Sleep-Wake Cycle And Disorders Flashcards
Rapid eye movement (REM) sleep
paradoxical sleep
Period of de-synchronized EEG activity during sleep
- rapid eye movements
- muscular paralysis of major muscle groups occurs (cant roll over but peripheral muscles may move)
- *classical dreaming occurs here
- penile/clitoral tumescence
Physiological effects:
- loss of motor tone
- increased brain oxygen use
- BP/pulse changes (usually gets higher, but can be higher in pathology or drugs. Gets lower in Non-REM sleep)
- increased ACh
- is believed to be the site of memory formation
starts with occurrence every 90 minutes of sleep and increases throughout the night
Non-REM sleep
Synchronized EEG activity. 4 stages and is the deepest form of sleeping
4 stages:
1) awake:
- open eyes = beta waves
- closed eyes = alpha waves
- both are very low amplitude but high frequency
2) N1 sleep:
- Light sleep and produces theta waves
3) N2 sleep:
- produces sleep spindles and K-complexes
- *site of bruxism occurring during sleep
4) N3 sleep
- deepest non-rem sleep
- delta waves (high amplitude, low frequency)
- *site of sleep walking, night terrors and bed wetting “wee and flee”
characteristics:
- slow waves
- moderate muscle tones (can roll over)
- slow/absent eye movements
- NO genital activity
- less dreaming
What are used to measure sleep?
EEG
Electromyogram
- measuring muscle paralysis
Electrooculogram
- detects eye movements
Major differences between REM and non-REM sleep
REM:
- beta waves
- lack of muscle tone
- rapid eye movements
- penile erection or vaginal secretion
- dreams occur
Non-REM (slow-wave sleep)
- theta/delta waves
- moderate muscle tone
- slow or absent eye movements
- no genital activity
- less dreaming and more nightmares/night terrors
What stage is the most common stage to be in throughout the night while sleeping?
REM sleep (25%)
What is the most common non-REM sleepover stage while sleeping?
N2 (45%)
How does REM sleep change over the course of a lifetime?
Decreases
- starts at 50% in newborns with total of 16 hrs on average
- adults (20s) = 20% with total of 8hrs on average
- elderly (60-70) = 15% with total of 6 hrs on average
common that stage 4 sleep just completely disappears in elderly populations
What is the key structure required for control of circadian rhythm?
The suprachiasmatic nucleus (SCN) area of the hypothalamus
- located just above the optic chiasm
Contains the biological clock that is responsible for organizing many of the body’s circadian rhythms
Pineal gland function in circadian rhythm
Endocrine gland that produces melatonin (serotonin-derived hormone)
- modulates sleep patterns
- production is triggered by darkness and fatigue
How does cortisol secretion work during sleep?
Decreases in 1st phase of sleep (N1)
Arises back up again once you begin to wake up
Reticular Activating System (RAS)
Neural circuit from the brain stem up to the thalamus that controls awakening and alertness
- uses NE as the primary transmitter
- damage to center = cant awaken = coma
- over stimulation = cant fall asleep
NE is associated with decreased REM sleep
Raphe nucleus
Serotonin neurons extending from raphe nucleus throughout the limbic system and forebrain
- primary neurotransmitter is serotonin
- active during sleep onset and begin to force someone into sleep
- serotonin neurons fire less as sleep prolongs, but is needed to both initate sleep and awaken someone from deep sleep -> REM sleep
- damage = cant fall asleep
- overstimulation = immediate sleep
holds almost all of the brains serotonergic neurons
Adenosine’s effect on sleep control
Neuromodulator that is released by neurons engaging in high levels of metabolic activity
- is believed to play a primary role in initiation of sleep (due to build up over the day)
caffeine is an antagonist of adenosine receptors = slows the build up of adenosine
ACh effect on sleep (dorsal pons/basal forebrain)
Long known to produce arousal and sleeplessness
- increase ACh in the dorsal pons and basal forebrain = desynchronization of the cortical regions of the cerebral cortex
- *increases REM sleep
Histamine effect in sleep
Originate in the hypothalamic tuberomammillary nucleus (TMN)
- promote and stabilize wakefulness and attention
- inhibts non-REM sleep
anti-histamines = sedation
Orexin (hypocretin-1)
Involved in wakefulness and auroral and produced in the hypothalamus
loss of orexin neurons causes narcolepsy
How to diagnose sleep disorders
Sleep logs
Sleep inventory (questionnaire)
Blood tests (rule out medical and thyroid problems)
Sleep study/polysomnography
- EEG oxygen levels and movements/patterns during sleep
What questions should you ask for sleep disorders?
Onset
Duration
Frequency
Course
Aggravating factors
Past and current treatments (and responses if any)
Insomnia
Chronic inability to sleep despite adequate opportunity to do so
- 9-15% of population
Primary insomnia:
- sleep is disrupted for prolonged periods not attributable to psychological factors. Tends to physical medical casues
- less common
Secondary/situational insomnia:
- transitory and usually has an attributable cause
- much more common
DSM-5 for insomnia
Unsatisfying sleep quality or quantity with 1 or more of the following disabilities
1) sleep initiation (sleep latency > 30 minutes)
2) sleep maintenance (wake time after sleep onset > 30 minutes)
* should be less than 12 times *
3) early-morning awakening (awake 30 minutes before scheduled time and before total sleep time = 6.5)
* very common in depression*
4) functional distress or improvement
Must be at least 3 nights a week for at least 3 months
not better explained by another sleep-wake disorder or due to substance use
How to measure sleep efficiency
Time asleep/time in bed
- < 85% is poor sleep efficiency
Behavioral sleep medicine
Identification of psychological factors that develop sleep disorders
Then apply validated treatments for sleep disorders
- cognitive and/or behavior therapies
- non-pharmacological treatment in insomnia is effective and should be considered first line before using medications*
- all sleep disorder treatment should include sleep hygiene as an adjunct as well
CBT in insomnia (CBTi)
Stepwise procedure to first improve sleep quality and then quantity
1) restrict time spent in bed to amount of sleep that is currently feasible, slowly increase sleep overtime
- also try to “re set” the biological clocks and align bedtime and rise time with specific times
2) use therapy strategies fro reducing sleep interference (worries mange stress, calming mind)
3) expose the patient to bright light upon waking
OTC sleep medications
Some combination of Diphenhydramine/ Benadryl
Provides anti-H1 activity to induce sedation and drowsiness
- contraindicated in prostate cancer patients
Sometimes used in combo w/ acetaminophen or alcohol
causes hangover effects and anti-cholinergic side effects
tolerance develops quickly and becomes an habitual issue, bad since it can stress the liver out
Sedative/hypnotic drugs
Benzos, NBDRs and Z-drugs
Z-drugs are 1st line pharmacological agents for insomnia
- administered for 4 weeks and not every night. tapered off slowly to avoid adverse effects: rebound insomnia, hangover effects, dependence and anterograde amnesia
DONT mix with alcohol
Benzos are contraindicated in patients with chronic insomnia
Ramelton
Newest drug in use and mimics the body regulation of the hormone melatonin.
- best used for people with problems in initiating sleep
- not good for those with trouble staying asleep
not a lot of evidence, but only minor dependence compared to benzos
Obstructive sleep apnea
- Loud snoring that is then preceded by periods of apnea and then waking up to snore again (subconsciously)
Extremely high rate of under diagnosis
Likely a leading cause in secondary insomnia
Risk factors:
- age > 40
- obesity
- males > females
Treatment:
- CPAP/BIPAP machine
- benzos, Z-drugs, and barbiturates are contraindicated
Central sleep apnea
Brain doesn’t send proper signals that control breathing. Similar to obstructive sleep apnea except:
- snoring is less common and not loud
- chest pain is present
- low tolerance for exercise
Treatment:
- address underlying neurological disorder
- stop opioid medications (if on)
- BIPAP/CPAP machine
Nightmare vs sleep terror
Nightmare = bad dream during REM sleep
- patient can remember the nightmare
- more likely in patients with PTSD and isolation behaviors
Sleep terror = recurrent episodes of the person awakes suddenly in stage 4 sleep (NON-REM) in a panic, but no recollection of the night terror in the morning.
- patient has complete amnesia of the night terrors
- most common in little kids and often subside by 10 yrs of age
- very uncommon in adults (2%) and are often indicative of underlying neurologic disorders
Nightmare treatment:
Non PTSD-associated nightmares = Image-reversal therapy is 1st-line
- visualize the end of nightmare and it usually goes away
PTSD-associated nightmares: image-reversal therapy with CBTi and Prazosin (a1/2 blocker, which decreases NE levels)= 1st-line
- DONT use clonazepam and venlafaxine
Night terror treatment
Usually self-limited (goes away as they get older)
Otherwise no treatment. Can try therapy if intense as well as educate the parents or guardians about sleep terrors
- often looks way worse then they actually are
Somnambulism (sleepwalking)
Occurs in non-REM sleep
- preforms activities that are usually performed during a state of full consciousness
- dont try to wake up just take them back to bed if possible.
- black box warning for Z-drugs because they increase sleepwalking and sleep driving = death*
- don’t prescribe these drugs to patients with history of sleep walking
REM behavioral disorder treatments
Sleep behavior disorder where the patient acts out their dream in it’s entirety. Can get violent.
Modify the sleep environment (especially if injury is possibility)
Medications = clonazepam (not in elderly, sleep apnea or dementia patients)
- melatonin (rameltion) can be an adjuvant agent
Sleep paralysis
Abnormal awakening from REM sleep where muscle paralysis is still active with hallucinations
- tell them to “count back from 20 when this happens” usually it goes away
Hypnapompic (sleep hallucinations right after wakening up)
Hypnagogic (sleep hallucinations right before going to sleep)
Changes to REM sleep based on pathology and medications/drugs
Elderly: decreases in REM and N3 sleep
Depression: increases REM sleep time, but latency is decreased (wake up earlier and is called insomnia)
- “ Shitty REM”
Narcolepsy: decreases REM latency
Alcohol and barbiturates/benzos = decrease REM and N3 sleep
- hence why benzos can be used in sleep walking/night terrors
NE agonists = decreases REM sleep
What controls the extraocular movements in REM sleep?
The paramedian pontine reticular formation (PPRF)
What is the standard hypnogram patterns
- Goes through REM -> N3 -> REM throughout the night
- REM sleep increases over time
- deep sleep decreases over time
Norepinephrine effect on sleep
Long known that catecholamine agonists produce arousal and sleeplessness in the brain
- specifically in the locus coeruleus*
- decreased NE neuron firing rates in the locus coeruleus occurs as sleep deepens and prolongs
What TCA can be used for insomnia?
Doxepin
What drug is an orexin receptor antagonist that is rather new and is indicated insomnia?
Suvorexant
- antagonizes orexin receptors
- not used often in practice
- contraindicated in narcolepsy
Narcolepsy
Excessive daytime sleepiness w/ recurrent episodes of rapid-onset overwhelming sleepiness
- at least 3 times a week for at least 3 months
- feels refreshed when awakening from sleep (compared to insomnia, OSA and MDD)
Caused by a decrease in orexin (hypocretin-1) neurons
Often shows hypnagogic and hypnopompic hallucinations as well as sleep paralysis
- also can present w/ or without cataplexy
Treatment:
- good sleep hygiene
- daytime = stimulants
- night time = sodium oxybate (GHB)
Enuresis
Nighttime urinary incontinence > 2 times a week for at least 3 months
- MUST be older than 5 years old
Treatment:
- behavioral modification = 1st line (scheduled voids, nighttime fluid restriction) and positive reinforcement)
- refractory only = oral desmopressin (ADH analog) is preferred over imipramine (although both can be used
