Benefits Of Proton Pump Inhibitors Research Articles

Proton Pump Inhibitor for Gastrointestinal Bleeding in Patients with Myocardial Infarction on Dual-Antiplatelet Therapy: A Nationwide Cohort Study.

Guidelines provide various recommendations for the use of proton pump inhibitors (PPI) to prevent upper gastrointestinal (UGI) bleeding in acute myocardial infarction (MI) treatment with dual antiplatelet therapy (DAPT). We evaluated the effects of PPIs in reducing the risk of severe UGI bleeding in patients with MI receiving DAPT. This retrospective cohort study included patients admitted for acute MI between 2014 and 2018, based on a nationwide health claims database in Korea. Primary outcome was admission for severe UGI bleeding requiring transfusion within 1 year of MI diagnosis. A multivariable Cox regression model was used to calculate the association between PPI use and severe UGI bleeding risk. Of 100,556 patients with MI on DAPT (mean age, 63.7 years; 75.4% men), 37% were prescribed PPIs. Based on risk assessment for UGI bleeding, among 6,392 (6.4%) high-risk and 94,164 (93.6%) low-risk patients, 50.5% and 35.8% received PPIs, respectively. Overall, 0.5% of the patients experienced severe UGI bleeding within 1 year after MI. The use of PPI was associated with a reduced risk of severe UGI bleeding (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.47-0.70; P < 0.001). The benefits of PPIs were consistent in high-risk (HR, 0.71; 95% CI, 0.45-1.13; P = 0.147) and low-risk (HR, 0.54; 95% CI, 0.43-0.68; P < 0.001) patients (P for interaction = 0.481). Among Korean patients with MI receiving DAPT, PPIs were underutilized, even among those at high risk of severe UGI bleeding. Nonetheless, PPI use reduced severe UGI bleeding in low- and high-risk groups.

Pathogenesis and management of gastroesophageal reflux disease-associated cough: a narrative review.

Gastroesophageal reflux disease (GERD)-associated cough is defined as a special GERD with a predominant cough symptom and is a common cause of chronic cough. This review summarizes our current understanding on the pathogenesis and management of GERD-associated cough. Main literatures on the pathogenesis and management of GERD-associated cough were reviewed and our understandings derived from the published studies were showed then. Although esophageal-tracheobronchial reflex mainly underlies the pathogenesis of GERD-associated cough, its counterpart-tracheobronchial-esophageal reflex might exist and initiate the cough due to reflux induced by upper respiratory tract infection through the signaling of transient receptor potential vanilloid 1 linking airway and esophagus. The presence of reflux-associated symptoms such as regurgitation and heartburn along with coughing suggests an association between cough and GERD, which is supported by the objective evidence of abnormal reflux as detected by reflux monitoring. Although there is no general consensus, esophageal reflux monitoring provides the main diagnostic criteria for GERD-associated cough. Despite that acid exposure time and symptom associated probability are useful and mostly employed reflux diagnostic criteria, they are imperfect and far from being the gold standard. Acid suppressive therapy has long been recommended as the first choice for GERD-associated cough. However, the overall benefits of proton pump inhibitors have been controversial and need to be further assessed, especially in patients with cough due to non-acid reflux. Neuromodulators have demonstrated potential therapeutic effects for refractory GERD-associated cough, for which anti-reflux surgery may also be a promising treatment option. Tracheobronchial-esophageal reflex might initiate reflux-induced cough provoked by the upper respiratory tract infection. It is necessary to optimize the current standards and to explore new criteria with higher diagnostic potency. Acid suppressive therapy is the first choice for GERD-associated cough, followed by neuromodulators and anti-reflux surgery for refractory GERD-associated cough.

Inhibitory protonové pumpy – známe je dobře? Jsou skutečně tak bezpečné? – část 1

Proton pump inhibitors (PPIs) are one of the most commonly used drug groups. More than 10% of patients being chronically treated in the adult population. Often patients with a high risk of vascular or renal impairment. In addition to the unquestionable effect in the treatment and in the prophylaxis of gastroduodenal diseases, PPIs have been promoted in combination with antithrombotic therapy in order to reduce bleeding in the gastrointestinal tract. In both of these indications, this is a chronic treatment, often for several years. Drug regulatory agencies (EMAs or FDA) warn against chronic PPIs use, warning of a number of serious side effects. However, chronic administration of PPIs is a common practice. It is therefore time to evaluate the benefit and risk of this important drug group. First of all, it should be noted that PPIs operate not only at the level of the classical gastric proton pump (H+/K+ ATPase), but also block the activity of the sister vacuolar proton pump (V-H+-ATPase) in a number of other organs or organelles, namely lysosomes of all somatic cells. Similarly, PPIs block the activity of a number of transporters and metabolic enzymes. Action at this level is likely to surprise the gastroenterologist. There is no doubt about the benefits of PPIs in the indication of treatment and prevention of ulcerative or reflux disease. However, what are the evidence to reduce the risk of gastriontestinal bleeding in antithrombotic treatment? In this area we have data at the level of observational studies, the decrease in the risk of bleeding by about a third is significant. However, with a relatively low incidence of bleeding in the gastrointestinal tract, the absolute decrease in risk is small, hovering at 0.3%. The observed number need to treat is around 250, i.e. for every 250 PPIs treated, we will prevent one bleeding (usually not critical). On the other hand, there are increasingly work that finds a higher incidence of cardiovascular events, renal failure, bronchial asthma and nervous disabilities in chronic PPIs treatment. In a population at high cardiovascular risk, i.e. in a typical population where we add antithrombotic treatment to PPIs, the risk is significant. The number need to harm value is around 50. Thus, in the chronic use of PPIs, the risk outweighs the benefit.

Use of proton pump inhibitors in dialysis patients: a double-edged sword?

Large cohort-based studies have shown that proton pump inhibitors (PPIs) are linked to rare but multiple and varied secondary events when used in the general population. Although clinicians accept the negative effects of PPIs on renal function, there is a lack of available data regarding the potential consequences of their use by dialysis patients in whom the risk of gastrointestinal bleeding is quite high. This review aims to highlight the risks and benefits of PPIs use in dialysis patients. To summarize, the benefit on the reduction of high digestive bleeding seems certain, but without any beneficial impact on overall survival. The impact on quality of life seems to be significant. The data on the occurrence of peritonitis during PPIs treatment are very contradictory. There is evidence regarding the occurrence of hypomagnesaemia in haemodialysis patients with PPIs; which may lead to increase bone fragility. New data show an increased cardiovascular risk and even a risk of death linked to the use of PPIs on dialysis. Several mechanisms of IPP toxicity are advanced to explain these findings.

Prevention of gastrointestinal bleeding in patients receiving oral anticoagulants: focus on proton pump inhibitors

The review addresses the issue of the gastrointestinal bleeding (GIB) development in patients receiving oral anticoagulants, and the proton pump inhibitors (PPIs) efficiency in reducing of such complications. Epidemiological data on the prevalence of GIB in the presence of nonwarfarin oral anticoagulants (NOACs) and warfarin intake are presented. The factors that increase the risk of bleeding associated with the use of anticoagulants are discussed, including the potential drug-drug interactions and patients’ dietary habits. A description of the scales that assess the bleeding risks during anticoagulant therapy is given. In the second part of the article the principles of prevention and minimization of the GIB risks in the presence of oral anticoagulants treatment are presented. In the context of evidence-based medicine, the PPIs’ role in reducing the risk of GIB is fully discussed. The results of recent large-scale randomized clinical trials and meta-analyses are described in detail, suggesting the benefits of PPIs in the decreasing the risk of the upper gastrointestinal tract bleeding when NOACs and warfarin are prescribed, especially with concomitant therapy with acetylsalicylic acid. So, PPIs can be considered as one of the effective drug prevention “tools” of these complications.

Patients' Perceptions of Proton Pump Inhibitor Risks and Attempts at Discontinuation: A National Survey.

Little is known about how reports on the adverse effects of proton pump inhibitors (PPIs) impact patients' perceptions of these drugs and medication use. We sought to determine patients' level of concern about PPI adverse effects and its association with attempts to discontinue these drugs. This study is an online survey of US adults who use PPIs for gastroesophageal reflux disease. Topics included awareness of and concern about PPI adverse effects, prior discussion with providers, and attempts to stop PPI because of concern about adverse effects. For the primary analysis, we used logistic regression to identify associations between having attempted to stop PPI and concern about PPI-related adverse effects, a provider's recommendation to stop, risk of upper gastrointestinal bleeding (UGIB), age, and gender. Among 755 patient participants, mean age was 49 years (s.d. 16), 71% were women, and 24% were at high risk of UGIB. Twenty percent of patients were able to write in ≥1 reported adverse effect, and 46% endorsed awareness of ≥1 adverse effect when presented with a list, most commonly chronic kidney disease (17%). Thirty-three percent of patients were slightly concerned, 32% somewhat concerned, and 14% extremely concerned about adverse effects. Twenty-four percent of patients had discussed PPI risks and benefits with a provider, and 9% had been recommended to stop. Thirty-nine percent had attempted to stop their PPI, most (83%) without a provider recommendation. Factors associated with an attempt at stopping PPI included: (i) provider recommendation to stop (odds ratio [OR] 3.26 [1.82-5.83]); (ii) concern about adverse effects (OR 5.13 [2.77-9.51] for slightly, 12.0 [6.51-22.2] for somewhat, and 19.4 [9.75-38.7] for extremely concerned); and (iii) female gender (OR 1.64 [1.12-2.39]). Patients at high risk of UGIB were as likely to have attempted to stop as others (OR 0.98 [0.66-1.44]). Concern about PPIs is common and strongly associated with attempts at discontinuation, even without a provider's recommendation. Notably, individuals at high risk of UGIB, who benefit from PPIs, were equally likely to have tried stopping PPIs as others. Providers should proactively discuss the risks and benefits of PPIs with their patients, who may otherwise make unwise decisions about PPI management on their own.

Clinical outcomes of laryngopharyngeal reflux treatment: A systematic review and meta-analysis.

To investigate the therapeutic benefit of proton pump inhibitors (PPIs) over placebo in patients with laryngopharyngeal reflux (LPR) and to analyze the epidemiological factors of heterogeneity in the literature. An electronic literature search was conducted to identify articles published between 1990 and 2018 about clinical trials describing the efficiency of medical treatment(s) on LPR. First, a meta-analysis of placebo randomized controlled trials (RCTs) comparing PPIs versus placebo was conducted according to diet. The heterogeneity, response to PPIs, and evolution of clinical scores were analyzed for aggregate results. Second, a systematic review of diagnosis methods, clinical outcome of treatment, and therapeutic regimens was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The search identified 1,140 relevant publications, of which 72 studies met the inclusion criteria for a total of 5,781 patients. Ten RCTs were included in the meta-analysis. The combined relative risk was 1.31 in favor of PPIs and increased to 1.42 when patients did not receive diet recommendations. Randomized controlled trials were characterized by a significant heterogeneity due to discrepancies in clinical therapeutic outcomes, diagnosis methods (lack of gold standard diagnostic tools), and therapeutic scheme. The epidemiological analysis of all articles supports the existence of these discrepancies in the entire literature. In particular, many symptoms and signs commonly encountered in LPR are not assessed in the treatment effectiveness. The lack of diagnosis precision and variability of inclusion criteria particularly create bias in all reported and included articles. This meta-analysis supports a mild superiority of PPIs over placebo and the importance of diet as additional treatment but demonstrates the heterogeneity between studies, limiting the elaboration of clear conclusions. International recommendations are proposed for the development of future trials. Laryngoscope, 129:1174-1187, 2019.

Does the treatment of proton pump inhibitors reduce dysplasia or adenocarcinoma development in Barrett's esophagus?

Besides reducing the reflux symptoms, the benefit of proton pump inhibitors (PPI) in the treatment of Barrett's esophagus (BE) is not exactly known. The data in the literature show that although the PPI treatment does not reduce the Barrett's segment length, it can reduce dysplasia or the development of early-stage adenocarcinoma (odds ratio (OR): 0.46). Therefore, treatments with PPI may be considered in patients with a diagnosis of BE and at a high risk of adenocarcinoma, even though they are not symptomatic.

ANTISECRETORY TREATMENT FOR PEDIATRIC GASTROESOPHAGEAL REFLUX DISEASE - A SYSTEMATIC REVIEW.

Proton pump inhibitors and histamine H2 receptor antagonists are two of the most commonly prescribed drug classes for pediatric gastroesophageal reflux disease, but their efficacy is controversial. Many patients are treated with these drugs for atypical manifestations attributed to gastroesophageal reflux, even that causal relation is not proven. To evaluate the use of proton pump inhibitors and histamine H2 receptor antagonists in pediatric gastroesophageal reflux disease through a systematic review. A systematic review was performed, using MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials databases. The search was limited to studies published in English, Portuguese or Spanish. There was no limitation regarding date of publication. Studies were considered eligible if they were randomized-controlled trials, evaluating proton pump inhibitors and/or histamine H2 receptor antagonists for the treatment of pediatric gastroesophageal reflux disease. Studies published only as abstracts, studies evaluating only non-clinical outcomes and studies exclusively comparing different doses of the same drug were excluded. Data extraction was performed by independent investigators. The study protocol was registered at PROSPERO platform (CRD42016040156). After analyzing 735 retrieved references, 23 studies (1598 randomized patients) were included in the systematic review. Eight studies demonstrated that both proton pump inhibitors and histamine H2 receptor antagonists were effective against typical manifestations of gastroesophageal reflux disease, and that there was no evidence of benefit in combining the latter to the former or in routinely prescribing long-term maintenance treatments. Three studies evaluated the effect of treatments on children with asthma, and neither proton pump inhibitors nor histamine H2 receptor antagonists proved to be significantly better than placebo. One study compared different combinations of omeprazole, bethanechol and placebo for the treatment of children with cough, and there is no clear definition on the best strategy. Another study demonstrated that omeprazole performed better than ranitidine for the treatment of extraesophageal reflux manifestations. Ten studies failed to demonstrate significant benefits of proton pump inhibitors or histamine H2 receptor antagonists for the treatment of unspecific manifestations attributed to gastroesophageal reflux in infants. Proton pump inhibitors or histamine H2 receptor antagonists may be used to treat children with gastroesophageal reflux disease, but not to treat asthma or unspecific symptoms.

Ilaprazole for the treatment of gastro-esophageal reflux

ABSTRACTIntroduction: Despite the undoubted benefit of proton pump inhibitors (PPIs), they have several shortcomings, such as a slow onset of action and a remarkable inter-individual variability, that limit the complete success of these drugs. Recently, a new PPI, ilaprazole, has been developed and used in GERD patients.Areas covered: The present review provides an update on the following points: current knowledge of GERD mechanisms; limitations of actual therapies; pharmacokinetic profile and metabolism of ilaprazole; initial studies on the therapeutic efficacy of ilaprazole in GERD.Expert opinion: Compared with all other approved PPIs, ilaprazole has shown an extended plasma half-life, a metabolism not significantly influenced by CYP2C19 genetic polymorphism and similar safety. This characteristics account for a low inter-individual variability, particularly in Asian populations, a higher suppression of gastric acid secretion, a more rapid acid control and consequent quicker symptom relief and a better effect on nocturnal acidity. However, clinical investigations assessing the efficacy of ilaprazole in the management of GERD are lacking and therefore the potential improvements achievable with ilaprazole in the current standard of care for acid-suppressing treatment must be confirmed in large and randomly controlled clinical trials enrolling patients with both erosive and non-erosive reflux disease.

Are higher doses of proton pump inhibitors better in acute peptic bleeding?

Although there is broad consensus about the benefits of proton pump inhibitors in acute upper peptic bleeding, there is still controversy over their optimal dosing. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified six systematic reviews including 27 randomized trials addressing this question. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded high-dose proton pump inhibitors probably result in little or no difference in re-bleeding rate or mortality. The risk/benefit and cost/benefit balance probably favor use of low-doses.

Proton pump inhibitor use represents an independent risk factor for myocardial infarction

BackgroundThere is substantial debate regarding the development of acute coronary syndrome in patients using proton pump inhibitors (PPIs) combined with clopidogrel. However, data remain limited to address the effect of PPIs alone on the subsequent risk of myocardial infarction (MI). We aimed to explore the subsequent risk of MI in PPI users who had no previous history of MI. MethodsThe records of inpatients and outpatients with PPI prescriptions were retrieved from the Taiwan National Health Insurance Research Database between 2000 and 2009. We conducted two different study designs, the first using propensity score (PS)-matching analyses and the second using case-crossover analyses. The risk of developing MI for PPI users was analyzed in the PS-matched study. The association between risk of MI and prior PPI exposure was further validated in the case-crossover study. ResultsIn the PS-matched study, we included 126,367 PPI users and 126,367 PS-matched PPI non-users. After 120days of follow-up, PPI use was associated with a 1.58-fold greater risk of MI (adjusted hazard ratio [HR]=1.58, 95% confidence interval [CI]=1.11 to 2.25). In the case-crossover study, adjusted odds ratios of PPI for MI risk were 4.61 (95% CI=1.76 to 12.07) for the 7-day window and 3.47 (95% CI=1.76 to 6.83) for the 14-day window. ConclusionsUse of PPIs may be independently associated with an increased risk of MI. However, the benefits of PPIs may greatly outweigh the risks of adverse cardiovascular effects, with number needed to harm of 4357.

Proton Pump Inhibitors – Their Pharmacological Impact on the Clinical Management of Acid-Related Disorders

Acid secretion or intragastric pH play a very important role in the pathophysiology of acid-related disorders such as peptic ulcer (PU), gastrooesophageal reflux disease (GERD) or nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal lesions. Proton pump inhibitors (PPIs) represent the most potent/effective antisecretory drugs for these indications. For the selection among the various agents (omeprazole/esomeprazole (CAS 73590-58-6/119141-88-7), pantoprazole (CAS 102625-70-7), lansoprazole (CAS103577-45-3), rabeprazole (CAS 117976-83-3)) some features of their pharmacokinetic (PK) and pharmacodynamic (PD) properties should be considered as the clinical outcome depends on systemic drug exposure (PK) and elevation of intragastric pH about certain threshold levels (PD). The present review updates PK, PD and clinical data to provide some guidance between the PPIs which differ somewhat in their metabolic pattern and drug interaction potential. Based on 24-h intragastric pH assessments the relative potencies of the PPIs compared to omeprazole were in healthy volunteers (in GERD patients): 0.42 (0.59), 1.0 (0.8), 1.0 (1.0), 1.25 (1.25) and 2.0 (1.4) for pantoprazole, lansoprazole, omeprazole, esomeprazole and rabeprazole, respectively. In general, the clinical benefits of PPI are well documented but some patients can be regarded as non-responders and thus represent a challenge for future clinical research.

Comparison of Daily Average Consumption Between Different Proton Pump Inhibitors in Patients with Gastroesophageal Reflux Disease

Purpose: Numerous randomized clinical trials have shown the benefits of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD). Due to inadequate symptom control of once daily dosing, approximately 12-20% of patients use twice daily dosing of PPIs. The objective of this study was to compare daily average consumption (DACON) among GERD patients treated with different branded and generic PPIs. Methods: We conducted a retrospective database analysis using commercial enrollees from a large U.S. health plan from February 2008 to December 2009. Adult GERD patients with ≥1 medical claim with ICD-9 diagnosis codes 530.1, 530.10-530.12, 530.81, or 787.1, ≥1 PPI Rx claim during the identification period of February 2009 to September 2009, and continuous eligibility for 12 months before and 6 months after the index date were identified. The date of the first PPI Rx claim during the identification period was considered as the index date. DACON was defined as quantity of medication dispensed over the number of days with medication. We controlled for age, gender, region, GERD severity, plan type, pre-index Quan-Charlson comorbidity score (CCI), DACON, and costs and utilization. Results: Among 185,506 GERD patients identified, 2.3% were taking dexlansoprazole, 5.0% lansoprazole, 9.6% esomeprazole, 19.6% rabeprazole, 30.2% pantoprazole, and 33.3% omeprazole at the index date. Over half of the patients (56.47%) were branded PPI users and 43.53% (n=80,749) were generic PPI users at the index date. Patients in the branded PPI group were more likely to be younger (51.32 vs. 52.25 years, p<0.001), female (57.00% vs. 55.36%, p<0.001), reside in the southern part of the United States (57.65% vs. 48.00%, p<0.001), use point-of-service (56.54% vs. 53.06%, p<0.001) and exclusive provider organization (15.32% vs. 12.92%, p<0.001) health plans and had lower CCI (0.81 vs. 0.90, p<0.001) compared to patients in the generic PPI group. The highest DACON was among omeprazole users (1.32), followed by users of lansoprazole (1.20), rabeprazole (1.18), pantoprazole (1.16), esomeprazole (1.15) and dexlansoprazole (1.04). After risk adjustment, branded PPI users had a lower DACON (1.09 vs. 1.28, p<0.001) compared to generic PPI users. Conclusion: There were differences in DACON values between the different PPIs with dexlansoprazole showing the lowest and omeprazole showing the highest DACON. Branded PPI users showed lower DACON compared to generic PPI. The potential impact of reduced DACON on patient adherence, length of treatment and total and GERD-related healthcare resource utilization and costs requires further evaluation. Disclosure: Dr Mody - Employee: Takeda Pharmaceuticals International, Inc. All other authors were contracted research vendors for this study for Takeda Pharmaceuticals international, Inc. This research was supported by an industry grant from Takeda Pharmaceuticals International, Inc. funded this project.

Nocturnal reflux and sleep disturbances: An overlooked link in the past

Gastro-oesophageal reflux disease (GORD) is highly prevalent n western countries. The main clinical manifestations are repreented by heartburn and regurgitation and they are commonly used or the diagnosis of GORD, although their accuracy is far from optial [1]. The above symptoms can occur during the daytime and lso throughout the nocturnal period. In the past, the progressively idespread use of 24-h oesophageal pH-metry showed that the ajority of reflux events belong to the post-prandial periods, whilst hey are much less frequent during the night time [2]. This temporal istribution of abnormal reflux episodes provided the rationale to xplain, at least in part, the benefit of proton pump inhibitors (PPIs) n patients with GORD. In fact, these drugs are more effective durng the daytime, when proton pumps are activated by fractionated eals, than through the night time, when their main pharmacoogical target does not work because of sleep [3]. Despite the above ndings, in the last decade we have witnessed a mounting evidence f the role of night time GORD in provoking a decreased quality of ife, a variety of sleep disorders and diminished work performances 4]. Several epidemiological surveys have confirmed that nocturnal eflux symptoms, in particular heartburn and regurgitation, can be eported by 2 out of 3 patients with GORD [5] and the relationship etween GORD and sleep disorders has been recently established y many studies which have clearly demonstrated that 47–57% of he GORD patients and approximately 25% of the US adult genral population report having heartburn that awakens them from leep during the night [6,7]. Of the GORD patients, 63% report that hey are unable to sleep well, 42% are unable to sleep during a ull night, 39% have to take naps during the day and 34% have to leep in a seated position because of night time heartburn [7]. It as also been shown that sleep deprivation per se can adversely nfluence GORD, in that the inability to have a complete rest during he night is a potential mechanism for increasing the perception of ymptoms in patients with GORD [8]. Another important issue is he still poorly understood role of nocturnal reflux in determining xtra-oesophageal and particularly respiratory symptoms because f the well-known longer-lasting duration and the slower clearing f supine refluxes compared with the daytime ones [9]. Finally, the se of impedance-pH monitoring has shown that nocturnal weakly

Balancing the Risks and Benefits of Proton Pump Inhibitors

Balancing the Risks and Benefits of Proton Pump Inhibitors

Failing the Acid Test

Failing the Acid Test

The effect of ranitidine versus proton pump inhibitors on gastric secretions: a meta‐analysis of randomised control trials

Aspiration of acid into the lungs is an infrequent but potentially devastating complication of general anaesthesia. Routine practice often includes use of pharmacological agents to reduce gastric volume and increase gastric pH. The aim of this study was to compare the net benefit of proton pump inhibitors with histamine 2 blockers in a meta-analysis. Electronic databases were searched for trials that compared ranitidine vs proton pump inhibitors in their effect on volume and pH of gastric fluid aspirates. We identified nine trials of which seven were suitable for meta-analysis. Pooled outcomes suggest that premedication with ranitidine is more effective than proton pump inhibitors in reducing the volume of gastric secretions (by an average of 0.22 ml.kg(-1); 95% confidence interval 0.04-0.41) and increasing gastric pH (by an average of 0.85 pH units; 95% confidence interval -1.14 to -0.28).

Pantoprazole: from drug metabolism to clinical relevance

Background: Conditions requiring inhibition of acid secretion, such as gastro-oesophageal reflux disease (GORD), peptic ulcers, non-ulcer dyspepsia or the use of NSAIDs, are very common, and their prevalence is expecting to rise as they are seen predominantly amongst the elderly. Among the drugs available to inhibit acid secretion, proton pump inhibitors (PPI) have been shown to have the best efficacy–safety ratio and have been used widely. Objective: This paper was intended to provide an overall presentation of one of these PPIs, pantoprazole. Method: This study was first intended to give an overview of pantoprazole, so a Medline search was conducted using pantoprazole as unique search term, without publication date restriction. We found 826 references for pantoprazole and selected some of the most relevant publications to conduct this review. Results/conclusion: Five different PPIs are commercially available: omeprazole, pantoprazole, rabeprazole, lansoprazole and esomeprazole. Pantoprazole differs from other PPIs by a selective binding to the ion transport pathway, a good stability at neutral pH values, and a relatively robust plasma concentration-time curve. These pharmacokinetic differences may not be fully converted into pharmacodynamic differences of pantoprazole versus other PPIs. Pantoprazole has been assessed in most of the clinical situations where acid suppression is required, and showed great efficacy and an excellent safety profile. Some safety concerns were raised with long-term use of PPIs, but they are well balanced by the benefit of PPIs for patients with conditions such as GORD or peptic ulcer.

Pharmacologic properties of proton pump inhibitors.

Since their introduction into clinical practice in the 1980s, proton pump inhibitors (PPIs) have proved to be of enormous value in the management of acid peptic disorders. They have become the treatment of choice for most, if not all, acid-related gastrointestinal disorders, including gastroesophageal reflux disease, peptic ulcer, and Zollinger-Ellison syndrome. With approval of an intravenous formulation, the benefits of PPIs are extended to critically ill patients for whom oral drug administration is often unsuitable. Five PPIs are approved for clinical use in the United States. Although they share a common core structure and mechanism of action, it is important to understand the general pharmacology of these agents and how they differ from histamine2-receptor antagonists in order to optimize PPI therapy.