Benzodiazepine hypnotics in the elderly

Abstract

A review is presented of the changes that occur in the pharmacodynamics of benzodiazepines during normal ageing and as a result of disease. Controlled studies in which subjects of different ages have received single doses of diazepam, temazepam, nitrazepam and flunitrazepam have consistently shown an increase in the response to benzodiazepines in the elderly which is not explained by the effects of disease or by altered plasma concentrations. In general, healthy elderly subjects have a 2-3 fold greater response compared with the young. This change appears to be due to a change in the post-receptor mechanism of action. Cerebral diazepam concentrations are similar in young and elderly rats, though older animals also show an increased response and no consistent changes have been demonstrated in brain receptor binding. However, benzodiazepine-induced increases in GABA binding and GABA-induced increases in post-synaptic inhibition have been reported to be greater in aged animals.Regular daily dosing with most benzodiazepines leads to drug accumulation which is proportional to the elimination half-life. Regular dosing with diazepam, chlordiazepoxide, nitrazepam and flurazepam has also been found to produce more sedation in the elderly, particularly long stay patients who have a high incidence of dementia, and those with a low albumen or chronic renal failure. A controlled trial of 1 week's dosing with 5 mg of nitrazepam or 20 mg of temazepam in elderly in-patients showed that these doses produced significant impairment of psychomotor performance the morning after the last dose. Only about 50% of the patients were affected and many of these were frail patients with mild dementia on rehabilitation or long stay wards. The doses prescribed for these types of patients should not exceed 2.5 mg of nitrazepam or 10 mg temazepam. elderly: A report from the Boston Collaborative Drug Surveillance Program. Br J Clin Pharmacol 1978:5:407-13. 43. Greenblatt D J, Allen M D. Shader R I. Toxicity of hieh dose peterJ Cook, B.Sc, M.D., M.R.C.P.Physician with

Characteristics associated with benzodiazepine usage in elderly outpatients in Taiwan

“…The elderly are more susceptible to potential adverse consequences of benzodiazepine use as their altered pharmacokinetics and pharmacodynamics lead to a slower rate of benzodiazepine metabolism, and more sensitive benzodiazepine receptors (Cook, 1986;Greenblatt and Shader, 1991). Prescribing long-acting benzodiazepines, higher dosages of short-acting benzodiazepines, or use of benzodiazepines for prolonged periods are considered inappropriate in the elderly (Beers, 1997;McLeod et al, 1997;Fick et al, 2003).…”

Cognitive effects of long‐term benzodiazepine use in older adults

“…Furthermore, research has documented BZ-associated morbidity in older adults including dependence, increased risk of falls and hip fractures, and drug toxicity that can be mistaken for neurologic or psychiatric disorders (Grypmonpre et al, 1988;Ray et al, 1989;Sorock and Shimkin 1988;Whitcup and Miller, 1987). BZ accumulation and the intensity and duration of drug response are increased in the elderly due to agerelated changes in drug metabolism and, possibly, some alteration in cerebral response (Cook, 1986;Greenblatt et al, 1991;Pomara et al, 1985). Thus, it is reasonable to suggest that any adverse cognitive effects associated with chronic use would be at least as great in this population as in a younger cohort and, perhaps, longer lasting.…”

The Pharmacokinetics of Suriclone after Single- and Multiple-Dose Administration in Healthy Elderly Volunteers

“…However, suriclone caused less sedation than the benzodiazepines both in volunteers and in patients with generalised anxiety disorder (Ansseau et al 1991). Many drugs including the benzodiazepines exhibit altered pharmacokinetics in the elderly (Cook 1986), and their use is associated with a higher risk Peak plasma concentrations of suriclone (Cmax) occur about 90 minutes after ingestion, and the terminal elimination half-life is about 2 hours. Suriclone undergoes extensive hepatic metabolism; the sulphoxides and N-oxides of suriclone are pharmacologically active metabolites recognised by antibodies.…”