The costs in terms of morbidity and mortality as a result of postural instability in the elderly are enormous. In financial terms alone it is estimated that the cost to the nation of hip fractures, just one of the consequences of falls, are in excess of $7 billion per year. Recent interest in the epidemiology of falls and hip fractures has shown that drug administration and specifically sedative administration increases the risk of failing and of hip fractures in the elderly. The overall goals of the proposed research are to examine the sensitivity of the elderly to benzodiazepine-induced impairment of balance (postural sway) and to define the patient and drug-related characteristics which predict that impairment of balance. By defining the plasma concentration-response relationship for impairment of balance in both young and elderly individuals after both single and chronic dosing it will be possible to determine if age increases sensitivity to drug impairment of balance. Benzodiazepines with differing pharmacokinetic properties (eg. half life, active vs inactive metabolites, differing routes of metabolism) will be compared to determine the drug characteristics least, likely to effect balance. By examining the postural sway of those individuals who demonstrate the greatest drug induced effect it will be possible to define the group of patients at most risk of benzodiazepine impairment in balance. Chronic dosing will allow investigation of the effects of age on the development of tolerance to benzodiazepine-induced impairment of balance.
| Robin, D W; Lee, M; Hasan, S S et al. (1993) Triazolam in cirrhosis: pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther 54:630-7 |
