Age-related changes affect the way drugs are metabolised (pharmacokinetics), as well as the effect of the drugs (pharmacodynamics). Owing to interindividual variability, however, significance and occurrence cannot be predicted (3).
Age-related changes affect the absorption, distribution, metabolism and elimination of drugs. Gastric acid secretion, gastrointestinal blood flow, pancreatic trypsin and gastrointestinal motility are reduced. The number of absorbing cells is also reduced, which consequently decreases the absorption rate and alters the distribution rate, leading to delayed onset of drug effect. The plasma concentration of albumin decreases in old age, leading to an increased free fraction of active drug. It is the free fraction that reflects the pharmacological activity of a drug (5). The permeability of the blood-brain barrier increases, permitting diffusion of large, fat-soluble molecules. These last two age-related changes can cause a higher concentration of active ingredient for a given drug dose in the body of older patients compared to younger ones (2, 3).
Fat-soluble drugs have a larger distribution volume in older people of normal weight. This is due to the proportional increase in fat (because of decreasing muscle mass) and less intracellular water. The consequence may be delayed clearance and hence a prolonged drug half-life (3).
A declining glomerular filtration rate and/or underlying disease may affect kidney function. Drugs with a narrow therapeutic index that are excreted via the kidneys should therefore be used with particular caution. Impaired kidney function results in a prolonged drug half-life and risk of adverse effects (3, 4).
Pharmacodynamic effects include therapeutic effects, adverse effects and toxic effects. These depend mainly on the drug concentration at the receptor site, the receptor response, response triggered in the cell and homeostatic mechanisms. The number, sensitivity and density of receptors change with increasing age. As a result, less active ingredient is needed to block a receptor and thereby achieve blockade and clinical efficacy (3). Receptor density is dynamic, however. It is reduced through prolonged use of agonists. Although receptor density generally declines in older people, it may be substantially increased by prolonged use of antagonists. Clinically, the latter effect may lead to rebound effects: in other words, problems may recur in exacerbated form when the drug is discontinued (3–5).
Due to the aforementioned pharmacokinetic changes, older people are more likely to have higher concentrations of active ingredient – particularly of fat-soluble drugs – at the receptor sites than younger adults (2, 3, 5).