CRC Handbook on Pharmacology of Aging [antikvár]

introduction Paula B. Goldberg The pharmacological aspects of aging have only recently come to the foreground as an area requiring investigation and attention. Most likely this is due to the realization that as normal function declines with age, as homeostatic and adaptive capacities decline with age, and as the incidence of diseases increases with age, the elderly members in our society find themselves major consumers of drugs. As a result, they also find themselves in difficulties stemming from overmedication and drug misuse. Problems surrounding drug use or misuse by the elderly result from a sparse knowledge of the manner in which the elderly respond to drugs that may be different from the manner in which the very young and adults respond to drugs. Upon approaching drug compendia and learned texts of pharmacology, one immediately becomes impressed by the paucity of information regarding drug action and drug use in geriatric populations. In general, when mechanisms of drug action are investigated, be it in laboratory animals or in man, usually it is done in only one age group or in as homogeneous an age group as possible. The same can be said for studies on drug toxicity and drug disposition. As pertains to studies in animals, age is not the usual basis for animal selection nor the characteristic reported in the literature. Rather, animals are selected on the basis of weight. Depending on the species used and the weight range selected, the ages of the individual animals may represent a very narrow or a very wide range. For example, in using rats as the animal model, the following considerations may apply. Sprague-Dawley rats, weighing between 200 and 300 g, because of their obesity, represent very young animals, that are relatively close in age. On the other hand, Fischer 344 rats or Wistar rats, which are much leaner, weighing between 200 and 300 g, represent adult animals whose ages may vary between perhaps 4 and 12 months. Using dogs as an animal model, without selecting for strain, the difficulties also become apparent. A 6 to 10 kg dog may be an old small strain or a very young large strain. Thus, experimentation in animals using weight as a criterion may mask significant results, or conversely, bring out significance where there might not be any. Furthermore, these considerations may apply to cases of divergent results obtained from different laboratories. But most important, studies on mechanisms of drug action, drug toxicity, and drug disposition do not take into consideration the age factor at all, so there is very little information on differences or similarities in relation to age. With respect to drug trials in humans, the situation is also one Of lack of information in older populations. Because of practical and ethical considerations, drugs are not commonly tested in old subjects or patients. The usual volunteer is a subject or patient between 18 and 40 years of age, and most likely male. Thus, drug information gathered in such an "average" population may be inappropriate for application in other, younger or older populations. It comes as no surprise then, that elderly patients encounter greater difficulty from drug use than younger adults. Aside from the practical, clinical need for information, pharmacological aspects of aging are being delved into because of their utility in elucidating basic mechanisms of aging. This is accomplished through experimentation with drugs whose basic mechanism of action at the cellular and molecular level is relatively well understood. By studying the effects of such drugs in a model of aging over a wide range of ages, differences in drug action with age can help dissect the fundamental change that occurs in that model. For example, autonomic agonists and antagonists, acting at neuroeffector junctions, can be used to uncover age-related changes in the neural environment and in the postjunctional effectors; enzyme inhibitors and stimulants (e.g., digitalis glycosides, barbiturates) can help uncover age-related changes in different enzyme systems. Thus, pharmacogerontology can play a vital