4.6 Pharmacotherapy of sleep disorders

Question 1

What disease states, meds, and substances are associated w insomnia?

Answer 1

• Anxiety, mood disorders
• Caffeine, nicotine
• Modafinil, beta agonists, BBs, thyroid meds, bupropion, decongestants, methylphenidate

Question 2

What defines insomnia disorders?

Answer 2

Difficulties w sleep initiation, sleep maintenance, and/or early-morning awakening

Question 3

How often and long must sxs occur for it to be an insomnia disorder?

Answer 3

Takes place at least 3 nights/week for at least 3 months

Question 4

What is 1st line tx for insomnia disorders?

Answer 4

1st line tx is always non-pharm
- CBT and behavioral therapies ARE 1st LINE
- Sleep hygiene principles

Question 5

Which drug class is the most commonly used sleep meds?

Answer 5

Z-hypnotics (zolpidem, eszopiclone, zaleplon)

Question 6

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

Answer 6

It is lower in these pt groups - 5 mg

Question 7

What is a common SE of eszopiclone (lunesta)?

Answer 7

Metallic taste

Question 8

What kind of substrates are z-hypnotics and how is their metabolism affected?

Answer 8

3A4 substrates - metabolism is impacted by 3A4 inhibition and induction

Question 9

What are SEs of z-hypnotics?

Answer 9

• Somnolence, dizziness, ataxia, headaches
• Paracomnias: unusual actions while a person is sleeping; warning for all sleep meds

Question 10

Is there an abuse potential w z-hypnotics?

Answer 10

Yes, they are controlled substances - potential for abuse

Question 11

What happens if a pt uses z-hypnotics w other CNS depressants?

Answer 11

Additive effects - the effects of both drugs is greater

Question 12

Which benzo is used for sleep?

Answer 12

Temazepam

Question 13

What are the SEs of temazepam?

Answer 13

Drowsiness, dizziness, cognitive impairment, increased fall risk

Question 14

What do all FDA approved meds for insomnia have?

Answer 14

Sleep behaviors warning

Question 15

What meds are considered melatonin receptor agonists?

Answer 15

• Ramelteon
• Tasimelteon

Question 16

What is ramelteon CI w?

Answer 16

Fluvoxamine

Question 17

What are SEs of ramelteon?

Answer 17

GI upset, next day somnolence, hyperprolactinemia, prolactinoma

Question 18

What is tasimelteon approved for?

Answer 18

FDA approved for non-24 sleep-wake disorder (blind) in adults

Question 19

What substrates are ramelteon and tasimelteon and what is the caution w this?

Answer 19

1A2 substrates: watch for 1A2 inducers and inhibitors

Question 20

What drugs are in the orexin receptor antagonists class?

Answer 20

• Suvorexant
• Lemborexant
• Daridorexant

Question 21

How much sleep should a pt taking orexin receptor antagonists get?

Answer 21

At least 7 hrs of sleep

Question 22

What are orexin receptor antagonists CI in?

Answer 22

CI in narcolepsy - causes narcolepsy-like SEs

Question 23

What substrate is orexin receptor antagonists?

Answer 23

3A4 substrate

Question 24

What is the MOA of doxepin (silenor)?

Answer 24

TCA - low doses exert effect through H1 receptor antagonism

Question 25

What are SEs of doxepin (silenor)?

Answer 25

Anticholinergic SEs

Question 26

What is trazodone not approved for but still used in?

Answer 26

Not FDA approved for insomnia but clinically still used for insomnia

Question 27

What is a SE of trazodone why?

Answer 27

May see daytime hangover due to long half life

Question 28

What is mirtazapine used for and when?

Answer 28

Clinically used as sleep agent, esp in pts w depression who have difficulty sleeping

Question 29

What is quetiapine not used for?

Answer 29

Low dose quetiapine is not recommended for use in insomnia UNLESS there is co-morbid psychiatric disorder

Question 30

Is diphenhydramine/doxylamine recommended for insomnia?

Answer 30

Not recommended by AASM

Question 31

When can melatonin be considered for insomnia?

Answer 31

Can be considered in jet lag and pts w low melatonin levels

Question 32

What substrate is melatonin?

Answer 32

1A2

Question 33

What can german chamomile cause?

Answer 33

Allergic rxns in pts w daisy or ragweed allergies

Question 34

What is the diagnosis criteria of obstructive sleep apnea?

Answer 34

Pt must have evidence of at least 5 obstructive apneas per hr of sleep confirmed by polysomnography

Question 35

What are SEs of OSA?

Answer 35

- Excessive daytime sleepiness, snoring, pauses in breathing during sleep, headache, irritability - Sore throat, ED, impaired memory, GERD, mood disturbances

Question 36

Many pts have both apnea and insomnia. What should be treated first?

Answer 36

Apnea

Question 37

When should a pt undergo polysmonography?

Answer 37

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

Question 38

What are txs of sleep apnea?

Answer 38

- Weight loss (adjunctive rather than curative) - Smoking cessation - Alcohol and CNS depressants - Sleep on side rather than back - CPAP

Question 39

What should be done if an overweight/obese pt comes in for insomnia?

Answer 39

Consider assessment for sleep apnea prior to initiating meds

Question 40

What can excessive daytime sleepiness from OSA be treated w?

Answer 40

Modafinil or armodafinil - Review CPAP adherence first and possibility of RLS or PLMS

Question 41

What should be done first if a pt is being treated for apnea and insomnia?

Answer 41

Ensure OSA is addressed first before recommending sedative/hypnotic drug therapy

Question 42

What is the narcolepsy triad?

Answer 42

- Excessive daytime sleepiness - Cataplexy - Hallucinations - Sleep paralysis

Question 43

What are the txs for cataplexy from narcolepsy?

Answer 43

- 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

Question 44

What are the txs for excessive daytime sleepiness from narcolepsy?

Answer 44

- Modafinil/armodafinil: associated w possible life threatening rash - Sodium oxybate - Pitolisant and solriamfetol recently FDA approved

Question 45

What is the MOA of pitolisant (wakix)?

Answer 45

H3 receptor antagonist/ inverse agonist

Question 46

What is pitolisant (wakix) CI in?

Answer 46

CI in severe hepatic impairment

Question 47

What does pitolisant (wakix) cause that's CV related?

Answer 47

Prolongs QT interval

Question 48

What substrate is pitolisant (wakix)?

Answer 48

- 2D6/3A4 substrate

Question 49

How does pitolisant (wakix) affect OCs?

Answer 49

It is a weak 3A4 inducer so it may reduce effectiveness of OCs

Question 50

Avoid use of pitolisant (wakix) w what drug class?

Answer 50

Avoid use w centrally-acting H1 receptor antagonists (OTC antihistamines)

Question 51

What is the MOA of solriamfetol (sunosi)?

Answer 51

DA NE reuptake inhibitor (DNRI)

Question 52

What is solriamfetol (sunosi) indicated for?

Answer 52

Indicated for improvement in wakefulness in adults w EDS due to narcolepsy or OSA

Question 53

What is the dosing of solriamfetol (sunosi) in pts w moderate renal impairment?

Answer 53

- Start 37.5 mg - May increase to 75 mg after at least 7 days

Question 54

What is the dosing of solriamfetol (sunosi) in pts w severe renal impairment?

Answer 54

Starting and max dose is 37.5 mg

Question 55

What are warnings associated w solriamfetol (sunosi)?

Answer 55

- BP, HR increases - Avoid in unstable CV disease and arrhythmias

Question 56

What are cautions associated w solriamfetol (sunosi)?

Answer 56

- Caution in pts w hx of psychosis or bipolar disorder: decrease dose or d/c if psychiatric sxs develop - Caution w dopaminergic drugs

Question 57

What are drugs of choice for tx of shift work sleep disorder?

Answer 57

Modafinil and armodafinil are drugs of choice

Question 58

When should modafinil and armodafinil be taken to tx shift work sleep disorder?

Answer 58

Taken 1 hr before work period starts during "wake time"

Question 59

What are drug txs for restless legs syndrome?

Answer 59

- Gabapentin enacarbil: prodrug of gabapentin, may be considered 1st line - DA agonists (IR): pramipexole, ropinirole

Question 60

What supp may be considered for restless legs syndrome?

Answer 60

Iron supp may be considered