Chronic constipation is a therapeutic challenge for physicians. Traditional treatments such as diet, fiber, and laxatives are associated with limited efficacy, and patients often report inadequate symptom relief when taking them. Nonpharmacologic therapies, such as biofeedback training and surgery, are reserved for specific subtypes or refractory cases of constipation.
In a recent supplement to Reviews in Gastroenterological Disorders, Lawrence R. Schiller, MD, discusses the pathophysiology of constipation and emerging pharmacologic therapies. The author describes potential targets in the enteric nervous system (ENS) and evaluates emerging pharmacologic therapies that focus on them. For example, interneurons in the ENS express serotonin type 4 (5-HT4) receptors, which, when activated, enhance the peristaltic reflex. Pharmacologic agents that are 5-HT4 receptor agonists, such as tegaserod, have been shown to be effective therapies for chronic constipation in large clinical trials. Prucalopride, another 5-HT4 agonist, was also shown to be effective; however, studies were suspended because of safety concerns regarding cardiac arrhythmias.
Other potential targets in the ENS have not been studied extensively; these include opiate antagonists (endogenous opiates and ?-opiate receptors act to slow peristalsis), cellular growth factors such as neurotrophin-3 (shown to increase colonic motility), and chloride-channel activators (chloride channels mediate fluid secretion in the gut). The author concludes that understanding the physiology of the colon will aid in the development of better treatments for patients with constipation.
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