Pharmacological therapies for IBS-C are designed to alleviate abdominal discomfort and enhance bowel function. In patients with IBS-C, fiber supplements may help soften stools and decrease straining, but may also lead to increased gas production and bloating. Osmotic laxatives like milk of magnesia are frequently used to soften stools and increase stool frequency in IBS-C patients. In addition, two drugs approved for use in severe IBS-C adult cases are linaclotide (Linzess) and lubiprostone (Amitiza).

Linaclotide is a 14-amino acid peptide agonist that targets the intestinal epithelium's membrane-spanning guanylate cyclase-C (GC-C). This results in increased synthesis of cyclic GMP. The subsequent chain of biological events involves enhanced chloride and bicarbonate release into the intestinal lumen, leading to water secretion and improved motility. This mechanism of action helps alleviate symptoms of constipation. Additionally, some cellular cyclic GMP may be exported, and may reduce visceral pain by acting on primary afferent nerves innervating the gastrointestinal tract. Linaclotide is approved for two conditions: IBS-C and chronic idiopathic constipation or CIC. The recommended daily dose is 290 μg for IBS-C and 145 μg for CIC, respectively. Despite its therapeutic benefits, linaclotide has several common side effects. These include diarrhea (which can be severe), gas, abdominal pain, and headache.

Lubiprostone is a prostanoic acid derivative that stimulates the small intestine's type 2 chloride channel (ClC-2). This leads to increased chloride-rich fluid secretion, which enhances intestinal motility and reduces intestinal transit time, relieving constipation. Over half of the patients treated with lubiprostone experience a bowel movement within 24 hours of taking a single dose. A lower dose of 8 μg twice daily has been found effective for treating IBS-C. Long-term therapy with lubiprostone does not result in loss of efficacy, meaning the drug continues to work effectively even when used over a long period. However, if lubiprostone is discontinued abruptly, constipation may return to its pretreatment severity. Gradual dose reduction is not typically required but should be considered for some patients based on clinical judgment.

Adverse effects include nausea, headache, diarrhea, allergic reactions, and dyspnea. The occurrence of nausea is likely due to delayed gastric emptying caused by the drug. It has minimal systemic absorption and primarily acts only in the lumen of the bowel. Its low bioavailability reduces the risk of systemic side effects. Despite its minimal absorption, lubiprostone is designated category C for pregnancy and should be avoided in women of childbearing age.