When drug therapy gets old: pharmacokinetics and pharmacodynamics in the elderly

The age-related changes in the functions and composition of the human body require adjustments of drug selection and dosage for old individuals. Drug excretion via the kidneys declines with age, the elderly should therefore be treated as renally insufficient patients. The metabolic clearance is primarily reduced with drugs that display high hepatic extraction (‘blood flow-limited metabolism’), whereas the metabolism of drugs with low hepatic extraction (‘capacity-limited metabolism’) usually is not diminished. Reduction of metabolic drug elimination is more pronounced in malnourished or frail subjects. The water content of the aging body decreases, the fat content rises, hence the distribution volume of hydrophilic compounds is reduced in the elderly, whereas that of lipophilic drugs is increased. Intestinal absorption of most drugs is not altered in the elderly. Aside of these pharmacokinetic changes, one of the characteristics of old age is a progressive decline in counterregulatory (homeostatic) mechanisms. Therefore drug effects are mitigated less, the reactions are usually stronger than in younger subjects, the rate and intensity of adverse effects are higher. Examples of drug effects augmented is this manner are postural hypotension with agents that lower blood pressure, dehydration, hypovolemia, and electrolyte disturbances in response to diuretics, bleeding complications with oral anticoagulants, hypoglycemia with antidiabetics, and gastrointestinal irritation with non-steroidal anti-inflammatory drugs. The brain is an especially sensitive drug target in old age. Psychotropic drugs but also anticonvulsants and centrally acting antihypertensives may impede intellectual functions and motor coordination. The antimuscarinic effects of some antidepressants and neuroleptic drugs may be responsible for agitation, confusion, and delirium in elderly. Hence drugs should be used very restrictively in geriatric patients. If drug therapy is absolutely necessary, the dosage should be titrated to a clearly defined clinical or biochemical therapeutic goal starting from a low initial dose.