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What is the definition of insomnia?
complaint of disturbed sleep in the presence of an adequate opportunity and circumstance for sleep
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What factors are associated with idiopathic (Primary) insomnia?
- chronic stress
- poor sleep hygiene
- learned insomnia
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What factors contribute to comorbid (Secondary) insomnia?
- dementia, depression, anxiety disorders
- GERD
- pain
- asthma
- substance abuse
- restless leg syndrome
- sleep apnea
- circadian rhythm disorders
- periodic limb movement disorder
- stimulants
- diuretics
- caffeine
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What is chronic insomnia?
at least 3 nights/wk for a month
most often associated with comorbid disorders
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What is acute insomnia?
- one night to a few weeks
- most often associated with emotional or physical stressors (illness, jetlag)
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What are the 2 stages of sleep?
REM and nonREM
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nonREM sleep is divided into what 4 stages?
- light sleep
- intermediate sleep
- deep sleep (physical well-being)
- deep sleep (physical well-being)
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What are the characteristics of REM sleep?
- physiological changes occur (BP, HR, RR)
- dreaming
- necessary for learning and mood regulation
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How long does a sleep cycle last?
1.5-2 hours
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How many times in a night does the sleep cycle repeat?
4-5 times
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Which stages increase as the number of cycles increases?
Stage 2 and REM
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Which part of the night contains the most stage 3 and stage 4 sleep?
the first half
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What happens to the sleep cycle as people age?
- stage 3 and stage 4 decrease
- stage 1 increases
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How many people actually respond to non-pharmacological tx of insomnia?
50-80%
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What is Cognitive-behavioral therapy (CBT)?
- sleep hygiene education:
- regular sleep schedule
- exercise
- avoid stimulants and caffeine before bed
- ensure comfortable sleep environment
- stimulus-control therapy:
- associate bedroom w/sleep
- only go to bed when tired
- avoid napping
- leave bedroom if unable to sleep within 15-20 minutes
- return to bed only when tired
- relaxation therapy:
- meditation
- sleep restriction:
- temporarily induce sleep deprivation (not recommended)
- yoga
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What drugs are used for insomnia?
- estazolam
- flurazepam
- quazepam
- temazepam
- triazolam
- eszopiclone
- zaleplon
- zolpidem
- amitriptyline
- doxepin
- trazodone
- ramelteon
- diphenhydramine
- doxylamine
- melatonin
- valerian
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Which BZDs (sedative hypnotics) are used for insomnia?
- estazolam
- flurazepam
- quazepam
- temazepam
- triazolam
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What is the MOA of BZDs?
bind to GABA receptor, increasing the activity of GABA when it binds to GABAA
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What part of insomnia do BZDs affect?
- decrease sleep latency
- increase total sleep time
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What are the side effects of BZDs?
- daytime sedation/hangover
- anterograde amnesia
- pregnancy category X
- complex sleep behaviors
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What DI do BZDs have?
all except temazepam are metabolized by 3A4 which increases CNS depression when used with other CNS depressants including alcohol
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Which BZD has the longest half-life?
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Which BZD has shortest half-life?
triazolam (means more likely to have anterograde amnesia)
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Which BZD has no active metabolites?
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Who should not take BZDs?
pts with COPD or sleep apnea d/t respiratory depressant effects
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Which BZDs should you recommend for insomnia?
- temazepam for sure
- maybe estazolam, but it's more expensive and has more DI
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What BZD-Receptor Agonists (BZD-RAs) are used for insomnia?
- eszopiclone (Lunesta)
- zaleplon (Sonata)
- zolpidem (Ambien)
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What is the MOA of BZD-RAs?
bind near the BZD receptor on GABA causing increased GABA activity
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What is the effect on sleep of BZD-RAs?
- decreased sleep latency
- increase total sleep time (not zaleplon)
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Which BZD-RA can have the dose repeated if planning on sleeping at least 4 more hours?
zaleplon (Sonata)
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How is eszopiclone (Lunesta) dosed?
- lower doses for sleep latency
- higher doses to increase total sleep time
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What are the side effects of BZD-RAs?
- HA
- dizziness
- bitter taste
- pregnancey cat C (except zolpidem - class B)
- complex sleep behaviors
all are metabolized by 3A4, careful with CNS depressants
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Which BZD-RA has shortest half-life?
zaleplon (Sonata)
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Which BZD-RA has an active metabolite?
eszopiclone (Lunesta)
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Who should use caution in using BZD-RAs?
- pts w/COPD or sleep apnea b/c of respiratory depressant effects
- depression - risk of suicidality
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What is the MOA for ramelteon (Rozerem)?
- Melatonin receptor agonism
- M1 and M2 specific
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What effects are produced by melatonin receptors?
- M1 - sedation
- M2 - circadian rhythm
- M3 - not for sleep
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What effect on sleep does ramelteon (Rozerem) have?
- decrease sleep latency
- possibly increase total sleep time
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What are the SE of ramelteon (Rozerem)?
- HA
- dizziness
- fatigue
- nausea
- preg C
- complex sleep behaviors
- metabolized by 3A4, careful with CNS depressants
- high-fat meals significantly increase levels
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What ADs are used for insomnia?
- amitriptyline (Elavil)
- doxepin (Sinequan)
- trazadone (Desyrel)
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What is the MOA for ADs in insomnia?
produce sedation by blocking histamine, ACh, NE, and 5-HT presynaptic receptors
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What effect do ADs have on sleep?
- decrease sleep latency
- increase total sleep time
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What are the SE of ADs?
- TCAs - anticholinergic
- trazadone (Desyrel) - HA, OH, lethargy
- preg C and enter breastmilk
- risk of suicidality
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What antihistamines are used for insomnia?
- diphenhydramine (Benadryl, Nytol, Sominex)
- doxylamine (Unisom)
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What is the MOA for antihistamines in insomnia?
block H1 and muscarinic receptors in the brain resulting in sedation
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What effect do antihistamines have on sleep?
- decrease sleep latency
- increase total sleep time
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What are the SE of antihistamines?
- anticholinergic
- avoid in breastfeeding
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What is a major drawback to using antihistamines for insomnia?
tolerance develops in a week = no chronic use
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What herbal products are used for insomnia?
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When should you take melatonin?
1h before desired sleep time
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What specific indications may melatonin be good for?
- shift-workers
- jet lag
- blindness
- ADHD
- autism
- low melatonin levels
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Which drugs should be recommended for acute insomnia?
- BZD (temazepam)
- BZD-RA (zolpidem IR)
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Which drugs should be recommended for chronic insomnia?
- Approved:
- zolpidem CR (Ambien)
- eszopiclone (Lunesta)
- ramelteon (Rozerem)
- Consider:
- trazodone (Desyrel)
- zolpidem IR (Ambien)
- temazepam
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Which drugs should be avoided in elderly w/insomnia?
- short half-life BZD
- TCAs
- antihistamines
- consider:
- trazodone (Desyrel)
- zolpidem IR (Ambien)
- start at 1/2 dose
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What should be used in peds/adolescents with insomnia?
melatonin
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What should be used in pregnant women with insomnia?
- zolpidem (Ambien):
- cat B
- compatible with breastfeeding
avoid BZDs
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What should be checked in pts with restless leg syndrome?
ferritin levels
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What can be done about restless leg syndrome?
- Intermittent sx:
- levodopa/carbidopa (Sinemet) q HS prn
- Daily sx:
- pramipexole (Mirapex)
- ropinirole (Requip)
- 2h before bed
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