Sleep Flashcards
Is sleep a passive activity?
No
Homeostatic activity of sleep is thought to be triggered by this molecule
Adenosine
“fatigue factor”
Adenosine release in pontine tegmentum and basal forebrain acts on these neurons
Ventral lateral preoptic nucleus (VLPO)
Adenosine is derived from the breakdown of this
Glycogen
What are the two main functions of sleep?
Homeostatic and Circadian functions
This is released in pontine tegmentum and basal forebrain, and acts on ventro lateral preoptic nucleus (VLPO) nucleus
Adenosine
Summed electrical activity across sleep
Desynchronized discharge that can be separated by frequency (speed) and amplitude (power)
Electroencephalographic (EEG)
What is the frequency of delta waves in an EEG?
Less than 4 Hz
What is the frequency of theta waves in an EEG?
4-7 Hz
What is the frequency of alpha waves in an EEG?
8-15 Hz
What is the frequency of beta waves in an EEG?
16-31 Hz
What is the frequency of gamma waves in an EEG?
> 32 Hz
EEG waveform that is <4 Hz
Delta
EEG waveform that is 4-7 Hz
Theta
EEG waveform that is 8-15 Hz
Alpha
EEG waveform that is 16-31 Hz
Beta
EEG waveform that is >32 Hz
Gamma
What is the primary EEG waveform when awake with eyes open?
Beta (16-31 Hz)
What is the primary EEG waveform when awake with eyes closed?
Alpha (8-15 Hz)
What is the primary EEG waveform in Stage 1 of sleep?
Theta (4-7 Hz)
What is the primary EEG waveform in Stage 2 of sleep?
Theta (4-7 Hz), sleep spindles and K complexes
Sleep spindles and K complexes are seen in this sleep stage
Stage 2
What is the primary EEG waveform in stages 3 and 4 of sleep?
Delta (< 4Hz)
What is the primary EEG waveform in REM?
Beta (16-31 Hz)
These are high amplitude, slow frequency waves followed by electropositive surge
K complexes
These are brief bursts of alpha waves
Sleep spindles
Sleep spindles are brief bursts of this waveform, seen in stage 2 of sleep
Alpha waves
Stage of sleep that is difficult to rouse with confusion upon waking
Stage 4
Stage of sleep that is associated with bet wetting, sleep walking and talking, and night terrors
Stage 4
Is muscle tone low or high in non-REM sleep?
Low
(low EMG and EOG activity)
Is heart rate reduced or increased in non-REM sleep?
Reduced
Is BP reduced or increased in non-REM sleep?
Reduced
Is respiration reduced or increased in non-REM sleep?
Reduced
In REM sleep, brain waves resemble this stage of sleep in that they are fast and low
Stage 1
Is muscle tone low or high in REM sleep?
Normal
Muscles of respiration, cardiac, and eye movement are normal tone
Is heart rate reduced or increased in REM sleep?
Increased
Is respiration reduced or increased in REM sleep?
Irregular
Is EMG activity low or high in REM sleep?
Low
This EOG component may protect sleep by reducing the effects of external stimuli
May also promote consolidation of memory and neuronal plasticity
Sleep spindles
What age do infants start to have REM and NREM becoming evident? (ultradian rhythm)
6 months
At this age, sleep moves towards a night activity (circadian rhythm)
3 years
At midlife, sleep efficiency and time start to decline, with notable loss of these stages
3 and 4
Cholinergic pathways involved in wakefulness are located in these two nuclei
Pedunculopontine and Laterodorsal tegmental
These pathways involved in wakefulness are located in pedunculopontine and laterodorsal tegmental nucleus
Cholinergic
Cholinergic pathways are inhibited by onset of this type of sleep
Non-REM
Neural system involved in wakefulness that is in the dorsal raphe nucleus
Serotonergic
Neural system involved in wakefulness that is in the locus coeruleus
Noradrenergic
Neural system involved in wakefulness that is in the ventral periaqueductal gray
Dopaminergic
Neural system involved in wakefulness that is in the tuberomammillary nucleus
Histaminergic
Neural system involved in wakefulness that is from the lateral hypothalamus
Orexin (formerly hypocretin)
VLPO activity may be triggered by accumulation of this molecule
Adenosine
VLPO releases this neurotransmitter
GABA
Does VLPO promote or inhibit sleep?
Promotes
(inhibits wakefulness pathways via release of GABA)
REM sleep is related to activation of these two nuclei
Pedunculopontine and laterodorsal tegmental nucleus
(which have cholinergic pathways)
Cholinergic projections from pons to these two structures regulate atony during REM
Medulla and spinal cord
Cholinergic projections to these two structures trigger phasic eye and cardiac/respiratory activity during REM
Hypothalamus and Thalamus
Sleep is promoted by activity of this nucleus
Ventrolateral preoptic nucleus (VLPO)
Wakefulness is associated with activity of this nucleus
Histaminergic tuberomammillary nucleus (TMN)
Wakefulness-sleep switch may be triggered by this compound located in key nuclei of sleep/wakefulness
Orexin
Neurons of this nuclei fire in a circadian pattern with a 24 hour period
Suprachiasmatic
(may be regulated by light input and melatonin secretion)
Melatonin is secreted by this gland
Pineal gland
Melatonin acts on this nucleus
Suprachiasmatic nucleus (“master clock”)
Orexin is a neurotransmitter that maintains sleep or wakefulness?
Wakefulness
This neurotransmitter system activates REM during sleep
Acetylcholine
Excessive daytime sleeping
Hypersomnia
Sudden and uncontrollable onset of REM sleep during wake state
Narcolepsy
Parasomnia where person acts out dream during sleep and muscles may not be atonic
REM sleep disorder
Sleep walking and sleep terrors are associated with this parasomnia
Non-REM sleep arousal disorders
These are effective for short-term treatment of insomnia
Sedating antihistamines
Sedating antihistamines MOA in sleep involves central blockage of these 2 receptors
Histamine-1 and cholinergic
Treatment for insomnia with sedation MOA related to central blockage of histamine-1 and cholinergic receptors
Sedating antihistamines
Are sedating antihistamines safe for use during breastfeeding?
Probably
Insomnia drug type that is contraindicated with alcohol or any CNS depressant, anticholinergics, or monoamine oxidase inhibitors
Sedating antihistamines
This type of drug is considered alternative drug option for patients needing restorative sleep but cannot be treated with a depressant
Antidepressants
Trazodone and Doxepin are this type of drug for insomnia
Antidepressants
What is the MOA of Valerian for insomnia?
unknown, may prolong GABA activity
Valerian is an alternative medication used to treat this
Insomnia
Valerian can treat insomnia, potentially by prolonging this activity
GABA
This drug is indicated to promote the onset of sleep
Not a controlled substance so may be a viable sleep aid for patients with history of substance abuse
Ramelteon
Type of melatonin receptor that regulates sleepiness
Meltonin-1
Type of melatonin receptor that helps body shift from day and night
Melatonin-2
This drug with a non-sedation MOA is an agonist at the melatonin-1 and melatonin-2 receptors believed to be involved in regulation of circadian sleep rhythms
Ramelteon
Ramelteon is an agonist of these two receptors
Melatonin-1 and -2
What is the MOA of Ramelteon in insomnia?
Indicated to promote the onset of sleep
Agonist at the melatonin-1 and -2 receptors
What effect do sedating antihistamines have on REM?
REM is decreased
(sleep time increased)
What effect does Ramelteon have on REM?
May suppress REM
Ambien is this drug
Zolpidem
Z-drug used for short-term sleep induction
Zolpidem (Ambien)
Controlled release of this Z-drug is used for short-term sleep maintenance
Zolpidem (Ambien)
Z drug used for short-term sleep induction
Zaleplon
Z drug used for sleep induction and maintenance
Eszopiclone
What is the MOA of Z drugs (Zolpidem, Zaleplon, Eszopiclone) in insomnia?
Enhancement of GABA-benzodiazepine receptor complex
(“non benzodiazepine GABA-A agonist”)
Type of drug for insomnia with minimal to no antianxiety, muscle relaxant or anticonvulsant activity
Little disruption of the sleep stage pattern
Z drugs (Zolpidem, Zaleplon, Eszopiclone)
What is the half life of Zolpidem?
3 hours
What is the half life of Zaleplon?
1 hour
What is the half life of Eszopiclone?
6 hours
Z drug with half life of 3 hours
Zolpidem
Z drug with half life of 1 hour
Zaleplon
Z drug with half life of 6 hours
Eszopiclone
This is an antagonist to Z drugs
Flumazenil
Triazolam has a half life of 2 hours and is this type of drug used to treat insomnia
Benzodiazepine
This drug’s allosteric binding site activation results in enhancement of GABA-associated hyperpolarization
Benzodiazepine
What effect do benzodiazepines have on the sleep stages?
Increase stage 2
Decrease stages 3, 4, and REM
Do Z drugs or Benzodiazepines have Sedation, antianxiety, muscle relaxant and anticonvulsant activity?
Benzodiazepines
(Z drugs have minimal activity)
Insomnia drug type that increases stage 2 sleep while decreasing stages 3, 4, and REM
Benzodiazepines
Are benzodiazepines safe during pregnancy?
No
This benzodiazepine has an active metabolite
Flurazepam
Is Temazepam safe during breastfeeding?
Probably
Is dependence seen with use of benzodiazepines?
Yes
Withdrawal symptoms following abrupt discontinuation
This is a Benzodiazepine binding site blocker
Antidote for overdose
Flumazenil
Insomnia drug with sedative effects related to active metabolite trichloroethanol
Chloral Hydrate
Chloral Hydrate sedative effects are related to this active metabolite
Trichloroethanol
Drug that is an Orexin (hypocretin) antagonist used to promote and maintain sleep
Suvorexant
Suvorexant is an antogonist to this, and is used to promote and maintain sleep
Orexin (hypocretin)
What is the half life of Suvorexant?
12 hours
(is associated with considerable grogginess and hangover)
Is dependence seen with use of Suvorexant?
yes
Insomnia drug that is also used in Alzheimer’s
As with any sleep aid in elderly or cognitive-impaired patients, increased risk of falls is still a concern
Suvorexant
What is the MOA of Suvorexant for insomnia?
Orexin (hypocretin) antagonist
Used to promote and maintain sleep
MOA of this insomnia drug is central anticholinergic and antihistaminic
Sedating antihistamines
This is the drug of choice for patients with history of drug abuse needing sleep aids
Trazodone
As a Complementary and Alternative Med, this drug may be ideal for patients on the cusp of needing pharmacotherapy for sleep
Valerian
This drug has some value in treating sleep problems related to circadian (shift) problems, some reports of memory disruption and reduced libido, some risk of physical dependence
Ramelteon (and Tasimelteon)
What insomnia drug should be used for patients with sleep problems related to circadian (shift) problems?
Ramelteon
(and Tasimelteon)
Do Z drugs affect the quality of sleep?
Very good sleep
Lower dose of this insomnia drug should be given in women due to slower metabolism
Zolpidem
This type of drug for insomnia can cause powerful amnesia
Z drugs
This type of drug should be given when stage 4 and REM suppression is desired
Benzodiazepines
Sleep paralysis is a side effect of this insomnia drug
Suvorexant
Narcolepsy may be caused by a deficiency in this
Hypocretin
What is the tetrad of symptoms of narcolepsy?
Sleep attacks
Cataplexy
Hypnagogic and Hypnopompic hallucinations
Sleep paralysis
Sleep attacks, cataplexy, hypnagogic and hypnopompic hallucinations, and sleep paralysis are a tetrad of symptoms seen in this condition
Narcolepsy
Narcolepsy pharmacological treatment is with these
Mixed catecholamine agonists (“stimulants”)
Dextroamphetamine, methamphetamine, lisdexamfetamine, methylphenidate, modafinil, armodafinil treat this part of narcolepsy
Excessive daytime sleepiness
Fluoxetine, imipramine, nortriptyline, protriptyline, venlafaxine, selegiline treat this part of nacrolepsy
Cataplexy
Benefit of these 2 drugs for naroclepsy is lost when combined with alpha-antgonists (e.g. prazosin)
Modafinil and Armodafinil
Modafinil and Armodafinil benefit is lost when combined with this type of drug
Alpha-antagonists (such as Prazosin)
Cardiac arrhythmias, Visual changes, Hypertension and Dependence are serious adverse reactions to these 2 drugs for narcolepsy
Modafinil and Armodafinil
MOA of this type of drug for narcolepsy is indirect stimulation of norepinephrine (low dose) and dopamine (higher dose) activity
Direct stimulation of norepinephrine and dopamine receptors
Mixed monoaminergic agonists
Low doses of mixed monoaminergic agonists results in indirect stimulation of this activity
Norepinephrine
Higher doses of mixed monoaminergic agonists results in indirect stimulation of this activity
Dopamine
Mixed monoaminergic agonists directly stimulate these 2 types of receptors
Norepinephrine and Dopamine
Growth suppression when used long-term, Psychosis and depression, Hypertension, Cardiac arrhythmias (black box warning) and Seizures are serious adverse effects of this type of drug for narcolepsy
Mixed monoaminergic agonists
Mixed monoaminergic agonists should not be given with either of these 2 types of drugs
Monoamine oxidase inhibitors
CNS drugs
Mixed monoaminergic agonists are contraindicated in patients with either of these two conditions
Epilepsy
Cardiovascular or cerebrovascular disease
Disorder characterized by repeated episodes of arousal during sleep associated with vocalization and/or complex motor behaviors
Upon awakening from these episodes, individual is completely awake, alert, and not confused/disoriented
REM sleep behavior disorder
Benzodiazepine that is the preferred treatment for REM sleep behavior disorder
Clonazepam
(melatonin may be a second drug)
This is a comorbidity associated with sleep walking
Obsessive-compulsive disorder
This is a comorbidity associated with sleep terrors
Depression or anxiety
What is the pharmacological treatment for both REM and non-REM sleep disorders?
Benzodiazepines
What is the pharmacotherapy used to treat restless leg syndrome?
Usually the dopamine agonist therapies used in Parkinson’s
(direct agonists appear superior to indirect agonists)
