What treatment options are recommended for an adult patient with constipation, considering their past medical history and potential underlying causes?

Treatment of Constipation in Adults

Start with polyethylene glycol (PEG) as first-line pharmacological therapy for chronic idiopathic constipation, with strong evidence supporting its efficacy, tolerability, and cost-effectiveness. 1, 2

Initial Assessment and Non-Pharmacological Measures

Before initiating pharmacological treatment, rule out secondary causes and optimize basic interventions:

• Check TSH, serum calcium, and basic metabolic panel to exclude hypothyroidism, hypercalcemia, and hypokalemia as reversible causes 3
• Review all medications systematically for constipating effects, including antacids, anticholinergics, and antiemetics 3
• Rule out mechanical bowel obstruction before escalating laxative therapy, particularly if there is abdominal pain, nausea, or fecal loading on imaging 3
• Ensure adequate fluid intake and dietary fiber, though fiber compounds like Metamucil are unlikely to control opioid-induced constipation 1
• Implement scheduled toileting after meals and encourage exercise if feasible 1, 4

First-Line Pharmacological Treatment

Polyethylene glycol (PEG) receives the strongest recommendation from the 2023 AGA-ACG guidelines:

• Dose: PEG 17 grams (one capful) in 8 oz water once or twice daily 1, 2
• Trial duration: 4-12 weeks before considering escalation 2, 3
• Advantages: Moderate-quality evidence, durable response over 6 months, well-tolerated, cost-effective 2
• Common side effects: Abdominal distension, loose stool, flatulence, nausea (generally well-tolerated) 2

Second-Line Options: Stimulant Laxatives

If PEG alone is insufficient or for rescue therapy:

• Bisacodyl 10-15 mg orally once daily (strong recommendation for short-term use ≤4 weeks or rescue therapy) 1, 2
• Senna 2 tablets every morning, titrate up to maximum 8-12 tablets per day (conditional recommendation; start low and titrate) 1, 2
• Sodium picosulfate (strong recommendation, but contraindicated in CHF, hypermagnesemia, severe renal impairment; increased hyponatremia risk in elderly) 2

Critical Safety Considerations for Magnesium-Based Laxatives

• Magnesium hydroxide 30-60 mL daily or magnesium citrate can be effective 1
• CONTRAINDICATED if creatinine clearance <20 mL/min due to hypermagnesemia risk 2
• Avoid long-term use due to potential toxicity 4

Third-Line: Prescription Secretagogues

If symptoms persist after 4-12 weeks of PEG ± stimulant laxatives, escalate to prescription agents rather than continuing to increase laxative doses 3:

Linaclotide (Strong Recommendation)

• Dose: 145 mcg orally once daily 2
• Mechanism: Guanylate cyclase-C agonist that stimulates chloride secretion and intestinal fluid 1
• Particularly effective for constipation with significant abdominal pain/bloating (superior to osmotic laxatives for both constipation and visceral pain) 3

Plecanatide (Strong Recommendation)

• Alternative secretagogue with similar mechanism to linaclotide 1, 2
• Use when linaclotide is not tolerated or unavailable 2

Lubiprostone (Conditional Recommendation)

• Dose: 24 mcg twice daily for chronic idiopathic constipation 5
• Take with food and water to reduce nausea 5
• Contraindicated in mechanical GI obstruction 5
• Caution: Syncope and hypotension reported, especially with first dose 5
• Dosage adjustment required for hepatic impairment: Child-Pugh B: 16 mcg twice daily; Child-Pugh C: 8 mcg twice daily 5

Fourth-Line: Prokinetic Agent

Prucalopride (Strong Recommendation)

• Dose: 2 mg orally once daily 1, 2, 3
• Mechanism: Selective 5-HT4 receptor agonist that enhances colonic motility through high-amplitude propagated contractions 3
• Consider if secretagogues fail or are not tolerated 2
• Works through a different mechanism than osmotic/stimulant laxatives 2

Special Situation: Opioid-Induced Constipation

For constipation clearly related to opioid therapy that has not responded to standard laxatives:

Preventive Strategy

• Prophylactic stool softener + stimulant laxative (senna, docusate 2 tablets every morning) when initiating opioids 1
• Increase laxative dose when increasing opioid dose 1

Treatment Algorithm

1. Titrate stool softener/laxatives with goal of one non-forced bowel movement every 1-2 days 1
2. If constipation persists, add bisacodyl, lactulose 30-60 mL daily, or PEG 1
3. Check for fecal impaction (treat with glycerin suppositories or manual disimpaction if present) 1, 3
4. Consider Fleet, saline, or tap water enema (avoid in neutropenia or thrombocytopenia) 1

Peripherally Acting Mu-Opioid Receptor Antagonists

When standard laxatives fail in opioid-induced constipation:

• Methylnaltrexone 0.15 mg/kg subcutaneously every other day (maximum once daily) 1
• Naloxegol (FDA-approved for opioid-induced constipation in chronic noncancer pain) 1
• Naldemedine (FDA-approved for opioid-induced constipation in chronic noncancer pain) 1
• Do NOT use in mechanical bowel obstruction or postoperative ileus 1
• Note: Effectiveness not established for diphenylheptane opioids (e.g., methadone) 5

Critical Management Pitfalls

• Discontinue docusate immediately if used alone—it provides no therapeutic benefit and is less effective than stimulant laxatives 3
• Do not continue escalating laxative doses indefinitely—if no response after 4-12 weeks of PEG, switch to prescription agents 2, 3
• Avoid fiber supplements for opioid-induced constipation—they are unlikely to be effective 1
• Consider anorectal testing if no response to first-line laxatives to identify defecatory disorders (dyssynergic defecation, pelvic floor dysfunction) 3
• Set realistic expectations: Complete symptom resolution is often not achievable; drug treatment is one component of multimodal management 3