that calorically restricted mice also remain healthier for a longer time. Drugs that mimic caloric restriction have been shown to increase lifespan in the nematode Caenorhabditis elegans, as well as other species, including mice. Metformin and rapamycin each increase life span in these species when given alone and appear to have synergistic effects when given together. Sirtuins, a class of endogenous protein deacetylase enzymes, may be linked to life span in some species, but activators (such as resveratrol) of certain sirtuins have not been shown to prolong life in mice. Assuming that safer alternatives to metformin or rapamycin can be found, should everyone over the age of 40 or 60 years take such a drug? Few would maintain that a simple increase in the years of life—life span—is desirable unless accompanied by an increase in the years of healthy life—“health span.” Provocative research suggests that variables such as telomere length on chromosomes may predict prospective life span and that proteins in the blood of young animals may “rejuvenate” older animals, but these studies provide no guidance regarding the current treatment of diseases in older patients.
Important changes in responses to some drugs occur with increasing age in many individuals. For other drugs, age-related changes are minimal, especially in the “healthy old.” Drug usage patterns also change as a result of the increasing incidence of disease with age and the tendency to prescribe heavily for patients in nursing homes. General changes in the lives of older people have significant effects on the way drugs are used. Among these changes with advancing age are the increased incidence of several simultaneous diseases, nutritional problems, reduced financial resources, and—in some patients—decreased dosing adherence (also called compliance) for a variety of reasons. The health practitioner should be aware of the changes in pharmacologic responses that may occur in older people and should know how to deal with these changes. Finally, dependent elders are sometimes abused physically or financially by caregivers at home or in nursing homes, and the health practitioner should investigate abuse as a cause of nonadherence, as well as bruises, dehydration, and other morbidities.
In the general population, measurements of functional capacity of most of the major organ systems show a decline beginning in young adulthood and continuing throughout life. As shown in Figure 60–1, there is no “middle-age plateau” but rather a linear decrease beginning no later than age 45. However, these data reflect the mean and do not apply to every person above a certain age; approximately one third of healthy subjects have no age-related decrease in, for example, creatinine clearance up to the age of 75. Some of these changes result in altered pharmacokinetics.
FIGURE 60–1 Effect of age on some physiologic functions.
(Adapted, with permission, from Kohn RR: Principles of Mammalian Aging. Copyright copy; 1978 by Prentice-Hall, Inc. Used by permission of Pearson Education, Inc.)
CHAPTER 60 Special Aspects of Geriatric Pharmacology 1059
For the pharmacologist and the clinician, the most important of these is the decrease in renal function. Other changes and concurrent diseases may alter the pharmacodynamic characteristics of particular drugs in certain patients.
A. Absorption
There is little evidence of any major alteration in drug absorption with age. However, conditions associated with age may alter the rate at which some drugs are absorbed. Such conditions include altered nutritional habits, greater consumption of nonprescription drugs (eg, antacids and laxatives), and changes in gastric emptying, which is often slower in older persons, especially in older diabetics.
B. Distribution