The use of drug therapy in elderly individuals has increased substantially in recent years driven by increased numbers of older adults, the results of clinical trials including older adults, and a less nihilistic approach to therapy in this age group. As a consequence, the majority of drug therapy is prescribed to older adults. An understanding of the principles of pharmacology and appropriate application to the individual older person is necessary for all those who develop, regulate, and prescribe and monitor drug therapies in older adults. A further challenge is the need to optimally individualise drug therapy in older adults who constitute a very heterogeneous group ranging from healthy, fit community dwelling individuals taking no regular medication to frail institutionalized individuals with multiple comorbidities and polypharmacy.
When prescribing for older patients, it is important to consider pharmacokinetic and pharmacodynamic changes observed in normal aging, the likely effects of the individual's genetics and intercurrent disease, as well as evidence for therapeutic efficacy, and safety and the patient's total exposure to medications. In this chapter, we begin by describing the changes in pharmacokinetics and pharmacodynamics associated with aging and frailty. We then discuss adverse drug reactions and relevant issues in drug development, regulation, and pharmacoeconomics.
Pharmacokinetic processes determine the relationship between drug input (dose, dosage form, frequency, route of administration) and the concentration of drug achieved over time. The major components of pharmacokinetics are bioavailability, distribution, and clearance. While changes in many of these parameters have been described with aging, the most consistent and marked change in pharmacokinetics in older adults is the increase in interindividual variability.
Bioavailability (F) is the proportion of drug reaching the systemic circulation after administration. Bioavailability depends on the route of administration, the chemical properties of the drug, the absorption of the drug, and the amount of drug that is cleared (first pass loss) before reaching the systemic circulation. Bioavailability of drugs administered by the intravascular route is 100% by definition, and is not affected by aging. Factors that influence bioavailability of medications for common extravascular routes of administration, and any known changes that occur with aging, are shown in Table 8-1. Bioavailability is the ratio of the area under the concentration–time curve (AUC) when the drug is given extravascularly to that when it is given intravenously (Figure 8-1). Bioavailability (F) is expressed as a fraction or percentage:
The bioavailability of a drug given extravascularly can vary with age. As shown in Figure 8-1, with aging, absorption is often slower so the maximal plasma concentration is reached later (longer Tmax) and is lower (lower Cmax). However, the extent of absorption is usually complete in older adults so the area under the curve (bioavailability) is not affected. Drugs that require an acidic environment for absorption, such as ketoconazole, ampicillin, and iron, may have ...