S57 - Sleep Wake Disorders Flashcards
Classification of sleep disorders.
Difficulty in falling and staying asleep.
Disturbance in quality of sleep.
Excessive daytime sleepiness.
Primary insomnia is the most common for of dysomnias
true
Parasomnias are night terrors, sleep walking
true
NREM has four stages – 1,2,3 and 4 (< 45 min falling asleep).
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%).
REM – low voltage, mixed frequency.
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.
70-120 is sleep cycle that consist of Non-REM and REM
true
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.
true
NREM – five brain regions: dorsal raphe (DR), hypothalamus, basal forebrain, thalamus, medulla.
true
REM – cholinergic cells in the mesencephalic, medullary, and pons regions
true
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.
true
OTC treatment for primary insomnias
Antihistamines (diphenhydramine FDA approved)
melatonin
L-tryptophan
Valarein
L-tryptophan – agent alone removed by the FDA; caused 27 deaths to eosinophilia-myalgia.
true
Chloral Hydrate – oldest agent metabolized to trichloroethanol with a half-life = 8 hrs. REM/NREM are not markedly altered.
true
“Mickey fin”
Low-dose doxepin 3-6 mg FDA approved for insomnia maintenance.
true
Zolpidem (Ambien®) – selectively binds to the BZ-1 receptor producing minimal anxiolytic effects and no muscle relaxant and antiepileptic effects.
true
Use to help people FALL ASLEEP
Zolpidem (Ambien®)
CYP3A4 activity lower in women but this is one of the few drugs shown to have a PK difference
true
use lower doses in women
Nonbenzodiazepines GABAA Agonists.
Zaleplon (Sonata®)
No tolerance, rebound insomnia or next day psychomotor activities
true
Use to help people FALL ASLEEP
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.
true
Used to help people FALL ASLEEP and ALSO STAY ASLEEP
Nonbenzodiazepines. – Ramelteon (Rozerem®).
Melatonin receptor agonist (M1 and M2) with one active metabolite (MII – has 1/10 and 1/5 potency).
true
Nonbenzodiazepines. – Ramelteon (Rozerem®).
Do not take with food - increase AUC 31% and increase Cmax 22% with a delay of Tmax by 45 minutes.
true
Nonbenzodiazepines. – Ramelteon (Rozerem®).
Drug interactions – fluvoxamine (increase 190 fold AUC, increase 70 fold Cmax)
true
Benzodiazepines (BZ)
Reduce number of awakenings.
Increase total sleep time.
Increase stage 2 sleep, decreases durations of stages 1, 3 and 4.
true
Benzodiazepines (BZ).
Anterograde amnesia
true
Suvorexant (Belsomra®) – orexin receptor antagonist that decreases hyperarousal and improves sleep (C-IV).
true
FDA approval August 2014
Lemobrant (Dayvigo®)- FDA approved Dec. 2019.
Orexin receptor antagonist (OX1R, OX2R) used for sleep onset and maintenance.
true
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.
true
What is the typical length of one sleep cycle?
70-120 minutes
Does the pharmacokinetic profile of zolpidem differ between males and females?
YES… females need lower doses.
What are the pharmacologic class of agents used for insomnia?
GABA-A agonists, BDZs, M1/M2, OX1R/OX2R
GABA-A agonists,
Zolpidem (Ambien®)
Zaleplon (Sonata®)
M1/M2
Ramelteon (Rozerem®).
OX1R/OX2R
Suvorexant (Belsomra®)
Lemobrant (Dayvigo®)-
