Studies on (H(+)-K+)-ATPase inhibitors of gastric acid secretion. Prodrugs of 2-[(2-pyridinylmethyl)sulfinyl]benzimidazole proton-pump inhibitors. Controlling gastric pH: the impact of newer agents on the critically ill patient. Effectiveness of omeprazole in seven patients with Zollinger-Ellison syndrome resistant to histamine H2-receptor antagonists. Rx drugs

Drugs online research references

J Med Chem. 1991 Mar;34(3):1049-62.
Studies on (H(+)-K+)-ATPase inhibitors of gastric acid secretion. Prodrugs of 2-[(2-pyridinylmethyl)sulfinyl]benzimidazole proton-pump inhibitors.

Sih JC, Im WB, Robert A, Graber DR, Blakeman DP.

Research Laboratories, Upjohn Company, Kalamazoo, Michigan 49001.

The synthesis of N-substituted benzimidazole (H(+)-K+)-ATPase or proton-pump inhibitors is described. These compounds were prepared to function as prodrugs of the parent N-H compound and evaluated for their ability to inhibit gastric (H(+)-K+)-ATPase and gastric acid secretion. The prodrugs reported rely on either in vivo esterase hydrolysis for liberation of the parent compound (type I and type II) or require an acid environment for release of the active drug (type III and type IV). The N-(acyloxy)alkyl-substituted benzimidazoles 9, 11, and 24 showed improved chemical stability in the solid state and in aqueous solutions when compared to their parent N-H compounds. When given orally, 24 was found to be twice as potent as omeprazole in both the Shay rat and inactivation of gastric (H(+)-K+)-ATPase in the rat. The N-ethoxy-1-ethyl-substituted benzimidazoles 48-50 were found equally as effective as the N-H compound for inhibition of rat (H(+)-K+)-ATPase activity. In the Shay rat 48 at 10 mg/kg was approximately twice as active as parent timoprazole.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1848293&dopt=Abstract

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DICP. 1990 Nov;24(11 Suppl):S31-4.
Controlling gastric pH: the impact of newer agents on the critically ill patient.

Earnest DL.

University of Arizona Health Science Center, Tucson 85724.

The critically ill patient is at increased risk for developing erosive injury of the stomach, duodenum, and esophagus. To date, the most effective way to prevent and treat this problem is by assuring excellent intensive care support and by reducing gastric acid secretion. The histamine H2-receptor antagonists (H2RAs) are effective in both prevention and treatment of such gastric mucosal injury. Newer agents are available that have potential for use in this setting, although none have been studied as extensively in critically ill patients as have the H2RAs. These new agents include proglumide, pirenzepine, misoprostol, omeprazole, and somatostatin. To date, only the latter has been extensively studied in critically ill patients. Omeprazole, which suppresses acid very effectively, may be problematic in the critically ill, limited by its oral dosage form, acid-labile properties, and potential drug interactions.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1980181&dopt=Abstract

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Dig Dis Sci. 1986 Jul;31(7):693-9.
Effectiveness of omeprazole in seven patients with Zollinger-Ellison syndrome resistant to histamine H2-receptor antagonists.

Delchier JC, Soule JC, Mignon M, Goldfain D, Cortot A, Travers B, Isal JP, Bader JP.

The inhibitory effect of omeprazole, a benzimidazole derivative, on gastric acid secretion was investigated in seven patients with Zollinger-Ellison syndrome resistant to treatment with large doses of histamine H2-receptor antagonists administered alone or in combination with pirenzepine. In two patients with an acute form of the syndrome, rapid control of acid overproduction was achieved with 180-mg intravenous and 120-mg oral daily doses, respectively. The other five patients, who were free of complication, initially received a standard regimen of omeprazole 60 mg orally once a day; dosage was subsequently adjusted until the basal acid output, measured 1 hr before the next dose of the drug, was less than 10 mmol/hr. The initial daily dose proved to be adequate in three patients and had to be increased to 80 mg and 60 mg bid, respectively in the remaining two patients. In all patients omeprazole therapy resulted in clinical recovery and rapid healing of mucosal lesions. The seven patients have now been followed up for 4-24 months (average 15 months). The adequacy of the daily dosage was periodically reassessed by measuring basal acid output in the hour preceding the morning dose. In one patient initially treated with 180 mg/day, dosage could be reduced to 60 mg/day. In three others, who were initially controlled with 60 mg/day, dosage had to be increased during follow-up. Despite adequate control of gastric acid secretion, one patient underwent total gastrectomy and tumor resection and another died of extensive liver metastases. The five patients still receiving omeprazole remain free of symptoms and mucosal lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2873001&dopt=Abstract

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