Sedative Hypnotics Flashcards
progression of sedative hypnotics
anxiolysis sedation hypnosis anesthesia death
use of barbiturates
induce anesthesia
rarely used
use of benzodiazepines
anxiety
insomnia
epilepsy
use of non-benzodiazepines (z drugs)
insomnia
safest for use
GABA receptor for sedative/hypnotic
alpha1
GABA receptor for anxiolytic and muscle relaxant
alpha2
GABA receptor for anticonvulsant
alpha3
GABA receptor for amnesia
alpha5
barbiturate action at GABA receptor
increase duration of opening
increases efficacy of GABA
benzodiazepine action at GABA receptor
increase frequency of opening
increases potency of GABA
barbiturates to recognize
thiopental
pentobarbital
amobarbital
phenobarbital
thopental
short acting barbiturate
used for amnesia prior to surgery
phenobarbital
long acting barbiturate
used for seizures
side effects of barbiturates
dose dependent respiratory depression
induction of liver enzymes
low margin of safety
increases porphyrin production- do not use with porphyria
benzodiazepine side effects/toxicity
tolerance to sedation and euphoria
cross tolerance with other CNS depressants
physical dependence- withdrawal symptoms
advantages of benzo use for insomnia over barbiturates
higher margin of safety than barbiturates- plateaus before bad effects
no cyp induction
milder withdrawal
therapeutic use of bentos #1
insomnia- reduces time to sleep and increases total sleep time moderate REM decrease increase stage 2 decrease stage 4 REM rebound when ended
flurazepam half life
40-100 (longest)
flurazepam use
short term mild/moderate insomina
flurazepam activity
prodrug
peak metabolite plasma concentration 1-3h
flurazepam delivery/absorption
good absorption orally
lorazepam half life
10-20hours
lorazepam use
short term mild/moderate insomnia with anxiety
lorazepam activity
slow
no active metabolites
lorazepam delivery/absorption
oral- slow
IM- good
temazepam half life
10-40h
temazepam use
short term severe insomina
temazepam delivery/absorption
slow and erratic oral absorption
temazepam warnings
distorts normal sleep pattern
do not use during pregnancy
triazolam half life
short term acute insomnia (jet lag)
**doesn’t work for frequent awakenings
triazolam activity
fast acting- peak plasma levels 1h
triazolam delivery/absorption
good oral
triazolam warnings
higher abuse potential (fast acting)
more severe withdrawal with chronic use
use #2 of benzos
amnesia during anesthesia for procedures
midazolam
benzo for amnesia
short term use
half life 2-6h
benzo overdose treatment
maintain respiration rule out narcotics by giving naloxone gastric lavage hemodialysis flumazenil
naloxone
drug for narcotic overdose
flumazenil
benzo antagonist that reverses respiratory depression
very short acting- requires close monitoring
causes withdrawal symptoms
do not give flumazenil to
seizure history
barbiturate or TCA overdose
careful with ethanol intoxication
z drugs
benzodiazepine receptor agonsits
insomnia drugs with highest margin of safety
z drugs
MOA of z drugs
interacts with alpha1 receptors
z drug that is non selective
eszopiclone
effects of z drugs
hypnosis with little muscle relaxant or anticonvulsant effects
use of z drugs
decrease latency without affecting sleep cycles
why are z drugs better than benzos
less: anti anxiety, anticonvulsant, muscle relaxant, impact on REM sleep
z drug metabolism
liver
change dose for elderly and liver disease
3 z drugs
zolpidem
zaleplon
eszopiclone
zolpidem half life
2-2.5h
medium duration
zolpidem form
tablet
controlled release tablet
sublingual, lingual
zolpidem metabolism
CYP 3A4
zolpidem ADR
dizziness
diarrhea
GI irritation
zolpidem residual sleepiness
confusion and falls in elderly
memory impairment at high doses
zaleplon half life
1h
shorts duration
approved for use during night
zaleplon metabolism
aldehyde oxidase- works in patients with liver dysfunction
zaleplon ADR
impaired fertility
color disturbances
zaleplon tolerancee
rebound insomnia at high doses
eszopiclone half life
6h
longest duration
eszopiclone metabolism
CYP 3A4
eszopiclone ADR
taste disturbance
xerostomia
eszopiclone residual sleepiness
next day memory impairment
psychomotor impairment
rebound insomnia
z drugs causing rebound insomina
zaleplon
eszopiclone
longest duration z drug
eszopiclone
shortest duration z drug
zaleplon
CYP 3A4 metabolized z drugs
zolpidem
eszopiclone
suvorexant
orexin receptor antagonist used for insomina
ramelteon
synthetic melatonin- against at SCM MT1 and MT2 receptors
do not give sedative-hypnotics to
obstructive sleep apnea
