Treatment Of Acid-related Diseases Research Articles

Treatment of Acid-related Diseases Using Potassium-competitive Acid Blockers

Proton pump inhibitors (PPIs) have several limitations to their efficacy including insufficient acid suppression, slow onset of action, and variable efficacy among patients due to CYP2C19 metabolism. Potassium-competitive acid blockers inhibit H+-K+-ATPase in a reversible and K+-competitive manner, are novel acid suppressive drugs with rapid onset of action, meal independence, and prolonged control of intragastric acidity compared to PPIs. Potassium-competitive acid blockers exhibited non-inferior therapeutic efficacies on reflux esophagitis, gastric ulcers, and Helicobacter pylori eradication. The review is focused on the unmet needs across the acid-related diseases and recent updates on clinical studies using vonoprazan and tegoprazan.

Incorporation of Student Pharmacists into a Proton Pump Inhibitor Deprescribing Telehealth Program for Rural Veterans.

Background: Proton pump inhibitors (PPIs) are among the most widely prescribed class of medications in the United States. Although effective in the treatment of acid related disease, inappropriate PPI use is prevalent, and long-term PPI use has been associated with adverse effects. Objectives: This evaluation explores the novelty of a student-pharmacist directed PPI deprescribing telehealth program with the goals of (1) determining whether PPIs are appropriately prescribed in Veterans via remote student-led chart reviews, (2) identifying if a gap exists between urban and rural Veterans prescribed a PPI, and (3) assessing the feasibility of integrating student pharmacists into the PPI deprescribing process utilizing telehealth visits through a pilot study. Methods: Student pharmacists evaluated PPI appropriateness in Veterans at the William S. Middleton Veterans Hospital. Students collected data via remote chart reviews, compared appropriateness of PPI therapy in rural versus urban Veterans, and conducted a deprescribing pilot call study in rural Veterans with inappropriate PPI indications. Clinical decision-making was agreed upon in collaboration with pharmacist preceptors, however all means of communication with Veterans was performed by student pharmacists. Results: 51% of Veterans were found to have an inappropriate indication for their PPI, though comparison of inappropriate PPI use in rural versus urban Veterans was not statistically significant (n=170, p-value 0.34). 83% of Veterans agreed to proceed with PPI deprescribing and 71% of Veterans ended the pilot study with at least some degree of PPI dose reduction (n=33). Conclusion: Inappropriate PPI use among rural and urban Veterans is prevalent, however a significant difference was not observed between the two cohorts. Student pharmacists are capable of successful telehealth deprescribing interventions in collaboration with pharmacists.

Novel Cocrystals of Vonoprazan: Machine Learning-Assisted Discovery.

Vonoprazan (VPZ) is the first-in-class potassium-competitive acid blocker (P-CAB), and has many advantages over proton pump inhibitors (PPIs). It is administered as a fumarate salt for the treatment of acid-related diseases, including reflux esophagitis, gastric ulcer, and duodenal ulcer, and for eradication of Helicobacter pylori. To discover novel cocrystals of VPZ, we adopted an artificial neural network (ANN)-based machine learning model as a virtual screening tool that can guide selection of the most promising coformers for VPZ cocrystals. Experimental screening by liquid-assisted grinding (LAG) confirmed that 8 of 19 coformers selected by the ANN model were likely to create new solid forms with VPZ. Structurally similar benzenediols and benzenetriols, i.e., catechol (CAT), resorcinol (RES), hydroquinone (HYQ), and pyrogallol (GAL), were used as coformers to obtain phase pure cocrystals with VPZ by reaction crystallization. We successfully prepared and characterized three novel cocrystals: VPZ–RES, VPZ–CAT, and VPZ–GAL. VPZ–RES had the highest solubility among the novel cocrystals studied here, and was even more soluble than the commercially available fumarate salt of VPZ in solution at pH 6.8. In addition, novel VPZ cocrystals had superior stability in aqueous media than VPZ fumarates, demonstrating their potential for improved pharmaceutical performance.

Эволюция лечения кислотозависимой патологии

В статье рассмотрены основные этапы развития и совершенствования антисекреторной терапии, начиная от антацидов и заканчивая современными ингибиторами протонной помпы (ИПП). Сделан вывод, что в настоящее время основными препаратами для лечения кислотозависимой патологии являются ИПП, которые условно делятся на препараты I и II поколения. Препараты II поколения являются более эффективными и безопасными, поскольку меньше зависят от полиморфизма CYP2C19 и обладают наименьшим потенциалом побочных эффектов и межлекарственных взаимодействий. Наиболее безопасным ИПП для длительного лечения кислотозависимой патологии, особенно при необходимости приема других препаратов, является пантопразол.

Adverse events of vonoprazan in the treatments of acid-related diseases: a systematic review and meta-analysis.

vonoprazan, a novel potassium-competitive acid blocking agent, has better clinical outcomes in the treatment of acid-related diseases. However, some adverse events have been associated with vonoprazan for the treatment of acid-associated diseases. Therefore, this systematic review and meta-analysis aimed to explore the safety and tolerability of vonoprazan for acid-associated diseases. electronic databases were retrieved to determine randomized controlled trials (RCTs) of vonoprazan for acid-associated diseases with any adverse effects and discontinuation. this systematic review and meta-analysis conforming to the selection criteria included 18 RCTs with a total of 7,932 participants. Compared with proton pump inhibitors, oral vonoprazan treatment showed no significant increase in the incidence of adverse effects (95 % CI = 0.987-1.095, p = 0.141). Diarrhea or loose stools analysis showed that there was a statistically significant difference between vonoprazan and proton pump inhibitors (PPIs) treatment (95 % CI = 0.661-0.966, p = 0.021). However, there was no significant difference in constipation, rash or eruption, nausea or vomiting, bloating or abdominal pain, dysgeusia, nasopharyngitis, neurological disorders, upper respiratory tract infection and abnormal investigations between vonoprazan and PPIs treatment. vonoprazan, which has better tolerability and safety, may significantly decrease diarrhea and loose stools in acid-related patients compared with PPIs. Our meta-analysis led to safer strategies for treating acid-related diseases. More high-quality studies with larger sample sizes are needed to further elucidate its efficacy and safety.

Щодо ефективності застосування пантопразолу при кислотозалежних захворюваннях у дітей

У статті розглядається місце пантопразолу в терапії кислотозалежних захворювань у дітей. Підкреслено, що в практичній гастроентерології окрім оригінальних інгібіторів протонної помпи (брендів) використовують також препарати-генерики, які, на відміну від оригінальних інгібіторів протонної помпи, є набагато доступнішими для більшості пацієнтів. Метою висвітленої в статті роботи було вивчення клінічної ефективності генеричного препарату пантопразолу (Золопент) при лікуванні кислотозалежних захворювань у дітей. Золопент проявив себе як високоефективний антисекреторний препарат для лікування кислотозалежних захворювань (хронічного гастродуоденіту, виразкової хвороби, гастроезофагеальної рефлюксної хвороби) у дітей, що добре переноситься дітьми й не викликає побічних реакцій.

Количественный анализ скорости антисекреторного эффекта комбинированного ингибитора протонной помпы Эзолонг

Актуальность. Лечение кислотозависимых заболеваний является актуальной проблемой современной гастроэнтерологии, что обусловлено широким распространением этой группы нозологий в структуре заболеваний желудочно-кишечного тракта. Ведущее место в лечении этих заболеваний занимают ингибиторы протонной помпы. Критериями их выбора является время начала действия, выраженность и длительность кислотосупрессии, устойчивость эффекта в течение суток, наличие различных дозировок препарата. Именно поэтому в последние годы предпочтение отдается комбинированным препаратам. Сейчас в Украине используется новое поколение комбинированных средств, представителем которых является Эзолонг. Это лекарственное средство, которое кроме высококачественного эзомепразола (в дозировке 20 или 40 мг) содержит еще и антацид в виде натрия гидрокарбоната (1080 мг). Именно это сочетание делает данный препарат уникальным. Цель: определить скорость воздействия комбинированного препарата Эзолонг (эзомепразол 40 мг + натрия гидрокарбонат 1080 мг) на состояние желудочной кислотопродукции и степень ее ингибирования при использовании разовой дозы препарата. Материалы и методы. Под наблюдение было взято 20 пациентов с различными формами хронического гастродуоденита. Уровень кислотопродукции оценивался с помощью внутрижелудочного рН-мониторинга с применением ацидографа АГ-1. Далее больные получали разовую дозу Эзолонга (40 мг) и находились под наблюдением в течение 3 часов. Результаты. Проанализировав скорость антисекреторного действия разовой дозы Эзолонга, выявили, что у большинства больных (95 %) прием данного препарата приводит к повышению уровня интрагастрального рН до гипоацидных цифр (от 3,0 до 7,8), у некоторых пациентов отмечаются даже анацидные значения рН. Доказано, что для Эзолонга характерно быстрое начало действия (в среднем 6 минут) и достоверное повышение рН до выраженной гипо­ацидности. Выводы. Прием Эзолонга обеспечивает активное, мощное и длительное подавление желудочной кислотопродукции, является эффективным и безопасным при лечении кислотозависимых заболеваний.

Pantoprazole pretreatment elevates sensitivity to vincristine in drug-resistant oral epidermoid carcinoma in vitro and in vivo

Resistance to chemotherapeutic agents is a major cause of treatment failure in patients with oral cancer. Proton pump inhibitors (PPIs), essentially H+-K+-ATPase inhibitors which are currently used in the treatment of acid related diseases, have demonstrated promising antitumor and chemo-sensitizing efficacy. The main purpose of the present study was to investigate whether pantoprazole (PPZ, one of PPIs) could increase the sensitivity of chemoresistant oral epidermoid carcinoma cells (KB/V) to vincristine (VCR) and elucidate the underlying action mechanism. Results showed that combination treatment of PPZ and VCR synergistically inhibited the proliferation of KB/V cells in vitro and in vivo. Furthermore, administration of PPZ and VCR not only induce apoptosis and G2/M phase arrest in KB/V cells but also suppress the migration and invasion of KB/V cells. The mechanism underlying synergistic anti-tumor effect of PPZ and VCR was related to the inhibition of the function and expression of P-glycoprotein (P-gp) and the down-regulation of EGFR/MAPK and PI3K/Akt/mTOR signaling pathways in KB/V cells. Additionally, we observed that PPZ treatment induced an increase in lysosomal pH and inhibited the activity of lysosomal enzyme acid phosphatase in KB/V cells, which could functionally reduce the sequestration of VCR in lysosomes and sensitized KB/V cells to VCR. In conclusion, our study demonstrated that PPZ could be included in new combined therapy of human oral cancer (especially on VCR-resistant therapy) together with VCR.

Adherence of patients to medical recommendations (compliance) as an important factor in increasing the effectiveness of treatment (by example of acid-dependent diseases)

List of medical terms has been recently supplemented with relatively new notions of compliance (adherence), which means “consent, compliance with your wishes” in English. They are used to denote the patient’s strict adherence to medical recommendations, especially with regard to pharmacotherapy (use of the drug at the recommended dose with the necessary frequency and duration), correction of lifestyle, rationalization of dietary habits, getting rid of bad habits. High compliance is very important in the treatment of acid-related diseases: organizing a lifestyle, following advice on dietary restrictions and habits, avoiding stressful situations and physical exertion significantly affect the effectiveness of therapeutic measures in gastroesophageal reflux disease, gastric ulcer and duodenal ulcer, non-atrophic gastritis, Zollinger-Ellison syndrome, chronic gastritis induced by nonsteroidal anti-inflammatory drugs. Optimization of compliance (adherence), control over the implementation of prescriptions, elimination of factors that impede the realization of medical recommendations will improve the effectiveness of treatment of acid-related diseases. The key to successful treatment of any pathology is an active involvement of a patient in the treatment process.

Does the use of proton pump inhibitors increase the risk of hypomagnesemia: An updated systematic review and meta-analysis.

Background:Proton pump inhibitors (PPIs) are commonly used in the treatment of acid-related diseases; however, the association between the use of PPIs and potential risk of hypomagnesemia is controversial.Methods:In the present study, databases including PubMed, EMBASE, MEDLINE, PsycINFO, CINAHL, the Cochrane Library, and 4 Chinese databases were searched since the inception until April 2018. Previous observational studies on the incidence of hypomagnesemia in individuals exposed to PPIs were included.Results:This systematic review involved 15 studies including 129,347 participants, and the sample size varied from 52 to 95,205. Meta-analysis of 14 studies indicated that the use of PPIs increased the risk of hypomagnesemia [RR, 1.44, 95% CI, 1.13–1.76; I2, 85.2%]. Subgroup analysis revealed that the use of PPI was not associated with the incidence of hypomagnesemia in outpatients [RR, 1.49; 95% CI, 0.83–2.14; I2, 41.4%] and hospitalized patients [RR, 1.05; 95% CI, 0.81–1.29; I2, 62.1%], respectively. The use of PPIs was not related to the risk of hypomagnesemia based on the cut-off values of 1.8 mg/dL [RR, 1.73; 95% CI, 0.87–2.58; I2, 65.2%], 1.7 mg/dL [RR, 1.48; 95% CI, 0.90–2.06; I2, 87.6%], and 1.6 mg/dL [RR, 0.98; 95% CI, 0.69–1.27; I2, 67.9%].Conclusion:The association between the exposure to PPI and the incidence of hypomagnesemia remained unclear. Due to the remarkable heterogeneity in previous studies, a definitive conclusion could not be drawn. Further research should be conducted to investigate the relationship between the use of individual PPI and potential risk of hypomagnesemia, and a dose-response analysis may be required.

Vonoprazan: A Novel and Potent Alternative in theTreatment of Acid-Related Diseases.

Although proton pump inhibitors (PPIs) have been used widely, acid-related diseases are still associated with a huge burden on the health care system. Recently, the efficacy and safety of a new acid suppressant named vonoprazan in the treatment of acid-related diseases have been evaluated by a series of studies. As a novel potassium-competitive acid blocker, vonoprazan may provide reversible acid suppression by preventing K+ from binding to gastric H+/K+-ATPase. It has been clinically used for the short-term treatment of gastroesophageal reflux disease (GERD), peptic ulcer disease and Helicobacter pylori (H. pylori) infection in Japan. The healing rate of GERD and gastric ulcers by vonoprazan is more than 95 and 90%, respectively; also, it is effective in curing PPI-resistant GERD. It increases H. pylori eradication rate to more than 88% as part of both first-line and second-line therapy. It is also effective in the eradication of clarithromycin-resistant H. pylori strains. All of these short-term studies show vonoprazan is safe and well-tolerated. As a safe and effective acid inhibitor, vonoprazan might be a novel alternative in the treatment of acid-related diseases.

Short-term efficacy of potassium-competitive acid blocker following gastric endoscopic submucosal dissection: a propensity score analysis

Background: Endoscopic submucosal dissection (ESD) is a promising method for the resection of superficial gastric neoplasms. Vonoprazan is a novel potassium-competitive acid blocker (P-CAB) that is currently considered as a potential alternative to proton pump inhibitors (PPIs) for the treatment of acid-related diseases. However, the utility of vonoprazan in ESD-related ulcers is unclear. Therefore, we compared the short-term efficacies of vonoprazan and the PPI lansoprazole in ESD-related ulcer healing during the first two weeks following intervention.Methods: This study included 115 superficial gastric neoplasms that were treated by ESD at Hiraka General Hospital between April 2015 and January 2017. Patients treated with P-CAB (20 mg vonoprazan, n = 62) or PPI (30 mg lansoprazole, n = 53) were compared using propensity-score matching analysis. Primary outcome was rate of ulcer reduction at two weeks after ESD. Secondary outcomes were coverage ratio of ulcer base by granulation tissue and incidence of postoperative bleeding.Results: The rate of ulcer reduction was significantly higher (median [range], 80.6% [67.6%–94.5%] vs. 62.7% [33.4%–85.2%]; p < .0001) and coverage ratio of the ulcer base by granulation tissue was significantly accelerated (median [range], 84.1% [67.7%–95.3%] vs. 61.9% [12.1%–90.1%]; P < 0.0001) in the P-CAB group compared with the PPI group. Postoperative bleeding was not observed in either group.Conclusions: P-CAB achieved rapid artificial ulcer healing with promotion of granulation tissue formation. However, conventional PPI with initial intravenous infusion might be sufficient for prevention of postoperative bleeding following gastric ESD.

Diagnosis and treatment of acid-related diseases in patients with diabetes mellitus

The article describes the features of the diagnosis and treatment of acid-related diseases, such as peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD) in patients with diabetes mellitus (DM). The diagnosis of acid-related diseases in patients with DM should consider the data of endoscopy and morphological study of biopsie, H. pylori infection, diabetes compensation, non-alcoholic fatty liver disease, a possible associated pathology of the thyroid gland, consumption of gastrotoxic drugs. Treatment of PUD and GERD in patients with diabetes is based both on the elimination of their major etiological factors, and the elimination of symptoms of the disease and improving the quality of life of these patients, which is achieved by means of adequate glycemic control, lifestyle modification and nutritional and pharmacological correction. During the acid-supressive therapy pantoprazole should be preferred.

Vonoprazan fumarate for the management of acid-related diseases

ABSTRACTIntroduction: Proton pump inhibitors (PPIs) display a number of limitations and unmet clinical needs that have prompted the development of novel drugs to improve the outcomes of acid-related diseases, including the eradication of H. pylori. In this context, a new synthesized potassium-competitive acid blocker (P-CAB), vonoprazan, showed higher suppression of gastric acid secretion.Areas covered: This review discusses the current knowledge regarding the efficacy of vonoprazan in the treatment of acid-related diseases, with a particular focus on its use in Helicobacter pylori eradication.Expert opinion: Vonoprazan showed some advantages over PPIs in terms of the pharmacokinetic and pharmacodynamic profile: fast onset of action without requiring acid activation and specific administration timing, more potent and prolonged inhibition of acid secretion, including a better nighttime acid control, and a less antisecretory variability. Recent evidence suggests that vonoprazan can be preferred to PPIs as maintenance therapy for reflux esophagitis and eradication of Helicobacter pylori owing to its stronger antisecretory effect. Moreover, vonoprazan displays favorable safety and tolerability profiles, even though long-term studies on the effects of vonoprazan are required.

Clinical Implications of Emerging Data on the Safety of Proton Pump Inhibitors.

Proton pump inhibitors (PPI) are among the safest class of drugs used by all care providers, including gastroenterologists. They are the mainstay in treatment of acid-related disease, in particular, gastroesophageal reflux disease. Without them, many patients would experience a major decrement in their quality of life. However, no drug is without side effects or adverse events. In the past decade, numerous reports, principally case control studies and meta-analyses, have raised questions about important adverse events related to the use of PPIs. This has affected not only physicians' prescribing habits but patients' concerns about using these medications, particularly long term. Several FDA warnings are listed including those related to long bone fractures, interaction with clopidogrel, enteric infections, and hypomagnesaemia. More recently, concerns regarding PPIs and cardiovascular events have resurfaced as have issues related to kidney disease and dementia. The methodology of these studies allows us to find an association with these events but does not provide us with sufficient evidence to determine causality. In general, the findings of the available studies do not fit with our clinical experience nor is the magnitude of the association sufficient to result in a major change in our practice. Nevertheless, the recent literature has resulted in our careful reevaluation of PPI use across both FDA indications and in general. This article will critically review the literature regarding potential PPI adverse events and attempt to place them in perspective for the practicing physician.

EFFECTIVENESS OF RABEPRAZOLE FOR THE TREATMENT OF ACID-RELATED DISEASES

The analysis of modern data about the effectiveness of rabeprazole in the treatment of acid-related diseases is performed. The European Consensus Maastricht 5 recommends a preferred use of rabeprazole in the schemes of eradication of Helicobacter pylori. Clinical studies confirmed the high efficiency of rabeprazole for the treatment of GERD, and prevention of NSAID-induced gastropathy. Modern and effective generic of rabeprazole is Rabiet.

Potassium-competitive acid blockers: Advanced therapeutic option for acid-related diseases.

Acid-related diseases (ARDs), such as peptic ulcers and gastroesophageal reflux disease, represent a major health-care concern. Some major milestones in our understanding of gastric acid secretion and ARD treatment reached during the last 50years include 1) discovery of histamine H2-receptors and development of H2-receptor antagonists, 2) identification of H+,K+-ATPase as the parietal cell proton pump and development of proton pump inhibitors (PPIs), and 3) identification of Helicobacter pylori (H. pylori) as the major cause of peptic ulcers and development of effective eradication regimens. Although PPI treatments have been effective and successful, there are limitations to their efficacy and usage, i.e. short half-life, insufficient acid suppression, slow onset of action, and large variation in efficacy among patients due to CYP2C19 metabolism. Potassium-competitive acid blockers (P-CABs) inhibit H+,K+-ATPase in a reversible and K+-competitive manner, and exhibit almost complete inhibition of gastric acid secretion from the first dose. Many pharmaceutical companies have tried to develop P-CABs, but most of their clinical development has been discontinued due to safety concerns or a similar efficacy to PPIs. Revaprazan was developed in Korea and was the first P-CAB approved for sale. Vonoprazan, approved in 2014 in Japan, has a completely different chemical structure and higher pKa value compared to other P-CABs, and exhibits rapid onset of action and prolonged control of intragastric acidity. Vonoprazan is an effective treatment for ARDs that is especially effective in healing reflux esophagitis and for H. pylori eradication. P-CABs, such as vonoprazan, promise to further improve the management of ARDs.

Synthesis and Characterization of Triazole-Linked Bistetrahydrobenzofuran Derivatives as Anti-Ulcer Agents

A pair of triazole-linked bistetrahydrobenzofuran derivatives were prepared in high yields through Cu (II)-catalyzed click reaction under mild conditions. All of the intermediates and target compounds were characterized by NMR, IR, ESI-MS and elemental analysis. Thein vitroH+/K+-ATPase inhibitory effect for the target compounds were also evaluated by MTT methods, and the (E)-isomer of the bistetrahydrobenzofurans exhibited the better H+/K+-ATPase inhibitory activities than the commercial omeprazole with the IC50of 37.90 μM. The bioactive compound might be potentially used as anti-ulcer agents in the treatment of acid-related diseases.

Synthesis and &lt;i&gt;In Vitro&lt;/i&gt; Anti-Ulcer Effect of Bisabolangelone Oxime Ether Derivatives

Four bisabolangelone oxime ether derivatives were synthesized and separated as potential anti-ulcer agents. Their structures were characterized by NMR, IR and ESI-MS. Preliminarily H+/K+-ATPase activity evaluation indicated that all the target oxime ethers exhibited the better H+/K+-ATPase inhibitory activities than the commercial omeprazole with the IC50of 17~46 μM. These compounds might be used as potential anti-ulcer agents in the treatment of acid-related diseases.

Synthesis and &lt;i&gt;In Vitro&lt;/i&gt; Anti-Ulcer Effect of Triazolo-Methyl Tetrahydrobenzofuran Oxime Ether Derivatives

The triazolo-methyl tetrahydrobenzofuran oxime ether isomers were prepared through Cu (II)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction in a high-yielding three-step reaction sequence under mild conditions. All of the intermediates and target compounds were characterized by NMR, IR, ESI-MS and elemental analysis. The in vitro anti-ulcer activity evaluation indicated the (Z)-oxime isomer of triazolo-methyl tetrahydrobenzofuran oxime ether exhibited most potent H+/K+-ATPase inhibitory effect with the IC50˰̵̱̼͆ͅ˰̶̿˰̅˾́̅˰μ̝˾ These compounds could be potentially used as anti-ulcer agents for the treatment of acid related diseases.