Evidence About the Pharmacological Management ofCONSTIPATIONPART 2: IMPLICATIONS FOR PALLIATIVE CAREConstipation remains a challenging problemfor patients and caregivers in home healthcare.Part 1 of this two-part series discussed thescope, physiology, and evidence-based practice for nonpharmacological interventions forconstipation. This second article will focus onevidence-based pharmacological preventionand management of constipation, medicationcost, and implications for palliative care.Matthew Pitlick, PharmD, BCPS, andDeborah Fritz, PhD, RNvol. 31 no. 4 April 2013Home Healthcare NurseCopyright 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.207

While eliminating causative factors and increasing fluid/fiberintake should be attempted when possible, these are ofteninappropriate or unreasonable options in palliative care. Manymedications are available and differ in efficacy, safety, adverseeffect profile, overall tolerability, and cost.Case Study IntroductionMr. M. is a 66-year-old African American man whowas diagnosed with multiple myeloma 3 monthsago after complaints of bone pain and fatigue. Hisproblem list includes anemia, hypercalcemia,and well-controlled diabetes mellitus on oralmedications. He is receiving lenalidomide, dexamethasone, and melphalan to treat his cancer. Heis not eligible for an autologous stem cell transplantation. Ms. M. states that her husband hasless energy to do the activities he has enjoyedsince retirement. Although his bone pain is nowwell controlled, she is concerned that his chronicconstipation is affecting his quality of life.Mr. M.’s current medications are: lenalidomide orally 25 mg daily,dexamethasone orally 40 mg in the morning,melphalan orally 6 mg daily,zoledronic acid 4 mg IV every 4 weeks,metformin orally 1,000 mg twice daily (BID),morphine sulfate ER orally 30 mg BID,morphine sulfate IR orally 10 mg every 2 to 3hours as needed for breakthrough pain, and docusate sodium orally 200 mg BID.focuses on pharmacologic treatment of constipation and implications for palliative care patients.Pharmacological TherapyBulk-Forming LaxativesThese agents’ bulk-forming laxatives, includingmethylcellulose, polycarbophil, and psyllium, bulkstool contents, increase retention of water, and increase the rate of stool transit through the intestine (Powell & Fleming, 2011). These actions resultin increased stool frequency. Bulk-forming laxatives may take 3 to 5 days for effect but can takelonger. Adequate fluid intake (1.5–2 L) is requiredfor use. Abdominal distention and flatulence arecommon adverse effects but can resolve with continued use. In general, these laxatives should not beused in palliative care situations, as they can causeobstructions of the esophagus, stomach, small intestine, and colon, especially with inadequate fluidintake (Powell & Fleming, 2011; Spinzi et al., 2009).Psyllium has been associated with anaphylacticreactions, as well (Ho et al., 2008). The palliativecare patient, generally, cannot tolerate or intakethe amount of fluid needed for bulk-forming laxatives to work properly and safely.BackgroundEmollientsThe goal of patient management for home healthcare providers, in particular for palliative carepatients, is the improvement of quality of lifeissues that affect the physical and psychologicalwell-being of their patients. These issues may include pain, fatigue, reduced mobility, and, commonly, constipation. Constipation continues tochallenge home healthcare providers, especiallyin palliative care. For a detailed definition of constipation, please refer to Part 1 of this article(Fritz & Pitlick, 2012). In an effort to improvesymptoms of constipation, pharmacologic measures may be necessary. This second part articleCommonly known as stool softeners, these agentswork by increased wetting and softening fecalmass, which allows for easier passage of stool.Softening of stools generally occurs in 1 to 3 days(Powell & Fleming, 2011). Docusate is the mostcommonly used stool softener and should be usedto prevent painful defecation and straining in situations when this should be avoided such as severe hypertension, cardiovascular disease, andrecent surgery or myocardial infarction. Docusatemay increase fecal soiling, otherwise there arevery few side effects associated with these agents(Powell & Fleming, 2011). Stool softeners are208 Home Healthcare Nursewww.homehealthcarenurseonline.comCopyright 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

ineffective in treating constipation and should notbe used as monotherapy for treatment of constipation (Gallegos-Orozco et al., 2012). However, theywork well when combined with stimulant laxatives and lead to a softer, easier stool to pass asthe stimulant causes laxation (Locke et al., 2000;Powell & Fleming, 2011; Weitzel & Goode, 2012).LubricantMineral oil can soften stool and prevent straining, similar to emollients. It typically works in 2to 3 days. However, safety concerns severelylimit its use. Lipid pneumonia can result fromaspiration, especially in the very ill and elderly.In addition, absorption of Vitamins A, D, E, and Kcan be disrupted. Other adverse effects such aspruritus and soiling can occur as well (Leung etal., 2011; Powell & Fleming, 2011). Given theseissues, mineral oil should not be recommended inpalliative care situations (Locke et al., 2000;Powell & Fleming, 2011; Weitzel & Goode, 2012).Osmotic LaxativesThese agents include glycerin, polyethylene glycol(PEG, brand name: Miralax), lactulose, sorbitol,and saline laxatives such as magnesium hydroxide, citrate, phosphate, and sodium phosphate.These agents draw water into the colon throughosmosis, leading to a softer stool, and induce abowel movement. Adverse effects are commonamong these laxatives (except glycerin and PEG)and elderly patients tend to be more susceptible.Glycerin is a very safe and effective laxative foracute evacuation. It is available in suppositoryform and induces bowel movement in 30 minutes.Adverse effects are rare but may include mildrectal irritation.PEG is an osmotic laxative with adequate efficacy and a favorable adverse effect profile. PEGpossesses fewer adverse effects than other osmotic laxatives because it is not absorbed systemically or metabolized by colonic bacteria. Forconstipation during palliative care, PEG is an excellent choice because of its wetting and stimulation effects with low incidence of adverse effects.Possible adverse effects include abdominal pain,electrolyte disturbances, and dehydration; however, incidence is lower than that for other laxatives (Clemens & Klaschik, 2008). Additionally,PEG must be dissolved in a glass of water (8 oz),which can be an issue if the patient is fluid restricted or cannot tolerate excess fluids. There isvol. 31 no. 4 April 2013an abundance of evidence showing efficacy andsafety with PEG over placebo (Locke, et al., 2000;Powell & Fleming, 2011; Ramkumar & Rao, 2005;Weitzel & Goode, 2012). Unlike other laxatives,PEG has been shown safe when used up to 6 to12 months (Powell & Fleming, 2011; Singh & Rao,2010). PEG has been shown superior to lactuloseas well (Ramkumar & Rao, 2005).Lactulose and sorbitol are hyperosmotic laxatives that work in a similar way. In addition toaltering fluid activity, these agents decrease pH inthe colon, which increases colonic peristalsis.This increases stool frequency and consistency.Adverse effects include flatulence, nausea,abdominal discomfort or bloating, diarrhea, andelectrolyte imbalances. Lactulose has been shownto be superior to placebo for chronic constipation and effective in opioid-induced constipation(Liu, 2011). Sorbitol is similar to lactulose, is morecost-effective, and causes less nausea. However,hyperglycemia may occur with sorbitol, so it isimportant to monitor patients with diabetes.Lactulose and sorbitol could be useful in palliativecare situations; however, there are not enough studies in this patient population and more frequent useof the laxative is needed. See Box 1 for evidencebased practice regarding lactulose and PEG.Saline laxatives include magnesium hydroxide, citrate, sulfate, phosphate, and sodium phosphates. These agents act primarily by osmosis inthe small and large intestines (oral) or colon(rectal). They increase the intraluminal pressureBox 1. Evidence-Based Practice:Lactulose Versus Polyethylene GlycolLactulose versus polyethylene glycol for chronicconstipation (Lee-Robichaud et al., 2010).Research Problem: To determine if lactuloseor polyethylene glycol is more effective to treatchronic constipation.Methods: Comprehensive literature review withmeta-analysis of randomized controlled trialscomparing lactulose to polyethylene glycol.Results: Ten randomized controlled trials were included. Polyethylene glycol was found to be betterthan lactulose in outcomes of stool frequency andform of stool.Implications for home healthcare practice:Polyethylene glycol should be considered overlactulose for treatment of chronic constipation.SORT LEVEL: BHome Healthcare NurseCopyright 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.209

A very commonccause ofcconstipation inpalliative careppatients is opioids.pOpioids decreaseOgastric motility,gleading to harderlesstools and nottolerance developsto constipation as it does with otheropioid-related adverse effects.and intestinal motility. These laxatives should beused for occasional, acute evacuation only, as theycan result in fluid loss and electrolyte imbalances.Special consideration (i.e., renal impairment,chronic heart failure, or sodium-restricted diets)for patients with risk of hypermagnesemia, hypernatremia, and hyperphosphatemia need to betaken into account (Locke et al., 2000; Powell &Fleming, 2011; Weitzel & Goode, 2012). Bowelmovement typically occurs in a few hours afteroral dose or within 1 hour after rectal administration (Powell & Fleming, 2011). There is an overalllack of efficacy data with saline laxatives (Ho etal., 2008; Leung et al., 2011; Liu, 2011), especiallyin chronic constipation (Brandt et al., 2005).Stimulant LaxativesThese laxatives, including senna and bisacodyl,exhibit effects in the colon to increase intestinalmotility by local irritation of the mucosa or onnerves and smooth muscle (Singh & Rao, 2010).Stimulant laxatives are often used in combinationwith stool softeners and are used frequently in palliative care. These laxatives are commonly usedto treat opioid-induced constipation. Commonadverse effects include abdominal pain/crampingand fluid/electrolyte imbalance. In addition,senna can turn urine a pink or red color. Antacids,proton pump inhibitors, and histamine-2 receptor antagonists should be avoided with bisacodylas these medications can cause the breakdownof enteric coating of bisacodyl, resulting in a210 Home Healthcare Nurseless effective drug (Locke et al., 2000; Powell &Fleming, 2011; Weitzel & Goode, 2012). In thepast, clinicians have hesitated using stimulantlaxatives due to the theoretical potential ofharming the colon with chronic use. It wasthought that stimulant laxative use leads to“cathartic colon,” damaging the enteric nervoussystem and leading to physical dependence oflaxatives (Leung et al., 2011). However, littleevidence exists that this occurs when given inappropriate doses (Leung et al., 2011). Bisacodylhas been shown to be significantly better thanplacebo in treatment of acute constipation,improving stool frequency and consistency(Kienzle-Horn et al., 2006). There is also evidenceshowing the superiority of bisacodyl over placebo in chronic constipation; however, there islittle evidence in regard to use of senna and littleis known about the risks of long-term use ofstimulant laxatives (Leung et al., 2011). Clinically,bisacodyl and senna are considered equallyeffective with similar risks. See Box 1 for evidencebased practice regarding bisacodyl.Chloride Channel ActivatorThis is a new drug class that includes lubiprostone (brand name: Amitiza). This agent increasesintraluminal fluid secretion that helps to softenstool and accelerate GI transit time. Currently,lubiprostone is approved only for chronicidiopathic constipation in adults. Evidenceshows lubiprostone improves straining, stoolconsistency, and overall constipation severity(Johanson & Ueno, 2007). Bowel movementsgenerally occur in 1 to 2 days. Common adverseeffects include headache, diarrhea, and nauseawith less common adverse effects being abdominal distention, pain, and flatulence. In addition,this medication should be taken with food. Oneadvantage of this laxative over older laxatives isthat it does not cause electrolyte disturbances.Because of the high cost and lack of long-termstudies, lubiprostone should be reserved forthose whom other laxatives fail and is not to beused for occasional constipation (Liu, 2011;Powell & Fleming, 2011; Singh & Rao, 2010).Opioid Receptor AntagonistsCurrently, there are two opioid receptor available:alvimopan (brand name: Enterg) and methylnaltrexone (brand name: Relistor). These agentsdo not affect the analgesic effects of opioidswww.homehealthcarenurseonline.comCopyright 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

because they do not cross the blood–brain barrier.Alvimopan is an oral gastrointestinal (GI)-specificmu-receptor antagonist approved for short-termuse in hospitalized patients after bowel surgery.It is only available through a special program(EASE), and the hospital must be registered before the drug is administered (Singh & Rao,2010). Adverse effects include nausea and vomiting. Alvimopan is contraindicated in patientsreceiving therapeutic opioid doses for greaterthan 7 days before surgery as these patients maybe more sensitive to the drug’s effects. However,it is unlikely that palliative care patients will usethis medication given the contraindication