Abstract
Laxatives are among the most commonly used drugs or additives. Most are quite safe when used judiciously, intermittently when possible, and in the absence of contraindications. Bulking agents and nonabsorbable compounds such as lactulose can cause bloating but have very few serious adverse effects except for the allergic reaction to psyllium preparations. Osmotic laxatives containing poorly absorbable ions such as magnesium or phosphate can cause metabolic disturbances, particularly in the presence of renal impairment. However, if taken intermittently, in the absence of conditions such as ileus or bowel obstruction, they have few adverse effects. Polyethylene glycol solutions are emerging as an effective and safe mode of treatment for chronic constipation. Of stimulant laxatives, senna compounds and bisacodyl are the most commonly used. Although there are data to support the neoplastic potential of this class of drugs inin vitro studies, epidemiologic data in humans so far has not established a clear link between these laxatives and colonic neoplasia. The link between stimulant laxatives and structural changes, such as the “cathartic colon” or enteric nerve damage, is not well established either. Danthron compounds should be avoided because of hepatotoxicity.
Similar content being viewed by others
References
Schiller LR. Clinical pharmacology and use of laxatives and lavage solutions. J Clin Gastroenterol 1999;28:11–8.
Noble JA, Grannis FW. Acute esophageal obstruction by a psyllium-based bulk laxative [letter]. Chest 1984;86:800.
Shulman LM, Minagar A, Weiner WJ. Perdiem causing esophageal obstruction in Parkinson's disease. Neurology 1999;52:670–1.
Vergeau B, Nizou C, Ciribilli JM, Grandpierre G. A case of esophageal obstruction after ingestion of a granular laxative [letter]. Endoscopy 1995;27:462.
Perez-Piqueras J, Silva C, Jaqueti J,et al. Endoscopic diagnosis and treatment of an esophageal bezoar resulting from bulk laxative ingestion. Endoscopy 1994;26:710.
William M. The extra pharmacopoeia of Martindale. Reynolds JE, ed. London: Pharmaceutical Press, 1989:1073–1112, 1057–8.
Elliot D, Glover GR. Large bowel perforation due to excessive bran ingestion. Br J Clin Pract 1983;37:32–3.
Souter WA. Bolus obstruction of gut after use of hydrophilic colloid laxatives. BMJ 1965;1:166–8.
Vaswani SK, Hamilton RG, Valentine MD, Adkinson NF. Psyllium laxative-induced anaphylaxis. Allergy 1996;51:266–8.
Busse WW, Schoenwetter WF. Asthma from psyllium in laxative manufacture. Ann Intern Med 1975;83:361–2.
Terho ja Martti Torkko EO. Occupational asthma from psyllium laxatives [in Finnish]. Duodecim 1980;96:1213–6.
Nelson WL. Allergic events among health care workers exposed to psyllium laxatives in the workplace. J Occup Med 1987;29:497–9.
Suhonen R, Kantola I, Bjorksten F. Anaphylactic shock due to ingestion of psyllium laxative. Allergy 1983;38:363–5.
Dutau G, Rittie JL, Rance F, Juchet A, Bremont F. New food allergies. Presse Med 1999;28:1553–9.
Ford MA, Cristea G Jr, Robbins WD, Gentes GR, Harper SJ, Rindone JP. Delayed psyllium allergy in three nurses. Hosp Pharm 1992;27:1061–2.
Bergmann JF, Chassany O, Petit A, Triki R, Caulin C, Segrestaa JM. Correlation between echographic gastric emptying and appetite: influence of psyllium. Gut 1992;33:1042–3.
Rigaud D, Paycha F, Meulemans A, Merrouche M, Mignon M. Effect of psyllium on gastric emptying, hunger feeling and food intake in normal volunteers: a double blind study. Eur J Clin Nutr 1998;52:239–45.
Bandla HP, Davis SH, Hopkins NE. Lipoid pneumonia: a silent complication of mineral oil aspiration. Pediatrics 1999;103:E19.
Schneider L. Pulmonary hazard of the ingestion of mineral oil in the apparently healthy adult: a clinoroentgenologic study. N Engl J Med 1949;240:284–91.
Qureshi T, Melonakos TK. Acute hypermagnesemia after laxative use. Ann Emerg Med 1996;28:552–5.
Gerard SK, Hernandez C, Khayam-Bashi H. Extreme hypermagnesemia caused by an overdose of magnesium-containing cathartics. Ann Emerg Med 1988;17:728–31.
Schelling JR. Fatal hypermagnesemia. Clin Nephrol 2000;53:61–5.
Matsuo H, Nakamura K, Nishida A, Kubo K, Nakagawa R, Sumida Y. A case of hypermagnesemia accompanied by hypercalcemia induced by a magnesium laxative in a hemodialysis patient. Nephron 1995;71:477–8.
Dharmarajan TS, Patel B, Varshneya N. Cathartic-induced life threatening hypermagnesemia in a 90-year-old woman with apparent normal renal function. J Am Geriatr Soc 1999;47:1039–40.
Alison LH, Bulugahapitiya D. Laxative induced magnesium poisoning in a 6-week old infant. BMJ 1990;300:125.
Woodard JA, Shannon M, Lacouture PG, Woolf A. Serum magnesium concentrations after repetitive magnesium cathartic administration. Am J Emerg Med 1990;8:297–300.
Nir-Paz R, Cohen R, Haviv YS. Acute hyperphosphatemia caused by sodium phosphate enema in a patient with liver dysfunction and chronic renal failure. Ren Fail 1999;21:541–4.
Orias M, Mahnensmith RL, Perazella MA. Extreme hyperphosphatemia and acute renal failure after a phosphorus-containing bowel regimen. Am J Nephrol 1999;19:60–3.
Ehrenpreis ED, Wieland JM, Cabral J, Estevez V, Zaitman D, Secrest K. Symptomatic hypocalcemia, hypomagnesemia, and hyperphosphatemia secondary to Fleet's Phospho-Soda colonoscopy preparation in a patient with a jejunoileal bypass. Dig Dis Sci 1997;42:858–60.
Vukasin P, Weston LA, Beart RW. Oral Fleet Phospho-Soda laxative-induced hyperphosphatemia and hypocalcemic tetany in an adult: report of a case. Dis Colon Rectum 1997;40:497–9.
Escalante CP, Weiser MA, Finkel K. Hyperphosphatemia associated with phosphorus-containing laxatives in a patient with chronic renal insufficiency. South Med J 1997;90:240–2.
Fine A, Patterson J. Severe hyperphosphatemia following phosphate administration for bowel preparation in patients with renal failure: two cases and a review of the literature. Am J Kidney Dis 1997;29:103–5.
Filho AJ, Lassman MN. Severe hyperphosphatemia induced by a phosphate-containing oral laxative. Ann Pharmacother 1996;30:141–3.
Fass R, Do S, Hixson LJ. Fatal hyperphosphatemia following Fleet Phospo-Soda [sic] in a patient with colonic ileus. Am J Gastroenterol 1993;88:929–32.
Zipser RD, Bischel MD, Abrams DE. Hypocalcemic tetany due to sodium phosphate ingestion in acute renal failure. Nephron 1975;14:378–81.
Wiberg JJ, Turner GG, Nuttall FQ. Effect of phosphate or magnesium cathartics on serum calcium: observations in normocalcemic patients. Arch Intern Med 1978;138:1114–6.
Schuchmann GD, Barcia PJ. Phosphate absorption from fleet enemas in adults. Curr Surg 1989;46:120–2.
AHFS drug information. Bethesda, MD: American Society of Hospital Pharmacists, 1993:1806–8.
Kaupke C, Sprague T, Gitnick GL. Hypernatremia after the administration of lactulose. Ann Intern Med 1977;86:745–6.
Nelson DC, McGrew WR Jr, Hoyumpa AM Jr. Hypernatremia and lactulose therapy. JAMA 1983;249:1295–8.
Gazda-Smith E, Synhavsky A. Hypernatremia following treatment of theophylline toxicity with activated charcoal and sorbitol. Arch Intern Med 1990;150:689–92.
Allerton JP, Strom JA. Hypernatremia due to repeated doses of charcoal-sorbitol. Am J Kidney Dis 1991;17:581–4.
Aradhye S, Brensilver JM. Sodium phosphate-induced hypernatremia in an elderly patient: a complex pathophysiologic state. Am J Kidney Dis 1991;18:609–11.
Cummings JH. Laxative abuse. Gut 1974;15:758–66.
Fleischer N, Brown H, Graham DY, Delena S. Chronic laxative-induced hyperaldosteronism and hypokalemia simulating Bartter's syndrome. Ann Intern Med 1969;70:791–8.
Wrong O. Aldosterone and electrolyte movements in the colon. BMJ 1968;1:379–80.
Shields R, Mulholland AT, Elmslie R. Action of aldosterone upon the intestinal transport of potassium, sodium, and water. Gut 1966;7:686–96.
Nataf C, Desmazures C, Giraudeaux V, Bernier JJ. Laxative-induced intestinal protein loss in normal subjects. Gastroenterol Clin Biol 1981;5:187–92.
Pahor M, Guralnik JM, Chrischilles EA, Wallace RB. Use of laxative medication in older persons and associations with low serum albumin. J Am Geriatr Soc 1994;42:50–6.
DiPalma JA, DeRidder PH, Orlando RC, Kolts BE, Cleveland MB. A randomized, placebo-controlled, multicenter study of the safety and efficacy of a new polyethylene glycol laxative. Am J Gastroenterol 2000;95:446–50.
Corazziari E, Badiali D, Bazzocchi G,et al. Long term efficacy, safety, and tolerability of low daily doses of isosmotic polyethylene glycol electrolyte balanced solution (PMF-100) in the treatment of functional chronic constipation. Gut 2000;46:522–6.
Dunnick JK, Hailey JR. Phenolphthalein exposure causes multiple carcinogenic effects in experimental model systems. Cancer Res 1996;56:4922–6.
Dunnick JK, Hardisty JF, Herbert RA,et al. Phenolphthalein induces thymic lymphomas accompanied by loss of the p53 wild type allele in heterozygous p53-deficient (±) mice. Toxicol Pathol 1997;25:533–40.
Gadacz TR, Gaginella TS, Phillips SF. Inhibition of water absorption by ricinoleic acid. Evidence against hormonal mediation of the effect. Am J Dig Dis 1976;21:859–62.
Gaginella TS, Chadwick VS, Debongnie JC, Lewis JC, Phillips SF. Perfusion of rabbit colon with ricinoleic acid: dose-related mucosal injury, fluid secretion, and increased permeability. Gastroenterology 1977;73:95–101.
Stewart JJ, Bass P. Effect of intravenous C-terminal octapeptide of cholecystokinin and intraduodenal ricinoleic acid on contractile activity of the dog intestine. Proc Soc Exp Biol Med 1976;152:213–7.
Wienbeck M, Wallenfels M, Kortenhaus E. Ricinoleic acid and loperamide have opposite motor effects in the small and large intestine of the cat. Z Gastroenterol 1987;25:355–63.
Donowitz M, Binder HJ. Effect of dioctyl sodium sulfosuccinate on colonic fluid and electrolyte movement. Gastroenterology 1975;69:941–50.
Saunders DR, Sillery J, Rachmilewitz D. Effect of dioctyl sodium sulfosuccinate on structure and function of rodent and human intestine. Gastroenterology 1975;69:380–6.
Abramowiecz M. Safety of stool softeners. Med Lett Drugs Ther 1977;19:45–6.
Fox DA, Epstein ML, Bass P. Surfactants selectively ablate enteric neurons of the rat jejunum and gut electrical parameters in the rat jejunum. J Pharmacol Exp Ther 1983;227:538–44.
Morrow DM, Rapaport MJ, Strick RA. Hypersensitivity to aloe. Arch Dermatol 1980;116:1064–5.
Tolman KG, Hammar S, Sannella JJ. Possible hepatotoxicity of Doxidan. Ann Intern Med 1976;84:290–2.
Steer HW, Colin-Jones DG. Melanosis coli: studies of the toxic effects of irritant purgatives. J Pathol 1975;115:199–205.
Walker NI, Bennett RE, Axelsen RA. Melanosis coli. A consequence of anthraquinone-induced apoptosis of colonic epithelial cells. Am J Pathol 1988;131:465–76.
Ghadially FN, Walley VM. Pigments of the gastrointestinal tract: a comparison of light microscopic and electron microscopic findings. Ultrastruct Pathol 1995;19:213–9.
Krbavcic A, Pecar S, Schara M, Muller K, Wiegrebe W. Anthranoid free radicals found in pseudomelanosis coli. Pharmazie 1998;53:336–8.
Benavides SH, Morgante PE, Monserrat AJ, Zarate J, Porta EA. The pigment of melanosis coli: a lectin histochemical study. Gastrointest Endosc 1997;46:131–8.
Hoshi O, Iwanaga T, Fujino MA. Selective uptake of intraluminal dextran sulfate sodium and senna by macrophages in the cecal mucosa of the guinea pig. J Gastroenterol 1996;31:189–98.
Koskela E, Kulju T, Collan Y. Melanosis coli. Prevalence, distribution, and histologic features in 200 consecutive autopsies at Kuopio University Central Hospital. Dis Colon Rectum 1989;32:235–9.
Siegers CP, von Hertzberg-Lottin E, Otte M, Schneider B. Anthranoid laxative abuse—a risk for colorectal cancer? Gut 1993;34:1099–101.
Nusko G, Schneider B, Schneider I, Wittekind C, Hahn EG. Anthranoid laxative use is not a risk factor for colorectal neoplasia: results of a prospective case control study. Gut 2000;46:651–5.
Heiburn N. Roentgen evidence suggesting enterocolitis associated with prolonged cathartic abuse. Radiology 1943;41:486–91.
Muller-Lissner S. What has happened to the cathartic colon? Gut 1996;39:486–8.
Joo JS, Ehrenpreis ED, Gonzalez L,et al. Alterations in colonic anatomy induced by chronic stimulant laxatives: the cathartic colon revisited. J Clin Gastroenterol 1998;26:283–6.
Campbell WL. Cathartic colon. Reversibility of roentgen changes. Dis Colon Rectum 1983;26:445–8.
Smith B. Effect of irritant purgatives on the myenteric plexus in man and the mouse. Gut 1968;9:139–43.
Krishnamurthy S, Schuffler MD, Rohrmann CA, Pope CE. Severe idiopathic constipation is associated with a distinctive abnormality of the colonic myenteric plexus. Gastroenterology 1985;88:26–34.
Riemann JF, Schmidt H. Ultrastructural changes in the gut autonomic nervous system following laxative abuse and in other conditions. Scand J Gastroenterol Suppl 1982;71:111–24.
Dugan AM. Salmonella typhimurium as a test system for detecting the mutagenic activity of environmental pollutants. Tsitol Genet 1994;28:37–41.
Tikkanen L, Matsushima T, Natori S. Mutagenicity of anthraquinones in the Salmonella preincubation test. Mutat Res 1983;116:297–304.
Brown JP, Brown RJ. Mutagenesis by 9,10-anthraquinone derivatives and related compounds in Salmonella typhimurium. Mutat Res 1976;40:203–24.
Brown JP, Dietrich PS. Mutagenicity of anthraquinone and benzanthrone derivatives in the salmonella/microsome test: activation of anthraquinone glycosides by enzymic extracts of rat cecal bacteria. Mutat Res 1979;66:9–24.
Venturini S, Tamaro M. Mutagenicity of anthraquinone and azo dyes in Ames' Salmonella typhimurium test. Mutat Res 1979;68:307–12.
Krivobok S, Seigle-Murandi F, Steiman R, Marzin DR, Betina V. Mutagenicity of substituted anthraquinones in the Ames/Salmonella microsome system. Mutat Res 1992;279:1–8.
Heidemann A, Volkner W, Mengs U. Genotoxicity of aloeemodin in vitro and in vivo. Mutat Res 1996;367:123–33.
Sandnes D, Johansen T, Teien G, Ulsaker G. Mutagenicity of crude senna and senna glycosides in Salmonella typhimurium. Pharmacol Toxicol 1992;71:165–72.
Muller SO, Eckert I, Lutz WK, Stopper H. Genotoxicity of the laxative drug components emodin, aloe-emodin and danthron in mammalian cells: topoisomerase II mediated? Mutat Res 1996;371:165–73.
Schorkhuber M, Richter M, Dutter A, Sontag G, Marian B. Effect of anthraquinone-laxatives on the proliferation and urokinase secretion of normal, premalignant and malignant colonic epithelial cells. Eur J Cancer 1998;34:1091–8.
Lee H, Tsai SJ. Effect of emodin on cooked-food mutagen activation. Food Chem Toxicol 1991;29:765–70.
al-Dakan AA, al-Tuffail M, Hannan MA. Cassia senna inhibits mutagenic activities of benzo[a]-pyrene, aflatoxin B1, shamma and methyl methanesulfonate. Pharmacol Toxicol 1995;77:288–92.
Toyoda K, Imaida K, Shirai T, Imazawa T, Takahashi M. Relationship between bisacodyl-induced urolithiasis and rat urinary bladder tumorigenesis. J Toxicol Environ Health 1993;39:59–78.
Mori H, Yoshimi N, Iwata H,et al. Carcinogenicity of naturally occurring 1-hydroxyanthraquinone in rats: induction of large bowel, liver and stomach neoplasms. Carcinogenesis 1990;11:799–802.
Mori H, Sugie S, Niwa K, Yoshimi N, Tanaka T, Hirono I. Carcinogenicity of chrysazin in large intestine and liver of mice. Jpn J Cancer Res 1986;77:871–6.
Mori H, Sugie S, Niwa K, Takahashi M, Kawai K. Induction of intestinal tumours in rats by chrysazin. Br J Cancer 1985;52:781–3.
Mereto E, Ghia M, Brambilla G. Evaluation of the potential carcinogenic activity of Senna and Cascara glycosides for the rat colon. Cancer Lett 1996;101:79–83.
Mascolo N, Mereto E, Borrelli F,et al. Does senna extract promote growth of aberrant crypt foci and malignant tumors in rat colon? Dig Dis Sci 1999;44:2226–30.
Lyden-Sokolowski A, Nilsson A, Sjoberg P. Two-year carcinogenicity study with sennosides in the rat: emphasis on gastrointestinal alterations. Pharmacology 1993;47(Suppl 1):209–15.
Kleibeuker JH, Cats A, Zwart N, Mulder NH, Hardonk MJ, de Vries EG. Excessively high cell proliferation in sigmoid colon after an oral purge with anthraquinone glycosides. J Natl Cancer Inst 1995;87:452–3.
Van Gorkom BA, Karrenbeld A, van Der Sluis T, Koudstaal J, de Vries EG, Kleibeuker JH. Influence of a highly purified senna extract on colonic epithelium. Digestion 2000;61:113–20.
Jacobs EJ, White E. Constipation, laxative use, and colon cancer among middle-aged adults. Epidemiology 1998;9:385–91.
Sonnenberg A, Muller AD. Constipation and cathartics as risk factors of colorectal cancer: a meta-analysis. Pharmacology 1993;47(Suppl 1):224–33.
Nusko G, Schneider B, Muller G, Kusche J, Hahn EG. Retrospective study on laxative use and melanosis coli as risk factors for colorectal neoplasma. Pharmacology 1993;47(Suppl 1):234–41.
Pommer W, Bronder E, Klimpel A, Helmert U, Greiser E, Molzahn M. Urothelial cancer at different tumor sites: role of smoking and habitual intake of analgesics and laxatives. Results of the Berlin Urothelial Cancer Study. Nephrol Dial Transplant 1999;14:2892–7.
Kune GA. Laxative use not a risk for colorectal cancer: data from the Melbourne Colorectal Cancer Study. Z Gastroenterol 1993;31:140–3.
Longnecker MP, Sandler DP, Haile RW, Sandler RS. Phenolphthalein-containing laxative use in relation to adenomatous colorectal polyps in three studies. Environ Health Perspect 1997;105:1210–2.
Dukas L, Willet WC, Colditz GA, Fuchs CS, Rosner B, Giovannucci EL. Prospective study of bowel movement, laxative use, and risk of colorectal cancer among women. Am J Epidemiol 2000;151:958–64.
Author information
Authors and Affiliations
About this article
Cite this article
Xing, J.H., Soffer, E.E. Adverse effects of laxatives. Dis Colon Rectum 44, 1201–1209 (2001). https://doi.org/10.1007/BF02234645
Issue Date:
DOI: https://doi.org/10.1007/BF02234645