Sleep Disorders (L19)

____________= inability to initiate/maintain sleep

____________= excessive and uncontrollable daytime sleepiness

insomnia, narcolepsy

during REM sleep the brain becomes ________ and the body becomes ________

this is also when dreams occur and the eyes more rapidly

activated, relaxed

during REM sleep the ______ becomes activated and the _______ becomes relaxed

this is also when dreams occur and the eyes more rapidly

brain, body

insomnia associated factors

-pain

-psychiatric disorders like anxiety or depression

-substance abuse/use

-meds like SSRIs, stimulants, __________, and/or opioids

glucocorticoids

pharmacotherapy for insomnia

-____________ hypnotics

-___________ receptor agonists

-__________ receptor antagonists (DORAs)

-BZDs

-antihistamines

-antidepressants

-antipsychotics

non-benzodiazepine, melatonin, orexin

pharmacotherapy for insomnia: non-BZD hypnotics

binds __________ to the GABA_A receptor to enhance the inhibitory action of GABA in the CNS

selectively

pharmacotherapy for insomnia: non-BZD hypnotics

binds selectively to the __________ receptor to enhance the inhibitory action of __________ in the CNS

GABA

pharmacotherapy for insomnia: non-BZD hypnotics

Eszopiclone (Lunesta): can it be used for sleep onset, maintenance, or both

both (intermediate half-life)

pharmacotherapy for insomnia: non-BZD hypnotics

Zaleplon (Sonata): can it be used for sleep onset, maintenance, or both

onset (short half-life)

pharmacotherapy for insomnia: non-BZD hypnotics

Zolpidem (Ambien): can it be used for sleep onset, maintenance, or both

both (short-intermediate half-life)

pharmacotherapy for insomnia: non-BZD hypnotics

Zolpidem (Ambien) middle of the night fast-acting, low dose: can it be used for sleep onset, maintenance, or both

maintenance (short half-life)

pharmacotherapy for insomnia: non-BZD hypnotics (Eszopiclone, Zaleplon, and diff. formulations of Zolpidem)

which one can only be used for sleep onset?

Zaleplon (since it has a short half-life)

pharmacotherapy for insomnia: non-BZD hypnotics (Eszopiclone, Zaleplon, and diff. formulations of Zolpidem)

which two can be used for either sleep onset or sleep maintenance?

Eszopiclone or Zolpidem (standard or ER, not the middle-of-night one)

pharmacotherapy for insomnia: non-BZD hypnotics (Eszopiclone, Zaleplon, and diff. formulations of Zolpidem)

which formulation/type of Zolpidem can only be used for maintenance insomnia and not for sleep onset?

low-dose (middle of the night)

pharmacotherapy for insomnia: non-BZD hypnotics (Eszopiclone, Zaleplon, and diff. formulations of Zolpidem)

AEs: headache, drowsiness, dizziness

this medication is on the _______ ________

Beers list (not for elderly patients)

pharmacotherapy for insomnia: non-BZD hypnotics (Eszopiclone, Zaleplon, and diff. formulations of Zolpidem)

can elderly patients take these?

NO (on beers list)

pharmacotherapy for insomnia: _____________ (melatonin-receptor agonist)

Ramelteon

pharmacotherapy for insomnia: Ramelteon (_________-receptor agonist)

melatonin

pharmacotherapy for insomnia: Ramelteon (melatonin-receptor __________)

agonist

pharmacotherapy for insomnia: Ramelteon (melatonin-receptor agonist)

is it recommended for problems with sleep onset or maintenance?

onset (not for maintenance)

pharmacotherapy for insomnia: Ramelteon (melatonin-receptor agonist)

it is only recommended for sleep onset

AEs: well-tolerated, even in _________

elderly🙂

pharmacotherapy for insomnia: Ramelteon (melatonin-receptor agonist)

it is only recommended for sleep onset

can it be used in elderly patients?

yes🙂

pharmacotherapy for insomnia: Ramelteon (melatonin-receptor agonist)

it is only recommended for sleep onset

can it be used in patients with history of substance abuse?

yes🙂

pharmacotherapy for insomnia: Ramelteon (melatonin-receptor agonist)

it is only recommended for sleep onset

full benefits may take up to _________

6 weeks

pharmacotherapy for insomnia: DORAs (which stands for _______-________ receptor ____________)

dual-orexin antagonists

pharmacotherapy for insomnia: DORAs

Orexin is a _________ neurotransmitter

so, blocking it _______ signaling

stimulating, clams (decreases)

pharmacotherapy for insomnia: DORAs

Orexin is a neurotransmitter that is responsible for ___________ wakefulness and __________ sleepy pathways

promoting, suppressing

pharmacotherapy for insomnia: DORAs

Orexin is a neurotransmitter that is responsible for promoting wakefulness and suppressing sleepy pathways

DORAs ________ it → to promote sleep

block (inhibit)

pharmacotherapy for insomnia: DORAs

Orexin is normally stimulating → so, blocking (antagonizing) it instead promotes sleep

clinical use: FDA-approved class ________ for insomnia

C-4 (controlled)

pharmacotherapy for insomnia: DORAs= Dual-Orexin Receptor Antagonists (Lemborexant, Suvorexant, Daridorexant)

is this class used to help sleep onset, maintenance, or both?

both

pharmacotherapy for insomnia: DORAs= Dual-Orexin Receptor Antagonists (Lemborexant, Suvorexant, Daridorexant)

these can be used for either sleep onset or maintenance

which of them has the longest half-life?

Lemborexant

pharmacotherapy for insomnia: DORAs= Dual-Orexin Receptor Antagonists (Lemborexant, Suvorexant, Daridorexant)

these can be used for either sleep onset or maintenance

this class has potential drug interactions with _________ inhibitors/inducers

CYP3A4

pharmacotherapy for insomnia: DORAs= Dual-Orexin Receptor Antagonists (Lemborexant, Suvorexant, Daridorexant)

these can be used for either sleep onset or maintenance

not associated with tolerance, rebound insomnia, or withdrawal

can these be used in elderly patients?

yes (at a low dose)

pharmacotherapy for insomnia: DORAs= Dual-Orexin Receptor Antagonists (Lemborexant, Suvorexant, Daridorexant)

these can be used for either sleep onset or maintenance

caution: this class is contraindicated in ___________ !!

narcolepsy (duh🤣)

pharmacotherapy for insomnia: Lemborexant, Suvorexant, Daridorexant

what class do these belong to?

DORAs (Dual-Orexin Receptor Antagonists → Lemborexant, Suvorexant, Daridorexant)

pharmacotherapy for insomnia: Eszopiclone, Zaleplon, Zolpidem

what class do these belong to?

Non-BZD hypnotics

pharmacotherapy for insomnia: Sedative-Hypnotic BZDs (Estazolam, Flurazepam, Temazepam, Triazolam)

which of these can only be used for sleep onset issues?

Triazolam (short half-life)

pharmacotherapy for insomnia: Sedative-Hypnotic BZDs (Estazolam, Flurazepam, Temazepam, Triazolam)

which of these has the longest half-life?

Flurazepam (40-114 hours!!)

pharmacotherapy for insomnia: Sedative-Hypnotic BZDs (Estazolam, Flurazepam, Temazepam, Triazolam)

can these be used in elderly patients?

NO (can cause memory problems and increase the risk of falls)

pharmacotherapy for insomnia: Sedative-Hypnotic BZDs (Estazolam, Flurazepam, Temazepam, Triazolam)

AEs: tolerance and dependance, residual daytime sedation, rebound insomnia, _________ ___________ (d/t impaired encoding of new information), ________ problems and increased risk of _________

anterograde amnesia, memory, falls (AVOID in elderly)

pharmacotherapy for insomnia: OTC Antihistamine Sleep Aids

____-gen antihistamines that cross the BBB into the CNS and block H1 receptors → cause drowsiness

1st (Diphenhydramine, Doxylamine)

pharmacotherapy for insomnia: OTC Antihistamine Sleep Aids

1st-gen antihistamines that cross the BBB into the CNS and block H1 receptors → cause drowsiness

the two examples are _______ and _________

diphenhydramine, doxylamine

pharmacotherapy for insomnia: OTC Antihistamine Sleep Aids (Diphenhydramine, Doxylamine)

1st-gen antihistamines that cross the BBB into the CNS and block H1 receptors → cause drowsiness

__________ use is not recommended

regular (chronic)

pharmacotherapy for insomnia: OTC Antihistamine Sleep Aids (Diphenhydramine, Doxylamine)

1st-gen antihistamines that cross the BBB into the CNS and block H1 receptors → cause drowsiness

regular/chronic use is not recommended d/t development of __________

tolerance

pharmacotherapy for insomnia: OTC Antihistamine Sleep Aids (Diphenhydramine, Doxylamine)

1st-gen antihistamines that cross the BBB into the CNS and block H1 receptors → cause drowsiness

regular/chronic use is not recommended

AEs: associated with a higher incidence of _________ sedation

daytime

pharmacotherapy for insomnia: OTC Antihistamine Sleep Aids

Diphenhydramine: avoid in _________ and do not use with _________ ___________ medications used for Alzheimer’s disease

AEs: ______________ effects

elderly, cholinesterase inhibitors, anticholinergic

pharmacotherapy for insomnia: Sedating Antidepressants like _____________

Trazodone

pharmacotherapy for insomnia: Sedating Antidepressants like Trazodone, Amitriptyline, Doxepin, or Mirtazapine

often prescribed in the absence of depression

__________ comes in 3mg and 6mg tablets for insomnia and is for patients having trouble with the maintenance of sleep

Doxepin

pharmacotherapy for insomnia: Sedating Antidepressants like Trazodone, Amitriptyline, Doxepin, or Mirtazapine

often prescribed in the absence of depression

Doxepin comes in 3mg and 6mg tablets for insomnia and is for patients having trouble with the ___________ of sleep

maintenance

pharmacotherapy for insomnia: Sedating Antidepressants like Trazodone, Amitriptyline, Doxepin, or Mirtazapine

often prescribed in the absence of depression

__________ is a popular option used for managing insomnia d/t use of SSRI antidepressants

Trazodone

pharmacotherapy for insomnia: Antipsychotics like _______ or ________

Quetiapine or Olanzapine

pharmacotherapy for insomnia: _____________ like Quetiapine or Olanzapine

antipsychotics

pharmacotherapy for insomnia: antipsychotics like Quetiapine or Olanzapine

NOT 1st-line! should only be used with appropriate indication (psychosis, agitation)

can these be used in elderly?

no

pharmacotherapy for insomnia: sedative hypnotics (BZDs and Non-BZDs)

use __________ at the ________ effective dose and for a ________ duration

intermittently, lowest, short

Narcolepsy core features include excessive daytime sleepiness with irresistible “sleep attacks”

some pts experience ____________= sudden loss of muscle tone triggered by emotions

cataplexy

Narcolepsy core features include excessive daytime sleepiness with irresistible “sleep attacks” and some pts have cataplexy

pathophysiology: associated with a loss of _________

orexin (which is supposed to promote wakefulness → this is why DORAs are contraindicated in narcolepsy)

Narcolepsy core features include excessive daytime sleepiness with irresistible “sleep attacks”

pathophysiology: associated with a loss of Orexin

diagnosis: clinical history plus ______ _______

sleep study

what is cataplexy that some pts experience in narcolepsy?

sudden loss of muscle tone or paralysis

cataplexy in narcolepsy is the sudden, transient episodes of muscles weakness or paralysis during wakefulness

it can be triggered by _______ __________

strong emotions (laughter, excitement, anger, suprise)

narcolepsy disease management

________ at regularly scheduled times throughout the day

naps

narcolepsy disease management

naps at regularly scheduled times throughout the day

__________ may be taken early in the day to increase wakefulness

stimulants

narcolepsy disease management: cataplexy prophylaxis

use _______, _________, or _________ to suppress REM

TCAs, Venlafaxine, Duloxetine

narcolepsy disease management: cataplexy treatment

__________ ________ is indicated for the treatment of cataplexy or excessive daytime sleepiness

sodium oxybate (c-III)

________ _______ _________

symptoms include urge to move legs, often with uncomfortable sensations

worst at rest or night, improves with movement

restless leg syndrome

restless leg syndrome

symptoms include urge to move legs, often with uncomfortable sensations (worst at rest or night, improves with movement)

etiology: due to dysfunction with __________ in the brain’s basal ganglia circuits

dopamine

restless leg syndrome

symptoms include urge to move legs, often with uncomfortable sensations (worst at rest or night, improves with movement)

etiology: due to dysfunction with dopamine in the brain’s basal ganglia circuits and reduced CNS ________ stores

iron (treatment with iron replacement)

restless leg syndrome

symptoms include urge to move legs, often with uncomfortable sensations (worst at rest or night, improves with movement)

etiology: due to dysfunction with dopamine in the brain’s basal ganglia circuits and reduced CNS iron stores

________ agonists can be used as treatment

dopamine (Ropinirole or Pramipexole)

restless leg syndrome

symptoms include urge to move legs, often with uncomfortable sensations (worst at rest or night, improves with movement)

etiology: due to dysfunction with dopamine in the brain’s basal ganglia circuits and reduced CNS iron stores

dopamine agonists like _________ or _________ can be used

Ropinirole, Pramipexole

Ropinirole or Pramipexole (dopamine agonists) can be used to treat which sleep disorder?

restless leg syndrome

Sodium Oxybate (C-III) can be used to treat which sleep disorder?

narcolepsy (± cataplexy)