MEDLINE Abstracts: Medical Management of the Patient With Gastrinoma
MEDLINE Abstracts: Medical Management of the Patient With Gastrinoma
Welage LS, Berardi RR.
J Am Pharm Assoc (Wash). 2000;40(1):52-62.
Objective: To review the comparative efficacy and safety of the proton pump inhibitors (PPIs)--omeprazole, lansoprazole, pantoprazole, and rabeprazole--in the management of acid-related diseases.
Data Sources: English-language journal articles retrieved from a MEDLINE search from 1990 to the present using these index terms: proton pump inhibitors, omeprazole, lansoprazole, pantoprazole, rabeprazole, and each of the acid-related diseases.
Study Selection: Clinical trials and pertinent review articles that discussed the pharmacology, pharmacokinetics, efficacy, and safety of PPIs in the management of acid-related disease.
Data Extraction: By the authors.
Data Synthesis: PPIs are substituted benzimidazoles that inhibit gastric acid secretion by covalently binding to the proton pump (H+/K+ ATPase). All undergo extensive hepatic metabolism and conjugation. The four agents differ in their metabolism by and effects on specific hepatic enzymes and thus in their ability to interact with other medications. PPIs are important agents used for eradicating Helicobacter pylori, in treating peptic ulcer disease, gastroesophageal reflux disease, Zollinger-Ellison syndrome, and upper gastrointestinal bleeding, and for preventing acid aspiration. Short-term side effects of the four agents are similar. The long-term safety of pantoprazole and rabeprazole appears similar to that of omeprazole and lansoprazole. Pantoprazole, which is in the final stages of approval for marketing in the United States, will be available in both an oral and injectable formulation.
Conclusion: Based on superior efficacy profiles, PPIs are the drugs of choice in managing patients with peptic ulcer disease, gastroesophageal reflux disease, and Zollinger-Ellison syndrome. The decision to select one PPI versus another is most likely to be based on the agents' acquisition costs, formulations, FDA-labeled indications, and overall safety profiles. Intravenous or parenteral pantoprazole may become the preferred antisecretory agent for patients unable to take oral medications (e.g., critically ill patients and those with Zollinger-Ellison syndrome).
Qureshi W, Rashid S.
Postgrad Med. 1998;104(1):155-158, 163-164.
Zollinger-Ellison syndrome is a rare disorder characterized by severe peptic ulcer disease, gastric acid hypersecretion, and non-beta islet cell tumors of the pancreas. Most gastrinomas are found within an anatomic area known as the gastrinoma triangle. However, they commonly occur in extrapancreatic sites in multiple endocrine neoplasia type 1 syndrome. In patients in whom Zollinger-Ellison syndrome is suspected, laboratory evidence of hypergastrinemia and hyperacidity establishes the diagnosis. Until the advent of proton pump inhibitors, total gastrectomy was the treatment of choice. Therapy with these agents (eg, omeprazole, lansoprazole) can prevent ulcer disease. However, surgical removal of gastrinomas offers a chance for cure and can improve longevity by preventing the malignant spread of the tumors.
Gaztambide S, Vazquez JA.
J Endocrinol Invest. 1999;22(2):144-146.
Medical treatment is the elective therapy for patients with gastrinoma when the tumor is not found at surgery or is unresectable or when there is a metastatic disease. H2-blockers and omeprazole are able to control gastric acid secretion and, in addition, somatostatin analogues decrease gastrin levels. A new long-acting and slow release formulation of a somatostatin analogue (lanreotide, SR-L) has been developed. We treated two patients suffering from gastrinoma, total gastrectomy and hepatic metastases with 30 mg intramuscular injections of SR-L every 15 and 10 days, respectively, for a seven-month period. After the treatment, gastrin levels decreased from 35,494 and 15,086 ng/l to 3,211 and 167 ng/l (92 and 98% below pre-treatment levels) in case 1 and 2 respectively, with a relief of symptoms and no side effects.
Langtry HD, Markham A.
Drugs. 1999;58(4):725-742.
Rabeprazole is an inhibitor of the gastric proton pump. It causes dose-dependent inhibition of acid secretion and has a more rapid onset of action than omeprazole. Duodenal ulcers healed faster after treatment with rabeprazole 20 or 40 mg/day than placebo or ranitidine 150 mg 4 times daily and at a generally similar rate to omeprazole 20 mg/day in patients with duodenal ulcers; rabeprazole was similar or superior to these agents in relieving symptoms. Rabeprazole 20 and 40 mg/day healed gastric ulcers faster than placebo, and rabeprazole 20 mg/day healed ulcers at a similar healing rate to omeprazole 20 mg/day in well controlled 6-week studies. Gastric ulcer symptom relief with rabeprazole was similar or superior to that provided by omeprazole or placebo. In 8-week studies in patients with gastro-oesophageal reflux disease (GERD), rabeprazole 10, 20 and 40 mg/day were more effective than placebo, rabeprazole 20 mg/day was more effective than ranitidine 150 mg twice daily, and rabeprazole 20 mg/day was similar in efficacy to omeprazole 20 mg/day. Symptom relief with rabeprazole in 8-week trials in patients with GERD was superior to that provided by placebo, and similar to ranitidine or omeprazole. Rabeprazole was similar to omeprazole and superior to placebo in both maintenance of healing and prevention of symptoms in patients with healed GERD in 1-year studies. One-week triple therapy with rabeprazole 20 mg twice daily plus 2 antibacterial agents achieved > or = 90% Helicobacter pylori eradication, but, as would be expected, a regimen of rabeprazole 20 mg twice daily plus 1 antibacterial agent was less successful. The drug was as effective as omeprazole and lansoprazole as part of triple therapy for H. pylori eradication. Rabeprazole successfully reduced acid output to target levels and prevented further pathological changes in 10 patients with Zollinger-Ellison syndrome. Usual dosages of rabeprazole are 20 mg/day for 4 weeks to treat duodenal ulcers, 6 weeks for gastric ulcers and 8 weeks for GERD, although some patients with duodenal ulcer may respond to a 10 mg/day dosage. For long term maintenance of GERD healing, 10 or 20 mg daily doses are adequate. Patients with hypersecretory states may need individualised dosages starting at 60 mg/day. The drug was well tolerated in clinical trials, with headache, rash, infection, diarrhoea and flu syndrome as the most common adverse events. In conclusion, rabeprazole appears to be a well tolerated proton pump inhibitor with a rapid onset of action and a low potential for drug interactions. The drug may be used to achieve healing and the relief of symptoms of duodenal ulcer, gastric ulcer and GERD, maintain GERD healing, and can form part of effective regimens to eradicate H. pylori.
Richardson P, Hawkey CJ, Stack WA.
Drugs. 1998;56(3):307-335.
Proton pump inhibitors (PPIs) are drugs which irreversibly inhibit proton pump (H+/K+ ATPase) function and are the most potent gastric acid-suppressing agents in clinical use. There is now a substantial body of evidence showing improved efficacy of PPIs over the histamine H2 receptor antagonists and other drugs in acid-related disorders. Omeprazole 20 mg/day, lansoprazole 30 mg/day, pantoprazole 40 mg/day or rabeprazole 20 mg/day for 2 to 4 weeks are more effective than standard doses of H2-receptor antagonists in healing duodenal and gastric ulcers. Patients with gastric ulcers should receive standard doses of PPIs as for duodenal ulcers but for a longer time period (4 to 8 weeks). There is no conclusive evidence to support the use of a particular PPI over another for either duodenal or gastric ulcer healing. For Helicobacter pylori-positive duodenal ulceration, a combination of a PPI and 2 antibacterials will eradicate H. pylori in over 90% of cases and significantly reduce ulcer recurrence. Patients with H. pylori-positive gastric ulcers should be managed similarly. PPIs also have efficacy advantages over ranitidine and misoprostol and are better tolerated than misoprostol in patients taking nonsteroidal anti-inflammatory drugs (NSAIDs). In endoscopically proven gastro-oesophageal reflux disease, standard daily doses of the PPIs are more effective than H2-receptor antagonists for healing, and patients should receive a 4 to 8 week course of treatment. For severe reflux, with ulceration and/or stricture formation, a higher dose regimen (omeprazole 40 mg, lansoprazole 60 mg, pantoprazole 80 mg or rabeprazole 40 mg daily) appears to yield better healing rates. There is little evidence that PPIs lead to resolution of Barrett's oesophagus or a reduction of subsequent adenocarcinoma development, but PPIs are indicated in healing of any associated ulceration. In Zollinger-Ellison syndrome, PPIs have become the treatment of choice for the management of gastric acid hypersecretion.
Welage LS, Berardi RR.
J Am Pharm Assoc (Wash). 2000;40(1):52-62.
Objective: To review the comparative efficacy and safety of the proton pump inhibitors (PPIs)--omeprazole, lansoprazole, pantoprazole, and rabeprazole--in the management of acid-related diseases.
Data Sources: English-language journal articles retrieved from a MEDLINE search from 1990 to the present using these index terms: proton pump inhibitors, omeprazole, lansoprazole, pantoprazole, rabeprazole, and each of the acid-related diseases.
Study Selection: Clinical trials and pertinent review articles that discussed the pharmacology, pharmacokinetics, efficacy, and safety of PPIs in the management of acid-related disease.
Data Extraction: By the authors.
Data Synthesis: PPIs are substituted benzimidazoles that inhibit gastric acid secretion by covalently binding to the proton pump (H+/K+ ATPase). All undergo extensive hepatic metabolism and conjugation. The four agents differ in their metabolism by and effects on specific hepatic enzymes and thus in their ability to interact with other medications. PPIs are important agents used for eradicating Helicobacter pylori, in treating peptic ulcer disease, gastroesophageal reflux disease, Zollinger-Ellison syndrome, and upper gastrointestinal bleeding, and for preventing acid aspiration. Short-term side effects of the four agents are similar. The long-term safety of pantoprazole and rabeprazole appears similar to that of omeprazole and lansoprazole. Pantoprazole, which is in the final stages of approval for marketing in the United States, will be available in both an oral and injectable formulation.
Conclusion: Based on superior efficacy profiles, PPIs are the drugs of choice in managing patients with peptic ulcer disease, gastroesophageal reflux disease, and Zollinger-Ellison syndrome. The decision to select one PPI versus another is most likely to be based on the agents' acquisition costs, formulations, FDA-labeled indications, and overall safety profiles. Intravenous or parenteral pantoprazole may become the preferred antisecretory agent for patients unable to take oral medications (e.g., critically ill patients and those with Zollinger-Ellison syndrome).
Qureshi W, Rashid S.
Postgrad Med. 1998;104(1):155-158, 163-164.
Zollinger-Ellison syndrome is a rare disorder characterized by severe peptic ulcer disease, gastric acid hypersecretion, and non-beta islet cell tumors of the pancreas. Most gastrinomas are found within an anatomic area known as the gastrinoma triangle. However, they commonly occur in extrapancreatic sites in multiple endocrine neoplasia type 1 syndrome. In patients in whom Zollinger-Ellison syndrome is suspected, laboratory evidence of hypergastrinemia and hyperacidity establishes the diagnosis. Until the advent of proton pump inhibitors, total gastrectomy was the treatment of choice. Therapy with these agents (eg, omeprazole, lansoprazole) can prevent ulcer disease. However, surgical removal of gastrinomas offers a chance for cure and can improve longevity by preventing the malignant spread of the tumors.
Gaztambide S, Vazquez JA.
J Endocrinol Invest. 1999;22(2):144-146.
Medical treatment is the elective therapy for patients with gastrinoma when the tumor is not found at surgery or is unresectable or when there is a metastatic disease. H2-blockers and omeprazole are able to control gastric acid secretion and, in addition, somatostatin analogues decrease gastrin levels. A new long-acting and slow release formulation of a somatostatin analogue (lanreotide, SR-L) has been developed. We treated two patients suffering from gastrinoma, total gastrectomy and hepatic metastases with 30 mg intramuscular injections of SR-L every 15 and 10 days, respectively, for a seven-month period. After the treatment, gastrin levels decreased from 35,494 and 15,086 ng/l to 3,211 and 167 ng/l (92 and 98% below pre-treatment levels) in case 1 and 2 respectively, with a relief of symptoms and no side effects.
Langtry HD, Markham A.
Drugs. 1999;58(4):725-742.
Rabeprazole is an inhibitor of the gastric proton pump. It causes dose-dependent inhibition of acid secretion and has a more rapid onset of action than omeprazole. Duodenal ulcers healed faster after treatment with rabeprazole 20 or 40 mg/day than placebo or ranitidine 150 mg 4 times daily and at a generally similar rate to omeprazole 20 mg/day in patients with duodenal ulcers; rabeprazole was similar or superior to these agents in relieving symptoms. Rabeprazole 20 and 40 mg/day healed gastric ulcers faster than placebo, and rabeprazole 20 mg/day healed ulcers at a similar healing rate to omeprazole 20 mg/day in well controlled 6-week studies. Gastric ulcer symptom relief with rabeprazole was similar or superior to that provided by omeprazole or placebo. In 8-week studies in patients with gastro-oesophageal reflux disease (GERD), rabeprazole 10, 20 and 40 mg/day were more effective than placebo, rabeprazole 20 mg/day was more effective than ranitidine 150 mg twice daily, and rabeprazole 20 mg/day was similar in efficacy to omeprazole 20 mg/day. Symptom relief with rabeprazole in 8-week trials in patients with GERD was superior to that provided by placebo, and similar to ranitidine or omeprazole. Rabeprazole was similar to omeprazole and superior to placebo in both maintenance of healing and prevention of symptoms in patients with healed GERD in 1-year studies. One-week triple therapy with rabeprazole 20 mg twice daily plus 2 antibacterial agents achieved > or = 90% Helicobacter pylori eradication, but, as would be expected, a regimen of rabeprazole 20 mg twice daily plus 1 antibacterial agent was less successful. The drug was as effective as omeprazole and lansoprazole as part of triple therapy for H. pylori eradication. Rabeprazole successfully reduced acid output to target levels and prevented further pathological changes in 10 patients with Zollinger-Ellison syndrome. Usual dosages of rabeprazole are 20 mg/day for 4 weeks to treat duodenal ulcers, 6 weeks for gastric ulcers and 8 weeks for GERD, although some patients with duodenal ulcer may respond to a 10 mg/day dosage. For long term maintenance of GERD healing, 10 or 20 mg daily doses are adequate. Patients with hypersecretory states may need individualised dosages starting at 60 mg/day. The drug was well tolerated in clinical trials, with headache, rash, infection, diarrhoea and flu syndrome as the most common adverse events. In conclusion, rabeprazole appears to be a well tolerated proton pump inhibitor with a rapid onset of action and a low potential for drug interactions. The drug may be used to achieve healing and the relief of symptoms of duodenal ulcer, gastric ulcer and GERD, maintain GERD healing, and can form part of effective regimens to eradicate H. pylori.
Richardson P, Hawkey CJ, Stack WA.
Drugs. 1998;56(3):307-335.
Proton pump inhibitors (PPIs) are drugs which irreversibly inhibit proton pump (H+/K+ ATPase) function and are the most potent gastric acid-suppressing agents in clinical use. There is now a substantial body of evidence showing improved efficacy of PPIs over the histamine H2 receptor antagonists and other drugs in acid-related disorders. Omeprazole 20 mg/day, lansoprazole 30 mg/day, pantoprazole 40 mg/day or rabeprazole 20 mg/day for 2 to 4 weeks are more effective than standard doses of H2-receptor antagonists in healing duodenal and gastric ulcers. Patients with gastric ulcers should receive standard doses of PPIs as for duodenal ulcers but for a longer time period (4 to 8 weeks). There is no conclusive evidence to support the use of a particular PPI over another for either duodenal or gastric ulcer healing. For Helicobacter pylori-positive duodenal ulceration, a combination of a PPI and 2 antibacterials will eradicate H. pylori in over 90% of cases and significantly reduce ulcer recurrence. Patients with H. pylori-positive gastric ulcers should be managed similarly. PPIs also have efficacy advantages over ranitidine and misoprostol and are better tolerated than misoprostol in patients taking nonsteroidal anti-inflammatory drugs (NSAIDs). In endoscopically proven gastro-oesophageal reflux disease, standard daily doses of the PPIs are more effective than H2-receptor antagonists for healing, and patients should receive a 4 to 8 week course of treatment. For severe reflux, with ulceration and/or stricture formation, a higher dose regimen (omeprazole 40 mg, lansoprazole 60 mg, pantoprazole 80 mg or rabeprazole 40 mg daily) appears to yield better healing rates. There is little evidence that PPIs lead to resolution of Barrett's oesophagus or a reduction of subsequent adenocarcinoma development, but PPIs are indicated in healing of any associated ulceration. In Zollinger-Ellison syndrome, PPIs have become the treatment of choice for the management of gastric acid hypersecretion.
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