Clinical pharmacology and physiology of ageing: implications for drug therapy.


The size of the oldest old section of the population is rising and as a consequence the prevalence of
frailty is rising. The physiological changes with age have important implications for both the
pharmacokinetics and pharmacodynamics of drugs. Changes in pharmacokinetics include the reduction
in renal clearance of water soluble substances including drugs such as aminoglycosides, lithium and
digoxin. These examples are of drugs not only cleared renally but also with a narrow therapeutic window
making the risk of toxicity much higher. The physiological reduction in liver volume reduces the hepatic
clearance of lipid soluble drugs. In addition, the increase in the proportion of lipid tissue per kg body
weight (increasing the apparent volume of distribution) increases the elimination half life (t1/2z) of lipid
soluble drugs independently of the prolongation due to reduced clearance. In addition to these changes
caused by age related physiology, frailty is associated with further prolongation of t1/2z. Other age
related physiological changes with important implications for clinical practice include changes
associated with less efficient homeostasis such as reduced baroreflex efficiency and reduced efficiency
of balance maintenance. These changes may be potentiated by prescribed medication. Cognitive
ageing is associated with reduced attention and decline in some types of memory as well as slower
processing. These effects however are very small in magnitude compared to the effects of pathology
such as Alzheimer’s disease. Dementia of any aetiology will adversely affect both compliance with
medication regimens as well as the technique of administration where relevant.