Proton pump inhibitors: an update

Since their introduction in the late 1980s, proton pump inhibitors have demonstrated gastric acid suppression superior to that of histamine H2-receptor blockers. Proton pump inhibitors have enabled improved treatment of various acid-peptic disorders, including gastroesophageal reflux disease, peptic ulcer disease, and nonsteroidal antiinflammatory drug-induced gastropathy. Proton pump inhibitors have minimal side effects and few significant drug interactions, and they are generally considered safe for long-term treatment. The proton pump inhibitors omeprazole, lansoprazole, rabeprazole, and the recently approved esomeprazole appear to have similar efficacy.     

Une cause rare d’hémorragie digestive: la polypose gastrique induite par inhibiteur de la pompe à protons au long cours

Proton pump inhibitors are responsible with gastric polyps’ development. Generally asymptomatic, their proliferative and inflammatory properties may trigger a digestive hemorrhage.We report the rare case of a 73-year-old man treated by a long-term proton pump inhibitor for a gastro-esophageal reflux disease. Gastrointestinal bleeding and iron deficiency anemia require a gastroscopy which reveals diffuse glandulocystic and hyperplastic gastric polyps. After a polypectomy therapy failure, an argon plasma coagulation treatment of the most inflammatory polyps is processed. The proton pump inhibitor is stopped and the control gastroscopy done one month later does not find any inflammatory polyps.This case report is a chronic digestive hemorrhage due to gastric polyposis secondary long-term treatment by proton pump inhibitor.This case demonstrates the efficiency, the simplicity of a treatment by argon plasma coagulation compared to treatment by polypectomy. The case also shows the polyposis regression after stopping proton pump inhibitors and introducing a treatment by histamine H2-receptor antagonists.     

Prise en charge des hémorragies digestives aiguës hautes : utilisation des médicaments à visée hémostatique

Pharmacological treatments such as terlipressin or somatostatin and its analogues are effective in controlling variceal bleeding in patients with cirrhosis. They should be started immediately if cirrhosis is clinically diagnosed, without waiting for endoscopic confirmation of portal hypertension signs. They also improve the efficiency of emergency sclerotherapy.Proton pump inhibitors are probably useful to prevent recurrent bleeding in patients with peptic ulcer, but improvement on survival has not yet been shown. The main benefit is observed in case of ulcer with high risk of recurrent bleeding. If proton pump inhibitors are used, they must be administrated at high dosages and intravenously.New trials are required to determine the optimal duration of the haemostatic pharmacological treatment in patients with cirrhosis and to confirm clinical interest in the use of proton pump inhibitors in case of ulcer bleeding.     

Studies on the intracellular pharmacodynamic properties of proton pump inhibitors and the inhibitory mechanism of acid secretion]

In recent studies, proton pump inhibitors, such as omeprazole, were found to be transformed into sulfenamide derivatives in the acid space of isolated parietal cells. It is considered that these sulfenamide derivatives mainly inhibit H+, K(+)-ATPase activity. To clarify the inhibitory mechanism of proton pump inhibitors, we studied the effect on acid secretion of the isolated parietal cells. Proton pump inhibitors inhibited histamine-, carbachol- and gastrin-stimulated 14C-aminopyrine accumulation. Db-cAMP stimulation was also inhibited by these inhibitors. Consequently, it is believed that the origin of H+, K(+)-ATPase was located in the final stage of the acid production.     

Recent effectiveness of proton pump inhibitors for severe reflux esophagitis: the first multicenter prospective study in Japan

Proton pump inhibitors are the first-line treatment for reflux esophagitis. Because severe reflux esophagitis has very low prevalence in Japan, little is known about the effectiveness of proton pump inhibitors in these patients. This prospective multicenter study assessed the effectiveness of proton pump inhibitors for severe reflux esophagitis in Japan. Patients with modified Los Angeles grade C or D reflux esophagitis were treated with daily omeprazole (10 or 20 mg), lansoprazole (15 or 30 mg), or rabeprazole (10, 20, or 40 mg) for 8 weeks. Healing was assessed endoscopically, with questionnaires administered before and after treatment to measure the extent of reflux and dyspepsia symptoms. Factors affecting healing rates, including patient characteristics and endoscopic findings, were analyzed. Of the 115 patients enrolled, 64 with grade C and 19 with grade D reflux esophagitis completed the study. The healing rate was 67.5% (56/83), with 15 of the other 27 patients (55.6%) improving to grade A or B. No patient characteristic or endoscopic comorbidity was significantly associated with healing rate. Reflux and dyspepsia symptoms improved significantly with treatment. The low healing rate suggests the need of endoscopic examination to assess healing of reflux esophagitis at the end of therapy. (UMIN000005271)     

Endoscopic stage classification of peptic ulcer and characterization of the healing process by proton pump inhibitors]

Proton pump inhibitors are highly effective for gastric acid secretion and have been shown to be superior to histamine H2-receptor antagonists. The superiority of proton pump inhibitors over H2-receptor antagonists was more pronounced in duodenal ulcers. Omeprazole reduced the time required by H2-receptor antagonists the healing of duodenal ulcers by 2/3 to 1/2. On the other hand, unusual endoscopic findings, such as shallow white coat or protrusion of the ulcer floor, were noted in the healing stage of gastric ulcers with H2-receptor antagonists. Whereas these findings were rarely seen with conventional drugs. Histologically, the protrusion was made up granulation tissue consisting of cell infiltration and renewed capillaries with or without regenerated epithelia. These unusual endoscopic findings may be observed in the peptic ulcers treated with proton pump inhibitors.     

幽门螺杆菌根除治疗方案比较

目的 对本院门诊患者根除幽门螺杆菌的常规疗法进行比较。方法 选择2002年11月至2004年10月于我院门诊由胃镜活检病理诊断幽门螺杆菌感染行根除治疗且资料完整的患者789例,质子泵抑制剂组376例,铋剂组303例,质子泵抑制剂＋铋剂组110例。其中,国产奥美拉唑组140例,进口奥美拉唑组197例;质子泵抑制剂＋阿莫西林组327例,铋剂＋阿莫西林组270例;质子泵抑制剂＋克拉霉素组174例,铋剂＋克拉霉素组61例;质子泵抑制剂＋甲硝唑组82例,铋剂＋甲硝唑组98例;质子泵抑制剂＋替硝唑组163例,铋剂＋替硝唑组152例。停药1个月以上行13C-呼气试验,比较各根除方案的根除率。结果789例患者的研究结果显示铋剂＋两种抗生素与质子泵抑制剂＋两种抗生素的根除率分别为63.7％和71.0％,两组间差异有统计学意义（P=0．043）;铋剂＋阿莫西林＋另一种抗生素与质子泵抑制剂＋阿莫西林＋另一种抗生素的根除率分别为65．2％和75,8％,两组间差异有统计学意义（P=0.004）。结论 以质子泵抑制剂为基础的根除方案优于以铋剂为基础的方案。     

Efficacy of esomeprazole in patients with acid-peptic disorders.

Esomeprazole (Nexium) is a new proton pump inhibitor that provides more effective acid control compared with other proton pump inhibitors. In patients with gastroesophageal reflux disease, standard doses of esomeprazole maintain intragastric pH above 4 for significantly longer periods compared with standard doses of other proton pump inhibitors after 5 days of treatment. Esomeprazole is approved for the treatment of symptomatic gastroesophageal reflux disease, the healing of erosive esophagitis, and maintenance of healing. In clinical trials, esomeprazole 40 mg once daily for up to 8 weeks provided higher rates of healing of erosive esophagitis and a greater proportion of patients with sustained resolution of heartburn, than either omeprazole 20 mg or lansoprazole 30 mg once daily. For the maintenance of healing, esomeprazole 20 mg once daily provided significantly higher rates of maintained healing of erosive esophagitis after 6 months of treatment compared with lansoprazole 15 mg once daily. Esomeprazole is also approved for use as part of a triple-drug therapy regimen in combination with amoxicillin and clarithromycin for the eradication of Helicobacter pylori in patients with duodenal ulcer disease. The side effect profile of esomeprazole is similar to that of omeprazole. Many patients with acid-related disorders may benefit from the more rapid symptom relief, higher rates of healing of erosive esophagitis, and improved maintenance of healing that can be achieved with esomeprazole.     

Proton pump inhibitor-induced rhabdomyolysis and hyponatremic delirium

Many consider proton pump inhibitors (PPIs) to be devoid of adverse effects; however, PPIs can cause serious adverse effects. We report on the case of an emergency department patient with omeprazole-induced hyponatremic delirium and rhabdomyolysis. Proton pump inhibitors are initially overlooked as a cause of hyponatremia and myopathy in the emergency department, as with our case. This case is also unique because no publication has reported on both hyponatremia and severe myopathy after PPI therapy. The patient recovered completely after cessation of omeprazole and initiation of intravenous saline hydration and desmopressin infusion.     

Reducing adverse effects of proton pump inhibitors

Proton pump inhibitors effectively treat gastroesophageal reflux disease, erosive esophagitis, duodenal ulcers, and pathologic hypersecretory conditions. Proton pump inhibitors cause few adverse effects with short-term use; however, long-term use has been scrutinized for appropriateness, drug-drug interactions, and the potential for adverse effects (e.g., hip fractures, cardiac events, iron deficiency, Clostridium difficile infection, pneumonia). Adults 65 years and older are more vulnerable to these adverse effects because of the higher prevalence of chronic diseases in this population. Proton pump inhibitors administered for stress ulcer prophylaxis should be discontinued after the patient is discharged from the intensive care unit unless other indications exist.     

Rabeprazole: the role of proton pump inhibitors in Helicobacter pylori eradication

Proton pump inhibitors have become one of the cornerstones in the treatment of Helicobacter pylori infection. Rabeprazole (Pariet) is a substituted benzimidazole proton pump inhibitor with potent gastric acid suppression properties. Its high acid-base dissociation constant allows activation over a broader pH range, resulting in quick, irreversible binding to the H+/K+-ATPase pump, and a more rapid onset of action compared with omeprazole, lansoprazole and pantoprazole. Unlike other proton pump inhibitors, the metabolism of rabeprazole is primarily via a nonenzymatic reduction to the thioether derivative, and the cytochrome P450 isoenzyme 2C19 is only partly involved in its metabolism. The effect of genetic polymorphism in cytochrome P450 isoenzyme 2C19 on the pharmacokinetics and pharmacodynamics of rabeprazole is therefore limited. In humans, once-daily dosing of 5-40 mg of rabeprazole inhibits gastric acid secretion in a dose-dependent manner. In vitro studies have shown that rabeprazole possesses more potent antibacterial properties against the growth of H. pylori than other proton pump inhibitors. Furthermore, its thioether derivative has more potent inhibitory in vitro activity against the growth and motility of clarithromycin-resistant H. pylori than other proton pump inhibitors or commonly used antimicrobials. Despite these inherent favorable characteristics of rabeprazole, randomized controlled trials have largely shown equivalence amongst proton pump inhibitors when used with two antibiotics in the eradication of H. pylori, with cure rates of 75-89% on an intent-to-treat basis. However, rabeprazole appears to consistently achieve such comparable eradication rates even when used at reduced doses (10 mg twice daily) as part of clarithromycin-based triple therapy.     

Rational prescribing: practice audit and drug switch in dyspepsia management

Growing demands on limited healthcare resources and budgets have led to an increased focus on the costs associated with the purchase of drugs. Consequently, approaches to treatment for various disease states are now dictated not only by issues such as best medical benefits, but also by the cost of the drug that is used. As such, drug-switching strategies have become increasingly common practice where, although the clinical benefits offered by the various medications for a specific condition may be similar, the cost differentials are notable. Application of this switch procedure has recently been assessed in the context of the management of acid-related gastrointestinal disorders and has demonstrated that switching patients to therapy with the proton pump inhibitor lansoprazole from H2-receptor antagonists or other proton pump inhibitors not only offers therapeutic advantages but also has important financial implications in general practice with regard to cost savings.     

Antireflux surgery in the proton pump inhibitor era

Although proton pump inhibitors (PPIs) are now the first-line treatment for gastroesophageal reflux disease (GERD), surgery still has several specific indications. We review the current treatment of GERD and discuss how antireflux surgery fits into the overall scheme.     

An overview of the pharmacology, efficacy, safety and cost-effectiveness of lansoprazole

Lansoprazole is a proton pump inhibitor that reduces gastric acid secretion in a dose-dependent manner via inhibition of H+/K+-adenosine triphosphatase in gastric parietal cells. It also exhibits antibacterial activity against Helicobacter pylori in vitro. During almost 10 years of clinical use, lansoprazole has proved effective and well tolerated in a wide range of acid-related disorders, including gastro-oesophageal reflux disease (GORD), duodenal ulcers, gastric ulcers, non-steroidal anti-inflammatory drug-related ulcers, as well as non-ulcer dyspepsia and acid hypersecretion. It is also used, in combination with antibiotics, for H. pylori eradication. In the above indications, lansoprazole has generally proved to be superior to the histamine H2-receptor antagonists, and is at least as effective as the other currently available proton pump inhibitors. This review aims to evaluate the pharmacology, efficacy, safety and cost-effectiveness of lansoprazole in acid-related disorders, with particular emphasis on its use in GORD and H. pylori eradication regimens.     

Suppression of gastric acid production by proton pump inhibitor treatment facilitates colonization of the large intestine by vancomycin-resistant Enterococcus spp. and Klebsiella pneumoniae in clindamycin-treated mice

Proton pump inhibitor treatment of clindamycin-treated mice elevated the gastric pH and facilitated the establishment of colonization of the large intestine by vancomycin-resistant Enterococcus spp. (75 to 80%, versus 20 to 25% for saline-treated controls) and Klebsiella pneumoniae (90%, versus 30% for saline-treated controls). These findings demonstrate a mechanism by which proton pump inhibitor therapy could contribute to the dissemination of nosocomial pathogens.     

Possible mechanisms for (H+ + K+)-ATPase inhibition by proton pump inhibitors, omeprazole, lansoprazole and SCH 28080]

Proton pump inhibitors are classified into two distinct types, and the mechanisms are reviewed. Substituted benzimidazole such as omeprazole and lansorrazole, inhibit (H+ + K+)-ATPase by reacting with SH groups of enzyme after the drugs are transformed into their active forms in the acidic environment of the intracellular canaliculi of parietal cells. This type of enzyme inhibition results in potent and long-lasting inhibition of gastric acid secretion. On the other hand, substituted imidazo pyridines, such as SCH 28080, inhibit (H+ + K+)-ATPase by competing with K+. This inhibition is reversible and the antisecretory effect is short-lived. Recent studies on DNA cloning and sequencing for (H+ + K+)-ATPase have led to a better understanding of enzyme structure and also the sites of action of the proton pump inhibitors.     

H2受体拮抗剂与质子泵抑制剂在缓解急性乙醇中毒致胃黏膜损伤中的时效性比较

目的探讨H2受体拮抗剂和质子泵抑制剂(PPI)缓解急性胃黏膜损伤的时效性研究。方法对2008年1月-2010年1月在急诊科就诊的98例急性乙醇中毒后胃黏膜损伤患者,随机分为对照组50例,治疗组48例。常规给予休息、保暖,补液,维持水、电解质、酸碱平衡,维持循环功能等治疗基础上,对照组给予H2受体拮抗剂治疗,治疗组给予PPI治疗。通过观察急性胃黏膜损伤患者上消化道症状及体征,记录不同饮酒及饮酒量,并根据患者就诊时间及不同饮酒组治疗后上消化道症状完全缓解时间进行比较。结果治疗组上消化道症状缓解所需时间与对照组比较差异有统计学意义(P<0.001),不同饮酒组上消化道症状缓解时间上差异有统计学意义(P=0.000)。结论 PPI在缓解急性乙醇中毒所致胃黏膜损伤的时效上更明显,具有临床价值。     

Gastroesophageal reflux disease: current treatment approaches.

Gastroesophageal reflux disease is a common, usually lifelong, disorder resulting from chronic abnormal exposure of the lower esophagus to gastric contents. Motor dysfunction of the lower esophageal sphincter is the primary cause of this disease. At this writing, no medical therapies can completely resolve abnormal lower esophageal sphincter function; therefore, the treatment of gastroesophageal reflux disease centers on suppression of intragastric acid secretion. Available acid-suppressant medications include proton pump inhibitors, H2-receptor antagonists, and antacids. Of these, the proton pump inhibitors are recognized generally as the mainstays of both short-term and long-term therapy for gastroesophageal reflux disease. All have a low incidence of side effects and are well tolerated by most patients. Five proton pump inhibitors are available currently for patients with gastroesophageal reflux disease. Of these, esomeprazole has shown greater efficacy in controlling intragastric acidity than the others. For patients with erosive esophagitis, esomeprazole has demonstrated higher healing rates and more rapid sustained resolution of heartburn than omeprazole or lansoprazole after up to 8 weeks of once-daily treatment. Because new therapies for gastroesophageal reflux disease are highly effective, patients can be reassured that their disease will be well controlled and their symptoms resolved with a safe and appropriate treatment.     

Suboptimal response to ferrous sulfate in iron-deficient patients taking omeprazole

Iron deficiency anemia is commonly encountered in outpatient practice. Gastric acid is one of the important factors for optimum absorption of iron. Proton pump inhibitors are very commonly prescribed medications. One of the debated effects of proton pump inhibitors is on oral iron absorption. Their effect on absorption of oral iron supplementation in iron-deficient patients has not been studied. At the Cooper Hematology Outpatient office, we reviewed charts of iron-deficient anemic patients who were on omeprazole for the last 4 years. Fifty patients having no apparent ongoing blood loss, having other causes of anemia especially that of chronic diseases ruled out, and on omeprazole while starting ferrous sulfate therapy for iron deficiency were selected for chart review. The iron-study results at the start of oral ferrous sulfate therapy and at 3 months follow-up were compared to evaluate the response of ferrous sulfate. The mean hemoglobin change was 0.8 ± 1.2 g/L. The mean change in ferrtin values was 10.2 ± 7.8 μg/L. Only 16% of the patients had a normal response to hemoglobin levels (rise of >2 g/dL), and only 40% had a normal response to ferritin levels (rise of >20 μg/dL). The average age of patients having a suboptimal response to both hemoglobin and ferritin was significantly higher compared with that of the patients with an optimal response. Omeprazole and possibly all proton pump inhibitors decrease the absorption of oral iron supplementation. Iron-deficient patients taking proton pump inhibitors may have to be treated with high dose iron therapy for a longer duration or with intravenous iron therapy.     

Proton pump inhibitors: update on their role in acid-related gastrointestinal diseases

Gastric acid is pathogenic in many gastrointestinal disorders, such as gastroesophageal reflux disease and peptic ulcer disease. Proton pump inhibitors (PPIs) are the antisecretory drugs of choice for serious acid-related conditions. Ample recent data exist to explicate virtually every aspect of the clinical management of acid-peptic disorders with PPIs. Although all PPIs are effective, there are some differences in their clinical performance, particularly in terms of the degree and speed of gastric acid suppression. Rapid onset of acid suppression may be particularly relevant to newer approaches, such as 'on-demand' or intermittent therapy for non-erosive reflux disease and shorter regimens for Helicobacter pylori eradication. New data, in addition, highlight differences in PPI metabolism that may both affect efficacy and predispose patients to drug-drug interactions. PPI selection should involve the awareness of these issues.