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exam 4 > Sleep > Flashcards

Sleep Flashcards

1
Q

How do sedatives work? (four items)

A

Calms anxiety, decreases excitement and activity, does not produce drowsiness, and does not impair performance

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2
Q

Do anxiolytics cause sleepiness or sedation

A

NO, anxiolytics are antianxiety medications that do not produce sleep or sedation. Not all anxiolytics are sedatives

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3
Q

What do hypnotics do? (three things)

A

sleep-inducing, implies restful and refreshing sleep, NOT HYPNOTIZED

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4
Q

What are narcotics? (two points)

A

Sleep producing, opioids or illegal drugs

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5
Q

What structures does the reticular formation extend through? (3)

A

through the central core of the medulla oblongata, pons and midbrain

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6
Q

What is the reticular formation composed of (2)

A

white matter and loosely clustered neurons

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7
Q

What does the reticular formation do?

A

contains dopamine, adrenergic, serotonergic, and cholinergic neurons and regulates sleep-wake transitions and synchronization of EEG

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8
Q

What are the 3 stages of sleep?

A

Wakefulness, NREM, REM

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9
Q

How many stages are there in NREM and what are they?

A

4 stages
Stage 1= dozing
Stage 2= unequivocal sleep
Stage 3= voltage increase, frequency decrease
stage 4= delta waves

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10
Q

What stage does REM look similar to on an EE? (1, 2, 3, 4, or awake)?

A

similar to awake on the EEG

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11
Q

What are four factors that regulate sleep?

A

age, sleep history, drug ingestion, and circadian rhythms

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12
Q

What is chronopharmacology?

A

the circadian clock picture essentially

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13
Q

Which neurotransmitters regulate sleep? (8)

A

epinephrine, norepinephrine, dopamine, serotonin, histamine, acetylcholine, adenosine, GABA

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14
Q

What neurotransmitter is the main target for sleep medications?

A

GABA

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15
Q

Neuromodulators of sleep (5)

A

Growth Hormone, prolactin, cortisol, melatonin, endogenous peptides

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16
Q

four components of GABA neurotransmission

A

GABAa receptors, GABAb receptors, GABA transporters (GAT-1), GABA transaminase (GABA-T)

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17
Q

How many subunits are there on GABAa receptor

A

5 subunits

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18
Q

What kind of ion channel is GABAa receptor

A

Chloride ion channel

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19
Q

What are the orthosteric sites on GABAa receptor (2)

A

a1 and B2

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20
Q

What are the allosteric sites on GABAa receptor (2) and what three things target them?

A

benzodiazepines, ethanol, glucocorticoid target a1 and gamma2

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21
Q

What drug targets the channel pore of GABAa receptor

A

picrotoxin

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22
Q

Mechanism of action Benzodiazepines

A

facilitate the action of GABA by increasing the frequency of the channel opening. a1-5

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23
Q

what is the name of the drug class that are non-benzodiazepines that act at the BZD receptor

A

z-hypnotics

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24
Q

what 3 drugs are part of z-hypnotics

A

zolpidem, zaleplon, eszopiclone

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25
Q

What specific receptors do non benzodiazepines work on?

A

BZ1 receptors of a1 on GABAa receptors

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26
Q

What drug is a BZD antagonist used for overdose treatment

A

flumazenil

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27
Q

what is an inverse BZD agonist

A

B carbolines

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28
Q

How do barbiturates work

A

increase the duration of GABAa receptor channel opening and have direct effects on GABAa AT HIGH DOSES

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29
Q

1 position alkylation of BZDS produces

A

active metabolites like oxazepam

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30
Q

annealing the 1-2 bond of BZDs with triazole or imidazole ring yields ____ affinity and ____ half-life

A

high, decreased

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31
Q

the half life of diazepam is ___ (long or short)

A

long

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32
Q

What gets removed from diazepam and at what position to make oxazepam, and active metabolite?

A

dealkylated at 1 position

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33
Q

What is desmethyldiazepam

A

the intermediate between diazepam and oxazepam

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34
Q

Which BZDS have slow elimination and active metabolites? (6)

A

Chlordiazepoxide, Diazepam, Flurazepam, Clorazepate, Quazepam, Prazepam

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35
Q

Which two drugs are anticonvulsants and sedatives?

A

Diazepam and Clonazepam

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36
Q

True or False: Prazepam is commonly used in the US

A

FALSE, currently unavailable in US

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37
Q

Which was the first BZD?

A

Chlordiazepoxide, Diazepam, Flurazepam, Clorazepate, Quazepam, Prazepam

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38
Q

Which BZDS have intermediate elimination rates? (5)

A

Alprazolam, Lorazepam, Clonazepam, Oxazepam, and Temazepam

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39
Q

Which two BZDs are rapidly eliminated

A

Midazolam (VERSED) and Triazolam

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40
Q

What kind of sleeplessness is best for BZDs that have slow elimination and formation of active metabolites?

A

patients who wake up in the middle of the night

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41
Q

BZDs that are rapidly eliminated cause rapid tolerance (T/F)

A

True

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42
Q

Intermediate to rapidly eliminated BZDs should be used in 2 populations

A

elderly, patients with hepatic problems

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43
Q

What does taking BZDs with food do

A

delays absorption

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44
Q

Increase lipid solubility will increase speed of delivery to _____

A

the brain

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45
Q

True/False: BZDs are not a concern during pregnancy and breastfeeding

A

false, cross placental barrier and are detected in breast milk

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46
Q

Which are more dangerous at high doses, barbiturates or BZDs?

A

Barbiturates, may cause coma at doses that are too high whereas BZDs hit a plateau

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47
Q

Respiratory depression is a major concern for what drug class when combined with other agents?

A

BZDs

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48
Q

What is the result of BZDs on REM sleep? Which stages of sleep does it effect?

A

decreases REM sleep, decreases stages 3 and 4

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49
Q

Side effects of BZDs are ____ dependent

A

dose

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50
Q

What is Flumazenil used for

A

BZD antagonist for overdose

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51
Q

what is the max cumulative dose of Flumazenil for overdose?

A

3mg

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52
Q

What is the initial dose of Flumazenil for overdose

A

0.2mg IV over 30 seconds

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53
Q

What are some side effects of Flumazenil

A

induce convulsions, panic attacks, agitation, confusion, n/v, headache

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54
Q

is zolpidem short term or long term

A

short term

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55
Q

is zaleplon short term or long term

A

short term

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56
Q

is eszopiclone short term or long term

A

long term

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57
Q

how are z-hypnotics metabolized

A

cyp3a4

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58
Q

do z-hypnotics have less or more negative side effects on sleep patterns than BZDs

A

less!

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59
Q

FDA mandates that we must warn patients of what for z-hypnotics

A

weird behaviors during sleep, sleep cooking, sleep sex, sleep driving, sleep eating

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60
Q

Flunitrazepam is also called

A

roofies

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61
Q

Zolpidem can be used illicitly and is called

A

zombie pills or A-minus

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62
Q

is phenobarbital long acting or short acting

A

long acting

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63
Q

is pentobarbital long acting or short acting

A

short acting

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64
Q

What do Barbiturates do to REM sleep

A

decrease REM

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65
Q

Barbiturates may cause ____ and ____ depression

A

cardiovascular and respiratory

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66
Q

What part of the brain is GABAb receptor located in?

A

limbic system

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67
Q

what is the presynaptic ion for GABAb receptor? (increase or decrease)

A

Ca2+ decrease

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68
Q

What is the postsynaptic ion for GABAb receptor? (increase or decrease)

A

K+ increase

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69
Q

What are two drug agonists of GABAb receptors?

A

baclofen and GHB

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70
Q

Three antagonist drugs of GABAb receptor

A

phaclofen, saclofen, and 2-hydroxysaclofen

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71
Q

What are the two other names for GHB?

A

Xyrem and sodium oxybate

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72
Q

What should be given with GHB if it is chosen by a provider?

A

Give with concomitant stimulant use during the day to decrease excessive daytime sleepiness and decrease cataplexy (sudden loss of muscle tone during the day)

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73
Q

What is the target of GHB?

A

GABAa GABAb and GHB receptors

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74
Q

Liquid ecstasy, liquid x, juice, scoops are all street names for what drug

A

GHB, Sodium oxybate, Xyrem

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75
Q

Acute effects of GHB include 6 things

A

loss of reflexes/consciousness
amnesia
N/V
headache
seizures
death

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76
Q

How can you treat someone who has been spiked with GHB

A

THERE IS NO ANTAGONIST, supportive treatment only

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77
Q

Explain the levels of melatonin over the course of a day

A

melatonin begins being produced in the evening, peaks at night, and declines to low daytime amounts in the morning

78
Q

what gland produces melatonin

A

pineal gland

79
Q

What are the two melatonin agonists

A

Ramelteon and Tasimelteon

80
Q

Ramelteon is metabolized by what cyp

A

CYP1A2

81
Q

What kind of sleeplessness are melatonin agonists used for

A

insomnia characterized by difficulty with sleep onset

82
Q

What is the benefit of melatonin agonists for patients?

A

No abuse, no withdrawal, no dependency, non-controlled substance

83
Q

Receptor target of Ramelteon and Tasimelteon

A

high affinity for MT1 and MT2 melatonin receptors in the suprachiasmatic nucleus

84
Q

which drug is an orphan product

A

tasimelteon

85
Q

which drug can be used to treat non-24 hour sleep wake disorders in blind individuals?

A

tasimelteon

86
Q

where are oxerin receptors in the brain

A

hypothalamus

87
Q

what does oxerin do?

A

regulate wakefulness, arousal, and thermoregulation

88
Q

what is the target of suvorexant

A

orexin receptor antagonist, OX1 and OX2 in hypothalamus

89
Q

What are the indications of trazodone

A

antidepressant and hypnotic under investigation

90
Q

What OTC drugs can be used as a hypnotic (3)

A

Antihistamines (diphenhydramine, doxylamine, pyrilamine)

91
Q

What are the signs of sedative-hypnotic overdose?

A

depressed respiration, low blood pressure, no reflexes, hypothermia

92
Q

Disease states, medications, substances associated with insomnia (12)

A

anxiety, caffeine, modafinil, amphetamines, beta-agonists, beta-blockers, nicotine, thyroid meds, mood disorders, bupropion, decongestants, methylphenidate

93
Q

The DSM-5 renamed sleep disorder chapter to what

A

sleep/wake disorders to recognize its more than just not being able to sleep

94
Q

two sleep related movement disorders

A

restless leg syndrome and periodic leg movements in sleep (PLMS)

95
Q

two breathing related sleep disorders

A

obstructive sleep apnea and central sleep apnea

96
Q

two types of circadian rhythm sleep-wake disorders

A

non-24-hr sleep-wake (blind) and shift work type

97
Q

what is insomnia

A

difficulties with sleep initiation, sleep maintenance, and/or early morning waking

98
Q

how often must insomnia take place and how long must it be present

A

3 times per week for at least 3 months

99
Q

what kind of sleep disorder can be classified as transient (jet lag), short term (up to 4 weeks), and long term (more than 4 weeks)

A

insomnia

100
Q

what five medications are used to help sleep onset only

A

zolpidem, eszopiclone, zaleplon, triazolam, ramelteon

101
Q

what four medications are used for sleep maintance only

A

suvorexant, doxepin, eszopiclone, zolpidem

102
Q

what three medications can be used for both sleep onset and sleep maintenance

A

zolpidem, eszopiclone, and temazepam

103
Q

What is the first line therapy for sleep disorders

A

non-pharmacological and sleep hygiene

104
Q

What class of medications (bonus if you can name them) are used most commonly for sleep disorders

A

z-hypnotics (zolpidem, eszopiclone, zaleplon)

105
Q

what is intermezzo and what is it approved for

A

sublingual dosage form of zolpidem that is used if a patient wakes up in the middle of the night with at least 4 hours of sleep left

106
Q

What is the initial dose of zolpidem in women and the elderly

A

5 mg, lower to reduce fall risk

107
Q

what do some patients complain of when taking lunesta (eszopiclone)

A

metallic taste

108
Q

z-hypnotics are metabolized by what enzyme

A

cyp3a4

109
Q

four side effects of z hypnotics

A

somnolence, dizziness, ataxia, headaches

110
Q

what are parasomnias and what drug class causes them

A

z hypnotics, unusual actions while a person is sleeping

111
Q

T/F, Z-hypnotics are not controlled substances

A

false, high potential for misuse

112
Q

what causes more daytime hangover, z-hypnotics or BZDs

A

Z-hypnotics

113
Q

Which is the preferred BZD for sleep

A

temazepam

114
Q

side effects of BZDs for insomnia

A

drowsiness, dizziness, cognitive impairment, increased fall risk

115
Q

what are warning associated with doxepin for sleep

A

suicidality and sleep behaviors

116
Q

all sleep medications have what warning

A

odd sleep behaviors (sleep sex)

117
Q

Melatonin agonist have a greater affinity for melatonin receptors than melatonin, true or false

A

TRUE

118
Q

Two contraindications of ramelteon

A

with fluvoxamine or angioedema with past used

119
Q

how fast is sleep onset after taking ramelteon

A

30 minutes, see results after 3 weeks

120
Q

side effects of ramelteon

A

GI upset, next day somnolence, hyperprolactinemia, prolactinoma

121
Q

what is the dose of ramelteon

A

8mg 30 minutes before bedtime

122
Q

what is the unique indications of tasimelteon

A

non-24 sleep wake disorder in adults (BLIND)

123
Q

Addition side effects of tasimelteon

A

increased ALT, nightmares, unusual dreams

124
Q

dose of tasimelteon

A

20mg before bedtime on empty stomach at the same time every night

125
Q

melatonin agonists are substrates of which enzyme

A

1a2

126
Q

suvorexant dose

A

10mg 30 minutes before bed, must have at least 7 hours to sleep

127
Q

what is the warning associate with taking 20mg of suvorexant

A

warning against daytime driving

128
Q

Contraindication of suvorexant, lemborexant, and daridorexant

A

CI in narcolepsy due do cause narcolepsy-like side effects

129
Q

what enzyme metabolizes suvorexant, lemborexant, and daridorexant

A

3a4

130
Q

dose of lemborexant

A

5mg at bedtime with at least 7 hours of sleep

131
Q

dose of daridorexant

A

25mg at bedtime with at least 7 hours of sleep

132
Q

At what doses of suvorexant, lemborexant, daridorexant respectively should the patient be advised to avoid daytime driving

A

20mg, 10mg, and 40mg

133
Q

what happens to onset of effects of orexin receptor antagonists if the medication is taken with high-fat, high calorie meals, or food in general

A

the absorption is delayed and the effects are delayed

134
Q

orexin receptor antagonists can worsen what

A

depression and suicidal ideation

135
Q

doxepin receptor target

A

H1 receptor antagonism at low doses

136
Q

what kind of side effects are common on doxepin

A

anticholinergic side effects (4 Can’ts. CAN’T-See – blurred vision; CAN’T-Pee – urinary retention; CAN’T-Spit – dry mouth; CAN’T-Shit – constipation)

137
Q

True or false, trazodone is approved for insomnia

A

False

138
Q

What property of trazodone causes daytime hangover

A

long-half life

139
Q

how does the AASM feel about using trazodone for sleep

A

recommends against, though is clinically effective

140
Q

Mirtazapine is best used for sleep if patients have what other condition

A

clinically effective if patient has depression and difficulty sleeping

141
Q

what dose of mirtazapine is more effective (high or low)

A

low, 7mg is more sedating than 30mg

142
Q

Quetiapine recommendation for insomnia

A

not recommended for insomnia unless patient has a comorbid psychiatric disorder

143
Q

what kind of antipsychotic is quetiapine

A

atypical

144
Q

what is the recommendation for diphenhydramine for insomnia by AASM

A

not recommended

145
Q

side effects of diphenhydramine

A

anticholinergic and paradoxical hyperactivity, especially in children

146
Q

What co-morbid conditions should diphenhydramine be avoided in (3)

A

narrow angle glaucoma, acute asthma, and BPH due to anticholinergic effects

147
Q

what is melatonin metabolized by

A

1a2

148
Q

what kind of sleep issue should melatonin be used for

A

jet lag

149
Q

What should we warn patients about with german chamomile for sleep

A

allergic reactions in patients with daisy or ragweed allergies

150
Q

what is a CI of Kava

A

hepatotoxicity

151
Q

what is the FDA approved duration for sleep medication

A

short term use of 10 days…

152
Q

Patient must have evidence of at least _ obstructive apneas per hour of sleep confirmed by polysomnography

A

5

153
Q

what are the two obstructive apnea signs

A

daytime sleepiness, nocturnal breathing disturbances

154
Q

What are the symptoms of obstructive sleep apnea

A

daytime sleepiness, snoring, pauses in breathing, headache, irritability, sore throat, erectile dysfunction, impaired memory, GERD, mood disturbances

155
Q

How do you treat insomnia and sleep apnea

A

treat sleep apnea first. Many patients have both that will need to be treated.

156
Q

When should a patient get polysomnography (6)

A

significant cardiorespiratory disease, potential muscle weakness due to neuro-muscular condition, sleep-related hypoventilation, chronic opioid medication use, hx of stroke, severe insomnia

157
Q

non-pharm treatments of obstructive sleep apnea (4)

A

weight loss, smoking cessation, avoid alcohol and other CNS depressants, sleep on side instead of back

158
Q

What is a cpap and what should it be used for

A

continuous positive airway pressure for sleep apnea

159
Q

what two drugs can be used for excessive daytime sleepiness

A

modafinil and armodafinil

160
Q

what should be reviewed first before initiating modafinil and armodafinil for daytime sleepiness

A

CPAP adherence and possibility of RLS or PLMS

161
Q

What is narcolepsy

A

recurring episodes of irresistible need to sleep, fall asleep, or nap at least 3 times per week over the last 3 months

162
Q

What is common for narcoleptics

A

sleep paralysis

163
Q

What is the narcolepsy tetrad

A

EDS, cataplexy, hallucination, and sleep paralysis

164
Q

three drugs used for cataplexy

A

sodium oxybate (xyrem/GHB)
Xywav
lumryz

165
Q

what electrolyte is GHB high in

A

sodium (also called sodium oxybate)

166
Q

what age is Xywav approved for

A

adults and children 7 or older

167
Q

How is the sodium content of Xywav compared to GHB?

A

Xywav has lower sodium content

168
Q

Lumryz is IR and can be used for children

A

False, Lumryz is ER and is for adults only

169
Q

when should lumryz be taken

A

once at night

170
Q

sodium content of lumryz

A

high

171
Q

what is a black box warning for lumryz

A

respiratory depression and misuse

172
Q

what is a life threatening risk of taking modenafil and armodafinil for EDS

A

life-threatening rash

173
Q

in addition to cataplexy, GHB can be used for what tetrad of narcolepsy

A

EDS (excessive daytime sleepiness)

174
Q

what two drugs were recently approved for EDS

A

pitolisant and solriamfetol

175
Q

What is the receptor target of pitolisant

A

H3 receptor antagonist/inverse agonist

176
Q

Pitolisant is contraindicated in patients who have ____

A

severe hepatic impairment and moderate/severe renal impairment

177
Q

what enzyme does pitolisant induce or inhibit

A

3a4 inducer

178
Q

what medication should we be worried about having reduced efficacy when taken with pitolisant

A

oral contraceptive due to inducing cyp3a4 metabolism

179
Q

What OTC should pitolisant be avoided being used with

A

h1 receptor antagonists like OTC antihistamines

180
Q

what is a side effect of pitolisant

A

QTc prolongation

181
Q

What two neurotransmitters does solriamfetol prevent being uptaken

A

dopamine and norepinephrine

182
Q

is solriamfetol an agonist or inhibitor

A

inhibitor, prevents uptake of neurotransmitters

183
Q

what is the indication of solriamfetol

A

improve wakefulness in adults with EDS due to narcolepsy and OSA

184
Q

What is the starting and max dose of solriamfetol for patients with moderate renal impairment

A

37.5mg starting, max 75mg after at least 7 days

185
Q

what is the starting and max dose of solriamfetol for patients with severe renal impairment

A

37.5 is starting and max dose

186
Q

What patients should not get solriamfetol

A

patients with unstable CVD and arrhythmias, caution in patients with history of psychosis or Bipolar disorder

187
Q

what are the two drugs of choice for shift work sleep disorder

A

modafinil and armodafinil, taken 1 hour before the work period starts

188
Q

what is restless leg syndrome

A

the urge to move the legs in response to an uncomfortable or unpleasant sensation that begins or worsens during periods of rest, is partially relieved by movement, or is worse in the evening or night

189
Q

gabapentin enacarbil is a potential first line agent approved for what type of sleep/wake disorder

A

restless leg syndrome

190
Q

what two dopamine agonists may be used for RLS

A

pramipexole or ropinirole

191
Q

what supplement is recommended for restless leg syndrome

A

iron supplementation

exam 4 (7 decks)

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