Geriatric Dosing Considerations

Geriatric patients experience age-related physiological changes that alter drug pharmacokinetics and pharmacodynamics, increasing the risk of adverse drug reactions. Older adults, typically defined as those aged 65 years and older, represent a growing proportion of the population and consume a disproportionate share of prescription medications. The combination of altered drug handling, multiple chronic conditions, and polypharmacy creates a complex therapeutic environment that requires careful dose individualization.

Gastric pH rises with age due to reduced gastric acid secretion and increased prevalence of atrophic gastritis. This change can alter the ionization and dissolution of weakly acidic and weakly basic drugs. Gastric emptying and intestinal motility slow with age, potentially delaying drug absorption, though the overall extent of absorption is generally preserved. Reduced splanchnic blood flow may further slow absorption, particularly in patients with heart failure or vascular disease.

Age-related changes in the skin, including thinning of the epidermis and reduced vascularity, can affect transdermal drug absorption. The absorption of sublingual and buccal preparations appears to be less affected by aging, making these routes potentially advantageous in older patients.

Body composition changes substantially with age. Total body water decreases by approximately 10 to 15%, reducing the volume of distribution for hydrophilic drugs. Lean body mass declines while adipose tissue increases proportionally, expanding the volume of distribution for lipophilic drugs. These changes mean that a standard dose of a hydrophilic drug such as digoxin produces a higher concentration in older patients, while a standard dose of a lipophilic drug such as diazepam distributes more extensively and has a prolonged elimination half-life.

Serum albumin concentrations decline modestly with age and more substantially in frail or malnourished elderly patients. Reduced albumin binding increases the free fraction of highly bound acidic drugs such as warfarin and phenytoin, potentially enhancing their effect and toxicity. Alpha-1-acid glycoprotein levels may increase with age and chronic illness, reducing the free fraction of basic drugs.

Hepatic mass and liver blood flow decrease with age, reducing the clearance of drugs that undergo hepatic metabolism. The reduction in clearance affects drugs with both high and low hepatic extraction ratios, though the mechanisms differ. For high-extraction drugs, reduced liver blood flow is the primary factor. For low-extraction drugs, reduced hepatocyte mass and enzyme activity are more important.

The activity of specific cytochrome P450 isoforms may decline at different rates. Cross-sectional studies suggest that CYP3A4 activity is reduced by approximately 30% in older adults, while CYP2D6 activity appears relatively preserved. Phase II conjugation reactions are generally less affected by aging than Phase I reactions. The net effect of these changes is that many hepatically cleared drugs have prolonged half-lives in older patients, requiring dose reduction or extended dosing intervals.

Renal function declines progressively with age, even in the absence of overt kidney disease. The glomerular filtration rate decreases by approximately 10% per decade after age 40, and this decline is accelerated by hypertension, diabetes, and cardiovascular disease. Because serum creatinine production decreases with age due to reduced muscle mass, the serum creatinine concentration may remain within the normal range despite substantially reduced renal function. Calculation of creatinine clearance using the Cockcroft-Gault equation or estimation of GFR using the CKD-EPI equation is essential for appropriate dose adjustment in older adults.

The reduced renal clearance of drugs such as digoxin, aminoglycosides, and lithium necessitates dose reduction in older patients. Failure to account for age-related renal decline is a common cause of adverse drug reactions in geriatric practice.

Polypharmacy and Inappropriate Prescribing

Polypharmacy, commonly defined as the concurrent use of five or more medications, is highly prevalent in older adults and increases the risk of drug-drug interactions, adverse effects, and medication nonadherence. The Beers Criteria, developed by the American Geriatrics Society, identifies potentially inappropriate medications for older adults and includes drugs that should generally be avoided, drugs to use with caution, and drug-drug interactions of particular concern. Examples include benzodiazepines, anticholinergics, and nonsteroidal anti-inflammatory drugs.

The START (Screening Tool to Alert Doctors to the Right Treatment) and STOPP (Screening Tool of Older Person’s Prescriptions) criteria provide evidence-based guidance for initiating appropriate therapy and avoiding inappropriate medications. These tools complement the Beers Criteria and help clinicians optimize prescribing in geriatric patients.

Reduced Homeostatic Reserve and Deprescribing

Older adults have reduced homeostatic reserve, meaning their physiological systems are less able to compensate for drug-induced perturbations. Orthostatic hypotension from antihypertensives, hypoglycemia from antidiabetic agents, and bleeding from anticoagulants are all more common and more dangerous in older patients. The principle of start low and go slow is fundamental to geriatric prescribing, with initial doses typically 25 to 50% lower than the usual adult starting dose.

Deprescribing, the systematic process of identifying and discontinuing medications that are no longer appropriate, is increasingly recognized as an essential component of geriatric pharmacotherapy. The goal of deprescribing is to reduce the burden of polypharmacy and eliminate drugs for which the potential harms outweigh the benefits, particularly in patients with limited life expectancy or advanced frailty.