A Case of Bradycardia and Urinary Symptoms from Donepezil Therapy

Patient Background:

An 82-year-old female with a history of mild Alzheimer’s dementia was initiated on donepezil 10 mg nightly to enhance cognitive function and memory performance. The patient had no significant cardiovascular history and was otherwise clinically stable prior to therapy initiation.

Learn more about Alzheimer here Alzheimer’s Disease: A Comprehensive Scientific Overview

Clinical Presentation:

After several weeks of treatment, her family observed increased urinary urgency during the day and frequent nocturnal awakenings to urinate. Believing these symptoms to be due to overactive bladder, her primary care provider prescribed oxybutynin 5 mg twice daily for symptomatic control.

Check out a case scenario on urinary frequency Diuretic-Related Urinary Frequency in an Older Adult

A few weeks later, during a routine follow-up visit, the patient reported lightheadedness and fatigue. Her heart rate was recorded at 48 beats per minute, and an ECG confirmed sinus bradycardia.

Clinical Issue Identified:

The patient’s constellation of symptoms — urinary frequency and bradycardia — are both consistent with adverse cholinergic effects of donepezil, a reversible acetylcholinesterase inhibitor. By increasing acetylcholine concentrations in the central nervous system, donepezil improves cognition in Alzheimer’s disease. However, elevated acetylcholine levels also stimulate peripheral muscarinic receptors, producing unwanted parasympathetic effects such as urinary frequency, gastrointestinal upset, and cardiac conduction slowing.

The subsequent addition of oxybutynin, a potent antimuscarinic agent, represents a pharmacologic mismatch — it antagonizes acetylcholine’s effects, directly opposing the therapeutic action of donepezil. This addition not only undermines the intended cognitive benefit but also introduces further anticholinergic risks (confusion, constipation, dry mouth, and delirium) in an elderly, cognitively vulnerable patient.

Pharmacist Intervention and Clinical Management:

Medication Review and Assessment:

• Recognize that the urinary frequency and bradycardia likely stem from donepezil’s cholinergic activity.

• Confirm the temporal relationship between donepezil initiation and the onset of urinary symptoms.

• Identify the pharmacodynamic opposition between donepezil and oxybutynin, leading to therapeutic antagonism.

Therapeutic Optimization:

• Deprescribe oxybutynin to eliminate the anticholinergic burden and avoid interference with donepezil’s efficacy.

• Consider reducing donepezil to 5 mg nightly or switching to an alternative cholinesterase inhibitor (e.g., rivastigmine patch) if urinary side effects remain intolerable.

• Avoid use of systemic antimuscarinics; if urinary symptoms persist, nonpharmacologic measures or peripherally selective β₃-agonists (e.g., mirabegron) may be safer alternatives.

Monitoring and Safety Measures:

• Perform cardiac monitoring for bradyarrhythmia or symptomatic hypotension; consider cardiology review if bradycardia persists.

• Reassess cognitive function and urinary symptoms 2–4 weeks after medication adjustments.

• Educate family members and caregivers about potential cholinergic and anticholinergic side effects to facilitate early detection.

Collaborative Communication:

• Communicate findings and recommendations to the prescriber to support deprescribing and medication reconciliation.

• Document the pharmacologic conflict and clinical impact to prevent recurrence of similar therapeutic duplications.

Clinical Rationale and Ramifications

This case exemplifies how symptom-focused prescribing without reviewing underlying causes can lead to drug–drug opposition and avoidable harm in older adults. The addition of oxybutynin to counteract donepezil-induced urinary frequency reflects a failure to recognize drug-induced etiology before initiating new therapy. The result was a reduction in donepezil’s cognitive benefit, increased risk of anticholinergic adverse effects, and emergence of symptomatic bradycardia, likely secondary to excessive cholinergic stimulation.

By identifying the mechanistic overlap and adjusting therapy, the pharmacist plays a crucial role in restoring therapeutic alignment, reducing medication burden, and preventing iatrogenic complications.

This case reinforces the principle that every new symptom in a medicated older adult warrants a medication review before adding another drug. Thoughtful deprescribing and awareness of opposing pharmacodynamic mechanisms are essential in optimizing therapy for patients with dementia and minimizing harm from avoidable medication conflicts.