Drugs and the elderly.

Drugs and the elderly H A Bird Rheumatologists unhesitatingly prescribe drugs for their patients, who are often elderly, living as we do in an era blessed with increasing longevity. Prudent prescribers will follow the cautionary guidelines on reduced dosing in the elderly offered in a variety of national formularies and textbooks. Fewer doctors will understand pharmacokinetics and pharmacodynamics, terms that may seem as indigestible as the topics themselves. 'Pharmacokinetics' is a mathematical analysis of the time course of a drug's concentration in the body, including the contributing factors of absorption , distribution, metabolism, and excretion. 'Pharmacodynamics' refers to the effect of a given concentration of a drug at its site of action. Both change with aging, the latter clearly being of more functional interest. Unfortunately, the plethora of pharmacokinetic studies in the elderly compared with the paucity of pharmacodynamic studies reflects the practical difficulties in executing them. ' Most drugs are absorbed by passive diffusion across the gut wall. In general, absorption is unaffected in the elderly.2 Drug distribution in the elderly may be reduced by changes in protein binding,3 red cell binding,4 body composition,5 and tissue permeability.6 As old people shrink their proportion of fat to muscle and water increases, reducing the distribution of volume for polar drugs such as digoxin, but increasing it for fat soluble drugs such as diazepam.8 If the volume of distribution for a drug is reduced, peak plasma concentrations will increase. Plasma albumin concentration also falls with age, permitting the unbound fraction of some drugs to increase, further enhancing their volume of distribution. Most drugs are eliminated by a first order process, so that the concentration of drug falls exponentially. The plasma half life (the time taken for the concentration to halve) is directly proportional to the amount of drug in the body available for elimination (volume of distribution) and inversely related to the clearance of the drug, by all routes. Even if clearance remains normal the change in distribution can thus alter the rate of removal, a factor that mainly accounts for the prolonged half life of diazepam in the elderly.9 The accepted fall in glomerular filtration rate to 50% by the ninth decade implies only a twofold increase in drugplasma concentrations, so increased renal clearance is only clinically significant for drugs with a narrow therapeutic index that are mainly excreted by the kidney-for example, digoxin. Additional renal impairment, either due to disease …