[Age as a factor in dose-response relationship of drugs].
Drug therapy in the elderly requires careful individualization of the dosage. Whether dose adjustment is due to altered pharmacokinetic or due to altered pharmacodynamic is a matter of experimental evidence which can be found by performing studies with simultaneous measurements of concentration and effect over time. The kinetic of drugs in the elderly can be characterized by an altered volume of distribution, an altered protein binding, an impaired metabolism and renal excretion. There is a wide interindividual variation of the alterations which are further influenced by environmental factors such as smoking and nutrition. In generalization of the results it can be assumed that the concentration of drugs is elevated in the elderly and that the excretion will be prolonged. Hence, it is safe to reduce the dose in the elderly. The influence of age on factors which determine the effect of drugs is much less investigated than the factors influencing the pharmacokinetic. With respect to side-effects, it seems that the elderly population is a population at special risk. However, it is unclear whether this finding is explained on a pharmacodynamic basis (e.g., enhanced receptor sensitivity, impaired homeostatic mechanisms), as analyses are lacking in investigating the relationship between concentration and effect. As there is no evidence besides a special situation with betablockers that aged patients require higher doses than younger ones, it is wise to use doses at the lower range for the treatment of aged patients. In case of new symptom side-effects of drugs should be considered as the underlying cause.
Gundert-Remy
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Abteilung für Klinische Pharmakologie, Zentrum für Pharmakologie, Göttingen.
D000368:Aged; D000369:Aged, 80 and over; D001711:Biotransformation; D004305:Dose-Response Relationship, Drug; D004358:Drug Therapy / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D008875:Middle Aged; D010599:Pharmacokinetics; D012307:Risk Factors