Current and emerging treatments for irritable bowel syndrome with constipation and chronic idiopathic constipation: focus on prosecretory agents.

Irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) are two common functional gastrointestinal disorders that impair quality of life and pose a significant economic burden to the health care system. Current therapeutic options include lifestyle modifications, over-the-counter (OTC) agents, antispasmodics, serotonin agonists, and lubiprostone and linaclotide, two prosecretory prescription drugs approved for the treatment of IBS-C and CIC. This review discusses the efficacy and safety of current treatments and emerging therapies for the treatment of IBS-C and CIC, with a focus on the prosecretory agents. A search of the PubMed database (1966-November 2014) was performed to identify relevant articles; clinical trials on emerging agents were also identified by searching the ClinicalTrials.gov registry. OTC laxatives may relieve constipation but do not treat abdominal pain and discomfort. Antispasmodics may provide short-term relief in patients with IBS-C, but their utility is limited by anticholinergic adverse effects. Tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors have shown benefit in providing global symptom relief and in improving abdominal discomfort, but further research is needed. Phase III clinical trials have demonstrated the efficacy of lubiprostone and linaclotide relative to placebo for the short-term treatment of IBS-C and CIC, with improvements reported in stool frequency, perceived constipation severity, and abdominal pain and discomfort. Relatively small response rates, higher costs, and adverse effects associated with lubiprostone and linaclotide will likely render these agents suitable as second-line therapies in the treatment of IBS-C and CIC. Emerging potential treatment options include prucalopride, plecanatide, elobixibat, and tenapanor. Several of these emerging therapies have novel mechanisms of action and may show promise in patients with IBS-C and CIC who have not responded to other therapies.

Evidence for therapeutic uses of nebulized lidocaine in the treatment of intractable cough and asthma.

OBJECTIVE: To summarize the efficacy and safety data for use of nebulized lidocaine in intractable cough and asthma. DATA SOURCES: A literature search was conducted using PubMed (through November 2012), International Pharmaceutical Abstracts (1970-December 2012), and Cochrane Library (up to 2012) with the search terms nebulization, nebulized or nebulised; administration, inhalation; cough; asthma; and lidocaine. Results were limited to human studies published in the English language. Referenced citations from relevant publications were also reviewed. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were reviewed for inclusion. Clinical trials and descriptive studies that discussed use of nebulized lidocaine for treatment of intractable cough and asthma were included in the review. DATA SYNTHESIS: Seventeen studies were identified for review. Seven studies (6 descriptive studies and 1 clinical trial) evaluating the use of nebulized lidocaine in intractable cough reported efficacy in doses ranging from 10 mg to 400 mg. Five clinical trials in asthma showed conflicting results regarding improvement in pulmonary function and glucocorticoid-sparing effects. General improvements in pulmonary function as well as the initial bronchoconstriction induced by nebulized lidocaine in subjects with baseline bronchial hyperreactivity were investigated in 5 studies. Overall, the available evidence does not appear to preclude the use of lidocaine as a treatment option for intractable cough after failure of traditional cough suppressants. Data on its use for short-term glucocorticoid-sparing effects in asthma are conflicting. Study limitations, including design, small sample size, and inconsistencies in method and adjunctive therapies, should be considered. Nebulized lidocaine is well tolerated; however, reports of initial bronchoconstriction have occurred. CONCLUSIONS: Although nebulized lidocaine is not first-line therapy in intractable cough and asthma, it may provide an alternative treatment option in patients who cannot tolerate or are unresponsive to other treatments. Appropriate monitoring precautions should be used to ensure patient safety.