Therapy For Peptic Ulcer Disease Research Articles

The end of the era of maintenance therapy for peptic ulcer disease?

The end of the era of maintenance therapy for peptic ulcer disease?

A gastroenterological list for the millennium.

To determine the 10 most significant advances in gastroenterology during this century as we approach the millennium, the authors polled 50 distinguished active clinicians and leading researchers in the field, including workers in liver disease and the pathology of the gut and its associated glands. Forty-five persons (90%) responded and listed 58 different items. These were then organized into four groups: group A, with 10 categories that received between 42 and 11 votes; group B, with 10 categories that received between 10 and 3 votes; group C, with 3 items receiving 2 votes each; and group D, with the remaining 14 items receiving 1 vote each. The respondents did not indicate their choices in rank order. The top 10 leading choices (group A, containing between 42 and 11 votes) included Helicobacter pylori, fiberoptic endoscopy, gastrointestinal imaging by radiograph and computed tomographic scan, Australia antigen including vaccines for hepatitis A and B, the molecular basis of colon cancer, liver transplantation, laparoscopic-assisted surgery, therapy for peptic ulcer disease including H2-receptor antagonists and proton pump inhibitors, the discovery of gastrointestinal hormones beginning with secretin, and lastly the discovery of the role for gluten in celiac disease.

Helicobacter pylori treatment instead of maintenance therapy for peptic ulcer disease: the effectiveness of case-finding in general practice.

Maintenance therapy with acid-inhibiting medication is common in general practice. Since the eradication of Helicobacter pylori has become the treatment of choice for peptic ulcer disease, H. pylori treatment could replace maintenance therapy in patients with an ulcer history. To determine the effectiveness of a full peptic ulcer disease history case-finding strategy, together with subsequent H. pylori testing and treatment, in discontinuing maintenance therapy. Patients were included from seven general practices, who had been using acid-inhibiting medication for more than 3 months in the period May 1996-May 1997. Patients with a history of proven peptic ulcer disease were tested, and treated with proton pump inhibitor-triple therapy if positive. Maintenance therapy was discontinued and restart within 12 months was monitored. Long-term acid suppression was used by 2.8% of the practice-populations. A peptic ulcer disease history was found in 18% of the patients, 73% of whom were offered the 'H. pylori test and treat' alternative. The majority responded: 92% of the H. pylori-infected patients were treated, 78% of whom successfully discontinued long-term medication. Implementing an 'H. pylori test and treat' strategy enabled one-third of the patients with a peptic ulcer disease history to stop maintenance therapy successfully. The strategy contributes to reduction of long-term drug use, but compliance needs improvement.

Pantoprazole: a new proton pump inhibitor in the management of upper gastrointestinal disease.

Pantoprazole, the third proton pump inhibitor (PPI) to become available, has been extensively investigated. Pantoprazole inhibits acid more powerfully than histamine H(2) receptor antagonists (H(2)RAs) and omperazole 20 mg and raises median 24-h gastric pH from about 1.5 to 3-4 in healthy volunteers and in duodenal ulcer patients to above 5. Results from studies have confirmed that pantoprazole is superior to H(2)RAs in speed of healing and symptom relief in patients with peptic ulcer. In patients with duodenal ulcer pantoprazole was as effective as omperazole 20 mg and in patients with gastric ulcer pantoprazole was statistically superior to omeprazole 20 mg after 4 weeks. In triple combination therapy of peptic ulcer disease, the mean eradication rate of Helicobacter pylori in data pooled from 32 pantoprazole-based studies was 86% and compliance with treatment was about 90%. Results pooled from 5 large clinical trials of gastroesophageal reflux disease showed healing rates significantly superior to those achieved with H(2)RAs and similar to those of other PPIs at 4 and 8 weeks. Symptom relief was more rapid with pantoprazole and maintenance treatment kept the majority of patients in remission; relapse rates at 1 year were 25-28% on 20 mg daily and 6-22% on 40 mg daily. Maintenance treatment with pantoprazole 40 mg has been shown to keep most patients with aggressive or refractory ulcer and reflux disease in remission for up to 3 years. Pantoprazole was also effective in the management of patients with Zollinger-Ellison syndrome. In volunteers given aspirin, pantoprazole 40 mg proved significantly superior to ranitidine and placebo in preventing the development of mucosal damage and was significantly better than placebo in preventing gastric ulcer and duodenal ulcer in arthritic patients on nonsteroidal antiinflammatory drugs. Clinical trials, postmarketing surveillance and long-term studies have confirmed that pantoprazole is effective and safe for the short- and long-term management of peptic ulcer and reflux disease, with side effects similar in incidence and type to those of H(2)RAs.

The pharmacoeconomic impact of antimicrobial therapy for peptic ulcer disease in a large urban jail.

To determine the pharmacoeconomic impact of antimicrobial treatment of peptic ulcer disease (PUD) in a large urban jail. Retrospective comparison of PUD-related pharmacy and laboratory expenditures over a 2-year period before and after the institution of a PUD treatment protocol with the priority of Helicobacter pylori eradication for inmates in Rikers Island Correctional Facility. After the protocol was adopted, total pharmacy-related and laboratory-related expenses for PUD care decreased by 40.2%, and expenditures for ranitidine declined by 52.2%. There was an increase in spending for antimicrobial agents and H. pylori antibody testing, but this was insignificant compared to the savings generated by decreased ranitidine usage. Annual savings in our facility as a result of this intervention were $123,449. Modern therapeutic strategies for PUD aimed at eradicating H. pylori can result in significant savings in the institutional setting; these savings are largely attributable to the decreased usage of histamine-2 receptor antagonists.

Adoption of New Pharmacotherapeutic Regimens: Analysis of Physician Prescribing for Peptic Ulcer Disease

OBJECTIVES. In February 1994, a National Institutes of Health (NIH) Consensus Development Conference panel unequivocally recommended antimicrobial therapy to eradicate H. pylori in the treatment of peptic ulcer disease (PUD). The goal of this study is to determine if these recommendations were followed by physicians treating PUD in an underserved population.METHODS. Computerized Pennsylvania Medicaid data were used to evaluate prescribing patterns among 997 patients newly treated for PUD between March 1, 1994 through March 31, 1995. Prescription of PUD therapy was assessed during the 12-month period following PUD diagnosis. Pharmacotherapy for the initial management of PUD, defined as the one-month period following the initial diagnosis, and for the follow-up period, defined as the 11-month period following the incident episode, was determined. The extent to which patients had an H. pylori or PUD invasive or noninvasive diagnostic procedure was examined. Rates of PUD outpatient physician encounters and in...

Prospects for the development of a vaccine against Helicobacter pylori.

Over 50% of the world population is chronically infected by the gastric pathogen, Helicobacter pylori, which is responsible for most peptic ulcer disease and is closely associated with adenocarcinoma of the stomach. Current therapies for peptic ulcer disease include antibiotic eradication of H. pylori infection. While effective, the high cost, difficulty of patient compliance with the treatment regimens, and risks of selection for resistant strains make these therapies impractical on a large scale. Studies of the pathogenesis of H. pylori have led to the identification of bacterial antigens as candidates for inclusion in novel vaccines against this disease. Both prophylactic and therapeutic vaccination have been demonstrated in animal models of Helicobacter infection. Preclinical evaluations of several antigens are at present under way and trials of vaccination in humans are planned.

Treatment of chronic gastroduodenal ulcers associated with Helicobacter Pylori-infection

Treatment of chronic gastroduodenal ulcers remains one of the most difficult and unsolved problems. The main difficulty that they try to overcome is their recurrent course. Nowadays the main directions of medical therapy of peptic ulcer disease are the decrease of intragastric acidity and sanation of gastroduodenal mucosa from Helicobacter Pylori. Treatment aimed at the destruction of Helicobacter Pylori allows to reduce the relapse rate to almost zero, provided it is successfully suppressed.

Upper Gastrointestinal Bleeding Following Major Surgical Procedures: Prevalence, Etiology, and Outcome

With continuing improvements in the medical therapy of peptic ulcer disease, the incidence of primary upper gastrointestinal bleeding (UGIB) has markedly declined. Nonetheless, in a subset of surgical patients, secondary UGIB following a major operation may still be a source of substantial morbidity. To further elucidate this problem, we reviewed 103 cases of overt UGIB following all major surgical procedures conducted in two hospitals between July 1982 and June 1994. The prevalence of postoperative UGIB during this period was 0.39%. The mean interval between initial operation and UGIB was 16 days (range 1–55 days) and there was a high incidence of associated sepsis (26%). The source of bleeding was defined endoscopically in all cases and included gastritis (69.9%), solitary ulcers (17.5%), and other causes (12.6%). Postoperative UGIB (nonvariceal) was most commonly seen following portacaval shunting operations but mortality rates were highest in patients who developed UGIB after cardiovascular operations. We conclude that: (1) postoperative UGIB has become a relatively uncommon but still formidable clinical problem; (2) erosive gastritis continues to be the major source of UGIB but acute ulcers, varices, and other causes contribute to the total; and (3) postoperative UGIB is most likely to be fatal in cardiovascular patients and those who develop concurrent sepsis and/or multiorgan failure.

The Continued Use of Placebo-Controlled Clinical Trials in the Study of Peptic Ulcer Disease: A Sponsor Perspective

Investigators and institutional reviews boards who/which have participated in recent controlled gastroenterology clinical research studies assessing new therapies for peptic ulcer disease have questioned the continued use of a placebo-control when efficacious therapies for peptic ulcer disease are currently available. As the sponsor of such studies, Glaxo is of the opinion that the use of placebo-controlled clinical research studies is appropriate in certain situations. In choosing between the use of an active comparator or placebo-controlled trial Glaxo recommends an assessment of the severity of the disease and the morbidity associated with use of placebo treatment. It further recommends the need to assess the efficacy of placebo therapy to establish the baseline remission rate for the disease. Glaxo suggests an assessment of the safety data for the new chemical entity under investigation, and if such data are lacking, minimize patient risk employing suggested study designs that maximize patient utiliza...

Eradication of Helicobacter pylori in general practice.

To determine the current management of patients with Helicobacter pylori infection in general practice with regard to the selection of patients, testing for the presence of the organism, the choice of eradication therapy and the occurrence of symptoms during follow-up. Cross-sectional survey involving the retrospective collection of data from patient medical records. Five general practices in the Fife region of Scotland during June and July 1995. The proportion of patients appropriately selected for eradication therapy and the success of treatment as assessed by remission of symptoms during follow-up. Of 154 patients studied, 80% received eradication therapy for peptic ulcer disease, the remainder for non-ulcer dyspepsia or gastrooesophageal reflux. Fifty-six different regimens were used, the most common combination of drugs being omeprazole plus amoxycillin. H. pylori status was known in only one-third of patients before treatment and in only 15% after treatment. More than half of patients complained of recurrent symptoms of dyspepsia during follow-up after eradication therapy and 47% required further treatment. In terms of the selection of patients and testing for H. pylori, the overall management using eradication therapy was acceptable in less than half of patients. In particular, the management of patients with ulcer disease associated with either ulcerogenic drugs or previous complications failed to provide the essential protection against the high risk of future haemorrhage or perforation. The findings of this study indicate an urgent need for improved education if therapy for the eradication of H. pylori is to be used appropriately and safely.

Review Pulmonary- Allergy, Dermatological, Gastrointestinal & Arthritis: Current therapies for peptic ulcer disease

The area of antiulcer research has changed dramatically over the past three years due to the introduction of proton pump inhibitors and the discovery of the link between Helicobacter pylori and peptic ulcer disease. Established agents such as ranitidine and famotidine have secured their place in the world market, but a number of novel agents are currently under investigation and could lead to new therapies in the future. This article reviews the the existing treatments available and their side effects, whilst briefly discussing the new compounds which have been disclosed in the recent patent literature.

Recent trends in mortality from peptic ulcer disease in Finland.

The enormous change of medical therapy of peptic ulcer disease in the 1970s has resulted in a significant decrease of elective ulcer surgery. It has been speculated whether this might be reflected in the mortality of the disease. Therefore, in the present study, the mortality rate of the disease was evaluated in Finland during the past 17 years covering the dramatic change in the medical therapy: the introduction of H2-receptor antagonists. This was done with a population-based epidemiological study by analyzing 1262 death certificates of people dying from peptic ulcer disease in Finland between 1972 and 1989. The study showed that there has been almost twofold increase in the mortality of the disease between 1972 and 1989 in Finland. This was mainly due to the significantly increased number of fatal ulcer hemorrhages in older people, but also mortality from ulcer perforations increased. This unfavorable epidemiological progress was most striking among elderly women and became manifest during the 1980s. We conclude that mortality from peptic ulcer disease has significantly increased in Finland due to fatal ulcer hemorrhages and perforations. This epidemiological change became manifest in the 1980s, concurrently with the dramatic change in the medical therapy of peptic ulcer disease.

Tuberculosis in relation to a history of peptic ulcer disease and treatment of gastric hyperacidity.

Previous studies described an excess of tuberculosis among persons with a history of partial gastrectomy for the treatment of peptic ulcer disease. It is unknown if any contemporary therapies for peptic ulcer disease, such as histamine type 2 antagonists and antacids, are also associated with elevated risks of tuberculosis. A case-control study was conducted during 1988-1990 in the Seattle-King County Tuberculosis Clinic to address these questions. Self-administered questionnaires were completed by 135 cases with active tuberculosis and 380 controls. A history of daily antacid use was reported by 11 cases (8%) and 23 controls (6%), corresponding to an adjusted odds ratio of 0.9 (95% confidence interval 0.4-2.0). A history of daily histamine type 2 antagonist use was reported by nine cases (7%) and 18 controls (5%) with an adjusted odds ratio of 0.8 (95% confidence interval 0.3-2.1). Our results, while based on a relatively small number of subjects, suggest that treatment for peptic ulcer disease has no influence on the occurrence of tuberculosis.

Lansoprazole for Maintenance Therapy of Peptic Ulcer Disease

Seventy-one patients with peptic ulcer (44 gastric ulcer and 27 duodenal ulcer patients) were enrolled in this study. After the ulcers had healed with 2 months of treatment with lansoprazole (LPZ) 30 mg/day, patients were divided into two groups: 43 in the half-dose q.d. group and 28 in the weekend full-dose group. Fourteen (23%) of the 43 patients in the half-dose q.d. group and 14 of the 28 (50%) in the weekend full-dose group failed to continue taking the drug for 6 months owing to poor compliance (p < 0.05). None of the 30 patients who continued to take the maintenance dose of LPZ experienced ulcer recurrence during the 6-month follow-up period, whereas 71% of the patients who stopped taking LPZ experienced recurrence (p < 0.01). In conclusion, maintenance therapy using the half-dose q.d. administration schedule was superior to weekend full-dose administration because of the better patient compliance and a lower ulcer recurrence rate.

Gastric and duodenal anti-ulcer activity of sulpiride, a dopamine D2 receptor antagonist, in rats

The gastric and duodenal anti-ulcer activity of sulpiride, a dopamine D2 receptor antagonist, was studied on various types of experimentally induced ulcers in rats, viz., pylorus ligation and water immersion + restraint stress-induced gastric ulcers, gastric mucosal damage induced by nonsteroidal anti-inflammatory drugs and reserpine, and duodenal ulcers induced by cysteamine hydrochloride. It has been found to possess significant anti-ulcer activity against all these models. In 19 h pylorus ligated rats, it significantly reduced the gastric secretion, increased the fucose and sialic acid concentration of the gastric juice and reduced its protein content, thus increasing the total carbohydrate:protein (TC/PR) ratio. These results suggest that the antisecretory and gastric mucosal barrier strengthening effects of sulpiride may be responsible for its anti-ulcer activity. A central component also appears to be involved in its anti-ulcer action against water immersion + restraint stress model. The results of this study provide a rationale for its beneficial effect seen in the therapy of peptic ulcer disease.

Formulary management of antiulcer drugs: economic considerations.

Peptic ulcer disease (PUD) is a common medical problem costing billions of dollars annually around the world. Since the availability of the first histamine H2-receptor antagonist, cimetidine, many economic analyses have been conducted to compare the impact of this drug class on resource consumption. H2-Antagonists have been shown to reduce mortality, hospitalisations, ambulatory care visits and endoscopy use caused by PUD. Because of changing risk factors and variations in diagnosis, it remains controversial whether these drugs have had a long term impact on PUD incidence and prevalence. Three studies conducted after the introduction of cimetidine showed it to reduce total direct medical healthcare expenditures, despite increases in drug costs. Studies investigating the short term treatment of PUD show mixed results because of diverse study designs and different comparator drugs. No specific therapy appears consistently superior economically because of variations in population studies, ulcer relapse rates and drug acquisition costs. However, maintenance therapy for PUD has been shown to be cost-effective. When compared with surgery--an extremely efficacious option--maintenance therapy (both daily and intermittent) is cost-effective over at least a 10-year period. Within the maintenance therapy options, daily ranitidine has been shown to be more cost-effective than intermittent therapy for up to 2 years. Omeprazole is the least costly and most efficacious treatment for gastroesophageal reflux disease (GORD or GERD) compared with ranitidine and/or lifestyle modification alone. It has also been shown that the costs for empirical treatment of GORD are offset by the costs of additional investigation of those who do not have the disease. Thus the decision of whether to treat empirically should be based on physician and patient preferences, and not on costs. The use of misoprostol for ulcers caused by nonsteroidal anti-inflammatory drugs is somewhat controversial. Three studies examining the short term (3-month) costs of misoprostol generally show it to be cost saving or cost neutral. Misoprostol is consistently more cost beneficial in elderly or other high risk patients. Results are highly sensitive, however, to several parameters, such as patient type, ulcer severity and rate, drug costs and patient compliance. One study examining prophylaxis using misoprostol over 1 year showed it to be a generally expensive therapy for primary prevention, but was more cost effective for those with a proven GI bleed in the previous year.(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical relevance of basic research in peptic ulcer disease

Historically, the interplay between basic research and clinical observation has been essential in the development of new therapies for peptic ulcer disease. That histamine is an important regulator of acid secretion emerged from basic research, followed by the clinical development and use of the H2-receptor antagonists. Basic research contributed again by defining the importance of H+/K(+)-ATPase in acid secretion, resulting in a new class of useful antisecretory agents. Basic studies also gave us prostaglandins (PG) as mucosal protective agents. As 'replacement' therapy, clinicians have found that PG are protective against non-steroidal anti-inflammatory drug (NSAID)-induced gastric ulcer (GU). Physiologic studies established that somatostatin is a potent inhibitor of acid secretion, providing the stimulus for clinical studies in Zollinger-Ellison (ZE) Syndrome with a synthetic analog (octreotide). Work on isoforms of the parietal cell gastrin receptor has shown differences in the cytoplasmic domain for G protein coupling. This will aid in understanding how receptor changes and coupling to second messengers relate to the aetiopathogenesis of abnormal gastric secretion. Immune cells express mRNA for histamine, muscarinic and gastrin receptors, supporting the relevance of mucosal immunology in gastroenterology, especially in light of Helicobacter pylori-associated gastritis and ulcers. Lab research has revealed a potential role for basic fibroblast growth factor (bFGF), and another endogenous peptide BPC-15, in ulcer healing. The former substance may be responsible for the antiulcer efficacy of sucralfate. Intensive basic work on how H. pylori organisms attach to gastric cells and initiate inflammatory reactions in the mucosa will have unquestionable impact on improved therapy for peptic ulcer disease.

Pharmacology of gastric acid inhibition

Gastric acid secretion is precisely regulated by neural (acetylcholine), hormonal (gastrin), and paracrine (histamine; somatostatin) mechanisms. The stimulatory effect of acetylcholine and gastrin is mediated via increase in cytosolic calcium, whereas that of histamine is mediated via activation of adenylate cyclase and generation of cAMP. Potentiation between histamine and either gastrin or acetylcholine may reflect postreceptor interaction between the distinct pathways and/or the ability of gastrin and acetylcholine to release histamine from mucosal ECL cells. The prime inhibitor of acid secretion is somatostatin. Its inhibitory paracrine effect is mediated predominantly by receptors coupled via guanine nucleotide binding proteins to inhibition of adenylate cyclase activity. All the pathways converge on and modulate the activity of the luminal enzyme, H +, K +-ATPase, the proton pump of the parietal cell. Precise information on the mechanisms involved in gastric acid secretion and the identification of specific receptor subtypes has led to the development of potent drugs capable of inhibiting acid secretion. These include competitive antagonists that interact with stimulatory receptors (e.g. muscarinic M 1-receptor antagonists and histamine H 2-receptor antagonists) as well as non-competitive inhibitors of H +, K +-ATPase (e.g. omeprazole). The histamine H 2-receptor antagonists (cimetidine, ranitidine, famotidine, nizatidine and roxatidine acetate) continue as first-line therapy for peptic ulcer disease and are effective in preventing relapse. Although they are generally well tolerated, histamine H 2-receptor antagonists may cause untoward CNS, cardiac and endocrine effects, as well as interfering with the absorption, metabolism and elimination of various drugs. The dominance of the histamine H 2-receptor antagonists is now being challenged by omeprazole. Omeprazole reaches the parietal cell via the bloodstream, diffuses through the cytoplasm and becomes activated and trapped as a sulfenamide in the acidic canaliculus of the parietal cell. Here, it covalently binds to H +, K +-ATPase, the hydrogen pump of the parietal cell, thereby irreversibly blocking acid secretion in response to all modes of stimulation. The main potential drawback to its use is its extreme potency which sometimes leads to virtual anacidity, gastrin cell hyperplasia, hypergastrinaemia and, in rats, to the development of carcinoid tumours. The cholinergic receptor on the parietal cell has recently been identified as an M 3 subtype and that on postganglionic intramural neurones of the submucosal plexus as an M 1 subtype. Muscarinic M 1-receptor antagonists such as pirenzepine and telenzepine inhibit acid secretion to a similar degree as do non-specific antagonists such as atropine, but with greatly reduced anticholinergic side-effects. Muscarinic M 1-receptor antagonists are as effective as histamine H 2-receptor antagonists in healing duodenal and probably gastric ulcers.

Eradication of Helicobacter pylori and Its Effect in Peptic Ulcer Disease

Since Helicobacter pylori was first cultured 10 years ago, there have been remarkable changes in our approach to the therapy of peptic ulcer disease. We now know that 90% of duodenal ulcer patients and 70% of all gastric ulcer patients are infected with H. pylori. Evidence is presented that the relapse rate of both duodenal and gastric ulcers can be substantially reduced if the bacterium is eradicated from the patient's stomach. Some of the anti-H. pylori eradication regimens currently available are discussed, with particular emphasis on the relative merits of standard triple therapy and an omeprazole/amoxycillin combination.