Exam 2: Sleep disorder Flashcards
Types of sleep disorders
Insomnia
sleep apnea
narcolepsy
circadian rhythm disorders
parasomnia
restless legs syndrome
Signs and symptoms of sleep disorders
Excessive daytime sleepiness (EDS)
Impaired daytime functioning
Irregular breathing
increased movement during sleep
Irregular sleep and wake cycle
Difficulty falling asleep
Cause of insomnia (drugs) MUST KNOW
Alcohol, caffeine, nicotine
alpha blockers
ACEi/ARBs
Diuretics
Statins
cholinesterase inhibitors
Anticholinergics
H2RAs
SSRIs/SNRIs
CNS stimulants
Opioids
bronchodilators
Corticosteroids
Decongestants
Risk for chronic insomnia
Psych conditions
- depression,anxiety,SUD,ptsd
Medical conditions
-COPD,rheum, CV,hyperthyroid, nocturia, GERD, DM,Cancer, preg, menopause
Neurological conditions
- neurodegenerative, neuromuscular, brain tumor, headache syndromes
Insomnia definition
persistent sleep difficulty w/ adequate sleep opportunity + associated daytime dysfunction
Transient insomnia
several days
Short term insomnia
<3 months
Chronic insomnia
at least 3 nights/week for 3 months +
Women are twice as likely to be affected by insomnia T/F
true
Treatment for transient/short term insomnia
Correct underlying sleep complaint
avoid ADR of medication (short term)
- identify stressor/resolve
- keep sleep diary
Sleep hygiene principles
maintain a regular sleep schedule
avoid napping
establish a calm bedroom setting
do not spend time in bed if awake
limit intake of nicotine, caffeine, alcohol
exercise regularly but not close to bedtime
avoid large meal close to bedtime
avoid watching the clock
considerations for selection of specific sleep medication:
- desirability for daytime anxiolytic effect
- need for next day early morning cognitive sharpness
- interactions with other medications
- patient’s specific insomnia complaints
Treatment of long-term insomnia
First line: cognitive behavioral therapy (CBT-I)
CBT-I +/- medications»_space; only meds
If rapid improvement is necessary: use CBT-I + medications (taper)
Sleep ONSET insomnia tx
Older age/cognitive dysfunction/opioid use:
- DORA (daridorexant, lemoborexant, suvorexant)
- Ramelteon
>avoid next morning residual sedation
- Ramelteon
No reason to avoid first line BZRA:
- DORA
- Z drugs (eszopiclone, zaleplon, zolpidem)
- ramelteon
>want to avoid next morning residual sedation
- Zolpidem IR, zaleplon IR
- ramelteon
Sleep maintenance/mixed insomnia tx
Older age/cognitive dysfunction/opioid use:
- DORA (daridorexant, lemoborexant, suvorexant)
- DOXEPIN (low dose)
No reason to avoid first line BZRA:
- DORA
- Z drugs (eszopiclone/zolpidem)
- DOXEPIN (low dose)
Of benzos approved for insomnia, which has the most favorable safety profile?
Temazepam
Meds with dual indication for sleep onset + maintenance that have higher risk of next morning residual sedation include
DORAs
Zolpidem ER
eszopiclone
Zopiclone
First-line agent with less next morning residual sedation
Doxepin
Ramelteon
BZDRA
most commonly used to treat insomnia
Many are FDA approved but not all
includes newer non benzo gaba agonists and traditional benzos
BZDRA label caution for
COMPLEX SLEEP BEHAVIORS (think ambien, sleep walk)
anaphylaxis
facial angioedema
BZDRA MOA
agonist effect on GABA receptor
Benzo characteristics
Reduce sleep latency
Increase stage 2 and delta sleep
Anxiolytic
side effects are dose dependent
Caution use of benzos in:
sleep apnea
substance abuse
alcohol use
CNS depressant use
withdrawal (if high dose/long time)
Z drug characteristics
more selective
increase total sleep time
less disruptive of sleep stages
Generally less withdrawal, tolerance, and rebound insomnia
Z drug caution
associated with parasomnic episodes with amnesia (sleep walk/drive/eat)
How do you individualize BZDRA?
based on its PK profile and patient presentation
Benzo boxed warnings (3)
- use with opioids = profound sedation, resp depression, coma, death
- can lead to abuse = addiction = overdose/death
- can lead to physical dependence (withdrawal reactions, reduce risk by taper)
Z drugs boxed warning (1)
complex sleep behaviors
can result in serious injuries including death
D/C immediately if experience
Use of benzos in older adults
AVOID
- increase sensitivity = dependence, risk of fall, mv crash
OK if:
- seizure disorder
- rapid eye movement sleep behavior disorder
- benzo withdrawal
- ethanol withdrawal
- severe gen anxiety
- periprocedural anesthesia
Faster onset BZDRAs (tmax)
Flurazepam (0.5-1)
Zaleplon (1)
Temazepam (1.2-1.6)
Zolpidem (0.6-4)
Longer duration BZDRAs (Thalf)
Quazepam (39 hrs)
Estazolam (10-24)
Eszopiclone (6hr)
Temazepam (3.5-18.4hr)
BZD with lower daily dose
Triazolam 0.125-0.5 mg
Estazolam 1-2mg
Z drug with lower daily dose
Eszopiclone 1-3 mg
Zolpidem 1.75-12.5
BZD with higher daily dose
Flurazepam 15-30 mg
Temazepam 7.5-30mg
Quazepam 7.5-15mg
Z drug with higher daily dose
Zaleplon 5-20mg
Zolpidem 1.75-12.5
How does food alter BZDRAs onset of effect?
delays onset
T half of __________ is increased in the elderly
eszopiclone
t half of __________ is increased in the elderly
n-desalkylflurazepam (flurazepam metabolite)
T max of _______ differs based on fasting vs fed and also formulation (IR vs ER)
Zolpidem
Dosing of _____ differs based on formulation, gender, indication
zolpidem
Eszopiclone (lunesta) use
sleep maintenance + sleep onset
early morning awakening
Can be used longer than other agents ~6 months
delayed by food
Duration: 6-9 hrs of effect
major CYP3A4 substrates (4) used for sleep disorder tx
Eszopiclone (lunesta)
- monitor use w/ strong INHIBITOR (reduce dose to 1 mg (max 2mg)
Zaleplon (sonata)
- interaction with INDUCERS (cimetidine, rifampin)
DORAs (-rexant)
- dose reduce in weak INHIBITORS
- not recommend w/ moderate-strong inhibitors
Modafinil and armodafinil (inducers)
- may decrease the effectiveness of contraceptives
Eszopiclone (lunesta) ADR
headache
dysgeusia (metal taste)
nervousness/anxiety
xerostomia
infection
stomach upset
Zaleplon (sonata) use
Sleep onset
short term insomnia (30 days max)
Ultra short-acting, rapid onset
- less next morning residual sedation
AVOID HIGH FAT MEAL - delay
DOES NOT reduce night time awakening
Zaleplon (sonata) ADR
headache
nausea
abdominal pain
Zolpidem use
depends on formulation
AVOID in severe hepatic impairment d/t risk of encephalopathy
Intermezzo
zolpidem SL
middle of night awakening
take if more than 4hrs until wake up
F: 1.75 mg
M: 3.5 mg
Edular
Zolpidem SL
sleep ONSET (off label maintenance)
5mg, 10mg
take immediately before bedtime (w/ ≥7-8 hrs planned sleep before wake)
Ambien CR
zolpidem ER TAB
onset or maintenance
F: 6.25mg
M: 6.25-12.5mg
b4 bed w/ ≥7-8hr b4 wake
Ambien
zolpidem IR tab
onset (off label maintenance)
F: 5mg
M: 5-10mg
b4 bed w/ ≥7-8hr b4 wake
Generic zolpidem IR capsule
Sleep onset (off label maintenance)
M and F: 7.5 mg
if 5mg of another zolpidem IR product not effective, may increase to 7.5
b4 bed w/ ≥7-8hr b4 wake
DORAs
Dual orexin A and B receptor antagonists
- suvorexant
- Lemborexant
- daridorexant
DORA moa
turns off wake signaling
assists in onset/maintenance
INTERACTS CYP3A4
DORA contraindication
narcolepsey
(dora makes u sleepy)
DORA use
AT bedtime w/ ≥7 hr b4 wake
DORA drug onset
Lemborexant (dayvigo) <30 min
Suvorexant (belsomra) <30 min
Daridorexant (daridorexant) 30 min
Dora drug thalf
Daridorexant (Quviviq) 8 hr
Suvorexant (belsomra) 12hr
Lemborexant (dayvigo) 17-19 hr
Suvorexant (belsomra) ADR
sleep paralysis
abnormal dreams
URTI
drowsiness/dizziness/headache
Lemborexant (dayvigo) ADR
Complex sleep behaviors
abnormal dreams
Which DORA has warning for next day drowsiness and increased fall risk?
Lemborexant (dayvigo)
NEXT DAY DROWSINESS = risk of fall
- CNS depression may persist for SEVERAL days after d/c
Which DORA has drug onset delayed by food?
Daridorexant (quiviviq)
Daridorexant (quiviviq) ADR
Complex sleep behaviors
HALLUCINATIONS
Sleep paralysis
Ramelteon (Rozerem)
Melatonin receptor agonist
- MT1 = induce sleepiness
- MT2 = regulate circadian
1>2
T half 1-2.6 hrs
Ramelteon use
Long term use, sleep ONSET insomnia
Less rebound / abuse potential
Avoid ramelteon if
severe liver disease
patient already treated with BZDRA (not as effective)
ALSO TAKING FLUVOXAMINE (contraindication)
Why is Fluvoxamine contraindicated with Ramelteon?
Strong CYP1A2 inhibition
Ramelteon ADR
headache
dizziness
somnolence
Doxepin
Tricyclic antidepressant (TCA)
Doxepin use
Sleep MAINTENANCE insomnia
Doxepin dose
3mg - 6mg a day
(lower than dosing for depression)
Do not take within 3 hrs of a meal
Sleep Drugs with food effect
Doxepin (3 hrs!!)
Daridorexant (quiviviq)
BZDRAs
Doxepin BBW
suicidality
Melatonin
not approved by FDA
3mg - 5 mg QHS over 4 weeks
Melatonin use
sleep onset
shift workers
jet lag
When to avoid melatonin use
Alzheimers
- 2018 NICE guildlines; HA/dizziness not suitable
autoimmune conditions (immune modulator)
- can alleviate or exacerbate conditions
first gen antihistamines
Diphenhydramine
Doxylamine
AVOID IN OLDER ADULTS
Tolerance to sedative effect develops quickly
Anticholinergic ADR
Trazodone dosing
12.5 mg to 100mg QHS
Trazodone use
For pt w/ hx substance abuse +/- depression
Off label: may improve sleep continuity (maintenance)
Not recommended for chronic insomnia by VA or AASM
Trazodone BBW
suicidal ideation
Trazodone ADR
carryover sedation
alpha-adrenergic block
- orthostasis, careful fall risk
TAPER
RARE: priapism (erection)
Other off label insomnia therapies
TCA: amitriptyline
A2 agonist: Mirtazapine
Gabapentin
Elderly - insomnia rx
ramelteon
low dose doxepin
eszopiclone
zolpidem
Pregnancy - insomnia rx
diphenhydramine
doxylamine
low dose doxepin
Sleep apnea definition
stop breathing during sleep followed by o2 desat –> arousal from sleep to restart breathing
more common in men, AA, hispanic
Types of sleep apnea
Central (CSA)
- impair respiratory drive
Obstructive (OSA)
- upper airway collapse
Mixed
Obstructive sleep apnea etiology
linked to cardio/cerebrovascular morbitity/mortality/ indepednent of other risk factors (HTN risk, drug-resistant)
Associated w/ motor vehicle accident, depression, increased cancer risk, stroke, CV disease
Obstructive sleep apnea treatment
- behavior (weight loss, alter sleep position, avoid Etoh/sedatives)
- CPAP machine (standard of treatment)
- use daytime sleepiness meds
AVOID - cns depressant
- weight gain drugs (ex: TCAs)
Can improve BP and slow systemic disease onset
OSA: excessive daytime sleepiness meds
- modafinil
- armodafinil
- solriamfetol (sunosi)
- pitolisant (WAKIX)
OSA: alcohol
alcohol
- avoid or reduce within 2-4 hrs prior to sleep
- can exacerbate OSA, worsen daytime sleepiness, promote weight gain
OSA: cns depressants
benzos
z drugs
barbituates
gabapentin
sedating antidepressants
antihistamines
opioids, etc
- may exacerbate OSA + worsen daytime sleepiness
- use EXTREME caution with opioid medications
Modafinil and armodafinil schedule/approval
CIV
FDA approved for EDS in OSA and narcolepsy
Modafinil and armodafinil use
Administer in the morning
promotes awakeness
avoid use in pregnancy
use in CAUTION: cardiovascular disease
DO NOT USE if left ventricular hypertrophy
Modafinil and armodafinil DDI
May decrease the effectiveness of contraceptives by inducing CYP3A4
Modafinil and armodafinil ADR
headache!!!!
dizziness, nausea, xerostomia
anxiety, nervousness, dyspepsia
back pain, rhinitis
SJS/TEN/DRESS reported
Modafinil and armodafinil warnings
mania, exacerbation of psychotic symtpoms
CV events, chest pain, HTN, tachycardia
skin: SJS/TEN/DRESS reported
Modafinil/armodafinil MOA
increase alpha, decrease delta/theta
effects on dopamine, GABA, 5HT
Armo = R enantiomer
Solriamfetol (Sunosi) schedule/approval
CIV
FDA-approved EDS: OSA and narcolepsy
Solriamfetol (Sunosi) moa
dopamine and NE reuptake inhibitor
Solriamfetol (Sunosi) use
QAM
avoid use within 9 hrs planned bedtime (interfere w/ sleep)
AVOID use in unstable CV disease, arrhythmias (can cause tachy/htn)
Solriamfetol (Sunosi) contraindication
MAOI - avoid use with or within 14 days
Solriamfetol (Sunosi) ADR
headache, anxiety, insomnia, decreased appetite, nausea
Pitolisant (WAKIX) schedule/approval
Not controlled
FDA for narcolepsy
Off label EDS in OSA
Pitolisant (WAKIX) moa
antagonist/inverse agonist at histamine 3 receptors
Pitolisant (WAKIX) use
QAM
if pt is a CYP2D6 poor metabolizer = lower the dose
Major substrate CYP2D6 and CYP3A4 (dose adjust)
dose adjust renal impairment
Pitolisant (WAKIX) contraindication
severe hepatic impairment
Pitolisant (WAKIX) warning
may prolong QT in patients with KNOWN arrhythmias
Pitolisant (WAKIX) ADR
HEADACHE!!!!!
anxiety, musculoskeletal pain, URI
drugs that cause URI
Suvorexant (belsomra) ADR
Pitolisant (WAKIX)
Headache ADR (bolded)
Pitolisant (WAKIX)
Modafinil/armodafinil
Narcolepsy definition
impairment of both onset and offset of REM and NREM
Narcolepsy tetrad
- excessive/irresistible daytime sleepiness
- cataplexy
- hypnagogic hallucinations
- sleep paralysis
Narcolepsy patho
loss of normal function of hypocretin-orexin neurotransmitter system
commonly slips into sleep phases throughout the day
2 types of narcolepsy
type 1: with cataplexy (25-50/100k requires medical treatment)
type 2: without cataplexy (20-34/100k)
Narcolepsy treatment
good sleep hygiene
scheduled daytime naps
Avoid drugs that worsen daytime sleepiness
No disease modifying treatment yet
Drugs that worsen daytime sleepiness
benzodiazepines
opiates
antipsychotics
antiepileptics
alcohol
Narcolepsy treatment goal
achieve normal alertness during conventional waking hours
Treat symptoms:
- cataplexy
- excessive daytime sleepiness (EDS)
- REM sleep abnormalities
Narcolepsy EDS treatment
Modafinil
Armodafinil
Solriamfetol (sunosi)
Pitolisant
^ also for OSA
AMPHETAMINES
METHYLPHENIDATE
SODIUM OXYBATE (xyrem, lumryz)
OXYBATE SALTS (Xywav)
Sodium oxybate schedule/approval
CIII Xyrem
Approved for cataplexy or EDS in adults with narcolepsy
Sodium oxybate BBW (3)
- CNS depression
- Abuse/misuse
- Restricted access
Sodium oxybate use
give on EMPTY stomach
≥ 2 hrs after eating
Give while patient in bed
LIE DOWN IMMEDIATELY AFTER DOSE AND REMAIN IN BED
1st dose: in bed
2nd dose: 2.5 - 4 hours later
Sodium Oxybate MOA
CNS depressant, knocks you out, very strong
active moiety = GHB (gaba metabolite)
Sodium oxybate ADR
confusion
headache, dizziness
weight loss/decreased appetite
urinary incontinence
drowsiness
depression
Somnambulism
anxiety
Sodium oxybate COUNSELING
REMS:
INSTRUCT not to engage in hazardous activities req. mental alertness or motor coordination (at least 5 hrs after taking sodium oxybate)
ER sodium oxybate oral suspension (LUMRYZ) use
QHS
give on an empty stomach ≥2 hrs
administer while the patient is in med - lay down immediately after and remain.
MIX: 80ml water + dose
Give within 30 min of mixing
Oxybate salts (Xywav)
not just sodium –
contains calcium, magnesium, potassium, sodium
otherwise similar to Xyrem
REM supressing drugs for cataplexy in narcolepsy
- VENLAFAXINE (SNRI)
- duloxetine (SNRI)
- fluoxetine (SSRI)
- clomipramine (TCA)
+Pitolisant
+sodium oxybate
Abrupt withdrawal = status cataplecticus (severe nearly rebound cataplexy that can last several hours!!)
Circadian rhythm disorder
abnormalities in sleep wake pattern
- may present as insomnia +/ EDS
Different types of circadian rhythm disorders (6)
Delayed sleep-wake phase disorder
advanced sleep wake phase disorder
non-24hr sleep wake rhythm disorder
irregular sleep-wake rhythm disorder
Jet lag disorder
shift-work disorder
Jet lag disorder treatment
napping
timed light exposure
melatonin
ramelteon
Z drugs, benzos (risk of next day drowsiness)
Shift work disorder
Sleep hygiene, napping, exposure to bright lights at night, darkness during day, CBT-I
melatonin, ramelteon, suvorexant
Z drugs, benzos
Modafinil, armodafinil
Restless legs syndrome definition
paresthesias felt deep in calf muscles/thighs/ARMS
urge to keep limbs in motion
OFTEN BILATERAL
elderly,women, 10% adults, onset ≥40
Restless Legs Syndrome is associated with
CKD
iron deficiency
Vitamin B or folate deficiency
pregnancy
peripheral neuropathies
RLS: rule out other conditions
Nutrition
- iron deficiency (ferritin ≤75ng/mL)
- Vitamin B/folate deficiency
- Reduce caffeine and alcohol use
- weight loss
Smoking cessation
Regular moderate exercise
Sleep
Withdrawal of medications
Withdrawal of medications that may cause RLS
Central antihistamines
- meclizine
- hydroxyzine
- benadryl
- doxylamine
Antidepressants
- TCA, SSRI, SNRI (not bupropion)
Antipsychotics
Anti-nausea drugs that block dopamine (metoclopramide, promethazine)
Nonpharm treatment RLS
Sx relief: walking, biking, soaking limbs, leg massage
Activity to improve mental alertness
Yoga? acupuncture?
Rx for RLS - intermittent sx
carbidopa-levodopa
BZDRA (clonazepam most well studied)
Rx for RLS - chronic persistent sx
for painful RLS
A2 delta Calcium channel ligands
- pregabalin
- gabapentin (FDA approved)
Dopamine agonists (lower dose than PD)
- IR pramipexole
- ropinirole
- rotigotine
//increase dose – increase RLS severity – MONITOR
BZDRA: carryover sedation
