Examining linaclotide for the treatment of chronic idiopathic constipation

ABSTRACT

Introduction

Chronic idiopathic constipation (CIC) is characterized by infrequent bowel movements and hard stools lasting for at least three months or longer. This disease affects 8-12% of the US population and 10-17% of the world population. Treatment and management involve identifying the primary cause, changing dietary habits, and adequate physical activity. Linaclotide is a guanylate cyclase-agonist acting locally in the luminal surface of the intestinal enterocyte leading to a signal transduction cascade, activation of the cystic fibrosis transmembrane conductance regulator (CFTR), thus increasing secretion of chloride and bicarbonate into the intestinal lumen with eventual increased intestinal fluid and faster transit time.

Areas Covered

We reviewed multiple studies and did a thorough literature review on CIC including its pathophysiology. Through this literature review we were able to discuss and give the context and rationale for drug regimens indicated for CIC.

Expert Opinion

The era we live in right now is akin to nutrient-rich and fertilized soil as knowledge and resources are abundant. The opportunities and potential are endless. Constipation being more extensively studied, our understanding of medications and diseases broadens, leading to novel medications being discovered. Linaclotide is a pioneer in this aspect and can pave the way for future generations.

KEYWORDS:

• Linaclotide
• Chronic idiopathic constipation
• CIC
• Constipation
• Bowel preparation
• CFTR
• cGMP

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Article Highlights

• CIC is a relatively common disease affecting as much as approximately 8%–12% of the US population and approximately 10-17% of the world population.

• Treatment of CIC starts with conservative management with proper diet and exercise.

• A stepwise approach in the management of CIC is encouraged and advised however starting immediately on Linaclotide seems to have no ill effects.

• Pharmacologic management of CIC has multiple options however the degree of improvement and convenience of Linaclotide is second to none.

• More and more studies have emerged that Linaclotide is very well tolerated and has a promising potential to be a standard for bowel preparation.

• The mechanism of action of Linaclotide has also shown that it improves significant pain and discomfort with improvement in constipation.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Table 1. Medications used in treating and managing Chronic Idiopathic Constipation (CIC).

Additional information

Funding

This paper is not funded.