Treatment Of Acid-peptic Diseases Research Articles

Effectiveness of Omeprazole in Acid Peptic Disease: A Real-World, Patient-Reported Outcome Measures Study.

Objectives This prospective study assessed the effectiveness and patient satisfaction of four-week omeprazole therapy in acid peptic disease (APD). Methods This was an observational, post-marketing, real-world evidence, patient-reported outcome(PRO) measures study. Patients visiting the five study sites across India with symptoms ofAPD, andwho were prescribed oral omeprazole (20/40 mg per day) for at least four weeks were enrolled after obtaining informed consent. Study assessments includedfrequency and severity of symptoms and overall satisfaction reported by the patients using the Patient Assessment of Gastrointestinal Disorder Symptom Severity Index (PAGI-SYM) questionnaire. The satisfaction with therapy was reported by the patients using the Treatment Satisfaction Questionnaire for Medication (TSQM) questionnaire. Both PAGI-SYM and TSQM were reported by patients on days 14 and 28. Omeprazole safety was assessed based on the adverse events reported by the patients. Results A total of 96 (62 males and34 females) patients were included in the study, of which 38.54% had significant findings related to APD at baseline.The proportion of patients with symptoms reduced to 16.67% on day 14and 8.33% on day 28 with omeprazole therapy. The PAGI-SYM total scores at baseline were 41.32 (15.487), which reduced to 20.86 (11.620) on day 14 (p < 0.0001), and to 8.93 (8.361) on day 28 (p < 0.0001). Significant reductions were also seen in individual symptom scores. The TSQM total scores increased to 36.67 (range: 13 to 63) on day 28 from 34.69 (range: 12 to 58) on day 14. Improvement in scores for all domains of TSQM (effectiveness, convenience, and global satisfaction) was seen on day 28. Improvement in reflux symptoms was reported by 46.74% and 68.48% of patients on day 14 and day 28, respectively. Four (4.17%) patients reported adverse events, which were of mild severity and were unrelated to omeprazole. Conclusions Omeprazole provides significant improvement in PAGI-SYM and TSQM questionnaires on day 14 and day 28.Patients reported the omeprazole-based therapy as effective, convenient, and satisfactory. Omeprazole therapy is safe and effective for the treatment of APD and shows good improvement in APD in patients suffering from duodenal ulcers, gastric ulcers, and reflux oesophagitis.

Evaluation of CYP2C19 Gene Polymorphisms in Patients with Acid Peptic Disorders Treated with Esomeprazole.

BackgroundCYP2C19 is a highly polymorphic gene that encodes an enzyme with the same name and whose function is associated with the metabolism of many important drugs, such as proton pump inhibitors (such as esomeprazole, which is used for the treatment of acid peptic disease). Genetic variants in CYP2C19 alter protein function and affect drug metabolism. This study aims to genotypically and phenotypically characterize the genetic variants in the CYP2C19 gene in 12 patients with acid peptic disorders and different therapeutic profiles to proton pump inhibitor (PPI) drugs. The patients were randomly selected from a controlled, randomized and blinded clinical pilot trial of 33 patients. We determined the presence and frequency of single nucleotide polymorphisms (SNPs) within exons 1–5 and 9, the intron-exon junctions, and a fragment in the 3ʹ UTR region of the CYP2C19 gene using Sanger sequencing. Undescribed polymorphisms were analyzed by free online bioinformatics tools to evaluate the potential molecular effects of these genetic variants.ResultsWe identified nine polymorphisms, six of which had no reported functions. One of these genetic variants, with a functional impact, not yet reported (p.Arg132Trp) was predicted by bioinformatic tools as potentially pathogenic. This finding suggests that p.Arg132Trp could be related to poor metabolizers of drugs metabolized by CYP2C19.ConclusionWe identified the genotype spectrum of variants in CYP2C19. The genotype spectrum of variants in CYP2C19 could predict the treatment response and could support to evaluate clinical efficacy in patients treated with esomeprazole.

Proton Pump Inhibitors : The Controversies to Consider

Heartburn is ailing the masses. By one estimate. 20% of the Western population experiences acid reflux at least once a week and shelling out buckets of cash S25.6 billion worldwide in 2008 to alleviate those hot, sour. acidic pains in the chest. Proton pump inhibitors (PPIs) am one of the most commonly prescribed classes of medications in the primary care setting and are considered a major advance in the treatment of acid-peptic diseases. Since the introduction of omeprazok in 1989. several other PPIs have become available in combating various acid-peptic disorders, including gastroesophageal reflux disease, peptic ulcer disease, and nonsteroidal anti-inflammatory drug-induced gastropathy. The intravenous form of pantoprazole is now available. and the U.S. Food and Drug Administration (FDA) approved the newest dexlansoprazole in 2012. Although H2 blockers are less expensive thanPPIs, but PPIs provide superior acidsuppression, healing rates and symptom relief.Therefore, PPIs may be more cost-effectivethan H2 blockers. especially in patients withmore severe acid-peptic disorders, because oftheir lower and less frequent dosingrequirements and their comparatively shorterduration of required therapy.

Proton Pump Inhibitors : The Controversies to Consider

Heartburn is ailing the masses. By one estimate. 20% of the Western population experiences acid reflux at least once a week and shelling out buckets of cash S25.6 billion worldwide in 2008 to alleviate those hot, sour. acidic pains in the chest. Proton pump inhibitors (PPIs) am one of the most commonly prescribed classes of medications in the primary care setting and are considered a major advance in the treatment of acid-peptic diseases. Since the introduction of omeprazok in 1989. several other PPIs have become available in combating various acid-peptic disorders, including gastroesophageal reflux disease, peptic ulcer disease, and nonsteroidal anti-inflammatory drug-induced gastropathy. The intravenous form of pantoprazole is now available. and the U.S. Food and Drug Administration (FDA) approved the newest dexlansoprazole in 2012. Although H2 blockers are less expensive thanPPIs, but PPIs provide superior acidsuppression, healing rates and symptom relief.Therefore, PPIs may be more cost-effectivethan H2 blockers. especially in patients withmore severe acid-peptic disorders, because oftheir lower and less frequent dosingrequirements and their comparatively shorterduration of required therapy.

Acid peptic diseases: pharmacological approach to treatment

Acid peptic disorders are the result of distinctive, but overlapping pathogenic mechanisms leading to either excessive acid secretion or diminished mucosal defense. They are common entities present in daily clinical practice that, owing to their chronicity, represent a significant cost to healthcare. Key elements in the success of controlling these entities have been the development of potent and safe drugs based on physiological targets. The histamine-2 receptor antagonists revolutionized the treatment of acid peptic disorders owing to their safety and efficacy profile. The proton-pump inhibitors (PPIs) represent a further therapeutic advance due to more potent inhibition of acid secretion. Ample data from clinical trials and observational experience have confirmed the utility of these agents in the treatment of acid peptic diseases, with differential efficacy and safety characteristics between and within drug classes. Paradigms in their speed and duration of action have underscored the need for new chemical entities that, from a single dose, would provide reliable duration of acid control, particularly at night. Moreover, PPIs reduce, but do not eliminate, the risk of ulcers in patients taking NSAIDs, reflecting untargeted physiopathologic pathways and a breach in the ability to sustain an intragastric pH of more than 4. This review provides an assessment of the current understanding of the physiology of acid production, a discussion of medications targeting gastric acid production and a review of efficacy in specific acid peptic diseases, as well as current challenges and future directions in the treatment of acid-mediated diseases.

Guide to the Use of Proton Pump Inhibitors in Adult Patients

Proton Pump Inhibitors (PPIs) are widely used in the treatment of acid-peptic diseases. Their mechanism of action involves inhibition of the H-K-adenosine triphosphatase enzyme present in the parietal cells of the gastric mucosa. Because PPIs are the most potent inhibitors of gastric acid secretion available, they effectively alleviate acid-peptic symptoms and facilitate healing of inflamed or ulcerated mucosa. Although the use of PPIs is nowadays short term in patients with Helicobacter pylori-related peptic ulcer disease, these drugs are increasingly used long term, frequently for a lifetime, in patients with typical or atypical symptoms of gastro-oesophageal reflux disease, and in NSAID or aspirin users at risk for gastrotoxicity and related complications, such as bleeding, perforation and gastric outlet obstruction. This review outlines the essentials of PPI pharmacology, the safety and adverse profiles of the various available agents, and balances them against their clinical short- and long-term benefits. PPI use, prophylactically or with a therapeutic intent may also be combined with other strategies, such as endoscopic therapy, surgery or antibacterial use. Various clinical endpoints, such as symptom relief, mucosal healing, prevention of disease recurrence or complications, and cancer chemoprevention, are discussed and unmet needs are highlighted.

Impiego degli Inibitori della Pompa protonica (IPP) in Piemonte: indagine sulle abitudini prescrittive dei Medici di Medicina Generale

Proton Pump Inhibitors (PPIs) (Omeprazole, Lansoprazole, Pantoprazole, Rabeprazole and Esomeprazole), one of the most commonly prescribed classes of medications in the primary care setting, are considered a major advance in the treatment of acid-peptic diseases. In Italy PPIs are reimbursed by National Health Service on the basis of CUF (Commissione Unica del Farmaco) 1 and 48 Notes. In 2002 and 2003 a significant increase in PPIs consumption and expenditure have been documented, showing differences between regions. The aim of this study is to investigate and monitor, at regional level, type and entity of PPIs use through a drug utilization study, evaluating prescribing behaviour and compliance of PPIs treatments with CUF Notes indications. The study has been carried out on a sample of 436 General Practitioners belonging to 22 Piemonte’s ASL (Aziende Sanitarie Locali). The data analysis shows that acid-related pathologies are significantly more common in patients with at least 50 years of age and the most frequent condition is represented by gastroesophageal reflux disease. Despite the general conditions of PPIs use by General Practitioners in terms of duration and dosage of therapy result in most cases (from 49% to 80% for duration and from 54% to 97% for dosage) compliant with what proposed by CUF Notes, in some cases the same CUF Notes indications seem to be not observed. Consequently the Piemonte Region has decided to plan a guideline on PPIs rational use. Such guideline, expected to be introduced in the regional area, may also be considered as an instrument able to lead to a more appropriate expenditure for this drug class. Moreover, in order to control PPIs expenditure, pharmacoeconomic methodologies can be applied allowing to identify the most cost - effective active substance and therapeutic scheme, overcoming CUF Notes which consider all PPIs use under the same reimbursement conditions.

Pantoprazole: a new and more specific proton pump inhibitor

Pantoprazole is the third proton pump inhibitor (PPI) to be launched for the treatment of acid-peptic diseases. Like other drugs in this class, pantoprazole causes long-lasting inhibition of acid secretion by inactivating the parietal cell H+/K+-ATPase. Compared with H2 antagonists, pantoprazole results in faster pain relief, more rapid ulcer healing, healing of resistant ulcers and far greater efficacy in oesophageal reflux disease. The three PPIs currently available display almost identical efficacy in the treatment of acid-peptic diseases and when included as part of Helicobacter pylori eradication regimes. However, pantoprazole shows improvements in selectivity and pharmacokinetic properties compared with omeprazole and lansoprazole. The bioavailability of pantoprazole is considerably higher than omeprazole, remains constant upon repeated dosing, and is unaffected by food. Significantly, pantoprazole does not influence hepatic cytochrome P450 activity and does not therefore interact with co-administered drugs. This is in contrast to omeprazole, which inhibits P450, and lansoprazole, which appears to weakly induce multiple metabolic pathways. Although pantoprazole is entering an antisecretory market dominated by omeprazole and ranitidine, it has a number of potential advantages. In this respect it is worth recalling that enhanced specificity and the absence of drug interactions were decisive factors in determining market share in the H2 antagonist era. Pantoprazole may therefore achieve significant market penetration, particularly at the expense of lansoprazole and the H2 blockers.

Current Status of Gastric Proton Pump Inhibitors in the Treatment of Acid-Peptic Disease

Proton pump inhibitors represent an important advance in the treatment of acid-peptic disease. Omeprazole, the prototype of the drug class, produces a profound and sustained degree of gastric acid suppression. Recent studies confirm earlier reports that omeprazole 20 mg/d is generally more effective than standard histamine2 receptor antagonist (H2RA) dosage regimens in treating duodenal ulcer (DU), gastric ulcer (GU), and erosive esophagitis. Omeprazole tends to accelerate DU and GU healing, especially during the first 2 weeks of treatment, and also accelerates mucosal healing in patients with all grades of esophagitis. Omeprazole is the drug of choice for treating patients with large or refractory ulcers, severe or refractory erosive esophagitis, Barrett's esophagus, and Zollinger-Ellison syndrome. Maintenance therapy with omeprazole seems to reduce ulcer recurrence and esophagitis, but optimal treatment regimens must be established. Dual therapy with omeprazole and amoxicillin shows encouraging results in eradicating Helicobacter pylori, reducing duodenal ulcer recurrence rates, and altering the natural history of peptic ulcer disease. Further studies are required to determine the efficacy of omeprazole in preventing nonsteroidal anti-inflammatory drug-induced ulcers and stress-related mucosal bleeding, and in treating upper gastrointestinal bleeding. Omeprazole is well-tolerated in the majority of patients receiving either short-term or long-term treatment. The type and frequency of adverse effects are similar to those reported with the H2RAs. There is no evidence to support genotoxicity or hypergastrinemia-induced enterochromaffin-like cell carcinoid of the stomach in patients receiving omeprazole treatment for more than 5 years. Omeprazole interacts selectively with hepatic P-450 and may potentially interact with phenytoin, warfarin, or diazepam. Pharmacoeconomic studies suggest that treatment with omeprazole provides a significant cost-savings over the H2RAs in patients with moderate to severe erosive esophagitis and possibly in patients with DU. Lansoprazole, a newly developed proton pump inhibitor, seems to offer no clear advantage over omeprazole.

Drug Interactions with Antiulcer Agents: Considerations in the Treatment of Acid-Peptic Disease

All of the antiulcer agents have been implicated in drug interactions. These agents generally influence the absorption, metabolism, or elimination of other medications. However, these interactions can lead to alterations in pharmacodynamic response. The mechanisms by which antiulcer agents produce drug interactions differ among the agents. It is beyond the scope of this article to review all of the drug interactions that have been reported with antiulcer agents. However, it is the intent to provide the reader with a detailed understanding of the mechanisms by which antiulcer agents may interact with other medications and to provide insight into factors that may influence the potential magnitude or clinical consequences of these interactions. An understanding of antiulcer drug interactions will aid pharmacists in assisting clinicians with drug selection and/or monitoring of drug interactions. Specifically, pharmacists can assist with the identification of potential antiulcer drug interactions and develop strategies designed to minimize adverse consequences of these interactions.

Omeprazole: a new drug for the treatment of acid-peptic diseases

Omeprazole is the first of a new class of gastric antisecretory drugs, proton pump inhibitors. It inhibits the H+,K(+)-adenosinetriphosphatase enzyme of the gastric parietal cell, resulting in potent, long-lasting suppression of basal and stimulated acid secretion. The drug is currently approved for treatment of gastroesophageal reflux disease and Zollinger-Ellison syndrome. In clinical trials, treatment with omeprazole results in rapid healing of duodenal ulcers; it is also effective in treating gastric ulcer disease. It is uniformly well tolerated without significant adverse effects, although animal studies linked profound long-term suppression of gastric acid secretion with the development of gastric carcinoids. Potential future uses include the prophylaxis of ulceration secondary to stress or use of nonsteroidal anti-inflammatory drugs, and the prophylaxis of recurrent peptic ulcer disease.

The evolution of peptic ulcer therapy. A role for temporal control of drug delivery.

The treatment of acid peptic disease has involved a series of attempts to control gastric acid secretion in order to heal and to prevent recurrence of duodenal ulcers. Early treatment attempted to heal by neutralizing gastric acid with diet modification, the Sippy diet, and Doll's milk drip. Just before the turn of the century, surgeons began performing gastric resections. In 1943, Dr. Lester Dragstedt performed the first truncal vagotomy to limit cholinergic stimulation of gastric acid secretion. This led to surgery that combined gastric resections with vagotomy. In 1970, the first parietal cell vagotomy was performed. This microsurgical technique limited vagal initiation of acid secretion while minimizing the impact on other gastrointestinal functions. By the 1960s, pharmacological intervention included antacids to neutralize acid and anticholinergics to reduce the amount of acid produced. These treatments varied in their effectiveness, and some of them caused significant side effects. In 1976, treatment of acid peptic disease began a new phase with the introduction of the first H2 receptor antagonist, cimetidine. Ranitidine, the second H2 receptor antagonist, produced greater acid suppression in the morning and at night with bid dosing than cimetidine with quid dosing. The knowledge that there is a circadian pattern in acid production, with higher levels between 10 PM and 2 AM, resulted in the development and use of a single evening dose of ranitidine. Ongoing research continues to investigate the effects of dose timing and the influence of more potent acid-suppressing agents. Finally, the issue of maintenance therapy and gastric acid secretion was addressed. The clinical advantage that ranitidine has over cimetidine in the prevention of ulcer recurrence can be attributed to its control of nocturnal acid suppression.

Should Safety Concerns with Available Ulcer Treatment Influence Drug Selection?

With the identification of the parietal cell receptors for gastric acid secretion coupled with the introduction of cimetidine in 1977, treatment of acid-peptic diseases was transformed from empiric therapy to an approach based on a clearer understanding of human physiology. Today, physicians are confronted with an array of antiulcer agents that differ within their drug class (e.g., the H2-receptor antagonists) as well as in their mechanisms of action (e.g., neutralize acid, alter mucosal defensive factors, or suppress acid secretion). With minor exceptions, the clinical efficacy of the available antiulcer drugs can be regarded as comparable. Thus, the safety profile becomes the next consideration when choosing among similarly effective drug products. Of the available antiulcer agents, the H2-receptor antagonists as a class have an excellent safety profile, as indicated by more than 25 years of cumulative clinical experience and postmarketing surveillance. Important safety issues with currently available antiulcer drugs, i.e., H2-receptor antagonists, sucralfate, prostaglandin E analogues, and the newest antiulcer agent, omeprazole, are reviewed to place them into perspective for the clinician.

Profound Gastric Acid Inhibition: Advantages and Potential Hazards

More potent gastric acid-inhibiting drugs with a longer duration of action are being produced. The latest H2 receptor antagonists are examples of this tendency, and the first H+-K+ ATPase antagonist omeprazole is the most potent gastric acid-reducing agent currently known. The benefits of profound gastric acid inhibition in the treatment of acid peptic diseases have been demonstrated in clinical studies. Omeprazole achieves faster healing and symptom relief of duodenal ulcer than H2 receptor blockers. Particularly in the treatment of refractory ulcers and reflux oesophagitis, treatment with omeprazole is very effective. However, gastric acid has an important physiologic role. The potential consequences of profound inhibition of gastric acid include intragastric bacterial colonization and hypergastrinaemia. Bacterial overgrowth of the stomach renders the gut more susceptible to enteric infections and may facilitate nosocomial infections in compromised patients. Another possible repercussion of intragastric bacteria is the formation of N-nitroso compounds with carcinogenic potency. Serum gastrin levels increase with decreasing gastric acidity. Hypergastrinaemia has a trophic effect on the gastric mucosa and gastric endocrine cells. In animal experiments ECL-cell hyperplasia and carcinoid formation have been observed as a result of high serum gastrin levels. In man similar abnormalities have been recorded in diseases accompanied by hypergastrinaemia, such as pernicious anaemia or the Zollinger-Ellison syndrome. To date there are no reports in man describing these effects after profound drug-induced hypochlorhydria, but no controlled studies have yet been done. From the available data we may conclude that profound inhibition of gastric acid secretion has clinical advantages. The risks involved will most probably be very small during short periods of treatment. At present it is not possible to establish to what extent and for what time profound acid inhibition is safe.

Prostaglandins in peptic ulcer disease. An overview of current status and future directions.

Naturally occurring prostaglandins almost certainly play an important role in maintaining the integrity of the gastrointestinal mucosa. Clinical evidence available to date indicates that synthetic analogues of prostaglandins heal gastroduodenal ulcer only in doses that suppress gastric acid. However, non-antisecretory doses of prostaglandins may eventually have a role in the treatment of ulcer disease by maintaining ulcer healing and preventing recurrence. This possibility along with the potential of prostaglandins to prevent gastroduodenal mucosal injury caused by NSAIDs, alcohol, aspirin and stress, if supported by the results of ongoing clinical trials, may prove to be a major therapeutic advance for the treatment of acid peptic disease.

Treatment of Acid-Peptic Diseases by Inhibition of Gastric H+,K+-ATPase

Treatment of Acid-Peptic Diseases by Inhibition of Gastric H+,K+-ATPase

Gastrointestinal cytoprotective effects of misoprostol

The cytoprotective effects of misoprostol, a synthetic analog of prostaglandin E1, were investigated in healthy human subjects using randomized and placebo-controlled studies. Misoprostol significantly inhibited established aspirin (975 mg q.i.d.)-induced gastric microbleeding at 50 micrograms q.i.d., and to some extent, but not significantly, at 25 micrograms q.i.d. Misoprostol also reduced acid and chloride secretion significantly at 50 micrograms q.i.d., but not at 25 micrograms q.i.d. When administered concurrently with aspirin 650 mg q.i.d., misoprostol 25 micrograms q.i.d. significantly inhibited aspirin-induced fecal blood loss without affecting plasma salicylate concentration. The fact that misoprostol was tested at a sub-therapeutic gastric antisecretory dose (25 micrograms) indicates that the inhibition of fecal blood loss was not due to its gastric antisecretory property. Misoprostol tended to reduce antral erosion and DNA content of gastric fluid, but increased mucus concentrations in subjects with ethanol-induced damage. However, the dose of ethanol used produced gastric damage in only six of the 10 subjects and did not provide a satisfactory baseline. Misoprostol attenuated the drop in transmucosal potential difference induced by sodium taurocholate. It is concluded that misoprostol has cytoprotective activity in man. These effects may be of great importance in the treatment of acid peptic disease of the gastrointestinal tract.

Effects of ranitidine and of cimetidine on pentagastrin-stimulated gastric acid secretion

We compared the effect of oral and intravenous ranitidine, a new H2-receptor antagonist, with that of cimetidine on pentagastrin-stimulated gastric acid secretion in normal subjects. Ranitidine in intravenous doses of 20, 60, and 100 mg and oral doses of 100, 150, and 200 mg inhibited acid secretion. Only the 100 mg iv ranitidine dose was substantially more effective than cimetidine. Comparable dose-related decreases in gastric secretory volume were observed. Acid inhibition correlated strongly (r = 0.90) with plasma ranitidine concentration, with the estimated plasma concentration producing 50% inhibition (IC50) being 95 ng/ml. Maximal acid inhibition achieved was 87.3%. We conclude that ranitidine is a potent inhibitor of gastric acid secretion and should be a valuable addition to the medical treatment of acid-peptic disease.

The Impact of Cimetidine on the Treatment of Acid-Peptic Disease

The Impact of Cimetidine on the Treatment of Acid-Peptic Disease

Pharmacology and clinical use of antacids

The pharmacology of antacids, with particular reference to their clinical use in treating acid-peptic disease, is discussed. Liquid antacid suspension should be given at least as often as one hour after each meal and at bedtime. Inthe treatment of the acute phase of acid-peptic disease, hourly antacid is recommended. The dose should be planned in terms of milliequivalents of acid neutralizing capacity and should be adjusted according to the type of disease under treatment. All antacids have side effects, the most serious of which are metabolic. In clinical terms, the harmful sustemicside effects of calcium carbonate and sodium bicarbonate outweigh their benefit as neutralizing agents; they should rarely be employed in the treatment of acid-peptic disease. The more common antacid side effects of diarrhea (magnesium hydroxide) and constipation (aluminum hydroxide) are best managed by appropriately alternating the agents or by using one of the various antacid mixtures.