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Midazolam is a short-acting benzodiazepine in adults with an elimination half-life of 1.5–2.5 hours. [13] In the elderly, as well as young children and adolescents, the elimination half-life is longer. [44] [66] Midazolam is metabolised into an active metabolite alpha
[citation needed] For example, the equivalent dose of diazepam in an elderly individual on lorazepam may be half of what would be expected in a younger individual. [7] [8] Equivalent doses of benzodiazepines differ as much as 20 fold. [9] [10] [11]
A short elimination half-life and a rapid onset of action are characteristics which increase the abuse potential of a benzodiazepines. [18] The following table provides the elimination half-life, approximate equivalent doses, speed of onset of action, and duration of behavioural effects. [32] [33]
Long-acting compounds have a half-life of 40–250 hours. They have a risk of accumulation in the elderly and in individuals with severely impaired liver function, but they have a reduced severity of rebound effects and withdrawal. Examples are diazepam, clorazepate, chlordiazepoxide, and flurazepam.
Lorazepam-glucuronide is more water-soluble than its precursor, so gets more widely distributed in the body, leading to a longer half-life than lorazepam. Lorazepam-glucuronide is eventually excreted by the kidneys, [ 98 ] and, because of its tissue accumulation, it remains detectable, particularly in the urine, for substantially longer than ...
Improved reaction times were noted at 52 weeks in elderly patients free from benzodiazepines. This is an important function in the elderly, especially if they drive a car due to the increased risk of road traffic accidents in benzodiazepine users. [136] At the 24-week follow-up, 80% of people had successfully withdrawn from benzodiazepines.
In the elderly, long-term benzodiazepine therapy is a risk factor for amplifying cognitive decline, [29] although gradual withdrawal is associated with improved cognitive status. [30] A study of alprazolam found that 8 weeks administration of alprazolam resulted in deficits that were detectable after several weeks but not after 3.5 years. [31]
Diazepam is often recommended due to its long elimination half-life and also because of its availability in low potency doses. The non-benzodiazepine Z drugs such as zolpidem, zaleplon, and zopiclone should not be used as a replacement for benzodiazepines, as they have a similar mechanism of action and can induce a similar dependence.