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Laxative

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(Redirected from Stimulant laxatives)
"Purgative" redirects here. For other uses, see Purgation.
Glycerin suppositories used as laxatives.

Laxatives, purgatives, or aperients are substances that loosen stools[1] and increase bowel movements. They are used to treat and prevent constipation.

Laxatives vary as to how they work and the side effects they may 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, and may be administered orally or rectally.

Types

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Bulk-forming agents

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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 they can pass more easily through the intestines (lower part of the digestive tract).[2]

Properties

Bulk-forming agents generally have the gentlest of effects among laxatives,[1] making them ideal for long-term maintenance of regular bowel movements.

Dietary fiber

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

Emollient agents (stool softeners)

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Emollient laxatives, also known as stool softeners, are anionic surfactants that enable additional water and fats to be incorporated in the stool, making movement through the bowels easier.

Properties

  • Site of action: small and large intestines
  • Onset of action: 12–72 hours
  • Examples: Docusate (Colace, Diocto), Gibs-Eze[3]

Emollient agents prevent constipation rather than treating long-term constipation.[3]

Lubricant agents

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Lubricant laxatives are substances that coat the stool with slippery lipids and decrease colonic absorption of water so the stool slides through the colon more easily. Lubricant laxatives also increase the weight of stool and decrease intestinal transit time.[9]

Properties

  • Site of action: colon
  • Onset of action: 6–8 hours
  • Example: mineral oil[9]

Mineral oils, such as liquid paraffin, are generally the only nonprescription lubricant laxative available, but due to the risk of lipid pneumonia resulting from accidental aspiration, mineral oil is not recommended, especially in children and infants.[10][11] Mineral oil may decrease the absorption of fat-soluble vitamins and some minerals.[9]

Hyperosmotic agents

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Hyperosmotic laxatives cause the intestines to hold more water, creating an osmotic gradient, which adds more pressure and stimulates bowel movement.[12][10]

Properties

Lactulose works by the osmotic effect, which retains water in the colon; lowering the pH through bacterial fermentation to lactic, formic, and acetic acids; 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.[citation needed]

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, Cosmocol, CoLyte, Miralax, Movicol, NuLytely, Suprep, and Fortrans. Solutions of sorbitol (SoftLax) have similar effects.[citation needed]

Saline laxative agents

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Saline laxatives are nonabsorbable, osmotically active 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

Stimulant agents

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Stimulant laxatives are substances that act on the intestinal mucosa or nerve plexus, altering water and electrolyte secretion.[13] They also stimulate peristaltic action and can be dangerous under certain circumstances.[14]

Senna plant

Properties

Prolonged use of stimulant laxatives can create drug dependence by damaging the colon's haustral folds, making users less able to move feces through their 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.[15]

Miscellaneous

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

Properties

  • Site of action: colon, small intestine (see below) [citation needed]
  • Onset of action: 2–6 hours
  • Examples: castor oil[3]

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

Serotonin agonist

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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.[16]

Prucalopride (brand name Resolor) is a current drug approved for use in the EU since October 15, 2009,[17] in Canada (brand name Resotran) since December 7, 2011,[18] and in the United States since December 2018.

Chloride channel activators

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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.

Comparison of available agents

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Common stimulant laxatives[19][20]
Preparation(s) Type Site of action Onset of action
Cascara (casanthranol) Anthraquinone colon 36–8 hours
Buckthorn Anthraquinone colon 36–8 hours
Senna extract (senna glycoside) Anthraquinone colon 36–8 hours
Aloe vera (aloin) Anthraquinone colon 58–10 hours
Phenolphthalein Triphenylmethane colon 48 hours
Bisacodyl (oral) Triphenylmethane colon 66–12 hours
Bisacodyl (suppository) Triphenylmethane colon 160 minutes
Castor oil Ricinoleic acid small intestine 22–6 hours

Effectiveness

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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.[21] A randomized controlled trial found greater improvement from two sachets (26 g) of PEG versus two sachets (20 g) of lactulose.[22] 17 g per day of PEG has been effective and safe in a randomized, controlled trial for six months.[23] Another randomized, controlled trial found no difference between sorbitol and lactulose.[24]

For children, PEG was found to be more effective than lactulose.[25]

Problems with use

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Laxative abuse

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Some of the less significant adverse effects of laxative abuse include dehydration (which causes tremors, weakness, fainting, blurred vision, kidney damage), low blood pressure, fast heart rate, postural dizziness and fainting;[26] however, laxative abuse can lead to potentially fatal acid-base, and electrolyte imbalances.[26] For example, severe hypokalaemia has been associated with distal renal tubular acidosis from laxative abuse.[26] Metabolic alkalosis is the most common acid-base imbalance observed.[26] Other significant adverse effects include rhabdomyolysis,[26] steatorrhoea,[26] inflammation and ulceration of colonic mucosa,[26] pancreatitis,[26][27] kidney failure,[26][28][29] factitious diarrhea[26][30] and other problems.[26] The colon will need more quantities of laxatives to keep functioning, this will result in a lazy colon, infections, irritable bowel syndrome, and potential liver damage.

Although some patients with eating disorders such as anorexia nervosa and bulimia nervosa abuse laxatives in an attempt to lose weight, laxatives act to speed up the transit of feces through the large intestine, which occurs after the absorption of nutrients in the small intestine is already complete. Thus, studies of laxative abuse have found that effects on body weight reflect primarily temporary losses of body water rather than energy (calorie) loss.[26][31][32]

Laxative gut

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Physicians warn against the chronic use of stimulant laxatives due to concern that chronic use could cause the colonic tissues to get worn out over time and not be able to expel feces due to long-term overstimulation.[33] A common finding in patients having used stimulant laxatives is a brown pigment deposited in the intestinal tissue, known as melanosis coli.[citation needed]

Historical and health fraud uses

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Laxatives, once called "physicks" or "purgatives", were used extensively in historic medicine to treat many conditions for which they are now generally regarded as ineffective in evidence-based medicine.[34] Likewise, laxatives (often termed colon cleanses) may be promoted in alternative medicine for various conditions of quackery, such as "mucoid plaque".[35]

See also

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References

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  1. ^ a b c d e f "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. ^ a b c d e f g h Berardi M, Tietze KJ, Shimp LA, Rollins CJ, Popovich NG (2006). Handbook of Nonprescription Drugs (15th ed.). Washington, D.C.: American Pharmaceutical Association. ISBN 978-1582120744.
  4. ^ a b c "The Facts About Fiber" (PDF). www.aicr.org. American Institute for Cancer Research. Archived from the original (PDF) on 3 November 2014. Retrieved 3 November 2014.
  5. ^ Das, JL (2010). "Medicinal and nutritional values of banana cv. NENDRAN". Asian Journal of Horticulture. 8: 11–14. Archived from the original on 2014-11-03. Retrieved 2012-11-29.
  6. ^ "15 Foods That Cause Constipation (Caffeine, Chocolate, Alcohol)". MedicineNet. Retrieved 2017-12-12.
  7. ^ 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. S2CID 15280086.
  8. ^ 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. S2CID 31159565.
  9. ^ a b c Berardi M, Tietze KJ, Shimp LA, Rollins CJ, Popovich NG (2006). Handbook of Nonprescription Drugs (15th ed.). Washington, D.C.: American Pharmaceutical Association. ISBN 978-1582120744.
  10. ^ a b Krinsky, Daniel L. (November 30, 2020). Handbook of Nonprescription Drugs: An Interactive Approach to Self-Care, 20th Edition. 2215 Constitution Avenue, N.W. Washington, DC 20037-2985: The American Pharmacists Association. doi:10.21019/9781582123172.ch15. ISBN 978-1-58212-317-2.{{cite book}}: CS1 maint: location (link)
  11. ^ Bowles-Jordan, Jane. "Constipation". CPS. Retrieved March 20, 2020.
  12. ^ a b Berardi M, Tietze KJ, Shimp LA, Rollins CJ, Popovich NG (2006). Handbook of Nonprescription Drugs (15th ed.). Washington, D.C.: American Pharmaceutical Association. ISBN 978-1582120744.
  13. ^ Laxative (Oral Route) from Mayo clinic. Last updated: Nov. 1, 2012
  14. ^ 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.
  15. ^ Joo, Jae Sik; Ehrenpreis, Eli D.; Gonzalez, Leopoldo; Kaye, Mark; Breno, Susan; Wexner, Steven D.; Zaitman, Daniel; Secrest, K. (June 1998). "Alterations in Colonic Anatomy Induced by Chronic Stimulant Laxatives: The Cathartic Colon Revisited". Journal of Clinical Gastroenterology. 26 (4): 283–286. doi:10.1097/00004836-199806000-00014. PMID 9649012.
  16. ^ Research, Center for Drug Evaluation and. "Postmarket Drug Safety Information for Patients and Providers - Zelnorm (tegaserod maleate) Information". www.fda.gov. Retrieved 14 April 2018.
  17. ^ "European Medicines Agency EPAR summary for the public" (PDF). europa.eu. Archived from the original (PDF) on 14 April 2018. Retrieved 14 April 2018.
  18. ^ "Health Canada, Notice of Decision for Resotran". hc-sc.gc.ca. Archived from the original on 18 March 2017. Retrieved 14 April 2018.
  19. ^ Dharmananda, Subhuti. "SAFETY ISSUES AFFECTING HERBS: How Long can Stimulant Laxatives be Used?". Institute for Traditional Medicine. Retrieved 2010-03-19.
  20. ^ "Stimulant Laxatives". Family Practice Notebook, LLC. 2010-02-26. Retrieved 2010-03-19.
  21. ^ 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. S2CID 32055676.
  22. ^ 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.
  23. ^ 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. S2CID 10946562.
  24. ^ 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.
  25. ^ "BestBETs: Is polyethylene glycol safe and effective for chro..." Retrieved 2007-09-06.
  26. ^ a b c d e f g h i j k l 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. S2CID 29007249.
  27. ^ 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.
  28. ^ 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.
  29. ^ 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.
  30. ^ Oster JR, Materson BJ, Rogers AI (November 1980). "Laxative abuse syndrome". Am. J. Gastroenterol. 74 (5): 451–8. PMID 7234824.
  31. ^ 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.
  32. ^ "Acid-base and electrolyte abnormalities with diarrhea". www.uptodate.com. Retrieved 2017-12-12.
  33. ^ 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.
  34. ^ Stolberg, Michael (2003). "[The miraculous effects of taking laxatives. Success and failure of pre-modern medical treatment from the patients' perspective]". Wurzburger Medizinhistorische Mitteilungen. 22: 167–177. ISSN 0177-5227. PMID 15641192.
  35. ^ M., Raju, S. (2013-09-30). Illustrated medical pharmacology. JP Medical. ISBN 9789350906552. OCLC 870530462.{{cite book}}: CS1 maint: multiple names: authors list (link)
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