Long-term proton pump inhibitor use and gastrointestinal cancer

Proton pump inhibitors profoundly affect the stomach and have been associated with carcinoid tumors in female rats. There is now sufficient experience with this class of drugs to allow reasonable estimation of their safety in terms of cancer development in humans. Long-term use of proton pump inhibitors is associated with an increase in gastric inflammation and development of atrophy among those with active Helicobacter pylori infections. The actual risk is unknown but is clearly low. However, it can be markedly reduced or eliminated by H. pylori eradication. It is thus recommended that patients being considered for long-term proton pump inhibitor therapy should be tested for H. pylori infection and, if present, this pathogen should be eradicated. Oxyntic cell hyperplasia, glandular dilatations, and fundic gland polyps may develop in patients not infected with H. pylori, but these changes are believed to be reversible and without significant cancer risk.     

Intravenous proton pump inhibitor use in hospital practice

AIM: North American studies suggest that intravenous proton pump inhibitors are used inappropriately in hospital practice, but little is known of prescribing patterns in Europe. Our aim was to examine intravenous proton pump inhibitors prescribing in a single university teaching hospital. METHODS: Observational study of 101 consecutive hospital patients administered intravenous proton pump inhibitors over a 3-month period in a single hospital in Dublin, Ireland. Demographic, clinical, biochemical, haematological, endoscopic and follow-up data were collected and analysed. RESULTS: Sixty-five percent (65 of 101) of the patients had no objective evidence of gastrointestinal blood loss and 85 were haemodynamically stable before treatment. Two patients underwent endoscopic haemostasis before IV administration. The remaining 99 were treated for ulcer prophylaxis, presumed gastrointestinal haemorrhage, unrelated gastrointestinal conditions or for unknown reasons. Relatively senior nonconsultant staff prescribed intravenous therapy in most cases. Only six patients in the study were deemed to have received intravenous therapy for an appropriate indication. CONCLUSIONS: Intravenous proton pump inhibitors use in hospital practice is usually inappropriate. It may be that other valid indications exist within hospital practice, but these might reasonably be evaluated in randomized trials that would assess the risks and costs of intravenous treatments as well as their benefits.     

Safety of the long-term use of proton pump inhibitors

The proton pump inhibitors (PPIs) as a class are remarkably safe and effective for persons with peptic ulcer disorders. Serious adverse events are extremely rare for PPIs, with case reports of interstitial nephritis with omeprazole, hepatitis with omeprazole and lansoprazole, and disputed visual disturbances with pantoprazole and omeprazole. PPI use is associated with the development of fundic gland polyps (FGP); stopping PPIs is associated with regression of FGP. In the absence of Helicobacter pylori infec...     

质子泵和质子泵抑制剂研究进展

胃壁细胞H^ ,K^＋－ATP酶是一种质子泵，能特异性地将H^ 泵入胃腔，形成胃内高酸状态。质子泵抑制剂（PPI）为苯丙咪唑替代物，在体内转化为活性物质－－次磺酰胺，后者与H^ ,K^ －ATP酶共价结合，从而抑制该酶活性，抑制胃酸分泌，是治疗各种酸相关性疾病的首选药物。旧一代PPI如奥美拉唑，兰索拉唑和泮托拉唑的药代动力学个体差异大，与其他药物作用明显，起效时间慢，而新一代PPI如雷贝拉唑、伊索美拉唑起效快，抑酸效果更好，尤其在治疗胃食管反流性疾病（GERD）方面疗效更佳。     

Intravenous proton pump inhibitor therapy: a rationale for use

Proton pump inhibitors (PPIs) are used widely in the management of acid-related disorders and, for the majority of patients, oral therapy is highly effective. Not all patients with acid-related disorders respond completely to standard, once-daily PPI therapy, but most nonresponders will generally respond to an increase in the dose or frequency of PPI therapy. At equivalent doses, oral and intravenous (IV) PPIs produce comparable acid suppression; thus there are very few clinical indications for IV PPI therapy. IV PPIs are an appropriate substitute for oral PPIs, at an equivalent dose, for patients with, for example, gastroesophageal reflux disease, peptic ulceration, or Zollinger-Ellison syndrome, who cannot take oral medication. For patients with nonvariceal, upper gastrointestinal hemorrhage, profound acid suppression (gastric pH . 6.0) optimizes clot stability and reduces the risk of rebleeding; this is achieved most effectively with an initial IV PPI bolus followed by a continuous infusion. High-dose, IV PPI therapy is beneficial and cost-effective in patients who have a high-risk lesion at endoscopy and it should be preceded by effective endoscopic hemostasis if possible. IV PPIs, preoperatively and in the intensive care setting, effectively reduce gastric acidity, but there are no convincing data that this confers any significant clinical benefit compared with other therapeutic strategies.     

如何看待氯吡格雷与质子泵抑制剂的联合用药

随着双重抗血小板治疗(阿司匹林和氯吡格雷)作为预防心血管疾病用药的广泛应用,它所带来的消化道不良反应,尤其是严重消化道出血所致的病死率增加,日益引起人们的关注.质子泵抑制剂(PPI)被推荐作为降低双重抗血小板治疗所带来的消化道风险的主要用药,有临床肯定的预防效果.但随着PPI和双重抗血小板药物的长期联合应用,显示出中等程度的增加心脏负性事件的风险.     

Hemorrhagic polyps formed like fundic gland polyps during long-term proton pump inhibitor administration

We report a rare case of hemorrhagic gastric polyps resulting in anemia during long-term proton pump inhibitor (PPI) administration that endoscopically looked like a fundic gland polyp (FGP). A 44-year-old man presented complaining of anemia and tarry stools. Esophagogastroduodenoscopy (EGD) demonstrated multiple white edematous polyps in the corpus and antrum, which were considered to be FGPs. We attempted endoscopic hemostasis but hemorrhaging increased because of hemorrhagic polyps and vulnerable gastric mucosa. Re-bleeding occurred several times. Polyp resection was performed at 24 polyp sites. We also ceased the administration of PPI. Microscopically, polyps showed characteristics of hyperplasia in the foveolar epithelium, extensions of fundic glands, and edema of the stroma. The proliferation of parietal and chief cells was also observed. Immunohistochemically, aquaporin-4 (AQP4) and KCNQ1-positive parietal cells and dilated mucous glands were found from the basal side to the apical side of the mucosa. These findings were compatible with the development of lesions associated with the long-term administration of PPI. EGD revealed an improvement in the vulnerability of gastric mucosa and the development of polyps, with no further gastric polyps observed 1 year after discharge. Bleeding from polyps resembling FGPs is generally rare, with indications that long-term PPI administration may induce such bleeding.     

Clinical and cost impact of intravenous proton pump inhibitor use in non-ICU patients

AIM:To assess the appropriateness of the indication and route of administration of proton-pump-inhibitors (PPIs) and their associated cost impact. METHODS:Data collection was performed prospec-tively during a 6-mo period on 340 patients who re-ceived omeprazole intravenously during their hospital stay in non-intensive care floors. Updated guidelines were used to assess the appropriateness of the indication and route of administration. RESULTS:Complete data collection was available for 286 patients which wer...     

质子泵抑制剂与钙代谢和骨折的关系

质子泵抑制剂(PPI)是常用于治疗酸相关疾病的药物.PPI长期使用导致骨折的机制尚不清楚.一个可能的机制是PPI导致酸抑制,影响肠道钙的吸收,甲状旁腺素分泌增加,增加骨吸收.对于有骨折高危因素的患者PPI长期高剂量应用增加脊柱或髋骨骨折的危险.PPI应该有合适的适应证,为达到期望的治疗结果而不要超出必要的剂量和疗程.     

Persistent severe hypomagnesemia caused by proton pump inhibitor resolved after laparoscopic fundoplication

Magnesium deficiency can cause a variety of symptoms, including potentially life-threatening complications such as seizures, cardiac arrhythmias and secondary electrolyte disturbances. Hypomagnesemia can be a serious adverse effect to proton pump inhibitor(PPI) therapy, which is worrying due to the widespread use of PPIs. Current evidence suggest that the mechanism of PPI induced hypomagnesemia is impaired intestinal magnesium absorption. In this report, we present the case of a long-term PPI user with persistent hypomagnesemia with severe symptoms at presentation. He was unable to stop PPI treatment because of severe reflux symptoms, and was dependent on weekly intravenous magnesium infusions, until his magnesium levels finally normalized without the need for supplementation after a successful laparoscopic fundoplication.     

Rebuilding trust in proton pump inhibitor therapy

Introduction of proton pump inhibitor (PPI) therapy into clinical practice has revolutionized treatment approach to acid-related diseases. With its clinical success came a widespread use of PPI therapy. Subsequently, several studies found that PPIs were oftentimes overprescribed in primary care and emergency setting, likely attributed to seemingly low side-effect profile and physicians having low threshold to initiate therapy. However, now there is a growing concern over PPI side-effect profile among both patients and providers. We would like to bring more awareness to the currently available guidelines on PPI use, discuss clinical indications for PPIs and the evidence behind the reported side-effects. We hope that increased awareness of proper PPI use will make the initiation or continuation of therapy a well informed and an evidence-based decision between patient and physician. We also hope that discussing evidence behind the reported side-effect profile will help clarify the growing concerns over PPI therapy.     

The clinical importance of proton pump inhibitor pharmacokinetics

Achieving the optimal clinical response for patients with upper gastrointestinal peptic disease is important. This response depends on the pathology treated as well as on the choice of proton pump inhibitor. Here, we identify factors in specific disease therapy and proton pump inhibitor (PPI) pharmacokinetic and pharmacodynamic characteristics that help us achieve this goal. These include differences in PPI bioavailability and acid-suppressive effects. Available data indicate that PPIs appear to have similar potency on a milligram basis, and that omeprazole and lansoprazole are more frequently double dosed than pantoprazole. The lower propensity for double dosing with pantoprazole may also result in lower medication acquisition costs and a reduction in physician visits due to ineffective therapy with the standard dosing of these other agents.     

老年男性中长期使用质子泵抑制剂与骨微结构的相关性研究

探讨老年男性中长期使用质子泵抑制剂（proton pump inhibitors,PPI）与骨密度、骨微结构的相关性。收集2018年6月—2019年1月在江苏省人民医院老年医学科住院且年龄>60岁的男性患者资料进行回顾性研究,按照PPI服用情况,分为对照组（使用PPI时间<1周,50例）和PPI治疗组（服用PPI时间>3个月,30例）。分析患者生化指标、骨密度及骨小梁分数。PPI治疗组的体重、白蛋白水平较对照组降低,促甲状腺素水平较对照组升高（P<0.05）。PPI治疗组和对照组的股骨和腰椎骨密度差异均无统计学意义（P>0.05）,但PPI治疗组的腰椎骨小梁分数较对照组明显下降（P<0.05）。相关性分析发现,骨小梁分数与碱性磷酸酶(r=0.45,P=0.002)、体重指数（r=0.164,P=0.045）呈正相关,与年龄呈负相关(r=-0.291,P=0.025)。多元回归分析显示,骨小梁分数与碱性磷酸酶依然存在正相关性(β=0.437,P=0.023)。使用PPI超过3个月可明显影响骨微结构,骨微结构较骨密度更能反映PPI对骨的不良影响。