Sleep and Sleep Disorders + Drugs Flashcards
Which neurotransmitter drives REM sleep?
acetylcholine from the brainstem to the thalamus and cortex
describe the electrical activity of the various stages of sleep
Wake = alpha rhythm (eyes closed)
N1 = loss of alpha rhythm, decrease in frequency
N2 = spindles, K complexes
N3 = slow waves
REM = low amplitude, mixed frequency, theta, rapid eye movements
Which structure in the brain controls the circadian rhythm?
Suprachiasmatic nucleus of the hypothalamus - has an endogenous oscillation of around 24 hours
What does the Borbély 2 process model of sleep say?
There is a homeostatic drive to sleep (Process S)
There is a circadian rhythm which regulates sleep and many
physiologic processes (Process C)
Disruption of either of these components can cause sleep problems
What occurs in central sleep apnea?
Brain does not send a signal to the phrenic nerve to breathe
May be associated with congestive heart failure, medications – treat underlying cause
Does not present with snoring (obstructive sleep apnea)
type 1 versus type 2 narcolepsy
Type 1: with cataplexy, associated with loss of orexin/hypocretin neurons in the hypothalamus - occurs when REM related muscle atonia occurs during wake
Type 2: without cataplexy
Why do hallucinations and sleep paralysis occur with narcolepsy?
hypnogogic/hypnopompic hallucinations occur because REM intrusion into wake-sleep transition
sleep paralysis occurs because of REM related muscle atonia persisting into wake (usually briefly)
cataplexy occurs when REM related muscle atonia occurs during wake
what is the mainstay of therapy for insomnia?
Cognitive behavioral therapy for insomnia (CBT-I): treat underlying maladaptive thoughts which makes sleep difficult + work on proper sleep hygiene
parasomnias
sleep walking/talking, night terrors, may involve complex behaviors like driving a car
very common in children, usually grow out of them, if tx is needed give clonazepam
involve “partial” sleep of the brain - some areas remain active during sleep
with what diseases are REM Behavior Disorders associated?
fighting/punching/kicking in sleep, generally involving dream of being attacked - do NOT involve complex movements (driving a car, etc)
associated with synucleionpathies such as Parkinson’s Disease - may precede disease by many years
may be caused by SSRIs, can be treated with clonazepam or melatonin
How can restless leg syndrome be treated?
may be underlying iron deficiency
if not, Gabapentin is first-line therapy
what is the MOA of hypnotic benzodiazepines such as triazolam, temazepam, estazolam, flurazepam, and quazepam?
bind GABA(A) receptors and increase frequency of GABA-mediated chloride channel opening
rapid onset of action - used to treat insomnia; also have muscle relaxant and anticonvulsant properties
why are hypnotic benzodiazepines such as triazolam, temazepam, estazolam, flurazepam, and quazepam now considered alternative agents?
bind GABA(A) receptors and increase frequency of GABA-mediated chloride channel opening
now considered alternative due to long half-lives + high potential for tolerance/dependence
what are the adverse reactions of hypnotic benzodiazepines such as triazolam, temazepam, estazolam, flurazepam, and quazepam?
bind GABA(A) receptors and increase frequency of GABA-mediated chloride channel opening
adverse rxns: CNS depression, respiratory depression, high tolerance/decadence risk (schedule IV), withdrawal after abrupt cessation
group the following hypnotic benzodiazepines as short, intermediate, or long-acting:
a. temazepam
b. quazepam
c. triazolam
d. estazolam
e. flurazepam
short acting: triazolam
intermediate acting: temazepam, estazolam
long acting: flurazepam, quazepam
bind GABA(A) receptors and increase frequency of GABA-mediated chloride channel opening
what kind of drugs are triazolam, temazepam, estazolam, flurazepam, and quazepam? what is their MOA?
hypnotic benzodiazepines - treat insomnia (also have muscle relaxant and anticonvulsant properties)
bind GABA(A) receptors and increase frequency of GABA-mediated chloride channel opening
what kind of drugs are zolpidem, eszopiclone, and zaleplon? what is their clinical use?
non-benzodiazepines hypnotics - bind same site on GABA(A) to increase frequency of chloride channel opening
used to treat insomnia by decreasing sleep latency (time to sleep), rapid onset and short half-lives
help you get your Zzzzzzz’s
name 2 first-line options for sleep-onset insomnia and sleep maintenance / mixed insomnia
- zolpidem
- eszopiclone
non-benzodiazepines hypnotics - bind same site on GABA(A) to increase frequency of chloride channel opening
help you get your Zzzzzzz’s
what black box warning is mandated on zolpidem, eszopiclone, and zaleplon? what kind of drug are these?
non-benzodiazepines hypnotics - bind same site on GABA(A) to increase frequency of chloride channel opening —> treat insomnia
schedule IV controlled substances, but not common choices for abuse
FDA mandated black box warning for rare but serious complex sleep behaviors - sleep walking/eating/driving
what kind of drugs are ramelteon and tasimelteon, and what is their clinical use?
melatonin receptor agonists (MT1 and MT2) in suprachiasmatic nucleus of hypothalamus, >15x more potent than melatonin
used to treat sleep-onset insomnia (NOT used for sleep maintenance)
for what is ramelteon a first line option?
melatonin receptor agonist (MT1 and MT2) in suprachiasmatic nucleus of hypothalamus, >15x more potent than melatonin
first-line for sleep-onset insomnia (NOT used for sleep maintenance), but reduced efficacy compared to GABAergic non-benzodiazepine hypnotics (zolpidem, eszopiclone)
what side effects are associated with ramelteon?
melatonin receptor agonist used to treat sleep-onset insomnia
side effects: somnolence, nausea, dizziness, fatigue, endocrine changes (low testosterone, high prolactin)
no risk of dependence/abuse (not classified as controlled substance)
name a melatonin receptor agonist that is a first-line option for sleep-onset insomnia
ramelteon: agonist at MT1 and MT2 in suprachiasmatic nucleus of hypothalamus, >15x more potent than melatonin
used to treat sleep-onset insomnia (NOT used for sleep maintenance)
what kind of drugs are suvorexant, lemborexant, and daridorexant, and what is their clinical use?
dual orexin receptor antagonists (DORAs): antagonize orexin (OX) neurotransmitter at both OX1 and OX2 receptors in brain
orexin is a central promoter of wakefulness
DORAs are first line options for sleep maintenance or mixed insomnia, also second-line for sleep-onset insomnia
what is the function of the neurotransmitter orexin? how is this targeted in drug therapy?
orexin = central promoter of wakefulness
dual orexin receptor antagonists (DORAs): first line options for sleep maintenance or mixed insomnia, also second-line for sleep-onset insomnia
ex: suvorexant, lemborexant, daridorexant
for what condition are DORAs first-line options for? what about second-line?
DORAs = dual orexin receptor antagonists: block OX1 and OX2 receptors
orexin = NT which promotes wakefulness
first line for sleep maintenance or mixed insomnia; second line for sleep-onset insomnia
ex: suvOREXant, lembOREXant, daridOREXant
how can doxepin be used to treat insomnia? what kind of drug is this?
tricyclic antidepressant (TCA) with high selectivity to antagonize post-synaptic H1 receptors
used at doses much lower than those to treat depression, antihistaminic activity enhances sleep time and maintenance (long half life = long acting)
low dose is first-line for sleep maintenance or mixed insomnia (NOT indicated for sleep-onset insomnia)
name a TCA that is a first-line option for sleep maintenance or mixed insomnia
doxepin: has high selectivity to antagonize post-synaptic H1 receptors
used at doses much lower than those to treat depression, antihistaminic activity enhances sleep time and maintenance (long half life = long acting)
(NOT indicated for sleep-onset insomnia)
what are the side effects of doxepin when used at low enough doses to treat insomnia?
doxepin = TCA with high selectivity to antagonize H1 receptors —> enhanced sleep
side effects: somnolence, nausea, upper respiratory tract infections
which of the following is NOT a schedule IV controlled substance?
a. triazolam
b. doxepin
c. suvorexant
d. eszopiclone
e. flurazepam
b. doxepin = TCA selective for H1 (antagonize)
these are all used to treat insomnia
a. triazolam = short acting benzodiazepine
c. suvorexant = dual orexin receptor antagonist (DORA)
d. eszopiclone = non-benzodiazepine hypnotic
e. flurazepam = long acting benzodiazepine
note while the rest are schedule IV, only benzodiazepines pose a real dependence risk
also note ramelteon and tasimelteon (melatonin receptor agonists) are also not controlled substances
