Pharmacokinetic-pharmacodynamic crisis in the elderly.

Aging is characterized by a progressive loss of functional capacities of most if not all organs, a reduction in homeostatic mechanisms, and a response to receptor stimulation. Also, loss of water content and an increase of fat content in the body are reported. Therefore, understanding the influence of age-dependent changes in composition and function of the body on the pharmacokinetics and pharmacodynamics of drugs is important before prescribing drugs to elderly patients. In this study, a Medline search for articles published in the period between 1975 and June 2006 was conducted with use of the key words aging, pharmacokinetics, and pharmacodynamics to review data related to alteration in pharmacokinetics and pharmacodynamics in elderly patients. Analysis of data revealed that the most important pharmacokinetic changes in old age include a decrease in the excretory capacity of the kidney more than the decline in the rate of hepatic drug metabolism. On the other hand, pharmacodynamic changes in the elderly are frequent and commonly ascribed to alteration in the sensitivity to drugs, irrespective of changes in drug disposition. For instance, the sensitivity of the cardiovascular system to beta-adrenergic agonists and antagonists decreases in old age, and the incidence of orthostatic episodes in response to drugs that lower blood pressure increases. However, the central nervous system becomes vulnerable in the elderly to agents that affect brain function (eg, opioids, benzodiazepines, and psychotropic drugs). Therefore, these drugs must be used very cautiously in this age group. In conclusion, the complexity of the interactions between polypharmacy, comorbidity, altered pharmacodynamic sensitivity, and even modest changes in pharmacokinetics in elderly necessitate the medical approach "start low and go slow" for aged subjects, especially if drug therapy is considered beneficial or absolutely necessary for them.