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Pharmacologic Pharmacologic ConsiderationsConsiderations

GeriatricsGeriatrics

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IntroductionIntroduction

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 Physiologic Changes of Aging Affecting AbsorptionAffecting 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 Physiologic Changes of Aging Affecting DistributionAffecting 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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MetabolismMetabolism

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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EliminationElimination

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 Physiologic Changes of Aging Affecting EliminationAffecting 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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PharmacodynamicsPharmacodynamics

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 Major Drug Groups Requiring MonitoringMonitoring

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 Major Reasons for Adverse Drug Reactions in the ElderlyReactions 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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ComplianceCompliance

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