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Mechanisms of Drug-Induced Diarrhoea in the Elderly

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Abstract

In the rapidly increasing elderly population, diarrhoea as a result of drug therapy is an important consideration. The elderly consume a disproportionately large number of drugs for multiple acute and chronic diseases.

Drugs can compromise both immune and nonimmune responses. Aging decreases the quality and proportion of T cells which in turn reduces the production of secretory IgA, the primary immune response of the gut. Acid production in the stomach decreases with increasing age and this compromises its vital ‘self-sterilising’ function, thus increasing the risk of diarrhoea due to viral, bacterial and protozoal pathogens.

Other nonimmune defence mechanisms include the motility of the small intestine and the host—protective commensal bacteria of the colon. Drug induced hypomotility may result in bacterial overgrowth, deconjugation of bile salts and diarrhoea. Less commonly, diarrhoea may occur due to hypermotility because of a cholinergic-like syndrome. In the colon the host-protective commensal bacteria provide a powerful defence against pathogens. Disruption of this commensal population by antibiotic therapy may result in Clostridium difficile supra-infection which causes diarrhoea through toxin production. This is especially important in the elderly patient on chemotherapy for malignancy and those with multiple diseases. The organism responds to vancomycin, metronidazole and bacitracin. Metronidazole is the suggested drug of choice, with vancomycin reserved for relapses.

Drugs also cause diarrhoea by interfering with normal physiological processes. Drugs impair fluid absorption by activating adenylate cyclase within the small intestinal enterocyte which increases the level of cyclic AMP. This causes active secretion of Cl− and HCO3 −, passive efflux of Na+, K+ and water and inhibition of Na+ and Cl− into the enterocyte. Examples of these drugs (secretagogues) are bisacodyl, misoprostol and chenodeoxycholic acid (used to dissolve cholesterol gallstones).

Drugs may also affect a second mechanism that regulates water and electrolyte transport, the Na+,K+ exchange pump. The energy for this pump is provided by the ATPase mediated breakdown of ATP. ATPase may be inhibited by digoxin, auranofin, colchicine and olsalazine.

A number of drugs cause osmotic diarrhoea including antacids containing magnesium trisilicate or hydroxide. Lactulose is being used increasingly in compensated liver disease to increase protein tolerance and prevent hepatic encephalopathy. Sorbitol, an osmotic laxative agent also used in some liquid pharmaceutical preparations, induces diarrhoea by virtue of its osmotic potential.

Another mechanism by which drugs cause diarrhoea is by mucosal damage of the small and large bowel. In the small intestine mucosal damage causes diarrhoea and fat malabsorption, as may occur with neomycin and colchicine. In the colon, for example, gold salts and penicillamine cause colitis of varying severity.

Though the causes of diarrhoea are diverse, a drug-associated aetiology should always be considered and actively sought and addressed to prevent the complications of dehydration, electrolyte imbalance and undernutrition.

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References

  1. Zachariah KC, Vu MT. World Population Projections 1987–1988: short and long term estimates. Baltimore: Johns Hopkins University, 1988

    Google Scholar 

  2. Garibaldi RA, Nurse BA. Infections in the elderly. Am J Med 1986; 81: 53–8

    Article  PubMed  CAS  Google Scholar 

  3. Ratnaike RN. Diarrhoea in the elderly: epidemiological and aetiological factors. J Gastroenterol Hepatol 1990; 5: 449–58

    Article  PubMed  CAS  Google Scholar 

  4. Gambert SR, Guansing AR. Protein-calorie malnutrition in the elderly. J Am Geriatr Soc 1980; 28: 272–5

    PubMed  CAS  Google Scholar 

  5. Rybolt AH, Bennett RG, Laughon BE, et al. Protein-losing enteropathy associated with Clostridium difficile infection. Lancet 1989; I: 1353–5

    Article  Google Scholar 

  6. McEvoy A, Dutton J, James OFW. Bacterial contamination of the small intestine is an important cause of occult malabsorption in the elderly. BMJ 1983; 287: 789–93

    Article  PubMed  CAS  Google Scholar 

  7. Clough JD, Minis LH, Strober W. Deficient IgA antibody responses to arsanilic bovine serum albumin (BSA) in neonatally thymectomized rabbits. J Immunol 1971; 106: 1624–9

    PubMed  CAS  Google Scholar 

  8. Good R. Introduction to the proceedings of the clinical symposium on the recognition and management of immunodeficiency disorders. Vox Sang 1986; 51Suppl. 2: 1–13

    Article  PubMed  Google Scholar 

  9. Makinodan T, Kay MM. Age influence on the immune system. Adv Immunol 1980; 29: 287–330

    Article  PubMed  CAS  Google Scholar 

  10. Venarucci D, Vallese A, Catalini P, et al. Consideration on diminished immunologic defences in the elderly neoplastic subject. Panminerva Med 1993; 35: 154–8

    PubMed  CAS  Google Scholar 

  11. Giannella RA, Broitman SA, Zamcheck N. Gastric acid barrier to ingested micro-organisms in man: studies in vivo and in vitro. Gut 1972; 13: 251–6

    Article  PubMed  CAS  Google Scholar 

  12. Sack Jr GH, Pierce NF, Hennessey KN, et al. Gastric acidity in cholera and non-cholera diarrhoea. Bull World Health Organ 1972; 47: 31–6

    PubMed  Google Scholar 

  13. Hunt RH. The protective role of gastric acid. Scand J Gastroenterol 1988; 23: 34–9

    Article  Google Scholar 

  14. Axon AT. Potential hazards of hypochlorhydria in the treatment of peptic ulcer [review]. Scand J Gastroenterol 1986; 122 Suppl.: 17–21

    Article  CAS  Google Scholar 

  15. Giannella RA, Broitman SA, Zamcheck N. Influence of gastric acidity on bacterial and parasitic infections: a perspective. Ann Intern Med 1973; 78: 271–6

    PubMed  CAS  Google Scholar 

  16. Belitsos PC, Greenson JK, Yardley JH. Association of gastric hypoacidity with opportunistic enteric infections in patients with AIDS. J Infect Dis 1992; 166: 277–84

    Article  PubMed  CAS  Google Scholar 

  17. Blackman AH, Lambert DL, Thayer WR, et al. Computed normal values for peak acid output based on age, sex and body weight. Am J Dig Dis 1970; 15: 783–9

    Article  PubMed  CAS  Google Scholar 

  18. Dymock IW. The gastrointestinal system: the upper gastrointestinal tract. In: Brocklehurst JC, editor. Textbook of geriatric medicine and gerontology. Edinburgh: Churchill Livingstone, 1985: 508–21

    Google Scholar 

  19. Husebye E, Skar V, Hoverstad T, et al. Fasting hypochlorhydria with Gram positive gastric flora is highly prevalent in healthy old people. Gut 1992; 33: 1331–7

    Article  PubMed  CAS  Google Scholar 

  20. Aryeh H, Brady D, Schaal SE, et al. Gastric acidity in older adults. JAMA 1997; 278: 659–62

    Article  Google Scholar 

  21. Long J, DeSantis S, State D, et al. The effect of antisecretagogues on gastric microflora. Arch Surg 1983; 118: 1413–5

    Article  PubMed  CAS  Google Scholar 

  22. Hamilton I, O’Connor HJ, Wood NC, et al. Healing and recurrence of duodenal ulcer after treatment with tripotassium dicitrate bismuthate (TDB) tablets or cimetidine. Gut 1986; 27: 106–10

    Article  PubMed  CAS  Google Scholar 

  23. Papadopolous C, Kalantzis N, Rekoumis G, et al. A comparative trial of 400mg cimetidine twice daily and 100mg daily in the short-term treatment of duodenal ulceration. Curr Med Res Opin 1985; 9: 511–5

    Article  Google Scholar 

  24. Thorens J, Froehlich F, Schwizer W, et al. Bacterial overgrowth during treatment with omeprazole compared with cimetidine: a prospective randomised double blind study. Gut 1996; 39: 54–9

    Article  PubMed  CAS  Google Scholar 

  25. Walker KJ, Gilliland SS, Vance-Bryan K, et al. Clostridium difficile colonization in residents of long-term care facilities: prevalence and risk factors. J Am Geriatr Soc 1993; 41: 940–6

    PubMed  CAS  Google Scholar 

  26. Dixon JMS. The fate of bacteria in the small intestine. J Pathol Bacteriol 1960; 79: 131–40

    Article  PubMed  CAS  Google Scholar 

  27. Kent TH, Formal SB, LaBrec EH. Acute enteritis due to Salmonella typhimurium in opium-treated guinea pigs. Arch Pathol 1966; 81: 501–8

    PubMed  CAS  Google Scholar 

  28. Montgomery RD, Haboubi NY, Mike NH, et al. Causes of malabsorption in the elderly. Age Ageing 1986; 15: 235–40

    Article  PubMed  CAS  Google Scholar 

  29. Dharmsathaphorn K, Huott PA, Vongkovit P, et al. Cl secretion induced by bile salts: a study of the mechanism of action based on a cultured colonic epithelial cell line. J Clin Invest 1989; 84: 945–53

    Article  PubMed  CAS  Google Scholar 

  30. Binder HJ. Nutrient induced diarrhoea. In: Field M, editor. Diarrhoeal diseases. New York: Elsevier, 1991; 159–72

    Google Scholar 

  31. Ravdin JI, Guerrant RL. Infectious diarrhoea in the elderly. Geriatrics 1983; 38: 95–7, 99-101

    PubMed  CAS  Google Scholar 

  32. Cohn CK, Shrivastava R, Mendels J, et al. Double-blind multi-center comparison of sertraline and amitriptyline in elderly depressed patients. J Clin Psychiatry 1990; 51Suppl. B: 28–33

    PubMed  Google Scholar 

  33. Binder HJ, Donowitz M. A new look at laxative action. Gastroenterol 1975; 69: 1001–5

    CAS  Google Scholar 

  34. Ewe K. Diarrhoea and constipation. Ballieres Clin Gastroenterol 1988; 2: 353–84

    Article  CAS  Google Scholar 

  35. Antuono PG, Mentane Study Group. Effectiveness and safety of velnacrine for the treatment of Alzheimer’s disease: a double-blind, placebo-controlled study. Arch Intern Med 1995; 155: 1766–72

    Article  PubMed  CAS  Google Scholar 

  36. Zemlan FP, Keys M, Richter RW, et al. Double-blind placebo-controlled study of velnacrine in Alzheimer’s disease. Life Sci 1996; 58: 1823–32

    Article  PubMed  CAS  Google Scholar 

  37. Rivory LP. Irinotecan (CPT-11): a brief overview. Clin Exp Pharmacol Physiol 1996; 23: 1000–4

    Article  PubMed  CAS  Google Scholar 

  38. Bleiberg H, Cvitkovic E. Characterisation and clinical management of CPT-11 (irinotecan)-induced adverse events: the European perspective. Eur J Cancer 1996; 32ASuppl. 3: S18–23

    Article  PubMed  CAS  Google Scholar 

  39. Simon GL, Gorbach SL. The human intestinal microflora. Dig Dis Sci 1986; 31 Suppl.: 147S–62S

    Article  PubMed  CAS  Google Scholar 

  40. Rolfe RD. Interactions among micro-organisms of the indigenous intestinal flora and their influence on the host. Rev Infect Dis 1984; Suppl. 6: S73–9

    Google Scholar 

  41. Lesna M, Parham DM. Risk of diarrhoea due to clostridium difficule during Cefotaxime treatment: mortality due to C. difficult colitis in elderly people has been underestimated. BMJ 1996; 312: 778

    Article  PubMed  CAS  Google Scholar 

  42. Starr JM, Impallomeni M. Risk of diarrhoea, Clostridium difficule and cefotaxime in the elderly. Biomed Pharmacother 1997; 51: 63–7

    Article  PubMed  CAS  Google Scholar 

  43. Bennett GC, Allen E, Millard PH. Clostridium difficile diarrhoea: a highly infectious organism. Age Ageing 1984; 13: 363–6

    Article  PubMed  CAS  Google Scholar 

  44. Simor AE, Yake SL, Tsimidis K. Infection due to Clostridium difficile among elderly residents of a long-term-care facility. Clin Infect Dis 1993; 17: 672–8

    Article  PubMed  CAS  Google Scholar 

  45. Samore MH, Bettin KM, DeGirolami PC, et al. Wide diversity of Clostridium difficile types at a tertiary referral hospital. J Infect Dis 1994; 170: 615–21

    Article  PubMed  CAS  Google Scholar 

  46. Rubin MS, Bodenstein LE, Kent KC. Severe Clostridium difficile colitis. Dis Colon Rectum 1995; 38: 350–4

    Article  PubMed  CAS  Google Scholar 

  47. Bradbury AW, Barrett S. Surgical aspects of Clostridium difficile colitis. Br J Surg 1997; 84: 150–9

    Article  PubMed  CAS  Google Scholar 

  48. Talon D, Bailly P, Delmee M, et al. Use of pulsed-field gel electrophoresis for investigation of an outbreak of Clostridium difficile infection among geriatric patients. Eur J Clin Microbiol Infect Dis 1995; 14: 987–93

    Article  PubMed  CAS  Google Scholar 

  49. Fekety R, Kim KH, Batts DH, et al. Studies on the epidemiology of antibiotic-associated Clostridium difficile colitis. Am J Clin Nutr 1980; 33: 2527–32

    PubMed  CAS  Google Scholar 

  50. Teasley DG, Gerding DN, Olson MM, et al. Prospective randomised trial of metronidazole versus vancomycin for Clostridium difficile—associated diarrhoea and colitis. Lancet 1983; II(8358): 1043–6

    Article  Google Scholar 

  51. Samuel SC, Hancock P, Leigh DA. An investigation into Clostridium perfringens enterotoxin-associated diarrhoea. J Hosp Infect 1991; 18: 219–30

    Article  PubMed  CAS  Google Scholar 

  52. DuPont HL. Nosocomial salmonellosis and shigellosis [editorial]. Infect Control Hosp Epidemiol 1991; 12: 707–9

    Article  PubMed  CAS  Google Scholar 

  53. Clausen MR, Bonnen B, Tvede M, et al. Colonic fermentation to short-chain fatty acids is decreased in antibiotic-associated diarrhea. Gastroenterol. 1991; 101: 1497–504

    CAS  Google Scholar 

  54. Field M, Rao MC, Chang EB. Intestinal electrolyte transport and diarrheal disease: 1. N Engl J Med 1989; 321: 800–6

    Article  PubMed  CAS  Google Scholar 

  55. Field M, Rao MC, Chang EB. Intestinal electrolyte transport and diarrheal disease: 2. N Engl J Med 1989; 321: 879–83

    Article  PubMed  CAS  Google Scholar 

  56. Simon B, Kather H. Interaction of laxatives with enzymes of cyclic AMP metabolism from human colonie mucosa. Eur J Clin Invest 1980; 10: 231–4

    Article  PubMed  CAS  Google Scholar 

  57. Rachmilewitz D, Karmeli F, Okon E. Effects of bisacodyl on cAMP and prostaglandin E2 contents, (Na + K) ATPase, adenyl cyclase, and phosphodiesterase activities of rat intestine. Dig Dis Sci 1980; 25: 602–8

    Article  PubMed  CAS  Google Scholar 

  58. Ching CK, Lam SK. A comparison of two prostaglandin analogues (enprostil vs misoprostol) in the treatment of acute duodenal ulcer disease. J Gastroenterol 1995; 30: 607–14

    Article  PubMed  CAS  Google Scholar 

  59. Silverstein FE, Graham DY, Senior JR, et al. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 1995; 123: 241–9

    PubMed  CAS  Google Scholar 

  60. Won-Kim S, Kachur JF, Gaginella TS. Stereospecific actions of misoprostol on colonic electrolyte transport. Prostaglandins 1993; 46: 221–31

    Article  PubMed  CAS  Google Scholar 

  61. Pawlotsky JM, Ruszniewski P, Reyl-Desmars F, et al. Effects of PGE2, misoprostol, and enprostil on guinea pig enterocyte adenylate cyclase: clinical implications. Dig Dis Sci 1993; 38: 316–20

    Article  PubMed  CAS  Google Scholar 

  62. Chawla A, Karl PI, Riech RN, et al. Effect of olsalazine on sodium-dependent bile acid transport in rat ileum. Dig Dis Sci 1995; 40: 943–8

    Article  PubMed  CAS  Google Scholar 

  63. Csaky TZ, Hara Y. Inhibition of active intestinal sugar transport by digitalis. Am J Physiol 1965; 209: 467–72

    PubMed  CAS  Google Scholar 

  64. Pentland B, Pennington CR. Acute diarrhoea in the elderly. Age Ageing 1980 9: 90–2

    Article  PubMed  CAS  Google Scholar 

  65. Hardcastle J, Hardcastle PT, Kelleher DK, et al. Effect of auranofin on absorptive processes in the rat small bowel. J Rheumatol 1986; 13: 541–6

    PubMed  CAS  Google Scholar 

  66. Fondacaro JD, Henderson LS, Hardcastle PT, et al. Effect of auranofin (SK&F 39162) on water and electrolyte flux in canine small bowel: a possible diarrheogenic mechanism. J Rheumatol 1986; 13: 288–93

    PubMed  CAS  Google Scholar 

  67. Wallin BA, McCafferty JP, Fox MJ, et al. Incidence and management of diarrhea during longterm auranofin therapy. J Rheumatol 1988; 15: 1755–8

    PubMed  CAS  Google Scholar 

  68. Champion GD, Cairns DR, Bieri D, et al. Dose response studies and long term evaluation of auranofin in rheumatoid arthritis. J Rheumatol 1988; 15: 28–34

    PubMed  CAS  Google Scholar 

  69. Ehrenfeld M, Levy M, Sharon P, et al. Gastrointestinal effects of long-term colchicine therapy in patients with recurrent polyserositis (familial Mediterranean fever). Dig Dis Sci 1982; 27: 723–7

    Article  PubMed  CAS  Google Scholar 

  70. Campbell DES, Berglindh T. Pharmacology of olsalazine. Scand J Gastroenterol 1988; 23(48): 7–12

    Article  Google Scholar 

  71. Sandberg-Gertzen H, Jarnerot G, Bukhave K, et al. Effect of azodisal sodium and sulphasalazine on ileostomy output of fluid and PGE2 and PGF2 in subjects with a permanent ileostomy. Gut 1986; 27: 1306–11

    Article  PubMed  CAS  Google Scholar 

  72. Forston WC, Tedesco FJ. Drug induced colitis: a review. Am J Gastroenterol 1984; 79: 878–83

    Google Scholar 

  73. Schiller LR. Chronic diarrhoea of obscure origin In: Field M, editor. Diarrhoeal diseases. New York: Elsevier, 1991; 219–38

    Google Scholar 

  74. O’Brien J, Thompson DG, Burnham WR, et al. Beta blocking drugs accelerate the passage of carbohydrate to the colon [abstract]. Gut 1986; 27: 629

    Google Scholar 

  75. Fedorak RN, Rubinoff M. Basic investigations in a patient with diarrhea. In: Field M, editor. Diarrhoeal diseases. New York: Elsevier, 1991; 191–218

    Google Scholar 

  76. Krejs GJ, Walsh JH, Morawski SG, et al. Intractable diarrhea: intestinal perfusion studies and plasma VIP concentrations in patients with pancreatic cholera syndrome and surreptitious ingestion of laxatives and diuretics. Am J Dig Dis 1977; 22: 280–92

    Article  PubMed  CAS  Google Scholar 

  77. Bircher J, Muller J, Guggenheim P, et al. Treatment of chronic portal-systematic encephalopathy with lactulose. Lancet 1966; I: 890–3

    Google Scholar 

  78. Furniss LD. Nonsteroidal anti-inflammatory agents in the treatment of primary dysmenorrhea. Clin Pharm 1982; 1: 327–33

    PubMed  CAS  Google Scholar 

  79. Puri SK, Ho I, Hsu R, et al. Multiple dose pharmacokinetics, safety, and tolerance of velnacrine (HP 029) in healthy elderly subjects: a potential therapeutic agent for Alzheimer’s disease. J Clin Pharmacol 1990; 30: 948–55

    PubMed  CAS  Google Scholar 

  80. Cain GD, Reiner EB, Patterson M. Effects of neomycin on disaccharidase activity of the small bowel. Arch Intern Med 1968; 122: 311–41

    Article  PubMed  CAS  Google Scholar 

  81. Henley E. Sorbitol-based elixirs, diarrhea and enterai tube feeding [letter]. Am Fam Physician 1997; 55: 2084–6

    PubMed  CAS  Google Scholar 

  82. Baron A, Neumann C. PROTECT interim results: a large multi-center study of patients with type II diabetes: precose resolution of optimal titration to enhance current therapies. Clin Ther 1997; 19: 282–95

    Article  PubMed  CAS  Google Scholar 

  83. Bytzer P, Stokholm M, Andersen I, et al. Aetiology, medical history, and faecal weight in adult patients referred for diarrhoea: a prospective survey. Scand J Gastroenterol 1989; 25: 572–8

    Article  Google Scholar 

  84. Ratnaike RN, O’Halloran MW, Pasco NP, et al. Lactulose lowers arterial ammonia in hepatic failure. Am J Gastroenterol 1972; 58: 626–32

    PubMed  CAS  Google Scholar 

  85. Martin AE, Montgomery PA. Acarbose: an alpha-glucosidase inhibitor. Am J Health Syst Pharm 1996; 53: 2277–90

    PubMed  CAS  Google Scholar 

  86. Dobbins III WO, Herrero BA, Mansbach CM. Morphologic alterations associated with neomycin induced malabsorption. Am J Med Sci 1968; 255: 63–77

    Article  PubMed  Google Scholar 

  87. Stemmennann GN, Hayashi T. Colchicine intoxication: a reappraisal of its pathology based on a study of three fatal cases. Hum Pathol 1971; 2: 321–32

    Article  Google Scholar 

  88. Jackson CW, Haboubi NY, Whorwell PJ, et al. Gold induced enterocolitis. Gut 1986; 27: 452–6

    Article  PubMed  CAS  Google Scholar 

  89. Jarner D, Nielsen MA. Auranofin (SK&F 39162) induced enterocolitis in rheumatoid arthritis: a case report. Scand J Rheumatol 1983; 12: 254–6

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Medicine, The Queen Elizabeth Hospital, Woodville, South Australia, 5011, Australia

    Ranjit N. Ratnaike & Terry E. Jones

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Ratnaike, R.N., Jones, T.E. Mechanisms of Drug-Induced Diarrhoea in the Elderly. Drugs Aging 13, 245–253 (1998). https://doi.org/10.2165/00002512-199813030-00007

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