NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #223                                                                                                                          NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #223
         Carol Rees Parrish, MS, RDN, Series Editor
           The Clinician’s Toolkit for the Adult 
           Short Bowel Patient Part II: 
           Pharmacologic Interventions
                     Vanessa J. Kumpf                     Carol Rees Parrish
         The care of patients with short bowel syndrome (SBS) varies considerably. Patients seek a reasonable 
         return to a normal life after surgery resulting in SBS, as well as a path to optimize their health 
         going forward. Clinicians involved in the management of these patients struggle with the complexity 
         of care and heterogenicity between patients. Medications play a key role in addressing altered 
         GI function and managing symptoms that result from extensive intestinal resection. The shotgun 
         approach to medication management is well intentioned, but not recommended. Treatment 
         should instead be individualized for each patient based on functional capacity of the remaining 
         GI anatomy. A pharmacologic treatment plan should be developed using a methodical, stepwise 
         approach. Medications utilized in the treatment of SBS include antimotility agents, antisecretory 
         agents, antimicrobials (for treatment of bacterial overgrowth), and intestinal growth factors. The 
         purpose of Part II of this series is to guide the clinician on the availability of medications and to 
         develop a pharmacologic treatment plan that improves the quality of life for patients with SBS.
         INTRODUCTION
              hort bowel syndrome (SBS) is a complex               and benefit from diet modification, oral rehydration 
              malabsorptive disorder that most often               solutions  (ORS),  supplemental  electrolytes, 
         Sresults from an extensive intestinal resection           minerals, and vitamins aimed at replacing intestinal 
         due to a number of gastrointestinal pathologies.          losses, and medications that often target high 
         Management of SBS therefore is a challenge for            stool or ostomy output. Parenteral nutrition (PN) 
         clinicians nationwide and across multiple healthcare      or  intravenous  (IV)  fluid/electrolytes  may  be 
         disciplines. Patients with SBS struggle to maintain       required, especially during the process of intestinal 
         adequate fluid, electrolyte, and nutritional status       adaptation that occurs within the initial months to 
                                                                   years following extensive surgical resection.  
         Vanessa J. Kumpf, PharmD, BCNSP, FASPEN                       The extent of malabsorption in patients with 
         Clinical Pharmacist Specialist Vanderbilt  SBS will vary depending on the length and location 
         University Medical Center Nashville, TN Carol             of remaining bowel, its functional status, and the 
         Rees Parrish MS, RDN GI Nutrition Support                 length of time since the last surgical resection. 
         Specialist UVA Health Charlottesville, VA                 Treatment must therefore be individualized and 
         12                                                                  PRACTICAL GASTROENTEROLOGY • JULY 2022
           The Clinician’s Toolkit for the Adult Short Bowel Patient Part II: Pharmacologic Interventions
NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #223    NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #223
         take these factors into consideration. Medical              malnutrition, dehydration, chronic kidney disease, 
         management of SBS should focus on supportive                and metabolic bone disease.
         care and symptom control. Pharmacologic 
         treatment can work synergistically with dietary             First: Don’t Make Diarrhea Worse
         modification and ORS therapy to help control                Medication Considerations
         high stool outputs, minimize fluid and electrolyte          Essentially all orally administered medications 
         losses, enhance intestinal absorption, and decrease         are absorbed in the small intestine, so clinicians 
         PN/IV requirements. Medications are specifically            must anticipate impaired absorption in patients 
         targeted to treat the multiple factors that contribute      with SBS who often have rapid transit through 
         to diarrhea in patients with SBS, including rapid           the small intestine. Patients who have stomas 
         intestinal transit, increased GI secretions, bacterial      may report the presence of unabsorbed tablet or 
         overgrowth, and malabsorption of fat and bile salts.        capsule fragments within their ostomy effluent. 
         Intestinal growth factor therapy offers another             Switching from a solid dosage form to a liquid 
         targeted approach in the treatment of SBS.                  formulation has been recommended as a method 
             It is important to avoid the impulse to start           to improve absorption, but this recommendation 
         multiple medications at the same time. This                 is theoretical and not evidence based. In fact, 
         shotgun approach does not allow the clinician the           liquid formulations may contribute to increased 
         ability to distinguish between what may be helping          stool output if the liquid medication contains 
         versus what is not, or worse, not allow the clinician       sugar alcohol/s. Sugar alcohols (sorbitol, mannitol, 
         to distinguish the source of potential adverse              xylitol, maltitol, isomalt, erythritol, lactitol) are often 
         reactions. Patients with SBS often complain that            added to liquid medication preparations to enhance 
         the medical community fails to recognize the                solubility and palatability, but are potent cathartics 
         condition or appreciate its complexity. Healthcare          that can lead to an osmotic diarrhea. See Table 1 for 
         professionals who are well-intentioned may be               a list of commonly prescribed liquid preparations 
         providing patients with inaccurate advice due to            that contain sugar alcohol. 
         lack of experience managing SBS. Part I of this                 It  is  also  problematic  to  use  sustained, 
         series discussed the role of diet and hydration             controlled, delayed, slow-release, or enteric-coated 
                                                 1
         therapies in the management of SBS.  The purpose            medications in patients with SBS as the reduced 
         of Part II is to guide the clinician on the availability    intestinal surface area will result in accelerated 
         and use of medications aimed at managing SBS.               transit times and reduced absorptive capacity. It is 
                                                                     important to note that patients do not just malabsorb 
         Diarrhea Everywhere                                         food and liquids in SBS, but medications as well. 
         Although patients with SBS deal with many                   This in turn will alter the intended pharmacokinetic 
         challenging issues, high stool output often manifests       properties of these medications. Instead, consider 
         as their primary complaint. Dealing with the need to        an immediate release oral dosage form, chewable 
         make frequent trips to the bathroom and concern for         oral formulation, or alternative administration 
         fecal incontinence or a leaking ostomy have been            routes (e.g., transdermal, sublingual, rectal, and 
         reported to have a deleterious effect on lifestyle,         subcutaneous) when available or appropriate. 
         physical function, activities of daily living, and the 
                         2
         ability to travel.  This is why clinicians should make      Antidiarrheal Medications 
         considerable effort to control stool output when            Used to Slow Intestinal Transit
         managing patients with SBS. In addition to the              Patients with SBS experience accelerated intestinal 
         tangible improvements in quality of life, decreasing        motility. Opioids or opioid receptor agonists are 
         stool output will potentially minimize the risk of          often used to slow intestinal transit by inhibiting 
         complications resulting from malabsorption of               intestinal smooth muscle contraction. This allows 
         fluids and nutrients. Short-term complications of           more time for fluid and nutrient absorption and an 
         high stool output include dehydration, electrolyte          increased capacity of the small intestine. Opioid 
         abnormalities, and metabolic acidosis. Long-term            agonists may also contribute to an antidiarrheal 
         complications of high stool output can include              effect through an inhibition of GI secretions. 
         PRACTICAL GASTROENTEROLOGY • JULY 2022                                                                         13
         The Clinician’s Toolkit for the Adult Short Bowel Patient Part II: Pharmacologic Interventions
         NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #223
        Table 1. Commonly Prescribed Liquid                      Loperamide in particular has been shown to not 
        Medications Containing Sugar Alcohol                     only slow gut transit, but also provide improved 
                                                                                                                    3
         Medication Oral Suspension                Sugar         rectal function by increasing anal sphincter tone.  
                                                  Alcohol        Unlike its effect within the central nervous system 
                                                  Content        (CNS), the bowel slowing effect of opioids is 
                                                                                                                    4
         Acetaminophen (Tylenol)                  Sorbitol       not impacted by the development of tolerance.  
         160mg/5mL                                               Therefore, effective doses may remain constant 
                                                                 for months to years.  
         Acyclovir (Zovirax) 200mg/5mL            Sorbitol           Table 2 provides a list of antidiarrheal agents 
         Amantadine hydrochloride                 Sorbitol       used to slow intestinal transit time in patients with 
         (Symmetrel) 50mg/5mL                                    SBS. Both loperamide and diphenoxylate are 
         Amoxicillin / clavulanate (Augmentin)    Mannitol       considered first-line antimotility agents, although 
         200mg/28.5mg/5mL                                        loperamide is typically considered the preferred 
                                                                 agent for initial therapy. If aggressive dosing of 
         Diphenoxylate and Atropine (Lomotil)     Sorbitol       loperamide and/or diphenoxylate fails to achieve 
         2.5mg/0.025mg/5mL                                       a desired response, it is reasonable to consider 
                   ®                                             a more potent opioid narcotic. The advantages 
         Fer-In-Sol  (Ferrous sulfate)            Sorbitol       and disadvantages of each antimotility agent are 
         Liquid Iron Supplement                                  provided in Table 2 and can be used as a guide for 
         Furosemide (Lasix) 10mg/mL               Sorbitol       selecting the appropriate agent(s).
         Gabapentin (Neurontin) 250mg/5mL          Xylitol       Tips for Use of Antidiarrheal Agents:
         Glycopyrrolate (Robinul) 1mg/5mL         Sorbitol       1.  Check for Clostridium difficile prior to starting 
         Guaifenesin (Mucinex) 100 mg/5mL         Sorbitol           therapy, or when suspicion for infection arises 
         Lacosamide (Vimpat) 10mg/mL              Sorbitol           (yes, even end jejunostomies and ileostomies 
                                                                                                    5
         Lansoprazole (Prevacid) 3mg/mL           Mannitol           can acquire C. diff infection).
         Levetiracetam (Keppra) 100mg/mL          Maltitol        •  Antidiarrheal agents should be both 
                                                                     scheduled and taken 30-60 minutes before 
         Loperamide (Imodium) 1mg/7.5mL           Glycerin           meals/snacks to achieve maximum benefit. 
         Magnesium Hydroxide                      Sorbitol        •  Start with a single first-line agent, typically 
         (Milk of magnesia) 1200mg/15mL                              loperamide. 
         Magnesium Hydroxide (Concentrated        Sorbitol          o Dosage of loperamide should be escalated 
         milk of magnesia) 2400mg/10mL                                 in a stepwise manner, allowing at least 2-3 
         Metoclopramide (Reglan) 5mg/5mL          Sorbitol             days in the hospital setting while the patient 
         Mycophenolate mofetil (CellCept)         Sorbitol             is well monitored, and 3-5 days in the home 
         200mg/mL                                                      setting after each dosage increase to assess 
         Oseltamivir phosphate (Tamiflu)          Sorbitol             response. Stop increasing dose if benefit 
         6mg/mL                                                        is observed, adverse events occur, or the 
         Pyridostigmine bromide (Mestinon)        Sorbitol             recommended maximum dosage is reached 
         60mg/5mL                                                      (see Table 2). Tolerance is typically limited 
         Simethicone (Gas relief) 20mg/0.3mL      Maltitol             by obstructive symptoms, so carefully 
         Sodium polystyrene sulfonate             Sorbitol             monitor for the presence of nausea, 
         (Kionex) 15mg/60mL                                            vomiting, and abdominal pain or distention. 
         Valganciclovir (Valcyte) 50mg/mL         Mannitol          o Advise patients to purchase/request generic 
         Valproic acid (Depakene)                 Sorbitol             loperamide in large bottle quantities (less 
         250mg/5mL                                                     costly). Avoid blister packs (sometimes 
                                                                       difficult to open).
        14                                                                 PRACTICAL GASTROENTEROLOGY • JULY 2022
          The Clinician’s Toolkit for the Adult Short Bowel Patient Part II: Pharmacologic Interventions
                                                  NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #223
           o If loperamide offers no benefit, or is not         Medications Used to Reduce GI Secretions
              tolerated, switch to diphenoxylate/atropine.      Following extensive intestinal resection, gastric 
           o If loperamide provides partial (but                secretions are often increased for the first 6-12 
              suboptimal) improvement, add                      months after surgery due to loss of feedback 
              diphenoxylate/atropine and increase the           mechanisms from the resected bowel. The sheer 
              dose in a stepwise manner as above.               volume of secretions then contributes to total fecal 
                                                                losses. Gastric hypersecretion will also result in 
           o Consider use of systemic opioid narcotic           the dumping of acidic contents into the proximal 
              agents if maximum recommended doses of            small bowel and can alter normal fat digestion 
              the first-line agents fail.                       through the denaturation of pancreatic enzymes 
                                                                and destabilization of bile acids. Treating gastric 
           o Start at a low dose (see Table 2) and              hypersecretion not only decreases the sheer volume 
              advance in a stepwise manner as above.            of secretions, but also helps to restore the intestinal 
                                                                pH back to that which optimizes pancreatic enzyme 
           o The use of opioid agents containing                and bile salt activity. 
              acetaminophen is considered by the FDA                Table 3 provides a list of medications used 
              to have a lower abuse potential (C-III)           to reduce GI secretions. Proton pump inhibitors 
              when compared to the use of codeine or            (PPIs) are typically considered first-line agents 
              morphine as a single agent (C-II), which          and are highly effective early after intestinal 
              allows the ability to prescribe refills. But      resection. Histamine type 2 receptor (H2) 
              be cautious of the potential hepatotoxic          antagonists are considered second-line because 
                                                                of their decreased efficacy relative to PPIs in 
              effects of acetaminophen, especially when                                       6,7
                                                                patients with high outputs.  Even though the 
              given long-term or at high doses. Patients        gastric acid hypersecretion response is typically 
              should be instructed not to exceed 4g/            transient following intestinal resection, the use of 
              day of acetaminophen or consume alcohol           antisecretory agents is often continued long-term 
              when using this drug.                             as attempts to stop the therapy can be associated 
                                                                                              6
                                                                with worsening stool output.  It is still worthwhile 
           o Consider stopping diphenoxylate and                to periodically try stopping therapy and measuring 
              possibly stopping loperamide when                 effect on stool volume–if it goes up without other 
              switching to use of an opioid narcotic. It is     changes, then the patient still needs it. The decision 
              daunting for patients to maintain this high       to continue antisecretory therapy long-term should 
              pill count if stool output can be controlled      be  individualized  based  on  observed  benefit 
              with a stronger, single antidiarrheal agent.      versus risk of adverse effects. Long-term use of 
          •  A bedtime dose (and sometimes a higher             PPIs has been associated with hypomagnesemia, 
                                                                osteoporosis, kidney disease, and vitamin B12 
            bedtime dose) may help minimize trips to                        8-10
            the bathroom at night.                              deficiency.     However, the quality of evidence 
                                                                supporting these associations is consistently low 
          •  Provide patients with guidelines for dosage        to very low. The magnitude of absolute risk of 
            titration as therapeutic response may vary          developing an adverse effect with long-term use 
            with alterations in diet and/or changes in          of a PPI for individual patients is in fact modest.11 
            the course of their disease.                        It is prudent to periodically reevaluate patients on 
          •  Patients should be instructed to decrease or       long-term PPIs to ensure they are prescribed the 
            hold antimotility agents if they experience         lowest dose sufficient to manage their condition.
            nausea,  vomiting,  or  abdominal  pain/                Clonidine and octreotide are alternative 
            cramping. They may also need to decrease            antisecretory agents that have been used in 
            the dose if they experience excessive CNS           patients with SBS. Clonidine inhibits intestinal 
            effects, such as sedation or mental status          fluid secretion by stimulating alpha-adrenergic 
            changes.                                                                            (continued on page 22)
        PRACTICAL GASTROENTEROLOGY • JULY 2022                                                                   15