Sleep disorders Flashcards
Two physiologic states of sleep:
- Non-rapid eye movement (NREM) sleep
- Rapid eye movement (REM) sleep
which state of sleep is
Composed of stages 1-4
Usually how the sleep cycle begins
Non-rapid eye movement (NREM) sleep
how long is each stage in Non-rapid eye movement (NREM) sleep
5-15 mins
which state of sleep has
High levels of brain activity
Dream activity happens here
REM sleep
how are the physiologic functions during NREM sleep. Describe each (HR, rsp, etc)
reduced compared with wakefulness
1. HR - slowed 5-10 beats/minute, very regular
2. Rsp slowed slightly, regular
3. Bp tends to be lower than wakefulness
4. Seldom any penile erections
which NREM stage:
Decreased activity from wakefulness
Easily awakened during this stage
May feel like they “haven’t slept” if awakened
May have feeling of falling → hypnic myoclonia
stage 1
which NREM stage:
light sleep with spontaneous periods of muscle tone followed by muscle relaxation
Body is preparing to enter deep sleep
stage 2
which NREM stage:
“Delta wave” sleep
Time of mending
“Deeper” levels of mental functioning
If awakened during, are often disoriented
Brief arousals associated with amnesia
Typical period for enuresis, somnambulance, and night terrors
stage 3-4
describe the physiologic activity during REM sleep
Physiologic activity increased compared to NREM sleep
Much higher than NREM sleep, may be higher than awake
Almost every REM period in men accompanied by a partial or full penile erection
which state of sleep is near-total paralysis of skeletal muscles
REM Sleep
what is the most distinctive feature of REM Sleep
dreaming
May dream in NREM sleep, but usually don’t remember
Dreams are typically abstract, surreal
REM phases occur about every ____ (time)
90-100 minutes
Shorter periods earlier in sleep
Longer periods after a few hours into sleep cycle
More REM periods occur in ___ of the night
last third
how does serotonin affect sleep
less serotonin = less sleep
prevention of serotonin synthesis or destruction of dorsal raphe nucleus = decreased sleep
how does NOR affect sleep
more NOR = less sleep
increased firing of noradrenergic neurons (through drugs or other manipulations) = less REM sleep, increased wakefulness
how does melatonin affect sleep
less melatonin = less sleep
released naturally by our bodies’ pineal gland in response to low light conditions
how does dopamine affect sleep
more dopamine = less sleep
suppresses secretion of melatonin by the pineal gland; occurs naturally at the end of the “dark phase” (night)
what are the changes in REM sleep over time
Slowly decreases over time
- 80% of sleep time - 10-week premature infant
- 50% of sleep time - full-term infant
- 30-35% of sleep time - 2 year old child
- 20-25% of sleep time - 10 years old (stabilizes)
- <20% of sleep time - 65 years and up
what type of pt would exhibit this sleep pattern:
Regular cycling between stage 1 and stage 4 sleep
Prolonged stage 4 periods earlier in sleep period
REM sleep phases - gradually lengthen as the night goes on
Healthy young adult
what type of pt would exhibit this sleep pattern:
Decreased or absent deep sleep stages (3-4)
More easily awakened from sleep
Less regular cycles
Overall increased daytime fatigue and napping
Overall decreased quality of nocturnal sleep
Elderly adult
what sleep pattern in depressed pt is
Very common - 83% of depressed pts
insomnia
what sleep pattern in depressed pt is
Common, but less common than insomnia
Seen more with atypical depression
Hypersomnia
what sleep pattern in depressed pt is
More frequent wakeful periods
Longer wakeful periods
Increased wakefulness
what 6 sleep patterns could you see in depressed pts
- insomnia
- hyperinsomnia
- increased wakefulness
- Reduced sleep efficiency
- Increased sleep onset latency
- Reduced REM latency
how do you diagnose sleep disorders?
Thorough history is essential!
1. Is there a problem with falling asleep or staying asleep?
2. Is there excessive daytime sleepiness?
3. Are there abnormal movements or behavior during sleep?
4. Is there abnormal timing of the sleep-wake cycle?
5. Are there unusual life stressors precipitating the sleep problem?
6. What is the sleep environment like?
criteria for insomnia diagnosis
1+ of the following symptoms for 1 month:
1. Difficulty initiating or maintaining sleep
2. Nonrestorative or poor quality sleep
3. Early morning awakening
4. Symptoms occur despite adequate opportunity and circumstances for sleep
5. Impaired sleep produces deficits in daytime function
what is the duration of Transient Insomnia
< 7 d
what is the duration of acute insomnia
< 30 d
what is the duration of chronic insomnia
+30 d
which type of insomnia is often associated with anxiety
transient insomnia
what type of insomnia has no specific cause and is about <20% of chronic cases?
primary insomnia
what type of insomnia is secondary to other diseases like depression/anxiety, breathing-related, substance abuse/meds
comorbid insomnia
how does acute alc intake affect sleep
decreased sleep latency, REM sleep pattern changes, vivid dreams, frequent awakening
how does chronic alc abuse affect sleep
increased stage 1
decreased REM
how does alc withdrawal affect sleep
delayed sleep onset, intermittent awakening
how does Smoking (>1 ppd) affect sleeping
difficulty falling asleep
how does Excess stimulant intake affect sleeping
decreased total sleep time, delayed sleep onset
caffeine, cocaine, OTC cold medication
how does Sedative withdrawal affect sleeping
delayed sleep onset, intermittent awakening
tx for Comorbid Insomnia
Treat underlying cause
Some antidepressants (TCAs) and anxiolytics (benzodiazepines) have SE of sedation/somnolence
nonpharm tx for insomnia
Relaxation techniques
Meditation
Cognitive Behavioral Therapy
Regular Exercise
Sleep Hygiene
what is the first-line tx for insomnia
Cognitive Behavioral Therapy for Insomnia (CBT-I)
what is the 6 pharm tx for insomnia
- OTC 1st gen antihistamines - limited efficacy!
- Benzodiazepine Receptor Agonists
- melatonin agonist
- Benzodiazepines
- Dual Orexin Receptor Antagonists
- Antidepressants
Diphenhydramine
OTC 1st gen antihistamines
Benadryl, Sominex
Doxylamine
OTC 1st gen antihistamines
Zaleplon
Benzodiazepine Receptor Agonists
Zolpidem
Benzodiazepine Receptor Agonists
Eszopiclone
Benzodiazepine Receptor Agonists
Ramelteon
Melatonin agonists
Temazepam (Restoril)
Benzodiazepines
Temazepam (Restoril),
Benzodiazepines
alprazolam (Xanax)
Benzodiazepines
lorazepam (Ativan)
Benzodiazepines
clonazepam (Klonopin)
Benzodiazepines
oxazepam (Serax)
Benzodiazepines
Suvorexant (Belsomra)
Dual Orexin Receptor Antagonists
Lemborexant (Dayvigo)
Dual Orexin Receptor Antagonists
Daridorexant (Quviviq)
Dual Orexin Receptor Antagonists
Doxepin (Silenor)
antidepressant - low dosed TCA
Trazodone (Desyrel, Oleptro)
antidepressant
Mirtazapine (Remeron)
antidepressant
6 ways to enhance sleep hygiene
- Establish a Regular Sleep Schedule
- Cut Down on Excess Time in Bed
- Make Bedroom Comfortable
- Relax Before Bedtime
- Techniques to Make You Tired
- Regular exercise - ideally 6+ hrs before bedtime
- Light snack or warm drink near bedtime - things to avoid
- No exercise within 90 minutes of bedtime
- No over stimulating activities just before bed
- Avoid caffeine after lunchtime (caffeine half-life >4 hrs)
- No heavy meals within 2 hrs of bed or excess fluids immediately before bed
- No alcohol to induce sleep
- Do not look at clock when awakening
- No turning on light when getting up mid-sleep
narcolepsy usually begins at what age?
20s
what is the Classic tetrad of symptoms for narcolepsy
- Recurrent irresistible attacks of daytime sleepiness
- Cataplexy
- Hallucinations
- Sleep paralysis
clinical presentation of narcolepsy
- Recurrent irresistible attacks of daytime
sleepiness, Cataplexy, Hallucinations, Sleep paralysis - Recurrent irresistible attacks of daytime sleep - at least 3 months
- Cataplexy
- Hallucinations
- Hypnagogic (on falling asleep)
- Hypnopompic (on awakening)
- Intrusions of REM sleep elements into the transition between sleep and wakefulness - Sleep paralysis
how do you diagnose narcolepsy
Multiple sleep latency test (MSLT)
1. Recorded naps - show rapid onset of sleep and REM sleep (2 or more REM cycles during test)
2. Shortened REM latency period
tx for narcolepsy
- Forced naps
-
Stimulants
- Modafinil (Provigil) - least risk of abuse/dependence
- Methylphenidate (Ritalin), dextroamphetamine (Dexedrine) -
SSRIs, SNRIs
- Symptomatic tx of cataplexy, sleep paralysis, hallucinations
- Suppress REM sleep
epidemiology of somnambulism
- 15-17% of normal children 4-15 y/o
- Peaks ages 8-12 - MC in males
risk factors of Somnambulism
FHx of sleepwalking
GERD
Acute stress
Sleep deprivation
Obstructive Sleep Apnea
Episodes of semi-purposeful behavior during sleep
Somnambulism
Usually difficult to wake patient up
Usually no memory of episode upon awakening
tx for Somnambulism
- Avoid fatigue
- Minimize interventions (slapping, shouting)
- Lead patient back to bed
- Protect from accidents
- No bunk beds
- Gates across stairs - Locks on doors and windows
Involuntary, non-functional, forceful clenching, grinding, or rubbing of teeth during NREM sleep
Sleep-Related Bruxism
Sleep-Related Bruxism may be more likely to have what other associated symptoms
HA
TMJ disorders
mechanical tooth wear
tx for Sleep-Related Bruxism
- Occlusive splints
- Controlling anxiety
Misalignment between the environment and an individual’s sleep-wake cycle
Circadian Rhythm Disorders
what is the Normal sleep cycle
sleep propensity greatest in mid-afternoon and at night
6 types of Circadian Rhythm Disorders
- Delayed Sleep Phase Type
- Jet Lag Type
- Shift Work Type
- Advanced Sleep Phase Type
- Irregular Sleep-Wake Rhythm Type
- Non-24-Hour Sleep-Wake Rhythm Type
Persistent late sleep onset and late awakening times, with inability to fall asleep and
awaken at a desired earlier time
Delayed Sleep Phase Type
Delayed Sleep Phase Type is MC in what type of pts
younger
Sleepiness and alertness that occur at an inappropriate time of day relative to local time, occurring after repeated travel across more than one time zone
jet lag
which jet lag is worse
Eastward travel usually worse than westward
Insomnia during major sleep period or excessive sleepiness during major awake period associated with night shift work or frequently changing shift work
Shift Work Type
Persistent early sleep onset and early awakening times, with an inability to fall asleep and awaken at a desired later time
Advanced Sleep Phase Type
Advanced Sleep Phase Type is MC in what type of pts
elderly
Characterized by lack of a clearly defined circadian rhythm of sleep and wake
Irregular Sleep-Wake Rhythm Type
Irregular Sleep-Wake Rhythm Type is MC in what type of pts
Developmental disorders in children
Neurodegenerative diseases
Characterized by insomnia or excessive sleepiness that occurs because the intrinsic circadian pacemaker is not entrained to a 24-hour light/dark cycle
Non-24-Hour Sleep-Wake Rhythm Type
Non-24-Hour Sleep-Wake Rhythm Type is MC seen in what type of pts
blind pts
tx for Circadian Rhythm Disorders
- Promotion of sleep hygiene
- Attempt to synchronize sleep and wakefulness with the underlying circadian rhythm
- Advanced Sleep Phase Type - Bright light in evening
- Delayed Sleep Phase Type - Bright light in early morning
- Melatonin - Can help resynchronise
- Stimulants - caffeine, modafinil
breath cessation for at least 10 seconds
Apnea
decreased airflow with drop in oxygen saturation of at least 4%
Hypopnea
Subtypes of Apnea
- Central - absent ventilatory effort during the apneic episode
- Obstructive - persistent ventilatory effort persists throughout apneic episode, but no airflow occurs because of transient obstruction of the upper airway
- Mixed - absent ventilatory effort precedes upper airway obstruction during the apneic episode
risk factors for obstructive sleep apnea
- Anatomically narrowed upper airways
- Micrognathia, macroglossia, obesity, tonsillar hypertrophy - Ingestion of alcohol or sedatives before sleeping
- Nasal obstruction of any type
- Includes nasal congestion, e.g. the common cold - Hypothyroidism
- Cigarette smoking
classic pt for obstructive sleep apnea
obese, middle-aged male with HTN
PE of obstructive sleep apnea
HTN
Cor Pulmonale
Sleepy appearance
Narrowed oropharynx
Nasal obstruction
Nasal twang to speech
“Bull neck” appearance
lab findings of obstructive sleep apnea
Erythrocytosis
pt-reported and bed partner-reported symptoms of obstructive sleep apnea
pt-reported:
Excessive daytime somnolence
Morning sluggishness and headaches
Daytime fatigue
Cognitive impairment
Recent weight gain
Impotence
bed partner-reported:
Loud cyclical snoring
Witnessed apneas
Restlessness
Thrashing movements of the extremities
Personality changes, depression, or poor judgment
Work-related problems or intellectual deterioration
how to diagnose obstructive sleep apnea
- Home Overnight Pulse Oximetry
- Negative - High rule-out value - Overnight Polysomnography
- Measures EEG, electrooculography, EMG, ECG, pulse oximetry, respiratory effort and airflow
- Reveals apneic episodes lasting up to 60 sec
- Oxygen saturation falls, often to very low levels
- Bradydysrhythmias - sinus bradycardia, sinus arrest, or AV block may occur
- Tachydysrhythmias - paroxysmal SVT, a fib, or v tach may be seen once airflow is reestablished
tx for obstructive sleep apnea
- wt Loss - 10-20% of body weight
- Strict avoidance of alc and hypnotic meds
- Mechanical appliances to hold jaw forward
- Nasal continuous positive airway pressure (nasal CPAP):
- Given at night - Curative in many patients
- Polysomnography - usually needed to determine level of CPAP (usually
5–15 cm H2O) to stop obstruction
- Only 75% of pts continue to use after 1 yr - Supplemental O2 - can decrease hypoxia, but may lengthen apnea duration
- Surgical repair
which sleep disorder med
Facilitate GABA-mediated inhibition of cell firing by binding to the BZD receptor, a subunit of the GABA receptor complex
Benzo Receptor Agonists
which sleep disorder med
Reduce stage 1 NREM sleep; does not reduce stage 3 NREM sleep; may decrease REM sleep
Benzo Receptor Agonists
benzodiazepines DO reduce stage 3 NREM
pt-important effects of Benzo Receptor Agonists
Easier to fall asleep, increased total sleep time, less sleep awakening, less daytime sleepiness, improved ability to concentrate
pros vs cons of Benzo Receptor Agonists vs benzodiazepines
pros:
May be slightly safer for pts with chronic respiratory dysfunction (e.g. COPD)
May be less likely to cause tolerance
No reduction of deep sleep stages
cons:
No anxiolytic effects
all Benzodiazepine receptor agonist are what schedule drug
schedule IV
SE of Zaleplon
Headache (30-42%), dizziness, drowsiness, GI upset
interactions with Zaleplon
Avoid or use caution if taking in conjunction with any other sedative
High-fat meals impair absorption
which sleep disorder med has a
Very short half-life (0.5 hr)
Good for sleep-onset insomnia; Bad for sleep-maintenance insomnia
Little to no “hangover” or rebound insomnia
Not indicated for long-term use
Zaleplon (Sonata)
which drug has dosing available as extended-release tablet and mid-sleep dissolvable tablet
Zolpidem
SE of Zolpidem (Ambien)
Headache (7-19%), dizziness, drowsiness
DI of Zolpidem (Ambien)
Avoid using or use caution in conjunction with any other sedative
Do not take with meals or grapefruit juice
which insomnia med has
Longer half-life (1.5-2.4 hr)
Zolpidem (Ambien)
which Zolpidem dosage has
Good for sleep-onset insomnia, bad for sleep-maintenance insomnia; little to no “hangover” or rebound insomnia; not for long-term use
immediate release
which zolpidem dosage is
released more slowly; indicated for sleep-onset and sleep-maintenance insomnia; can impair activity the following day
Extended-release
SE of Eszopiclone (Lunesta)
Unpleasant (metallic) taste (8-34%), headache (15-21%), dizziness, drowsiness, impaired next-day activity
DI of Eszopiclone (Lunesta)
Avoid using or use caution in conjunction with any other sedative
Do not take with meals
DI of Eszopiclone (Lunesta)
Avoid using or use caution in conjunction with any other sedative
Do not take with meals
which sleep disorder med
Longest half-life of any BZD agonist (5-7 hrs)
Indicated for sleep-onset and sleep-maintenance insomnia
Eszopiclone (Lunesta)
Released at night into blood and CSF by pineal gland
melatonin
melatonin rises by ___ at night
10-30x
Increase in concentration blunted in elderly patients → ?
more nighttime awakenings
Prolonged use of exogenous melatonin can ?
desensitize receptors
what is recommended for melatonin if pt formerly had relief and now has stopped responding to therapy
take a break
SE of melatonin
Decreased nocturnal BP, drowsiness, worsening insomnia (receptor desensitization)
DI with melatonin
Avoid in patients taking warfarin (Coumadin)
CNS depressants
avoid melatonin in who?
hx of seizures
children
what med Binds with higher affinity to melatonin receptors than melatonin itself
Ramelteon (Rozerem)
SE of Ramelteon (Rozerem)
Dizziness, somnolence, fatigue
DI of Ramelteon (Rozerem)
fluvoxamine (Luvox; an SSRI)
caution in conjunction with other CNS depressants
Do not administer with a meal
Ramelteon (Rozerem) should not be given in what type of pts
history of seizures
children
what melatonin receptor agonist has a
Half-life of 1.5-5 hrs
Better for sleep onset than sleep maintenance insomnia
Binds with higher affinity to melatonin receptors
Ramelteon (Rozerem)
what med
Antagonize orexin receptors which facilitates sleep by decreasing the wake drive
Dual Orexin Receptor Antagonist
what is the Orexin system / Hypocretin system
- promotes and stabilizes wakefulness
- Orexin system → hypothalamus → wake-promoting neurotransmitters (histamine, acetylcholine, dopamine, serotonin, and norepinephrine)
SE of Suvorexant (Belsomra)
drowsiness, headache, dizziness, abnormal dreams, diarrhea
DI of Suvorexant (Belsomra)
- avoid using or use caution in conjunction with any other CNS depressant
- CYP34A inhibitors / inducers
- Leads to higher serum concentration of DORA
which dual orexin receptor antagonist
Peaks in 2 hours, intermediate half-life (up to 12 hrs)
Indicated for sleep-onset and sleep-maintenance insomnia
Recent meal may delay onset
Suvorexant (Belsomra)
SE of Lemborexant (Dayvigo)
drowsiness, fatigue, headache
DI of Lemborexant (Dayvigo)
avoid using or use caution in conjunction with any other CNS depressant
CYP34A inhibitors / inducers
which dual orexin receptor antagonist
Long half-life (17-19 hrs)
Indicated for sleep-onset and sleep-maintenance insomnia
Recent meal may delay onset
Lemborexant (Dayvigo)
which dual orexin receptor antagonist has no dose adjustment needed for elderly
Daridorexant (Quviviq)
SE of Daridorexant (Quviviq)
drowsiness, fatigue, headache, dizziness, nausea
DI of Daridorexant (Quviviq)
avoid using or use caution in conjunction with any other CNS depressant
CYP34A inhibitors / inducers
which Dual Orexin Receptor Antagonist
Intermediate half-life (8 hrs)
Indicated for sleep-onset and sleep-maintenance insomnia
Recent meal may delay onset
Daridorexant (Quviviq)
what sleep disorder med class has
significant DI with other CYP34A inhibitors / inducers
CI in narcoleptic patients
Orexin Receptor Antagonists
scheduling for ORA
IV
dosing of Modafinil (Provigil)
Narcolepsy - first thing in AM
Shift Work Disorder - 1 hour before beginning of shift
SE of Modafinil (Provigil)
Headache (34%, dose-dependent), decreased appetite, nausea, abdominal pain
DI of Modafinil (Provigil)
Avoid using or use caution if patient is taking in conjunction with any other stimulants
schedule of Modafinil (Provigil)
IV
what med is in the class: CND depressant; Gamma hydroxybutyrate (GHB)
Sodium Oxybates
which sleep disorder med MOA
metabolite of GABA; work on GABA-B receptors
Sodium Oxybates
SE of Sodium Oxybates
- Deep sedation; wt loss, nausea, vomiting, urinary incontinence, condusion, dizziness, HA (>10%); mood swings, worsening depression, somnambulance, psychosis (<10%)
- OD can results in rsp depression, coma, and death
DI of Sodium Oxybates
Avoid using with alcohol, other sedatives, or hypnotics
which sleep disorder med is
schedule III
Access is restricted in the U.S.
Must register with Risk Evaluation and Mitigation Strategies program if a patient or prescriber
Sodium Oxybates
