Luminary Learning Gastrointestinal Disorder- Issue 1

Pharmacological and Clinical Treatment of Irritable Bowel Syndrome •  21 Crofelemer Crofelemer is a plant-derived drug originating from Croton lechleri, which belongs to the proan- thocyanidin family. It was approved by FDA for the treatment of diarrhea associated with anti-HIV drugs [45]. It simultaneously targets two distinct channels, CFTR and calcium-activated chloride channel, both responsible for chloride and fluid secretion in the GI tract. Although it has been shown that crofelemer did not produce significant improvement in stool consistency, stool frequen- cy, urgency and adequate relief it increased the number of pain-free days in female IBS-D patients after 1 and 3 month therapy and was well tolerated [46]. Further studies evaluating the analgesic potential action of this drug are needed to draw a clear conclusion on its therapeutic potential. Antidepressants Antidepressants are commonly used in IBS-D. There are many plethora of evidences for point to the link between mood-related disorders and functional GI diseases. Emotional fluctuations that often occur in distressed patients correlate with IBS symptoms. Moreover, IBS patients are more likely to develop psychiatric disorders (depression, anxiety) and dementia [47, 48]. The bidirectional communication between the brain and the gut, so called brain-gut axis, may be exploited therapeutically in IBS patients. Some of the tricyclic antidepressants, selective serotonin re-uptake inhibitors and serotonin-norepinephrine reuptake inhibitors have already been employed in the treatment of IBS and proved effective in symptom relief via mood stabi- lization, modulation of pain perception and amelioration of GI motility and secretion. A recent meta-analysis confirmed the efficacy of antidepressants, including tricyclic antidepressants, in the treatment of IBS symptoms [49]. In a randomized, double-blind, placebo controlled study low dose amitriptyline (10 mg) successfully ameliorated IBS-D symptoms [50]. Fifty out of 54 patients completed an intention-to-treat study; 68 % of those receiving amitriptyline had a com- plete response defined as a loss of all symptoms over a 2 month trial period compared to only 28 % of the controls. Adverse effects were similar between the two groups. Pharmacological Treatment of Constipation-Predominant Irritable Bowel Syndrome (IBS-C) Polyethylene Glycol (PEG) 3350 The first-line therapy for patients suffering from IBS-C involves laxatives and dietary fibers. Although this approach may effectively and safely combat slowed intestinal transit and constipa- tion, it does not alleviate pain symptoms [51]. The effect of PEG 3350 plus electrolytes (PEG+E) on IBS-C has been tested in a randomized, double-blind, placebo controlled study by Chapman et al. [52]. One hundred thirty four patients received the treatment or placebo for 28 days. PGE+E was superior than placebo as assessed by spontaneous bowel movements (the primary endpoint), responder rates, stool consistency, and straining. There was no difference between PGE+E versus placebo in the mean severity score for abdominal discomfort/pain. PEG+E constitutes a well