Geriatric Considerations

Absorption Changes in Elderly Individuals

• Decreased gastric distribution → increase gastric pH

• Delayed gastric emptying and decreased GI motility

• Decrease splanchnic blood flow

• Impact → minimal (most drugs still absorbed well)

  • Exception: ketoconazole, iron, calcium

Distribution Changes in Elderly Individuals

• Increased body fat by 20-40% → lipophilic drugs (diazepam, amiodarone) have prolonged half life (increased Vd)

• Decreased total body water by 10-15% → hydrophilic drugs (digoxin, lithium) have increased peak levels (decreased Vd)

• Decreased plasma albumin → protein bound drugs (warfarin, phenytoin) have increased free drug fraction

Highly Protein Bound Drugs

Have increased risk with albumin

• Warfarin

• Phenytoin

• Heparin

• Amiodarone

• Furosemide

• Most statins (except pravastatin)

PEARL: decreased albumin → increased free drug → enhanced effect and toxicity risk

Hepatic Metabolism in Elderly Individuals

• ↓ liver mass (~20–30% by age 80)

• ↓ hepatic blood flow (20–50%)

• ↓ phase I metabolism (CYP450): most clinically significant

• Phase II (conjugation) relatively preserved

• Affected drugs:

  • Propranolol

  • Diltiazem

  • Verapamil

  • Morphine

  • Lidocaine

• No lab test to quantify hepatic capacity — use clinical judgment

Renal Excretion in Elderly Individuals

MOST CRITICAL

• Progressive ↓ GFR (~0.9%/yr after age 20)

• ↓ renal blood flow + ↓ tubular secretion

• ⚠ Serum creatinine is UNRELIABLE — low muscle mass masks reduced GFR

• Always use validated eGFR equations for dosing decisions

High Risk Renally Cleared Drugs that Require Dose Adjustments

• Anticoagulants:

  • DOACs (apixaban, rivaroxaban, dabigatran)

  • Enoxaparin

• Antibiotics:

  • Aminoglycosides

  • Vancomycin

  • Fluoroquinolones

• CV:

  • Digoxin

  • Atenolol

  • Sotalol

  • ACE inhibitors 

• Analgesics:

  • Morphine (M6G)

  • Gabapentin

  • Pregabalin  

• Others:

  • Metformin

  • Lithium

Pharmacokinetic Changes Summary

Increased Sensitivity

• Benzodiazepines: sedation, falls, cognitive impairment

• Opioids: ↑ mu-receptor sensitivity → respiratory depression, delirium

• Anticoagulants: greater bleeding risk at therapeutic levels

• Anti-diabetics: increased hypoglycemia risk

• Psychotropics: anticholinergic effects, EPS

Decreased Sensitivity

• Beta-adrenergic agonists/antagonists: reduced receptor density and responsiveness

• Some antihypertensives may have blunted efficacy

Impaired Homeostatic Mechanisms

• ↓ baroreceptor sensitivity → orthostatic hypotension (vasodilators, diuretics, alpha-blockers)

• ↓ thirst response → dehydration with diuretics  

• ↓ cognitive reserve → drug-induced delirium threshold lower

Double Jeapordy

Higher drug levels (PK) + Greater sensitivity (PD) = compounded risk in older adults

Polypharmacy: Geriatric Syndromes Exacerbated

• Falls

  • Sedatives

  • Antihypertensives

  • Anticholinergics

• Cognitive impairment/delirium

  • Anticholinergics

  • Benzodiazepines

  • Opioids

• Urinary incontinence

  • Diuretics

  • Cholinesterase inhibitors

• Functional decline and frailty

• Non-adherence from complex regimens

Polypharmacy: Risk Factors

• Multiple chronic conditions

• Multiple prescribers/sub-specialists

• Transitions of care

• Long term care settings

The Prescribing Cascade

• A new medication is prescribed to treat an adverse effect of an existing medication, misinterpreted as a new medical condition

• Clinical pearl: before adding any new medication, always ask if the current symptom could be caused by the current medication

High Risk Drug-Drug Combinations

• Anticoagulant + anti-platelet → major bleeding risk

• Multiple CNS depressants (opioids + benzodiazepines) → respiratory depression

• Multiple QT-prolonging agents → torsades de pointes

• Warfarin + NSAID → GI bleed / INR elevation

• ACE inhibitor + potassium-sparing diuretic → hyperkalemia

• CYP inhibition/induction interactions compounded by already-reduced hepatic capacity

High Risk Drug-Drug Interactions

• Anticholinergics in dementia → worsened cognition

• NSAIDs in CKD → acute kidney injury

• NSAIDs in heart failure → fluid retention, decompensation

• Beta-blockers in severe COPD → bronchoconstriction

• Opioids in fall history → increased fall risk

• Benzodiazepines in dementia → delirium, falls

• Fluoroquinolones in tendinopathy history → tendon rupture

AGS Beer Criteria

• Applies to adults >= 65 y/o (except hospice/palliative care)

• 1 → avoid in most older adults

  • Long acting benzodiazepines

  • First generation antihistamines

  • Chronic NSAIDs

  • Sliding scale insulin

• 2 → avoid with specific diseases

  • Anticholinergics in dementia

  • TCAs in fall history

  • NSAIDs in CKD/HF

• 3 → use with caution

  • Aspirin for primary prevention > 70 y/o

  • Dabigatran in adults > 75 y/o

  • Tramadol

• 4 → drug-drug interactions

  • Opioid and benzodiazepines

  • Warfarin and NSAIDs

  • ACE-I and K-sparing diuretic

• 5 → renal dose adjustment

  • Medications requiring dose reduction or avoidance based on kidney function → DOACs, metformin

Beers Criteria: Anticholinergics

• HIGH RISK

• Examples: diphenhydramine, hydroxyzine, antispasmodics, TCAs

• Effects:

  • Confusion

  • Urinary retention

  • Falls

  • Tachycardia

Beers Criteria: Benzodiazepines and Z-drugs

• AVOID

• Effects

  • Falls

  • Cognitive impairment

  • Dependence

Beers Criteria: antipsychotics

• BLACK BOX

• Avoid in dementia related behavioral symptoms → increased mortality

• Exceptions

  • Quetiapine, clozapine, pimavanzserin for Parkinson psychosis

Beers Criteria: opioids

• CAUTION

• Avoid with concurrent BZD use

• Avoid in fall history

• Tramadol → high risk of SIADH/hyponatremia

Beers Criteria: PPIs

• LIMIT

• Avoid beyond 8 weeks without clear ongoing indication: can cause C. diff, hypomagnesemia, and/or fractures

Beers Criteria: dabigatran and rivaroxaban

• CAUTION

• Higher bleeding risk in older adults compared to apixaban

• Consider renal function closely

STOPP Criteria

• Screening Tool of Older Persons' Prescriptions

• 65 indicators by physiological system

• Addresses DDIs, drug-disease, fall risk, duplication

• More sensitive than Beers for detecting ADEs in some studies

• European standard (Ireland)

• STOPPFrail

  • Designed for frail older adults with limited life expectancy (≤1 year)

  • Guides de-prescribing of medications unlikely to provide benefit within remaining lifespan

START Criteria

• Screening Tool to Alert to Right Treatment

• Identifies beneficial medications that are OMITTED

  • Statins in CV disease; anticoagulation in A-fib

  • Osteoporosis treatment after fragility fracture → vaccinations

• Addresses under-prescribing — the counterpart to overuse

MAI (Implicit Criteria)

• Evaluates each medication across 10 domains

  • Indication

  • Effectiveness

  • Correct dosage

  • Directions

  • Drug-drug interactions

  • Drug-disease interactions

  • Duplication

  • Duration

  • Cost-effectiveness

• Highly individualized and time-intensive

Dose Adjustment in Older Adults

• Start low, go slow - but don’t stop too low

• Begin at 25–50% of standard adult dose

• Titrate slowly — longer intervals between changes

• Monitor more frequently during titration

• Ensure therapeutic targets are achieved

• Renal dose adjustment

  • ALWAYS calculate eGFR before prescribing renally cleared drugs

  • DO NOT rely on serum creatinine alone

  • Narrow therapeutic index drugs (digoxin, lithium, aminoglycosides): consider cystatin C-based eGFR

  • Regular reassessment — eGFR may decline further with acute illness

• Hepatic metabolism

  • No reliable lab test for hepatic metabolic capacity

  • Prefer Phase II drugs when possible

    • "LOT" drugs: Lorazepam, Oxazepam, Temazepam over diazepam

• Therapeutic drug monitoring when available (digoxin, vancomycin, phenytoin) → check free levels

When to De-prescribe

• Time to benefit exceeds life expectancy

• Medication was prescribed for a resolved condition

• Adverse effects outweigh benefits

• No clear indication identifiable

• Therapeutic duplication exists

• Goals shifted toward comfort-focused care

Common Targets for De-prescribing

• Proton pump inhibitors (>8 weeks without indication)

• Benzodiazepines and Z-drugs

• Antipsychotics in dementia without psychosis

• Statins with limited life expectancy and no active CVD

• Bis-phosphonates after 3–5 years (drug holiday)

• Cholinesterase inhibitors in advanced dementia

• Chronic NSAIDs

De-Prescribing Process

1. Compile complete medication list (including OTC, supplements, herbals) 

2. Identify inappropriate/unnecessary meds (Beers/STOPP) 

3. 3. Prioritize (highest risk, least benefit first) 

4. Plan taper when needed (BZDs, opioids, beta-blockers, SSRIs — do NOT stop abruptly) 

5. Monitor for withdrawal/recurrence 

6. Document & communicate

ARMOR Framework for Medication Review

A: Assess

• Compile and assess all current medications, including OTC drugs, supplements, and herbals

R: Review

• Review each medication for potential adverse effects, toxicity, and drug interactions

M: Minimize

• Minimize the total number of medications

• Eliminate those without clear indications

O: Optimize

• Optimize doses for age related changes

• Adjust schedules to simplify regimens

R: Reassess

• Reassess at regular intervals → with each visit, acute illness, and care transition

Long Term Care Residents

• Highest risk for polypharmacy — multiple chronic conditions and multiple prescribers

• Federal regulations require regular medication regimen reviews

• Antipsychotic reduction programs are mandated in many facilities

Multiple Sub-Specialites

• Each specialist prescribes within their domain without full awareness of the complete medication list

• PA's role as primary care provider/care coordinator is critical for reconciliation

Frail Older Adults/Limited Life Expectancy

• STOPPFrail criteria guide de-prescribing

• Shift from disease-oriented to symptom-oriented prescribing

• Beers Criteria explicitly exclude hospice/end-of-life patients

Transitions of Care

• Hospital admission, discharge, and transfers = high-risk periods for medication errors

  • Up to 50% of medication errors occur during transitions of care

• Medication reconciliation at EVERY transition is essential

Clinical Pearls in Geriatric Pharmacology

• PK changes (especially decreased renal clearance and altered distribution) requires systemic dose adjustment → never rely on serum creatinine alone

• Pharmacodynamic sensitivity is increased for many drug classes, creating a double jeopardy effect compounding PK changes

• Before adding and new medications, always ask could this symptom be an adverse effect of a current medication (avoid the prescribing cascade)

• Apply Beers Criteria and STOPP/START at every medication review — but use clinical judgment as these are guides, not mandates

• De-prescribing is a clinical skill requiring the same rigor as prescribing, including monitoring and follow-up

• "Start low, go slow — but don't stop too low": individualize therapy to achieve therapeutic goals while minimizing risk

• Medication reconciliation at every visit and every transition of care is a patient safety imperative