic changes. Medications may or may not provide a benefit (based on very low-certainty evidence) for infants whose symptoms remain bothersome, despite nonmedical interventions or parental reassurance. If a medication is required, there is no clear evidence based on summary data for omeprazole, esomeprazole (in neonates), H₂antagonists, and alginates for symptom improvements (very low-certainty evidence). Further studies with longer follow-up are needed. In older children with GORD, in studies with summary data extracted, there is very low-certainty evidence that PPIs (rabeprazole and pantoprazole) may or may not improve GORD outcomes. No robust data exist for other medications. Further RCT evidence is required in all areas, including subgroups (preterm babies and children with neurodisabilities).
Topics: Adolescent; Child; Humans; Infant; Infant, Newborn; Esomeprazole; Gastroesophageal Reflux; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Rabeprazole; Ranitidine
PubMed: 37635269
DOI: 10.1002/14651858.CD008550.pub3 -
British Journal of Clinical Pharmacology Jul 2022Nocturnal acid breakthrough has been considered an unmet need of proton-pump inhibitors. Tegoprazan, a novel potassium-competitive acid blocker, is expected to show... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
Nocturnal acid breakthrough has been considered an unmet need of proton-pump inhibitors. Tegoprazan, a novel potassium-competitive acid blocker, is expected to show improved properties for this unmet need. This study was aimed to compare night-time acid suppression by tegoprazan with that by vonoprazan or esomeprazole, and to explore the effect of CYP2C19 phenotypes on acid-suppressive effects.
METHODS
A randomized, open-label, 3-period, 6-sequence crossover study was conducted. A single oral dose of tegoprazan 50 mg, vonoprazan 20 mg or esomeprazole 40 mg was administered at night in each period. Continuous intragastric pH was monitored at baseline and after each dosing.
RESULTS
Sixteen healthy subjects (6 CYP2C19 extensive metabolizers, 5 intermediate metabolizers, 5 poor metabolizers) completed the study. After a single dose of tegoprazan, intragastric pH increased more rapidly to over 4 at approximately 1 hour compared to the other treatments, and elevated intragastric pH was maintained stably at night. Tegoprazan exhibited night-time acid suppression for slightly but not significantly longer than vonoprazan, and greater than esomeprazole; % time at pH ≥ 4 at night was 66.0%, 60.5% and 36.1% for tegoprazan, vonoprazan and esomeprazole, respectively. Night-time acid suppression by tegoprazan and vonoprazan was not dependent on CYP2C19 phenotypes, while that by esomeprazole tended to be influenced by CYP2C19 phenotypes.
CONCLUSION
Tegoprazan produced more rapid, potent and well sustained night-time acid suppression vs. vonoprazan or esomeprazole when administered at night. Furthermore, tegoprazan showed no CYP2C19 phenotype dependency in acid suppression. It suggests the potential of tegoprazan, especially in preventing nocturnal acid breakthrough.
Topics: Benzene Derivatives; Cross-Over Studies; Cytochrome P-450 CYP2C19; Esomeprazole; Gastric Acid; Humans; Hydrogen-Ion Concentration; Imidazoles; Proton Pump Inhibitors; Pyrroles; Sulfonamides
PubMed: 35146797
DOI: 10.1111/bcp.15268 -
The Journal of the Association of... Aug 2023In the last 3 decades, omeprazole has proved its mettle in managing acid peptic diseases (APDs). It has established itself as the first line of therapy for duodenal and... (Review)
Review
BACKGROUND
In the last 3 decades, omeprazole has proved its mettle in managing acid peptic diseases (APDs). It has established itself as the first line of therapy for duodenal and gastric ulcers, gastroesophageal reflux disease (GERD), ulcers due to nonsteroidal anti-inflammatory drugs (NSAID), and Zollinger-Ellison syndrome (ZES).
OBJECTIVES
The purpose of this literature review is to assess the effectiveness of omeprazole as compared to the other proton pump inhibitors (PPIs) currently in use and its safety and efficacy in special populations, including the pediatric and geriatric populations.
RESULTS
Omeprazole was found to be the most effective PPI in the management of APDs due to its rapid action, good antioxidant effects, and effectiveness against nocturnal acid breakthroughs. Its safety and tolerance have been proved in various randomized controlled trials.
CONCLUSION
Omeprazole is the prototypical drug in the management of APDs and has withstood the test of time. After 3 decades, omeprazole remains the drug of choice in managing APD.
Topics: Humans; Child; Aged; Omeprazole; Proton Pump Inhibitors; Gastroesophageal Reflux; Stomach Ulcer; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 37651247
DOI: 10.59556/japi.71.0322 -
Gastroenterology Aug 2019
Topics: Dexlansoprazole; Esomeprazole; Female; Homeostasis; Humans; Postmenopause
PubMed: 31260666
DOI: 10.1053/j.gastro.2019.06.006 -
Chinese Medical Journal Jul 2022High-dose dual therapy (HDDT) with proton pump inhibitors (PPIs) and amoxicillin has attracted widespread attention due to its favorable efficacy in eradicating... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
High-dose dual therapy (HDDT) with proton pump inhibitors (PPIs) and amoxicillin has attracted widespread attention due to its favorable efficacy in eradicating Helicobacter pylori (H. pylori). This study aimed to compare the efficacy and safety of high-dose PPI-amoxicillin dual therapy and bismuth-containing quadruple therapy for H. pylori rescue treatment.
METHODS
This was a prospective, randomized, multicenter, non-inferiority trial. Patients recruited from eight centers who had failed previous treatment were randomly (1:1) allocated to two eradication groups: HDDT (esomeprazole 40 mg and amoxicillin 1000 mg three times daily; the HDDT group) and bismuth-containing quadruple therapy (esomeprazole 40 mg, bismuth potassium citrate 220 mg, and furazolidone 100 mg twice daily, combined with tetracycline 500 mg three times daily; the tetracycline, furazolidone, esomeprazole, and bismuth [TFEB] group) for 14 days. The primary endpoint was the H. pylori eradication rate. The secondary endpoints were adverse effects, symptom improvement rates, and patient compliance.
RESULTS
A total of 658 patients who met the criteria were enrolled in this study. The HDDT group achieved eradication rates of 75.4% (248/329), 81.0% (248/306), and 81.3% (248/305) asdetermined by the intention-to-treat (ITT), modified intention-to-treat (MITT), and per-protocol (PP) analyses, respectively. The eradication rates were similar to those in the TFEB group: 78.1% (257/329), 84.2% (257/305), and 85.1% (257/302). The lower 95% confidence interval boundary (-9.19% in the ITT analysis, - 9.21% in the MITT analysis, and -9.73% in the PP analysis) was greater than the predefined non-inferiority margin of -10%, establishing a non-inferiority of the HDDT group vs. the TFEB group. The incidence of adverse events in the HDDT group was significantly lower than that in the TFEB group (11.1% vs. 26.8%, P < 0.001). Symptom improvement rates and patients' compliance were similar between the two groups.
CONCLUSIONS
Fourteen-day HDDT is non-inferior to bismuth-containing quadruple therapy, with fewer adverse effects and good treatment compliance, suggesting HDDT as an alternative for H. pylori rescue treatment in the local region.
TRIAL REGISTRATION
Clinicaltrials.gov, NCT04678492.
Topics: Amoxicillin; Anti-Bacterial Agents; Bismuth; Drug Therapy, Combination; Esomeprazole; Furazolidone; Helicobacter Infections; Helicobacter pylori; Humans; Potassium Citrate; Prospective Studies; Proton Pump Inhibitors; Tetracycline; Treatment Outcome
PubMed: 36193978
DOI: 10.1097/CM9.0000000000002289 -
World Journal of Gastroenterology Nov 2022Fexuprazan, a novel potassium-competitive acid blocker, reversibly suppresses the K/H-ATPase enzyme in proton pumps within gastric parietal cells. Fexuprazan's... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Fexuprazan, a novel potassium-competitive acid blocker, reversibly suppresses the K/H-ATPase enzyme in proton pumps within gastric parietal cells. Fexuprazan's suppression of gastric acid was maintained in healthy individuals for 24 h in a dose-dependent manner.
AIM
To compare fexuprazan to esomeprazole and establish its efficacy and safety in patients with erosive esophagitis (EE).
METHODS
Korean adult patients with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg or esomeprazole 40 mg once daily for eight weeks. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy at week 8. The secondary endpoints included the healing rate of EE at week 4, symptom response, and quality of life assessment. Safety profiles and serum gastrin levels were compared between the groups.
RESULTS
Of the 263 randomized, 218 completed the study per protocol (fexuprazan 40 mg, = 107; esomeprazole 40 mg, = 111). Fexuprazan was non-inferior to esomeprazole regarding the healing rate at week 8 [99.1% (106/107) 99.1% (110/111)]. There were no between-group differences in the EE healing rate at week 4 [90.3% (93/103) 88.5% (92/104)], symptom responses, and quality of life assessments. Additionally, serum gastrin levels at weeks 4 and 8 and drug-related side effects did not significantly differ between the groups.
CONCLUSION
Fexuprazan 40 mg is non-inferior to esomeprazole 40 mg in EE healing at week 8. We suggest that fexuprazan is an alternative promising treatment option to PPIs for patients with EE.
Topics: Adult; Humans; Esomeprazole; Gastrins; Quality of Life; Esophagitis; Peptic Ulcer; H(+)-K(+)-Exchanging ATPase; Drug-Related Side Effects and Adverse Reactions
PubMed: 36504556
DOI: 10.3748/wjg.v28.i44.6294