Pharmacology of Hypnotics Flashcards
What is insomnia?
difficulty in either falling asleep or staying asleep through the night
What are the types of insomia?
-transient (2-3 days)
-short-term (<3 weeks)
-long term (>3 weeks)
What neurochemicals are involved in activating the cortisol system (“ascending arousal system”) for wakefulness?
-norepinephrine
-serotonin
-histamine
-dopamine
-acetylcholine
What are the natural neurotransmitter of induction/regulation of sleep?
-melatonin
-GABA (dominates during sleep)
-galanin
What benzodiazepines (GABA receptor agonists) are FDA approved to treat insomnia?
-estazolam
-flurazepam
-quazepam
-triazolam
-temazepam
What nonbenzodiazepines GABA receptor agonists (Z-drugs) are FDA approved for insomnia?
-zolpidem
-zaleplon
-eszopiclone
What melatonin receptor agonist are FDA approved for insomnia?
-ramelton
-tasimelton
What histamine 1 receptor antagonist is FDA approved for insomnia?
doxepin
What dual orexin receptor antagonist (DORA) is FDA approved for insomnia?
-suvorexant
-lemborexant
-daridorexant
What is the MOA of benzodiazepines?
do not substitute for GABA, bind allosteric site GABA receptor and enhance the inhibitory effects of GABA (Cl- channel opening)
What benzodiazepines can be used for sleep onset insomnia?
all FDA approved benzos for insomnia
-triazolam
-temazepam
-estazolam
-quazepam
-flurazepam
Which benzodiazepine is short-acting?
triazolam
also why it cannot be used for sleep maintenance insomnia like other benzos
preferred to avoid hangover sedation in the morning
What is the Black Box Warning of Benzodiazepines?
amnesic parasomnia episodes= sleep eating, sleep walking, sleep driving
What are the adverse effects of Benzodiazepines?
-dose dependent decrease in REM and N3 slow-wave sleep
-subject to abuse and overdose (respiratory depression)
-withdrawal
-amnesia
-amnesic parasomnia episodes (Black Box Warning)
-residual effects into the next day (fatigue and drowsiness, psychomotor, neurological dysfunction)= more common with long t1/2, quazepam and flurazepam
What is the MOA of GABA receptor agonists (Z-drugs)?
selectively bind to areas close to (but distinct from) benzo recognition site on GABA and potentiates inhibitory effects of GABA
What Z-drugs may only be used for sleep onset insomnia?
-zolpidem
-zaleplon
What are the adverse effects of Z-drugs?
-amnesia
-amnesic parasomnia episodes
-GI disturbances, including N/V
-incoordination
-drowsiness, dizziness, headache and fatigue
-depression, confusion
-tolerance with long term use/high doses
-dependance (withdrawal symptoms)
-clinical abuse
What is the Black Box Warning of Z-drugs?
rare but serious injuries and/or death due to unusual sleep behaviors while not awake
What are the contraindications of Z-drugs?
-avoid using in pt who have already experienced an episode of complex sleep behavior
-caution in pt who are depressed especially if suicidal
What is the role of melatonin in sleep regulation?
at nighttime melatonin is produced and binds to melatonin receptors (MT1 and MT2) which activates the expression of clock genes= maintains circadian rhythm and regulates sleep
What is the MOA of Ramelteon?
dual MT1 and MT2 receptor agonist= induces drowsiness
What are the indications of Ramelteon?
sleep onset insomnia (transient insomnia)
What is the MOA of Tasimelteon?
dual melatonin agonist at MT1 and MT2 but has higher affinity for MT2 receptor, making it effective at entraining the circadian clock
What is the indication of Tasimelteon?
non-24 hour sleep wake disorder which effects most totally blind people who have the inability to synchronize their internal clock to the external enviroment
What is the MOA of doxepin?
binds H1R= produces drowsiness
What is the indication of doxepin?
sleep maintenance insomnia
What is the MOA Suvorexant?
orexin neuropeptide (OXs) receptors 1 and 2 (which regulates transition between wakefulness and sleep) antagonist, promotes sleep
What are the indications of Suvorexant?
-sleep onset insomnia
-sleep maintenance insomnia (due to long t1/2 , 17-19h, dose dependent)
What is the MOA of Lemborexant?
orexin neuropeptide (OXs) receptors 1 and 2 (which regulates transition between wakefulness and sleep) antagonist, promotes sleep
What is the indication of Lemborexant?
-sleep onset insomnia
-sleep maintenance insomnia (due to long t1/2)
What is the MOA of Daridorexant?
orexin neuropeptide (OXs) receptors 1 and 2 (which regulates transition between wakefulness and sleep) antagonist, promotes sleep
What are the indications of Daridorexant?
-sleep onset insomnia (rapidly absorbed)
-sleep maintenance insomnia (tmax= 2h, t1/2= 8h)
What are the adverse effects of Daridorexant?
headache, fatigue, excess sleepiness
What are Daridorexant’s next day effects?
none, 80% eliminated after full nights sleep
