Sleep-Wake Disorders - Block 3 Flashcards
Describe the classifications of sleep disorders according to ICSD-3?
What are the types of sleep disorders according to the DSM5?
- Insomnia dx
- Hypersomnolence dx
- Narcolepsy
- Breathing related sleep dx
- Circadium rhythm sleep dx
- Non-REM sleep arousal dx
- Nightmare dx
- ReM sleep behaviour
- RLS
- Substance- or medication-induced sleep dx
What are the stages of the sleep cycle?
Describe the sleep patterns of an infant?
Up to 20 hrs, REM and NREM occurs at 3-6 months
* Cycles between active and quiet sleep
As you age how does sleep change from infancy?
Amount of nightly delta sleep declinses and amount of REM sleep increases
How is sleep affected in elderly?
Fragmented sleep with no delta sleep
What are the neurotransmitters for NREM?
GABA and adenosine
What are the neurotransmitters for REM?
Cholinergic (start)
Noradrenergic (stop)
What are the neurotransmitters for arousal and wakefulness?
D, NE, Ach, H, Neuropeptides, orexin (hypocretin), serotonin
What neurotransfitter is used of diagnostics for NT1?
orexin
What is insomnia?
The inability to initiate or maintain sleep -> daytime sleepiness
What constitutes chronic insomnia?
≥ 3/week and for ≥3 months
What are the characteristics of primary insomnia?
Hyperarousal state
What are the RF of insomnia?
Fixed: female, advanced age, family hx
Depression/anxiety
Unemployed
Separated/widowed
Low socioeconomic status
What are the causes of insomnia?
- Situational
- Medical
- Psychiatric
- Pharm-induced
What are situational causes of insomnia?
- Work or financial stress
- Jet lag/shift work
What are medical causes of insomnia?
- CV
- Respiratory
- Chronic pain
- Endocrine dx
- GI
- Neurologic
- Pregnancy
What are the psychiatric causes of insomnia?
- Mood dx
- Anxiety
- Substance use disorders
What are drugs that induce insomnia?
- Antiseizure
- Central adrenergic blockers
- Diuretics
- SSRI
- Steroids
- Stimulants
What is an examples of insomnia diagnostic tools?
Pittsburgh sleep quality index
What are the diagnostic criteria for insomnia
- Sleep disturbances/complaint
- Associated consequences
- Frequnecy
- Duration
- Adequate opportunity
- Relationship to another condition
What are the goals for treating insomnia?
- Correct the underlying complaint
- Consolidate sleep
- Improve daytime functioning and sleepiness
- Avoid ADR
What are the nonpharms for insomnia?
- CBT-I
- Stimulus control procedures
- Sleep hygiene recs
What are the components of CBT-I?
Cognitive + stimulus control + sleep restriction +/- relaxation therapies
What are ways to achieve stimulus control?
- Establish regular time to wake/sleep
- Sleep only to feel rested
- Go to bed only when sleepy
- Avoid trying to force sleep
- Avoid blue spectrum light
- Avoid daytime naps
- Schedule worry time during day
What are recs for good sleep hygiene?
- Exercise routinely but not close to HS
- Create comfortable leeping environment
- Reduce alcohol, caffeine, nicotine
- Avoid drinking large quantities of liquid
- Do something relaxing before HS
Pharm tx for insomnia?
- Antihistamines
- Sedating antidepressants
- Melatonin receptor agonists
- Dual orexin receptor antagonists
- Benzos
- Non-benzo GABAa agonists
Types of antihistamines for insomnia?
Diphenhydramine (Benadryl)
Doxylamine (Unisom)
Indications for using antihistamines for insomnia?
Mild insomnia for onset only due to tolerance and non-linear pk (increasing dose does nothing)
ADRs of antihist?
Anticholinergics: constipation, dry mouth and eyes
Types of sedating AD? INdication?
TCAs: amitriptyline (Elavil), Doxepin (Silenor), Nortriptyline (Pamelor)
Mirtazipine
Trazodone
How do you administer Doxepin?
30 mins prior to bed and separate from food by 3 hrs
ADRs of TCAs?
- Daytime sedation
- Anticholinergic effects
- Adrenergic block
- Cardiac conduction prolongation
Mirtazapine
ADR
Remeron
ADR: Weight gain, DLD, orthostatic hypotension, anticholinergic effects, daytime sedation
Trazodone
Indication, Admin, ADR
Indication: good in patients w/ a hx of substance abuse or SSRI and buproprion-induced insomnia
Admin: Shortly after a meal or snack increases absorption
ADR: Carryover sedation, a-adrenergic blockade, orthostasis, priapism, cardiac arrhythmias
BBW of sedating antidepressants?
- Suicidality
- Seratonin syndrome
- Withdrawal
What are the dual orexin receptor antagonists?
Suvorexant (Belsomra)
Lemborexant (DayVigo)
Daridorexant (Quviviq)
Dual orexin receptor antagonists
Indication, Admin, ADR, CI/Warning
Indication: Onset and maintence of insomnia
Admin: 30 min before bed and ≥ 7 hr before planned awakening
ADR: Complex sleep behaviors and REM sleep effects
CI: Narcolepsy, depression, worsens mood and trigger thoughts of suicide
Types of melatonin receptor agonists?
Ramelteon (Rozerem)
Tasimelteon (Hetlioz)
Melatonin receptor agonists
Admin, ADR, DDI
Admin: 30min-1hr of bed and separate from food
ADR: HA, DZ, somnolence, complex SB
DDI: Ramelteon is a substrate of CYP1A2, 2C9, and 3A4
What are the non benzo indicated for insomnia?
Zaleplon (Sonata)
Eszopiclone (Lunesta)
Zolpidem (Ambien)
Benzos for insomnia?
- Estazolam
- Flurazepam (Som-Pam)
- Quazepam (Doral)
- Temazepam (Restoril)
- Triazolam (Halcion)
Zolpidem
Dosing, Forms, Admin, ADR
Ambien
Dosing: 10 mg for males, 5 mg for females, elderly, hepatic impairment
Form: SRm SL, reduce strength
Admin: empty stomach
ADR: Weight gain, drowsiness, amnesia, DZ, HA, GI
Zaleplon
Indication, ADR, DDI
Sonata
Indication: Sleep onset only
ADR: DZ, HA, Somnolence
DDI: Levels increase with cimetidine and decrease with rifampin
Eszopiclone
ADR
Somnolence, unpleasant taste, HA, dry mouth
Benzos
Indications, CI, ADR, Caution
Indication: sedative, anxiolytic, muscle relaxant, antiseizure
CI: pregnancy, Substance use disorder, untreated sleep apnea
ADR: tolerance
Caution: elders, liver dys, med interactions
What are the benzos indicated for elderly? Why?
Lorazepam, Oxazepam, Temazepam: no active metabolites or hepatic metabolism
What are short acting benzos?
Midozolam, triazolam
What are the intermediate acting benzos?
- Estazolam
- Temazepam
- Oxazepam
- Lorazepam
What are the long-acting benzos?
- Flurazepam
- Quazepam
- Clonazepam
- Diazepam
What are the herbal agents for insomnia? Why are they not recommended by the guidelines?
Melatonin
L-tryptophan
Valerian
Not regulated
Melatonin
ADR, DDI
ADR: comnolence, Dz, HA, N
DDI: CNS depressants, anticoags/platelets, anticonvulsants, CYP1A2 and CYP2C19
L-tryptophan
DDI
Serotonergic meds
Valerian
ADR, DDI
ADR: somnolence, dx, ha, GI, excitability, vivid dream
DDI: CNS depressants
What are the AASM recs for sleep onset insomnia? Maintenance? Both?
Onset: Ramelteon, Triazolam, Zaleplon
Maintenance: Doxepin, Suvorexant
Both: Eszopiclone, Temazepam, Zolpidem
What ways can you evaluate insomnia therapy?
Monitoring: sleep diary (TST), questionaires, ADR
Follow up: 3-4 weeks until stable, afterwards, every 6 months
What is sleep apnea?
Repetitave episodes of cessation of breathing during sleep followed by blood o2 desaturation and brief arousal from sleep to restart breathing
How are most affected by sleep apnea?
Males, Affrican americans, hispanics
Diffentiate the types of sleep apnea?
Central: impairment of the respiratory drive (i.e. drug-induced)
OSA: Uppeer airway collapse and obstruction
Mixed: both CSA and OSA
How is sleep apnea diagnosed?
Respiratory disturbance index: number of apnea and hypopnea episodes documented by PSG, or home sleep study
MIld: 5-15 episodes/hr
Moderate: 15-30 episodes/hr
Severe: >30 episodes/hr
What is a cormoditity that contributes to OSA?
HTN and obesity
What are the non pharms for sleep apnea?
- Positive airway pressure (CPAP, BiPAP, AutoPAP)
- Weight reduction
- Surgery
- Positional therapies and oral appliances
- Hypoglossal nerve stimulators
How long should you reassess sleep apnea tx?
After 1-3 months for alertness and daytime sx and weight reduction
Pharms for sleep apnea?
- Avoid all CNS depressants
- Wake-promoting medications for EDS
What are the sx of narcolepsy?
EDS, cataplexy, hallucinations, sleep paralysis
Describe the characteristics of NT1?
- Loss of hypocretin/orexin
- Autoimmune
- HLADQB106:02
- Molecular mimicry
- Brain injury
- Tumor
- Stroke
What are the characteristics of NT2?
- Normal orexin levels
- Uncharacterized cause
What are the diagnostic criteria for NT1?
- EDS every day for ≥3 months
- Plus 1 or more of the following:
* CSF of ≤100 or 1/3 average
* Cataplexy and mean sleap latency ≤8 minutes plus:
* ≥2 sleep onset REM on MSLT
* 1 SOREMP on MSLT and 1 SOREMP within 15 minutes of sleep onset on PSG
What are the diagnostic criteria for NT2?
- EDS every day for ≥3 months
- Plus both of the following:
* CSF of >100 or 1/3 average
* No hx of Cataplexy and mean sleap latency ≤8 minutes plus either:
* ≥2 sleep onset REM on MSLT
* 1 SOREMP on MSLT and 1 SOREMP within 15 minutes of sleep onset on PSG
What are the goals of tx narcolepsy?
Achieve the fullest possible reutn to normal function:
* Management of EDS and REM sleep abnormalities
What are the non-pharm for narcolepsy?
- Sleep hygiene
- Schedules ≥ 2 daytime naps (15 minutes)
Pharm tx of narcolepsy?
EDS: Modafinil and armodafinil, stimulants, solriamfetol, pitolisant
REM sleep abnormalities: TCAs, SNRIs, SSRIs, selegiline
Both: sodium oxybate
What are the stimulants for wakefulness?
Modafinil (Provigil)
Armodafinil (Nuvigil)
Modafinil and Armodafinil
ADR, Indication, DDI
ADR: SJS/TEN, insomnia, HTN, tachy, HA, ax, N
Indication: EDS associated with narcolepsy, OSA
DDI: reduce effectiveness of hormonal contraceptives
What are the approved stimulants for narcolepsy? Off-label?
Dextroamphetamine
Methylphenidate
Methamphetamine and mixed amphetamine salts
Solriamfetol
MOA, ADR, DDI
Sunosi - CIV
Indication: narcolepsy
MOA: NDRI
ADR: insomnia, HTN, tachy, ax, irratibility, HA, decreased appetite, n
DDI: Washout period with MOAIs for 14 days
Pitolisant
MOA, INdication, ADR
MOA: H3 antagonist/inverse agonist
INdication: cataplexy
ADR: QT prolongation
Antidepressants indicated for narcolepsy?
TCAs: Nortriptyline (pamelor), Imipramine (Tofranil), Protriptyline (Vivactil)
SSRIs: Fluoxetine (Prozac)
SNRI: Venlafaxine (Effexor), Atomoxetine (strattera)
MAOIs: Selegiline (Zelapar)
What antidepressant is not helpful in REM for adults? Indicated for children?
Atomoxetine (Straterra)
What antidepressant is good for cataplexy?
Selegiline (Zelapar)
What is the difference between Xyrem and Xyway?
Xyway is the low sodium formulation for narcoleptics with HTN or HF
Types of CNS depressants for narc?
Sodium oxybate (Xyrem)
Low sodium formulation (Xyway)
Sodium oxybate
Admin, ADR
Admin: only available through REMS and CIII
* Take at bedtime and again 2.5-4 hr later
ADR: incontinece, dz, confusion, somnolence, n
Tx for EDS and/or caraplexy?
Seligine, pitolisant
Tx for EDS and/or REM ab?
Sodium oxybate or salts
What is the difference between jet lag and shift work disorder?
Jet lag: CR disruption from traveling across time zones, last 2-3 days, Eastward travel associated with longer jet lag duration
Shift work: CR disruption due to working shifts during normal sleep time (20% of workforce)
What are the rf for jet lag?
- Increased number of time zones
- Eastward travel
- Sleep loss during travel
- Lack of time cues during travel (sunlight)
- Advanced age
RF of shift work disorders?
- Social pressure
- Unwillingness to maintain consistent schedule on days not working
- Advanced age
Non pharm for jet lag?
- Sleep hygiene
- Sleep scheduling (trip >2 days)
* Shift sleep schedule 1 hr each day for 3 days prior to travel
Non pharm for shift work disorder?
- SLeep hygiene
- Planned napping
- Increase light exposure during night
- Limit light exposure during day
Pharm for CR disorders?
Improve alertness: Modafinil (shift work only), Caffeine
Improve sleep:
* BZRA: Benzo (Triazolam, temazepam) and Non-benzo (eszopiclone, zolpidem, zaleplon)
* Ramelteon
* Melatonin
Overall tx for sleep disorders?
Chart