What are the dangers of anticholinergics, such as diphenhydramine, oxybutynin, and tiotropium, in vulnerable populations?

Dangers of Anticholinergics in Vulnerable Populations

Anticholinergic medications pose significant risks in vulnerable populations, particularly causing cognitive impairment, delirium, falls, and functional decline in older adults, with evidence showing that patients with high anticholinergic burden are almost three times more likely to be admitted for delirium.

Cognitive and Neurological Effects

• Anticholinergic medications cause significant cognitive impairment including memory problems, confusion, and delirium, especially in older adults due to age-related decline in acetylcholine physiology 1
• These medications can lead to central nervous system (CNS) effects including hallucinations, agitation, confusion, and somnolence, particularly in the first few months of treatment 2
• Anticholinergic burden is associated with increased risk of cognitive decline, with more pronounced effects in patients over 75 years 1
• The cumulative effect of multiple anticholinergic medications (anticholinergic burden) significantly increases risk of adverse cognitive outcomes 3, 1

Physical and Functional Risks

• Anticholinergic medications commonly cause physical adverse effects including dry mouth, blurred vision, constipation, and urinary retention 1, 2
• These medications significantly increase fall risk in older adults, which can lead to fractures and serious injuries 3, 1
• Functional decline is common with long-term use, with decreased activities of daily living (ADL) scores documented in multiple studies 3, 1
• Anticholinergics can cause gastrointestinal effects including decreased motility, which may lead to paralytic ileus or toxic megacolon in patients with ulcerative colitis 2

Cardiovascular and Other Systemic Risks

• Anticholinergics may worsen hypertension and complicate blood pressure management 1
• These medications can aggravate symptoms of hyperthyroidism, coronary heart disease, congestive heart failure, and cardiac arrhythmias 2
• Heat prostration (fever and heat stroke due to decreased sweating) can occur when anticholinergics are administered in high environmental temperatures 2
• In men, anticholinergics can exacerbate benign prostatic hyperplasia symptoms and cause urinary retention 1, 2

Specific Risks in Older Adults

• Older adults are more sensitive to anticholinergic effects due to physiological changes in aging 1
• The Beers Criteria and STOPP/START criteria identify many anticholinergic medications as potentially inappropriate for older adults 3
• Studies show that approximately one-third of independent living older adults and half of those in long-term care facilities take medications with anticholinergic properties that may be unnecessary 3
• Higher Anticholinergic Risk Scale (ARS) scores are associated with statistically significantly increased risk of anticholinergic adverse effects in older patients 4

Medication-Specific Concerns

• Older antihistamines such as diphenhydramine have strong anticholinergic effects with significant CNS impairment 3
• Muscle relaxants like cyclobenzaprine have strong anticholinergic properties 3
• Overactive bladder medications like oxybutynin have broad muscarinic receptor blockade resulting in negative effects on vision, urination, constipation, and cognition 3, 2
• Tiotropium, while having fewer systemic effects than some anticholinergics, still requires monitoring in patients with moderate to severe renal impairment for potential anticholinergic side effects 5

Drug Interactions and Polypharmacy

• Concomitant use of anticholinergics with other anticholinergic drugs increases the frequency and severity of adverse effects 2
• Anticholinergics may alter the absorption of some concomitantly administered drugs due to effects on gastrointestinal motility 2
• When combined with other CNS-active substances, anticholinergics can cause enhanced performance impairment and sedation 1, 2
• Polypharmacy is associated with increased anticholinergic burden in advanced cancer and likely reflects the increasing use of medications with anticholinergic activity for symptom control 3

Clinical Recommendations

• Avoid anticholinergic medications in older adults whenever possible, particularly those with existing cognitive impairment, dementia risk factors, or narrow-angle glaucoma 1
• For patients requiring anticholinergic medications, use the lowest effective dose for the shortest duration possible 1
• Regularly review medication regimens to identify and reduce anticholinergic burden, particularly in older adults 3
• Consider deprescribing anticholinergic medications in older adults as part of medication management 3
• Monitor patients with moderate to severe renal impairment closely for potential anticholinergic side effects 5

Common Pitfalls and Caveats

• Anticholinergic effects are often overlooked or attributed to aging or underlying disease processes rather than medication effects 6
• The cumulative anticholinergic burden from multiple medications with modest anticholinergic activity may be underestimated 7
• Discontinuation of anticholinergic medications should be done gradually to avoid withdrawal symptoms 3
• Patients with dementia are particularly vulnerable to anticholinergic effects, yet paradoxically may be prescribed these medications for behavioral symptoms 8
• Anticholinergic medications may antagonize the effects of cholinesterase inhibitors used to treat dementia, potentially reducing their efficacy 2