Dose optimisation—the effect of age

Abstract

Although the absolute and relative size of the pensionable population is not currently rising, that population is ageing. As a result, prescriptions for elderly patients continue to increase. People over the age of 60 represent around 22% of the many western European populations, yet receive nearly 54% of the medication prescribed. Over the age of 75, the proportion of the population is around 14%, yet 33% of prescriptions are written for this group. Depending on the age group, between 20% and 30% are taking at least three drugs. A number of problems complicate the process of prescribing for elderly patients. Pharmacokinetic changes consequent upon the physiological changes associated with ageing result in a fall in the renal clearance of drugs. Similarly, the reduced proportion of body water seen in old age results in an increased volume of distribution, and hence elimination half-life of lipid-soluble drugs. Liver volume falls with increasing age, although in vitro studies demonstrate enzyme activity is normal. As a result of this, the clearance of hepatically metabolised drugs tends to fall with age. Over and above the effects of ageing, changes associated with frailty are also seen. These result additionally in a reduction in plasma albumin protein binding—clinically relevant only for acidic drugs very extensively bound—leading to a reduction in volume of distribution. In addition, reduced hepatic enzyme activity further reduces the hepatic clearance of drugs which undergo hepatic metabolism. In addition to age-related pharmacokinetic changes, changes in pharmacodynamics also occur. A change in pharmacodynamics implies a change in drug effect per unit concentration or change in sensitivity. The characterisation of such effects often requires formal concentration effect analysis to separate kinetic from dynamic effects. Increased sensitivity to benzodiazepines, warfarin, hypertensives, anaesthetics, neuroleptics are well described, as is the reduced sensitivity to the hypotensive effect of β-blockers and dystonic effects of neuroleptics. The higher prevalence of dose-related adverse drug reactions seen in elderly patients relates not only to age-associated pharmacokinetic and pharmacodynamic changes, but also to the increased prevalence of disease states and use of concomitant drug therapy. Indeed, numbers of drugs prescribed is probably the most important factor. Although age is only one determinant, these changes are clearly important determinants of the optimal dosage for older patients.