Pharmacology of Hypnotics

Question 1

What is insomnia?

Answer 1

difficulty in either falling asleep or staying asleep through the night

Question 2

What are the types of insomia?

Answer 2

-transient (2-3 days)
-short-term (<3 weeks)
-long term (>3 weeks)

Question 3

What neurochemicals are involved in activating the cortisol system (“ascending arousal system”) for wakefulness?

Answer 3

-norepinephrine
-serotonin
-histamine
-dopamine
-acetylcholine

Question 4

What are the natural neurotransmitter of induction/regulation of sleep?

Answer 4

-melatonin
-GABA (dominates during sleep)
-galanin

Question 5

What benzodiazepines (GABA receptor agonists) are FDA approved to treat insomnia?

Answer 5

-estazolam
-flurazepam
-quazepam
-triazolam
-temazepam

Question 6

What nonbenzodiazepines GABA receptor agonists (Z-drugs) are FDA approved for insomnia?

Answer 6

-zolpidem
-zaleplon
-eszopiclone

Question 7

What melatonin receptor agonist are FDA approved for insomnia?

Answer 7

-ramelton
-tasimelton

Question 8

What histamine 1 receptor antagonist is FDA approved for insomnia?

Answer 8

doxepin

Question 9

What dual orexin receptor antagonist (DORA) is FDA approved for insomnia?

Answer 9

-suvorexant
-lemborexant
-daridorexant

Question 10

What is the MOA of benzodiazepines?

Answer 10

do not substitute for GABA, bind allosteric site GABA receptor and enhance the inhibitory effects of GABA (Cl- channel opening)

Question 11

What benzodiazepines can be used for sleep onset insomnia?

Answer 11

all FDA approved benzos for insomnia
-triazolam
-temazepam
-estazolam
-quazepam
-flurazepam

Question 12

Which benzodiazepine is short-acting?

Answer 12

triazolam
also why it cannot be used for sleep maintenance insomnia like other benzos
preferred to avoid hangover sedation in the morning

Question 13

What is the Black Box Warning of Benzodiazepines?

Answer 13

amnesic parasomnia episodes= sleep eating, sleep walking, sleep driving

Question 14

What are the adverse effects of Benzodiazepines?

Answer 14

-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

Question 15

What is the MOA of GABA receptor agonists (Z-drugs)?

Answer 15

selectively bind to areas close to (but distinct from) benzo recognition site on GABA and potentiates inhibitory effects of GABA

Question 16

What Z-drugs may only be used for sleep onset insomnia?

Answer 16

-zolpidem
-zaleplon

Question 17

What are the adverse effects of Z-drugs?

Answer 17

-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

Question 18

What is the Black Box Warning of Z-drugs?

Answer 18

rare but serious injuries and/or death due to unusual sleep behaviors while not awake

Question 19

What are the contraindications of Z-drugs?

Answer 19

-avoid using in pt who have already experienced an episode of complex sleep behavior
-caution in pt who are depressed especially if suicidal

Question 20

What is the role of melatonin in sleep regulation?

Answer 20

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

Question 21

What is the MOA of Ramelteon?

Answer 21

dual MT1 and MT2 receptor agonist= induces drowsiness

Question 22

What are the indications of Ramelteon?

Answer 22

sleep onset insomnia (transient insomnia)

Question 23

What is the MOA of Tasimelteon?

Answer 23

dual melatonin agonist at MT1 and MT2 but has higher affinity for MT2 receptor, making it effective at entraining the circadian clock

Question 24

What is the indication of Tasimelteon?

Answer 24

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

Question 25

What is the MOA of doxepin?

Answer 25

binds H1R= produces drowsiness

Question 26

What is the indication of doxepin?

Answer 26

sleep maintenance insomnia

Question 27

What is the MOA Suvorexant?

Answer 27

orexin neuropeptide (OXs) receptors 1 and 2 (which regulates transition between wakefulness and sleep) antagonist, promotes sleep

Question 28

What are the indications of Suvorexant?

Answer 28

-sleep onset insomnia
-sleep maintenance insomnia (due to long t1/2 , 17-19h, dose dependent)

Question 29

What is the MOA of Lemborexant?

Answer 29

orexin neuropeptide (OXs) receptors 1 and 2 (which regulates transition between wakefulness and sleep) antagonist, promotes sleep

Question 30

What is the indication of Lemborexant?

Answer 30

-sleep onset insomnia
-sleep maintenance insomnia (due to long t1/2)

Question 31

What is the MOA of Daridorexant?

Answer 31

orexin neuropeptide (OXs) receptors 1 and 2 (which regulates transition between wakefulness and sleep) antagonist, promotes sleep

Question 32

What are the indications of Daridorexant?

Answer 32

-sleep onset insomnia (rapidly absorbed)
-sleep maintenance insomnia (tmax= 2h, t1/2= 8h)

Question 33

What are the adverse effects of Daridorexant?

Answer 33

headache, fatigue, excess sleepiness

Question 34

What are Daridorexant’s next day effects?

Answer 34

none, 80% eliminated after full nights sleep