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Sleep Wake Disorder Flashcards

1
Q

REM sleep is turned ON by…

A

cholinergic cells

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2
Q

REM sleep is turned OFF by…

A

noradrenergic cells

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3
Q

NT’s mediating NREM sleep include…

A

GABA

adenosine

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4
Q

Dopamine and Sleep

A

dopamine has an alerting effect

dec dopamine - promotes sleepiness

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5
Q

Neurochemicals involved in wakefulness

A

Cortex:
norepinephrine
acetylcholine

Hypothalamus:
histamine
neuropeptides (substance P, corticotropin releasing factor)

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6
Q

Common Etiologies of Insomnia

A

situational
medical
psychiatric

pharmacologically induced

  • anticonvulsants
  • central adrenergic blockers
  • diuretics
  • SSRIs
  • steroids
  • stimulants
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7
Q

Nonpharmacologic Therapy

A

sleep hygiene

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8
Q

Sedative Medications

A

reduce anxiety, calming effect

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9
Q

Hypnotic Medications

A

produce drowsiness

encourage onset and maintenance of sleep

more pronounced depression of CNS than sedation

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10
Q

Sedative Hypnotic Drugs: pharmacokinetics

A

lipid soluble
good distribution to the brain

active and inactive metabolites

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11
Q

MC treatments for insomnia

A 
estazolam
eszopiclone*
flurazepam
quazepam
temazepam
triazolam
zaleplon*
zolpidem*
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12
Q

Benzodiazepines: MOA, pharmacokinetics

A

facilitate inhibitory actions of GABA

BZRDA: benzodiazepine receptor agonist

active metabolites

additive CNS depression with many drugs

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13
Q

Benzodiazepines: uses

A 
acute anxiety
panic attack
generalized anxiety disorder
insomnia
skeletal muscle relaxation
seizure disorder
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14
Q

Benzodiazepines: toxicities

A

extension of CNS depression
tolerance
dependence

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15
Q

Benzodiazepines: biotransformation

A

Chlorodiazepoxide: drug of choice for alcohol withdrawal

Lorazepam: no active metabolite, drug of choice for elderly

Flurazepam: 2 active metabolites - long acting

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16
Q

No active metabolites

A

Lorazepam
Oxazepam
Zolpidem

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17
Q

Sedation: agents

A 
Alprazolam
Buspirone
Chlordiazepoxide
Clorazepate
Diazepam
Halazepam
Lorazepam
Oxazepam
Phenobarbital
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18
Q

Hypnosis: agents

A 
Chloral hydrate
Estazolam
*Eszopiclone
Lorazepam
Quazepam
Secobarbital
Temazepam
Triazolam
*Zaleplon
*Zolpidem
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19
Q

BZDRA: ADEs

A 
High doses:
daytime sedation
psychomotor incoordination
cognitive deficits
prolonged half lives in older pts

anterograde amnesia
rebound insomnia

caution regarding:
anaphylaxis
facial angioedema
complex sleep behaviors

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20
Q

Anterograde Amnesia

A

impairment of memory and recall of events occurring after the dose is taken

more likely to occur with short acting agents

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21
Q

Rebound Insomnia

A

inc wakefulness beyond baseline amounts after abrupt discontinuation

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22
Q

Sedative Hypnotics: interactions

A 
alcohol
antihistamines
antipsychotic drugs
opioid analgesics
tricyclic antidepressants
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23
Q

Sedative Hypnotics: overdosage

A

severe respiratory and cardiovascular depression

reversal: flumazenil (benzodiazepines, eszopiclone, zolpidem, zaleplon)

24
Q

Flumazenil

A

reversing agent for BZDRAs

antagonist at benzodiazepine site on GABA receptor

short half life

toxicities:
agitation, confusion
possible withdrawal syndrome

25
Zolpidem, Zaleplon, Eszopiclone
hypnotics not benzodiazepines -more selective CNS depressant effects can be antagonized by flumazenil
26
Zolpidem, Zaleplon, Eszopiclone: MOA, pharmacokinetics
bind to GABA receptor sites facilitate Cl channel opening additive CNS depression with ethanol and other depressants short half lives
27
Zolpidem, Zaleplon, Eszopiclone: clinical application
sleep disorders (esp when sleep onset is delayed)
28
Zolpidem, Zaleplon, Eszopiclone: ADEs
extension of CNS depressant effects dependence liability
29
Barbiturates: agents
``` Amobarbital Butabarbital Pentobarbital Phenobarbital Secobarbital [Thiopental] ```
30
Barbiturates: MOA
prolongs inhibitory effects of GABA and glycine binds to receptor site different form benzodiazepines **actions are NOT antagonized by flumazenil blocks glutamic acid and high concentration Na channels
31
Barbiturates: uses
anesthesia (thiopental) insomnia and sedation (secobarbital) seizure disorders (phenobarbital)
32
Barbiturates: toxicities
extension of CNS depressant actions tolerance dependence liability
33
Barbiturates and Carbamates: interactions
induce liver enzymes --> drug interactions precipitate acute intermittent porphyria chloral hydrate: displace coumarins - inc anticoagulant effects
34
Antihistamines
sedating properties diphenhydramine, doxylamine > pyrilamine tolerance anticholinergic side effects
35
Antidepressants
sleep continuity amitriptyline, doxepin, nortriptyline daytime sedation ADEs: anticholinergic activity adrenergic blockade cardiac conduction prolongation
36
Sedating Antidepressants: Mirtazapine
promotes sleep ADEs: daytime sedation weight gain
37
Sedating Antidepressants: Trazodone
taken at bedtime sedation, sleep continuity OK in patients with substance abuse (no dependence) ADEs: carryover sedation alpha adrenergic blockade priapism
38
Suvorexant
turns off wake signaling orexin (hypocretin) ADEs: somnolence sleep paralysis, cataplexy, other narcolepsy sx's
39
Orexin: primary role
control of sleep and arousal
40
Ramelteon
melatonin receptor agonist for sleep onset insomnia forms active metabolie CYP1A2 ADEs: headache dizziness somnolence OK for pts with hx of substance abuse effective for pts with COPD and sleep apnea
41
Melatonin
regulates circadian rhythm and sleep onset
42
Valerian
herbal sleep remedy inc GABA concentrations smells like old gym socks
43
Narcolepsy: 4 characteristic symptoms
excessive daytime sleepiness cataplexy hallucinations sleep paralysis
44
Excessive Daytime Sleepiness
impairment of onset and offset of REM and NREM arousals and disturbed sleep during the night
45
Cataplexy
sudden bilateral loss of muscle tone varied severity and duration no LOC precipitated by highly emotional situations
46
Hallucinations
falling asleep and on awakening brief, dreamlike experiences that intrude into wakefulness
47
Sleep Paralysis
episodic loss of voluntary muscle tone that occurs when the individual is falling asleep or waking conscious but not able to move or speak
48
Narcolepsy: pathophysiology
dysfunction of hypocretin/orexin autoimmune destruction of hypocretin producing cells environmental influence (no present at birth) genetic component **vaccines not associated with inc risk of narcolepsy
49
Wake Disorder: non pharmacologic treatment
good sleep hygiene 2+ daytime naps daily (15 min min)
50
Wake Disorder: Treatment; EDS
modafinil armodafinil methylphenidate
51
Wake Disorder: Treatment: cataplexy
Tricyclic antidepressants (TCA) Serotonin-norepinephrine reuptake inhibitors (SNRI) Selective serotonin reuptake inhibitors (SSRI) Monoamine oxidase inhibitors (MAOI) Imipramine, protriptyline, clomipramine, fluoxetine, and nortriptyline
52
Wake Disorder: Treatment: EDS, cataplexy, hallucinations
sodium oxybate
53
Modafinil, Armodafinil
standared for EDS do NOT treat cataplexy no risk of tolerance, withdrawal, abuse may reduce effectiveness of hormonal contraceptives ``` ADEs: headache nausea nervousness insomnia ```
54
Amphetamines, Methylphenidate
fast onset ``` ADEs: insomnia HTN palpitations irritability ``` amphetamines: more risk of abuse and tolerance
55
Cataplexy Treatment: MOA
block serotonin and NE reuptake in locus coeruleus and raphe subsequent suppression of REM sleep
56
Wake Disorder: TreatmentL hypersomnolence and cataplexy
selegiline - REM suppression - inc REM latency
57
Sodium Oxybate
changes sleep architecture to resemble normal sleep inc slow wave sleep dec nighttime awakenings inc REM efficiency do not use with other CNS depressants ``` ADEs: nausea somnolence confusion dizziness incontinence ```

PHA 550 (26 decks)

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