Intragastric Nitric Oxide/Nitrite in Helicobacter pylori-Infected Subjects

Background: Nitrite (NO₂-) in swallowed saliva is reduced to nitric oxide (NO) and other nitrogen oxides by the intragastric acidity. This mechanism is probably important for the intragastric clearance of ingested micro-organisms and nitrosating compounds. The study examines the balance between intragastric NO and NO₂- in relation to endogenous acid production and infection with Helicobacter pylori. Methods: Six healthy H. pylori-negative and six H. pylori-positive volunteers with no known gastroduodenal pathology were examined after an overnight fast. Gastric NO was measured using a chemiluminescence technique and pH as well as NO₂- were analysed in gastric aspirates. Results: Gastric NO was slightly lower in H. pylori     

不同质子泵抑制剂三联治疗幽门螺杆菌阳性糜烂性胃炎的疗效差异

目的 比较不同质子泵抑制剂(PPI)和抗生素三联疗法治疗幽门螺杆菌(Hp)阳性糜烂性胃炎的疗效差异.方法 将Hp阳性糜烂性胃炎545例随机给予奥美拉唑、埃索美拉唑、泮托拉唑、兰索拉唑或雷贝拉唑联合阿莫西林与克拉霉素三联疗法治疗7d,比较各组疗效差异.结果 埃索美拉唑组在缓解症状、改善胃镜下表现方面显著高于其它各组,雷贝...     

Proton Pump Inhibitors and Clopidogrel

Proton pump inhibitors are often prescribed for patients on clopidogrel to prevent gastrointestinal bleeding complications. Recent data suggest higher rates of adverse cardiovascular events in patients on proton pump inhibitors and clopidogrel, in comparison to patients on clopidogrel only. Both drugs are metabolized by similar pathways of the cytochrome P450 system, so proton pump inhibitors may inhibit the metabolism of clopidogrel to its active metabolite. This article reviews the pharmacodynamic and clinical evidence for this phenomenon.     

Reversible Pheripheral Edema in Female Patients Taking Proton Pump Inhibitors for Peptic Acid Diseases

Pheripheral edema was observed in five female patients after taking proton pump inhibitors omeprazole, lansoprazole, or pantoprazole for 7–15 days for peptic acid diseases in recommended standard doses. Edema disappeared two to three days after stopping therapy but reappeared in all five patients after being reexposed to the drugs. In three of the patients drug kinetic investigations were performed and revealed a slow metabolizer status. During dose-finding studies for intravenous proton pump inhibitors omeprazole and pantoprazole, three of six young female volunteers receiving omeprazole and two young female volunteers receiving pantoprazole developed peripheral edema within 8 hr when high doses of the proton pump inhibitors were applied by continuous infusion together with large volumes of fluid. The edema disappeared within 24 hr after stopping the infusion therapy. Serum hormone concentrations in these patients did not change during therapy, neither did the edema factor C1-esterase inhibitor. As a possible mechanism, a competitive inhibition at the receptor site of female hormones involved in water regulation is suspected.     

Long-term Safety Concerns with Proton Pump Inhibitors

Proton pump inhibitors (PPIs) are among the most widely prescribed medications worldwide. Their use has resulted in dramatic improvements in treatment of peptic ulcer disease and gastroesophageal reflux disease. Despite an acceptable safety profile, mounting data demonstrate concerns about the long-term use of PPIs. To provide a comprehensive review regarding the concerns of long-term PPI use, a literature search was performed to identify pertinent original and review articles. Despite study shortcomings, the collective body of information overwhelmingly suggests an increased risk of infectious complications and nutritional deficiencies. Data regarding any increased risk in gastric or colon malignancy are less convincing. PPIs have revolutionized the management and complications of acid-related disorders with a high margin of safety; however, with the data available, efforts to reduce the dosing of or discontinue the use of PPIs must be reassessed frequently.     

Treatment with Proton Pump Inhibitors Induces Tolerance to Histamine-2 Receptor Antagonists in Helicobacter pylori-Negative Patients

Background: Treatment with H₂ receptor antagonists (H₂RAs) and proton pump inhibitors (PPIs) induces hypergastrinemia and causes rebound hypersecretion of gastric acid after treatment, and during treatment with H₂RAs tolerance develops. In the present study we investigated whether a treatment period with a PPI induced tolerance to an H₂RA. Methods: Thirteen patients with esophagitis were given omeprazole for 90 days. Twenty-four-hour pH monitorings without and with ranitidine were performed before and after treatment with omeprazole. Blood samples and biopsy specimens from the oxyntic mucosa were analyzed for gastrin, histamine, and chromogranin A. Results: An increase in mucosal histamine and a reduction in the effect of ranitidine on gastric pH was found 14 days after discontinuing omeprazole compared with before treatment in Helicobacter pylori-negative but not in H. pylori-positive patients. Conclusions: Treatment with omeprazole reduces the effect of ranitidine in H. pylori-negative patients. This is caused by an increase in histamine released by the enterochromaffin-like cell secondarily to hypergastrinemia, corresponding to the tolerance towards H₂RAs seen in patients with Zollinger-Ellison syndrome.     

Strategies for Effective Discontinuation of Proton Pump Inhibitors

Purpose of Review

Proton pump inhibitors (PPIs) are effective for many conditions but are often overprescribed. Recent concerns about long-term risks have made patients re-evaluate their need to take PPIs chronically, though these population-based studies have methodological weaknesses. The goal of this review is to provide evidenced-based strategies for discontinuation of PPI therapy.

Recent Findings

Given that some patients experience rebound symptoms when abruptly stopping continuous PPI therapy due to its effect on hypergastrinemia, strategies focus on avoiding rebound. Tapering the PPI and then initiating a “step-down” approach with the use of alternative medications may be effective. “On-demand therapy” provides patients with the option to take intermittent PPI courses, reducing overall use and cost while preserving patient satisfaction. It is important for providers to consider ambulatory pH or pH/impedance testing to rule out diagnoses that may require alternative medications like neuromodulators.

Summary

A number of studies reviewed here can provide guidance in counseling patients on PPI discontinuation. It is important for the provider to obtain a baseline needs assessment for PPI therapy and to elucidate predictors of difficulty in discontinuation prior to initiating a strategy.

     

不同的质子泵抑制剂与氯吡格雷相互作用的研究进展

大量研究表明阿司匹林和氯吡格雷联合抗血小板可以降低急性冠状动脉综合征及冠状动脉支架植入术后复发心血管事件的概率。但由于联合抗血小板治疗会增加出血的风险,所以目前临床推荐加用质子泵抑制剂以预防胃肠道溃疡和出血。氯吡格雷和质子泵抑制剂均通过细胞色素P450同工酶系统代谢,质子泵抑制剂通过竞争性抑制细胞色素P450同工酶CYP2C19,而降低氯吡格雷的抗血小板活性,增加复发心血管事件的概率。最近的研究发现不同的质子泵抑制剂影响程度不同,泮托拉唑和埃索美拉唑对氯吡格雷作用影响较小,而奥美拉唑、雷贝拉唑和兰索拉唑对氯吡格雷的抗血小板活性抑制作用较大。     

Transmucosal Gastric Leak Induced by Proton Pump Inhibitors

Despite their remarkable safety profile and lack of clinical side effects, proton pump inhibitors (PPIs) induce a transmucosal gastric leak to non-electrolyte probes of various sizes. The ex vivo addition of PPIs to isolated rat gastric corpus increases transmucosal permeability in a dose-dependent manner, which corresponds with PPIs’ dose-dependent inhibition of acid secretion. Upon the addition of omeprazole, lansoprazole, or esomeprazole, a small decrease in transepithelial resistance and the concomitant stimulation of short circuit current was observed. Additionally, transepithelial flux of ¹⁴C-[d]-mannitol (MW 182.17) across the gastric mucosa increased by a mean of 68% immediately following the addition of 200 μM omeprazole. This flux increase was bidirectional. Omeprazole also increased the paracellular permeability to larger radiolabeled probes, including ¹⁴C-sucrose (MW 342.3) and ¹⁴C-polyethylene glycol (MW 4,000) by 118% and 350%, respectively. However, the flux of still larger probes, 10,000 and 70,000 MW dextrans, was not increased. Because PPIs are so widely used and are assumed to be innocuous, this transmucosal gastric leak must be further investigated, as it may carry considerable biomedical implications. Support: AstraZeneca, the Pennsylvania Department of Health, and the Sharpe/Strumia Foundation.     

Potential Costs of Inappropriate Use of Proton Pump Inhibitors

BackgroundProton pump inhibitors (PPIs) are commonly overused in hospitalized patients. The objectives of this study were to determine the extent of their inappropriate initiation in patients with low risk for gastrointestinal hemorrhage, factors associated with their continuation on discharge and potential cost of this trend.MethodsRetrospective examination of patients with low risk for gastrointestinal hemorrhage admitted to a tertiary-care teaching hospital over a 3-month period who received esomeprazole. The following information was collected: age, gender, PPI status (de novo or continued) and admitting diagnoses. Additional information collected from the de novo subgroup included indication for PPI, number of days on PPI and continuation of the drug on discharge. The cost of the medication was obtained from pharmacy records.ResultsFour hundred nine patients were admitted during the study period and 204 (49.9%) received PPI de novo. Among these, 155 patients (76%) had an inappropriate indication for PPI. Of these, 62 (40%) patients were continued on PPI on discharge. Older age was a significant predictor of continuation of PPI at discharge. The estimated cost of the inpatient and outpatient inappropriate use of PPI was $12,272 and $59,272, respectively.ConclusionsPPIs are overused in the majority of hospitalized patients with low risk for gastrointestinal bleeding and this practice gets perpetuated at discharge, especially in older patients. The cost of this phenomenon is alarming.     

A Study on the Efficacy of Proton Pump Inhibitors in Helicobacter pylori-Negative Primary Care Patients with Dyspepsia in Japan

Background/Aims

There have been few studies on the efficacy of proton pump inhibitors and the doses required to treat dyspeptic symptoms observed in clinical practice. The aim of this study was to compare the efficacy of different doses of omeprazole and different administration methods in Helicobacter pylori-negative, dyspeptic patients.

Methods

Patients with chronic upper abdominal symptoms within the previous 3 months were randomly divided into three groups: a daily, omeprazole 20 mg treatment group (OPZ20, n=61); a daily, omeprazole 10 mg treatment group (OPZ10, n=72); and an on-demand omeprazole 20 mg treatment group (on-demand, n=62). After 4 weeks of administration of the drug, symptom improvement rates were evaluated based on the Overall Global Severity score.

Results

The rates of symptom improvement after 4 weeks of treatment were 65.6% (40/61) in the OPZ20 group, 47.2% (34/72) in the OPZ10 group, and 50.0% (31/62) in the on-demand group. The OPZ20 group exhibited a significantly higher improvement rate (p=0.034) than the OPZ10 group. The OPZ20 group had significant improvements in regurgitation, postprandial fullness, vomiting, and bloating compared with the OPZ10 group.

Conclusions

Daily treatment with 20 mg of omeprazole was efficient in treating upper abdominal symptoms. Trial registration: ClinicalTrials.gov, number UMIN000002621.