PPI treatment for gastric ulcer patients in the elderly

Proton pump inhibitor (PPI) is an effective and safe medication for the elderly people for the treatment of peptic ulcer disease. However, some PPIs have been reported that they have metabolic interactions with some drugs. Therefore, drug-interactions should be considered when the PPI is prescribed to the elderly people. The number of NSAIDs ulcer patients is thought to increase along with the increase of those who take NSAIDs in the elderly. Although PPI is indispensable for the prevention of the NSAIDs ulcer, PPI has not obtained authorization for the purpose of prevention in Japan. PPIs are strongly expected to be approved for prevention of NSAIDs ulcer by the Japanese government in the near future.     

Diagnosis of gastric ulcer in the elderly

It is well known that gastric ulcers are most often found at anglus and upper corpus in the elderly. The number of gastric ulcer found at upper corpus hold half of all cases in the elderly patients with bleeding ulcer. Sixty percent of the elderly patients with bleeding ulcer took NSAIDs including low-dose aspirin in authors' hospital. Now it is easy to treat and cure bleeding ulcers due to development of endoscopic hemostasis and antiulcer drugs such as proton pump inhibitor(PPI). However, the elderly patients sometimes result in fatal outcome on bleeding from gastric ulcer. Therefore, it is important to prevent ulcer complications by PPI for the high-risk group such as elderly patients taking NSAIDs.     

Role of Helicobacter pylori eradication in the prevention of peptic ulcer in NSAID users

Helicobacter pylori (H. pylori) and non-steroidal anti-inflammatory drug (NSAID) are independent risk factors for peptic ulcers and ulcer complications and they have additive or synergistic effects. A meta-analysis showed that the OR for the incidence of peptic ulcer was 61.1 in patients infected with H. pylori and also taking NSAID when compared to patients uninfected with H. pylori and not taking NSAID. H. pylori eradication may prevent NSAID-induced ulcers in NSAID naive patients. In patients receiving long-term NSAID, proton pump inhibitor(PPI) is more effective in the prevention of ulcer recurrence and bleeding. However, H. pylori eradication should be considered in patients receiving long -term PPI maintenance treatment to prevent the development of corpus gastritis and gastric atrophy.     

Drug therapy for the elderly patients with gastric ulcer

The number of patients with low dose aspirin or non-steroidal anti-inflammatory drug-related gastric ulcers is steadily increasing. The elderly patients have higher risk to develop gastric ulcers during these treatments. For the treatment and prophylactic therapy of the ulcers in the elderly, the following points should be recognized. (1) The drugs that are prescribed for ulcer diseases may interact with drugs that have been administered for the treatment of the pre-existing diseases. (2) The decreased motor function of gastrointestinal tract frequently observed in the elderly may interfere with the normal absorption of the drugs administered for the treatment of ulcers. (3) The impaired renal function of the elderly may elevate plasma concentration of administered drugs that are expected to be excreted from kidneys. (4) Appropriate guidance for patients is necessary to keep the compliance of drug therapy for prophylactic treatment of low dose aspirin or non-steroidal anti-inflammatory drugs.     

The treatment and prevention for NSAID ulcer in the elderly

Elderly people are more prone to develop NSAID ulcer. Therefore in a society of large elderly population, NSAID ulcer happens to be an important health issue. This iatrogenic disease often leads to complications including gastrointestinal bleeding and perforations that may cause severe morbidity and mortality among the elderly patients. For the treatment and prevention of NSAID ulcer, medication with a feasible minimal dose of NSAID is recommended. When the use NSAID can not be avoided or discontinued, a simultaneous administration of PPI or PG-analogue or a high dose of H2-receptor blocker is required. Proper attention should be paid to NSAID ulcer in the elderly due to its huge negative impacts on quality of life, attributing not only to physical and mental sufferings but also to the burden of medical expenses.     

Helicobacter pylori eradication therapy for gastric ulcer in elderly

Sixty-five-years or older person accounts for 23% of the population in Japan. Hence, Helicobacter pylori (H. pylori) eradication therapy is performed in many elderly patients. Urea breath test and H. pylori stool antigen test for diagnosis of H. pylori infection before and after eradication therapy are recommended from the point of being a noninvasive test and providing accurate diagnosis. H. pylori eradication therapy in Japan consists of the PPI/AMPC/CAM as the first therapy, and PPI/AMPC/MNZ as the second therapy. Eradication therapy rate and adverse effect rate of H. pylori eradication therapy for elderly patients are the same as for young people. It is not necessary to avoid H. pylori eradication therapy merely because of high age in elderly patients. However, it is necessary to be careful regarding drug interactions in patients who are taking multiple drugs.     

Guidelines in the management of gastric ulcer with special reference to elderly patients

Special care must be taken for peptic ulcer disease in the elderly because of more frequent complications such as major bleeding that require hospitalization and may sometimes result in fatal outcome. In addition, elderly patients are more vulnerable to such complications due to accompanying systemic diseases such as cardiovascular, pulmonary or liver diseases. Therefore, it is important to prevent ulcer complications for the high-risk group in the elderly. For the prevention and treatment of ulcer disease in elderly patients, medication with fewer drug-interactions given in simple dose schedule is preferable for better compliance as well as for reducing side effects. Furthermore, consideration on cost-effectiveness of the treatment is increasingly important because of severe burden on the health insurance system. In an attempt to give better and more efficient management strategy for gastric ulcer, evidence-based clinical guideline is being prepared under the support of Japanese Ministry of Health and Welfare. Rational management of ulcer disease in the elderly, however, requires deliberate consideration of each patient status and stringent, inflexible application of the guideline should be avoided.     

Prevention of anti‐inflammatory drug‐induced gastrointestinal damage: Benefits and risks of therapeutic strategies

Patients who take non‐steroidal anti‐inflammatory drugs (NSAIDs) may develop serious gastrointestinal (GI) side effects in both the upper and lower GI tract. Those at risk should be considered for prevention with misoprostol, proton pump inhibitor (PPI) or COX‐2 selective inhibitor (coxib) therapy. A coxib or an NSAID+PPI combination is considered to have comparable GI safety profiles, but evidence from direct comparison is limited. PPIs are effective in the prevention of upper GI events in endoscopy trials and in a few, small, outcome trials in patients at risk. Coxibs have been evaluated in endoscopic ulcer studies and clinical outcome trials, and shown to significantly reduce the risk of upper GI ulcer and complications. Moreover, unlike PPIs, coxibs significantly reduce toxicity in the lower GI tract compared with NSAIDs. Coxibs and possibly some NSAIDs also increase the risk of developing serious cardiovascular events, an effect which may depend on the drug, dose and duration of therapy. It is not known whether concomitant low‐dose aspirin use, which occurs in more than 20% of patients, will reduce the incidence of cardiovascular events, although concomitant aspirin increases the risk of developing serious GI events in patients taking either an NSAID or a coxib. Such patients may require additional PPI co‐therapy. Current prevention strategies with an NSAID+PPI, misoprostol or a coxib must be considered in the individual patient with GI and cardiovascular risk factors. A PPI+coxib is indicated in those at highest risk (e.g. previous ulcer bleeding). PPI therapy must be considered for the treatment and prevention of NSAID‐induced dyspepsia.     

Prevention of anti-inflammatory drug-induced gastrointestinal damage: benefits and risks of therapeutic strategies

Patients who take non-steroidal anti-inflammatory drugs (NSAIDs) may develop serious gastrointestinal (GI) side effects in both the upper and lower GI tract. Those at risk should be considered for prevention with misoprostol, proton pump inhibitor (PPI) or COX-2 selective inhibitor (coxib) therapy. A coxib or an NSAID+PPI combination is considered to have comparable GI safety profiles, but evidence from direct comparison is limited. PPIs are effective in the prevention of upper GI events in endoscopy trials and in a few, small, outcome trials in patients at risk. Coxibs have been evaluated in endoscopic ulcer studies and clinical outcome trials, and shown to significantly reduce the risk of upper GI ulcer and complications. Moreover, unlike PPIs, coxibs significantly reduce toxicity in the lower GI tract compared with NSAIDs. Coxibs and possibly some NSAIDs also increase the risk of developing serious cardiovascular events, an effect which may depend on the drug, dose and duration of therapy. It is not known whether concomitant low-dose aspirin use, which occurs in more than 20% of patients, will reduce the incidence of cardiovascular events, although concomitant aspirin increases the risk of developing serious GI events in patients taking either an NSAID or a coxib. Such patients may require additional PPI co-therapy. Current prevention strategies with an NSAID+PPI, misoprostol or a coxib must be considered in the individual patient with GI and cardiovascular risk factors. A PPI+coxib is indicated in those at highest risk (e.g. previous ulcer bleeding). PPI therapy must be considered for the treatment and prevention of NSAID-induced dyspepsia.     

Prevention and treatment of nonsteroidal anti-inflammatory drug-induced gastric ulcers with proton pump inhibitor

Nonsteroidal anti-inflammatory drug is usefulness, but it was well known that have often complicated gastric ulcers. Proton pump inhibitors (PPI) have gained worldwide popularity for the suppression of gastric acid production. PPI is used and shows most efficacies for gastric ulcer. In this paper we would like to discuss about prevention and treatment of nonsteroidal anti-inflammatory drug-induced gastric ulcers with PPI.     

Current issues of NSAID-induced gastrointestinal ulcer in Japan

Non-steroidal anti-inflammatory drug (NSAID) induced serious gastrointestinal ulcer and its complications are increasing in accord with expanding elderly population in Japan. In particular, bleeding ulcers associated with the use of low-dose aspirin are now the most frequent cause of emergent admission in many institutions. Despite of the evidence-based guidelines to prevent and treat NSAID ulcers, current Japanese health insurance policy does not allow appropriate re-imbursement for internationally acknowledged preventive and therapeutic measures. Recently, however, clinical trials to apply for the prevention of NSAID or low-dose aspirin induced ulcer have begun. In addition, a cyclooxygenase 2 specific inhibitor, celecoxib is introduced after a long process of approval. Taken together, we will be able to prevent and treat these iatrogenic ulcers based not on the dubious medications such as mucosal defense agents but on the drugs such as PPI with scientifically solid evidence.     

Perforated peptic ulcer disease in the elderly

There has been a marked decrease in elective surgery for peptic ulcer disease following introduction of medical therapies including H2-receptor antagonists (H2-RA) and proton pump inhibitors (PPI). By contrast, the incidence of emergency surgery for perforated peptic ulcer(PPU) has remained relatively unchanged, and potentially increased. Conservative treatment of PPU should be selected based on the physical condition of the patient. Open and laparoscopic repair of PPU are made with peritoneal lavage and omental patch closure of perforation. Laparoscopic repair of PPU seems better than open repair for low-risk patients. However, open repair for high-risk patients of PPU should not be delayed, and prognosis is affected primarily by concomitant medical comorbidity in the elderly.     

老年人复合性溃疡102例胃镜与临床疗效分析

目的：探讨老年人复合性溃疡主要临床表现,溃疡好发部位和治疗效果评价。方法：分析研究102例老年人复合性溃疡与对照组的临床表现,溃疡好发部位,治疗效果等临床资料。结果：老年人复合性溃疡具有临床表现不典型,上消化道出血等并发多的特点,滥用NSAIDS或／和H—pylori感染是其发病主要原因,其高位胃溃疡、球后溃疡较对照组高。结论：对老年人有不典型溃疡症状应尽早做胃镜检查,胃镜检查时要注意少见部位的观察,减少漏诊。祛除内因、合理用药。选用高效PPI三联或四联抗HP治疗是提高老年人复合性溃疡治愈的关键。     

Proton pump inhibitor formulary considerations in the acutely ill. Part 1: Pharmacology, pharmacodynamics, and available formulations

OBJECTIVE: To review important proton pump inhibitor (PPI) pharmacologic, pharmacokinetic, and pharmacodynamic principles in acutely ill patients, compare PPI formulation options for patients unable to swallow a tablet or capsule, and provide clinicians with guidance when making hospital formulary decisions with this class of agents. DATA SOURCES: MEDLINE (1966-May 2005) and the Cochrane Library databases were searched using the key words proton pump inhibitor, acid suppression, peptic ulcer disease, gastrointestinal bleeding, stress ulcer prophylaxis, and critical illness. Bibliographies of cited references were reviewed, and a manual search of abstracts from recent gastroenterology, critical care, and surgery scientific meetings was completed. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated, and all information deemed relevant was included for this review. DATA SYNTHESIS: PPIs have become a mainstay for acute acid suppression in hospitalized patients over other therapeutic options. Various commercially available PPI products are available for administration, either enterally or parenterally, to patients unable to swallow a tablet or capsule. Newer oral PPI formulations offer numerous advantages over older products. The results of studies comparing the pharmacokinetics and pharmacodynamics of different PPI dosage forms and routes of administration are among the factors to consider when making formulary decisions. CONCLUSIONS: While the introduction of new PPI products has expanded the therapeutic options for acid suppression in acutely ill patients, a number of unresolved questions remain surrounding the interchangeability of these products, the clinical significance of one PPI formulation over the other, and how oral/enteral PPI therapy should be used as step-down therapy after parenteral PPI therapy.     

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.     

Selection of antibiotics and planning of eradication for H. pylori infection

There is general agreement that H. pylori should be eradicated in patients with peptic ulcers. But the optimal therapeutical regimen to be used still remains a matter for many investigations. An increase in the prevalence of antibiotic-resistant H. pylori strains has been reported recently. The recommended drugs for the eradication in Japan are clarithromycin (CAM) and amoxicillin (AMPC) because metronidazole (MNZ) is anti-parasites drug in Japan. A total of 392 H. pylori strains in the last twelve years were tested for sensitivity to CAM, MNZ, and AMPC. The Primary resistance of H. pylori to CAM, MNZ, and AMPC were found in 10.2%, 26.5%, and 0.3% strains, respectively. The resistant strains to CAM were gradually increasing in the last few years. The eradication therapies which do not increase antibiotics resistant strains after eradication failure were reported. The recommendation for eradication in patients with peptic ulcer disease includes those with bleeding ulcers. The pretreatment with proton pump inhibitors (PPI) does not influence the success of PPI-based triple therapy in eradicating H. pylori.     

79例老年上消化道出血临床分析

目的 :探讨老年上消化道出血的原因和不同制酸剂对出血的治疗效果。方法 :对我院 1998年 1月至2 0 0 4年 6月共 79例老年上消化道出血患者的临床资料进行回顾性分析。男 4 5例 ,女 34例 ,年龄 6 0～ 85岁 ,平均 6 7 6岁 ,患者被随机分为两组分别接受洛赛克和法莫替丁治疗。统计治疗 3天的总有效率和引起出血的原发疾病百分比。结果 :引起出血的原发疾病中 ,胃、十二指肠溃疡 30例 (38 0 %) ,胃黏膜病变 2 8例 (35 4 %) ,门静脉高压症并发食管静脉曲张破裂出血 14例 (17 7%) ,上消化道肿瘤 5例 (6 3%) ,其他 2例 (2 5 %)。洛赛克组总有效率 95 2 %,法莫替丁组总有效率 78 4 %(P <0 0 5 )。结论 :老年上消化道出血主要由胃、十二指肠溃疡和胃黏膜病变引起。质子泵抑制剂洛赛克治疗老年上消化道出血疗效显著。     

Proton pump inhibitor for maintenance therapy of peptic ulcer]

The strategy for peptic ulcer therapy has been changing with the clinical application of the gastric proton pump inhibitor (PPI). In Japan, Miyoshi et al and Takemoto et al reported an earlier reepithelialization of peptic ulcer with omeprazole (OME) or lansoprazole (LAN) than famotidine (FAM). Miyoshi et al also reported that there was no significant difference between OME and FAM in ulcer relapse rate during a one year follow-up period. Therefore, there were two problems. One is application of PPI for prevention of ulcer relapse, and the other is the more accurate diagnosis of ulcer healing. Application of PPI for maintenance therapy is not yet realized in Japan, but, Lauritsen et al had already reported on the efficacy and safety of OME, 20 mg, three days a week and 10 mg, daily in prevention of duodenal ulcer relapse. Reepithelialization (red scar) is already established as a starting point of maintenance therapy, and from Miyake's report, a white scar is believed a favorable (non relapsing) end point.     

Gastric epithelial cell modality and proton pump inhibitor

Proton pump inhibitors (PPIs) are now commonly used for the treatment of acid related diseases such as peptic ulcer and reflux esophagitis. Because of their ability to produce direct inhibition of the proton pump, PPIs provide more sustained increase of the gastric pH than H(2)-receptor (H(2)R) antagonists. Diverse reports have been published on gastric epithelial cell modality associated with PPI treatment both in animal models and clinical settings. The present review summarizes the recent accumulated evidence on gastric epithelial cell modality associated with PPI treatment, including the formation of gastric carcinoid tumors and fundic gland polyps, and the development of gastric mucosal atrophy. Long-term PPI treatment has been reported to cause enlargement of the parietal cells and enterochromaffin-like cells, and to decrease the number of chief cells without affecting A-like cell. Although the development of gastric carcinoid tumors after chronic PPI treatment has been reported in animal studies, no such occurrences have been demonstrated in humans. The effect of PPIs on the formation of fundic gland polyps and the development of atrophic gastritis should be investigated in future studies.