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Pharmacologic
Considerations
Geriatrics

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Introduction
 In the US, the elderly (>65y/o) constitute ~12% of
the total population, but account for almost 30% of
total drug expenditure
 Age-related physiologic changes make the elderly
susceptible to adverse effects
 Understanding the influence these changes have
on the pharmacokinetics and pharmacodynamics of
the elderly is essential to prevent harm

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Physiologic Changes of Aging
Affecting Absorption
 Physiologic change
– Decreased gastric acidity
– Decreased gastrointestinal blood flow
– Delayed grastric emptying
– Slowed intestinal transit time
 General clinical effect
– None on passive diffusion or bioavailability for most drugs
– Decreased active transport: Decreased bioavailability for
some drugs
– Decreased first-pass effect: Increased bioavailability for
some drugs
 Special considerations
– Antacids decrease absorption of acidic drugs: digitalis,
phenytoin, tetracycline
– Anticholinergics: Slow GI motility and absorption rate

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Physiologic Changes of Aging
Affecting Distribution
 Decreased Total body water
– Decreased Volume Distribution
– Increased Plasma Conc. of water soluble drugs
– Lower doses are required: Lithium, digoxin, ethanol, etc
 Decreased Lean body mass and Increased body fat
– Increased Volume Distribution, Longer (t½) of water
soluble drugs
– Accumulation into fat of lipid soluble drugs: Benzos, etc
 Decreased Serum Albumin
– Increased unbound fraction of highly protein bound drugs
– Binds acidic drugs: warfarin, phenytoin, digitalis, etc
 Decreased Alpha1 Acid glycoprotein
– Increased unbound fraction of highly protein bound drugs
– -Binds basic drugs: lidocaine and propranolol, etc

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Metabolism
 Determined
– Primarily by hepatic function and blood flow
– Capacity of the liver to metabolize drugs does not appear
to decline consistently with age for all drugs

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Elimination
 Determined
– Primarily by renal function
– Declines with age and is worsened by co-morbidities
– Decline is not reflected in an equivalent rise in serum
creatinine since creatinine production is reduced due to
lower muscle mass

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Physiologic Changes of Aging
Affecting Elimination
 Physiologic change
– Decreased GFR
– Decreased renal blood flow
– Decreased renal mass
 General clinical effect
– Decreased clearance, Increased (t½) of renally eliminated
drugs

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Pharmacodynamics
 Pharmacodynamic changes in the elderly have
been less extensively studied
 Evidence of enhanced end-organ responsiveness
or “sensitivity” to medications with aging
 Enhanced “sensitivity” may be due
– Changes in receptor affinity
– Changes in receptor number
– Post-receptor alteration
– Age-related impairment of homeostatic mechanisms
Example: decreased baroreceptor reflexes

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Major Drug Groups Requiring
Monitoring
 CNS drugs
– Sedative-hypnotics: Benzodiazepines and barbiturates
– Analgesics: Opioids
– Antipsychotic, antidepressants: Haloperidol, lithium, TCAs
 Cardiovascular drugs
– Antihypertensives: Thiazides, beta-blockers
 Antiarrhythmic drugs
– Quinidine and procainamide: ↓ clearance and ↑ (t½)
 Antimicrobial drugs
– Beta-lactams and aminoglycosides: ↓ clearance
 Anti-inflammatory drugs
– NSAIDs: GI bleed and irritation

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Major Reasons for Adverse Drug
Reactions in the Elderly
 Positive relationship between number of drugs taken
and incidence
 Overall incidence is estimated to be at least twice
that in the younger population
 Prescribing errors
– Polypharmacy
– Drug interactions with other prescriptions
– Unawareness of age related physiologic changes
 Drug usage errors
– “Hidden ingredients”: OTCs

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Compliance
 There are several practical obstacles to compliance
that the prescriber must recognize
– Forgetfulness
– Prior experience
– Physical disabilities
 Recommendations to improve compliance
– Take careful drug history
– Prescribe only for a specific and rational indication
– Define goal of drug therapy
– High index of suspicion regarding drug reactions and
interactions
– Simplify drug regimen