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Article Excerpt
Byline: CHARLES A. CEFALU, MD
ABSTRACT: Age-related changes that affect drug distribution, such as increased total body fat, decreased muscle mass, and decreased total body water, necessitate reduction in the dosage of water- and lipid-soluble agents. Because creatinine clearance declines with age, the dosage of agents that are excreted primarily by the kidney must also be lowered to prevent toxicity. Examples include aminoglycosides, fluoroquinolones, penicillins, procainamide, lithium, angiotensin-converting enzyme inhibitors, and digoxin. A good rule of thumb to follow until creatinine clearance can be calculated is to reduce the total dose by half in frail elderly persons or in those with established renal disease. Anticholinergic agents should be used with caution because they are associated with urinary retention, heart block, constipation, dry mouth, blurred vision, sedation, and acute or chronic confusion in elderly patients.
KEY WORDS: pharmacotherapy, polypharmacy, adverse events, geriatric care
Elderly patients, particularly those aged 85 years or older (the "oldest old"), take an average of 5 to 8 drugs each day. This is attributable principally to the number of chronic conditions that affect this age group. Polypharmacy heightens the risk of significant drug-drug interactions and other adverse events, particularly in frail elderly persons. Moreover, many drugs that are used safely by younger persons are inappropriate for older ones because of age-related changes and comorbid conditions that affect absorption, distribution, metabolism, and elimination.
A number of reports have shown that the risk of adverse drug events in elderly patients rises with comorbidity; increasing numbers of medications; inappropriate medications; the use of antipsychotics, anticoagulants, diuretics, and antiepileptics; and the use of multiple prescribers and pharmacies by patients and caregivers.1-4
Here I review the principal considerations that affect prescribing practices for elderly patients and offer strategies that will help prevent or minimize adverse drug reactions.
AGE-RELATED PHARMACOKINETIC CHANGES
The normal aging processes that affect the major organ systems should prompt a reduction in the dosages of specific classes of drugs, particularly those eliminated mainly by the kidney or metabolized by the liver or whose effect is primarily on the CNS. Basic guidelines for prescribing that take into account normal changes of aging are reviewed in Table 1. The principal drugs that are considered potentially inappropriate in elderly patients are listed in Table 2.
Distribution. Changes related to aging, such as increased total body fat, decreased muscle mass, and decreased total body water, necessitate dosage reductions in elderly persons.5,6 These changes dramatically reduce the volume of distribution for water-soluble compounds and for compounds distributed only in lean tissue, such as digoxin and lithium. Moreover, the age-related rise in body fat increases the volume of distribution of lipid-soluble compounds, such as diazepam. The clearance of such compounds is significantly prolonged, which increases the risk of adverse events.
Elimination. Because aging of the kidney is associated with decreased creatinine clearance, the dosage of agents that are excreted primarily by the kidney must be reduced in order to prevent toxicity. This is especially true in the oldest patients, in whom creatinine clearance slows dramatically.
A frequently used formula for determining creatinine clearance in men is ([140 - age]) X lean body weight [kg]/72 X serum creatinine level [mg/dL]).7 For women, the total is multiplied by 0.85. Blood urea nitrogen and serum creatinine levels may be in the normal range despite significant reductions in creatinine clearance. One study of nursing home residents indicated that 1 of 3 renally excreted drugs was inappropriately dosed based on the calculated creatinine clearance.8
Agents that require dosage reduction in patients with reduced creatinine clearance include the aminoglycosides, fluoroquinolones, penicillins, procainamide, lithium, angiotensin-converting enzyme (ACE) inhibitors, digoxin, metformin,...
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