Continuing Education Activity

Bisacodyl is a medication used in the management and treatment of chronic or functional constipation. This activity outlines the indications, actions, and contraindications for bisacodyl as a valuable agent in the treatment of constipation. This activity will also highlight the mechanism of action, adverse event profile, and contraindication of bisacodyl to treat patients with constipation and related conditions.

Objectives:

• Identify the mechanism of action of bisacodyl.
• Describe the potential adverse effects of bisacodyl.
• Review the potential for toxicity and its manifestations with bisacodyl.
• Explain how interprofessional team strategies for improving care coordination and communication can advance bisacodyl use and improve outcomes.

Indications

Bisacodyl [4,4’-diacetoxy-diphenyl-(pyridyl-2)-methane], a diphenylmethane derivative stimulant laxative, has been available as a laxative since 1952.[1][2][3] It is an effective and well-tolerated treatment for patients with constipation. It improves bowel function, constipation-related symptoms, and disease-related quality of life (QOL).[1] It has been used as a first-line laxative for functional constipation management. More recently, it has been used to facilitate bowel preparation before investigational procedures (i.e., colonoscopy, sigmoidoscopy), surgery, or pharmacologic provocation during colonoscopy manometry.[2][3] Bisacodyl is effective when administered to patients with neuropathy.[3] 

Bisacodyl appears superior to the other drugs for changing the number of bowel movements per week.[4] Its effect occurs in the large intestine within 6 to 12 hours following oral ingestion and within 15 to 60 minutes after rectal administration.[1][5][6] Bisacodyl is classified as having level 4 evidence regarding its safety and efficacy for chronic constipation in a systematic review.[1] In 2005, The American College of Gastroenterology Chronic Constipation Task Force stated that there are insufficient data to recommend the efficacy of stimulant laxative for the management of chronic constipation.[7]

Mechanism of Action

Bisacodyl’s target of action is the gastrointestinal tract.[2] Absorption from the GI tract is minimal because its formulation is a coated tablet, which is resistant to destruction in the stomach and small intestine and thus achieves transit to the colon in its intact form. It then dissolves in the colon and ensures a laxative effect after oral intake.[2][6][7] Intestinal deacetylase and bacterial enzymes hydrolyze bisacodyl to a deacetylated active metabolite, bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM), which stimulates the intestinal mucosa, causing peristalsis, which is responsible for the laxative action.[5][6] 

BPHM has a dual activity in the colon, including an anti-absorptive-secretory effect and a direct prokinetic effect by stimulating parasympathetic nerve endings in the colonic mucosa.[6][8][9] It acts locally in the large bowel by stimulating the colon’s myoelectrical and motor activity and intestinal secretion, thus enhancing the colon’s motility, reducing overall colonic transit time, and increasing the water content of the stool.[10][2][11] 

Ratnaike et al. demonstrated that bisacodyl impairs fluid absorption by activating adenylate cyclase in the small intestinal enterocytes, which increases the amount of cyclic AMP, and causes the active secretion of Cl- and HCO3-, passive efflux of Na+, K+ and water, and inhibition of Na+ and Cl- absorption into the enterocyte.[12] Bisacodyl may also exhibit its laxative effect by decreasing the expression of aquaporin 3 (AQP3) in the colon, therefore inhibiting water transfer from the intestinal tract to the vascular side of the cells.[13] 

Bassotti et al. investigated the effect of a 10 mg bisacodyl solution. They found that about 90% of patients with slow transit constipation showed motor response characterized by one or more high amplitude propagated contractions (HAPCs).[14] Min et al. conducted a study showing that bisacodyl increases sigmoid colon longitudinal muscle tone through direct action on the smooth muscle, but not in the colonic circular muscle, suggesting that bisacodyl could be effectively used administered to manage constipation in patients with neuropathy because bisacodyl improves the spatiotemporal-coordinated pattern of HAPCs.[3]

Administration

Bisacodyl administration can be via oral or rectal routes.[1][2][6] In adults, bisacodyl is given in doses of 5 to 10 mg tablet daily administered at night or bedtime because it works within 6 to 12 hours following administration when taken orally so that the therapeutic effect will occur in the morning. It also can be given in 10 mg as an enema or suppository administered in the morning because bisacodyl will work within 15 to 60 minutes following rectal administration. Doses of 10 to 20 mg are given by mouth for complete bowel evacuation, followed by 10 mg as a suppository the next morning.[6] 

In children from 3 to 10 years old, bisacodyl oral or rectal is given in doses of 5 mg per day in one dose at night. Children over ten years old or older can be given up to 10 mg per day in one dose a day at night.

Continued use of bisacodyl may decrease its efficacy, which occurs because bisacodyl increases the production of PGE2, which decreases the expression of AQP3. The effectiveness of compounds that decrease AQP3 expression in the colon can be reduced by continued use.[13]

Adverse Effects

The most common adverse effects, seen in more than 5 percent of patients taking bisacodyl, are diarrhea, abdominal pain (mainly in the upper abdomen), and headache.[1] Although it is unlikely that chronic use of bisacodyl is harmful to the colon, it could induce abdominal discomfort and cramping pain.[15] But, it is generally well-tolerated, safe, and effective for adults and children.[16] Joo JS et al. showed that 45 percent of patients using bisacodyl or other laxatives (phenolphthalein, senna, and casanthranol) more than three times per week for one year or longer (This is defined as chronic stimulant laxative use.) had subsequent radiographic changes of colonic redundancy and dilation of colon, with loss of haustral markings which did not occur in the control groups.[17] It may suggest that these agents cause a neuronal injury or damage to colonic longitudinal musculature.[17] 

Myenteric plexus or smooth muscle damage due to stimulant laxatives is rare, and it is unclear if this is due to constipation or laxative use.[18] The association between stimulant laxatives and colorectal neoplasm in humans remains inconclusive, and the data is lacking in human studies, but in vitro studies showed that bisacodyl was found to induce proliferative epithelial lesions, including a transitional-cell carcinoma, but only in the urinary bladder epithelium of rats.[15] Other side effects of bisacodyl include muscle weakness, nausea, vomiting, anorexia, and rectal irritation.[19] It also has correlations with salt overload, hypokalemia, and protein-losing entropy.[20] Ajani et al. reported a case that showed that bisacodyl correlates with colonic ischemia (CI), but the explanation for bisacodyl-induced CI is not clear.[21]

Rectal administration of bisacodyl may cause rectal mucosa irritation and a sensation of burning and mild proctitis. Bisacodyl has some interactions with other drugs such as digoxin, antacids, and H2-receptor antagonist. Wang et al. conclude that bisacodyl interferes with digoxin absorption, with a resultant reduction of the serum digoxin concentration.[22] Antacid and H2-receptor antagonists cause the enteric coating to dissolve too rapidly and may result in gastric or duodenal irritation when administered within one hour of bisacodyl tablets.

Contraindications

Bisacodyl's primary indicated use is for adults or children with constipation, especially chronic constipation. Bisacodyl is contraindicated in patients with acute gastrointestinal diseases such as appendicitis or diarrhea, with ileus or suspected bowel obstruction, bowel perforation, colitis, toxic megacolon, having severe dehydration, electrolyte imbalance (i.e., hypokalemia, hyponatremia, metabolic alkalosis or acidosis), or are allergic or hypersensitive to bisacodyl.[5][23] Rectal administration of bisacodyl suppositories is also a contraindication in patients with inflammation or an ulcer in the distal colon (ulcerative proctitis) and/or anal fissures.[16]

Monitoring

Bisacodyl becomes deacetylated in the colon to its active metabolite. Its metabolite conjugates to the mono-glucuronide in the wall of the intestine or liver. [24] Bisacodyl's absorption from the gastrointestinal tract is minimal. Therefore only a small amount of bisacodyl's absorbed metabolite gets excreted in the urine as the glucuronide.[6] There was no correlative relationship found between the plasma concentrations of the metabolite and the laxative effect, suggesting that systemic absorption was not a requirement for the laxative action, and the effect of bisacodyl was subject to local mediation.[2] 

Monitoring bisacodyl's metabolite is possible in human urine, serum, and stool within 24 hours after ingestion.[24] A serum electrolyte test is necessary when the patient is taking bisacodyl and shows symptoms of acid/base disturbances. Procedures used to analyze bisacodyl's metabolites are gas chromatography-mass spectrometry (GC-MS) and liquid chromatography. [24] The concentrations of bisacodyl diphenol, a metabolite of bisacodyl, in the patient's urine and serum were determined using bisphenol A as the internal standard.[24]

Toxicity

Overdosing of bisacodyl can induce diarrhea, leading to electrolyte disturbances, including hypokalemia, hypocalcemia, metabolic acidosis, or alkalosis, which may also produce vomiting and muscle weakness. Short-term use (3 days) of the recommended dose does not show any effect on serum electrolytes.[2] A case report of chronic abuse of bisacodyl in a female patient showed a frequent and repetitive formation of urinary calculi with rapid double J stent encrustation.[25] The treatment of laxative abuse is to cease the causative agent; this becomes challenging because constipation may occur again after stopping this drug, leading to patient distress.[26] Bisacodyl is not recommended for use for more than four weeks due to harmful long-term colonic effects and possible carcinogenic risk of stimulant laxatives; epidemiological studies investigating its effects and safety over longer terms are warranted.[9]

Enhancing Healthcare Team Outcomes

Constipation is a common disease that affects children and adults, especially the elderly. Unmanaged constipation can progress to fecal impaction, which further impairs patients' quality of life and increases healthcare costs. Constipation is one of the most prevalent outpatient diagnoses among gastrointestinal disorders.[26] There are many pharmacologic agents for constipation, including over-the-counter (OTC) laxative products, rectal suppositories, and enemas. Oral products can be classified as bulking agents, stool softeners, stimulant laxatives, and osmotic laxatives.[23] 

It can be challenging for the healthcare team because there are no accepted guidelines for choosing the best agent. The clinician should discuss all problems with the patient and coordinate with nurses or the caregiver to maximize the quality of service, thus increasing the patient's quality of life. The provider should consider all risks and benefits of using a laxative, especially a bisacodyl, in the management of constipation to minimalize the adverse effect. Besides using bisacodyl as a stimulant laxative, it is also essential to focus on individual therapy based on the symptoms and pathophysiology of the patient's disease to make a better follow-up to improve the outcome of this disorder. Pharmacists need to be engaged with both the patient, nursing staff, and the clinician. These products are available OTC, and the burden of counseling and making recommendations may fall 100% to the pharmacist. The pharmacist should contact the patient's physician if there are any concerns over the patient's use of bisacodyl. Nurses should also understand the ramifications and potential adverse effects of these agents, and take a thorough medication history, including OTC agents, so the treating clinician has a clearer picture of the patient's case. This approach represents the type of collaborative interprofessional team approach necessary to drive an optimal outcome for the patient. [Level 5]

Despite being used for symptomatic relief, laxatives are also misused by individuals who present with eating disorders like anorexia nervosa or bulimia, individuals who engaged in certain types of athletic training, including sports with set weight limits, and surreptitious laxative abusers who use the drugs to cause factitious diarrhea and may have a medical disorder. The first step in treating laxative misuse is to determine what may be promoting the behavior. The individual who misuses the laxative has to stop the stimulant laxatives and replace them with osmotic supplements to establish regular bowel movements. Education and further treatment are required to maintain a healthy bowel program. Referral for psychiatric treatment is essential in the case of eating disorders such as bulimia or anorexia nervosa to lessen the reliance on laxatives as a method to alter perceived weight and shape.[27]