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Psychopharmacology > Chapter 10: Disorders of sleep and their tx > Flashcards

Chapter 10: Disorders of sleep and their tx Flashcards

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1
Q

what is the arousal spectrum regulated by

A

histamine
dopamine
norepinephrine
serotonin
acetylcholine
GABA
orexin

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2
Q

sx of deficient arousal

A

inattention
cognitive dysfunction
sleepiness

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3
Q

sx of excessive arousal

A

hypervigilance
cognitive dysfunction
panic/fear
hallucinations/psychosis

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4
Q

how do wake-promoting drugs target histamine

A

enhancement of histamine release

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5
Q

how do sleep-promoting drugs target histamine

A

blockage of H1 receptors

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6
Q

which 2 enzymes terminate the action of histamine

A

-MAOB converts N-methylhistamine to N-methyltransferase
-in the periphery it is terminated by diamine oxidase

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7
Q

what is best known as targets for antihistamines

A

postsynaptic H1 receptors

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8
Q

what are well known targets of heartburn medicine

A

postsynaptic H2 receptors

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9
Q

which receptor functions as an autoreceptor for histamine

A

presynaptic H3 receptors

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10
Q

what does histamine do at NMDA receptors

A

alter the action of glutamate

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11
Q

where do all histamine neurons arise

A

small area in the hypothalamus called the tuberomammillary nucleus

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12
Q

what brain structure regulates arousal, wakefulness, and sleep

A

tuberomammillary nucleus in the hypothalamus

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13
Q

what is the difference between orexin and hypocretin

A

nothing. 2 scientists discovered at the same time and named two different things

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14
Q

what does hypocretin usually refer to

A

gene or genetic products

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15
Q

what does orexin typically refer to

A

peptide neurotransmitters themselves

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16
Q

which neurons are localized exclusively in hypothalamic areas

A

orexin/hypocretin

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17
Q

what happens when there is diminished release of orexins/hypocretins onto downstream wake-promoting neurotransmitters

A

destabilized wakefulness

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18
Q

which neurons degenerate in narcolepsy

A

orexin/hypocretin

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19
Q

what receptors regulate the postsynaptic actions of orexin A and B

A

orexin1 and orexin 2 receptors

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20
Q

which type of orexin binds to orexin 1 receptors and what does that do

A

orexin A binds and leads to increased intracellular calcium and activation of the sodium-calcium exchanger

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21
Q

which orexins bind to orexin recepto 2 and what does that do

A

orexin A and B
either increased expression of NMDA glutamate receptors or inactivation of G-protein-regulated potassium channels

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22
Q

what functions does orexin play a role in

A

stabilizing wakefulness and regulating feeding behavior and reward

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23
Q

how do orexin neurons fire during wakefulness

A

fire with tonic frequency to maintain arousal

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24
Q

where does orexin stimulate acetylcholine release from

A

basal forebrain
pendunculopontine and laterodorsal tegmental area

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25
where does orexin stimulate dopamine release from
VTA
26
where do orexins stimulate release of norepinephrine from
locus coeruleus
27
where does orexins stimultate srotonin release from
raphe nuclei
28
where does orexin stimulate release of histamine from
tuberomammillary nucleus
29
how does the homeostatic sleep drive work
adenosine starts to accumulate as as the person tires throughout the day which ultimately lead to disinhibition of ventrolateral preoptic nucleus and release of GABA in the sleep circuit
30
what mediates the circadian wake drive
light acting on the suprachiasmatic nucleus
31
what happens when light acts on the suprachiasmatic nucleus
stimulates release of orexin which enhances release of other wake-promoting neurotransmitters
32
where is histamine released in the circadian wake drive and what does that do
released onto neurons throughout the cortex and VLPO and it inhibits the release of GABA
33
what happens in the circadian wake drive when light fades
NE and 5HT are released onto neurons in the hypothalamus causing negative feedback to inhibit orexin release. Without orexin wakefulness is no longer stabilized
34
how many times do ultradian cycles repeat during one night
4-5 times
35
what are the 5 ultradian cycles
REM NREM stages 1-4
36
which regions of the brain are activated during REM sleep
thalamus visual cortex limbic regions
37
Role of GABA in ultradian cycles
it is on all night and rises for the first few hours of sleep, plateaus, and steadily declines before arousal
38
role or orexin in ultradian cycles
decreases during first few hours of sleep, plateaus, then steadily rises before arousal
39
acetylcholine levels in ultradian cycles
lowest levels during stage 4 NREM levels peak during REM
40
levels of dopamine, norepinephrine, serotonin, and histamine in ultradian cycles
lowest during REM peaks during stage 2 NREM
41
what effect can disordered sleep have on your health
circulating levels of leptin (anorectic) and ghrelin (orexigenic) are disrupted leading to dysfunctional insulin, glucose, and lipid metabolism that increases risk for DM, obesity, cardio disease
42
cognitive effects of disordered sleep
24h sleep deprivation same as legal intoxication
43
what does REM sleep modulate
memory consolidation
44
what is NREM sleep good for
declarative and procedural memory
45
neurobiological effects of sleep disturbance
impairs hippocampal neurogenesis which may explain the behavioral effects of sleep disturbance
46
what happens in insomnia in relation to sleep/wake circuits
more a problem with not being able to shut off arousal circuits than inability to initiate sleep circuits
47
what subunits must receptors contain to be sensitive to benzodiazepines
two B subunits a Y subunit two A subunits
48
where do benzodiazepine bind to GABAA receptors
allosteric sites
49
how do benzodiazepines work to improve sleep
facilitate GABA neurotransmission in inhibitory sleep circuits arising from the hypothalamus and the VLPO
50
what receptor subunit is targeted by all GABAA PAMs
a1
51
what are the 2 dual orexin receptor antagonists (DORAs)
suvorexant lemborexant
52
how does suvorexant work differently than benzos and Z drugs
inhibits ability of orexin to promote release of wake-promoting neurotransmitters rather than increase GABA
53
what type of inhibitor are suvorexant and lemborexant
reversible. Inhibition is reversed as natural orexin builds up in the morning
54
what is the serotonergic hypnotic used for insomnia
trazadone
55
what receptors does trazadone antagonize
5HT2A, a1, and H1
56
how does Trazadone work
blocks serotonin, norepinephrine, and histaine to reduce arousal rather than stimulate sleep drive
57
what is the H1 receptor antagonist that is used as a hypnotic
doxepin at low doses
58
GABAA receptor occupancy threshold for inducing sleep
25-30%
59
DORA receptor occupancy threshold for sleep induction
around 65%
60
behavioral treatments for insomnia
sleep hygiene relaxation training stimulus control therapy sleep restriction therapy intensive sleep retraining
61
what is one of the most common causes of daytime sleepiness
obstructive sleep apnea
62
central disorders of hypersomnolence
idiopathic hypersomnia narcolepsy
63
diagnostic criteria for idiopathic hypersomnia
-excessive daytime sleepiness for at least 3 months -short sleep-onset latency period -fewer than 2 periods of REM at onset of sleep (polysomnography)
64
what is cataplexy
sudden loss of muscle tone often triggered by strong emotions
65
why does cataplexy occur in narcolepsy
profound loss of orexin neurons in the hypothalamus causes low daytime levels which destabilizes motor function resulting in intrusion of motor inhibition and loss of motor tone during wakefulness
66
which polymorphism is present in 90% of those with narcolepsy
HLA DQB1-0602
67
4 circadian rhythm disorders
shift work disorder advanced sleep phase disorder delayed sleep phase disorder non-24-hour sleep-wake disorder
68
what does shift work disorder increase your risk of
cardiometabolic issues cancer GI disease mood disorders
69
what is advanced sleep phase disorder
go to sleep earlier than desired wake earlier than desired usually by 6h outside normal sleep/wake times
70
how do you dx advanced sleep phase disorder
sleep and/or actigraphy for at least 1wk morningness-eveningness questionnaire (MEQ)
71
what is delayed sleep phase disorder
unable to sleep until early morning hours then sleep late into the day
72
delayed sleep phase disorder is associated with polymorphisms in what gene
CLOCK
73
who is primarily affected by non-24-hour sleep-wake disorder
blind people
74
circadian treatment for delayed sleep phase disorder and shift work disorder
morning light/evening melatonin
75
circadian treatment for advance sleep phase disorder
early evening light and early morning melatonin
76
how does melatonin regulate circadian rhythm
acts at M1 and M2 sites on the suprachiasmatic nucleus
77
melatonergic hypnotic that improves sleep onset but not necessarily maintenance
ramelteon
78
Classification of ramelteon
M1/M2 agonist
79
what is the worlds most widely consumed psychoactive drug
caffeine
80
how does caffeine promote wakefulness
blocks the effects of adenosine buildup and restores affinity of D2 for dopamine over adenosine. Enhanced dopamine is wake-promoting
81
which neurotransmitters are enhanced by amphetamine and methylphenidate
dopamine norepinephrine
82
wake-promoting action of methylphenidate
NDRI
83
wake-promoting action of amphetamines
dopamine releasers and competitive VMAT2 inhibitors
84
what is approved for the treatment of narcolepsy but not OSA or shift work disorder
amphetamine
85
what is approved for treatment of narcolepsy AND OSA and shift work disorder
Modafinil armodafinil
86
modafinil and DAT
weak inhibitor with incomplete occupancy
87
what properties of modafinil allow it to promote wakefulness without promoting abuse
slow rise in plasma levels w/ incomplete DAT occupancy
88
how does dopamine release from modafinil cause arousal
cortex is aroused by dopamine release leading to downstream release of histamine and further activation of lateral hypothalamus with orexin with orexin release
89
does modafinil still work in patients with a loss of hypothalamic orexin neurons in narcolepsy
yes
90
effectiveness of modafinil for narcolepsy
effective but not as much as methylphenidate or amphetamine
91
wake-promoting NDRI that is more potent than wellbutrin but less potent than amphetamines and has a short half-life
solriamfetol
92
classification of pitolisant
H3 presynaptic antagonist
93
how does pitolisant work
blocks normal action of presynaptic H3 autoreceptors to inhibit histamine release. This causes disinhibition of presynaptic histamine which is wake-promoting
94
what is the thought behind why sodium oxybate (GHB) works to treat disorders of hypersomnia
rather than waking you up, it promotes such good sleep you are more alert during the day
95
how is GHB formed
from GABA
96
actions of sodium oxybate
full agonist at GHB receptors partial agonist at GABAB receptors
97
what med can reduce hypnagogic hallucinations and sleep paralysis
sodium oxybate

Psychopharmacology (13 decks)

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