No abstract

SUMMARYThe effect of loperamide and naloxone on mouth-to-caecum transit time was evaluated by the lactulose hydrogen breath test in four men and four women. Each subject underwent tests during the administration of placebo, loperamide (12-16 mg po), naloxone (40 ,ug/kg/h by a three-hour intravenous infusion), and loperamide plus naloxone, carried out at intervals of one or two weeks. The transit time was significantly longer after loperamide, and this effect was antagonised by the concomitant administration of naloxone whereas naloxone administered alone had no effect on mean transit time. No clinically important side effects were reported.Morphine changes the motility pattern in the gastrointestinal tract,' decreases the propulsion of its contents,2 3 reduces gastric4 and intestinal secretions5 and increases water and ions absorption.6 7 Loperamide, an opioid agonist,

Impairment of non-cholinergic innervation of the lower oesophageal sphincter has been suggested in idiopathic achalasia. As opioid nerves are present in the lower oesophageal sphincter and opioid peptides affect lower oesophageal sphincter motility, the effect of an opioid agonist, morphine (100 ,uggkg iv), and an opioid blocker, naloxone (80 ,ug/kg iv), on lower oesophageal sphincter motor function was assessed in 10 healthy subjects and in 10 patients with untreated idiopathic achalasia on separate days and in randomised order. In addition, in six ofthe patients, naloxone 0x8 mg iv was injected 60 minutes after morphine and recordings continued for a further five minutes. Lower oesophageal sphincter pressure was monitored by a sleeve device. In the healthy subjects morphine decreased (p<0-01) resting lower oesophageal sphincter pressure by 4 (1) mm Hg (23 (8)%). In the achalasia patients the effect was more marked, lower oesophageal sphincter pressure being reduced (p<001) by 11 (2) mm Hg (46 (8)%). Naloxone reversed lower oesophageal sphincter pressure to basal. Both absolute and percentage decreases after morphine were significantly greater (p<005) in the achalasia patients than in the healthy subjects. Swallow induced lower oesophageal sphincter relaxation was significantly decreased (p<005) by morphine in the healthy subjects but not in the achalasia patients. Naloxone had no effect on resting lower oesophageal sphincter pressure or swallow induced relaxation in either healthy subjects or achalasia patients. In conclusion achalasia patients are hypersensitive to the effect of morphine on resting lower oesophageal sphincter pressure. This finding is unlikely to be the result ofa denervation process involving opioid nerves. (Gut 1993; 34: 16-20) Idiopathic achalasia is a disease ofthe oesophagus characterised by absent peristalsis, impaired lower oesophageal sphincter relaxation after swallows and often a high lower oesophageal sphincter resting pressure.' Achalasia is thought to be determined by a visceral neuropathy which probably involves the vagal preganglionic and the postganglionic nerve fibres of the oesophagus.2 During the past years the attention has been focused mainly on the lower oesophageal sphincter, and some results suggest that noncholinergic inhibitory nerves are impaired4 whereas cholinergic innervation is at least partly preserved.Opioid nerves have been shown in the myenteric plexus of normal lower oesophageal sphincter in man" and various opioid receptors have been identified in the opossum lower oesophageal sphincter, in the sphincter muscle and the nerve fibres surrounding it.'" Furthermore, evidence exists that opioid peptides affect lower oesophageal sphincter motor function."-'5 In particular one study'4 showed that an opioid agonist, morphine, administered to healthy subjects determined a decrease and an opioid blocker, naloxone, an increase, although modest, in lower oesophageal sphincter pressure. The latter finding may suggest that endogenous opioids contribute to th...

Orocecal transit time was assessed with lactulose hydrogen breath test in 12 obese patients during intravenous infusion of placebo or naloxone 40 micrograms/kg/hr given in randomized order and in double-blind conditions. Transit time was also evaluated in 22 healthy controls. Orocecal transit was significantly (P less than 0.01) longer in the obese patients, during placebo treatment (median 130, range 100-200 min) than in the healthy controls (median 75, range 40-170 min). Compared with placebo, transit time in the obese subjects was delayed (P less than 0.05) during naloxone treatment (median 150, range 100-230 min).

The within-subject repeatability of orocecal transit assessed with lactulose hydrogen breath test was evaluated in 15 healthy volunteers and 16 constipated or obese patients. The test was repeated twice in each subject. Mean (SD) transit time was 105 (63) and 103 (60) min in the first and second series of tests, respectively, showing that the first measurement did not affect the second. The within-subject repeatability of the test was related to the length of transit, the scatter of the differences between the first and second test being greater with the increase of the mean gastrointestinal transit time. The 95% coefficient of repeatability was 84 min for all measurements and 30 and 118 min, respectively, for transit times under and over 100 min. The lowest reproducibility of the test was found in constipated patients with prolonged orocecal transit.