Patients with ulcerative colitis uniformly have disease involving the distal colon. When patients have disease limited to the left colon or symptoms suggestive of active rectal inflammation, guidelines recommend topical rectal therapies as first-line agents either as monotherapy or in conjunction with oral products. Rectal delivery modalities offer the advantage of delivering high local concentrations of active medication to the site of maximal inflammation with minimization of systemic side effects. Methods of rectal administration include suppositories, liquid enemas and foams. Suppositories are limited to the treatment of rectal disease, and patients often have difficulty retaining the liquid enema secondary to its high volume and consistency. Rectal foams reliability extend to the descending and sigmoid colon with application. Foams are further characterized by increased viscosity, lower volumes, finer dispersion on the colonic mucosa, and increased adhesiveness to the colonic mucosa compared with liquid enemas. Additionally, rectal foam agents demonstrate equal efficacy to their liquid enema counterparts yet consistently yield better patient tolerance, lower incidence of side effects, and increased patient acceptability. Currently available agents include 5-aminosalicylic acid and corticosteroids, both first and newer generation. This review focuses on clinical trials assessing efficacy, tolerability, and patient preferences for these agents as well as describing the currently available rectal foam products.
Chronic constipation is a frequently reported medical disorder that reduces patients' quality of life and imposes a significant economic burden on the health care system. Symptoms of constipation are diverse and include infrequent bowel movements, hard stool, straining at stool, sensations of anorectal obstruction and feelings of incomplete evacuation. Patients with chronic constipation can be categorized into one of three main groups based on their underlying pathophysiology: normal transit constipation; colonic inertia; and pelvic floor dyssynergia. Specialized tests (i.e., anorectal manometry, radio-opaque marker study) may be required in some patients to help distinguish the different subtypes of constipation and to guide appropriate therapy. Although the underlying mechanism of constipation differs among patients, serotonin (5-hydroxytryptamine (5-HT)) appears to have an important role in colonic motility in some patients. Previous research has demonstrated that stimulation of 5-HT4 receptors improves symptoms of chronic constipation in some patients. Prucalopride, a selective 5-HT4 agonist, relieved symptoms of constipation in phase II and phase III clinical trials. In this monograph, we review the pharmacology, mechanism of action, efficacy and safety of the selective 5-HT4 agonist prucalopride in patients with chronic constipation.
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