Laxative

Short description: Agents that relax and loosen the bowels and stools

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.

## Contents

* 1 Types
* 1.1 Bulk-forming agents
* 1.1.1 Dietary fiber
* 1.2 Emollient agents (stool softeners)
* 1.3 Lubricant agents
* 1.4 Hyperosmotic agents
* 1.5 Saline laxative agents
* 1.6 Stimulant agents
* 1.7 Miscellaneous
* 1.8 Serotonin agonist
* 1.9 Chloride channel activators
* 2 Comparison of available agents
* 2.1 Effectiveness
* 3 Problems with use
* 3.1 Laxative abuse
* 3.2 Laxative gut
* 4 Historical and health fraud uses
* 5 See also
* 6 References

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

Properties

* Site of action: small and large intestines
* Onset of action: 12–72 hours
* Examples: dietary fiber, Metamucil, Citrucel, FiberCon[3]

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

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

* Fruits, such as bananas,[5] though this depends on their ripeness,[6] kiwifruits,[7] prunes,[8] apples (with skin), pears (with skin), and raspberries[1]
* Vegetables, such as broccoli, string beans, kale, spinach,[4] cooked winter squash, cooked taro and poi, cooked peas, and baked potatoes (with skin)[1]
* Whole grains
* Bran products[1][4]
* Nuts
* Legumes, such as beans, peas, and lentils[1]

### 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 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

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

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

Properties

* Site of action: colon
* Onset of action: 12–72 hours (oral), 0.25–1 hour (rectal)
* Examples: glycerin suppositories (Hallens), sorbitol, lactulose, and PEG (Colyte, MiraLax)[12]

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

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

* Site of action: small and large intestines
* Onset of action: 0.5–3 hours (oral), 2–15 minutes (rectal)
* Examples: sodium phosphate (and variants), magnesium citrate, magnesium hydroxide (milk of magnesia), and magnesium sulfate (Epsom salt)[3]

### Stimulant agents

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

* Site of action: colon
* Onset of action: 6–10 hours
* Examples: senna, bisacodyl[3]

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

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

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

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

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

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

### Laxative abuse

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

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

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

* ATC code A06
* Bowel management
* Cathartic
* Dietary fiber
* Diuretic
* Maltitol
* Enema
* Suppository
* Transanal irrigation

## References

1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 "Constipation". National Digestive Diseases Information Clearinghouse. http://digestive.niddk.nih.gov/ddiseases/pubs/constipation/Constipation_508.pdf.
2. ↑ Bulk-forming agent entry in the public domain NCI Dictionary of Cancer Terms
3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 Handbook of Nonprescription Drugs (15th ed.). Washington, D.C.: American Pharmaceutical Association. 2006. ISBN 978-1582120744.
4. ↑ 4.0 4.1 4.2 "The Facts About Fiber". American Institute for Cancer Research. http://www.aicr.org/assets/docs/pdf/brochures/facts-about-fiber.pdf.
5. ↑ Das, JL (2010). "Medicinal and nutritional values of banana cv. NENDRAN". Asian Journal of Horticulture 8: 11–14. http://www.cabdirect.org/abstracts/20103272020.html;jsessionid=2B9A2FDF37186F0DA0A347FF227D606D. Retrieved 2012-11-29.
6. ↑ "15 Foods That Cause Constipation (Caffeine, Chocolate, Alcohol)" (in en). MedicineNet. http://www.medicinenet.com/top_foods_that_cause_constipation/page2.htm.
7. ↑ "Kiwifruit promotes laxation in the elderly.". Asia Pac J Clin Nutr 11 (2): 164–8. 2002. doi:10.1046/j.1440-6047.2002.00287.x. PMID 12074185.
8. ↑ "Chemical composition and potential health effects of prunes: a functional food?". Critical Reviews in Food Science and Nutrition 41 (4): 251–86. 2001. doi:10.1080/20014091091814. PMID 11401245.
9. ↑ 9.0 9.1 9.2 Handbook of Nonprescription Drugs (15th ed.). Washington, D.C.: American Pharmaceutical Association. 2006. ISBN 978-1582120744.
10. ↑ 10.0 10.1 Krinsky, Daniel L. (November 30, 2020) (in en). 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. https://pharmacylibrary.com/doi/book/10.21019/9781582123172.
11. ↑ Bowles-Jordan, Jane. "Constipation". http://proxycheck.lib.umanitoba.ca/libraries/online/proxy.php?http://www.e-therapeutics.ca/?p=mzLm9vCs3qxZyEUHPZaNJ7uOeM6sKtN-Az2x-dKQMNz0daKJqHkuaoQKNMbtytXe&logintype=auto&auto=true.
12. ↑ 12.0 12.1 Handbook of Nonprescription Drugs (15th ed.). Washington, D.C.: American Pharmaceutical Association. 2006. ISBN 978-1582120744.
13. ↑ Laxative (Oral Route) from Mayo clinic. Last updated: Nov. 1, 2012
14. ↑ "Alterations in colonic anatomy induced by chronic stimulant laxatives: the cathartic colon revisited". J Clin Gastroenterol 26 (4): 283–6. 1998. doi:10.1097/00004836-199806000-00014. PMID 9649012.
15. ↑ 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
16. ↑ Research, Center for Drug Evaluation and. "Postmarket Drug Safety Information for Patients and Providers - Zelnorm (tegaserod maleate) Information". https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm103223.htm.
17. ↑ "European Medicines Agency EPAR summary for the public". http://www.emea.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/001012/WC500053995.pdf.
18. ↑ "Health Canada, Notice of Decision for Resotran". http://www.hc-sc.gc.ca/dhp-mps/prodpharma/sbd-smd/drug-med/sbd_smd_2012_resotran_141157-eng.php#a2.
19. ↑ Dharmananda, Subhuti. "SAFETY ISSUES AFFECTING HERBS: How Long can Stimulant Laxatives be Used?". Institute for Traditional Medicine. http://www.itmonline.org/arts/laxatives.htm.
20. ↑ "Stimulant Laxatives". Family Practice Notebook, LLC. 2010-02-26. http://www.fpnotebook.com/GI/Pharm/StmlntLxtv.htm.
21. ↑ "A randomized, multicenter comparison of polyethylene glycol laxative and tegaserod in treatment of patients with chronic constipation". Am. J. Gastroenterol. 102 (9): 1964–71. 2007. doi:10.1111/j.1572-0241.2007.01365.x. PMID 17573794.
22. ↑ "Comparison of a low dose polyethylene glycol electrolyte solution with lactulose for treatment of chronic constipation". Gut 44 (2): 226–30. 1999. doi:10.1136/gut.44.2.226. PMID 9895382.
23. ↑ "A randomized, multicenter, placebo-controlled trial of polyethylene glycol laxative for chronic treatment of chronic constipation". Am. J. Gastroenterol. 102 (7): 1436–41. 2007. doi:10.1111/j.1572-0241.2007.01199.x. PMID 17403074.
24. ↑ "Cost-effective treatment of constipation in the elderly: a randomized double-blind comparison of sorbitol and lactulose". Am J Med 89 (5): 597–601. 1990. doi:10.1016/0002-9343(90)90177-F. PMID 2122724.
25. ↑ "BestBETs: Is polyethylene glycol safe and effective for chro...". http://www.bestbets.org/cgi-bin/bets.pl?record=00901.
26. ↑ 26.00 26.01 26.02 26.03 26.04 26.05 26.06 26.07 26.08 26.09 26.10 26.11 "Laxative abuse: epidemiology, diagnosis and management". Drugs 70 (12): 1487–1503. 2010. doi:10.2165/11898640-000000000-00000. PMID 20687617.
27. ↑ "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. 2001. 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. et al. (1994). "Renal failure associated with laxative abuse". Psychother Psychosom 62 (3–4): 200–2. doi:10.1159/000098619. PMID 7531354.
29. ↑ "Renal injury associated with laxative abuse". South Med J 80 (10): 1304–6. 1987. doi:10.1097/00007611-198710000-00024. PMID 3660046.
30. ↑ "Laxative abuse syndrome". Am. J. Gastroenterol. 74 (5): 451–8. November 1980. PMID 7234824.
31. ↑ "Controlling weight by purgation and vomiting: A comparative study of bulimics". Journal of Psychiatric Research 19 (2–3): 337–341. 1985. doi:10.1016/0022-3956(85)90037-8. PMID 3862833.
32. ↑ "Acid-base and electrolyte abnormalities with diarrhea". http://www.uptodate.com/contents/acid-base-and-electrolyte-abnormalities-with-diarrhea-or-ureteral-diversion.
33. ↑ "Alterations in colonic anatomy induced by chronic stimulant laxatives: the cathartic colon revisited". Journal of Clinical Gastroenterology 26 (4): 283–6. June 1998. 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. ISBN 9789350906552. OCLC 870530462.

* v
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Pharmacology: major drug groups

Gastrointestinal tract/
metabolism (A)|

* stomach acid
* Antacids
* H2 antagonists
* Proton pump inhibitors
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Other ATC (V)|

* Antidotes
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* v
* t
* e

Drugs for constipation (laxatives and cathartics) (A06)

Stool softeners|

* Docusate

Stimulant laxatives|

* Bisacodyl
* Bisoxatin
* Cascara
* Castor oil
* Dantron
* Oxyphenisatine
* Phenolphthalein
* Senna glycosides
* Sodium picosulfate

Bulk-forming laxatives|

* Dietary fiber
* Ethulose
* Ispaghula
* Methylcellulose
* Polycarbophil calcium
* Sterculia
* Triticum

Lubricant laxatives|

* Liquid paraffin
* Mineral oil
* White petrolatum (petroleum jelly)

Osmotic laxatives|

* Lactitol
* Lactulose
* Laminarid
* Magnesium carbonate
* Magnesium citrate
* Magnesium hydroxide (milk of magnesia)
* Magnesium oxide
* Magnesium peroxide
* Magnesium sulfate
* Mannitol
* Pentaerythritol
* Polyethylene glycol (macrogol)
* Sodium phosphate
* Sodium sulfate
* Sodium tartrate
* Sorbitol

Enemas|

* Bisacodyl
* Dantron
* Glycerol
* Oil
* Sodium laurilsulfate
* Sodium lauryl sulfoacetate
* Sodium phosphate
* Sorbitol

Opioid antagonists|

* Naloxone (Oxycodone/naloxone)
* PAMORAs
* Alvimopan
* Axelopran
* Bevenopran
* Methylnaltrexone
* Naldemedine
* Naloxegol

Others|

* Linaclotide
* Lubiprostone
* Oxyphenisatine
* Prucalopride
* Tegaserod
* Ulimorelin

* v
* t
* e

Irritable bowel syndrome (IBS)

Causes or potential causes|

* Unknown

Management|

* Low-FODMAP diet
* Gluten-free diet
* Soluble fiber
* Laxatives
* Antispasmodics
* Psychotherapy
* Tricyclic antidepressants
* SSRIs
* Probiotics
* Eluxadoline

Related topics|

* Gut–brain axis
* Hypothalamic–pituitary–adrenal axis
* Sympathetic nervous system

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