Inhibition of pancreaticobiliary secretion by loperamide in humans

Abstract

effects of loperamide on pancreaticobiliary functions are Loperamide, a peripherally acting opiate receptor agonist poorly investigated. Inhibition of gallbladder emptying or with antidiarrheal action, inhibits ileal and colonic motor pancreatic enzyme secretion by loperamide may have imfunction. It was determined whether loperamide also affects portant clinical implications because stasis of bile is a major gallbladder emptying and pancreatic enzyme secretion in hufactor contributing to the formation of gallstones 6-10 and bemans. Plasma cholecystokinin (radioimmunoassay), gallbladcause impairment of pancreatic enzyme secretion may induce der volume (ultrasonography), and intraduodenal bilirubin or aggravate maldigestion. 11-13 and amylase output (spot sampling) were measured at regularThe aim of this study, therefore, was to determine the intervals before and during intraduodenal perfusion of an effect of loperamide on basal and meal-stimulated gallbladder amino acid meal in 8 healthy subjects: once without and once motility and pancreatic enzyme secretion in healthy volunwith pretreatment of 8 mg loperamide, ingested 13 and 4 teers. Gallbladder emptying and pancreatic enzyme secretion hours before the start of the meal. Loperamide decreased were studied in response to an intraduodenal amino acid basal amylase output from 3.2 { 0.5 to 1.0 { 0.5 kU/h meal to circumvent possible influences of loperamide on gas-(P õ .005) and abolished basal bilirubin output (21 { 5 vs.tric emptying or on the digestion of nutrients. 14 0 { 0 mmol/h; P õ .005) into the duodenum. Loperamide increased basal gallbladder volume from 28 { 4 to 39 { 4 PATIENTS AND METHODS mL (P õ .0001) but was without effect on basal plasma cholecystokinin (2.7 { 0.3 vs. 3.0 { 0.3 pmol/L). During Subjects. Eight healthy volunteers (3 women and 5 men; age the amino acid meal, pretreatment with loperamide inhibited range, 19-27 years) participated in the studies. None of the volunamylase output from 5.1 { 0.8 to 1.6 { 0.4 kU/h (P õ .001), teers was taking any medication or had a history of gastrointestinal bilirubin output from 39 { 6 to 18 { 6 mmol/h (P õ .0005) symptoms or surgery. The study protocol was approved by the and gallbladder contraction from 47% { 3% to 26% { 6% ethical committee of the University Hospital Nijmegen, and all sub-(P õ .05), whereas loperamide enhanced amino acid-stimu-jects gave their written informed consent before entering the study.

Human pancreatic exocrine response to nutrients in health and disease

“…49 If only essential amino acids with stimulatory potency were perfused, even 150 mmol/min induced a sustained twofold increase in amylase secretion (53 U/min v 85 U/min). 48 Constant duodenal perfusion of essential amino acids at a higher dose (800 mmol/min) caused a short lived (,30 min) peak trypsin output (basal: 25 U/min, peak: 160 U/min) followed by a stable 50% maximal enzyme output (about 120 U/min) throughout amino acid perfusion (.5 hours). 16 Doubling the protein content of an otherwise unchanged low caloric test meal also doubled cumulative lipase output.…”

Regulation of cholecystokinin secretion in humans

“…In humans, loperamide enhanced post-prandial CCK secretion and inhibited amino acid-stimulated gallbladder contraction. 65 The effects of other opiates and the exact site of action for stimulating CCK secretion remain to be determined.…”

Loperamide-Induced Acute Pancreatitis

“…Loperamide, a peripheral acting opiate [6], has very rarely been associated with pancreatitis. The first case report on this possible association, published in French, described a 57-year-old woman with a history of a cholecystectomy, who had taken 4 mg of loperamide therapeutically and presented 2 hours later with lower abdominal pain and an elevated amylase that normalized in several days.…”

“…Loperamide is a synthetic agonist of peripheral opiate receptors and used in treatment of diarrhea [6]. The effect on diarrhea is primarily due to an inhibition of intestinal secretion and gut motility [10].…”