Term
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Definition
STAGE 1:
relaxed wakefulness, initiates sleep
STAGE 2:
alpha wave
light sleep
rest for brain/muscles (50% adult sleep)
STAGE 3-4:
delta sleep
deep sleep
slow wave sleep (SWS)
feeling of rejuvenation, immune system enhanced, growth hormone secreted, protein synthesis
STAGE 5:
rapid eye movement (REM) sleep
dreaming occurs (20-30% adult sleep)
low muscle tone, learning and mood regulation
1st REM within 90 minutes of sleep onset |
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Term
| why is it good to use SSRIs and trazodone together? |
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Definition
serotonergic antidepressants decrease SWS
tazodone is a 5HT-2A/2C antagonist that increases SWS
given together to help maintain good sleep |
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Term
elements to good sleep hygiene = lifestyle modifications
everyone should implement these before adding pharmacological therapy |
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Definition
relax before bedtime:
comfortable sleep environment, temperature, noise, avoiding illuminated clocks, phone
routine and sufficient exercise:
3-4x per week
not too close to bedtime (increased wakefulness)
maintaining consistent bed and awakening times
limit alcohol, nicotine, caffeine intake
avoid large amounts of liquid in the evenings
sleep hygiene counseling:
develop regular sleep and wake pattern
limit bedroom activities to sleep and intimacy
avoid daytime napping
develop relaxing routine for 1 hour prior to sleep
exercise daily, but not within 2 hours of bed
avoid late meals/drinks
avoid keeping clock near the bed
avoid alcohol, caffeine, and nicotine |
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Term
| characteristics of primary insomnia |
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Definition
endogenous abnormality in sleep cycle or circadian rhythm
dyssomnias: abnormal amount, timing, quality of sleep (insomnia, narcolepsy, sleep apnea, circadian rhythm)
parasomnias: abnormal behavior/physiologic events in sleep |
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Term
| characteristics of secondary/comorbid insomnia |
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Definition
ACUTE:
emotion/physical stress
environmental stressors (light, noise)
CHRONIC:
medical, psychiatric disorders
sleep scheduling (shift work)
medications
substance abuse
BioPsychoSocial approach:
biological factors: hyperthyroidism, circadian rhythm disruption, pain
psychological factors: emotional stress/anxiety, "late night person"
social/environmental example: environmental stressors - light, sound, uncomfortable bed |
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Term
| behavioral modification strategies |
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Definition
LIFESTYLE MODIFICATIONS SHOULD BE ENFORCED PRIOR TO AND DURING THE USE OF ANY OTC OR PRESCRIPTION SLEEP AID THERAPY
stimulus control:
limit time to fall asleep to 20-30 minutes
if patient is not asleep in set time period they are instructed to leave the bedroom and engage in relaxing activity until they feel sleepy
should not nap the next day and attempt to retire at optimal time
paradoxical intention:
reduces sleep-related "performance anxiety"
patient attempts to stay awake for as long as possible, and fight the urge to sleep
decreases sleep latency when patient goes to bed
should not nap the next day and attempt to retire at optimal time |
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Term
| how should sedatives/hypnotics (benzodiazepines/non-benzodiazepine/misc.) be dosed? |
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Definition
take on an EMPTY STOMACH for fast absorption and to decrease daytime hangover
high fat/heavy meal will delay PO absorption and decrease onset of effect for all
tolerance/dose escalation possible with BZDs |
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Term
| properties of benzodiazepines used for sleep (flurazepam, temazepam, triazolam, quazepam, estazolam) |
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Definition
reduce sleep latency and increase total sleep time
also anxiolytic, anticonvulsant, and muscle relaxant effects
SHOULD BE TAPERED IF USED FOR GREATER THAN 30 DAYS
rebound insomnia, potential seizures (withdrawal)
tolerance (loss of efficacy), may need increased dose
higher abuse potential: euphoria
control schedule IV
often worsen sleep apnea:
muscle relaxant effects - central apneas
decrease REM sleep and decrease SWS (stages 3 and 4)
AVOID IN SLEEP APNEA, SUBSTANCE ABUSE HISTORY
T1/2 PROLONGED IN ELDERLY: ASSOCIATED WITH FRACTURES/FALLS |
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Term
| general properties of nonbenzodiazepine hypnotics (zolpidem, zaleplon (sonata), eszopiclone (lunesta)) |
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Definition
SIMILAR EFFICACY TO BZD with fewer ADRs, less rebound insomnia
minimal impact on sleep architecture
can cause impaired memory and motor skill deficits during daytime (falls/hip fractures more likely in untreated insomnia) |
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Term
| which Z-hypnotic has the longest and shortest half life? |
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Definition
shortest t1/2 = zaleplon (sonata) = 1 hr
longest t1/2 = eszopiclone (lunesta) = 4-6 hours
moderate t1/2 = zolpidem = 2-3 hours |
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Term
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Definition
duration of action = 6-8 hours
reduces sleep latency and midnight awakenings |
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Term
| uses of zaleplon (sonata) |
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Definition
reduces sleep latency
can be used for middle of night awakenings |
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Term
| uses of eszopiclone (lunesta) |
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Definition
| reduces sleep latency, wake time after sleep onset, # of awakenings, and increases total sleep time |
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Term
| side effects of Z-hypnotics |
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Definition
dizziness, HA, somnolence
rare sleep behavior disorder: sleep eating, psychosis
do not have BZD like anxiolytic and muscle relaxant effects
REBOUND EFFECTS, WITHDRAWAL, AND TOLERANCE MINIMAL
eszopiclone has 10-25% incidence of "UNPLEASANT TASTE" and more reports of "hallucinations" than other 2 agents
zolpidem has higher rates of rebound insomnia than other agents
3A4 INHIBITORS (macrolides, azoles, fluoxetine) increase plasma levels of zolpidem and eszopiclone |
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Term
| half lives of BZD used for insomnia |
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Definition
flurazepam t1/2 = 8 hours
quazepam t1/2 = 39 hours
temazepam t1/2 = 10-15 hours
triazolam t1/2 = 2 hours |
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Term
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Definition
approved for SLEEP ONSET INSOMNIA
melatonin increases at bedtime, antagonized by light
M1 receptor regulates sleepiness
M2 receptor regulates day and night body phases (circadian rhythm)
SHORT DURATION OF ACTION
t1/2 = 1-3 hours
NOT EFFECTIVE FOR SLEEP MAINTENANCE
substrate of CYP1A2 (smokers may need higher doses)
melatonin or melatonin agonists may be preferred for those at risk for falls or at high risk for daytime performance problems
preferred in those with schedule or time zone change induced insomnia |
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Term
| properties of 1st generation antihistamines used for insomnia |
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Definition
diphenhydramine, doxylamine, hydroxyzine
in many OTC INSOMNIA PREPARATIONS
increase fall risk in elderly
HIGH ANTICHOLINERGIC ADRS
"hang-over" effects
should be limited to 7-10 days of use |
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Term
| use of trazodone for sleep |
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Definition
trazodone is a 5HT-2A/2C antagonist, H1 and alpha agonist
used at subtherapeutic antidepressant doses (50-150 mg)
increase stage 3 and 4 sleep (SWS)
CAN BLOCK SLOW WAVE SLEEP DISRUPTIONS OF SSRIS |
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Term
| use of TCAs for sleep (amitriptyline, nortriptyline, doxepin) |
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Definition
**anticholinergic effects
RESERVED FOR COMPELLING INDICATIONS (I.E. PAIN)
doses less than those used for antidepressant effects |
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Term
| use of mirtazepine (remeron) for sleep |
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Definition
inverse relationship between dose and sedation
RESERVED FOR COMPELLING INDICATIONS (DEPRESSION/ANXIETY) |
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Term
| rapidly absorbed and short half-life agents that are preferred for those with DIFFICULTY FALLING ASLEEP |
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Definition
zaleplon
ramelteon
triazolam |
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Term
| longer acting agents that are preferred for those who have TROUBLE STAYING ASLEEP |
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Definition
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Term
| duration of insomnia treatment |
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Definition
drug therapy should not be chronic except in extraordinary situations (PRN use)
limit exposure to drugs to 4-6 weeks in general |
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Term
| characteristics of sleep apnea |
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Definition
respiratory cessations during sleep with or without arousals to restore breathing
choking/gasping/snoring to elicit brief recurrent awakenings during sleep
RECURRENT OXYHEMOGLOBIN DESATURATIONS AND AROUSALS FROM SLEEP
results in non-restorative sleep, decreased SWS, decreased REM, EXCESSIVE DAYTIME SLEEPINESS
3 S's:
snoring
sleepiness
significant other report of sleep apnea episodes
sleepiness is one of the potentially most morbid symptoms of sleep apnea, owing to the accidents that can occur as a result of it
MOST COMMON IN:
middle aged
high BMI
large neck circumference
underlying upper airway obstruction
SERIOUS, POTENTIALLY LIFE-THREATENING CONDITION
associated with HTN, stroke, MI, arrhythmias, depression, insulin resistance diabetes, sleep related accidents and increased all cause mortality
diagnosed with overnight polysomnography |
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Term
| nighttime and daytime symptoms of sleep apnea |
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Definition
NIGHTTIME:
SNORING, usually loud, habitual, and bothersome to others
WITNESSED APNEAS, which often interrupt the snoring and end with a snort
GASPING AND CHOKING sensations that arouse the patient from sleep, though in a very low proportion relative to the number of apneas they experience
NOCTURIA
INSOMNIA
RESTLESS SLEEP, with patients often experiencing frequent arousals and tossing or turning during the night
DAYTIME:
NONRESTORATIVE SLEEP (i.e. "waking up as tired as when they went to bed")
MORNING HEADACHE, DRY OR SORE THROAT
EXCESSIVE DAYTIME SLEEPINESS (begins during quiet activitys; as the severity worsens sleepy during activities that require alertness (school, work, driving)
COGNITIVE DEFICITS; memory and intellectual impairment (short-term memory, concentration)
DECREASED VIGILANCE
MORNING CONFUSION
PERSONALITY AND MOOD CHANGES including depression and anxiety
SEXUAL DYSFUNCTION including impotence and decreased libido
GERD
HYPERTENSION
DEPRESSION |
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Term
| central and obstructive sleep apnea |
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Definition
central sleep apnea:
brain fails to initiate respirations
BZD, alcohol, opiates, CNS depressants may prevent arousals that restore breathing
obstructive sleep apnea:
blockage of airway in the rear of throat
causes mini arousals - fragmented and poor sleep
often presented as gasps for air
snoring often, but not always present
as many as 20-30 arousals per hour |
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Term
| central and obstructive sleep apnea |
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Definition
central sleep apnea:
brain fails to initiate respirations
BZD, alcohol, opiates, CNS depressants may prevent arousals that restore breathing
obstructive sleep apnea:
blockage of airway in the rear of throat
causes mini arousals - fragmented and poor sleep
often presented as gasps for air
snoring often, but not always present
as many as 20-30 arousals per hour |
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Term
| risk factors for obstructive sleep apnea |
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Definition
M>F
increased weight (esp. neck area)
obesity
central fat distribution
postmenopausal state
alcohol use
sedative use
smoking
habitual snoring with daytime somnolence
supine sleep position
rapid eye movement sleep
facial bone structure-flat facial features
increased age/decreased muscle tone
can affect ANY age group
Mallampati Class - "crowded airway"
mechanical and structural problems in the airway:
large tongue (scalloping)
elongated uvula
low lying palate
narrow palate
narrow space between back of uvula and palate
enlarged tonsils and adenoids
forehead and chin should align/poorly developed chin
hypolasia of cheeks |
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Term
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Definition
EXCESSIVE DAYTIME SLEEPINESS
falling asleep at inappropriate times
working, driving
learning, memory, and concentration difficulties
depression/anxiety/irritability
headache
nocturia: fight or flight
decreased metabolism (weight gain)
hypertension:
body compensates for hypoxemia
fight/flight response (increased NE)
HTN REFRACTORY TO DRUG THERAPY UNTIL SLEEP APNEA CORRECTED
increased inflammatory cytokines
increased risk of heart attack or stroke
increased mortality |
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Term
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Definition
continuous positive airway pressure (CPAP) = GOLD STANDARD
weight loss for obese
removal of tonsils/adenoids (pediatric)
uvulopalatopharyngoplasty
mandibular advancement (dental device to extend jaw)
STIMULANT MEDICATION ADJUNCTS FOR RESIDUAL DAY TIME SEDATION |
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Term
| drug therapy for residual daytime sleepiness |
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Definition
ADJUNCTIVE TO lifestyle modifications and CPAP!
modafinil (provigil)
armodafinil (nuvigil)
CAUTION: MAY HIDE RECOGNITION OF ESSENTIAL CPAP ADJUSTMENTS BY REMOVING DAYTIME SLEEPINESS |
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Term
| ADRs of modafinil and armodafinil |
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Definition
schedule IV controlled substance
HA, nausea, nervousness, anxiety, insomnia
caution in patients with cardiac abnormalities
monitor blood pressure
Sevens-Johnson syndrome: usually within first 5 weeks of treatment |
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Term
| stimulants for residual sleepiness |
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Definition
control II substances
IMMEDIATE RELEASE FORMULATIONS PREFERRED
methylphenidate, amphetamines
ADRs:
insomnia, HA, nervousness, irritability, overstimulation, tremor, dizziness |
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Term
| classic narcolepsy symptom tetrad |
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Definition
cataplexy:
decreased muscle tone while the patient is awake
sleep paralysis:
body is paralyzed when you are in REM sleep, but in narcolepsy, the patient is awake during the paralysis
excessive daytime sleepiness
hypnagogic hallucinations:
dream like symptoms while the patient is awake |
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Term
| characteristics of narcolepsy |
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Definition
EXCESSIVE DAYTIME SLEEPINESS +/- SUDDEN MUSCLE WEAKNESS
associated SLEEP ONSET REM PERIODS:
immediate onset of REM sleep
cataplexy develops over time:
bilateral loss of postural muscle tone
respiratory and ocular muscles never involved
lasts seconds to minutes
associated with intense emotion
may not fall down, may retain consciousness (head bob, knees buckle)
sleep attacks last 10-20 minutes
occur in monotonous situations
refreshed for 2-3 hours afterward |
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Term
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Definition
non-pharmacological therapy:
"prescribed" 20 minutes naps - lunch and 5:30 PM
minimize stressors to minimize cataplexy attacks
pharmacological therapy:
STIMULANTS FOR SLEEP ATTACKS (NARCOLEPSY)
decreased episodes, increased performance, increased time to fall asleep
methylphenidate most studied
mixed amphetamines
modafinil/armodafinil |
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Term
| treatment of cataplexy symptoms in narcolepsy |
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Definition
Antidepressants:
weak evidence for decreased cataplexy
TCA: clomipramine, imipramine, nortriptyline
SSRI: fluoxetine, sertraline, paroxetine
also venlafaxine, selegiline
SODIUM OXYBATE = IDEAL FOR NARCOLEPSY WITH CATAPLEXY |
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Term
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Definition
identical to GHN (endogenous neurochemical...and date rape drug)
sodium oxybate is a GHB and GABA-B agonist
consolidates disrupted sleep
treatment for cataplexy (sudden sleep onset in response to stimuli) and excessive daytime sleepiness in patients with narcolepsy
contraindicated with other sedative hypnotics
dosed at bedtime while in bed
onset within 30 minutes
food significantly decreases bioavailability |
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Term
| cardinal features of restless leg syndrome |
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Definition
URGE TO MOVE LIMBS ASSOCIATED WITH PARASTHESIAS OR DYSESTHESIAS
symptoms start or become worse at rest
at least PARTIAL RELIEF WITH ACTIVITY
worsening of symptoms in the evening or at night
increases with age
F>M
unpleasant or creepy-crawly feeling in legs when sitting or lying still
create urge to move
relieved with movement, massage, warm bath
worse at night, may affect arms too
causes difficulty falling and staying asleep
USUALLY GETS PROGRESSIVELY WORSE OVER TIME |
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Term
| medications that can induce restless leg syndrome |
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Definition
SSRI
CCB
dopamine antagonists |
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Term
| risk factors of restless leg syndrome |
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Definition
decreased DA transmission in striatum
uremia, CKD, Fe deficiency anemia, pregnancy, increased age
ferritin is a cofactor of hyrosine hydroxylase (synthesizes DA)
low brain iron stores even with serum Fe/ferritin normal
RLS PATIENTS SHOULD HAVE IRON, IRON STORES, AND FERRITIN LEVELS MONITORED |
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Term
| characteristics of periodic limb movement disorder |
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Definition
PLMs are involuntary movements during sleep or when awak
sequence of 0.5-15 seconds of muscle contractions at intervals of 5-90 seconds
causes arousals from sleep
predominance early in the sleep cycle |
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Term
| non-pharm adjunctive treatments for restless leg syndrome |
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Definition
physiotherapy
mild stretching
hot/cold baths
alerting activities
stop offending medications, if possible
avoid coffee, nicotine, alcohol |
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Term
| 1st line therapy for RLS/PLM |
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Definition
CORRECT DEFICIENCIES
Fe 325 mg BID-TID with 100-200 mg vitamin C over 2-6 months
no drug FDA approved for PLMs |
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Term
| 2nd line therapy for RLS (after resolving deficiencies) |
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Definition
DA agonists (ropinirole/pramipexole/levadopa)
ropinirole (hepatic clearance)
pramipexole (renal clearance)
BOTH DOSED 1-3 HOURS BEFORE HS (LOWER DOSES VS. PARKINSON'S)
50-80% may need re-dose around midnight (augmentation)
ADRs: daytime sedation, nausea, dizziness, hallucinations |
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Term
| 3rd line treatment of RLS/PLM |
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Definition
anticonvulsants: gabapentin, carbamazepine studied
benzodiazepine: clonazepam, temazepam |
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Term
| 4th line treatment of RLS/PLM |
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Definition
for severe resistant symptoms
opioids: propoxyphene, tramadol, oxycodone, methadone |
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