ABSTRACT
The gastric effects of synthetic secretin given in a depot preparation as subcutaneous injection or in different doses as intravenous infusion were studied in 10 healthy volunteers. Peptone-stimulated gastric acid secretion and serum gastrin were significantly suppressed with a clear dose-response inhibition of acid output. There was a significant correlation between percentage inhibition of acid secretion and plasma secretin concentrations which were greatly above those seen physiologically. Serum lipase and trypsin increased significantly. Most subjects lost fluid from diuresis and diarrhoea, so that serum sodium and total protein concentrations also increased significantly. These side effects cast doubt on the clinical value of prolonged infusions of pharmacological doses of synthetic secretion in critically ill patients.
Subject(s)
Gastric Mucosa/drug effects , Secretin/adverse effects , Adult , Dose-Response Relationship, Drug , Fasting , Female , Gastric Acid/metabolism , Gastrins/blood , Humans , Infusions, Parenteral , Injections, Subcutaneous , Lipase/blood , Male , Peptones/pharmacology , Potassium/blood , Sodium/blood , Trypsin/bloodABSTRACT
Two possibilities of an inhibition of gastric acid secretion are compared in regard to effectiveness and side effects. Combined i.v. bolus injection of 0.3 mg/kg cimetidine caused almost complete inhibition of peptone-stimulated acid secretion in normal volunteers and duodenal ulcer patients-radomized and double blind investigated-to the same extent as high dose secretin (3 CU/kg/h i.v. infusion) in normal volunteers. Postprandial gastrin was unchanged by combined drug application, but was suppressed by secretin. Temporary blurred vision, dry mouth, and signifiant increase of serum prolactin were side effects of the drug combination, whereas secretin caused dose-dependent diarrhoea, increaded diuresis and elecvation of serum lipase, trypsin, and sodium. Inhibition of acid secretion by combination of the antimuscarinic drug pirenzepine with the H2-receptor blocking substances cimetidine was almost complete, i.e. more effective than the combination of classic anticholinergics with H2-blockers tested so far. Inhibition of acid secretion by secretin was dose-dependent; the dosage clinically applied so far (10 CU/kg s.c. and 0.5 CU/kg/h i.v.) had the smallest effect. In spite of first favourable results with secretin in bleeding mucosal lesions, the observed side effects cast doubt on its broad clinical applicability. A controlled clinical trial of the combination of cimetidine plus pirenzepine as prophylaxis of bleeding from mucosal lesions in risk patients seems to be indicated.
