Lecture 19: Sleeping Disorders Flashcards
What are the two physiologic states of sleep?
- NREM sleep: stages 1-4.
- REM sleep: High levels of brain activity
In what phase do dreams happen?
REM sleep
When does NREM sleep occur?
The beginning of our sleep, with each stage lasting 5-15 minutes.
How does our sleep generally cycle?
How does NREM sleep present physiologically?
Marked decreases in most physiologic functions, such as pulse, respirations, BP, and rarely any penile erections.
People are generally peaceful compared to their waking state.
How does stage 1 of NREM sleep present?
- Minor decrease in activity
- EASILY AWAKENED
- Hypnic myoclonia - feeling of falling
How does stage 2 of NREM sleep present?
- Light sleep
- Periods of muscle tone and then relaxation
How does stage 3-4 of NREM sleep present?
Often called delta wave sleep.
- Time of mending for repairing and regeneration.
- Strengthening of the immune system.
- Deeper levels of mental functioning.
- Typical period for enuresis, somnambulance, and night terrors.
If someone is awoken from stage 3/4 NREM sleep, how are they likely to present?
- Disoriented.
- Amnesia of the waking event.
Constantly waking during this stage may cause immunodeficient conditions.
What frequency is a delta wave?
1-4 Hz.
Extremely slow.
What are the 2 big differences between REM and NREM sleep?
- REM sleep involves INCREASED physiologic activity, such as BP, HR, and RR.
Spontaneous penile erection is common.
Near-total paralysis of skeletal muscles - Most distinctive feature: dreaming (but usually don’t remember)
How does REM typically occur phase-wise?
Phases occur every 90-100 minutes.
First REM is usually < 10 mins
Later REMs are 15-40 mins
The last third of the night has the most REM periods.
Stage 4 is inversely related to REM sleep.
Describe how Stage 4 sleep is related to REM sleep.
Inversely proportional.
You begin with more stage 4 sleep and less REM sleep.
As the night goes on, you have more REM sleep than stage 4 sleep.
What is the general effect of low serotonin levels on sleep?
Less serotonin => less sleep
What is the general effect of more NE on sleep?
More NE => less sleep
What is the general effect of more melatonin on sleep?
More melatonin => more sleep
What is the general effect of increased dopamine on sleep?
More dopamine => less sleep
How does our REM sleep change as we get older?
We need it less and less, beginning at 50% as an infant and down to 20% as a senior.
Seniors require very little REM sleep.
When does REM sleep stabilize in terms of age?
At 10 years old, it generally stays at 25% until 65.
How does a typical young adult’s sleep pattern present?
- Regular cycling between stages 1-4.
- Prolonged stage 4 earlier in sleep.
- REM lengthens as night goes on.
How does a typical elderly adult’s sleep pattern present?
- Decreased/absent stage 3-4
- Easily awakened from sleep
- Less regular cycles
- Overall increased daytime fatigue and napping
- Overall DECREASED sleep quality
What is the most common abnormal sleep pattern in depressed patients?
Insomnia
What are the 3 abnormal sleep patterns seen in depressed patients?
- Insomnia
- Hypersomnia
- Increased wakefulness
Why is sleeping in depressed patients impaired?
- Reduced sleep efficiency
- Increased sleep onset latency
- Reduced REM latency
What is the diagnostic criteria for insomnia?
1+ of the following for 1 month:
* Difficulty initiating/maintaining sleep
* Nonrestorative or poor quality sleep
* Early morning awakening
Symptoms occur DESPITE adequate opportunity/circumstances for sleep
Impaired sleep producing daytime function deficits
What are the two types of insomnia?
- Primary insomnia: idiopathic (20%)
- Secondary/comorbid insomnia: Secondary to another condition.
What are the 3 duration types of insomnia?
- Transient insomnia: < 7 days
- Acute insomnia: < 30 days
- Chronic insomnia: > 30 days
How does alcohol abuse affect sleep?
- Increased stage 1
- Decreased REM
How does alcohol withdrawal affect sleep?
- Delayed sleep onset
- Intermittent awakening
What substances tend to affect sleep?
- Alcohol
- Smoking (> 1 ppd)
- Excess stimulant intake
- Sedative withdrawal
How do we treat secondary insomnia pharmacologically?
Treat underlying cause.
Consider TCAs or anxiolytics for SE of somnolence (but careful of abuse potential)
How do we treat insomnia non-pharmacologically?
- Relaxation techniques
- Meditation
- CBT
- Regular Exercise
- Sleep Hygiene
How do we improve sleep hygiene?
- Cut down on excess time in bed
- Establish a consistent schedule
- Make bedroom comfortable/dark
- Relax before bedtime
What is the first-line treatment for insomnia?
CBT
What are the pharmacologic options for insomnia?
- OTC 1st gen antihistamines (Diphenhydramine/doxylamine)
- Benzo receptor agonists (Zaleplon/Sonata, Zolpidem/Ambien, Eszopiclone/Lunesta)
- Melatonin agonists (Ramelteon/Rozerem, Melatonin OTC)
- Benzos (Temazepam/restoril, Flurazepam/Dalmane)
- Dual Orexin Receptor Antagonists (Newest class of drugs)
- Antidepressants (Doxepin/TCA, Trazodone, Mirtazapine/remeron)
Doxylamine preferred in pregnancy?
What is the concern with using benadryl for insomnia?
Loses efficacy overtime.
What is the concern with melatonin OTC?
- Unknown/inconsistent dosing
- Not FDA regulated
Advised to stick with one brand if it works.
What is the primary medication to AVOID with treating an obese insomniac?
Mirtazapine/Remeron
What is the MOA of a dual orexin receptor antagonist?
Antagonizes orexin, which naturally promotes wakefulness.
What are the examples of dual orexin receptor antagonists?
- Suvorexant/Belsomra
- Lemborexant/Dayvigo
- Daridorexant/Quviviq
When does narcolepsy typically begin?
20s
What is the classic tetrad of narcolepsy?
- Recurrent irresistible attacks of daytime sleepiness
- Cataplexy (muscle weakness/paralysis)
- Hallucinations
- Sleep Paralysis
Only 10-15% have all symptoms
How do you diagnose narcolepsy clinically?
- Occurs unexpectedly and at inappropriate times.
- Occurs daily for 3+ months, occuring 2-6 times a day.
What is cataplexy in narcolepsy often associated with?
Emotional triggers
What is hypnagogic and hypnopompic?
Hypnagogic: hallucinations upon falling asleep.
Hypnopompic: hallucinations upon awakening.
Intrusions of REM sleep elements in transition between sleep and wakefulness.
Pompoms = excited to awake
What suggests that narcoleptics are in REM sleep?
- Cataplexy symptoms
- Hallucinations symptoms
How do we completely diagnose narcolepsy?
Multiple sleep latency test (MSLT): recording naps
How do we treat narcolepsy?
- Forced naps regularly during the day.
- Stimulants (Modafinil is least risky, methylphenidate, dextroamphetamine)
- SSRIs/SNRIs (Symptomatic treatment and suppress REM)
What is somnambulism? Who is it MC in?
Episodes of sleep walking with semi-purposeful behavior.
Usually males.
Hard to wake them up
No memory of episode when it occurs
First 1/3 of night usually.
What are the risk factors for somnambulism?
- Family MHx of somnambulism
- GERD
- Acute stress
- Sleep deprivation
- Sleep Apnea
How do we treat somnambulism?
- Avoid fatigue
- Minimize interventions (don’t slap them)
- Lead them back to bed
- Protect from accidents
- Lock doors and windows
What is sleep-related bruxism?
Teeth-grinding during sleep.
Characterized by involuntary, non-functional, forceful clenching, grinding , or rubbing of teeth during NREM sleep.
What might suggest someone is having sleep-related bruxism?
- Headaches
- TMJ pain
- Sudden jaw clenching
How do we treat sleep-related bruxism?
- Occlusive splints
- Controlling anxiety
What are circadian rhythm disorders?
Chronic or recurrent sleep disturbances related to a misalignment between the environment and the individual’s sleep-wake cycle.
What are the subtypes of circadian rhythm disorders?
- Delayed sleep phase type (younger patients)
- Jet Lag type (eastward travel)
- Shift work type (night shift)
- Advanced sleep phase type (elderly)
- Irregular sleep-wake rhythm type (Developmental issue in kids)
- Non-24-hour sleep-wake rhythm type (blind patients)
How do we treat circadian rhythm disorders?
- Promotion of sleep hygiene
- Synchronize sleep
- Advanced sleep: bright light in evening
- Delayed sleep: bright light in early morning
- Melatonin: resynchronize
- Stimulants
What is sleep apnea? Hypopnea?
Apnea is breath cessation for at least 10 seconds!
Hypopnea: decreased airflow resulting in an spo2 drop of >= 4%
What are the subtypes of sleep apnea?
- Central: Absent ventilatory effort throughout episode
- Obstructive: Persistent ventilatory effort but obstructed
- Mixed: Absent ventilatory effort precedes the obstruction
What are the risk factors for obstructive sleep apnea?
- Micrognathia (small jaw)
- Macroglossia
- Obesity
- Tonsillar hypertrophy
- Alcohol/sedatives
- Nasal obstructions
- Hypothyroidism
- Cigarette smoking
What is the classic patient for obstructive sleep apnea?
Obese, middle-aged male with HTN.
What PE findings might suggest obstructive sleep apnea?
- HTN
- Cor Pulmonale (RV dysfunction)
- Sleepy apperance
- Narrowed oropharynx
- Nasal obstruction
- Nasal twang
- Bull neck appearance
How do we rule out obstructive sleep apnea?
Overnight pulse oximetry showing no significant spo2 drops.
How do we diagnose obstructive sleep apnea?
Overnight polysomnography (EEG, Electrooculography, EMG, EKG, pulse ox, and end tidal co2 monitoring)
What EKG changes might appear during sleep apnea?
- Bradydysrhythmias
- Tachydysrhythmias
How do we treat obstructive sleep apnea?
- Weight loss (10-20% loss can be curative)
- Avoid alcohol/hypnotic meds
- Mechanical device to hold jaw forward
- Nasal CPAP (most curative)
- Supplemental O2 (can lengthen apnea duration)
- Surgical repair
What are the 4 big pharmacotherapy options for sleep disorders?
- Benzo receptor agonists
- Melatonin agonists
- Dual orexin receptor antagonists
- Stimulants
What is the MOA of a benzo receptor agonist?
Facilitate GABA-mediated inhibition of cell firing via binding to the receptor, which is a subunit of the GABA receptor complex.
What stages of sleep do benzo receptor agonists affect?
- Stage 1 NREM sleep reduction.
- May decrease REM
- DOES NOT REDUCE STAGE 3
What is the main effect on sleep quality for benzo receptor agonists?
Reduced time to sleep onset (you fall asleep faster)
When are benzo receptor agonists preferred over benzos?
- Slightly safer for patients wth chronic respiratory dysfunction.
- Less likely to develop tolerance
- No reduction of deep sleep
What kind of drug is zaleplon/sonata?
Schedule IV, benzo receptor agonist.
When is zaleplon/sonata used?
Short half-life, not indicated for long-term use.
What is the BBW of zaleplon/sonata?
Do not use for complex sleep-related disorders.
What kind of drug is zolpidem/ambien?
Schedule IV, benzo receptor agonist.
What is the BBW for zolpidem/ambien?
Do Not Use for complex sleep-related disorders
What should you avoid when taking zolpidem/ambien?
- Meals
- Grapefruit juice
- Sedatives
When is zolpidem/ambien indicated?
- IR: Sleep-onset insomnia
- ER: sleep-onset and sleep-maintenance insomnia. May be drowsy.
What kind of drug is eszopiclone/Lunesta?
Schedule IV, benzo receptor agonist
What benzo receptor agonist has the longest half-life?
Eszopiclone/Lunesta
What is the danger of taking exogenous melatonin chronically?
Desensitized receptors
How should you educate regarding OTC melatonin use?
- Short-term
- Maintain consistent sleep hygiene
- Caution in hypotensive patients
- Do not take with coumadin
- Avoid if hx of seizures or young.
What is ramelteon/rozerem?
- Melatonin receptor agonist.
- Superior affinity for receptors.
What drug must you avoid with ramelteon/rozerem use?
Fluvoxamine/Luvox
What is ramelteon/rozerem generally best for?
Improving sleep onset
How do dual orexin receptor antagonists work?
Antagonize the orexin receptors, which decreases the wake drive.
What are the dual orexin receptor antagonists?
- Suvorexant
- Lemborexant
- Daridorexant
All Schedule IV!
Orex ants
Which CYP enzyme do dual orexin receptor antagonists interact with?
3A4 inhibitor/inducer
What are the half-lives of the dual orexin receptor agonists?
- Suvorexant: shortest, fastest peak
- Daridorexant: medium
- Lemborexant: longest
Which dual orexin receptor antagonists does not require a dosage adjustment for the elderly?
Daridorexant
Newest one.
What patients are orexin receptor antagonists CId in?
Narcoleptic patients
What drug is used for narcoleptic patients?
Stimulant, specifically modafinil/provigil
Schedule IV
What are the two indications for modafinil? Dosing time?
Narcoleptics: first thing in the AM.
Shift work: 1 hour prior to shift.
What are sodium oxybates?
- Metabolite of GHB (date-rape drug)
- Strong CNS depressant.
Schedule III drug!
What is required to prescribe sodium oxybate?
REMS program registration, due to the potential of date-rape.
