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Laxatives

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Last Update: September 4, 2021.

Continuing Education Activity

Constipation is a common diagnosis that requires proper evaluation and appropriate treatment. The approach to a patient with chronic constipation includes patient education, behavior modification, dietary changes, and laxative therapy. It is important to note that laxative therapy is not the only treatment for constipation. Initial management of constipation should include lifestyle changes such as increasing fluids, fiber-rich foods such as asparagus, broccoli, Brussels sprouts, cabbage, and spinach. When constipation is not controlled by lifestyle modification, treatment with laxatives should be a consideration. This activity describes the mode of action of various laxatives, including mechanisms of action, pharmacology, adverse event profiles, eligible patient populations, monitoring, and highlights the interprofessional team's role in managing conditions where laxative therapy is helpful.

Objectives:

  • Describe the mechanism of action of various classes of laxatives.
  • Review the indications for laxative therapy.
  • Summarize the potential adverse event profile for various classes of laxatives.
  • Outline interprofessional team strategies for improving care coordination and communication to properly use laxatives to improve patient outcomes.
Access free multiple choice questions on this topic.

Indications

Constipation is a common diagnosis that requires proper evaluation and appropriate treatment. The approach to a patient with chronic constipation includes patient education, behavior modification, dietary changes, and laxative therapy. It is important to note that laxative therapy is not the only treatment for constipation.  Initial management of constipation should include lifestyle changes such as increasing fluids, fiber-rich foods such as asparagus, broccoli, Brussels sprouts, cabbage, and spinach. When constipation is not controlled by lifestyle modification, treatment with laxatives should be a consideration.

Osmotic or stimulant laxatives are considered first-line. Prokinetics and secretagogues are the next steps when osmotic or stimulants are unable to control constipation.[1] Laxatives can also be useful in patients with irritable bowel syndrome, constipation, and opioid-induced constipation. Yasser Masri et al. have described the prophylactic use of laxatives in the intensive care unit (ICU) patients to prevent constipation.[2] Also, O'Brien et al. have suggested using laxatives during opioid administration in patients with sickle cell disease, particularly in post-surgical patients and even younger children.[3] In addition to alleviating constipation, laxatives are sometimes used to clear the bowels before procedures like colonoscopy.

Mechanism of Action

Types of laxatives are classified by the mechanism of action as follows:

  • Bulk-forming laxatives retain fluid in the stool and increase stool weight and consistency.[4] Psyllium, dietary fiber, carboxymethylcellulose, and methylcellulose are common examples. It is important to take ample amounts of water for bulk-forming agents to work. Lack of water, in turn, leads to bloating and can cause bowel obstruction.[5]
  • Osmotic agents contain substances that are poorly absorbable and draw water into the lumen of the bowel.[4] Milk of magnesia, lactulose, sorbitol, and polyethylene glycol (PEG) are common examples.
  • Prokinetic agents like cisapride and tegaserod work as agonists of 5-Hydroxytryptamine receptors.[4] They work on intrinsic neurons, releasing acetylcholine, and inducing mucosal secretion.[6] However, cisapride has since being withdrawn from the market due to concerns of severe cardiovascular side effects. Tegaserod is available under investigational new drug processes. Prucalopride, ATI-7505, and velusetrag are agents currently under investigation in this class.[6]
  • Lubricants like mineral oil aid in the passage of stools.[7]
  • Stimulant laxatives stimulate the myenteric plexus and the Auerbach plexus, which increase intestinal secretions and motility.[8] They also decrease the absorption of water from the lumen of the bowel.[5] Bisacodyl, senna, cascara, and sodium picosulfate (SPS) are common examples. Senna and cascara are present in herbal teas or remedies.[4]
  • Surface active agents like docusate lower surface tension, which leads to water and fats penetrating the stool.[9]
  • Linaclotide is a guanylate cyclase agonist and induces cGMP; this leads to cystic fibrosis transmembrane conductance regulator (CFTR), which, in turn, causes water and electrolyte secretion into the lumen.[10]
  • Lubiprostone, a chloride channel activator, leads to water and chloride secretion into the stool and softer stool consistency.[10]

Administration

Laxatives are usually taken orally or as suppositories. Oral formulations include tablets, capsules, chewable tablets, and liquids.

Adverse Effects

Most laxatives are safe when used appropriately and in patients without contraindications. Bulk-forming agents like lactulose can have adverse effects like bloating, nausea, vomiting, and diarrhea.[8] Stimulant laxatives are known to cause abdominal pain.[8]. Cisapride and tegaserod were withdrawn from the market after cardiovascular adverse effects, including prolonged QT interval that increases the risk for Torsades de Pointes.[4] 

Mineral oil can cause aspiration and lipoid pneumonia.[5] Osmotic agents like magnesium can cause metabolic disturbances, especially in the presence of renal involvement. Also, magnesium excretion depends on renal function, and its use requires caution in renal impairment.[4] Osmotic agents result in volume load and should be used with caution in renal or cardiac dysfunction.[11] With prokinetic agents, adverse effects like a headache, nausea, and diarrhea have been described.[10] Secretagogues like linaclotide can occasionally cause diarrhea.[10] 

Long-term stimulant laxative use has correlated with the loss of haustral folds in the colon; this could indicate neuronal or muscular injury caused by these agents.[12] In vitro studies have described stimulant laxatives like senna and bisacodyl as having neoplastic potential, but data is lacking in human studies so far.[13]

Contraindications

Generally, patients should avoid laxatives during pregnancy by most obstetricians, although bulk laxatives are considered safe during pregnancy. Stimulant laxatives are considered second-line.[14] Contraindications to bulk-forming agents include bedridden patients and those with altered cognition.[15] Psyllium agents are contraindicated in those with allergic reactions.[13]

Toxicity

Laxative abuse is not uncommon and found in patients with anorexia nervosa or bulimia nervosa and the elderly who continue to use laxatives once started for constipation. It also includes patients with surreptitious diarrhea.[16] Patients who misuse laxatives usually complain of diarrhea with alternating constipation, nausea, and vomiting.[17] These patients can present with dehydration and electrolyte imbalances like hyponatremia, hypokalemia, hyperuricemia, and hyperaldosteronism.[17] Dehydration and hypokalemia together can cause renal insufficiency.[18] In cases of diarrhea, potassium and volume depletion leads to increased aldosterone secretion, which further leads to a worsening of hypokalemia.[18] The treatment of laxative abuse is to quit the causative agent. The main challenges are rebound symptoms like weight gain, edema, and constipation, which are very distressing for the patient. Edema is due to renal retention of water. Diuretics should be used with caution to help with constipation and edema and increase patient tolerance when stopping the use of the drug. Renal function and electrolytes require careful monitoring. Diuretics can be tapered off over 3 months.[19]

Enhancing Healthcare Team Outcomes

Constipation is a commonly overlooked problem in clinic visits and inpatient settings, even though it causes significant distress to patients and leads to secondary complications like urinary retention, abdominal pain, and nausea. It is one of the most prevalent outpatient diagnoses among gastrointestinal disorders.[20] The role of specialists like gastroenterologists is to identify which patients need additional testing or more specific treatments.[20] Managing constipation includes taking a thorough history and physical examination to look for secondary causes of constipation. It is, however, challenging because there are no universally accepted guidelines. It should involve patient education and setting realistic expectations.

Healthcare staff, including clinicians (MDs, DOs, NPS, and PAs), nurses, pharmacists, and care staff, should work together for bowel management while in the hospital. Constipation is very common in the elderly when admitted inpatient and leads to prolonged hospital stays. Various interventions to manage constipation include the nurse maintaining stool charts and the clinician reviewing these charts to revise the laxative dose or switch to another laxative to maintain functional bowel movements while in the hospital.[21] [Level 5]

Review Questions

References

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Krogh K, Chiarioni G, Whitehead W. Management of chronic constipation in adults. United European Gastroenterol J. 2017 Jun;5(4):465-472. [PMC free article: PMC5446139] [PubMed: 28588875]
2.
Masri Y, Abubaker J, Ahmed R. Prophylactic use of laxative for constipation in critically ill patients. Ann Thorac Med. 2010 Oct;5(4):228-31. [PMC free article: PMC2954377] [PubMed: 20981183]
3.
O'Brien SH, Fan L, Kelleher KJ. Inpatient use of laxatives during opioid administration in children with sickle cell disease. Pediatr Blood Cancer. 2010 Apr;54(4):559-62. [PubMed: 20049931]
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Liu LW. Chronic constipation: current treatment options. Can J Gastroenterol. 2011 Oct;25 Suppl B:22B-28B. [PMC free article: PMC3206558] [PubMed: 22114754]
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Jin J. JAMA patient page. Over-the-counter laxatives. JAMA. 2014 Sep 17;312(11):1167. [PubMed: 25226492]
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Tack J, Müller-Lissner S. Treatment of chronic constipation: current pharmacologic approaches and future directions. Clin Gastroenterol Hepatol. 2009 May;7(5):502-8; quiz 496. [PubMed: 19138759]
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Twycross R, Sykes N, Mihalyo M, Wilcock A. Stimulant laxatives and opioid-induced constipation. J Pain Symptom Manage. 2012 Feb;43(2):306-13. [PubMed: 22248790]
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Andresen V, Layer P. Medical Therapy of Constipation: Current Standards and Beyond. Visc Med. 2018 Apr;34(2):123-127. [PMC free article: PMC5981595] [PubMed: 29888241]
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Johanson JF. Review of the treatment options for chronic constipation. MedGenMed. 2007 May 02;9(2):25. [PMC free article: PMC1994829] [PubMed: 17955081]
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Joo JS, Ehrenpreis ED, Gonzalez L, Kaye M, Breno S, Wexner SD, Zaitman D, Secrest K. Alterations in colonic anatomy induced by chronic stimulant laxatives: the cathartic colon revisited. J Clin Gastroenterol. 1998 Jun;26(4):283-6. [PubMed: 9649012]
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Xing JH, Soffer EE. Adverse effects of laxatives. Dis Colon Rectum. 2001 Aug;44(8):1201-9. [PubMed: 11535863]
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Schuster BG, Kosar L, Kamrul R. Constipation in older adults: stepwise approach to keep things moving. Can Fam Physician. 2015 Feb;61(2):152-8. [PMC free article: PMC4325863] [PubMed: 25676646]
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Roerig JL, Steffen KJ, Mitchell JE, Zunker C. Laxative abuse: epidemiology, diagnosis and management. Drugs. 2010 Aug 20;70(12):1487-503. [PubMed: 20687617]
17.
Oster JR, Materson BJ, Rogers AI. Laxative abuse syndrome. Am J Gastroenterol. 1980 Nov;74(5):451-8. [PubMed: 7234824]
18.
Copeland PM. Renal failure associated with laxative abuse. Psychother Psychosom. 1994;62(3-4):200-2. [PubMed: 7531354]
19.
Shirasawa Y, Fukuda M, Kimura G. Erratum to: Diuretics-assisted treatment of chronic laxative abuse. CEN Case Rep. 2014 Nov;3(2):215-216. [PMC free article: PMC5413666] [PubMed: 28509204]
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Costilla VC, Foxx-Orenstein AE. Constipation in adults: diagnosis and management. Curr Treat Options Gastroenterol. 2014 Sep;12(3):310-21. [PubMed: 25015533]
21.
Jackson R, Cheng P, Moreman S, Davey N, Owen L. "The constipation conundrum": Improving recognition of constipation on a gastroenterology ward. BMJ Qual Improv Rep. 2016;5(1) [PMC free article: PMC5051500] [PubMed: 27752319]
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