Reviews for Primary Care - Fall 2007 - (Page 23) Chronic Constipation and Functional Bowel Disorders are nausea, diarrhea, and headache.25 Nausea associated with lubiprostone is most common in the young female population, and in the phase III clinical trials was reported in approximately 30% of patients taking the standard dose of 24 g bid. The majority of these patients rated the nausea as mild to moderate. In the openlabel safety studies, discontinuation of lubiprostone due to nausea occurred in 6.6% of patients.59 Administration of lubiprostone with food appears to decrease the incidence of nausea.25 No clinically significant changes in serum electrolyte levels were seen in the safety studies done with lubiprostone. Likewise there appears to be a minimal likelihood of drug interactions with lubiprostone. The new drug application for lubiprostone in IBS-C was filed in July 2007.60 Preliminary data presented by Drossman and colleagues at Digestive Disease Week (DDW) 2007 are illustrated in Figure 9.61 These data indicate that lubiprostone is an effective therapy for IBS-C at a dose of 8 g twice daily compared with placebo and is well tolerated. Clinical Case J.P. is a 38-year-old with 7 years of hard and lumpy stools accompanied with straining and bloating. His symptoms are worsening. He is now having a bowel movement every 5-6 days. He often resorts to enemas to facilitate defecation. Over the last 6-12 months, he has curtailed his social activities and feels like his work productivity is suffering. He has failed multiple home remedies, dietary fiber, as well as over-the-counter laxatives. His primary care clinician advised him to use stool softeners, and he has failed. He then went on a trial of PEG 3350, which was effective for about 1 month; however, his symptoms recurred, and he actually got up to about twice the standard therapy (34 g/d). He periodically takes magnesium citrate to purge. Tegaserod 6 mg twice daily improved his stool form, but he had to discontinue that after it was voluntarily removed from the market. Prior medical history is unremarkable. He denies alarm features, and his physical exam is unremarkable. Panel: It is likely that a man like this is using enemas and other available over-the-counter medications. I would be getting further tests and likely performing a pelvic floor test mainly because I would be more worried about that than colon transit. His situation does not sound like slow transit or very slow transit, although it could be. Question: If we do a colon transit study and the markers accumulate in the rectosigmoid, is that de facto evidence that he has pelvic floor dysfunction? Can you take anything away from that? Panel: This information would not be all that useful for confirmation of pelvic floor dysfunction. Some people have used that as a marker of pelvic floor dysfunction, but published data suggest that that is not good enough. You have to do balloon expulsion testing and anorectal manometry specifically to look at pelvic floor relaxation with straining in this individual instead of relying on results from a marker study to make a diagnosis of pelvic floor dysfunction. Question: Can a good clinical history be useful in distinguishing between constipation subtypes (ie, slow transit, pelvic floor dysfunction, and IBS-C)? Panel: There are some hints in a well-conducted clinical history that may help identify a defecatory disorder. For example, symptoms of very prolonged defecation and excessive straining may point to a diagnosis of defecatory disorder. Unfortunately, the clinical studies that have been reported to date suggest that anorectal physiology testing is required to sort out the subtypes reliably. Clinicians not conducting anorectal physiology testing are more often than not going to be misled by the history alone. Therefore, the history and physical exam processes can be helpful, but Expert Panel Questions and Answers Question: What would you do next in the management of this patient? Is it time for a colon transit study in this patient? Panel: No, a colon transit study would be low yield in this gentleman, considering his history and reported response to tegaserod therapy in the past. Additionally, according to the recommendations from the American College of Gastroenterology, empiric laxative therapy is an appropriate approach to chronic constipation in the absence of alarm features.31 A trial with lubiprostone would be worth a try in this patient. If lubiprostone does not work or is not well tolerated, you probably would want to get some additional information, including a colon transit study and perhaps a balloon expulsion test if not an anorectal manometry on him as well. VOL. 1 NO. 1 2007 REVIEWS FOR PRIMARY CARE 23
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