Overuse of proton pump inhibitors

BACKGROUND: There have been concerns raised about the potential adverse effects of proton pump inhibitors, especially with long-term use. In particular, their potent action can suppress the features and delay the diagnosis of gastric cancer, while prolonged exposure may hasten the development of gastric carcinoids. AIM: To examine the use of proton pump inhibitors in patients at the major teaching hospital in Tasmania, Australia, principally to determine the appropriateness of the therapy according to published guidelines. METHODS: A retrospective review of the medical records of all patients prescribed any of the proton pump inhibitors at the hospital over a 7-month period, was performed. An extensive range of demographic and clinical variables was recorded for each patient. The patients were also asked a series of questions during their hospitalization to extract some of the relevant information - in particular, if and when they had undergone endoscopy. RESULTS: The 200 patients (52% males) had a mean age of 69 +/- 16.4 years. The most common indications for using proton pump inhibitors were acute gastrointestinal bleeding (20.9%), severe refractory ulcerating oesophagitis (17.3%), mild/moderate oesophageal reflux (17.3%) and refractory peptic ulcer (11.7%). A large number of patients were using a proton pump inhibitor for 'other' indications (39.6%). The prescribing of proton pump inhibitors satisfied the approved indications, as outlined in the Australian Schedule of Pharmaceutical Benefits, in only 37.1% of cases. Endoscopy had been performed in 54.1% of patients prior to commencing therapy with a proton pump inhibitor and within the next 7 days in another 12.8% of patients. Only 59% of patients had previously been treated with an H2-receptor antagonist before commencing therapy with a proton pump inhibitor. Even worse, only 58.5% of patients had used an H2-receptor antagonist before a proton pump inhibitor for mild/moderate oesophagitis. The median duration of proton pump inhibitor therapy for patients admitted to the hospital and already receiving one of the drugs was 450 days. Over half of the patients were being concurrently treated with other drugs which are known to cause or exacerbate gastro-oesophageal disease, and 18% were smokers. CONCLUSION: Whereas the proton pump inhibitors are undoubtedly effective agents, studies of their prescribing in practice consistently suggest over-use prior to endoscopy, use in patients who do not fit the approved criteria, and prescribing for indications in which 'less powerful' agents should have been sufficiently effective for the patient's symptoms. This poses economic and safety concerns, particularly in light of the suggestion that these drugs could delay the diagnosis of gastric cancer.     

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.     

Meta-analysis of proton pump inhibitors in treatment of bleeding peptic ulcers.

OBJECTIVE: To evaluate the efficacy of proton pump inhibitors (PPIs) compared with placebo and histamine receptor antagonists (H2RAs) for reducing the incidence of rebleeding, surgery, and death in acute gastrointestinal bleeding (GIB) associated with peptic ulcer disease. DATA SOURCES: A systematic search of the English-language literature was performed using MEDLINE, EMBASE, and Pre-MEDLINE (from 1966 to September 2000) and a manual search of references. STUDY SELECTION: Randomized, controlled trials evaluating any PPI for acute GIB in adults with the end points of rebleeding, surgery of death. DATA SYNTHESIS: Nine trials (1829 pts.) were included. The relative odds of rebleeding indicated a 50% reduction in the PPI-treated group (OR 0.50, 95% CI 0.33 to 0.77; p = 0.002, NNTB 9; 95% CI NNTB 6 to 13). The relative odds of surgery indicated a 53% reduction in the PPI-treated group (OR 0.47, 95% CI 0.29 to 0.77; p = 0.003; NNTB 17, 95% CI 12 to 35). The relative odds for mortality indicated a nonsignificant 8% decrease in the odds of death in the PPI-treated group (OR 0.92, 95% CI 0.46 to 1.83, p = 0.81; NNTB 323, 95% CI NNTB 47 to infinity to NNTH 33). CONCLUSIONS: PPIs are superior to H2RAs and placebo in preventing rebleeding and the need for surgery in patients with GIB, although they do not appear to reduce mortality.     

Lessons from two cases of anaphylaxis to proton pump inhibitors

What is known and Objective: Proton pump inhibitors (PPIs), which are widely used for the treatment of peptic ulcers and gastroesophageal diseases, reduce both basal and stimulated gastric acid secretion by inhibiting the parietal cell enzyme H(+)‐K(+)‐adenosine triphosphatase. There have been several reports of hypersensitivity reactions to PPIs but anaphylaxis is very rare. We report on two cases of anaphylaxis to PPIs. Case summary: Our two interesting and instructive cases of anaphylaxis to PPIs relate to the orally disintegrating form of lansoprazole and omeprazole. The first patient had taken esomeprazole 20 mg/day for 1 month without any side effects before experiencing anaphylaxis to lansoprazole. To our knowledge, this is the first report of anaphylaxis to the orally disintegrating form of lansoprazole. In the second case, the patient was misdiagnosed with penicillin allergy which she suffered from earlier. What is new and Conclusion: Physicians need to be more aware of the possibility of hypersensitivity to PPIs.     

Clinical effect of proton pump inhibitors on reflux esophagitis]

The clinical efficacy of proton pump inhibitors (PPI, omeprazole 20 mg or lansoprazole 30 mg), once daily, after breakfast, was studied in patients with erosive/ulcerative reflux esophagitis. The following results were obtained. 1) Twenty-four hour esophageal pH monitoring was performed before treatment and on 7th day of PPI medications. Omeprazole reduced the percent time pH less than 4 from 29.1 to 1.2 and lansoprazole from 68.0 to 2.4. 2) The cumulative disappearance rate of overall symptom was 52% after 1 week and 62% after 2 weeks with omeprazole these were 66% and 91%, and with lansoprazole respectively 3) The endoscopic healing rate was 63% was after 2 weeks and 76% after 4 weeks with omeprazole medication, and 76% and 97% respectively with lansoprazole. These results indicate that PPI medication inhibits the acid reflux almost completely and is a more useful therapeutic agent for GERD than H2-antagonists.     

长期使用质子泵抑制剂对肠道菌群的影响

目的观察胃食管反流病和消化性溃疡患者长期使用质子泵抑制剂治疗后肠道菌群变化。方法选取胃食管反流病及消化性溃疡患者60例（观察组）,口服奥美拉唑,20mg,每日2次,疗程8周;选取健康志愿者20例（对照组）;利用实时荧光定量聚合酶链反应（PCR）检测观察组患者服药前、服药后4周、8周及对照组健康者清晨粪便中大肠杆菌、肠球菌属、双歧杆菌属及乳酸杆菌属数量,并对各目标菌群数量进行比较分析。结果与对照组相比,观察组患者服药前及服药后4周粪便中4种目标菌群无明显变化（P〉0.05）,服药后8周,粪便中大肠杆菌（4.81±0.77）lonN/g及肠球菌属（5.24±0.63）lonN/g仍无显著变化（P〉0.05）,但双歧杆菌属（8.82±0.91）lonN/g及乳酸杆菌属（6.99±0.69）lonN/g明显减少（P〈0.05）。结论长期服用质子泵抑制剂后可致肠道双歧杆菌属及乳酸杆菌属数量明显下降,使肠道生物屏障受损,增加了肠源性感染风险。     

Factors affecting efficacy of proton pump inhibitors in NAID-induced gastric ulcers

AIM: To determine factors which may influence efficacy of therapy with proton pump inhibitors (PPI) in gastric ulcer (GU) induced by nonsteroid anti-inflammatory drugs (NAID). MATERIAL AND METHODS: Two groups of GU patients treated with PPI in 2001-2005 were identified: 41 cases when ulcer healing was not achieved for 3 weeks and more (study group) and 218 cases treated for this time successfully (controls). The groups did not differ significantly by gender (females 84.6 and 78.6%) and age (59.2 +/- 16.8 and 58.7 +/- 12.4 years). RESULTS: The patients of the study group had ulcers of 10 mm and more in size much more frequently than the controls (OR 12.5, CI 5.8-26). Also, rheumatoid arthritis (RA), ulcer history, intake of glucocorticosteroids, cytotoxic drugs, ineffective preventive treatment with PPI (OR 5.3, CI 3.4-8.4; OR 3.1, CI 1.5-6.0; OR 3.1, CI 1.6-6.0; OR 3.4, CI 1.7-6.7; OR 2.7, CI 1.3-5.6, respectively) were recorded in the study group more often. Helicobacter pylori was absent in 75.6% patients of the study group but these findings can not be compared with those in the controls as the majority of them had not been examined for gastric H. pylori. CONCLUSION: Large ulcer, RA, ulcer history, treatment with GCS, cytotoxic drugs, PPI and, probably, the absence of H. pylori decrease efficacy of PPI in gastric ulcer induced by NAID.     

质子泵抑制剂和结肠息肉相关性研究

目的探讨质子泵抑制剂(PPIs)和结肠息肉形成两者间的关系。方法将本院结肠息肉的患者设为病例组(154例),肠炎及未见异常者设为对照组(98例)。调查所有入组人员饮食及生活习惯、PPIs服用等情况,并测定血胃泌素水平。各因素先进行单因素分析,有统计学意义者进一步行多因素Logistic回归。结果单因素分析提示PPIs与结肠息肉的发生及生长部位有关(P0.05),结肠息肉组中服用PPIs的患者与未服用PPIs患者的胃泌素水平有显著差异[(115±19.4)ng/Lvs(66.4±8.4)ng/L],P0.001),但病例组与对照组两者间胃泌素水平无明显差异(P=0.191,P0.05),且进一步多因素Logistic分析提示PPIs变量无统计学意义(P=0.081,P0.05)。结论本研究无法证实与结肠息肉形成是否存在必然相关性,PPIs与结肠息肉之间是否存在关联尚待进一步研究。     

Use of proton pump inhibitors in the treatment of gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is a wide spread disease characterized by distinct clinical polymorphism manifesting with various symptoms and/or inflammatory changes of a distal portion of the esophagus. Current first-line therapy in GERD consists in administration of proton pump inhibitors (PPI) which promote faster relief of the symptoms and healing of erosive-ulcerous lesions of esophageal mucosa in GERD patients. Clinical efficacy of standard and novel PPI is compared. Wide use of PPI and their long-term courses require further study of PPI side effects which now lack attention from the clinical researchers.     

Evaluation of the effect of proton pump inhibitors on stomal ulcer]

Four reports on proton pump inhibitors related to the clinical effects on stomal ulcer were reviewed. Two reports were on omeprazole and the other two on lansoprazole, carried out in the pre-marketing stage. They are compared with two reports on H2-receptor antagonists (famotidine and ranitidine), which were also done in the pre-marketing stage. It appears that the proton pump inhibitors bring more rapid ulcer healing than H2-receptor antagonists without severe side effects, and there seems to be no difference in clinical effect between omeprazole and lansoprazole.     

Diagnosis and treatment of gastrinoma in the era of proton pump inhibitors

The Zollinger-Ellison syndrome is characterized pathophysiologically by a significant hypergastrinemia derived from a gastrin-secreting neuroendocrine tumor with a primary location in the pancreas or duodenum. Chronic hypergastrinemia in turn triggers gastric acid hypersecretion yielding in chronic or recurrent or refractory peptic ulcer disease and/or chronic diarrhea. One half of patients with ZES will have distant metastases in the liver by the time the diagnosis is established and one half of all patients with ZES will experience chronic diarrhea as chief complaint rather than peptic ulcer-related symptoms and signs. Gastrinomas have been reported to either manifest sporadically or to occur in conjunction with the genetic background of the MEN-I syndrome. Diagnosis is based on the patients history which is typically characterized by recurrent episodes of peptic ulcer disease or by severe reflux esophagitis and/or diarrhea or by acid-related symptoms which fail to respond to standard treatment regimens. Upper gastrointestinal tract endoscopy will provide evidence for peptic ulcer disease in anatomical regions located aborally the duodenal bulb within the descending part of the duodenum or even farther distally within the jejunum. Peptic ulcers frequently occur in groups indicating some substantial acid hypersecretion. A gastric pH > 2 is mutually exclusive for ZES. Increased serum gastrin levels confirm the diagnosis biochemically. Gastrin secretion can be determined in the basal state or following stimulation with secretin or calcium. High sensitivity and specificity for the diagnosis of ZES is provided by determining the ratio of basal versus pentagastrin-stimulated gastric acid secretion: The ratio of BAO / MAO > 0.6 is highly specific for gastrinoma. To localize the gastrin-secreting tumor computer-assisted tomography, endoscopic ultrasound, and somatostatin receptor scintigraphy provide useful help but most recently, endoscopic ultrasound with high resolution transducers appear to improve preoperative site localization. If modern imaging techniques fail to elucidate the site of the tumor, intraoperative diaphany may help to detect gastrinomas within the duodenal wall. Definitive treatment will only be achieved by total surgical resection of the gastrin-producing tumor in the pancreas or duodenum including dissection of the regional lymph nodes. Control of symptoms will have to be achieved by administration of highly potent proton pump inhibitors in up to 2-3-fold increased standard doses to inhibit gastric acid hypersecretion. Elevation of gastric pH > 4 will be the therapeutic target to protect the mucosa of the upper gastrointestinal tract. Basal acid output should be reduced to less than 10 mEq H(+) per hour which requires administration of highly potent proton pump inhibitors with a recommended starting dose of 60 mg omeprazole equivalents per day.