Physiologic changes with aging

Effects on a drug

Examples of drugs to use with caution (nonexhaustive list)

Clinical implications

Decreased body water

Lower volume of distribution for hydrophilic drugs

Ethanol, lithium

– May result in higher serum levels in older people

– Loading and usual maintenance doses (eg, digoxin) need to be reduced in older adults

Decreased lean body mass

Lower volume of distribution of drugs that bind to muscle

Digoxin

Increased fat stores

Higher volume of distribution of lipophilic drugs

Diazepam, fluoxetine, trazodone

Prolonged half-life and duration of action of medications

Decreased plasma protein (eg, albumin) levels

A higher percentage of drugs that is unbound or active

Diazepam, phenytoin, warfarin

Although age-related changes in drug-protein binding are not usually clinically relevant, significant changes in drug effect can occur with rapid changes in albumin related to acute illness or malnutrition

Reduced drug clearance by the liver due to reduction in hepatic volume and blood flow

Drug accumulation can lead to drug toxicity

Amlodipine, diazepam, diltiazem, ibuprofen, morphine, naproxen, nortriptyline, trazodone, verapamil

Dose reduction may be required, but adjustments need to be individualized since hepatic drug metabolism varies greatly from person to person

Reduction in first-pass metabolism due to a decrease in liver mass and blood flow

Increased bioavailability of drugs undergoing extensive hepatic first pass

Labetalol, nifedipine, propranolol

Dose reduction may be required

Decreased bioavailability of prodrugs activated in the liver

Enalapril, perindopril

Dose required for the therapeutic effect may be higher than usual

Reduced kidney function leads to decreased renal drug excretion

Drug accumulation and toxicity

Aminoglycoside, digoxin, fluoroquinolones, lithium, water-soluble beta-blockers (eg, atenolol), NSAIDs

Renally excreted drugs need ideal dose adjustment based on calculated creatinine clearancea (or eGFR if not available)

a Use the Cockcroft-Gault method of creatinine clearance calculation to estimate eGFR.