Loperamide 💊

🚫 Avoid if pseudomembranous colitis (C. difficile) is suspected - it may worsen toxin retention and precipitate toxic megacolon. 💊 Loperamide is an opioid-receptor agonist that reduces bowel motility and fluid loss, improving stool consistency.

🧠 About

• Antidiarrhoeal agent derived from the piperidine family (related to opiates but does not cross the blood–brain barrier at therapeutic doses).
• Acts locally in the gut to slow intestinal transit and enhance water reabsorption.
• Commonly used for acute non-infective diarrhoea, chronic diarrhoeal states (e.g. IBS-D), and to control ileostomy output.
• Onset within 1–3 hours; duration up to 10 hours.

⚙️ Mode of Action

• Binds to μ-opioid receptors in the myenteric plexus of the intestinal wall.
• Reduces peristaltic activity and increases anal sphincter tone, slowing stool passage and promoting fluid absorption.
• Does not cross the blood–brain barrier due to P-glycoprotein efflux transporters - minimal CNS effects unless abused in very high doses.
• Decreases secretion of electrolytes and water into the bowel lumen.

🎯 Indications

• Acute diarrhoea (including traveller’s diarrhoea).
• Chronic diarrhoea (e.g. in IBS, post-resection, or following radiotherapy).
• Control of high-output ileostomy or jejunostomy.
• Adjunct in faecal incontinence to reduce stool frequency and urgency.

💊 Dose

• Acute diarrhoea: 4 mg initially, then 2 mg after each loose stool (max 16 mg/day). Continue for up to 5 days. Stop if symptoms persist or patient becomes systemically unwell.
• Chronic diarrhoea: 4–8 mg daily in divided doses (titrate to response; max 16 mg/day).
• Faecal incontinence: 0.5–1 mg twice daily (low-dose titration preferred in elderly).
• High-output stoma: up to 2–4 mg QDS under specialist supervision.

⚠️ Cautions

• 🚸 Avoid in children under 12 years (risk of paralytic ileus).
• ❗ Do not use if C. difficile or other infectious diarrhoea suspected - risk of toxic megacolon.
• ⚕️ Caution in hepatic impairment or frailty - risk of CNS toxicity at higher plasma levels.
• 💧 Ensure adequate hydration and electrolyte replacement.

🚫 Contraindications

• Acute ulcerative colitis flare or pseudomembranous colitis.
• Bloody diarrhoea or high fever (possible infection).
• Intestinal obstruction, abdominal distension, or paralytic ileus.
• Acute dysentery with mucus and blood.

💊 Adverse Effects

• Common: constipation, abdominal cramps, nausea, dizziness, dry mouth.
• Occasional: flatulence, fatigue, or rash.
• Rare: paralytic ileus, toxic megacolon (especially if used in infectious diarrhoea).
• ⚠️ Very high doses (abuse) can cause cardiac arrhythmias due to QT prolongation and torsades de pointes.

🤰 Pregnancy and Breastfeeding

• Generally safe in pregnancy for short-term use, though avoid in first trimester if possible.
• Minimal transfer to breast milk - compatible with breastfeeding for short courses.

🩺 Clinical Pearls

• For hospitalised patients, always exclude infective diarrhoea before prescribing.
• In high-output stomas, combine with codeine phosphate and oral rehydration salts to optimise absorption.
• Patients with chronic diarrhoea due to bile salt malabsorption may benefit more from cholestyramine.

💡 Teaching Points

• Helps learners distinguish between opioid agonists (which act centrally, e.g. codeine) and loperamide (which acts peripherally).
• Excellent case-based teaching opportunity: “Why would loperamide worsen C. diff diarrhoea?” → because slowing transit traps toxins in the colon.
• Explain the concept of toxic megacolon as a risk of using antimotility agents in inflammatory or infective colitis.

📚 References

• BNF: Loperamide
• NICE CKS: Diarrhoea - adult assessment (2024)
• Farthing MJ. Gut 2015;64:84–92 - Antimotility drugs in diarrhoea.