22 Anxiolytic and hypnotic drugs Flashcards
22.01 BENZODIAZEPINES
Diazepam, oxazepam, nitrazepam, temazepam - actions
anxiolytic, hypnotic, amnestic, anticonvulsant and reduction in muscle tone
22.01 BENZODIAZEPINES
Diazepam, oxazepam, nitrazepam, temazepam - MOA
binds to benzodiazepine binding site on GABAA receptor to enhance channel opening by GABA
increased Cl− permeability reduces electrical excitability
22.01 BENZODIAZEPINES
Diazepam, oxazepam, nitrazepam, temazepam - abs/distrib/elim
given orally
diazepam is long acting due to active metabolite with long half-life
nitrazepam and temazepam have a medium duration
oxazepam is short acting
22.01 BENZODIAZEPINES
Diazepam, oxazepam, nitrazepam, temazepam - clinical use
anxiety and insomnia
nitrazepam and temazepam are used as hypnotics
other benzodiazepines also widely used for premedication, epilepsy and alcohol withdrawal
22.01 BENZODIAZEPINES
Diazepam, oxazepam, nitrazepam, temazepam - adverse effects
drowsiness and confusion
tolerance and dependence (with withdrawal symptoms) can occur, as can severe respiratory depression in combination with other CNS depressants (e.g. ethanol)
concerns have been raised about long-term dependence and the effect on cognition
22.01 BENZODIAZEPINES
Diazepam, oxazepam, nitrazepam, temazepam - special notes
flumazenil, an antagonist at the benzodiazepine binding site, is used to reverse the sedative effects of benzodiazepines (usually if severe respiratory depression) in anaesthetic or intensive care settings only
acts quickly and effectively when given by injection, but action lasts for only about 2h, so drowsiness tends to return
convulsions or withdrawal symptoms may occur, particularly in chronic users or mixed overdoses
22.02 Z-DRUGS
Non-benzodiazepine agonist at benzodiazepine receptor: zolpidem, zopiclone, zaleplon - actions
hypnotic (less anxiolytic, amnestic and muscle relaxant activity than benzodiazepines)
22.02 Z-DRUGS
Non-benzodiazepine agonist at benzodiazepine receptor: zolpidem, zopiclone, zaleplon - MOA
binds to benzodiazepine binding site on GABAA receptor (the more limited actions are due to selective action on BZ1 receptors) to enhance channel opening by GABA
reduces electrical excitability of neuronal cell membrane
22.02 Z-DRUGS
Non-benzodiazepine agonist at benzodiazepine receptor: zolpidem, zopiclone, zaleplon - abs/distrib/elim
given orally
zolpidem and zopiclone are short acting (half-life 2-3h and 6h, respectively)
zaleplon is very short acting
22.02 Z-DRUGS
Non-benzodiazepine agonist at benzodiazepine receptor: zolpidem, zopiclone, zaleplon - clinical use
insomnia
22.02 Z-DRUGS
Non-benzodiazepine agonist at benzodiazepine receptor: zolpidem, zopiclone, zaleplon - adverse effects
well tolerated
some drowsiness, confusion and dizziness
tolerance and dependence (with withdrawal symptoms) can occur
allergic reactions
enhances CNS depression caused by other drugs (e.g. ethanol)
concerns have been raised about long-term dependence and the effect on cognition
22.03 PARTIAL SEROTONIN AGONIST
Buspirone - actions
anxiolytic
22.03 PARTIAL SEROTONIN AGONIST
Buspirone - MOA
partial agonist at 5-HT1A receptors
acts presynaptically to inhibit firing of serotonergic neurons, particularly in the dorsal raphe nucleus
(actions on postsynaptic 5-HT1A receptors in amygdala also likely)
clinical response is not seen for 1-2 weeks, suggesting effects may require more complex, plastic changes
22.03 PARTIAL SEROTONIN AGONIST
Buspirone - abs/distrib/elim
given orally, but significant first-pass metabolism
half-life 2-3h, but effects are longer lasting, possibly due to metabolite with similar action
22.03 PARTIAL SEROTONIN AGONIST
Buspirone - clinical use
generalised anxiety disorder
