S57 - Sleep Wake Disorders

Question 1

Classification of sleep disorders.

Answer 1

Difficulty in falling and staying asleep.
Disturbance in quality of sleep.
Excessive daytime sleepiness.

Question 2

Primary insomnia is the most common for of dysomnias

Answer 2

true

Question 3

Parasomnias are night terrors, sleep walking

Answer 3

true

Question 4

NREM has four stages – 1,2,3 and 4 (< 45 min falling asleep).

Answer 4

Stage 1 – transition to sleep (0.5 – 7 min), low voltage EEG.
Stage 2 – sleep spindles 10-16 Hz EEG (50%).
Stage 3 and 4 – high amplitude, slow waves (20%).

Question 5

REM – low voltage, mixed frequency.

Answer 5

First cycle 5-7 min., cycle lengthens to total time of 70-120 min. with 4-6 cycles/night. Dreams occur in the last part.

Question 6

70-120 is sleep cycle that consist of Non-REM and REM

Answer 6

true

Question 7

Sleep neurotransmitters invloved include:

Norepinephrine (NE) – locus ceruleus (LC) maintains normal sleep pattern, inc. activity dec. REM sleep.

Serotonin (5-HT) – sleep regulation. Dec. or DR destruction reduces sleep.

Dopamine (DA) has a alerting effect. Inc. DA wakefulness; dec. causes sleepiness.

Answer 7

true

Question 8

NREM – five brain regions: 
dorsal raphe (DR), 
hypothalamus, 
basal forebrain, 
thalamus, 
medulla.

Answer 8

true

Question 9

REM – cholinergic cells in the mesencephalic, medullary, and pons regions

Answer 9

true

Question 10

Diagnostic criteria (DSM-5) – difficulty in falling asleep, maintaining sleep or nonrestorative sleep for at least three (3) months and 3 nights /week. Causes significant distress or impairment in function.

Answer 10

true

Question 11

OTC treatment for primary insomnias

Answer 11

Antihistamines (diphenhydramine FDA approved)
melatonin
L-tryptophan
Valarein

Question 12

L-tryptophan – agent alone removed by the FDA; caused 27 deaths to eosinophilia-myalgia.

Answer 12

true

Question 13

Chloral Hydrate – oldest agent metabolized to trichloroethanol with a half-life = 8 hrs. REM/NREM are not markedly altered.

Answer 13

true

“Mickey fin”

Question 14

Low-dose doxepin 3-6 mg FDA approved for insomnia maintenance.

Answer 14

true

Question 15

Zolpidem (Ambien®) – selectively binds to the BZ-1 receptor producing minimal anxiolytic effects and no muscle relaxant and antiepileptic effects.

Answer 15

true

Use to help people FALL ASLEEP

Question 16

Zolpidem (Ambien®)

CYP3A4 activity lower in women but this is one of the few drugs shown to have a PK difference

Answer 16

true

use lower doses in women

Question 17

Nonbenzodiazepines GABAA Agonists.
Zaleplon (Sonata®)
No tolerance, rebound insomnia or next day psychomotor activities

Answer 17

true

Use to help people FALL ASLEEP

Question 18

Treatment of insomnia
Eszopiclone (Lunesta®) – 1 mg, 2 mg and 3 mg tablets.
Dose < 2 mg for elderly patients.
FDA approved for up to 6 months.

Answer 18

true

Used to help people FALL ASLEEP and ALSO STAY ASLEEP

Question 19

Nonbenzodiazepines. – Ramelteon (Rozerem®).

Melatonin receptor agonist (M1 and M2) with one active metabolite (MII – has 1/10 and 1/5 potency).

Answer 19

true

Question 20

Nonbenzodiazepines. – Ramelteon (Rozerem®).

Do not take with food - increase AUC 31% and increase Cmax 22% with a delay of Tmax by 45 minutes.

Answer 20

true

Question 21

Nonbenzodiazepines. – Ramelteon (Rozerem®).

Drug interactions – fluvoxamine (increase 190 fold AUC, increase 70 fold Cmax)

Answer 21

true

Question 22

Benzodiazepines (BZ)
Reduce number of awakenings.
Increase total sleep time.
Increase stage 2 sleep, decreases durations of stages 1, 3 and 4.

Answer 22

true

Question 23

Benzodiazepines (BZ).

Anterograde amnesia

Answer 23

true

Question 24

Suvorexant (Belsomra®) – orexin receptor antagonist that decreases hyperarousal and improves sleep (C-IV).

Answer 24

true

FDA approval August 2014

Question 25

Lemobrant (Dayvigo®)- FDA approved Dec. 2019.

Orexin receptor antagonist (OX1R, OX2R) used for sleep onset and maintenance.

Answer 25

true

Question 26

Lemobrant (Dayvigo®)- FDA approved Dec. 2019.
Drug interactions: “strong” or moderate CYP3A4 inhibitors inducers – avoid. Max. 5 mg dose with weak CYP3A4 inhibitors. PD EtOH interactions;  AUC drugs CYP2B6 substrates.

Answer 26

true

Question 27

What is the typical length of one sleep cycle?

Answer 27

70-120 minutes

Question 28

Does the pharmacokinetic profile of zolpidem differ between males and females?

Answer 28

YES… females need lower doses.

Question 29

What are the pharmacologic class of agents used for insomnia?

Answer 29

GABA-A agonists, BDZs, M1/M2, OX1R/OX2R

Question 30

GABA-A agonists,

Answer 30

Zolpidem (Ambien®)

Zaleplon (Sonata®)

Question 31

M1/M2

Answer 31

Ramelteon (Rozerem®).

Question 32

OX1R/OX2R

Answer 32

Suvorexant (Belsomra®)

Lemobrant (Dayvigo®)-