4.6 Pharmacotherapy of sleep disorders Flashcards
What disease states, meds, and substances are associated w insomnia?
- Anxiety, mood disorders
- Caffeine, nicotine
- Modafinil, beta agonists, BBs, thyroid meds, bupropion, decongestants, methylphenidate
What defines insomnia disorders?
Difficulties w sleep initiation, sleep maintenance, and/or early-morning awakening
How often and long must sxs occur for it to be an insomnia disorder?
Takes place at least 3 nights/week for at least 3 months
What is 1st line tx for insomnia disorders?
1st line tx is always non-pharm
- CBT and behavioral therapies ARE 1st LINE
- Sleep hygiene principles
Which drug class is the most commonly used sleep meds?
Z-hypnotics (zolpidem, eszopiclone, zaleplon)
What is the initial dose of zolpidem in women and elderly?
It is lower in these pt groups - 5 mg
What is a common SE of eszopiclone (lunesta)?
Metallic taste
What kind of substrates are z-hypnotics and how is their metabolism affected?
3A4 substrates - metabolism is impacted by 3A4 inhibition and induction
What are SEs of z-hypnotics?
- Somnolence, dizziness, ataxia, headaches
- Paracomnias: unusual actions while a person is sleeping; warning for all sleep meds
Is there an abuse potential w z-hypnotics?
Yes, they are controlled substances - potential for abuse
What happens if a pt uses z-hypnotics w other CNS depressants?
Additive effects - the effects of both drugs is greater
Which benzo is used for sleep?
Temazepam
What are the SEs of temazepam?
Drowsiness, dizziness, cognitive impairment, increased fall risk
What do all FDA approved meds for insomnia have?
Sleep behaviors warning
What meds are considered melatonin receptor agonists?
- Ramelteon
- Tasimelteon
What is ramelteon CI w?
Fluvoxamine
What are SEs of ramelteon?
GI upset, next day somnolence, hyperprolactinemia, prolactinoma
What is tasimelteon approved for?
FDA approved for non-24 sleep-wake disorder (blind) in adults
What substrates are ramelteon and tasimelteon and what is the caution w this?
1A2 substrates: watch for 1A2 inducers and inhibitors
What drugs are in the orexin receptor antagonists class?
- Suvorexant
- Lemborexant
- Daridorexant
How much sleep should a pt taking orexin receptor antagonists get?
At least 7 hrs of sleep
What are orexin receptor antagonists CI in?
CI in narcolepsy - causes narcolepsy-like SEs
What substrate is orexin receptor antagonists?
3A4 substrate
What is the MOA of doxepin (silenor)?
TCA - low doses exert effect through H1 receptor antagonism
What are SEs of doxepin (silenor)?
Anticholinergic SEs
What is trazodone not approved for but still used in?
Not FDA approved for insomnia but clinically still used for insomnia
What is a SE of trazodone why?
May see daytime hangover due to long half life
What is mirtazapine used for and when?
Clinically used as sleep agent, esp in pts w depression who have difficulty sleeping
What is quetiapine not used for?
Low dose quetiapine is not recommended for use in insomnia UNLESS there is co-morbid psychiatric disorder
Is diphenhydramine/doxylamine recommended for insomnia?
Not recommended by AASM
When can melatonin be considered for insomnia?
Can be considered in jet lag and pts w low melatonin levels
What substrate is melatonin?
1A2
What can german chamomile cause?
Allergic rxns in pts w daisy or ragweed allergies
What is the diagnosis criteria of obstructive sleep apnea?
Pt must have evidence of at least 5 obstructive apneas per hr of sleep confirmed by polysomnography
What are SEs of OSA?
- Excessive daytime sleepiness, snoring, pauses in breathing during sleep, headache, irritability
- Sore throat, ED, impaired memory, GERD, mood disturbances
Many pts have both apnea and insomnia. What should be treated first?
Apnea
When should a pt undergo polysmonography?
ONLY if there is significant cardiorespiratory disease, potential respiratory muscle weakness due to neuromuscular condition, sleep-related hypoventilation, chronic opioid med use, hx of stroke, severe insomnia
What are txs of sleep apnea?
- Weight loss (adjunctive rather than curative)
- Smoking cessation
- Alcohol and CNS depressants
- Sleep on side rather than back
- CPAP
What should be done if an overweight/obese pt comes in for insomnia?
Consider assessment for sleep apnea prior to initiating meds
What can excessive daytime sleepiness from OSA be treated w?
Modafinil or armodafinil
- Review CPAP adherence first and possibility of RLS or PLMS
What should be done first if a pt is being treated for apnea and insomnia?
Ensure OSA is addressed first before recommending sedative/hypnotic drug therapy
What is the narcolepsy triad?
- Excessive daytime sleepiness
- Cataplexy
- Hallucinations
- Sleep paralysis
What are the txs for cataplexy from narcolepsy?
- Sodium oxybate (xyrem): GHB, high sodium content
- Xywav: for adults and children 7 yo or older, also approved for idiopathic hypersomnia in adults; lower sodium content
- Lumryz: for adults only; ER dosage form, once nightly dosing, high sodium content
What are the txs for excessive daytime sleepiness from narcolepsy?
- Modafinil/armodafinil: associated w possible life threatening rash
- Sodium oxybate
- Pitolisant and solriamfetol recently FDA approved
What is the MOA of pitolisant (wakix)?
H3 receptor antagonist/ inverse agonist
What is pitolisant (wakix) CI in?
CI in severe hepatic impairment
What does pitolisant (wakix) cause that’s CV related?
Prolongs QT interval
What substrate is pitolisant (wakix)?
- 2D6/3A4 substrate
How does pitolisant (wakix) affect OCs?
It is a weak 3A4 inducer so it may reduce effectiveness of OCs
Avoid use of pitolisant (wakix) w what drug class?
Avoid use w centrally-acting H1 receptor antagonists (OTC antihistamines)
What is the MOA of solriamfetol (sunosi)?
DA NE reuptake inhibitor (DNRI)
What is solriamfetol (sunosi) indicated for?
Indicated for improvement in wakefulness in adults w EDS due to narcolepsy or OSA
What is the dosing of solriamfetol (sunosi) in pts w moderate renal impairment?
- Start 37.5 mg
- May increase to 75 mg after at least 7 days
What is the dosing of solriamfetol (sunosi) in pts w severe renal impairment?
Starting and max dose is 37.5 mg
What are warnings associated w solriamfetol (sunosi)?
- BP, HR increases
- Avoid in unstable CV disease and arrhythmias
What are cautions associated w solriamfetol (sunosi)?
- Caution in pts w hx of psychosis or bipolar disorder: decrease dose or d/c if psychiatric sxs develop
- Caution w dopaminergic drugs
What are drugs of choice for tx of shift work sleep disorder?
Modafinil and armodafinil are drugs of choice
When should modafinil and armodafinil be taken to tx shift work sleep disorder?
Taken 1 hr before work period starts during “wake time”
What are drug txs for restless legs syndrome?
- Gabapentin enacarbil: prodrug of gabapentin, may be considered 1st line
- DA agonists (IR): pramipexole, ropinirole
What supp may be considered for restless legs syndrome?
Iron supp may be considered
