NOVEL THERAPEUTIC AGENTS IN CONSTIPATION

Abstract

Gastrointestinal (GI) disease is prevalent and considered for a large number of death worldwide. Recently many new drugs are developed to treat one of the common GI disorders, functional constipation. Linaclotide is a secretagogue agent, an agonist of the guanylate cyclase-C receptor. It is a safe and effective drug with diarrhea as the main side effect (Bassotti, 2018). Prucalopride is a prokinetic agent newly approved in Canada and by the United States Food and Drug Administration (US FDA) for treating chronic idiopathic constipation. Prucalopriderepresents its effect by stimulating 5-hydroxytryptamine receptor 4 (5-HT4), increasing GI motility in large bowl, accelerating gastric emptying and improving small bowel movement. Efficacy and safety of this drug is documented by different clinical trials. Prucalopride has also shown efficacy in pediatric constipation(Voelker, 2019; Tameez, 2019). Lubiprostone is another approved drug by FDA. It affects luminal GI epitheliumchloride channels, exhibits influx of chloride ions and water into the lumen, increasing intestinal motility represents anti constipation effect. Several randomized controlled trials proved the efficacy of drug in short term treatment although different side effects such as nausea, abdominal pain and bloating, discomfort and headache were also reported. According to researches lubiprostone is more effective but costlier in comparison with Prucalopride. The higher cost of lubiprostone should be considered as a main limiting factor for using this drug (Hayat, 2019). Mizagliflozin is known as a new class of drug for treatment of chronic constipation and irritable bowel syndrome with constipation. Drug is an inhibitor of the sodium-glucose co-transporter 1(SGLT1) in the small intestine epithelium. Although according to different clinical trials Mizagliflozin increases the number of spontaneous bowel movements (SBMs) per week and exhibits dose-dependent efficacy and good tolerability, it needs more long term clinical trials to show the effect of drug in quality of life(Fukudo, 2018). Also, the effect of probiotics as a treatment for constipation is under investigation. probiotics (Bifidobacterium longum) significantly improves constipation in elderly individuals (Martínez-Martínez, 2017). Interestingly, researchers propose new insight into probiotics establishment in human gut mucosal. They suggest that human stool microbiome is more similar to lower GI taxa than upper GI. Moreover, probiotics represent temporary and person feature-dependent effect on mucosal structure and transcriptome (Zmora, 2018). Development of new therapeutic in chronic constipation provides opportunity for physicians to treat patients who experience significant constipation symptoms.