Gastrointestinal Pharmacology

Amol Sharma, Satish Rao, Sharma, Amol, Rao, Satish

Chronic constipation is a common, persistent condition affecting many patients worldwide, presenting significant economic burden and resulting in substantial healthcare utilization. In addition to infrequent bowel movements, the definition of constipation includes excessive straining, a sense of incomplete evacuation, failed or lengthy attempts to defecate, use of digital manoeuvres for evacuation of stool, abdominal bloating, and hard consistency of stools. After excluding secondary causes of constipation, chronic idiopathic or primary constipation can be classified as functional defecation disorder, slow-transit constipation (STC), and constipation-predominant irritable bowel syndrome (IBS-C). These classifications are not mutually exclusive and significant overlap exists. Initial therapeutic approach to primary constipation, regardless of aetiology, consists of diet and lifestyle changes such as encouraging adequate fluid and fibre intake, regular exercise, and dietary modification. Laxatives are the mainstay of pharmacologic treatment for potential long-term therapy in patients who do not respond to lifestyle or dietary modification. After a failed empiric trial of laxatives, diagnostic testing is necessary to understand underlying anorectal and/or colonic pathophysiology. No single test provides a comprehensive assessment for primary constipation; therefore, multiple tests are used to provide complementary information to one another. Dyssynergic defecation, a functional defecation disorder, is an acquired behavioural disorder of defecation present in two-thirds of adult patients, where an inability to coordinate the abdominal, recto-anal, and pelvic floor muscles during attempted defecation exists. Biofeedback therapy is the mainstay treatment for dyssynergic defecation aimed at improving coordination of abdominal and anorectal muscles. A large percentage of patients with dyssynergic defecation also exhibit rectal hyposensitivity and may benefit from the addition of sensory retraining. Our understanding of the pathophysiology of STC is evolving. The advent of high-resolution colonic manometry allows for the improved identification of colonic motor patterns and may provide further insight into pathophysiological mechanisms. In a minority of cases of STC, identification of colonic neuropathy suggests a medically refractory condition, warranting consideration of colectomy. The pathophysiology of IBS-C is poorly understood with multiple etiological factors implicated. Pharmacological advances in the treatment of primary constipation have added therapeutic options to the armamentarium of this disorder. Drug development in the secretagogue, serotonergic prokinetic, and ileal bile acid transporter inhibition pathways has yielded current and future medical treatment options for primary chronic constipation.