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PHA 550 > Sleep Wake Disorder > Flashcards

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
Q

Zolpidem, Zaleplon, Eszopiclone

A

hypnotics

not benzodiazepines
-more selective

CNS depressant effects can be antagonized by flumazenil

26
Q

Zolpidem, Zaleplon, Eszopiclone: MOA, pharmacokinetics

A

bind to GABA receptor sites

facilitate Cl channel opening

additive CNS depression with ethanol and other depressants

short half lives

27
Q

Zolpidem, Zaleplon, Eszopiclone: clinical application

A

sleep disorders (esp when sleep onset is delayed)

28
Q

Zolpidem, Zaleplon, Eszopiclone: ADEs

A

extension of CNS depressant effects

dependence liability

29
Q

Barbiturates: agents

A 
Amobarbital
Butabarbital
Pentobarbital
Phenobarbital
Secobarbital
[Thiopental]
30
Q

Barbiturates: MOA

A

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
Q

Barbiturates: uses

A

anesthesia (thiopental)

insomnia and sedation (secobarbital)

seizure disorders (phenobarbital)

32
Q

Barbiturates: toxicities

A

extension of CNS depressant actions

tolerance

dependence liability

33
Q

Barbiturates and Carbamates: interactions

A

induce liver enzymes –> drug interactions

precipitate acute intermittent porphyria

chloral hydrate: displace coumarins - inc anticoagulant effects

34
Q

Antihistamines

A

sedating properties

diphenhydramine, doxylamine > pyrilamine

tolerance

anticholinergic side effects

35
Q

Antidepressants

A

sleep continuity

amitriptyline, doxepin, nortriptyline

daytime sedation

ADEs:
anticholinergic activity
adrenergic blockade
cardiac conduction prolongation

36
Q

Sedating Antidepressants: Mirtazapine

A

promotes sleep

ADEs:
daytime sedation
weight gain

37
Q

Sedating Antidepressants: Trazodone

A

taken at bedtime

sedation, sleep continuity

OK in patients with substance abuse (no dependence)

ADEs:
carryover sedation
alpha adrenergic blockade
priapism

38
Q

Suvorexant

A

turns off wake signaling orexin (hypocretin)

ADEs:
somnolence
sleep paralysis, cataplexy, other narcolepsy sx’s

39
Q

Orexin: primary role

A

control of sleep and arousal

40
Q

Ramelteon

A

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
Q

Melatonin

A

regulates circadian rhythm and sleep onset

42
Q

Valerian

A

herbal sleep remedy

inc GABA concentrations

smells like old gym socks

43
Q

Narcolepsy: 4 characteristic symptoms

A

excessive daytime sleepiness
cataplexy
hallucinations
sleep paralysis

44
Q

Excessive Daytime Sleepiness

A

impairment of onset and offset of REM and NREM

arousals and disturbed sleep during the night

45
Q

Cataplexy

A

sudden bilateral loss of muscle tone

varied severity and duration

no LOC

precipitated by highly emotional situations

46
Q

Hallucinations

A

falling asleep and on awakening

brief, dreamlike experiences that intrude into wakefulness

47
Q

Sleep Paralysis

A

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
Q

Narcolepsy: pathophysiology

A

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
Q

Wake Disorder: non pharmacologic treatment

A

good sleep hygiene

2+ daytime naps daily (15 min min)

50
Q

Wake Disorder: Treatment; EDS

A

modafinil
armodafinil
methylphenidate

51
Q

Wake Disorder: Treatment: cataplexy

A

Tricyclic antidepressants (TCA)
Serotonin-norepinephrine reuptake inhibitors (SNRI)
Selective serotonin reuptake inhibitors (SSRI)
Monoamine oxidase inhibitors (MAOI)

Imipramine, protriptyline, clomipramine, fluoxetine, and nortriptyline

52
Q

Wake Disorder: Treatment: EDS, cataplexy, hallucinations

A

sodium oxybate

53
Q

Modafinil, Armodafinil

A

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
Q

Amphetamines, Methylphenidate

A

fast onset

ADEs:
insomnia
HTN
palpitations
irritability

amphetamines: more risk of abuse and tolerance

55
Q

Cataplexy Treatment: MOA

A

block serotonin and NE reuptake in locus coeruleus and raphe

subsequent suppression of REM sleep

56
Q

Wake Disorder: TreatmentL hypersomnolence and cataplexy

A

selegiline

  • REM suppression
  • inc REM latency
57
Q

Sodium Oxybate

A

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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