Can metoprolol (beta-blocker) cause diarrhea in patients, particularly the elderly or those with a history of gastrointestinal disorders, and what is the mechanism behind it?

Metoprolol and Diarrhea: Etiology and Mechanism

Direct Answer

Metoprolol can cause diarrhea as an adverse effect, though this is relatively uncommon and the mechanism involves beta-adrenergic blockade affecting gastrointestinal motility regulation.

Evidence for Beta-Blockers Causing Diarrhea

While the provided guidelines focus primarily on other causes of diarrhea (chemotherapy, radiation, palliative care), the research evidence directly addresses beta-blocker-induced gastrointestinal effects:

• Propranolol (a non-selective beta-blocker) has been documented to cause severe diarrhea requiring drug discontinuation, with symptoms resolving upon cessation and recurring upon rechallenge 1
• The case report demonstrated dose-dependent diarrhea with propranolol 20 mg four times daily in a 71-year-old patient, which resolved at lower doses 1
• Beta-blockers are recognized among drugs that can induce diarrhea, though the exact mechanism is not always well-described 2

Mechanism of Action

The mechanism by which metoprolol (a beta-1 selective blocker) may cause diarrhea involves disruption of normal gastrointestinal motility regulation:

• Beta-adrenergic receptors physiologically modulate gastrointestinal motility, with beta-blockade increasing colonic motor activity 3
• Studies demonstrate that metoprolol increases sigmoid motility index in a dose-dependent manner in healthy subjects 3
• Beta-1 selective blockade with metoprolol also increases esophageal peristaltic amplitude in the distal smooth muscle portion 3
• The sympathetic nervous system normally exerts an inhibitory effect on gut motility through beta-adrenergic receptors; blocking these receptors removes this brake, leading to increased intestinal motor activity 3

Pathophysiological Classification

Drug-induced diarrhea can occur through several mechanisms 2, 4:

• Altered motility (most relevant for beta-blockers): Increased propulsive activity reduces transit time and water absorption 3, 4
• Changes in fluid secretion/absorption: Less likely with beta-blockers but possible through disruption of mucosal permeability 2
• Mucosal inflammation: Not typically associated with beta-blockers 4

Clinical Considerations

Risk Factors

• Elderly patients may be more susceptible to gastrointestinal side effects, as demonstrated in the case report of a 71-year-old patient 1
• Dose-dependent effects suggest higher doses of metoprolol may be more likely to cause symptoms 1, 3
• Patients with pre-existing gastrointestinal disorders may experience exacerbation of symptoms 3

Management Approach

• Consider metoprolol as a potential cause when diarrhea develops in patients receiving beta-blocker therapy 1
• Dose reduction may resolve symptoms without requiring complete discontinuation 1
• If diarrhea is severe, temporary discontinuation can confirm the diagnosis through resolution of symptoms 1
• Symptomatic treatment with loperamide or other opioid antimotility agents may be considered if the beta-blocker cannot be discontinued 2, 5

Important Caveats

• While metoprolol can cause diarrhea, this is not a common adverse effect and other causes should be thoroughly evaluated 2
• The mechanism is better established for non-selective beta-blockers (propranolol) than for beta-1 selective agents like metoprolol 1, 3
• Drug-induced diarrhea is usually mild to moderate and rarely necessitates treatment interruption 4