Proton Pump Inhibitors: Effective First-Line Treatment for Management of Dyspepsia

The aim of this study was to evaluate the reasons for trial exclusion among dyspeptic patients and estimate the proportion that may have benefited from proton pump inhibitor (PPI) therapy. Stringent inclusion criteria for enrollment in two multicenter functional dyspepsia trials included dyspepsia (predominant persistent/recurrent upper abdominal discomfort [UAD] during the prior 3 months) of at least moderate intensity during ≥30% of days during the prior 2 to 3 weeks. Exclusion criteria were mild/infrequent UAD; heartburn and UAD of equal frequency; predominant heartburn with UAD; endoscopic evidence of erosive esophagitis or Barrett’s or gastric and/or duodenal erosions (>5) or ulcers; irritable bowel syndrome (IBS); other gastrointestinal diagnoses; or other “non-categorized” disorders. Of 2,588 screened patients, 1,667 were excluded. Excluded patients by category had mild/infrequent UAD (12.5%, n=324), heartburn and UAD of equal frequency (1.1%, n=29), predominant heartburn with UAD (11.6%, n=300), endoscopic evidence of erosive esophagitis or Barrett's (6.2%, n=160), gastric and/or duodenal erosions (1.4%, n=36), gastric and/or duodenal ulcers (2.0%, n=53), IBS (7%, n=180), “other” gastrointestinal diagnoses (2.8%, n=73), or other “non-categorized” disorders (19.8%, n=512). Fifty-four percent of patients (902/1,667) had symptoms/diagnoses that would be expected to improve with PPI therapy. Individuals with IBS, “other,” or “non-categorized” disorders were considered to have symptoms unlikely to respond to PPI treatment. Empiric PPI treatment would be expected to provide symptom relief to the majority of dyspepsia sufferer who present in clinical practice. PPIs represent the best currently available therapy for acid-related disorders and should be considered the first-line management approach in patients with uninvestigated dyspepsia.     

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.     

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.     

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.     

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。     

质子泵抑制剂奥美拉唑对氯吡格雷抗血小板效应的影响

目的研究和探讨治疗剂量下奥美拉唑对氯吡格雷抗小板活性的影响。方法选择2009年12月—2011年1月入住内蒙古自治区人民医院心血管内科的急性冠脉综合征(ACS)病人与择期行经皮冠状动脉介入(PCI)治疗病人72例,记录基本情况,并随机分成奥美拉唑与氯吡格雷联合组(治疗组)与单用氯吡格雷组(对照组),通过流式细胞仪分别测定服药前和服药后第7天血小板P选择素阳性率。结果两组治疗前后血小板P选择素阳性率差异有统计学意义(P=0.0001)。两组间治疗前比较血小板P选择素阳性率差异无统计学意义(P=0.57),治疗后比较差异仍无统计学意义(P=0.82)。结论治疗剂量奥美拉唑短期内对氯吡格雷的抗血小板疗效无明显影响。