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. 1982 Nov;70(5):999–1008. doi: 10.1172/JCI110711

Studies of the Mechanism of the Antidiarrheal Effect of Codeine

Lawrence R Schiller 1,2, Glenn R Davis 1,2, Carol A Santa Ana 1,2, Stephen G Morawski 1,2, John S Fordtran 1,2
PMCID: PMC370312  PMID: 7130398

Abstract

To determine whether the antidiarrheal action of opiate drugs in humans is due to enhanced intestinal absorption rates, as suggested by recent experiments in animals, or is due to altered intestinal motility, as traditionally thought, we studied the effect of therapeutic doses of codeine on experimental diarrhea and on the rate of intestinal absorption of water and electrolytes in normal human subjects. Our results show that codeine (30-60 mg i.m.) markedly reduced stool volume during experimental diarrhea induced by rapid intragastric infusion of a balanced electrolyte solution. There was, however, no evidence that codeine stimulated the rate of intestinal absorption in the gut as a whole or in any segment of the gastrointestinal tract, either in the basal state or when absorption rates were reduced by intravenous infusion of vasoactive intestinal polypeptide. We also measured segmental transit times to determine whether and where codeine delayed the passage of fluid through the intestine. Codeine caused a marked slowing of fluid movement through the jejunum, but had no effect on the movement of fluid through the ileum or colon. In other studies, we found that the opiate antagonist naloxone did not significantly affect water or electrolyte absorption rates in the jejunum or ileum. We conclude (a) that therapeutic doses of codeine increase net intestinal absorption (and thereby reduce stool volume) by increasing the contact time of luminal fluid with mucosal cells, not by increasing the rate of absorption by the mucosal cells; and (b) that endogenous opiates do not regulate intestinal absorption in humans.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beubler E., Lembeck F. Inhibition of stimulated fluid secretion in the rat small and large intestine by opiate agonists. Naunyn Schmiedebergs Arch Pharmacol. 1979 Mar;306(2):113–118. doi: 10.1007/BF00498980. [DOI] [PubMed] [Google Scholar]
  2. Caldara R., Cambielli M., Masci E., Guslandi M., Barbieri C., Ferrari C. Effect of loperamide and naloxone on gastric acid secretion in healthy man. Gut. 1981 Sep;22(9):720–723. doi: 10.1136/gut.22.9.720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Caren J. F., Meyer J. H., Grossman M. I. Canine intestinal secretion during and after rapid distention of the small bowel. Am J Physiol. 1974 Jul;227(1):183–188. doi: 10.1152/ajplegacy.1974.227.1.183. [DOI] [PubMed] [Google Scholar]
  4. Coupar I. M. Inhibition by morphine of prostaglandin-stimulated fluid secretion in rat jejunum. Br J Pharmacol. 1978 May;63(1):57–63. doi: 10.1111/j.1476-5381.1978.tb07774.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Davis G. R., Santa Ana C. A., Morawski S. G., Fordtran J. S. Development of a lavage solution associated with minimal water and electrolyte absorption or secretion. Gastroenterology. 1980 May;78(5 Pt 1):991–995. [PubMed] [Google Scholar]
  6. Davis G. R., Santa Ana C. A., Morawski S. G., Fordtran J. S. Effect of vasoactive intestinal polypeptide on active and passive transport in the human jejunum. J Clin Invest. 1981 Jun;67(6):1687–1694. doi: 10.1172/JCI110206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Davis G. R., Santa Ana C. A., Morawski S., Fordtran J. S. Active chloride secretion in the normal human jejunum. J Clin Invest. 1980 Dec;66(6):1326–1333. doi: 10.1172/JCI109985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Davis G. R., Santa Ana C. A., Morawski S., Fordtran J. S. Active chloride secretion in the normal human jejunum. J Clin Invest. 1980 Dec;66(6):1326–1333. doi: 10.1172/JCI109985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dobbins J., Racusen L., Binder H. J. Effect of D-alanine methionine enkephalin amide on ion transport in rabbit ileum. J Clin Invest. 1980 Jul;66(1):19–28. doi: 10.1172/JCI109830. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Feldman M., Walsh J. H., Taylor I. L. Effect of naloxone and morphine on gastric acid secretion and on serum gastrin and pancreatic polypeptide concentrations in humans. Gastroenterology. 1980 Aug;79(2):294–298. [PubMed] [Google Scholar]
  11. Fordtran J. S., Locklear T. W. Ionic constituents and osmolality of gastric and small-intestinal fluids after eating. Am J Dig Dis. 1966 Jul;11(7):503–521. doi: 10.1007/BF02233563. [DOI] [PubMed] [Google Scholar]
  12. Fordtran J. S. Marker perfusion techniques for measuring intestinal absorption in man. Gastroenterology. 1966 Dec;51(6):1089–1093. [PubMed] [Google Scholar]
  13. Fordtran J. S., Rector F. C., Jr, Carter N. W. The mechanisms of sodium absorption in the human small intestine. J Clin Invest. 1968 Apr;47(4):884–900. doi: 10.1172/JCI105781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kachur J. F., Miller R. J., Field M. Control of guinea pig intestinal electrolyte secretion by a delta-opiate receptor. Proc Natl Acad Sci U S A. 1980 May;77(5):2753–2756. doi: 10.1073/pnas.77.5.2753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Karim S. M., Adaikan P. G. The effect of loperamide on prostaglandin induced diarrhoea in rat and man. Prostaglandins. 1977 Feb;13(2):321–331. doi: 10.1016/0090-6980(77)90011-9. [DOI] [PubMed] [Google Scholar]
  16. Lembeck F., Beubler E. Inhibition of PGE1 induced intestinal secretion by the synthetic enkephalin analogue FK 33-824. Naunyn Schmiedebergs Arch Pharmacol. 1979 Sep;308(3):261–264. doi: 10.1007/BF00501391. [DOI] [PubMed] [Google Scholar]
  17. Lord J. A., Waterfield A. A., Hughes J., Kosterlitz H. W. Endogenous opioid peptides: multiple agonists and receptors. Nature. 1977 Jun 9;267(5611):495–499. doi: 10.1038/267495a0. [DOI] [PubMed] [Google Scholar]
  18. Martin W. R., Eades C. G., Thompson J. A., Huppler R. E., Gilbert P. E. The effects of morphine- and nalorphine- like drugs in the nondependent and morphine-dependent chronic spinal dog. J Pharmacol Exp Ther. 1976 Jun;197(3):517–532. [PubMed] [Google Scholar]
  19. McKay J. S., Linaker B. D., Turnberg L. A. Influence of opiates on ion transport across rabbit ileal mucosa. Gastroenterology. 1981 Feb;80(2):279–284. [PubMed] [Google Scholar]
  20. Palmer K. R., Corbett C. L., Holdsworth C. D. Double-blind cross-over study comparing loperamide, codeine and diphenoxylate in the treatment of chronic diarrhea. Gastroenterology. 1980 Dec;79(6):1272–1275. [PubMed] [Google Scholar]
  21. Powell D. W. Muscle or mucosa: the site of action of antidiarrheal opiates? Gastroenterology. 1981 Feb;80(2):406–408. [PubMed] [Google Scholar]
  22. Sandhu B. K., Tripp J. H., Candy D. C., Harries J. T. Loperamide: studies on its mechanism of action. Gut. 1981 Aug;22(8):658–662. doi: 10.1136/gut.22.8.658. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Shee C. D., Pounder R. E. Loperamide, diphenoxylate, and codeine phosphate in chronic diarrhoea. Br Med J. 1980 Feb 23;280(6213):524–524. doi: 10.1136/bmj.280.6213.524. [DOI] [PMC free article] [PubMed] [Google Scholar]

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