What considerations should be taken when prescribing medications with anticholinergic (anticholinergic) properties, particularly those with mimetic effects?

Prescribing Medications with Anticholinergic Properties

When prescribing medications with anticholinergic properties, prioritize agents with the lowest anticholinergic burden, avoid combining multiple anticholinergic drugs, and systematically deprescribe these medications in elderly patients to prevent cognitive decline, falls, and functional impairment.

Understanding Anticholinergic Effects

Anticholinergic medications block acetylcholine receptors in both central and peripheral tissues, producing a predictable constellation of adverse effects 1, 2:

Central manifestations include:

• Agitated delirium, confusion, and hallucinations 3
• Disorientation and anxiety 3
• Cognitive impairment and memory deficits 4, 1
• Seizures in severe cases 3

Peripheral manifestations include:

• Dry mouth and mucous membranes 4, 3
• Constipation and hypoactive bowel sounds 3
• Urinary retention 4, 3
• Tachycardia 3
• Blurred vision and mydriasis 3
• Hot, dry, erythematous skin 3

High-Risk Medications to Avoid or Use Cautiously

First-generation antipsychotics with significant anticholinergic burden:

• Chlorpromazine causes sedation, anticholinergic effects, and orthostatic hypotension 4
• Methotrimeprazine (levomepromazine) produces sedating and anticholinergic effects 4

Tricyclic antidepressants:

• Amitriptyline and imipramine have balanced anticholinergic properties and should be started at 10 mg/day in elderly patients, with caution above 100 mg/day due to cardiac risks 4
• Nortriptyline has fewer anticholinergic properties than tertiary amines and is better tolerated 4

Antihistamines:

• Diphenhydramine causes anticholinergic effects, oversedation, and confusion, requiring caution in elderly patients 4
• Promethazine has dopamine antagonist properties with antihistaminergic and anticholinergic effects 4

Critical Drug Interactions and Contraindications

Avoid anticholinergics in patients with:

• Anticholinergic delirium or intoxication from drugs with anticholinergic properties (e.g., hallucinogens), as antipsychotics may worsen the condition 4
• Dementia or Parkinson's disease, where anticholinergic burden accelerates cognitive decline 4, 1
• Glaucoma, benign prostatic hypertrophy, or myasthenia gravis 4

Do not combine:

• Multiple anticholinergic agents, as this creates cumulative anticholinergic burden 1, 5
• Benztropine or trihexyphenidyl with antipsychotics in elderly Alzheimer's patients 4, 3

Elderly Population: Special Considerations

Older adults face disproportionate risk because:

• One-third to one-half of medications prescribed to elderly patients have anticholinergic activity 1
• Baseline cognitive impairment and reduced physiologic reserve increase vulnerability 3
• Anticholinergic burden predicts cognitive decline, functional impairment, falls, and mortality 1, 5, 6

In elderly patients, strongly anticholinergic medications should be avoided entirely 3

Systematic Deprescribing Algorithm

Step 1: Discontinue medications used solely to manage side effects of other drugs 3

• For example, stop anticholinergics prescribed to counteract extrapyramidal symptoms from antipsychotics 3

Step 2: Reduce doses to minimum effective levels 3

• Start with lower doses in older or frail patients (e.g., haloperidol 0.25-0.5 mg instead of 0.5-1 mg) 4

Step 3: Switch to alternatives with lower anticholinergic activity 3

• For antipsychotics: switch from high anticholinergic agents to those with lower burden while remaining within therapeutic range 3
• For antidepressants: switch from tertiary amine tricyclics (amitriptyline) to secondary amines (nortriptyline) 4, 3
• For overactive bladder: switch from anticholinergic agents to beta-3 adrenergic receptor agonists 3

Step 4: Use gradual tapering rather than abrupt discontinuation to avoid withdrawal symptoms or rebound worsening 3

Monitoring Requirements

Before initiating therapy:

• Record baseline measures of abnormal movements using the Abnormal Involuntary Movement Scale 4
• Obtain baseline electrocardiogram if prescribing agents that prolong QTc interval 4
• Measure orthostatic vital signs 7

During ongoing therapy:

• Assess for dyskinesias every 3-6 months 4
• Monitor for anticholinergic effects: dry mouth, constipation, urinary retention, confusion 4, 3
• Regular medication reviews to identify and minimize anticholinergic burden 3

Acute Anticholinergic Toxicity Management

Immediate treatment protocol 3:

• Stop all anticholinergic medications immediately, including first-generation antihistamines, muscle relaxants, overactive bladder agents, tricyclic antidepressants, phenothiazines, and anticholinergics used for antipsychotic side effects 3
• Administer physostigmine 0.5-1 mg IV in adults (0.01-0.02 mg/kg in children) to reverse both central and peripheral effects within minutes 3
• Provide supportive care with benzodiazepines for agitation 3

Common Pitfalls to Avoid

Do not use the AM/PM dosing strategy with first-generation antihistamines 3

• Bedtime dosing still causes significant daytime drowsiness and performance impairment due to prolonged half-lives 3

Anticholinergic effects persist longer than plasma drug levels 3

• Symptoms may continue even after drug levels decline, requiring extended monitoring 3

Do not assume all drugs within a class have equal anticholinergic burden 4, 3

• Significant variation exists even among similar medications (e.g., nortriptyline vs. amitriptyline) 4

Benefits of Deprescribing

Documented improvements from reducing anticholinergic burden 3:

• Prevention of falls 3
• Reversal of cognitive decline 3
• Improved functional status and activities of daily living scores 3
• Enhanced quality of life 6

Specific Clinical Scenarios

For COPD patients requiring bronchodilators:

• Ipratropium bromide (anticholinergic) has no effects on urine flow or pupil size at normal doses except with ill-fitting nebulizer masks allowing direct eye administration 4
• Anticholinergics are more effective than beta-2 agonists in COPD and do not cause the fall in PaO2 seen with beta-2 agonists 4
• No evidence of tolerance develops with chronic anticholinergic therapy in COPD 4

For agitated pediatric patients:

• Because of anticholinergic properties, antipsychotics may worsen conditions in patients presenting with intoxication from drugs with anticholinergic properties 4
• Monitor closely for paradoxical behavioral disinhibition, especially in younger children and those with developmental disabilities 4

For cancer patients with delirium:

• Antipsychotics and benzodiazepines can themselves cause increased agitation and delirium 4
• Use short-term medication in the lowest effective dose only if the patient has perceptual disturbances 4