ReviewWhen drug therapy gets old: pharmacokinetics and pharmacodynamics in the elderly
Introduction
Most of us want a long life, but that implies getting old. Aging is associated with many disconcerting problems, not the least of which concerns the efficacy and safety of drug therapy. The increase in life expectancy over the past decades makes this issue more acute, survival to old age seems to be more and more the norm.
The beginning of senescence is insidious. Although this process commences after maturation, it manifests itself prominently and progressively in the post-reproductive stages of live. Society has agreed, rather arbitrarily, to define elderly as individuals aged 65 years and older.
This review deals with the principles of drug use in the elderly and the age-related alterations in drug disposition and response, changes that result from the modifications of the functions and composition of the body associated with aging. The literature on the topic is vast, so this article makes no attempt to be comprehensive.
Section snippets
Biology of aging
Survival to old age requires a protected habitat, as wild animals usually die early from extrinsic hazards such as infection, predation, starvation, or cold (Kirkwood and Austad, 2000). Aging entails a gradual decrease in physiological fitness and reduced ability to respond to environmental demands. The reduction in homeostatic capablities is a fundamental feature of senescence, but the decline in functional reserve varies markedly between elderly persons (Lamy, 1991, Troen, 2003, Turnheim, 1998
Pharmacokinetics
All stages of the journey of a drug through the human body may be affected by aging, the most important pharmacokinetic change in the elderly being the reduction in renal drug elimination.
Pharmacodynamics
The pharmacokinetic guidelines for dose adjustment in the elderly given above disregard changes in the sensitivity to an agent. Aside from its concentration at the site of action, the magnitude of a drug effect depends on the number of receptors in the target organ, the ability of the cells to respond to receptor occupation (signal transduction), and on counterregulatory processes that tend to preserve the original functional equilibrium. Thus, in addition to pharmacokinetics, the
Antiaging or longevity medicine
Antiaging is a hot subject these days and there is brisk commerce in remedies that claim to slow, stop, or even reverse the aging process. But in spite of considerable hype to the contrary, there is no scientifically valid evidence that antiaging drugs presently on the market (ginseng, garlic, ginko biloba, chondroitin sulfate, DHEA, growth hormone, melatonin, fish oil, St Johns wort, procain) can increase longevity (Platt, 1990, Turnheim, 1995, Olshansky et al., 2002). In some cases these
Conclusions
Persons aged 65 or older are particularly susceptible to adverse drug reactions because of multimorbidity, the high number of medications used in this population, and age-associated changes in pharmacokinetic and pharmacodynamic properties. The rate of adverse drug effects is estimated to be 2-3 times higher in older individuals than in adult patients younger than 30 years (Turnheim, 1998). As much as one fifth of all hospital admissions of older subjects are attributed to adverse drug effects
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