60 - Pharmacotherapy of sleep

Question 1

disease states, medications, substances, associated with insomnia

Answer 1

• anxiety
• caffeine
• modafinil
• amphetamines
• beta-agonists
• BB
• nicotine
• thyroid meds
• mood disorders
• bupropion
• decongestants
• methylphenidate

Question 2

DSM-5 insomnia disorders

primary complaint of unsatisfying sleep quantity or quality

difficulties with sleep initiation ( __ ), sleep maintenance, and/or early-morning awakening

takes place at least ___ nights per week
present for at least ___ months

Answer 2

latency
3
3

Question 3

sleep onset only (5)

Answer 3

• zaleplon
• triazolam
• eszopiclone
• zolpidem
• ramelteon

Question 4

sleep maintenance only (4)

Answer 4

• suvorexant
• doxepin
• eszopiclone
• zolpidem

Question 5

sleep onset and sleep maintenance (3)

Answer 5

• eszopiclone
• zolpidem
• temazepam

Question 6

treatment of insomnia disorders

First line treatment is Non-PCOL
- sleep hygiene principles are necessary and should be counseled by the pharmacist - often need drug therapy

the z-hypnotics (3) are the most commonly used sleep meds

initial dose of zolpidem is lower in women and elderly - ___ mg

eszopiclone (Lunesta) - FDA approved for ___ term (6 months) use.
- patients complain of ___ taste

___ substrates - metabolism impacted by inhibition/induction

somnolence, dizziness, ataxia, headaches

parasomnias - unusual actions while a person is sleeping - warning on all sleep meds

controlled substances, additive effects with other CNS depressants

Answer 6

• zolpidem, eszopiclone, zaleplon
• 5 mg
• long
• metallic
• 3A4

Question 7

treatment of insomnia disorders

BZD
- longer acting agents more likely to cause ___
- ANY BZD can be used for insomnia
- MUST consider dose ___ to d/c (avoid life-threatening withdrawal, seizures, can take up to ___ months)
- ___ is the BZD used for sleep
- drowsiness, dizziness, cognitive impairment, increases fall risk

___ agonists: ramelteon, tasmelteon) for sleep onset

orexin antagonist for sleep onset of maintenance

doxepine (Silenor) - lower branded dose FDA approved for sleep (TCA)

all FDA approved insomnia medications have sleep ___ warning s

Answer 7

• hangover
• taper, 4
• temazepam

behavior

Question 8

melatonin receptor agonists - ramelteon

• greater affinity for melatonin receptors than melatonin
• attenuates the alerting signal from the suprachiasmatic nucleus to promote sleep
• CI with ___ or angiodema with past use
• sleep onset within ___ min ; may require up to ___ weeks of use to see effect
• ___ upset, next day __, hyper ___
• ___ substrates: watch for inducers/inhibitors

Answer 8

• fluvoxamine
• 30
• GI, somnolence, hyperprolactinemia
• 1A2

Question 9

melatonin receptor agonists - tasimelteon

• FDA approved for ___ sleep wake disorder in adults
• similar MOA, SE, and DI as ramelteon
• increased ALT, nightmares, unusual dreams
• ___ substrates: watch for inducers/inhibitors

Answer 9

• non-24
• 1A2

Question 10

orexin receptor antagonists (C-IV)

suvorexant
- 10 mg within 30 min of bedtime and at least ___ hours to sleep
- 10 mg - warn for impairment, 20 mg warn against daytime driving
- CI in ___ - causes ___ like SE
- ___ substrate

associated with potential for worsening depression/suicidal ideation

Answer 10

• 7
• narcolepsy, narcolepsy
• 3A4

Question 11

orexin receptor antagonists (C-IV)

lemborexant
- 5 mg within 30 min of bedtime and at least ___ hours to sleep
- onset may be delayed if taken with a meal
- decrease dose if moderate hepatic impairment
- 10 mg: avoid next day driving
- CI in ___ - causes ___ like SE
- ___ substrate

associated with potential for worsening depression/suicidal ideation

Answer 11

7
narcolepsy, narcolepsy
3A4

Question 12

orexin receptor antagonists (C-IV)

daridorexant
- 25 mg within 30 min of bedtime and at least ___ hours to sleep
- delayed absorption with a high fat, high calorie meal
- 50 mg: avoid next day driving
- CI in ___ - causes ___ like SE
- ___ substrate

associated with potential for worsening depression/suicidal ideation

Answer 12

7
narcolepsy, narcolepsy
3A4

Question 13

doxepin

TCA - low doses exert effect through ___ receptor antagonism
- useful for sleep onset and maintenance difficulties
- elderly = 3 mg
- duration of action about ___ hours
- ___ SEs

Answer 13

H1
- 7
- anticholinergic

Question 14

trazodone

• not FDA approved for ___
• highly sedating ____
• commonly used in low doses for sleep
• long t1/2 - may see daytime ___

Answer 14

• insomnia
• antidepressant
• hangover

Question 15

mirtazapine

• non-FDA approved for insomnia
• sedation is SE of lower doses
• clinically used as a sleep agent, especially in patients with ___ who have difficulty sleeping
• 7-15 mg at bedtime more sedating than 30 mg

Answer 15

depression

Question 16

quetiapine

• atypical antipsychotic with sedation side effects
• low dose is not recommended for use in insomnia unless there is a co-morbid ___ disorder

Answer 16

psychiatric

“glorfied antihistamine”

Question 17

OTC antihistimines and natural products

diphenhydramine/doxylamine
- not recommended by AASM
- ___ SE - avoid in elderly patients

Answer 17

anticholinergic

Question 18

OTC antihistimines and natural products

melatonin/chamomile
- melatonin can be considered for ___ and patients with low melatonin levels; ___ substrate
- german chamomile contains BZD like compoind; allergic reactions in patients with ___ or ___ allergies

Answer 18

• jet-lag, 1A2
• ragweed, daisy

Question 19

choosing treatment

• Academy of Sleep Medicine has stated that CBT and behavioral therapies are first line
• drug therapy is FDA-approved for ___ use (10 days)

Answer 19

short term

Question 20

DSM-5 criteria - obstructive sleep apnea

patient must have evidence of at least ___ obstructive apneas per hour of sleep confirmed by polysomnography
- symptoms include excessive daytime sleepiness, snoring, pauses in breathing during sleep, headache, irritability, sore throat, ED, impaired memory, GERD, mood disturbance
- clinically, there is greater recognition that many patients hae bpth apnea and ___ - both need treated with ___ treated first

Answer 20

5
insomnia, apnea

Question 21

AASM - diagnostic testing for sleep apnea

___ only if there is a significant ___ disease, potenitial repiratory muscle weakness due to neuromuscular condition, sleep related hypoventilation, chronic opioid medication use, stroke, or severe insomnia

Answer 21

polysomnography
cardiorespiratory

Question 22

treatment of sleep apnea

• weight loss, smoking cessation, avoid alcohol and CNS ___ , sleep on side
• if an overweight patient comines in for insomnia evaluation, consider looking ___ to medications
• ___ - continuous positive airway pressure
• excessive daytime sleepiness (EDS) can be treated with ___ or ___ - need to review CPCP adherence first and possibility of RLS or PLMS

when considering treating apnea and insomnia, ensure that the obstructive apnea is addressed before recommending ___ / ___ drug therapy

Answer 22

• depressants
• prior
• CPAP
• modafinil, armodafinil
• sedative/hypnotic

Question 23

DSM-5 criteria - narcolepsy

• recurring episodes of irresistible need to sleep

at least one of the following
- ___ episodes
- hypocretin deficiency
- ___ sleep latency

sleep paralysis may also occur

Answer 23

• cataplexy
• REM

Question 24

the narcolepsy tetrad

___ - occurs in 100% of patients, generally more severe in Type I narcolepsy
- narcolepsy with cataplexy or hypcretin deficiency syndrome

cataplexy - sudden loss of ___ tone triggered by ___ - 75%

hallucinations - 30-60%

sleep paralysis - 25-50%

all 4 symptoms - 10-33%

Answer 24

EDS
muscle, emotion

Question 25

# treatment of narcolepsy- cataplexy - sodium oxybate (Xyrem) - GHB - ___ sodium content - Xywav - for adults and children aged ___ or older, also approved for idiopathic hypersomnia in adults - ___ sodium - Lumryz - for adults only - ER dosage form, once nightly dosing, ___ sodium content

Answer 25

- 7 - high - lower - high

Question 26

# treatment of narcolepsy - excessive daytime sleepiness - **___ / ___: associated with possible life threatening ___** - **sodium oxybate** - methylphenidate, dextroamphetamine - **___ and ___ recently FDA-approved for EDS** - selegiline

Answer 26

- modafinil/armodafinil, rash - pitolisant, solriamfetol

Question 27

___ (Wakix) - FDA approved for excessive daytime sleepiness; efficacy in cataplexy - ___ receptor antagonist/inverse agonist - CI in severe ___ impairment - prolongs ___ interval - ___ / ___ substrate - weak ___ inducer - may reduce effectiveness of ___ - **avoid use with centrally acting ___ receptor antagonists (OTC ___)**

Answer 27

pitolisant - H3 - hepatic - QT - 3A4/2D6 - 3A4, OC - H, antihistamines

Question 28

___ (Sunosi) C-IV - ___ - ___ reuptake inhibitor (DNRI) - indicated for improvement in ___ in adults with excessive daytime sleepiness due to narcolepsy or obstructive sleep apnea - moderate ___ impairment - start ___ mg, may increase to ___ mg after at least 7 days - severe renal impairment - starting and max dose: ___ mg warnings - ___ and ___ increases; avoid in unstable CV disease and arrhythmias - use caution in patients with a history of psychosis or bipolar disorder - decrease dose or d/c if psychiatric symptoms develop - use with caution with ___ drugs

Answer 28

solriamfetol - dopamine-norepinephrine - wakefulness - renal, 37.5, 75 - 37.5 - BP, HR - dopaminergic

Question 29

# shift work sleep disorder ___ or ___ are drugs of choice, taken 1 hour before the work period starts during "wake time"

Answer 29

modafinil, armodafinil

Question 30

# restless legs syndrome urge to move the legs in response to an uncomfortable or unpleasant sensation that begins/worsens during periods of rest drug therapy - ___ enacarbil - prodrug, FDA-approved for RLS, growing evidence base for effectiveness, may be considered first line - dopamine agonists (IR formulation) - ___ or ___ - ___ supplementation may be considered - levodopa/carbidopa may be cosidered

Answer 30

- gabapentin - pramipexole, ropinirole - iron