A 52-YEAR-OLD WOMAN WITH WORSENING …

1 University of Tennessee Advanced Studies inPharmacy n43 MEDICALHISTORYES has a long history of mild constipation, averag-ing 2 to 3 bowel movements per week. Because occa-sional use of senna products provided temporary reliefin the past, she tried these agents again, believing theywould be helpful. She has no other chronic diseases orsymptoms and no history of renal A1-month trial of lifestyle changes, which include: Increased intake of dietary fiber (eg, bran cereal, whole-grain bread, fresh fruits, and vegetables) Increased fluid intake (an additional 4 glasses/day) Increased physical activity/regular exercise (walking 30 minutes/day at least 5 days/week or joining a health club) Addition of a bulk laxative (eg, psyllium) if lifestyle modifications do not produce any improvement after 1 monthCOMMENTARYA 1-month trial of lifestyle changes is the first lineof therapy for chronic constipation.

2 If these changesdo not result in any significant improvement after thistime, psyllium or some other bulk laxative should beadded to the factor involved in this scenario is that thispatient s mild constipation worsened after she wasreassigned to a different shift at work and her dailyroutine was disrupted. Although changes in workschedules have not been reported to cause chronicconstipation, concomitant changes in dietary and/orexercise patterns, in addition to the psychologicalstress associated with a new shift and a disruption indaily routine, could play a role. Therefore, ES shouldbe encouraged to readjust her daily routine, in addi-tion to increasing her intake of dietary fiber, drinkingmore fluids, and exercising says she followed the recommended lifestylechanges for 1 month, but had no significant increaseCASESTUDYA 52-YEAR-OLD WOMAN with WORSENING CONSTIPATION James C.

3 Eoff III, PharmD*BACKGROUNDES, a 52-YEAR-OLD WOMAN , complains of havingworsening constipation, abdominal discomfort, andbloating for the past 2 months, which began whenshe was reassigned from the 7 AMto 3 PMshift to the3 PMto 11 PMshift at work. Since then, she has beenhaving only 1 or 2 spontaneous bowel movementsper week. Self-treatment with over-the-counter(OTC) laxatives (specifically, senna products) initi-ates the urge to defecate, but also causes excessivestraining upon defecation.*Executive Associate Dean, Professor of ClinicalPharmacy, University of Tennessee College of Pharmacy,Memphis, correspondence to: James C. Eoff III, PharmD,Executive Associate Dean, Professor of Clinical Pharmacy,University of Tennessee College of Pharmacy, 847 Monroe Avenue, Suite 226, Memphis, TN 38163.

4 E-mail: STUDY44 Vol. 4, No. 2nFebruary 2007in bowel movement frequency or decrease in abdomi-nal symptoms or straining. She then started takingpsyllium, beginning with 1 tablespoon at bedtimeevery day and gradually increasing the dose to 1 table-spoon 3 times a day over a period of 3 weeks. She hasnow been taking the higher psyllium dose for the pastweek. ES now has 2 or 3 bowel movements per week,but complains of abdominal distention, flatulence,and very hard and dry stools that worsen the alreadyexcessive Increase fluid intake by drinking at least 1 glass ofwater or other fluid (8 oz) with each dose of psyllium. Discontinue psyllium and switch to an osmoticagent such as magnesium hydroxide (Milk ofMagnesia) if additional fluid intake has not relievedthe primary psyllium is taken with enough water orother fluid (8 oz with each dose)

5 , it may increase stoolbulk and hardness, making defecation more ES has increased her fluid intake with each psylliumdose, but her symptoms still persist, she should beinstructed to discontinue psyllium and switch to anOTCosmotic laxative such as magnesium agent containing a magnesium salt is a reasonabletreatment option for ES because she is in otherwisegood health and has no history of renal , these agents should be avoided in patientswith renal insufficiency or electrolyte discontinued psyllium and switched to magne-sium hydroxide, beginning with 2 tablespoons at bed-time each day. She increased the dose to 4 tablespoonsa day after 1 week of treatment with the lower dosebecause it had little effect. The higher dose was mod-erately effective for 4 or 5 weeks, resulting in a rela-tively normal bowel movement every 2 or 3 2 months, however, the laxative stopped work-ing, and ES reverted to having only 1 or 2 bowelmovements per Trial therapy with prescription osmotics such as lactulose and polyethylene glycol (PEG) 3350 Possible therapy with tegaserod (Zelnorm; Novartis Pharmaceuticals, East Hanover, NJ) or lubiprostone (Amitiza; Takeda Pharmaceuticals North America, Inc.)

6 , Lincolnshire, Ill; SucampoPharmaceuticals, Bethesda, Md)COMMENTARYES can be considered refractory because tradi-tional osmotic laxative therapy (magnesium hydrox-ide) is no longer working and she has already tried astimulant laxative (senna) but was distressed by theexcessive straining that it caused. Some refractorypatients can benefit from a trial of therapy withpoorly absorbed sugars such as lactulose and PEG3350. Although these prescription agents areapproved for occasional or short-term constipation,but not for chronic constipation, recent reports1-5and the Task Force on Chronic Constipation of theAmerican College of Gastroenterology6highly rec-ommend them for chronic constipation, with PEGhaving somewhat fewer side effects. However,because ES has a long history of mild constipationand a 6-month history of WORSENING and increasing-ly chronic constipation, therapy with newer prescrip-tion agents such as tegaserod and lubiprostone canalso be considered.

7 Both agents are approved for thetreatment of chronic constipation, with lubiprostonehaving no age restrictions7-9and tegaserod indicatedonly in patients younger than 65 because phase IIIstudies included relatively few patients over the ageof ,11 Tegaserod, a 5-hydroxytryptamine4(serotonin)receptor partial agonist, must be taken on an emptystomach for maximal therapeutic effects,10,11whereaslubiprostone must be taken with meals to minimizenausea, its most common side started therapy with PEG on a trial basis. Withindays, she was having more frequent bowel movements, with better stool consistency and less straining. ES hasnow been taking PEG for 3 months and is doing PEG is approved for short-term treat-ment (2 weeks or less), many patients remain on ther-apy with the agent for considerably longer periods ES require higher doses of PEGbecause of a repeated episode of WORSENING constipa-tion, and should she become unable to tolerate theCASE STUDYU niversity of Tennessee Advanced Studies inPharmacy n45side effects associated with higher doses (eg, diarrhea,nausea, abdominal bloating, cramping, and flatu-lence), therapy with tegaserod or lubiprostone is a rea-sonable ,2 REFERENCES1.

8 Brandt LJ, Prather CM, Quigley EM, et al. Systematicreview of the management of chronic constipation in NorthAmerica. Am J Gastroenterol. 2005;100(suppl 1) D, Rao SS. Efficacy and safety of traditionalmedical therapies for chronic constipation: systematicreview. Am J Gastroenterol. 2005;100 A, Camilleri M. Chronic constipation. N Engl JMed. 2003;349 W, Dreher R, Schnegg JF, Bula CJ. The treatmentof chronic constipation in elderly people: an update. DrugsAging. 2004;21 S, Brunton S, Carmichael B, et al. Management ofchronic constipation: recommendations from a consensuspanel. J Fam Pract. 2005;54 College of Gastroenterology ChronicConstipation Task Force. An evidence-based approach tothe management of chronic constipation in North J Gastroenterol. 2005;100(suppl 1) (lubiprostone) prescribing information. Lincolnshire,Ill: Takeda Pharmaceuticals North America, Inc; Bethesda,Md: Sucampo McKeage K, Plosker GL, Siddiqui MA.

9 Lubiprostone. ;66 JF, Gargano MA, Holland PC, et al. Multicenteropen-label study of oral lubiprostone for the treatment ofconstipation. Am J Gastroenterol. 2005;100(suppl) (tegaserod) prescribing information. East Hanover,NJ: Novartis Kamm MA, Muller-Lissner S, Talley NJ, et al. Tegaserod forthe treatment of chronic constipation: a randomized, dou-ble-blind, placebo-controlled multinational study. Am JGastroenterol. 2005;100 4, No. 2nFebruary 2007 NOTES