Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lansoprazole is an inhibitor of gastric H+,K(+)-ATPase, commonly referred to as the 'proton pump'. The pharmacodynamic effect of proton pump inhibition is to reduce gastric acid secretion. Long experience with H2 antagonists and more recently proton pump inhibitors has demonstrated the value of reducing gastric acid secretion in conditions where acid plays a key role in the pathogenesis of gastrointestinal inflammation and ulceration. The pharmacokinetics, pharmacodynamics and clinical safety of lansoprazole are discussed elsewhere in this supplement, and so this review will focus upon the European and American experience of the efficacy of lansoprazole in the treatment of peptic ulceration and gastro-oesophageal reflux.
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PMID:Clinical review of lansoprazole. 806 Aug 2

Gastro-oesophageal reflux disease (GORD) is a very common disorder of upper gastro-intestinal motility, differing widely in severity and prognosis. Medical therapy of GORD has involved antacids, alginates, prokinetic agents and antisecretory compounds, primarily H2 receptor antagonists and proton pump inhibitors. Knowledge of the pharmacokinetics of these compounds is important, to optimise the therapeutic benefit in each patient. GORD patients are often elderly and pharmacokinetics are move variable in this group. Furthermore, they often suffer from other diseases needing medical therapy and may need a combination of drugs to heal reflux oesophagitis and relieve reflux symptoms. The ideal therapy for GORD will have linear pharmacokinetics, a relatively long plasma half-life (t1/2), a duration of action allowing once daily administration, and a stable effect independent of interactions with food, antacids and other drugs. Over-the-counter antacids and alginates are widely used, buy may affect absorption of H2 receptor antagonists like cimetidine and ranitidine. Aluminium-containing antacids may, over time, cause toxicity in patients with renal insufficiency. In the treatment of GORD, cisapride presents important advantages over earlier prokinetic compounds, with a longer plasma t1/2, low penetration of the blood-brain barrier and fewer adverse effects. The group of H2 receptor antagonists is still the most frequently use therapy for GORD. Linear pharmacokinetics make dose adjustments easy and safe. In individual patients, suppression of gastric secretion is related to the area under the plasma concentration-time curve (AUC), but there is wide interindividual variation in the effect of the same oral dose. Only with frequent administration and high doses will acid suppression approximate that of proton pump inhibitors. Tolerance, with loss of effect over time, however, is most pronounced in this situation. H2 receptor antagonists seem well suited for on-demand treatment of reflux symptoms, due to the rapid onset of effect and a decrease likelihood of the development of tolerance. Effervescent formulations provide more rapid absorption and almost immediate clinical effect. Cimetidine, however, causes interference with the metabolism of several other drugs in common use. In elderly patients elimination is delayed and in patients with renal insufficiency, dose reductions of all H2 receptor antagonists are recommended. The most effective medical therapy for any severity of GORD, particularly in severe oesophagitis, are the proton pump inhibitors. The substituted benzimidazoles (omeprazole, lansoprazole and pantoprazole), are prodrugs which once trapped and activated in the acid milieu of the gastric glands potently suppress gastric secretion of acid and pepsin. Their long duration of action, more related to the slow turnover of parietal cell H(+)-K+ ATPase molecules, allows once daily administration in most patients. Interindividual variation in bioavailability sometimes calls for higher doses or twice daily administration. Acid suppression is closely related to the AUC. Omeprazole is prone to interaction with the metabolism of other drugs, some of which may e be clinically important. Lansoprazole seems to have an earlier onset of action than omeprazole, ascribed to higher bioavailability during the first days of treatment. Proton pump inhibitors have a slow onset of action, which makes them unsuited for on-demand therapy. Clinical practice in GORD calls for the use of not one but several substances, according to the severity and symptom pattern of the patient. Pharmacokinetic optimisation in the treatment of GORD is a question of selecting the most suitable substances and administration schemes within each group. Cisapride is superior to other prokinetics in terms of longer plasma t1/2 and less toxicity. Amongst H2 receptor antagonists, the more long-acting compounds, ranitidine and famotidine, will improve acidity control througho
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PMID:Pharmacokinetic optimisation in the treatment of gastro-oesophageal reflux disease. 911 86

Lansoprazole is a proton pump inhibitor that reduces gastric acid secretion. It has proved effective in combination regimens for the eradication of Helicobacter pylori and as monotherapy to heal and relieve symptoms of gastric or duodenal ulcers and gastro-oesophageal reflux. After initial healing, it may be used to prevent recurrence of oesophageal erosions or peptic ulcers in patients in whom H. pylori is not the major cause of ulceration and to reduce basal acid output in patients with Zollinger-Ellison syndrome. Usual dosages are 15 to 60 mg/day, although dosages of < or = 180 mg/day have been used in patients with hypersecretory states. In patients with duodenal or gastric ulcer, short term lansoprazole monotherapy was similar to omeprazole and superior to histamine H2 receptor antagonists in achieving healing rates > 90%. Lansoprazole was as effective a component of H. pylori eradication regimens as omeprazole, tripotassium dicitrato bismuthate (colloidal bismuth subcitrate) or ranitidine. Lansoprazole was superior to ranitidine in symptom relief and healing of gastro-oesophageal reflux disease and tended to relieve symptoms more rapidly than omeprazole, although initial healing was similar. As maintenance treatment, lansoprazole was similar to omeprazole and superior to ranitidine in relieving symptoms and preventing relapse. Lansoprazole was also superior to ranitidine in healing and relieving symptoms of oesophageal erosions associated with Barrett's oesophagus; healing was maintained for a mean of 2.9 years in > or = 70% of patients. Lansoprazole was also superior to ranitidine in prophylaxis of redilatation of oesophageal strictures. After > or = 4 years of use in patients with Zollinger-Ellison syndrome, lansoprazole 60 to 180 mg/day effectively controlled basal acid output. Dosages may be reduced in some patients once healing and symptom relief has been achieved. Preliminary studies of lansoprazole in patients at risk of aspiration pneumonia or stress ulcers show promise. Although studies show lansoprazole is potentially effective in treating gastrointestinal bleeding, future studies should assess patients' H. pylori status. Lansoprazole has been well tolerated in clinical trials, with headache, diarrhoea, dizziness and nausea appearing to be the most common adverse effects. Tolerability of lansoprazole does not deteriorate with age and the drug is well tolerated in long term use (< or = 4 years) in patients with Zollinger-Ellison syndrome or reflux disease. Thus, lansoprazole is an important alternative to omeprazole and H2 receptor antagonists in acid-related disorders. In addition to its efficacy in healing or maintenance treatment, it may provide more effective symptom relief than other comparator agents.
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PMID:Lansoprazole. An update of its pharmacological properties and clinical efficacy in the management of acid-related disorders. 927 7

The potential economic advantage of alternate-day therapy for GERD maintenance must be weighed against the potential cost of failure before it can be widely instituted. The studies presented have helped develop a clinical picture of the patients who may benefit from alternate-day therapy without risk of complications or potential increases in management costs. Bank et al., reporting on a group of patients, found that patients with Grade II-IV disease had a 61% success rate at two to eight years. Bank defined success as both maintenance of endoscopic healing and symptom control. Ladas et al. found a 66.7% success rate defined as clinical and endoscopic remission in Grades II-III disease. Kurucar et al. monitored symptom control and esophageal complications in his patients and found the regimen to have a 26% success rate in Grades III-IV disease. Lind et al. found that 83% of patients could remain symptom free with on-demand therapy if they were endoscopy-negative at baseline. The results of the Mantides et al. study are important because they imply that alternate-day omeprazole therapy may be more effective than alternatives for step-down treatment, such as ranitidine or cisapride. Furthermore, patients can be educated to increase their frequency of use if symptoms should arise. Not only does this give the patient a sense of self-empowerment over his or her disease state, but it avoids the cost of switching to a PPI due to failure with an H2RA or a motility agent. Alternate-day use of omeprazole should be attempted only during the maintenance phase of GERD therapy. Patients requiring >20 mg/d to achieve healing appeared to be poor candidates for alternate-day omeprazole maintenance therapy. Based on available studies, it would seem that patients with Grades 0-II GERD would benefit most from alternate-day therapy. A role for alternate-day therapy in Grades III-IV is apparent from the results presented but requires greater caution in view of the differing success rates (26-61%) in various studies. With Grades II-III esophagitis, a mean 24-hour gastric pH >6 and a gastric pH <4 less than 10% of the time during the initial healing phase with omeprazole 20 mg/d appeared to be associated with success on alternate-day therapy. Evidence that all marketed PPIs have similar success is not available and should not be extrapolated from the data presented. Evidence that downward dosage adjustments of PPIs versus extending dosage intervals are effective in the maintenance of GERD should be recognized. Lansoprazole has been approved for treating erosive esophagitis at 30 mg/d, with the maintenance dose established at 15 mg/d. Studies showing that lansoprazole 15 mg/d is more effective than alternate-day therapy with lansoprazole 30 mg exist, although similar studies with omeprazole have not been performed. The abstracts describing the use of alternate-day omeprazole accounted for all enrollees and included endoscopic grading or pH monitoring to document disease severity at baseline. Most also included these same objective measures as end points in combination with symptom control. This strengthens the data since the positive predictive value of typical symptoms is variable. However, there are also several significant limitations. Abstracts provide only limited information on methods. All studies other than Lind et al. lacked randomization. This study was also the only one that blinded patients to their treatment. Sample sizes for the majority of the trials were quite small. Statistical analyses were not performed on any of the trial results with the exception of the trial by Lind et al. In light of the lack of evidence of statistical significance as well as study design flaws, conclusions should be drawn cautiously. Larger well-designed trials looking at both the efficacy and cost-effectiveness of alternate day omeprazole are required before a definitive recommendation can be made.
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PMID:The efficacy of extended-interval dosing of omeprazole in keeping gastroesophageal reflux disease patients symptom free. 1036 30

Lansoprazole is an inhibitor of gastric acid secretion and also exhibits antibacterial activity against Helicobacter pylori in vitro. Current therapy for peptic ulcer disease focuses on the eradication of H. pylori infection with maintenance therapy indicated in those patients who are not cured of H. pylori and those with ulcers resistant to healing. Lansoprazole 30 mg combined with amoxicillin 1g, clarithromycin 250 or 500mg, or metronidazole 400 mg twice daily was associated with eradication rates ranging from 71 to 94%, and ulcer healing rates were generally >80% in well designed studies. In addition, it was as effective as omeprazole- or rabeprazole-based regimens which included these antimicrobial agents. Maintenance therapy with lansoprazole 30 mg/day was significantly more effective than either placebo or ranitidine in preventing ulcer relapse. Importantly, preliminary data suggest that lansoprazole-based eradication therapy is effective in children and the elderly. In the short-term treatment of patients with gastro-oesophageal reflux disease (GORD), lansoprazole 15, 30 or 60 mg/day was significantly more effective than placebo, ranitidine 300 mg/day or cisapride 40 mg/day and similar in efficacy to pantoprazole 40 mg/day in terms of healing of oesophagitis. Lansoprazole 30 mg/day, omeprazole 20 mg/day and pantoprazole 40 mg/day all provided similar symptom relief in these patients. In patients with healed oesophagitis. 12-month maintenance therapy with lansoprazole 15 or 30 mg/day prevented recurrence and was similar to or more effective than omeprazole 10 or 20 mg/day. Available data in patients with NSAID-related disorders or acid-related dyspepsia suggest that lansoprazole is effective in these patients in terms of the prevention of NSAID-related gastrointestinal complications, ulcer healing and symptom relief. Meta-analytic data and postmarketing surveillance in >30,000 patients indicate that lansoprazole is well tolerated both as monotherapy and in combination with antimicrobial agents. After lansoprazole monotherapy commonly reported adverse events included dose-dependent diarrhoea, nausea/vomiting, headache and abdominal pain. After short-term treatment in patients with peptic ulcer, GORD, dyspepsia and gastritis the incidence of adverse events associated with lansoprazole was generally < or = 5%. Similar adverse events were seen in long-term trials, although the incidence was generally higher (< or = 10%). When lansoprazole was administered in combination with amoxicillin, clarithromycin or metronidazole adverse events included diarrhoea, headache and taste disturbance. In conclusion, lansoprazole-based triple therapy is an effective treatment option for the eradication of H. pylori infection in patients with peptic ulcer disease. Preliminary data suggest it may have an important role in the management of this infection in children and the elderly. In the short-term management of GORD, lansoprazole monotherapy offers a more effective alternative to histamine H2-receptor antagonists and initial data indicate that it is an effective short-term treatment option in children and adolescents. In adults lansoprazole maintenance therapy is also an established treatment option for the long-term management of this chronic disease. Lansoprazole has a role in the treatment and prevention of NSAID-related ulcers and the treatment of acid-related dyspepsia; however, further studies are needed to confirm its place in these indications. Lansoprazole has emerged as a useful and well tolerated treatment option in the management of acid-related disorders.
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PMID:Lansoprazole: an update of its place in the management of acid-related disorders. 1169 67

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.
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PMID:An overview of the pharmacology, efficacy, safety and cost-effectiveness of lansoprazole. 1192

Gastro-oesophageal reflux disease, which is experienced daily by a significant proportion of individuals, may result in serious sequelae such as erosive oesophagitis. Short-term treatment with acid antisecretory therapy (a proton pump inhibitor or a histamine H(2) receptor antagonist) is highly effective in healing the erosive oesophagitis lesion. However, numerous studies confirm that unless maintenance therapy is initiated virtually all patients will experience oesophagitis relapse within 1 year, as well as an increasing severity of oesophagitis and risk for complications such as Barrett's oesophagus and adenocarcinoma. Studies evaluating the efficacy of proton pump inhibitor and H(2) antagonist maintenance therapy have found that only the proton pump inhibitors significantly reduce the incidence of oesophagitis relapse. Pharmacoeconomic studies have also confirmed that proton pump inhibitor maintenance therapy is cost effective, by virtue of the ability of these agents to reduce the incidence of relapse as well as prolong the time to relapse and increase the number of weeks per year that patients are without symptoms. Lansoprazole, a member of the proton pump inhibitor class of agents, has been extensively studied in the treatment of patients with a variety of acid-related disorders. Among those with erosive oesophagitis, maintenance therapy with lansoprazole 15 or 30mg once daily is highly effective in preventing relapse. Studies have documented that lansoprazole 15 and 30mg once daily for six months prevents oesophagitis relapse in up to 81 and 93% of patients, respectively, with comparable percentages of patients remaining in remission after 1 year of treatment. These high rates of remission have also been observed in studies of patients with lesions that were difficult to heal at baseline (resistant to healing with at least 3 months of H(2) antagonist therapy). Moreover, lansoprazole produces high remission rates regardless of the grade of erosive oesophagitis before acute healing. Among symptomatic patients with heartburn, lansoprazole provides rapid and effective relief of daytime and night-time heartburn and prevents relapse of symptoms. Lansoprazole has a wide margin of safety and is well tolerated when administered as monotherapy in short- and long-term clinical trials. Taken together these data suggest that proton pump inhibitor therapy represents the preferred and ideal long-term management strategy for the patient with erosive oesophagitis. Lansoprazole is a well-established member of this class of agents and, as such, has an extensive body of literature that supports its safety, tolerability and clinical efficacy in preventing relapse in these patients.
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PMID:Lansoprazole for maintenance of remission of erosive oesophagitis. 1201 78

Lansoprazole, a proton pump inhibitor, inactivates the H(+)/K(+)-ATPase pump in parietal cells, thereby suppressing basal and stimulated gastric acid secretion and increasing intragastric pH. After 8-12 weeks' treatment with lansoprazole, all children (n = 27) with esophagitis at baseline were healed (confirmed by endoscopy) and 76% of 62 evaluable children experienced improvements in overall gastroesophageal reflux disease (GERD) symptoms. In this noncomparative trial, 66 children (aged 1-11 years) with GERD with or without esophagitis received oral lansoprazole 15 or 30 mg once daily dependent on their weight. The drug is generally well tolerated in children with GERD. In the largest study, the most common treatment-related adverse events occurring during therapy were constipation and headache.
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PMID:Lansoprazole: in the management of gastroesophageal reflux disease in children. 1251 6

Approximately two thirds of pregnant patients develop heartburn. The origin is multifactorial, but the predominant factor is a decrease in LES pressure caused by female sex hormones, especially progesterone. Mechanical factors play a small role. Serious reflux complications during pregnancy are rare; therefore EGD and other diagnostic tests are infrequently needed. Symptomatic GERD during pregnancy should be managed with a step-up algorithm beginning with lifestyle modifications and dietary changes. Antacids or sucralfate are considered the first-line medical therapy. If symptoms persist, H2RAs should be used. Ranitidine is probably preferred because of its documented efficacy and safety profile in pregnancy, even in the first trimester. Proton-pump inhibitors are reserved for the woman with intractable symptoms or complicated reflux disease. Lansoprazole may be the preferred PPI because of its safety profile in animals and case reports of safety in human pregnancies.
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PMID:Gastroesophageal reflux disease during pregnancy. 1263 18

Lansoprazole is a proton pump inhibitor widely prescribed for gastroesophageal reflux and benign peptic ulcer disease. According to the manufacturer's package insert (TAP Pharmaceuticals, Lake Forest, IL, USA), the most common side-effects are diarrhea, headache and abdominal pain, which occur in approximately 3% of patients and are reversible with drug discontinuation. An unusual case of microscopic colitis is reported in a previously asymptomatic patient who developed new-onset diarrhea after initiation of lansoprazole. The case is reviewed and possible mechanisms of diarrhea secondary to proton pump inhibitors are discussed.
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PMID:Diarrhea associated with lansoprazole. 1270 56


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