
==== Front
Curr Res Pharmacol Drug Discov
Curr Res Pharmacol Drug Discov
Current Research in Pharmacology and Drug Discovery
2590-2571
Elsevier

S2590-2571(24)00025-7
10.1016/j.crphar.2024.100198
100198
Article
GERD: Latest update on acid-suppressant drugs
AL-Frejat Zyad zyadfrejat@gmail.com
ab
Martini Nafiza nafiza0968@gmail.com
bd
Esper Alia Aes7121@gmail.com
ad
Al-Frejat Diana dyanaalfryjat123@gmail.com
be
Younes Samer Yonessamer22@gmail.com
cd⁎
Hanna Majd Majd.Hanna@Stemosis.org
bd
a Faculty of Medicine, Al Baath University, Homs, Syria
b Faculty of Medicine, Damascus University, Damascus, Syria
c Faculty of Pharmacy, Tartous University, Tartous, Syria
d Stemosis for Scientific Research, Damascus, Syria
e Faculty of Dentistry, Syrian Private University, Damascus, Syria
⁎ Corresponding author. Department of Pharmacy, Tartous University, Syria. Yonessamer22@gmail.com
23 8 2024
2024
23 8 2024
7 10019818 5 2024
7 8 2024
19 8 2024
© 2024 The Authors
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
GERD is a very familiar diagnosis among health care providers due to its massive spread, and its symptoms can affect the quality of life for a respectable slice of its patients. Therefore, what can only be described as a logical consequence, a pursuit of a treatment that can both relieve symptoms and have minimal side effects is still ongoing to cover the large demographic affected by GERD. In the following review, analysis will be made of GERD, including possible regulatory activity, of certain drugs to the already discussed pathways involved in GERD patients.

Keywords

GERD
Antacids
PPI
H2-receptor antagonists
P-CABs
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pmc1 Introduction

GERD is considered a common disease with the typical symptom of heartburn, which affects more than 40% of the population among U.S. residents (Eisen, 2001). This spread of the disease, in addition to its well-documented effect on patients' quality of life (Eslick and Talley, 2009), is the reason behind substantial efforts both financially and scientifically in the pursuit of relief and reduced symptoms (Scarpignato et al., 2020), supported by speculations that GERD is even more common than previously thought due to the different definitions of heartburn among different communities and that GERD may present in an atypical way (e.g., Chronic cough, Sore throat, hoarseness.etc) (Malfertheiner and Hallerbäck, 2005).

Although proton pump inhibitors are very effective at treating GERD and relieving its symptoms (Klok et al., 2003), advancements have yet to stop after the FDA recently approved the use of the potassium competitive acid blocker vonoparzan, as it has been shown to be a more prominent and efficient root for treatment (St. Onge and Phillips, 2023).

Medical treatments for GERD include antacids, Histamine-h2 receptor antagonists, Proton Pump inhibitors, potassium-competitive acid blockers, and Prokinetics. Not to forget that lifestyle modifications should always be considered the first-line treatment and that surgical options are available (Kaltenbach et al., 2006).

2 Methods and materials

We conducted a review by searching the Google Scholar, PubMed, and Directory Open access Journal databases for relevant information using keywords such as GERD, pressure, hypertension, antihestamine, antiacids, PPI's, Potassium competitive acid blockers, Prokinetics, pain, blenching, vonoparzan, GERD symptoms, to identify primary comparative studies on treatment and management options for GERD. The quality and strength levels of the results were considered and when available meta-analyses and systematic reviews, large epidemiological studies and randomized control trials represented the main source of data.

3 Results

3.1 Lifestyle modifications

Lifestyle modifications are considered the first-line treatment for GERD (Kaltenbach et al., 2006); however, there has been some controversy regarding the efficacy of these modifications and their role in symptom relief. Studies have advised that the Triggers of GERD (e.g., citrus, tomatoes, highly spiced foods, fatty foods, fried foods, and chocolate) be identified and avoided in patients (Heidarzadeh-Esfahani et al., 2021; Zhang et al., 2021). In regards to Tobacco smoking, the only group that demonstrated an improvement in severe GERS upon cessation was healthy individuals with a normal BMI and who used antireflux medication at least weekly (Ness-Jensen et al., 2014).

it's worth noting that GERD symptoms can be aggravated by consuming nonvegetarian food and alcohol, as can the consumption of carbonated beverages (Seremet et al., 2015). Greasy food is often associated with nonerosive reflux disease, while high fat intake has been linked to the development of Barret's esophagus (Chirila et al., 2016). Conversely, the Mediterranean diet decreases the risk of GERD (Mone et al., 2016).

Improvements in GERD and esophagitis were noted in IBS patients when a strict gluten-free diet was applied (GOMES and DANTAS, 2014).

Stress plays a major role in triggering GERD; therefore, stress management strategies are recommended to help reduce symptoms (Yuan et al., 2019).

Postprandial reflux symptoms are managed by steering away from prostration after meals, consuming food within 3 h before sleeping, and overeating. The lateral decubitus position during sleep is recommended (Kaltenbach et al., 2006; Yuan et al., 2019; Piesman et al., 2007; Albarqouni et al., 2021; Schuitenmaker et al., 2022; Gerson and Fass, 2009; Ness-Jensen et al., 2016).

Exercising and losing weight have a significant impact on reducing symptoms of GERD, especially among overweight and obese individuals (de Bortoli et al., 2016; Nilsson et al., 2004).

3.2 Antacid

Accounting for a major class of OTC drugs sold globally, antacid drugs are worth billions of dollars spent by GERD patients in search of relief of heartburn, hyperacidity, and indigestion, as well as other symptoms related to this condition (Mbatchou et al., 2017; Mandel and Brodie, 2000).

Antacids work by counterpoising excess HCL in the stomach and inhibiting pepsin (Peterson et al., 1977). They showed to not just help with symptom relief but also to boost the effect of other acid suppression drugs, such as PPIs (Higuera-de-la-Tijera, 2018). Regarding their composition, salts of magnesium, aluminum, calcium, sodium, carbon, or bismuth are the main components of antacid products, they come in powders, tablets, or liquid forms. However, most antacids are composed of a mixture of two salts (Brown et al., 2012; Aggarwal et al., 2017). The most common compositions of antacids include the following:

Calcium carbonate: calcium carbonate abates GERD symptoms via two mechanisms. After reacting with gastric HCL, the formed calcium ions induce peristalsis in the esophagus, thus moving acid back to the stomach, while carbonate anions act as a buffer for excess H+ protons from HCL, hence decreasing H+ concentrations and raising ph. calcium carbonate can cause constipation and flatulence, systemic alkalosis and hypercalcemia on long-term use, and milk-alkali syndrome when it is overdosed (Mejia and Kraft, 2009).

Sodium bicarbonate: Sodium bicarbonate is often combined with citric acid, and the combination is fast to react with water to produce a sodium citrate solution, which releases carbon dioxide. Sodium citrate can increase stomach pH rapidly by neutralizing acid. Mild gas or bloating is expected due to stomach irritation (Carr et al., 2011).

Magnesium salts: Magnesium hydroxide Magnesium carbonate Magnesium trisilicate. The main side effects of magnesium salts are dose-related diarrhea, flushing, hypotension, vasodilation, and hypermagnesemia (Green et al., 1975).

Aluminum salts: Aluminum hydroxide, aluminum carbonate, and aluminum phosphate can cause hypomagnesemia, hypophosphatemia, constipation, and anemia.

3.3 H2 blockers

Since the FDA approved the use of the imidazole derivative cimetidine (the least potent H2 blocker, which requires a dose of approximately 800 mg (Somogyi and Gugler, 1983)) for the treatment of GERD in 1977, H2 blockers became one of the most common treatment regimens for GERD, followed by ranitidine, a basic substituted furan, in 1983, which has now raised great concerns regarding its safety, as it has been linked to the carcinogenic effect of NDMA (McGwin, 2020) and was withdrawn from markets in the U.S. (Aschenbrenner, 2020). In 1986, guinidinothiazole group member Famotidine, the most potent H2 blocker requiring a dosage of 40 mg (Schunack, 1987a), appeared. There was thought to be a correlation between famotidine and clinical improvement among COVID-19 patients (Freedberg et al., 2020), but further studies affirmed no link (Sethia et al., 2020). Finally, nizatidine was introduced in 1988 and has also been linked to excess NDMA exposure (Shaik et al., 2022). These drugs (excluding nizatidine) have the advantage of being available orally, intravenously, or intramuscularly (Schunack, 1987b). They can be prescribed or taken over the counter.

H2 receptors in parietal cells are the main targets of H2 blockers, which act as antagonists of histamine and block histamine receptors, consequently inhibiting histamine stimulation in parietal cells and acid secretion.

Although PPIs demonstrate a clear advantage in treating acid related esphoageal diseases, the use of H2RAS is continuedly used as an augmentation therapy for patients who have PPI resistant Acid disorders (Pandolfino et al., 2023).

H2 blockers are well tolerated (Lewis, 1991)and have a lower risk of causing bacterial overgrowth and infections than PPIs (Untersmayr, 2015). The main side effect of these drugs, headache, is their ability to cross the blood–brain barrier, and other side effects include drowsiness, fatigue, abdominal pain, constipation, and diarrhea (Pinto-Sanchez et al., 2017). It is worth noting that there are no absolute contraindications for H2 blockers.

3.4 PPI

PPIs have been the main treatment for acid disorders since the introduction of omeprazole in 1989. Six PPIs are currently available for use (omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole, and rabeprazole) (Robinson, 2005).

All PPIs are benzimidazole derivatives: heterocyclic organic molecules that include both a pyridine and benzimidazole moiety linked by a methylsulfinyl group (Orel et al., 2021; Savarino et al., 2021).

The use of tenatoprazole has undergone preliminary preclinical and clinical evaluation. With clinical use approval yet to come, this new form of PPI that has an adventitiously prolonged half-life can be superior to its benzimidazole relatives (Pati et al., 2020).

PPIs are membrane-permeable, acid-labile weak bases. With early activation and degradation by luminal gastric acid being the first problem to address in mind, a variety of delivery systems have been used to package these drugs, including enteric-coated tablets, gelatin capsules, or coated granules in powder form. packaging in combination with bicarbonate is also an option. Once clear of the stomach, PPIs are metabolized in the first parts of the small bowel. Lansoprazole, pantoprazole, and esomeprazole can be administered intravenously, which provides immediate acid suppression and is a natural fit for hospitalized patients for whom the oral route of administration is not appropriate (Sachs et al., 2006). Single-release PPIs have a short serum half-life (1–2 h), and considerable effort has been made to develop dual-release/or delayed-release formulations to counteract this shortcoming (Morelli et al., 2011; Vakily et al., 2009).

Once inside the body, proton pump inhibitors (PPIs) travel to activated gastric parietal cells, where they accumulate in acidic secretory canaliculi. When proton pump inhibitors (PPIs) enter the acidic environment of the stomach, they undergo a chemical reaction in which a chiral sulfoxide bond is cleaved due to the action of an acid catalyst. This process causes PPIs to become effective in reducing the production of acid in the stomach. - It is important to note that some PPIs, such as esomeprazole and dexlansoprazole, do not undergo this acid-catalyzed cleavage of the chiral sulfoxide bond. This process leads to the production of active sulfenic acid and/or sulfonamide compounds, which then bind covalently to cysteine residues on the H+/K + ATPase to prevent acid secretion. This inhibition can last for up to 36 h until new pumps can be synthesized. Although PPIs are generally thought to be equally effective in terms of clinical outcomes, their distinct pharmacologic properties may differ among individuals.

Unfortunately, up to 50% of patients taking PPIs for nonerosive GERD are dissatisfied with their treatment due to unresolved symptoms (Fass et al., 2005), and among patients taking PPIs twice per day, nearly 40% increase their dosage because of persistent nocturnal symptoms (Chey et al., 2010). This leads us to define the term.

“Nocturnal acid breakthrough” for the reactivation of gastric acid secretion overnight is a frequently encountered disadvantage for single-release PPI users receiving a single morning dose (Tutuian and Castell, 2004). Note that the escalation of dosing to twice daily is often performed in accordance with both the American Gastroenterology Association (Chen et al., 2023) and the American College of Gastroenterology (Katz et al., 2022) Practice Guidelines. Despite the frequency of this intervention, breakthrough symptoms are still observed among many patients (Chey et al., 2009). Pharmacologically, in healthy individuals, an intragastric pH below 4 is still present for 15% of the day despite a dosage of 40 mg esomeprazole given twice per day (Yuan and Hunt, 2008).

The prolonged-release PPI “rabeprazole-ER” is a 50 mg capsule containing 5 separate 10 mg tablets that are absorbed at intervals throughout the small intestine and colon. Compared with esomeprazole and conventional delayed-release rabeprazole, the ER of rabeprazole has been shown to be more effective at controlling nocturnal gastric acid secretion [48]. Imidazopyridines, such as tenatoprazole, possess a serum half-life of 7–8 h and may potentially offer an added advantage in clinical settings. These compounds have the potential to enhance efficacy and assist in overcoming certain limitations. The future implications of these findings could be significant in the field, warranting further investigation. (Sachs et al., 2006), Tenatoprazole showed a superior inhibitory effect on H+/K + ATPase and a substantially longer half-life of 7–8 h (which can increase to 14 h if taken in multiple doses) (Galmiche et al., 2005; Hunt et al., 2005; Thomson et al., 2006).

When comparing PPIs several studies have pointed out that esomeprazole is favorable over other PPIs when it comes to erosive esophagitis with a healing probability rate of 98% (Li et al., 2017).

However the nearest competitor is dexlansorpazole as it is seen as the best option for controlling nuctornal breakthrough acid symptoms (Dumra et al., 2023).

Some studies suggest that there might be a genetic component in overall patient response to PPI treatment relying on differences in CYP2C19 metabolism, ofcourse genetic testing is not clinically indicated in the course of GERD treatment, however rabeprazole is considered the best choice to tackle this obstacle as it does not depend on CYP2C19 for primary metabolism.

The side effects and complications of proton pump inhibitors (Fig. 1) are related to the long-term use of PPIs for Clostridium difficile, other enteric infections, and potentially community-acquired pneumonia according to retrospective observational studies (Eom et al., 2011); however, additional investigations are needed (Filion et al., 2014). In addition, suppressing acid release and elevating pH in the gastric lumen is one of the mechanisms underlying the disruption of the innate immune system. Therefore, susceptibility to maltitude of enteric infections is increased, including small intestinal bacterial growth (Lo and Chan, 2013; Bavishi and Dupont, 2011). PPIs can rarely cause hypomagnesemia, a condition where magnesium levels drop significantly, leading to serious complications like tetany, seizures, muscle weakness, delirium, and cardiac arrhythmias (Eom et al., 2011; Mackay and Bladon, 2010; Melloni et al., 2015; McDonald et al., 2015; Cheungpasitporn et al., 2015). Discontinuing PPIs after prolonged use can lead to higher acid levels than before treatment, a phenomenon known as rebound acid secretion (Ahmed, 2023). This is due to increased gastrin levels stimulating acid production. However, there are conflicting data on the association between PPI use and osteoporosis, bone fractures, dementia, kidney disease, and heart disease. Most evidence comes from retrospective studies with potential confounding factors, and prospective studies have not consistently supported these links. Concerns about malignancy due to prolonged gastrin elevation have not been substantiated in human studies, though fundic gland polyps may increase with long-term PPI use without a link to malignancy (Ahmed, 2023).Fig. 1 Current status of different p-CABS drugs.

Fig. 1

3.5 Potassium competitive acid blockers

Developed first in the 1980s, P-CAPS showed rapid effective reversible inhibition of the proton pump (H+/K + ATPase). However, most P-CAPs, such as the imidazopyridine compound SCH28080 from the Schering-Plough Corporation and linaparzan (Sugano, 2018), which showed no superiority over esomeprazole in the management of heartburn, were not available on the market because of its correlation with hepatotoxicity, so it was discontinued. Currently, there are three P-CAPSs on the market: Revaparzan, a pyrimidine derivative; Vonoparzan, a pyrrole derivative; and Tegoprazan, a benzimidazole (Fig. 2).Fig. 2 illustrates the prevalent complications and adverse reactions associated with prolonged PPI usage, along with the fundamental mechanisms responsible for each complication.

Fig. 2

Increasing worries and concerns about the safety profile of PPIs and the associated side effects of prolonged use have led to increased attention being given to P-CAPS as a potential dethroner of PPIs in the field of acid suppression (Moore and Vaezi, 2010; Rettura et al., 2021).

Potassium plays an essential role in the activation of the H+/K + ATPase in the apical membrane of parietal cells because it is required for its function. While resting the proton pump is confined to tubulovesicular regions of a parietal cell with low K+ concentrations and membranes that are impermeable to K+ and therefore incapable of activating and transporting H+ ions, when the parietal cell is stimulated, the tubulovesicular components merge with the cell apical membrane. After being exposed to K + -containing luminal fluid, the H+/K + -ATPase enzyme can begin to exchange H+ for K+ (Engevik et al., 2020; DuBose and Codina, 1996; Sakai et al., 2016).

Although there is a variety of classes of P-CAPS (imidazopyridine derivatives [BY841], imidazo-naphthyridine derivatives [soraprazan], imidazo-thienopyridines [SPI-447], and quinolone derivatives [SK&F96067]) (Tsukimi et al., 2000; Wurst and Hartmann, 1996; Simon et al., 2007). However, the mechanism of action remains similar. The characteristics of P-CAPS being lipophilic weak bases with limited pH stability gives them the ability to accumulate in acidic environments, such as those found in the canaliculi of parietal cells, there P-CAPS can bind ionically to the H+/K + ATPase and prevent further activation by K+.

Compared with conventional PPIs, which require 3–5 days to achieve maximal steady inhibition of acid secretion, P-CAPS are effectively absorbed and quickly accumulate in parietal cells (Andersson and Carlsson, 2005; Williams et al., 1998). For example, a single dose of Vonoparzan (20 mg) can increase the intragastric pH to nearly 7 in 4 h (Jenkins et al., 2015). Furthermore, vonoparzan has superior effects on nocturnal GERD symptoms compared with PPIs, as the mean nighttime pH above 4 after the administration of 20 mg vonoparzan on day 1 was greater than that after the administration of 20 mg esomeprazole or 10 mg rabeprazole (Oshima and Miwa, 2018).

The superiority of vonoprazan over conventional PPIs has extended to H.pylori treatment regimens as seen in (Chey et al., 2022) also it was found that vonprazan can even reduce treatment duration compared to PPI (1 week vs 2 weeks) (Ang et al., 2022).

That stated, the comparison between P-CABS and PPIs needs more investigation as most studies are focused in Asiatic populations, the superiority of PCABs over ppi is documented in westren studies regarding H.pylori eradication regimns, and severe esophagitis (Cheng et al., 2021), other acid related diseases require more research among western communities.(Table 1)Table 1 Investigations in the efficacy and safety of PCABs vs PPIs in gastric acid related diseases.

Table 1Gastric acid related disease	Study conductor	Country	Treatment used	Results	
Erosive esophagitis	Lee et al. (2019)
Lee et al. (2019)	South korea	Tegoprazan (100 mg)	Both doses of tegoprazan were non-inferior to esomeprazole 40 mg in treating EE	
Tegoprazan (50 mg)	
Esomeprazole (40 mg)	
Xiao et al. (2020)
Xiao et al. (2020)	56 centers in China, South Korea, Taiwan, and Malaysia	Vonoprazan (20 mg)	Vonoprazan is non-inferior in terms of EE healing when compared to Lansoprazole	
Lansoprazole (30 mg)	
Gastric ulcer	Cho et al. (2020)
Cho et al. (2020)	South Korea	Tegoprazan (100 mg)	Both doses of Tegoprazan used were non-inferior to lansoprazole in the treatment of Gastric ulcers	
Tegoprazan (50 mg)	
Lansoprazole (30 mg)	
Miwa et al. (2017)
Miwa et al. (2017)	Japan	Vonprazan (20 mg)
Lansoprazole (30 mg)	Vonoprazan is non-inferior to lansoprazole in treating both gastric and duodenal ulcers	
GERD	NCT02743949	33 centers in Belgium, Bulgaria, Czech Republic, Estonia, Poland, and the UK	Vonprazan (40 mg)	No significant difference between both vonoprazan doses and esomeprazole in terms of 24-h heartburn free periods and >1 sustained resolution of heartburn	
Vonprazan (20 mg)	
Esomeprazole (40 mg)	

The safety profile of short- and moderate-term use of P-Cabs is remarkable, and shows clear superiority over PPis (Xiao et al., 2020; Mizuno et al., 2020; Akiyama et al., 2020; Ashida et al., 2016, 2018; Yamashita et al., 2017). However, long-term usage may be associated with hypergastronemia (Uemura et al., 2018) and intestinal microbiome changes (Cochet and Peri, 2017; Marcus et al., 2012).

3.6 Prokinetics

Prokinetics are not considered acid-suppressant drugs. They work differently from acid-suppressing medications like proton pump inhibitors (PPIs) or H2 blockers. They are medications that stimulate contractions and motility in the gastrointestinal (GI) tract through some mechanism such as increasing lower esophageal sphincter pressure, enhancing esophageal peristalsis, accelerating gastric emptying, and Promoting overall GI motility.

While prokinetics may be used in treating certain gastrointestinal disorders, including some cases of GERD, they are not first-line treatments but sometimes used in combination with PPIs for certain patients. However, their use is limited due to potential side effects and varying efficacy. Some examples of prokinetic agents include.

3.6.1 Acotiamide

Acotiamide works on enhancing gastric emptying (Kusunoki et al., 2012; Nakamura et al., 2017) although it is mainly a cholinesterase inhibitor, Acotiamide has been shown to improve acetylcholine release. When acotiamide was added to patients on either PPIs or p-CABs, there was no difference in overall treatment compared to the placebo group, and the major difference occurred in the field of symptom-specific response for regurgitation (Yamashita et al., 2019).

3.6.2 Bethanechol

Bethanechol is a parasympathomimetic choline carbamate that selectively stimulates muscarinic receptors and has no effect on nicotinic receptors, urinary retention, postpartum urinary retention, or overflow incontinence caused by neurogenic atony of the bladder. The use of bethanechol in the treatment of GERD has been controversial, as although significant improvement was found in patients on bethanechol in a study by (Thanik et al., 1980), later studies by (Saco et al., 1982) showed no important relief, and not using bethanechol remains the preferred option (Bor et al., 2024).

3.6.3 Domperidone

Domperidone works as a peripheral D-2 receptor antagonist, based on a meta-analysis (Maddern et al., 1986), a combination of domperidone and PPI was shown to significantly reduce GERD and its symptoms (Zamani et al., 2022).

3.6.4 Itopride

Mainly in Asia, this acetylcholine esterase inhibitor and D-2 receptor antagonist is used for dyspepsia, demonstrated in GERD symptoms and a reduction in its recurrence when added to PPIs (Ezzat et al., 2011).

3.6.5 Metoclopramide

Metoclopramide works as a dopamine D2 and muscarine receptor blocker in the gastric pathway, three studies affirmed the positive effect of metoclopramide either as a sole treatment for heartburn (McCallum et al., 1977) or as a helpful aid to the H2 blocker cimetidine (Bright-Asare and El-Bassoussi, 1980; Lieberman and Keeffe, 1986).

3.6.6 Mosapride

Several studies have shown that a selective serotonin receptor agonist can provide minimal help as an adjuvant therapy to PPIs (Hsu et al., 2010; Cho et al., 2013).

3.6.7 Tegaserod

An aminoguanidine indole, which showed prokinetic potential in animals first in 1995 (Camilleri and Atieh, 2021), reached the market in 2002 as a possible treatment of choice for irritable bowel syndrome, but then it was removed by the FDA in 2007 due to concerns regarding its cardiovascular safety, which did not hold in place, as it was reapproved in 2019 before it was finally removed from the market by the manufacturer in 2022. Mainly two studies searched On the topic of tegaserod as a possible choice for GERD treatment, (Kahrilas et al., 2000) showed a significant impact of using tegaserod on reflux events compared to placebo, however, (Tutuian et al., 2006) reported no difference (2 days of therapy).

4 Conclusion

Although there seems to be a period in which every newly developed drug, such as H2 blockers and PPIs, has been used as the main treatment for GERD, p-CABS treatment is still needed. However, the downside of these drugs is very similar due to their shared function of acid suppression; other drugs that work to protect the mucosal layer of the GI tract are available but are less effective and can be used as adjunct therapies with PPIs or p-CAPS (Nishizawa et al., 2015). Surgical intervention should always be considered in the occurrence of stumbling upon persistent unresponsive GERD due to the risk of dangerous yet rare complications, such as Barrett's esophagus and esophageal adenocarcinoma (Lee et al., 2024).

Author contribution form Author's contribution

ZAF is the first Author, contributed to conceptualization editing & reviewing, Investigation,Original draft. NM contributed to conceptualization, investigation, original draft, editing & reviewing. AE contributed to conceptualization, investigation, original draft, editing & reviewing. DAF contributed to conceptualization, investigation, original draft, editing & reviewing. SY is the corresponding author, contributed to investigation, original draft, editing, reviewing & bibliography. MH is the supervisor, contributed to editing and reviewing, validation, supervision, and resources.

All authors reviewed and accepted the paper.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work responsed in this paper.

Data availability

The authors are unable or have chosen not to specify which data has been used.
==== Refs
References

Aggarwal D. Patel S. Santoro A. Access options Gazz. Med. Ital. Arch. Sci. Med. 176 9 2017 486 487
Ahmed A. JO C. Proton Pump Inhibitors (PPI) 2023 StatPearls Publishing
Akiyama J. Hosaka H. Kuribayashi S. Moriyasu S. Hisada Y. Okubo H. Efficacy of vonoprazan, a novel potassium-competitive acid blocker, in patients with proton pump inhibitor-refractory acid reflux Digestion 101 2 2020 174 183 30897577
Albarqouni L. Moynihan R. Clark J. Scott A.M. Duggan A. Del Mar C. Head of bed elevation to relieve gastroesophageal reflux symptoms: a systematic review BMC Fam. Pract. 22 2021 1 9 33388038
Andersson K. Carlsson E. Potassium-competitive acid blockade: a new therapeutic strategy in acid-related diseases Pharmacol. Ther. 108 3 2005 294 307 16000224
Ang D. Koo S.H. Chan Y.H. Tan T.Y. Soon G.H. Tan C.K. Clinical trial: seven-day vonoprazan- versus 14-day proton pump inhibitor-based triple therapy for first-line Helicobacter pylori eradication Aliment. Pharmacol. Ther. 56 3 2022 436 449 35665947
Aschenbrenner D.S. Ranitidine withdrawn from the market AJN The American Journal of Nursing 120 8 2020 23
Ashida K. Sakurai Y. Hori T. Kudou K. Nishimura A. Hiramatsu N. Randomised clinical trial: vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the healing of erosive oesophagitis Aliment. Pharmacol. Ther. 43 2 2016 240 251 26559637
Ashida K. Iwakiri K. Hiramatsu N. Sakurai Y. Hori T. Kudou K. Maintenance for healed erosive esophagitis: phase III comparison of vonoprazan with lansoprazole World J. Gastroenterol. 24 14 2018 1550 1561 29662293
Bavishi C. Dupont H.L. Systematic review: the use of proton pump inhibitors and increased susceptibility to enteric infection Aliment. Pharmacol. Ther. 34 11–12 2011 1269 1281 21999643
Bor S. Kalkan İ.H. Savarino E. Rao S. Tack J. Pasricha J. Prokinetics-safety and efficacy: the European society of neurogastroenterology and motility/the American neurogastroenterology and motility society expert review Neuro Gastroenterol. Motil. 36 5 2024 e14774
Bright-Asare P. El-Bassoussi M. Cimetidine, metoclopramide, or placebo in the treatment of symptomatic gastroesophageal reflux J. Clin. Gastroenterol. 2 2 1980 149 156 7002998
Brown M.J. Sharma P. Bennett P.N. Clinical Pharmacology 2012 Elsevier Health Sciences
Camilleri M. Atieh J. New developments in prokinetic therapy for gastric motility disorders Front. Pharmacol. 12 2021 711500
Carr A.J. Slater G.J. Gore C.J. Dawson B. Burke L.M. Effect of sodium bicarbonate on [HCO3−], pH, and gastrointestinal symptoms Int. J. Sport Nutr. Exerc. Metabol. 21 3 2011 189 194
Chen J.W. Vela M.F. Peterson K.A. Carlson D.A. AGA clinical Practice update on the diagnosis and management of extraesophageal gastroesophageal reflux disease: expert review Clin. Gastroenterol. Hepatol. 21 6 2023 1414 21.e3 37061897
Cheng Y. Liu J. Tan X. Dai Y. Xie C. Li X. Direct comparison of the efficacy and safety of vonoprazan versus proton-pump inhibitors for gastroesophageal reflux disease: a systematic review and meta-analysis Dig. Dis. Sci. 66 1 2021 19 28 32095968
Cheungpasitporn W. Thongprayoon C. Kittanamongkolchai W. Srivali N. Edmonds P.J. Ungprasert P. Proton pump inhibitors linked to hypomagnesemia: a systematic review and meta-analysis of observational studies Ren. Fail. 37 7 2015 1237 1241 26108134
Chey W.D. Mody R.R. Wu E.Q. Chen L. Kothari S. Persson B. Treatment patterns and symptom control in patients with GERD: US community-based survey Curr. Med. Res. Opin. 25 8 2009 1869 1878 19530980
Chey W.D. Mody R.R. Izat E. Patient and physician satisfaction with proton pump inhibitors (PPIs): are there opportunities for improvement? Dig. Dis. Sci. 55 12 2010 3415 3422 20397047
Chey W.D. Mégraud F. Laine L. López L.J. Hunt B.J. Howden C.W. Vonoprazan triple and dual therapy for Helicobacter pylori infection in the United States and europe: randomized clinical trial Gastroenterology 163 3 2022 608 619 35679950
Chirila I. Morariu I.D. Barboi O.B. Drug V.L. The role of diet in the overlap between gastroesophageal reflux disease and functional dyspepsia Turk. J. Gastroenterol. 27 1 2016 73 80 26728864
Cho Y.K. Choi M.G. Park E.Y. Lim C.H. Kim J.S. Park J.M. Effect of mosapride combined with esomeprazole improves esophageal peristaltic function in patients with gastroesophageal reflux disease: a study using high resolution manometry Dig. Dis. Sci. 58 4 2013 1035 1041 23053900
Cho Y.K. Choi M.G. Choi S.C. Lee K.M. Kim T.O. Park S.H. Randomised clinical trial: tegoprazan, a novel potassium-competitive acid blocker, or lansoprazole in the treatment of gastric ulcer Aliment. Pharmacol. Ther. 52 5 2020 789 797 32701188
Cochet F. Peri F. The role of carbohydrates in the lipopolysaccharide (LPS)/Toll-Like receptor 4 (TLR4) signalling Int. J. Mol. Sci. 18 11 2017
de Bortoli N. Guidi G. Martinucci I. Savarino E. Imam H. Bertani L. Voluntary and controlled weight loss can reduce symptoms and proton pump inhibitor use and dosage in patients with gastroesophageal reflux disease: a comparative study Dis. Esophagus 2016 197 204 25516110
DuBose T.D. Jr. Codina J.H. K-ATPase Curr. Opin. Nephrol. Hypertens. 5 5 1996 411 416 8937809
Dumra H. Sainani R. Pratap N. Singh B.P. Halder I. Shah J. Expert recommendations on optimizing the diagnosis and management of gastroesophageal reflux disease associated with comorbidities in the Indian population J Assoc Physicians India 71 8 2023 11 12
Eisen G. The epidemiology of gastroesophageal reflux disease: what we know and what we need to know Am. J. Gastroenterol. 96 8 2001 S16 S18 11510763
Engevik A.C. Kaji I. Goldenring J.R. The physiology of the gastric parietal cell Physiol. Rev. 100 2 2020 573 602 31670611
Eom C.S. Jeon C.Y. Lim J.W. Cho E.G. Park S.M. Lee K.S. Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis CMAJ (Can. Med. Assoc. J.) 183 3 2011 310 319 21173070
Eslick G.D. Talley N.J. Gastroesophageal reflux disease (GERD): risk factors, and impact on quality of life—a population-based study J. Clin. Gastroenterol. 43 2 2009 111 117 18838922
Ezzat W.F. Fawaz S.A. Fathey H. El Demerdash A. Virtue of adding prokinetics to proton pump inhibitors in the treatment of laryngopharyngeal reflux disease: prospective study J Otolaryngol Head Neck Surg 40 4 2011 350 356 21777555
Fass R. Shapiro M. Dekel R. Sewell J. Systematic review: proton-pump inhibitor failure in gastro-oesophageal reflux disease--where next? Aliment. Pharmacol. Ther. 22 2 2005 79 94
Filion K.B. Chateau D. Targownik L.E. Gershon A. Durand M. Tamim H. Proton pump inhibitors and the risk of hospitalisation for community-acquired pneumonia: replicated cohort studies with meta-analysis Gut 63 4 2014 552 558 23856153
Freedberg D.E. Conigliaro J. Wang T.C. Tracey K.J. Callahan M.V. Abrams J.A. Famotidine use is associated with improved clinical outcomes in hospitalized COVID-19 patients: a propensity score matched retrospective cohort study Gastroenterology 159 3 2020 1129 1131. e3 32446698
Galmiche J.P. Sacher-Huvelin S. Bruley des Varannes S. Vavasseur F. Taccoen A. Fiorentini P. A comparative study of the early effects of tenatoprazole 40 mg and esomeprazole 40 mg on intragastric pH in healthy volunteers Aliment. Pharmacol. Ther. 21 5 2005 575 582 15740541
Gerson L.B. Fass R. A systematic review of the definitions, prevalence, and response to treatment of nocturnal gastroesophageal reflux disease Clin. Gastroenterol. Hepatol. 7 4 2009 372 378 19111949
Gomes D.C. Dantas R.O. Ingestão de líquidos ácido e neutro em pacientes com doença do refluxo gastroesofágico Arq. Gastroenterol. 51 2014 217 220 25296082
Green Jr FW. Norton R.A. Kaplan M.M. Pharmacology and clinical use of antacids Am. J. Health Syst. Pharm. 32 4 1975 425 429
Heidarzadeh-Esfahani N. Soleimani D. Hajiahmadi S. Moradi S. Heidarzadeh N. Nachvak S.M. Dietary intake in relation to the risk of reflux disease: a systematic review Preventive Nutrition and Food Science 26 4 2021 367 35047433
Higuera-de-la-Tijera F. Efficacy of omeprazole/sodium bicarbonate treatment in gastroesophageal reflux disease: a systematic review Medwave 18 2 2018 e7179
Hsu Y.C. Yang T.H. Hsu W.L. Wu H.T. Cheng Y.C. Chiang M.F. Mosapride as an adjunct to lansoprazole for symptom relief of reflux oesophagitis Br. J. Clin. Pharmacol. 70 2 2010 171 179 20653670
Hunt R.H. Armstrong D. James C. Chowdhury S.K. Yuan Y. Fiorentini P. Effect on intragastric pH of a PPI with a prolonged plasma half-life: comparison between tenatoprazole and esomeprazole on the duration of acid suppression in healthy male volunteers Am. J. Gastroenterol. 100 9 2005 1949 1956 16128938
Jenkins H. Sakurai Y. Nishimura A. Okamoto H. Hibberd M. Jenkins R. Randomised clinical trial: safety, tolerability, pharmacokinetics and pharmacodynamics of repeated doses of TAK-438 (vonoprazan), a novel potassium-competitive acid blocker, in healthy male subjects Aliment. Pharmacol. Ther. 41 7 2015 636 648 25707624
Kahrilas P.J. Quigley E.M. Castell D.O. Spechler S.J. The effects of tegaserod (HTF 919) on oesophageal acid exposure in gastro-oesophageal reflux disease Aliment. Pharmacol. Ther. 14 11 2000 1503 1509 11069322
Kaltenbach T. Crockett S. Gerson L.B. Are lifestyle measures effective in patients with gastroesophageal reflux disease?: an evidence-based approach Arch. Intern. Med. 166 9 2006 965 971 16682569
Katz P.O. Dunbar K.B. Schnoll-Sussman F.H. Greer K.B. Yadlapati R. Spechler S.J. ACG clinical guideline for the diagnosis and management of gastroesophageal reflux disease Am. J. Gastroenterol. 117 1 2022 27 56 34807007
Klok R. Postma M. Van Hout B. Brouwers J. Meta‐analysis: comparing the efficacy of proton pump inhibitors in short‐term use Alimentary pharmacology & therapeutics 17 10 2003 1237 1245 12755837
Kusunoki H. Haruma K. Manabe N. Imamura H. Kamada T. Shiotani A. Therapeutic efficacy of acotiamide in patients with functional dyspepsia based on enhanced postprandial gastric accommodation and emptying: randomized controlled study evaluation by real-time ultrasonography Neuro Gastroenterol. Motil. 24 6 2012 540 5, e250-1
Lee K.J. Son B.K. Kim G.H. Jung H.K. Jung H.Y. Chung I.K. Randomised phase 3 trial: tegoprazan, a novel potassium-competitive acid blocker, vs. esomeprazole in patients with erosive oesophagitis Aliment. Pharmacol. Ther. 49 7 2019 864 872 30843245
Lee J. Lee I. Oh Y. Kim J.W. Kwon Y. Alromi A. Current status of anti-reflux surgery as a treatment for GERD Medicina (Kaunas) 60 3 2024
Lewis J.H. Safety profile of long-term H2-antagonist therapy Aliment. Pharmacol. Ther. 5 Suppl. 1 1991 49 57
Li M.J. Li Q. Sun M. Liu L.Q. Comparative effectiveness and acceptability of the FDA-licensed proton pump inhibitors for erosive esophagitis: a PRISMA-compliant network meta-analysis Medicine (Baltim.) 96 39 2017 e8120
Lieberman D.A. Keeffe E.B. Treatment of severe reflux esophagitis with cimetidine and metoclopramide Ann. Intern. Med. 104 1 1986 21 26 3940501
Lo W.K. Chan W.W. Proton pump inhibitor use and the risk of small intestinal bacterial overgrowth: a meta-analysis Clin. Gastroenterol. Hepatol. 11 5 2013 483 490 23270866
Mackay J.D. Bladon P.T. Hypomagnesaemia due to proton-pump inhibitor therapy: a clinical case series Qjm 103 6 2010 387 395 20378675
Maddern G.J. Kiroff G.K. Leppard P.I. Jamieson G.G. Domperidone, metoclopramide, and placebo. All give symptomatic improvement in gastroesophageal reflux J. Clin. Gastroenterol. 8 2 1986 135 140 3745846
Malfertheiner P. Hallerbäck B. Clinical manifestations and complications of gastroesophageal reflux disease (GERD) Int. J. Clin. Pract. 59 3 2005 346 355 15857335
Mandel Daggy Brodie Jacoby alginate‐raft formulations in the treatment of heartburn and acid reflux Alimentary pharmacology & therapeutics 14 6 2000 669 690 10848650
Marcus E.A. Inatomi N. Nagami G.T. Sachs G. Scott D.R. The effects of varying acidity on Helicobacter pylori growth and the bactericidal efficacy of ampicillin Aliment. Pharmacol. Ther. 36 10 2012 972 979 23009227
Mbatchou V.C. Nabayire K.O. Akuoko Y. Vernonia amygdalina Leaf: unveiling its antacid and carminative properties in Vitro Curr. Sci. 3 3 2017 148 155
McCallum R.W. Ippoliti A.F. Cooney C. Sturdevant R.A. A controlled trial of metoclopramide in symptomatic gastroesophageal reflux N. Engl. J. Med. 296 7 1977 354 357 319356
McDonald E.G. Milligan J. Frenette C. Lee T.C. Continuous proton pump inhibitor therapy and the associated risk of recurrent Clostridium difficile infection JAMA Intern. Med. 175 5 2015 784 791 25730198
McGwin G. The association between ranitidine use and gastrointestinal cancers Cancers 13 1 2020 24 33374592
Mejia A. Kraft W.K. Acid peptic diseases: pharmacological approach to treatment Expet Rev. Clin. Pharmacol. 2 3 2009 295 314
Melloni C. Washam J.B. Jones W.S. Halim S.A. Hasselblad V. Mayer S.B. Conflicting results between randomized trials and observational studies on the impact of proton pump inhibitors on cardiovascular events when coadministered with dual antiplatelet therapy: systematic review Circ Cardiovasc Qual Outcomes 8 1 2015 47 55 25587094
Miwa H. Uedo N. Watari J. Mori Y. Sakurai Y. Takanami Y. Randomised clinical trial: efficacy and safety of vonoprazan vs. lansoprazole in patients with gastric or duodenal ulcers - results from two phase 3, non-inferiority randomised controlled trials Aliment. Pharmacol. Ther. 45 2 2017 240 252 27891632
Mizuno H. Nishino M. Yamada K. Kamiyamamoto S. Hinoue Y. Efficacy of vonoprazan for 48-week maintenance therapy of patients with healed reflux esophagitis Digestion 101 4 2020 411 421 31129668
Mone I. Kraja B. Bregu A. Duraj V. Sadiku E. Hyska J. Adherence to a predominantly Mediterranean diet decreases the risk of gastroesophageal reflux disease: a cross-sectional study in a South Eastern European population Dis. Esophagus 29 7 2016 794 800 26175057
Moore J.M. Vaezi M.F. Extraesophageal manifestations of gastroesophageal reflux disease: real or imagined? Curr. Opin. Gastroenterol. 26 4 2010 389 394 20473157
Morelli G. Chen H. Rossiter G. Rege B. Lu Y. An open-label, parallel, multiple-dose study comparing the pharmacokinetics and gastric acid suppression of rabeprazole extended-release with esomeprazole 40 mg and rabeprazole delayed-release 20 mg in healthy volunteers Aliment. Pharmacol. Ther. 33 7 2011 845 854 21272047
Nakamura K. Tomita T. Oshima T. Asano H. Yamasaki T. Okugawa T. A double-blind placebo controlled study of acotiamide hydrochloride for efficacy on gastrointestinal motility of patients with functional dyspepsia J. Gastroenterol. 52 5 2017 602 610 27639387
Ness-Jensen E. Lindam A. Lagergren J. Hveem K. Tobacco smoking cessation and improved gastroesophageal reflux: a prospective population-based cohort study: the HUNT study Official journal of the American College of Gastroenterology| ACG. 109 2 2014 171 177
Ness-Jensen E. Hveem K. El-Serag H. Lagergren J. Lifestyle intervention in gastroesophageal reflux disease Clin. Gastroenterol. Hepatol. 14 2 2016 175 182. e3 25956834
Nilsson M. Johnsen R. Ye W. Hveem K. Lagergren J. Lifestyle related risk factors in the aetiology of gastro-oesophageal reflux Gut 53 12 2004 1730 1735 15542505
Nishizawa T. Suzuki H. Kanai T. Yahagi N. Proton pump inhibitor alone vs proton pump inhibitor plus mucosal protective agents for endoscopic submucosal dissection-induced ulcer: a systematic review and meta-analysis J. Clin. Biochem. Nutr. 56 2 2015 85 90 25759512
Orel R. Benninga M.A. Broekaert I.J. Gottrand F. Papadopoulou A. Ribes-Koninckx C. Drugs in focus: proton pump inhibitors J. Pediatr. Gastroenterol. Nutr. 72 5 2021 645 653 33847286
Oshima T. Miwa H. Potent potassium-competitive acid blockers: a new era for the treatment of acid-related diseases J Neurogastroenterol Motil 24 3 2018 334 344 29739175
Pandolfino J.E. Spechler S.J. Yadlapati R. Updates in the management of erosive esophagitis J. Fam. Pract. 72 8 Suppl. l 2023 S1 s12
Pati N.B. Velivela S. Mayasa V. Baggi R.B. Formulation and evaluation of delayed release enteric coated tablets of tenatoprazole, by optimizing the plymers Trends in Pharmaceutical Sciences 6 1 2020 21 28
Peterson W.L. Sturdevant R.A. Frankl H.D. Richardson C.T. Isenberg J.I. Elashoff J.D. Healing of duodenal ulcer with an antacid regimen N. Engl. J. Med. 297 7 1977 341 345 876324
Piesman M. Hwang I. Maydonovitch C. Wong R.K. Nocturnal reflux episodes following the administration of a standardized meal. Does timing matter? Official journal of the American College of Gastroenterology| ACG. 102 10 2007 2128 2134
Pinto-Sanchez M.I. Yuan Y. Bercik P. Moayyedi P. Proton pump inhibitors for functional dyspepsia Cochrane Database Syst. Rev. 3 3 2017 Cd011194
Rettura F. Bronzini F. Campigotto M. Lambiase C. Pancetti A. Berti G. Refractory gastroesophageal reflux disease: a management update Front. Med. 8 2021 765061
Robinson M. Proton pump inhibitors: update on their role in acid-related gastrointestinal diseases Int. J. Clin. Pract. 59 6 2005 709 715 15924600
Sachs G. Shin J.M. Howden C.W. Review article: the clinical pharmacology of proton pump inhibitors Aliment. Pharmacol. Ther. 23 Suppl. 2 2006 2 8 16700898
Saco L.S. Orlando R.C. Levinson S.L. Bozymski E.M. Jones J.D. Frakes J.T. Double-blind controlled trial of bethanechol and antacid versus placebo and antacid in the treatment of erosive esophagitis Gastroenterology 82 6 1982 1369 1373 7040158
Sakai H. Fujii T. Takeguchi N. Proton-potassium (H(+)/K(+)) ATPases: properties and roles in health and diseases Met Ions Life Sci. 16 2016 459 483 26860309
Savarino V. Marabotto E. Zentilin P. Demarzo M.G. de Bortoli N. Savarino E. Pharmacological management of gastro-esophageal reflux disease: an update of the state-of-the-art Drug Des Devel Ther 15 2021 1609 1621
Scarpignato C. Hongo M. Wu J.C. Lottrup C. Lazarescu A. Stein E. Pharmacologic treatment of GERD: where we are now, and where are we going? Ann. N. Y. Acad. Sci. 1482 1 2020 193 212 32935346
Schuitenmaker J.M. Kuipers T. Smout A.J. Fockens P. Bredenoord A.J. Systematic review: clinical effectiveness of interventions for the treatment of nocturnal gastroesophageal reflux Neuro Gastroenterol. Motil. 34 12 2022 e14385
Schunack W. What are the differences between the H2‐receptor antagonists? Aliment. Pharmacol. Ther. 1 1987 493s 503s 2908767
Schunack W. What are the differences between the H2-receptor antagonists? Aliment. Pharmacol. Ther. 1 Suppl. 1 1987 493s 503s 2908767
Seremet N. Karaagaoglu N. Kaner G. Tel K. Gastroesophageal reflux symptoms and nutritional preferences Stud. Ethno-Med. 9 3 2015 305 318
Sethia R. Prasad M. Mahapatra S.J. Nischal N. Soneja M. Garg P. Efficacy of famotidine for COVID-19: a systematic review and meta-analysis medRxiv 2020 2020.09. 28.20203463
Shaik K.M. Sarmah B. Wadekar G.S. Kumar P. Regulatory updates and analytical methodologies for nitrosamine impurities detection in sartans, ranitidine, nizatidine, and metformin along with sample preparation techniques Crit. Rev. Anal. Chem. 52 1 2022 53 71 32691615
Simon W.A. Herrmann M. Klein T. Shin J.M. Huber R. Senn-Bilfinger J. Soraprazan: setting new standards in inhibition of gastric acid secretion J Pharmacol Exp Ther 321 3 2007 866 874 17369284
Somogyi A. Gugler R. Clinical pharmacokinetics of cimetidine Clin. Pharmacokinet. 8 1983 463 495 6418428
St Onge E. Phillips B. Vonoprazan: a new potassium-competitive acid blocker Journal of Pharmacy Technology 39 3 2023 139 146
Sugano K. Vonoprazan fumarate, a novel potassium-competitive acid blocker, in the management of gastroesophageal reflux disease: safety and clinical evidence to date Therap Adv Gastroenterol 11 2018 1756283x17745776
Thanik K.D. Chey W.Y. Shah A.N. Gutierrez J.G. Reflux esophagitis: effect of oral bethanechol on symptoms and endoscopic findings Ann. Intern. Med. 93 6 1980 805 808 7004292
Thomson A.B. Cohen P. Ficheux H. Fiorentini P. Domagala F. Homerin M. Comparison of the effects of fasting morning, fasting evening and fed bedtime administration of tenatoprazole on intragastric pH in healthy volunteers: a randomized three-way crossover study Aliment. Pharmacol. Ther. 23 8 2006 1179 1187 16611279
Tsukimi Y. Ushiro T. Yamazaki T. Ishikawa H. Hirase J. Narita M. Studies on the mechanism of action of the gastric H+,K(+)-ATPase inhibitor SPI-447 Jpn. J. Pharmacol. 82 1 2000 21 28 10874584
Tutuian R. Castell D.O. Nocturnal acid breakthrough - approach to management MedGenMed 6 4 2004 11
Tutuian R. Mainie I. Allan R. Hargreaves K. Agrawal A. Freeman J. Effects of a 5-HT(4) receptor agonist on oesophageal function and gastro-oesophageal reflux: studies using combined impedance-manometry and combined impedance-pH Aliment. Pharmacol. Ther. 24 1 2006 155 162 16803614
Uemura N. Kinoshita Y. Haruma K. Yao T. Kushima R. Kanoo T. Rationale and design of the VISION study: a randomized, open-label study to evaluate the long-term safety of vonoprazan as maintenance treatment in patients with erosive esophagitis Clin. Exp. Gastroenterol. 11 2018 51 56 29416369
Untersmayr E. Acid suppression therapy and allergic reactions Allergo J Int 24 8 2015 303 311 28603686
Vakily M. Zhang W. Wu J. Atkinson S.N. Mulford D. Pharmacokinetics and pharmacodynamics of a known active PPI with a novel Dual Delayed Release technology, dexlansoprazole MR: a combined analysis of randomized controlled clinical trials Curr. Med. Res. Opin. 25 3 2009 627 638 19232037
Williams M.P. Sercombe J. Hamilton M.I. Pounder R.E. A placebo-controlled trial to assess the effects of 8 days of dosing with rabeprazole versus omeprazole on 24-h intragastric acidity and plasma gastrin concentrations in young healthy male subjects Aliment. Pharmacol. Ther. 12 11 1998 1079 1089 9845397
Wurst W. Hartmann M. Current status of acid pump antagonists (reversible PPIs) Yale J. Biol. Med. 69 3 1996 233 243 9165692
Xiao Y. Zhang S. Dai N. Fei G. Goh K.L. Chun H.J. Phase III, randomised, double-blind, multicentre study to evaluate the efficacy and safety of vonoprazan compared with lansoprazole in Asian patients with erosive oesophagitis Gut 69 2 2020 224 230 31409606
Yamashita H. Kanamori A. Kano C. Hashimura H. Matsumoto K. Tsujimae M. The effects of switching to vonoprazan, a novel potassium-competitive acid blocker, on gastric acidity and reflux patterns in patients with erosive esophagitis refractory to proton pump inhibitors Digestion 96 1 2017 52 59 28662503
Yamashita H. Okada A. Naora K. Hongoh M. Kinoshita Y. Adding acotiamide to gastric acid inhibitors is effective for treating refractory symptoms in patients with non-erosive reflux disease Dig. Dis. Sci. 64 3 2019 823 831 30465175
Yuan Y. Hunt R. Intragastric acid suppressing effect of proton pump inhibitors twice daily at steady state in healthy volunteers: evidence of an unmet need?: 128 Official journal of the American College of Gastroenterology | ACG. 103 2008 S50 S51
Yuan L.-Z. Yi P. Wang G.-S. Tan S.-Y. Huang G.-M. Qi L.-Z. Lifestyle intervention for gastroesophageal reflux disease: a national multicenter survey of lifestyle factor effects on gastroesophageal reflux disease in China Therapeutic advances in gastroenterology 12 2019 1756284819877788
Zamani N.F. Sjahid A.S. Tuan Kamauzaman T.H. Lee Y.Y. Islam M.A. Efficacy and safety of domperidone in combination with proton pump inhibitors in gastroesophageal reflux disease: a systematic review and meta-analysis of randomised controlled trials J. Clin. Med. 11 18 2022
Zhang M. Hou Z.-K. Huang Z.-B. Chen X.-L. Liu F.-B. Dietary and lifestyle factors related to gastroesophageal reflux disease: a systematic review Therapeut. Clin. Risk Manag. 2021 305 323
