On the surface, prescribing for older adults is similar to prescribing for younger adults, requiring understanding of drug indications, dosing, potential adverse reactions, and drug–drug interactions. However, prescribing for older adults is complicated by a variety of factors. Physiologic changes as patients get older result in alterations in drug metabolism and susceptibility to adverse events. The presence of multiple chronic conditions and multiple medications leads to potentially complex drug–drug and drug–disease interactions, as well as the need to balance multiple competing recommendations. Changes in cognitive function, manual dexterity, and social supports complicate adherence to medications, and heterogeneous goals of care require special attention. Because clinical trials that inform many practice guidelines are often conducted in younger patients, there can be ambiguity about the extent to which these evidence-based recommendations apply to older adults. Thus, mastering prescribing for older patients requires expertise not only in technical elements of drug use, but also in synthesizing evidence and biomedical and psychosocial factors into a coordinated plan of care that meets each individual’s unique needs. More details about polypharmacy can be found in Chapter 53, and more details about extrapolating the evidence from clinical research to older patients can be found in Chapter 74.
Drug Metabolism and Physiologic Effects in Older Adults
Pharmacokinetics refers to how the body handles a drug from the time it is ingested to the time it is excreted. This includes the processes of absorption, distribution, metabolism, and elimination. While each of these processes can vary with age, they are typically more influenced by genetic factors and by an individual’s diseases, environment, and other medications. For most older patients, changes in renal function have the greatest impact on pharmacokinetics.
Absorption of drugs is impacted by the size of the absorptive surface, gastric pH, splanchnic blood flow, and gastrointestinal (GI) tract motility. Most of these are relatively unaffected by age, but can be substantially affected by certain diseases and medications. Some medications, including vitamin B12, calcium, and iron, have decreased absorption in older adults as a result of reduced activity of active transport mechanisms.
Older patients have an increased fat-to-lean body mass ratio, decreased total-body water, and sometimes decreased serum albumin. Drugs that distribute in fat (eg, diazepam) may thus have a larger volume of distribution. Hydrophilic medications (eg, digoxin) will have a decreased volume of distribution, resulting in higher serum levels. Drugs that bind to serum proteins reach an equilibrium between bound (inactive) and free (active) drug. Use of 2 or more drugs that compete for protein binding (eg, thyroid hormone, digoxin, warfarin, phenytoin) can result in higher levels of free drug, requiring careful monitoring of drug levels and effects. In the case of testosterone, age-associated increases in sex-hormone binding globulin can result in ...