60 - Pharmacotherapy of sleep Flashcards
disease states, medications, substances, associated with insomnia
- anxiety
- caffeine
- modafinil
- amphetamines
- beta-agonists
- BB
- nicotine
- thyroid meds
- mood disorders
- bupropion
- decongestants
- methylphenidate
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
latency
3
3
sleep onset only (5)
- zaleplon
- triazolam
- eszopiclone
- zolpidem
- ramelteon
sleep maintenance only (4)
- suvorexant
- doxepin
- eszopiclone
- zolpidem
sleep onset and sleep maintenance (3)
- eszopiclone
- zolpidem
- temazepam
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
- zolpidem, eszopiclone, zaleplon
- 5 mg
- long
- metallic
- 3A4
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
- hangover
- taper, 4
- temazepam
behavior
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
- fluvoxamine
- 30
- GI, somnolence, hyperprolactinemia
- 1A2
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
- non-24
- 1A2
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
- 7
- narcolepsy, narcolepsy
- 3A4
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
7
narcolepsy, narcolepsy
3A4
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
7
narcolepsy, narcolepsy
3A4
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
H1
- 7
- anticholinergic
trazodone
- not FDA approved for ___
- highly sedating ____
- commonly used in low doses for sleep
- long t1/2 - may see daytime ___
- insomnia
- antidepressant
- hangover
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
depression
quetiapine
- atypical antipsychotic with sedation side effects
- low dose is not recommended for use in insomnia unless there is a co-morbid ___ disorder
psychiatric
“glorfied antihistamine”
OTC antihistimines and natural products
diphenhydramine/doxylamine
- not recommended by AASM
- ___ SE - avoid in elderly patients
anticholinergic
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
- jet-lag, 1A2
- ragweed, daisy
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)
short term
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
5
insomnia, apnea
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
polysomnography
cardiorespiratory
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
- depressants
- prior
- CPAP
- modafinil, armodafinil
- sedative/hypnotic
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
- cataplexy
- REM
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%
EDS
muscle, emotion
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
- 7
- high
- lower
- high
treatment of narcolepsy - excessive daytime sleepiness
- ___ / ___: associated with possible life threatening ___
- sodium oxybate
- methylphenidate, dextroamphetamine
- ___ and ___ recently FDA-approved for EDS
- selegiline
- modafinil/armodafinil, rash
- pitolisant, solriamfetol
___ (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 ___)
pitolisant
- H3
- hepatic
- QT
- 3A4/2D6
- 3A4, OC
- H, antihistamines
___ (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
solriamfetol
- dopamine-norepinephrine
- wakefulness
- renal, 37.5, 75
- 37.5
- BP, HR
- dopaminergic
shift work sleep disorder
___ or ___ are drugs of choice, taken 1 hour before the work period starts during “wake time”
modafinil, armodafinil
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
- gabapentin
- pramipexole, ropinirole
- iron
