10/24 Sleep - Menza Flashcards
importance of sleep
no real consensus on importance of sleep, but agreed that it plays roles in:
- restoration : many genes turned on during sleep
- energy conservation (although v little diff in caloric consuption b/w sleep and quiet wakefulness)
-
**brain fx**
- memory consolidation
- better clearance of metabolic byproducts and CSF by 60%
general pattern of EEG waves/features seen in diff stages of sleep
- awake
- calm wakefulness
- sleep
- stage 1
- stage 2
- stage 3/4
- REM sleep
- awake : beta waves (15-40Hz)
- calm wakefulness : alpha waves (9-14Hz)
sleep
-
stage 1 : theta waves (5-8Hz)
- see hypnic myoclonia (jerks as falling asleep)
-
stage 2 : sleep spindles, K complexes
- HR slows, body temp drops
-
stage 3/4 : delta waves (1-4Hz); deep, restorative sleep
- also when bedwetting, night terrors, and sleep walking happen
-
REM sleep : alpha/beta waves, similar to awake
- approx 90min after falling asleep
- first lasts 10min, each successive one gets longer (final up to an hour)
- DREAMING
- muscle atonia
sleep-wake cycle and the two-process model
1. Homeostatic Drive to Sleep (ventrolateral preoptic nucleus)
- increases with duration of waking (poss driven by buildup of adenosine)
- governed by need for sleep
2. Circadian Rhythms (suprachiasmatic nucleus)
- confines sleep and waking to different phases of daily cycle
- sleep-independent
- entrained to light-dark cycle
players involved in the sleep-wake cycle
arousal system and neurotransmitters
role of VLPO
arousal system and nts
- locus ceruleus : norepi
- tuberomammillary nucleus : histamine
- raphe nucleus : serotonin
role of orexin
ventrolateral preoptic nucleus : GABA
- downregulates secretion of NE, 5HT, hist, and ACh → sleep
orexin/hypocretin
what is it?
major role and how it accomplishes it
clinical app
peptide produced in hypothalamus that promotes wakefulness
- major role: integrate metabolic, circadian, and sleep debt info
- strong excitation of various brain nuclei w roles in wakefulness (DA, NE, hist, ACh systems)
clinical application: orexin blocker suvorexant (Belsomra) approved in 2014 for insomnia
sleep-wake cycle: role of SCN
suprachiasmatic nucleus
during day, SCN activity promotes arousal and maintains wakefulness
at night, SCN stimulation is turned off by melatonin
why does coffee keep you awake?
sleep debt results in rising levels of adenosine
caffeine is an adenosine blocker
- blocks the effect of adenosine in VLPO!
- preventing GABA from being released and downregulating the arousal systems!
dx: sleep problem
possible types
- primary sleep disorder
- idiopathic insomnia (most common)
- sleep disordered breathing
- obstructive sleep apnea
- central sleep apnea
- Restless Leg Syndrome (RLS) and PLMS
- narcolepsy
- circadian rhythm sleep-wake disorders
- secondary to psychiatric or medical disorder
- treatment-emergent (drug-related)
questions to ask during history
nature of the problem (difficulty falling sleep, waking up freq/early, tired during day?)
onset (relation to illness, med, stress)
too much noise during sleep???
- suggestive of sleep disordered breathing)
too much movement during sleep???
- suggestive of RLS/PLMS
anything odd?
sleep apnea
signs/sx
whats the problem and why?
treatment?
characterized by pauses or gaps in breathing due to obstruction of airway
primary sx: daytime tiredness
- snoring, gasping
- large neck size, obesity
- assoc with major med conds (HTN, CAD, MI, stroke)
- partner or patient may hear noise (snoring, gasping, choking)
problem: sleep, sleep a long a time, but are dead tired when waking up
why? sleeping but never really hitting deep sleep! having to rouse themselves out of sleep every so often to exert voluntary control over clearing airway
treatment: CPAP (continuous positive airway pressure)
sleep related movement disorders
- restless leg syndrome (RLS)
* tx: DA agonists - periodic limb movement disorder (PLMS)
- sleep related leg cramps
- sleep related bruxism
REM behavior disorder
typically, when you dream, all muscles except breathing apparatus are turned off
REM behavior disorder: dreaming without muscle paralysis
- leads to acting on dreams
- can lead to physical harm to pt or partner
- often related to other conds (Parkinson’s, cerebrovasc disease, LBD)
dx: polysomnogram with video maonitoring and arm/leg/head leads
tx: clonazepam
parasomnias
sleep walking
sleep eating
night terrors
- risk for self-injury
- usually ages out but persists it up to 15%
- much more likely with sleep deprivation, sedative use, alcohol, stress
- occur during transition b/w sleep and waking (NREM)
narcolepsy
narcoleptic tetrad
- excessive daytime sleepiness
-
sleep paralysis
- intrusion of REM sleep muscle paralysis into waking
-
cataplexy (loss of muscle tone, usually with strong emotion)
- intrustion of REM sleep muscle paralysis into full wakefulness
-
hypnagogic and hypnapompic hallucinations when going off to sleep or waking
- intrusion of REM into consciousness
- two types : Type 1 (w cataplexy) vs Type 2 (without cataplexy)
- loss of orexin cells in hypothalamus
tx: modafinil, stimulants, antidepressants (suppress REM)
insomnia
comorbid medical and psych conditions
medical conditions often comorbid with insomnia
- respiratory (asthma, COPD, bronchitis)
- GI (GERD)
- neurologic (demential, PD, HD)
- musculoskeletal (rheumatoid arthritis, fibromyalgia)
- endocrinologic (menopause, hyperthyroidism)
psychiatric conditions often comorbid with insomnia
- mood disorders (depression, BPD, dysthymia)
- anxiety disorders (GAD, panic disorder)
- psychoses (schizophrenia)
- substance abuse (alcohol, caffeine, sedatives)
medications known to cause insomnia
- antidepressants (SSRIs, SNRIs, MAOIs)
- antihypertensives (lipophilic beta blockers)
- bronchodilators (theophylline)
- nasal decongestants (pseudoephedrine, phenylpropanolamine)
- antiPD drugs (levodopa)
- corticosteroids (prednisone)
insomnia with no known cause
- difficulty falling asleep
- difficulty staying asleep
- waking too early
- poor quality of sleep
leading to next-day consequences
consequences of insomnia
- daytime dysfx
- psych disorders
- incr healthcare utilization
- decr ability to fx
- impact on others
- accidents
age, gender and insomnia
age : prevalence increases with age
- 20-50% incr in elderly
gender : more prevalent in women
- 1.4x under 45, 1.7x over 45 (often attributed to menopause)
insomnia tx
non-pharmacologic approaches
- sleep hygiene
- exercise
- relaxation
- CBT
pharmacologic approaches
- monoamine antagonists
- GABA agonists
- melatonin agonists
- orexin antagonists
model of chronic insomnia
combo of…
- predisposing factors
- predipitating factors
- perpetuating factors
CBT for insomnia
- stress control : reduce anxiety
- stimulus control : reduce conditioned arousal
- sleep consolidation (quality over quantity)
- exercise
- sleep hygiene
medications for insomnia
- meds that block alerting neurotransmitters are sleep-promoting
- anticholinergic
- antihistamine
- 5HT, DA, NE blocker
- orexin blocker (suvorexant)
- drugs that activate GABA pathways are sedating (mimic VLPO activation)
- melatonin receptor agonists
sedative hypnotics
benzodiazepine receptor agonists: act at GABA-A receptor
- incr frequency of Cl ion channel opening → hyperpolarization → sedation, amnesia, anxiolysis, myorelaxation, ataxia
scheduled (IV)
advantages
- rapid abs, tissue distribution
- proven effectiveness in tx of insomnia
- shortened sleep latency
- decr freq and duration of awakening
- incr total sleep time
disadvantages
- tolerance and dependence
- rebound insomnia
- occasionally odd, dangerous behavior
- next-day sedation
ramelteon
- potent selective MT1/MT2 (melatonin) receptor agonist (negligible affinity for MT3 sites)
- negligible affinity for GABA-A receptor complex, DA/5HT/ACh, glu, NE, opiate receptors
suvorexant
(Belsomra)
first orexin blocker
- v ltd clinical experience available (along with clinical trial data)
- schedule IV
- next-day sedation
