Sleep disorders Flashcards
What receptor does benzodiazepine act on?
BDZ receptor found on GABA-A receptor
By which mechanism (channel) does benzodiazepine work?
- enhances action of GABA
- increase frequency of GABA induced chloride channel
- inhibitory! (hyperpolarize)
What enzyme metabolizes GABA?
GABA transaminase
Where is GABA localized?
Basal ganglia
Name an antagonist of BDZ receptor and its main clinical use.
Flumazenil
waking up patients from anesthesia
Which receptors does buspirone bind and its actions?
Partial agonist for 5-HT1A - inhibition of adenylate cyclase and open K+ channel
binds dopamine D2 receptors
Name three benzodiazepines used to treat anxiety.
diazepam
alprazolam
lorazepam
Which of the benzodiazepines causes muscle relaxation?
diazepam
How does the duration of alprazolam compare to diazepam and to lorazepam?
alprazolam has shorter duration (panic disorder)
lorazepam has longest duration
How does lipophilicity affect the onset and rate of action?
diazepam vs. lorazepam
greater lipid solubility means faster absorption and entry into brain
- therefore, faster onset and shorter duration
- lorazepam is less lipophilic = longer duration of action (and no active metabolites)
Which BDZ is used as hypnotic?
Flurazepam
What is diazepam’s active metabolite?
desmethyldiazepam
What is unique about the metabolism of BDZ?
it is complex and active metabolite is formed in most (which can have long half-life)
What are the effects of BDZ on sleep stages?
decreased latency to sleep BUT increased stage 1 & 2 sleep decreased stage 3 & 4 & REM sleep AND rebound insomnia upon withdrawal...
What are some major adverse effects of BDZ? (6)
daytime sedation ataxia rebound insomnia tolerance and dependence occasional idiosyncratic excitement increased death rate (?)
