Advances in the management of constipation-predominant irritable bowel syndrome: the role of linaclotide.

Constipation-predominant irritable bowel syndrome (IBS-C) is a commonly prevalent and clinically challenging disorder to treat. Until recently, most therapeutic agents had limited ability to address the complexity of symptoms inherent to the syndrome. The development of linaclotide provides a physiologically sound approach to treatment of the multiple symptoms of IBS-C. Clinical trials demonstrate the efficacy of linaclotide, and a platform to better understand the symptomatology of IBS-C. Based on recent clinical evidence, linaclotide should be considered for patients with IBS-C because it improves abdominal pain and bowel symptoms. In phase III trials, linaclotide met the US Food and Drug Administration responder endpoint with a number needed to treat (NNT) of 5.1-7.9, and European Medicines Agency coprimary endpoints at 12 weeks with a NNT of 4.39-7.69, and at 26 weeks with a NNT of 4.93-5.68. It is safe and effective, with diarrhea reported as the most common adverse effect, which leads to discontinuation of the medication in approximately 5% of patients.

Anorectal physiology and pathophysiology in the elderly.

Anorectal medical disorders facing the elderly include fecal incontinence, fecal impaction with overflow fecal incontinence, chronic constipation, dyssynergic defecation, hemorrhoids, anal fissure, and pelvic floor disorders. This article discusses the latest advances in age-related changes in morphology and function of anal sphincter, changes in cellular and molecular biology, alterations in neurotransmitters and reflexes, and their impact on functional changes of the anorectum in the elderly. These biophysiologic changes have implications for the pathophysiology of anorectal disorders. A clear understanding and working knowledge of the functional anatomy and pathophysiology will enable appropriate diagnosis and treatment of these disorders.

Hyperinsulinemia euglycemia therapy for calcium channel blocker overdose: a case report.

We report the case of a patient with calcium channel blocker toxicity who was treated successfully with hyperinsulinemia euglycemia therapy, without prior use of vasopressors. The patient was a 60-year-old man with schizoaffective disorder who presented with severe hemodynamic compromise after an intentional overdose of 5,400 mg of extended-release diltiazem. He had been admitted to the hospital twice before for attempted suicide with diltiazem and nifedipine, respectively. During the previous admissions, conventional treatments were used, and complications included hemodynamic compromise, ischemic bowel requiring ileostomy, and a prolonged hospital stay. During the current admission, the patient's clinical condition failed to improve after treatment with charcoal, fluid resuscitation, calcium, and glucagon. Eight hours after admission, hyperinsulinemia euglycemia therapy was initiated; 3 hours later, the patient's hemodynamic status showed sustained improvement. His bradycardia and hypotension resolved without cardiac pacing or vasopressors. Hyperinsulinemia euglycemia therapy is a potentially life-saving treatment for calcium channel blocker toxicity. We suggest that such therapy should be considered early, in conjunction with conventional therapy, for the treatment of calcium channel blocker overdose in patients not responding to initial treatment.