Constipation
Constipation is a common gastrointestinal disorder characterized by infrequent, difficult, or incomplete defecation, often defined by fewer than three bowel movements per week, hard or lumpy stools, excessive straining, or a sensation of incomplete evacuation. The pathogenesis of constipation is multifactorial, involving alterations in colonic motility, dysfunction of the anorectal region, impaired rectal sensation, and changes in the gut microbiota. Contributing factors include inadequate dietary fiber or fluid intake, sedentary lifestyle, certain medications, metabolic or endocrine disorders, and psychological stress. Chronic constipation can lead to significant health impacts, such as hemorrhoids, anal fissures, fecal impaction, rectal prolapse, and a reduced quality of life due to discomfort, pain, and psychological distress.
Also known as functional constipation, this type occurs without an identifiable organic cause and is subdivided into normal transit constipation, slow transit constipation, and defecatory disorders. Normal transit constipation features normal colonic motility but with symptoms of constipation, often related to psychosocial factors or dietary habits. Slow transit constipation is characterized by delayed movement of stool through the colon, frequently associated with impaired colonic neuromuscular function. Defecatory disorders involve dysfunction of the pelvic floor or anal sphincter muscles, leading to impaired evacuation despite normal or even accelerated colonic transit.
This type results from identifiable causes such as medications (e.g., opioids, anticholinergics), metabolic and endocrine disorders (e.g., hypothyroidism, diabetes mellitus, hypercalcemia), neurologic conditions (e.g., Parkinson's disease, spinal cord injury), or structural abnormalities (e.g., colorectal cancer, strictures). Management focuses on addressing the underlying cause in addition to symptomatic treatment.
A distinct form of secondary constipation, opioid-induced constipation is caused by the binding of opioids to gastrointestinal tract receptors, reducing gut motility and increasing fluid absorption, which results in hard, dry stools and decreased frequency of defecation. This type is particularly prevalent in patients receiving chronic opioid therapy for pain management.
IBS-C is a functional bowel disorder characterized by recurrent abdominal pain or discomfort associated with altered bowel habits, predominantly constipation. The pathophysiology involves visceral hypersensitivity, altered gut-brain axis signaling, and dysregulated motility, often accompanied by bloating and abdominal discomfort.
Constipation is a prevalent condition worldwide, affecting an estimated 14–30% of the general population, with higher rates observed in women, the elderly, and individuals with lower socioeconomic status. Prevalence increases with age, particularly in those over 65 years, where it can exceed 30%. In pediatric populations, constipation is also common, especially during toilet training and school entry. The disorder accounts for a substantial proportion of primary care and gastroenterology visits, with significant economic implications due to healthcare utilization and reduced productivity. Chronic constipation is more frequently reported in Western countries, likely related to dietary and lifestyle factors, although underreporting and cultural differences in symptom perception may influence epidemiological data.
The diagnosis of constipation is primarily clinical, based on a thorough history and physical examination. Diagnostic criteria are standardized by the Rome IV criteria, which require the presence of at least two of the following symptoms for a minimum of three months: straining during at least 25% of defecations, lumpy or hard stools in at least 25% of defecations, sensation of incomplete evacuation or anorectal obstruction/blockage in at least 25% of defecations, manual maneuvers to facilitate defecation in at least 25% of defecations, and fewer than three spontaneous bowel movements per week. Additional evaluation includes assessment for alarm features such as rectal bleeding, weight loss, anemia, or family history of colorectal cancer, which may necessitate further investigation. Diagnostic procedures may include laboratory tests to exclude metabolic causes, colonoscopy or flexible sigmoidoscopy to rule out structural lesions, and specialized studies such as colonic transit studies, anorectal manometry, and balloon expulsion tests to evaluate for motility or defecatory disorders.
Elobixibat is an ileal bile acid transporter inhibitor that increases colonic bile acid concentrations, thereby enhancing intestinal secretion and motility to alleviate constipation symptoms. Guanilib, also known as plecanatide, is a guanylate cyclase-C agonist that stimulates intestinal fluid secretion and transit by increasing cyclic GMP levels, which facilitates bowel movements. Linaclotide acetate, another guanylate cyclase-C agonist, promotes chloride and bicarbonate secretion into the intestinal lumen, resulting in increased fluid content and accelerated transit, thereby relieving constipation. Prucalopride succinate is a selective serotonin 5-HT4 receptor agonist that stimulates colonic peristalsis, enhancing bowel motility and improving stool frequency in patients with chronic constipation. Methylnaltrexone bromide is a peripherally acting mu-opioid receptor antagonist used to treat opioid-induced constipation by counteracting opioid effects on the gut without affecting central analgesia. Polyethylene glycol 3350 is an osmotic laxative that retains water in the stool, increasing stool frequency and improving consistency. Lubiprostone is a chloride channel activator that increases intestinal fluid secretion, facilitating stool passage and easing symptoms of chronic idiopathic constipation and irritable bowel syndrome with constipation. Lactitol is a synthetic disaccharide laxative that is poorly absorbed and acts as an osmotic agent in the colon, drawing water into the bowel to soften stools and stimulate peristalsis. Sodium picosulfate is a stimulant laxative that is converted by colonic bacteria into its active form, directly stimulating colonic peristalsis and promoting bowel evacuation.
| Structure | Generic Name | CAS Registry Number | Molecular Formula | Molecular Weight |
|---|---|---|---|---|
 | elobixibat (Prop INN; USAN) | 439087-18-0 | C36 H45 N3 O7 S2 | 695.888 |
 | guanilib; plecanatide (Prop INN; USAN) | 467426-54-6 | C65 H104 N18 O26 S4 | 1681.886 |
 | linaclotide acetate (Prop INNM; USAN) | 851199-60-5 | C59 H79 N15 O21 S6 . C2 H4 O2 | 1586.788 |
 | prucalopride succinate (Prop INNM; USAN) | 179474-85-2 | C18 H26 Cl N3 O3 . C4 H6 O4 | 485.958 |
 | methylnaltrexone bromide (Prop INN; USAN) | 73232-52-7 | C21 H26 N O4 . Br | 436.339 |
| polyethylene glycol 3350 | ||||
 | lubiprostone (Rec INN; USAN) | 333963-40-9 | C20 H32 F2 O5 | 390.462 |
| 25322-68-3 | ||||
 | lactitol (Rec INN; BAN) | 585-86-4 | C12 H24 O11 | 344.312 |
 | sodium picosulfate | 10040-45-6 | C18 H13 N O8 S2 . 2 Na | 481.407 |
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