Laxative

"Purgative" redirects here. For other uses, see Purgation.

Laxatives (purgatives, aperients) are substances that loosen stools[1] and increase bowel movements. They are used to treat and prevent constipation. Laxatives vary based on how they work and the side effects they have. Certain stimulant, lubricant and saline laxatives are used to evacuate the colon for rectal and bowel examinations, and may be supplemented by enemas under certain circumstances. Sufficiently high doses of laxatives may cause diarrhea.

Some laxatives combine more than one active ingredient. Laxatives may be oral or suppository in form.

Uses

Types

Bulk-forming agents

Bulk-forming laxatives, also known as roughage, are substances, such as fiber in food and hydrophilic agents in over-the-counter drugs, that add bulk and water to stools so that they can pass more easily through the intestines (lower part of the digestive tract).[2]

Properties

Bulk-forming agents absorb water and should be taken with plenty of water.[3] Bulk-forming agents generally have the gentlest of effects among laxatives[1] and can be taken for long-term maintenance of regular bowel movements.

Dietary fiber

Foods that help with laxation include fiber-rich foods. Dietary fiber includes insoluble fiber and soluble fiber, such as:[4]

Emollient agents (stool softeners)

Emollient laxatives, also known as stool softeners, are anionic surfactants that enable additional water and fats to be incorporated in the stool, making it easier for them to move through the gastrointestinal tract.

Properties

Emollient agents should be taken with plenty of water. Emollient agents prevent constipation rather than treat long-term constipation.[3]

Lubricant agents

Main article: Lubricant

Lubricant laxatives are substances that coat the stool with slippery lipids and retard colonic absorption of water so that the stool slides through the colon more easily. Lubricant laxatives also increase the weight of stool and decrease intestinal transit time.[3]

Properties

Mineral oil is the only nonprescription lubricant. Mineral oil may decrease the absorption of fat-soluble vitamins and some minerals.[3]

Hyperosmotic agents

Hyperosmotic laxatives are substances that cause the intestines to hold more water within and create an osmotic effect that stimulates a bowel movement.[3]

Properties

Lactulose works by the osmotic effect, which retains water in the colon, lowering the pH through bacterial fermentation to lactic, formic and acetic acid, and increasing colonic peristalsis. Lactulose is also indicated in portal-systemic encephalopathy. Glycerin suppositories work mostly by hyperosmotic action, but the sodium stearate in the preparation also causes local irritation to the colon.

Solutions of polyethylene glycol and electrolytes (sodium chloride, sodium bicarbonate, potassium chloride, and sometimes sodium sulfate) are used for whole bowel irrigation, a process designed to prepare the bowel for surgery or colonoscopy and to treat certain types of poisoning. Brand names for these solutions include GoLytely, GlycoLax, CoLyte, Miralax, Movicol, NuLytely, Suprep, and Fortrans. Solutions of sorbitol (SoftLax) have similar effects.

Saline laxative agents

Saline laxatives are non-absorbable osmotic substances that attract and retain water in the intestinal lumen, increasing intraluminal pressure that mechanically stimulates evacuation of the bowel. Magnesium-containing agents also cause the release of cholecystokinin, which increases intestinal motility and fluid secretion.[3] Saline laxatives may alter a patient's fluid and electrolyte balance.

Properties

Saline laxatives should be taken with plenty of water.

Stimulant agents

Stimulant laxatives are substances that act on the intestinal mucosa or nerve plexus, altering water and electrolyte secretion.[8] They also stimulate peristaltic action and can be dangerous under certain circumstances.[9]

Properties

They are the most powerful among laxatives and should be used with care. Prolonged use of stimulant laxatives can create drug dependence by damaging the colon's haustral folds, making a user less able to move feces through the colon on their own. A study of patients with chronic constipation found that 28% of chronic stimulant laxative users lost haustral folds over the course of one year, while none of the control group did.[10]

Miscellaneous

Castor oil is a glyceride that is hydrolyzed by pancreatic lipase to ricinoleic acid, which produces laxative action by an unknown mechanism.

Properties

Long-term use of castor oil may result in loss of fluid, electrolytes, and nutrients.[3]

Serotonin agonist

These are motility stimulants that work through activation of 5-HT4 receptors of the enteric nervous system in the gastrointestinal tract. However, some have been discontinued or restricted due to potentially harmful cardiovascular side-effects.

Tegaserod (brand name Zelnorm) was removed from the general U.S. and Canadian markets in 2007, due to reports of increased risks of heart attack or stroke. It is still available to physicians for patients in emergency situations that are life-threatening or require hospitalization.[11]

Prucalopride (brand name Resolor) is a current drug approved for use in the EU October 15, 2009[12] and in Canada (brand name Resotran) on December 7, 2011.[13] It has not been approved by the Food and Drug Administration for use in the United States, but it is in development by Shire PLC.[14]

Chloride channel activators

Lubiprostone is used in the management of chronic idiopathic constipation and irritable bowel syndrome. It causes the intestines to produce a chloride-rich fluid secretion that softens the stool, increases motility, and promotes spontaneous bowel movements (SBM).

Comparison of available agents

Common stimulant laxatives[15][16]
Preparation(s) Type Site of action Onset of
Cascara (casanthranol) Anthraquinone colon 6–8 hours
Buckthorn Anthraquinone colon 6–8 hours
Senna extract (senna glycoside) Anthraquinone colon 6–8 hours
Aloe vera (aloin) Anthraquinone colon 8–10 hours
Phenolphthalein Triphenylmethane colon 8 hours
bisacodyl (oral) Triphenylmethane colon 6–12 hours
bisacodyl (suppository) Triphenylmethane colon 60 minutes
Castor oil ricinoleic acid small intestine 2–6 hours

Effectiveness

For adults, a randomized controlled trial found PEG [MiraLax or GlycoLax] 17 grams once per day to be superior to tegaserod at 6 mg twice per day.[17] A randomized controlled trial found greater improvement from two sachets (26 grams) of PEG versus two sachets (20 grams) of lactulose.[18] 17 grams per day of PEG has been effective and safe in a randomized controlled trial for six months.[19] Another randomized controlled trial found no difference between sorbitol and lactulose.[20]

For children, PEG was found to be more effective than lactulose.[21]

Problems with use

Laxative abuse

Some of the less significant adverse effects of laxative abuse include dehydration, hypotension, tachycardia, postural dizziness and syncope;[22] however, laxative abuse can lead to potentially fatal acid-base and electrolyte imbalances.[22] For example, severe hypokalaemia has been associated with distal renal tubular acidosis from laxative abuse.[22] Metabolic alkalosis is the most common acid-base imbalance observed.[22] Other significant adverse effects include rhabdomyolysis,[22] steatorrhoea,[22] inflammation and ulceration of colonic mucosa,[22] pancreatitis,[22][23] renal failure,[22][24][25] factitious diarrhea[22][26] and other problems.[22]

Although patients with eating disorders such as anorexia nervosa and bulimia nervosa frequently abuse laxatives in an attempt to lose weight, laxatives act to speed up the transit of feces through the large intestine, which occurs subsequent to the absorption of nutrients in the small intestine. Thus, studies of laxative abuse have found that effects on body weight reflect primarily temporary losses of body water rather than energy (calorie) loss.[22][27][28]

Laxative gut

Physicians warn against the chronic use of stimulant laxatives due to concern that chronic use causes the colonic tissues to get worn out over time and not be able to expel feces due to long-term overstimulation.[29] A common finding in patients having used stimulant laxatives is a brown pigment deposited in the intestinal tissue, known as melanosis coli.

Historical and non-mainstream medical use

Laxatives, then called physicks or purgatives, were used extensively in pre-modern medicine to treat a wide range of conditions for which they are now generally regarded as ineffective in modern evidence-based medicine. Likewise, laxatives (often termed colon cleanses) continue to be promoted by practitioners of alternative medicine for a range of conditions, including conditions that are not medically recognized, e.g. mucoid plaque.

See also

References

  1. 1 2 3 4 5 6 "Constipation" (PDF). www.digestive.niddk.nih.gov. National Digestive Diseases Information Clearinghouse. Retrieved 3 November 2014.
  2. ↑ Bulk-forming agent entry in the public domain NCI Dictionary of Cancer Terms
  3. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Berardi M, Tietze KJ, Shimp LA, Rollins CJ, Popovich NG (2006). Handbook of Nonprescription Drugs (15th ed.). Washington, D.C.: American Pharmaceutical Association. ISBN 1582120749.
  4. 1 2 3 "The Facts About Fiber" (PDF). www.aicr.org. American Institute for Cancer Research. Retrieved 3 November 2014.
  5. ↑ Das, JL (2010). "Medicinal and nutritional values of banana cv. NENDRAN". Asian Journal of Horticulture 8: 11–14.
  6. ↑ Rush EC, Patel M, Plank LD, Ferguson LR (2002). "Kiwifruit promotes laxation in the elderly.". Asia Pac J Clin Nutr 11 (2): 164–8. doi:10.1046/j.1440-6047.2002.00287.x. PMID 12074185.
  7. ↑ Stacewicz-Sapuntzakis M, Bowen PE, Hussain EA, Damayanti-Wood BI, Farnsworth NR (2001). "Chemical composition and potential health effects of prunes: a functional food?". Critical reviews in food science and nutrition 41 (4): 251–86. doi:10.1080/20014091091814. PMID 11401245.
  8. ↑ Laxative (Oral Route) from Mayo clinic. Last updated: Nov. 1, 2012
  9. ↑ Joo JS, Ehrenpreis ED, Gonzalez L, Kaye M, Breno S, Wexner SD, Zaitman D, Secrest K (1998). "Alterations in colonic anatomy induced by chronic stimulant laxatives: the cathartic colon revisited". J Clin Gastroenterol 26 (4): 283–6. doi:10.1097/00004836-199806000-00014. PMID 9649012.
  10. ↑ Alterations in Colonic Anatomy Induced by Chronic Stimulant Laxatives: The Cathartic Colon Revisited Joo et al. Journal of Clinical Gastroenterology. June 1998 Volume 26 Issue 4 pp 283 - 286. http://journals.lww.com/jcge/Abstract/1998/06000/Alterations_in_Colonic_Anatomy_Induced_by_Chronic.14.aspx
  11. ↑ Tegaserod, FDA Zelnorm (tegaserod maleate) Information
  12. ↑ European Medicines Agency EPAR summary for the public
  13. ↑ Health Canada, Notice of Decision for Resotran
  14. ↑ http://www.shire.com/shireplc/en/rd/pipeline Shire PLC, R and D projects, Resolor
  15. ↑ Dharmananda, Subhuti. "SAFETY ISSUES AFFECTING HERBS: How Long can Stimulant Laxatives be Used?". Institute for Traditional Medicine. Retrieved 2010-03-19.
  16. ↑ "Stimulant Laxatives". Family Practice Notebook, LLC. 2010-02-26. Retrieved 2010-03-19.
  17. ↑ Di Palma JA, Cleveland MV, McGowan J, Herrera JL (2007). "A randomized, multicenter comparison of polyethylene glycol laxative and tegaserod in treatment of patients with chronic constipation". Am. J. Gastroenterol. 102 (9): 1964–71. doi:10.1111/j.1572-0241.2007.01365.x. PMID 17573794.
  18. ↑ Attar A, Lémann M, Ferguson A, Halphen M, Boutron MC, Flourié B, Alix E, Salmeron M, Guillemot F, Chaussade S, Ménard AM, Moreau J, Naudin G, Barthet M (1999). "Comparison of a low dose polyethylene glycol electrolyte solution with lactulose for treatment of chronic constipation". Gut 44 (2): 226–30. doi:10.1136/gut.44.2.226. PMC 1727381. PMID 9895382.
  19. ↑ Dipalma JA, Cleveland MV, McGowan J, Herrera JL (2007). "A randomized, multicenter, placebo-controlled trial of polyethylene glycol laxative for chronic treatment of chronic constipation". Am. J. Gastroenterol. 102 (7): 1436–41. doi:10.1111/j.1572-0241.2007.01199.x. PMID 17403074.
  20. ↑ Lederle FA, Busch DL, Mattox KM, West MJ, Aske DM (1990). "Cost-effective treatment of constipation in the elderly: a randomized double-blind comparison of sorbitol and lactulose". Am J Med 89 (5): 597–601. doi:10.1016/0002-9343(90)90177-F. PMID 2122724.
  21. ↑ "BestBETs: Is polyethylene glycol safe and effective for chro...". Retrieved 2007-09-06.
  22. 1 2 3 4 5 6 7 8 9 10 11 12 Roerig JL, Steffen KJ, Mitchell JE, Zunker C (2010). "Laxative abuse: epidemiology, diagnosis and management". Drugs 70 (12): 1487–1503. doi:10.2165/11898640-000000000-00000. PMID 20687617.
  23. ↑ Brown NW, Treasure JL, Campbell IC (2001). "Evidence for long-term pancreatic damage caused by laxative abuse in subjects recovered from anorexia nervosa". International Journal of Eating Disorders 29 (2): 236–238. doi:10.1002/1098-108X(200103)29:2<236::AID-EAT1014>3.0.CO;2-G. PMID 11429987.
  24. ↑ Copeland PM; Molina, H.; Ohye, Ch.; MacIas, R.; Alaminos, A.; Alvarez, L.; Teijeiro, J.; Muñoz, J.; Ortega, I. (1994). "Renal failure associated with laxative abuse". Psychother Psychosom 62 (3–4): 200–2. doi:10.1159/000098619. PMID 7531354.
  25. ↑ Wright LF, DuVal JW (1987). "Renal injury associated with laxative abuse". South Med J 80 (10): 1304–6. doi:10.1097/00007611-198710000-00024. PMID 3660046.
  26. ↑ Oster JR, Materson BJ, Rogers AI (November 1980). "Laxative abuse syndrome". Am. J. Gastroenterol. 74 (5): 451–8. PMID 7234824.
  27. ↑ Lacey JH, Gibson E (1985). "Controlling weight by purgation and vomiting: A comparative study of bulimics". Journal of Psychiatric Research 19 (2–3): 337–341. doi:10.1016/0022-3956(85)90037-8. PMID 3862833.
  28. ↑ http://www.uptodate.com/contents/acid-base-and-electrolyte-abnormalities-with-diarrhea-or-ureteral-diversion
  29. ↑ Joo JS, Ehrenpreis ED, Gonzalez L, Kaye M, Breno S, Wexner SD, Zaitman D, Secrest K (June 1998). "Alterations in colonic anatomy induced by chronic stimulant laxatives: the cathartic colon revisited". Journal of Clinical Gastroenterology 26 (4): 283–6. doi:10.1097/00004836-199806000-00014. PMID 9649012.

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