Laxatives

Article Author:
Anam Bashir
Article Editor:
Omeed Sizar
Updated:
10/8/2019 2:34:34 PM
PubMed Link:
Laxatives

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 step 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 laxative in the intensive care unit (ICU) patients to prevent constipation.[2] Also, O'Brien et al. have suggested the use of 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work on intrinsic neurons, release acetylcholine, and induce mucosal secretion.[6] However, cisapride has since being withdrawn from the market due to concerns of severe cardiovascular side effects.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 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 into 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.

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 should be used with 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 have been described to cause diarrhea.[10] Long-term stimulant laxative use has been associated with the loss of haustral folds in the colon; this could indicate neuronal or muscular injury 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 are advised to 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 patients who are bedridden and those with altered cognition.[15] Psyllium agents are contraindicated in those with allergic reactions.[13]

Toxicity

Laxative abuse is common 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] With 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 in 3 months.[19]

Enhancing Healthcare Team Outcomes

Constipation is a commonly overlooked problem in clinic visits as well as inpatient, 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 doctors, 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 good bowel movements while in the hospital.[21] (Level V)


References

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[2] Masri Y,Abubaker J,Ahmed R, Prophylactic use of laxative for constipation in critically ill patients. Annals of thoracic medicine. 2010 Oct     [PubMed PMID: 20981183]
[3] O'Brien SH,Fan L,Kelleher KJ, Inpatient use of laxatives during opioid administration in children with sickle cell disease. Pediatric blood     [PubMed PMID: 20049931]
[4] Liu LW, Chronic constipation: current treatment options. Canadian journal of gastroenterology = Journal canadien de gastroenterologie. 2011 Oct     [PubMed PMID: 22114754]
[5] Leung L,Riutta T,Kotecha J,Rosser W, Chronic constipation: an evidence-based review. Journal of the American Board of Family Medicine : JABFM. 2011 Jul-Aug     [PubMed PMID: 21737769]
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[9] Twycross R,Sykes N,Mihalyo M,Wilcock A, Stimulant laxatives and opioid-induced constipation. Journal of pain and symptom management. 2012 Feb     [PubMed PMID: 22248790]
[10] Andresen V,Layer P, Medical Therapy of Constipation: Current Standards and Beyond. Visceral medicine. 2018 Apr     [PubMed PMID: 29888241]
[11] Johanson JF, Review of the treatment options for chronic constipation. MedGenMed : Medscape general medicine. 2007 May 2     [PubMed PMID: 17955081]
[12] 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. Journal of clinical gastroenterology. 1998 Jun     [PubMed PMID: 9649012]
[13] Xing JH,Soffer EE, Adverse effects of laxatives. Diseases of the colon and rectum. 2001 Aug     [PubMed PMID: 11535863]
[14] Siegel JD,Di Palma JA, Medical treatment of constipation. Clinics in colon and rectal surgery. 2005 May     [PubMed PMID: 20011345]
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[16] Roerig JL,Steffen KJ,Mitchell JE,Zunker C, Laxative abuse: epidemiology, diagnosis and management. Drugs. 2010 Aug 20     [PubMed PMID: 20687617]
[17] Oster JR,Materson BJ,Rogers AI, Laxative abuse syndrome. The American journal of gastroenterology. 1980 Nov     [PubMed PMID: 7234824]
[18] Copeland PM, Renal failure associated with laxative abuse. Psychotherapy and psychosomatics. 1994     [PubMed PMID: 7531354]
[19] Shirasawa Y,Fukuda M,Kimura G, Erratum to: Diuretics-assisted treatment of chronic laxative abuse. CEN case reports. 2014 Nov     [PubMed PMID: 28509204]
[20] Costilla VC,Foxx-Orenstein AE, Constipation in adults: diagnosis and management. Current treatment options in gastroenterology. 2014 Sep     [PubMed PMID: 25015533]
[21] Jackson R,Cheng P,Moreman S,Davey N,Owen L,     [PubMed PMID: 27752319]