Potential Targets in Constipation Research: A Review

Abstract

Background: Constipation is one of the most frequent abnormalities of the gastrointestinal system that affects the patient’s quality of life. Constipation is more common in women and affects them more frequently as they get older. Many constipated patients take over-the-counter drugs for treatment, but some do not respond to these medicines and need newer, more expensive drugs. Still, many patients are not completely satisfied with these medicines. Unlike other areas, constipation research is not given much importance. Objective: This review discusses targets such as ClC-2, CFTR, opioid receptors, and 5HT-4 receptors, which are important in constipation therapy. The recent focus is also on the gut microbiome with the help of various randomized controlled trials. Pharmacological advances have also added novel targets such as IBAT, PAR-2, and intestinal NHE-3 for constipation treatment. Methods: This review summarises the research on these targets collected from various databases. ClC-2 and CFTR are involved in intestinal chloride secretion followed by sodium or water, which increases stool passage. Non-cancer pain treatment with opioids targeting opiate receptors is considered in 40–90% of patients, which causes constipation as a side effect. On activation, 5HT-4 receptors increase gastrointestinal motility. IBAT is responsible for transporting bile acid into the liver. Bile acid will reach the colon by inhibiting IBAT, stimulating colonic motility, and providing a laxative effect. Activation of the ghrelin receptor results in prokinetic activity in both animals and humans. Intestinal NHE-3 mediates the absorption of Na+ and the secretion of hydrogen into the intestine. Many reports show that PAR-2 is involved in the pathogenesis of gastrointestinal diseases. The gut microbiota influences the peristaltic action of the intestine. Conclusion: Drugs working on these targets positively impact the treatment of constipation, as do the drugs that are currently in clinical trials acting on these targets. The results from the ongoing clinical trials will also provide some valuable information regarding whether these medications will meet the patients’ needs in the future.

Efficacy and Safety of Lactulose and Polyethylene Glycol in the Treatment of Constipation: A Meta-Analysis

“…However, there is currently a lack of comprehensive evaluation of the efficacy and safety of these two drugs in the treatment of constipation. The results of this meta-analysis show that PEG and lactulose are equally effective in treating constipation, and the safety of both drugs is similar [21][22] . This study conducted a meta-analysis comparing the efficacy and safety of PEG and lactulose in the treatment of constipation.…”

Efficacy and Molecular Mechanism of Quercetin on Constipation Induced by Berberine via Regulating Gut Microbiota

“…The prevalence of DIC is high, and, according to surveys, about 10% to 15% of people will experience DIC, which is especially common in patients with chronic illnesses who have been taking medications for a long time. DIC will not only affect the life quality of the patient [ 1 ], but also influence how well the patient absorbs medication, which influences how effective the medication is [ 2 ], and even further leads to anal fissure, hemorrhoids, intestinal obstruction, and other serious complications [ 3 ]. Early intervention for DIC is essential.…”

Causal association between constipation and risk of colorectal cancer: a bidirectional two-sample Mendelian randomization study

“…The quest to identify modifiable risk factors for CRC is of paramount importance to develop effective preventive strategies (3,4). Among the potential risk factors, constipation, characterized by infrequent bowel movements or difficulty passing stools, has garnered attention for its potential association with CRC risk (5,6). Previous observational studies have generated substantial controversy regarding the causal relationship between constipation and CRC (7)(8)(9)(10)(11).…”