sedatives hypnotics Flashcards
sedative
reduce anxiety, produce calming effect w/o impairing mental function
sedative
reduce anxiety, produce calming effect w/o impairing mental function
hypnotic
produce state of drowsiness, facilitate onset/maintenance of sleep
sleep function
restoration/repair
optimize storage of memories
sleep stages (ultradian rhythm)
90min, 4-5/night
1 - transition 2 - longest 3 - sort deep delta wave sleep SWS 4 - long deep delta wave sleep SWS 5 - REM
sleep initiation
time to fall asleep (30min)
hypnotic
produce state of drowsiness, facilitate onset/maintenance of sleep
sleep function
restoration/repair
optimize storage of memories
sleep stages (ultradian rhythm)
90min, 4-5/night
1 - transition 2 - longest 3 - sort deep delta wave sleep SWS 4 - long deep delta wave sleep SWS 5 - REM
sleep initiation
time to fall asleep (30min)
sleep efficiency
time sleeping / time in bed (>85%)
arousal pathway
cholinergic, aminergic, orexin
tuberomammillary nucleus
locus coeruleus
dorsal raphe nucleus
sleep promoting pathway
GABA
VLPO
orexin
stabilized sleep/wake transition
GABA
inhibitory
sleep induction/maintenance
executive functions
melatonin
secreted from pineal gland in darkness
dyssomnias
disturbance in normal rhythm/pattern of sleep
parasomnias
sleep terrors, nightmares, sleep walking
insomnia S/S
delayed sleep onset
early morning wake-ups
unrefreshing sleep
trouble maintaining sleep
transient insomnia
short-term insomnia
3days-3wks
personal stressor
Tx: intermittent hypnotics
chronic insomnia
> 3wks
no identifiable stressor
Tx: complete medical evaluation
ideal hypnotic
no active metabolites
rapid sleep induction
sleep maintenance
no adverse effects
benzodiazepines MOA
bind allosteric site on GABA-A receptor complex, increase frequency of channel openings, increase affinity of GABA for receptor
benzodiazepines addiction
GABA regulation of VTA DAergic neurons
benzodiazepines withdrawal
rebound insomnia (decrease dose slowly)
triazolam
slow-acting BZD (
temazepam, estazolam
intermediate-acting BZD (12-24hr)
sleep maintenance insomnia
conjugated w/glucuronide
flurazepam
long-acting BZD (>24hr)
sleep onset and maintenance insomnia
active metabolite
quazepam
long-acting BZD (>24hr)
sleep maintenance insomnia
benzodiazepines absorption
lipophilic
rapidly absorbed
completely distributed
benzodiazepines metabolism
active metabolites: flurazepam
inactive metabolites: triazolam
conjugated: temazepam (safe for elderly, liver impaired)
benzodiazepines use
prolong stage 2 sleep
suppress stage 3 and 4 sleep (SWS)
suppress REM sleep, prolong REM latency
benzodiazepine other use
antiepileptic general anesthesia muscle relaxation anti-nausea, anti-vertigo alcohol withdrawal
benzodiazepine SE
CNS - somnolence, drowsiness, sedation
pregnancy - cross placental barrier, cleft palate (1st trimester), floppy infant syndrome (3rd trimester)
elderly - confusion, amnesia, falls, fractures
paradoxical psychological effects - excitement, anxiety, mild euphoria, hallucinations
benzodiazepine Rx interactions
potentiates opiates & sedatives
benzodiazepine OD
if given w/other CNS depressants
Tx: flumazenil - rapid reversal of sedation, may cause SE in pts dependent on BZD
benzodiazepine contraindications
h/o alcoholism or drug abuse
liver impairment
elderly (lower dose)
selective BZD receptor agonists (Z drugs)
rapid onset, short duration
less tolerance, dependence, abuse
doesn’t affect stage 4 sleep
Z drug MOA
selectively bind alpha1 subunits of GABA-A receptor (sedation, amnesia)
zolpidem
Z drug
short-term insomnia (sleep onset)
30min onset
2.5hr duration
inactive metabolites (CYP3A)
SE: somnolence, amnesia
zaleplon
Z drug
short-term insomnia (sleep onset and maintenance)
30min onset
1hr duration
inactive metabolites (CYP3A)
SE: drowsiness, Rx interactions
eszopiclone
Z drug
insomnia (sleep maintenance)
alpha1 and alpha 3 (on switch)
30min onset
6hr duration
metabolized by CYP3A4
SE: rebound insomnia, unpleasant taste, dry mouth, drowsiness, Rx interaction
barbiturates
selectively bind GABA-A receptor at allosteric site, prolonging duration of Cl- channel opening
SE: P450 inducers, low therapeutic index, high potential for dependence/abuse
melatonin receptor agonists
maintain circadian rhythms
selectively binds MT1 (sleepiness) and MT2 (phase-shifting) receptors in SCN
metabolized by CYP3A
less abuse, tolerance, dependence, doesn’t affect stage 4 sleep
ramelteon
melatonin receptor agonist
sleep onset insomnia
first-pass metabolism CYP1A2
t1/2 = 1-3hr
SE: somnolence, increase serum prolactin
tasimelteon
melatonin receptor agonist
non 24-hr sleep disorder
first-pass metabolism CYP1A2, CYP3A4
t1/2 = .5-3hrs
Rx interactions: CYP1A2 (fluvoxamine), CYP3A4 (ketoconazole)
suvorexant
orexin receptor antagonist
selectively blocks binding of orexin to OX1 and OX2 receptors
improves sleep inset, reduces sleep maintenance
t1/2 = 12hr
SE: daytime sleepiness
