1. Dietary and lifestyle measures
Adverse psychosocial issues should be identified and addressed. Patients should be instructed on normal defecatory function and optimal toileting habits, including regular timing, proper positioning, and abdominal pressure. Adequate dietary fluid and fiber intake should be emphasized. A trial of fiber supplements is recommended (Table 15–4). Increased dietary fiber may cause distention or flatulence, which often diminishes over several days. Response to fiber therapy is not immediate, and increases in dosage should be made gradually over 7–10 days. Fiber is most likely to benefit patients with normal colonic transit, but it may not benefit patients with colonic inertia, defecatory disorders, opioid-induced constipation, or irritable bowel syndrome; it may even exacerbate symptoms in these patients. Regular exercise is associated with a decreased risk of constipation. When possible, discontinue medications that may be causing or contributing to constipation. Probiotics are widely promoted to patients in direct advertising for treatment of constipation. A 2014 meta-analysis of randomized controlled trials suggests probiotics improve stool frequency and consistency; however, more study is needed.
Table 15–4.Pharmacologic management of constipation. ||Download (.pdf) Table 15–4. Pharmacologic management of constipation.
|Agent ||Dosage ||Onset of Action ||Comments |
|Fiber Laxatives |
|Bran powder ||1–4 tbsp orally twice daily ||Days ||Inexpensive; may cause gas, flatulence |
|Psyllium ||1 tsp once or twice daily ||Days ||(Metamucil; Perdiem) |
|Methylcellulose ||1 tsp once or twice daily ||Days ||(Citrucel) Less gas, flatulence |
|Calcium polycarbophil ||1 or 2 tablets once or twice daily ||12–24 hours ||(FiberCon) Does not cause gas; pill form |
|Guargum ||1 tbsp once or twice daily ||Days ||(Benefiber) Non-gritty, tasteless, less gas |
|Stool Surfactants |
|Docusate sodium ||100 mg once or twice daily ||12–72 hours ||(Colace) Marginal benefit |
|Mineral oil ||15–45 mL once or twice daily ||6–8 hours ||May cause lipoid pneumonia if aspirated |
|Osmotic Laxatives |
|Magnesium hydroxide ||15–30 mL orally once or twice daily ||6–24 hours ||(Milk of magnesia; Epsom salts) May cause hypermagnesemia if chronic kidney disease |
|Lactulose or 70% sorbitol ||15–60 mL orally once daily to three times daily ||6–48 hours ||Cramps, bloating, flatulence |
|Polyethylene glycol (PEG 3350) ||17 g in 8 oz liquid once or twice daily ||6–24 hours ||(Miralax) Less bloating than lactulose, sorbitol |
|Stimulant Laxatives |
|Bisacodyl ||5–20 mg orally as needed ||6–8 hours ||May cause cramps; avoid daily use if possible |
|Bisacodyl suppository ||10 mg per rectum as needed ||1 hour || |
|Cascara ||4–8 mL or 2 tablets as needed ||8–12 hours ||(Nature’s Remedy) May cause cramps; avoid daily use if possible |
|Senna ||8.6–17.2 mg orally as needed ||8–12 hours ||(ExLax; Senekot) May cause cramps; avoid daily use if possible |
|Lubiprostone ||24 mcg orally twice daily ||12–48 hours ||Expensive; may cause nausea. Contraindicated in pregnancy |
|Linaclotide ||145 mcg orally once daily || ||Expensive; contraindicated in pediatric patients |
|Plecanatide ||3 mg once daily || ||Expensive; contraindicated in pediatric patients |
|Tap water ||500 mL per rectum ||5–15 minutes || |
|Sodium phosphate enema ||120 mL per rectum ||5–15 minutes ||Commonly used for acute constipation or to induce movement prior to medical procedures |
|Mineral oil enema ||100–250 mL per rectum ||5–15 minutes ||To soften and lubricate fecal impaction |
|Agents used for Acute Purgative or to Clean Bowel Prior to Medical Procedures |
|Polyethylene glycol (PEG 3350) ||4 L orally administered over 2–4 hours ||< 4 hours ||(GoLYTELY; CoLYTE; NuLYTE, MoviPrep) Used to cleanse bowel before colonoscopy |
|Magnesium citrate ||10 oz orally ||3–6 hours ||Lemon-flavored |
Laxatives may be given on an intermittent or chronic basis for constipation that does not respond to dietary and lifestyle changes (Table 15–4). There is no evidence that long-term use of these agents is harmful.
Treatment usually is initiated with regular (daily) use of an osmotic laxative. Nonabsorbable osmotic agents increase secretion of water into the intestinal lumen, thereby softening stools and promoting defecation. Magnesium hydroxide, nondigestible carbohydrates (sorbitol, lactulose), and polyethylene glycol are all efficacious and safe for treating acute and chronic cases. The dosages are adjusted to achieve soft to semi-liquid movements. Magnesium-containing saline laxatives should not be given to patients with chronic renal insufficiency. Nondigestible carbohydrates may induce bloating, cramps, and flatulence. Polyethylene glycol 3350 (Miralax) is a component of solutions traditionally used for colonic lavage prior to colonoscopy and does not cause flatulence. When used in conventional doses, the onset of action of these osmotic agents is generally within 24 hours. For more rapid treatment of acute constipation, purgative laxatives may be used, such as magnesium citrate. As a purgative prior to surgical, endoscopic, or radiographic procedures, polyethylene glycol solutions (GoLYTELY, CoLYTE, NuLYTE, MoviPrep) may be used. Polyethylene glycol solutions (2–4 L administered over 2–4 hours) are balanced osmotic and electrolyte solutions that do not cause any significant fluid or electrolyte shifts and may be used safely in almost all patients. Magnesium citrate may cause hypermagnesemia.
For patients with incomplete response to osmotic agents, stimulant laxatives may be prescribed as needed as a “rescue” agent or on a regular basis three or four times a week. These agents stimulate fluid secretion and colonic contraction, resulting in a bowel movement within 6–12 hours after oral ingestion or 15–60 minutes after rectal administration. Oral agents are usually administered once daily at bedtime. Common preparations include bisacodyl, senna, and cascara (Table 15–4).
Several agents stimulate intestinal chloride secretion either through activation of chloride channels (lubiprostone) or guanylcyclase C (linaclotide and plecanatide), resulting in increased intestinal fluid and accelerated colonic transit. In multicenter controlled trials, patients treated with lubiprostone 24 mcg orally twice daily, linaclotide 145 mcg once daily, or plecanatide 3 mg once daily increased the number of bowel movements compared with patients treated with placebo. Because these agents are expensive, they should be reserved for patients who have suboptimal response or side effects with less expensive agents.
D. SEROTONIN 5-HT-RECEPTOR AGONIST
Stimulation of 5-HT4-receptors in the colon leads to increased release of acetylcholine within smooth muscle of the intestinal tract, which stimulates high-amplitude peristaltic contractions in the proximal colon. Prucalopride is a high-affinity 5-HT4-agonist that is approved in the United States for the treatment of chronic constipation (2 mg once daily). In six clinical trials, 19–38% of patients treated with prucalopride experienced at least three spontaneous bowel movements per week, which was 5–23% more than with placebo. In contrast to prior, less-selective 5-HT4-agonists (cisapride, tegaserod), which were removed from the market due to adverse cardiovascular events, prucalopride does not have affinity for hERG K+ channels and does not appear to have any cardiovascular risk.
E. OPIOID-RECEPTOR ANTAGONISTS
Long-term use of opioids can cause constipation by inhibiting peristalsis and increasing intestinal fluid absorption. Methylnaltrexone (450 mg orally once daily), naloxegol (12.5–25 mg orally once daily), and naldemedine (0.2 mg orally once daily) are mu-opioid receptor antagonists that block peripheral opioid receptors (including in the gastrointestinal tract) without affecting central analgesia. They are approved for the treatment of opioid-induced constipation in patients receiving opioids for chronic noncancer pain (see Chapter 5). A subcutaneous formulation of methylnaltrexone also is approved for treatment of patients receiving palliative care for advanced illness who have not responded to conventional laxative regimens.
Severe impaction of stool in the rectal vault may result in obstruction to further fecal flow, leading to partial or complete large bowel obstruction. Predisposing factors include medications (eg, opioids), severe psychiatric disease, prolonged bed rest, neurogenic disorders of the colon, and spinal cord disorders. Clinical presentation includes decreased appetite, nausea and vomiting, and abdominal pain and distention. There may be paradoxical “diarrhea” as liquid stool leaks around the impacted feces. Firm feces are palpable on digital examination of the rectal vault. Initial treatment is directed at relieving the impaction with enemas (saline, mineral oil, or diatrizoate) or digital disruption of the impacted fecal material. Long-term care is directed at maintaining soft stools and regular bowel movements (as above).