Key Facts

The elderly are the largest consumers of prescribed medications and the most vulnerable to adverse drug effects. Age-related physiological changes, multi-morbidity, and polypharmacy combine to create a high-risk prescribing environment.

Epidemiology

• UK: >65s represent ~18% of population but receive ~50% of all prescriptions
• ~30% of >65s take ≥5 regular medications
• ADRs: ~10% of hospital admissions in elderly; >70% preventable
• Falls: medication-related falls account for significant morbidity and mortality

Pharmacokinetic Changes

• Absorption: relatively unchanged; slight reduction in gastric acid and motility
• Distribution: increased body fat → increased Vd for lipophilic drugs (diazepam, amiodarone); decreased lean body mass → decreased Vd for water-soluble drugs; decreased albumin → increased free fraction
• Metabolism: reduced hepatic blood flow (~40% decrease), reduced CYP450 activity → slower drug metabolism
• Excretion: reduced GFR (~1 mL/min/year decline after 40) → reduced renal drug clearance; serum creatinine may be misleadingly normal due to reduced muscle mass

Pharmacodynamic Changes

• Increased sensitivity to CNS drugs (benzodiazepines, opioids)
• Increased sensitivity to anticoagulants
• Impaired baroreceptor reflexes → postural hypotension with antihypertensives
• Reduced beta-adrenoceptor sensitivity → reduced response to beta-agonists
• Impaired thermoregulation → hypothermia risk with sedatives

Pathophysiology

• Physiological reserve declines with age → reduced ability to compensate for drug effects
• Homeostatic mechanisms (baroreceptors, glucose regulation, temperature) less effective
• Cognitive impairment → medication non-adherence and error
• Frailty → increased vulnerability to adverse drug effects

Common ADR Presentations in Elderly

• Falls: sedatives, antihypertensives (postural hypotension), anticholinergics, hypoglycaemics
• Confusion/delirium: anticholinergics, opioids, benzodiazepines, corticosteroids, digoxin toxicity
• GI bleeding: NSAIDs, anticoagulants, antiplatelet agents (especially combined)
• Constipation: opioids, anticholinergics, calcium channel blockers, iron
• Urinary retention: anticholinergics, opioids
• Electrolyte disturbance: diuretics (hyponatraemia, hypokalaemia), ACE-i (hyperkalaemia)
• Hypoglycaemia: sulfonylureas, insulin — particularly dangerous in elderly (masquerades as confusion/falls)

Prescribing Cascade

• Very common in elderly: ADR misdiagnosed as new condition → new drug → further ADRs
• Examples: NSAID → hypertension → antihypertensive → postural hypotension → fall → fracture

Red Flags

• Acute confusion: drug-induced until proven otherwise (anticholinergics, opioids)
• Falls: medication review should be part of every falls assessment
• AKI: 'triple whammy' — NSAID + ACE-i + diuretic
• Unexpected deterioration after medication change → suspect ADR

Medication Review Tools

• STOPP/START criteria: most widely validated in UK/Europe
• Beers criteria: American Geriatrics Society
• Anticholinergic Burden Calculator (ACB): quantify cumulative anticholinergic load
• NO TEARS: Need, Open questions, Tests, Evidence, Adverse effects, Risk, Simplification

Bloods

• U&Es: renal function — serum creatinine may underestimate impairment; calculate eGFR or CrCl
• LFTs: hepatic function
• FBC: drug-induced cytopenias, anaemia from GI bleeding
• HbA1c: glycaemic targets may be relaxed in frail elderly
• Calcium, vitamin D, bone profile: osteoporosis screening and drug monitoring
• Drug levels: TDM for narrow TI drugs (digoxin, phenytoin, lithium)

Other Assessments

• Lying/standing BP: assess postural hypotension
• Cognitive assessment: AMT, MMSE — baseline and if confusion develops
• Falls risk assessment: multifactorial including medication review
• Frailty assessment: Clinical Frailty Scale, Rockwood — guides treatment intensity

General Principles

• 'Start low, go slow': start at 50% of adult dose for many drugs; titrate gradually
• Regular medication review: at least annually; more frequently if frail, in care home, or recent hospital discharge
• Deprescribe: identify and stop unnecessary/harmful medications
• Simplify regimens: once-daily dosing, combination tablets, dosette boxes
• Adherence support: carer involvement, blister packs, medication reminders

Key Prescribing Considerations

• Renal function: always calculate; adjust doses accordingly
• Avoid anticholinergics: if possible — ACB score should be minimised
• Avoid benzodiazepines/Z-drugs: falls, confusion, paradoxical agitation — deprescribe if possible
• NSAIDs: avoid if possible — GI bleeding, renal impairment, fluid retention, cardiovascular risk
• BP targets: may be more lenient in frail elderly (≥150/90 mmHg in ≥80 years per NICE NG136)
• HbA1c targets: relaxed in frail elderly (53–64 mmol/mol or higher) to avoid hypoglycaemia
• Statins: consider stopping in frail elderly with limited life expectancy and no recent CVD event

Falls Prevention

• Review and reduce fall-risk medications
• Avoid polypharmacy where possible
• Lying/standing BP assessment
• Home hazard assessment

Referral Criteria

• Geriatric medicine: complex polypharmacy, frailty, falls
• Clinical pharmacology/pharmacy: structured medication review
• Falls clinic: medication-related falls
• Old age psychiatry: medication management with dementia

• Structured medication review reduces ADRs, falls, and hospitalisations
• Deprescribing in appropriate patients is safe and improves outcomes
• Falls prevention (including medication review) significantly reduces fall-related injuries and fractures
• Patient satisfaction often improves with reduced pill burden
• Failure to address inappropriate prescribing in elderly contributes to significant preventable morbidity and mortality

Potentially Inappropriate Medications in Elderly (STOPP Examples)

Age-Related PK Changes Summary