Sleep-Wake Disorders- Krysiak

Which two main phases make up a normal sleep cycle?

Non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep

During which NREM stages does deep (delta) sleep occur?

• idk how imp

Stages 3 and 4 of NREM sleep

How many NREM/REM cycles does an adult typically experience each night and how long is one cycle?

• idk how imp

Four to six cycles, each lasting 70–120 minutes

What age-related change in sleep is common in the elderly?

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Lighter, more fragmented sleep with reduced slow-wave (delta) sleep

Which neurotransmitters are sleep promoting?

GABA, adenosine

Which neurotransmitters are wake promoting?

DA, NE, Ach, Histamine

The DSM-5 classifies sleep-wake disorders into 10 categories.

What are they?

• idk how imp, just RECOGNIZE

• insomnia

• hypersomnolence

• narcolepsy

• breathing-related sleep disorders

• circadian rhythm sleep disorders

• non-REM sleep arousal disorder

• nightmare disorder

• REM sleep behavior disorder

• restless leg syndrome (RLS)

• substance/ medication induced sleep disorder

List the DSM-5 criteria regarding frequency and duration for diagnosing chronic insomnia.

Sleep difficulty at least three nights per week for at least three months

What’s the main difference between primary and comorbid/ secondary insomnia?

Primary insomnia is endogenous—> secondary/comorbid insomnia is a symptom of another medical disorder

What classes of meds commonly cause insomnia?

• anticonvulsants

• central adrenergic blockers

• diuretics

• SSRIs

• steroids

• stimulants

What are the 3 categories of insomnia?

• transient—> acute stressor, resolves quickly

• short-term—> associated with stress, treated like transient

• chronic—> requires careful assessment, nonpharm approaches

Is insomnia normally treated with or without pharm therapy?

WITHOUT—> 70-80% of insomnia can be treated with non-pharm and have a positive response

List non-pharm options for insomnia:

• stimulus control therapy

• sleep restriction

• relaxation therapy

• cognitive therapy

• paradoxical intention

• biofeedback

• education on sleep hygiene

What are some recommendations for good “sleep hygiene”?

• exercise routinely

• create a comfy environment

• d/c or reduce alcohol, caffeine, and nicotine

• avoid drinking large amounts of liquids in the evening

• do something relaxing before bed

List the drugs that are benzodiazepine receptor agonists (BZDRAs):

• temazepam

• estazolam

• quazepam

• flurazepam

• triazolam

Which BZDRA is preferred in the elderly for insomnia?

Temazepam

Answer the following about BZDRAs:

• MOA

• C- ___ medication

• warnings

• duration of therapy

• MOA: bind to GABA_A in the brain—> hyperpolarize neuron

• C-IV medication

• warnings:

  • avoid in pregnancy, sleep apnea, substance abuse history, and hepatic disease

• SHORT TERM USE ONLY (ex: 7-10 days)

Why should BZDRAs be used cautiously in elderly patients?

half-lives are prolonged in older patients—> risk of drug accumulation

Why should BZDRAs NOT be abruptly discontinued?

rebound insomnia

List the non-benzodiazepine receptor agonists (NBRAs):

• Eszopiclone

• Zaleplon

• Zolpidem

  • Zolpmist—> oral spray

  • Edluar, Intermezzo—> SL tablet

What is the max dose of zolpidem (Ambien) in females and the elderly?

5 mg

Which is preferred first line for insomnia?

a. benzos

b. NBRAs

b. (bc less likelihood of withdrawal, tolerance, and rebound insomnia)

What are 2 important drug interactions with Zaleplon (Sonata)?

Cimetidine and Rifampin

Should NBRAs be taken with or without food before bed?

WITHOUT—> food decreases absorption

List the melatonin receptor agonists:

• Ramelteon

• Tasimelteon

tip: all have “mel” in the middle= melatonin receptor agonists

What is the indication for each melatonin receptor agonists?

• Ramelteon—> sleep-onset insomnia

• Tasimelteon—> ONLY for non 24 hours sleep-wake disorder

Which melatonin receptor agonist is NOT a controlled substance and is a good option for pts. with a history of substance abuse?

Ramelteon

Difference between Ramelteon and melatonin?

• taking melatonin—> simply increases the levels of that hormone in your body

• taking ramelteon—> influences receptor in your brain that responds to melatonin, allows for enhanced effects on sleep induction

List the Dual Orexin Receptor Antagonists (DORAs):

• Suvorexant

• Lemborexant

• Daridorexant

tip: all have “orex” in the middle of the name—> orexin receptor antagonists

How do dual orexin receptor antagonists (DORAs) promote sleep?

They block orexin A and B receptors, turning off wake signaling—> DO NOT INDUCE SLEEPINESS

Answer the following about DORAs:

• C-___ medication

• ADRs

• which has the shortest t 1/2?

• C/I

• C-IV medication

• ADRs:

  • Next-day somnolence, narcolepsy associated events, suicidal thoughts, worsening depression

• Daridorexant has the shortest t ½

• C/I in NARCOLEPSY!!!!

Which OTC antihistamine is often used for insomnia and why is long-term use discouraged?

Diphenhydramine—> tolerance develops quickly and anticholinergic side effects occur

What low-dose antidepressant (≤6 mg) is FDA-approved for sleep maintenance insomnia?

Doxepin

What is another insomnia agent that is popular for its use in patients prone to substance abuse.

trazodone

List 2 herbals used for insomnia?

valerian root and melatonin (still not recommended in guidelines)

Patients with short-term or chronic insomnia should be evaluated after ______ of therapy.

a. one month

b. two months

c. one week

d. two weeks

c.

What insomnia agents should you use in each of the following scenarios:

• help falling asleep

• help staying asleep

• help falling and staying asleep

Describe the classic narcolepsy tetrad.

• Excessive daytime somnolence (EDS)

  • irresistible urge to sleep

• cataplexy

  • sudden bilateral loss of muscle tone

• hallucinations

• sleep paralysis

Patients with narcolepsy should take ≥__ scheduled daytime naps.

2

First-line pharmacologic agents for narcoleptic EDS:

Modafinil or armodafinil

What are the warnings with modafinil and armodafinil?

• idk how imp

• CNS effects

• derm effects (SJS, DRESS)

• use caution in CV disease, hepatic impairment, and tourette’s

What is the 2nd line tx for narcoleptic EDS therapy?

amphetamines

Answer the following about amphetamines:

• names

• C-___ medication

• names

  • dextroamphetamine- FDA approved

  • methyphenidate- FDA approved

  • dextro+amphetamine

  • lisdexamfetamine

• C-II medications

What boxed warnings accompany sodium oxybate?

CNS depression, abuse/misuse potential (GHB)—> REMS PROGRAM

When is Sodium oxybate C/I?

use with sedative-hypnotics or alcohol

How is sodium oxybate dosed each night?

Two divided doses: first at bedtime in bed, second 2.5–4 hours later.

What is restless leg syndrome (RLS)? Difference between primary and secondary RLS?

• paresthesias that are usually felt deep in calf muscle—> can also appear in thighs and arms with the urge to keep limbs in motion

• primary—> idiopathic

• secondary—> iron deficiency, CKD, and pregnancy

What is the diagnostic criteria for RLS?

• idk how imp

WHAT CLASS IS 1st LINE TX FOR RLS? List the FDA approved drugs.

Dopamine agonists—> ropinirole, pramipexole, rotigotine

Warnings with ropinirole and pramipexole?

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• may exacerbate dyskinesias

• may cause orthostatic hypotension

Which dopamine agonist is available as a transdermal patch for RLS?

Rotigotine

What antiepileptic pro-drug is also FDA-approved for RLS symptoms?

Gabapentin enacarbil

What are some non-FDA approved therapies for RLS?

• idk how imp

• levodopa/carbidopa

• opioids

• sedative-hypnotics