Sleep, Attention, & Consciousness

Question 1

Effects of ACh on sleep

Answer 1

Muscarinic agonists and AChEIs activate REM

Antimuscarinic drugs cause drowsiness but decrease REM

Question 2

Effects of histamine on sleep

Answer 2

Histamine inhibits the REM-ON switch promoting wakefulness

Antihistamines promote drowsiness and sleep

Question 3

Effects of adenosine on sleep

Answer 3

Accumulation of adenosine signals time to sleep

Adenosine antagonists (caffeine) increases alertness

Question 4

Mechanism of Benzo action in sleep

Answer 4

Agonists at GABA-A1 receptors in the cortex which mediate sleep, amnestic, and anticonvulsant actions

Question 5

Benzodiazepines used for sleep + Pharmacokinetics

Answer 5

Triazolam - short half-life; good effect on sleep latency, can see rebound insomnia next day

Temazepam - medium half-life; minimal effect on sleep latency due to slow absorption

Flurazepam - long half-life with active metabolite; can accumulate in elderly due to impaired hepatic clearance

Question 6

Adverse effects of benzodiazepines in sleep

Answer 6

Daytime sedation
Anterograde amnesia
Rebound insomnia
Psychologic and physical dependence (Schedule IV)

Question 7

Benzodiazepines vs. Z drugs

Answer 7

Both decrease sleep latency, increase sleep duration with increased Phase 2 (light sleep)

Most benzos, barbiturates, and ethanol decrease phase 3-4 deep sleep and REM with REM rebound leading to nightmares; Z drugs have minimal effect on sleep architecture

Question 8

Treatment of benzodiazepine overdose

Answer 8

Flumazenil

Question 9

Ramelteon

Answer 9

Melatonin (MT1 and MT2) receptor agonist - induces sleepiness and regulation of circadian rhythms via SCN of hypothalamus

Reduces sleep latency time - good treatment of insomnia characterized by difficulty with sleep onset

Question 10

Trazodone

Answer 10

Serotonin antagonist / reuptake inhibitor (SARI)

Uses: Patients with co-morbid substance abuse/depression

Adverse effects: Orthostasis, Priapism

Question 11

Use of TCADs in insomnia

Answer 11

Block reuptake of 5HT and NE; antagonist action at histamine and muscarinic cholinergic receptors

Option for insomnia patients with co-morbid depression and substance abuse

Adverse reactions: Anticholinergic / antihistaminic side effects; cardiac conduction disturbances in overdose

Question 12

Diphenhydramine

Answer 12

Histaminic and muscarinic antagonist; produces drowsiness

Not indicated for use in insomnia

Question 13

Characteristics of Z drugs

Answer 13

1st line therapy for insomnia

Little effect on sleep stages III, IV, and REM
Negligible anticonvulsant or myorelaxant properties at therapeutic doses
Low tolerance and abuse potential

Question 14

Z Drug Adverse Effects

Answer 14

Drowsiness, amnesia, headache, GI complains

Rebound effects or next-day psychomotor performance alteration minimal with Zolpidem and Zaleplon, increased with Eszopiclone

Tolerance, dependence, withdrawal are possible but less likely than with benzodiazepines; still schedule IV

Question 15

What are the 3 types of ADHD?

Answer 15

Inattention type, characterized by inability to initiate, maintain, shift, or terminate attention

Hyperactive/Impulsive Type

Combined inattention/hyperactive type

All types require evidence of impairment before age 12 with symptoms present in at least 2 settings

Question 16

What is the epidemiology of ADHD?

Answer 16

3-8% of school-aged children
4% of adults

Males > Females

Question 17

What is the role of psychiatric comorbidity in ADHD?

Answer 17

65% of children with ADHD experience psychiatric comorbidity, including:

Major depression
Anxiety / social phobia
Oppositional / conduct disorder
Antisocial personality disorder 
Substance abuse

Question 18

Stimulant treatments for ADHD

Answer 18

Methylphenidate derivatives - Focalin/Ritalin (short acting) vs. Concerta (long acting)

Amphetamine salts - Adderall (short acting)

Question 19

Non stimulant-based treatment of ADHD

Answer 19

NRIs (Atomoxetine)
NDRIs (Buproprion)
TCADs
Alpha-agonists (Clonidine) - for hyperactivity

Question 20

Delirium

Answer 20

A state of fluctuating confusion, inattention, and misperceptions (illusions/hallucinations)

Question 21

Stupor

Answer 21

A sleep-like state from which the patient can be aroused only by vigorous stimuli

Question 22

Coma - Definition

Answer 22

A sleep-like state in which the patient is unresponsive to external stimuli and there are no sleep-wake cycles or attempts to communicate

Defined as GCS < 8; patients are unable to follow commands, speak recognizable words, or open either eye

Question 23

Vegetative State - Definition

Answer 23

Eyes open spontaneously, sleep-wake cycles re-establish, but there is no sign of cognitive function (perception, communication, or purposeful motor activity)

Persistent VS = duration 1 month
Permanent VS = duration 3 months (non-traumatic) or duration 12 months (traumatic)

Question 24

Minimally conscious state (MCS)

Answer 24

Eyes open spontaneously and sleep cycles resume; arousal level may be normal at times with reproducible, though inconsistent, behavioral displays of perception, communication, or purposeful motor activity

Question 25

Decerebrate posturing

Answer 25

Upper and lower extremity extension Suggests lesion of upper brainstem Worse prognosis than decorticate

Question 26

Decorticate posturing

Answer 26

Upper extremity flexion with lower extremity extension | Suggests lesion of cerebral hemisphere

Question 27

Components of brain death

Answer 27

1. Unresponsiveness / Deep Coma (GCS = 3) 2. No cerebrally modulated motor response to painful stimuli (spinal reflexes may be present; seizures or flexor/extensor posturing may NOT) 3. All brainstem reflexes are absent (pupils, corneals, oculovestibular, oculocephalic, gag, cough, respiratory effort) 4. Core body temperature of 32.2 (90F) 5. Toxicology is non-explanatory 6. Adequate BP (SBP > 90) and pulse (>50)

Question 28

Stage 1 Sleep

Answer 28

Transition phase with EEG similar to wakefulness

Question 29

Stage 2 Sleep

Answer 29

Light sleep Accounts for 50% of total sleep

Question 30

Stages 3 and 4 Sleep

Answer 30

EEG is very slow; deepest level of sleep Disorders of arousal (sleep walking and night terrors) occur during Stages 3 and 4 sleep, earlier in the night

Question 31

REM Sleep

Answer 31

Cycles occur every ~90 minutes, concentrated toward the later part of the night EEG looks awake but arousal threshold is higher than in SWS; muscles are paralyzed except for eyes and diaphragm, heart beats and respirations are irregular REM behavior disorder occurs

Question 32

Delayed sleep phase syndrome

Answer 32

Misalignment of alerting system with social demands; Larks want to sleep and wake early; if remain awake late, wake early resulting in EDS Night owls want to sleep late and wake late; experience EDS when awakened before alerting rhythms rise

Question 33

Insomnia - Contributing factors

Answer 33

Predisposing factors: Anxiety, worry, moodiness Precipitating factors: Anything causing a sleepless night Perpetuating factors: Catastrophizing about sleep, self-medication with ETOH and drugs

Question 34

Restless Leg Syndrome

Answer 34

Primary RLS is due to DA abnormalities and can be worsened by psychotropic medications (SSRIs, TCAs, Lithium) and antihistamines Increased risk with iron deficiency anemia (ferritin replacement if < 55)

Question 35

REM Behavior Disorder

Answer 35

Failure of skeletal muscle inhibition during REM leads to acting out dreams Treatment: Clonazepam, Melatonin

Question 36

Narcolepsy

Answer 36

EDS followed by cataplexy Cataplexy = short, sudden episode of lost muscle tone triggered by emotion; varies from slight facial weakness to total collapse

Question 37

Excessive Daytime Sleepiness - DDx

Answer 37

High Epworth score due to: ``` Insufficient sleep / poor sleep habits Circadian rhythm disorders - delayed sleep phase, shift-work, jet lag Sleep apnea Narcolepsy Idiopathic hypersomnia Drug use / withdrawal Restless leg syndrome ```

Question 38

Fatigue - DDx

Answer 38

Low Epworth score due to: Anxiety DepressionConditioned / learned insomnia

Question 39

How do we 'entrain' to a 24 hour day?

Answer 39

Morning light from the retina travels to the SCN via the RHT; SCN signals the pineal gland and inhibits production of melatonin In the absence of light this inhibition is removed, melatonin is constitutively produced, and people will "free run" on a 24.2 hour day

Question 40

How is sleep and wakefulness regulated by temperature?

Answer 40

Sleep is best on the descending curve of core body temperature; awakening occurs spontaneously 2-3 hours after body temperature begins to rise

Question 41

Zolpidem

Answer 41

Most widely prescribed hypnotic agent Effective for reducing sleep latency and nocturnal awakenings due to rapid oral absorption and short half-life; increases total sleep time and efficacy

Question 42

Zaleplon

Answer 42

Effective for decreasing sleep latency; NOT effective for preventing nighttime awakenings or increasing total sleep time Best for use in treatment of night time awakenings; can get the patient back to sleep (rapid onset) but eliminated by morning with little hangover (short half life)

Question 43

Eszoplicone

Answer 43

Longer half life Z drug agent; relatively safer for long term use without development of tolerance, dependence, or abuse

Question 44

Which region of the brain is the sleep/wake switch?

Answer 44

Hypothalamus

Question 45

Which region of the brain is the NREM/REM switch?

Answer 45

Brainstem

Question 46

Narcolepsy

Answer 46

Patients have reduction in the number of hypocretin / orexin neurons, which destabilizes the sleep/wake switch Patients experience unwanted transitions into sleep during wakefulness as well as frequent periods of awakening during sleep; patients quickly enter REM sleep at any time and experience REM-like episodes such as loss of muscle tone while awake (cataplexy) Treat with naps, stimulants, Na oxybutyrate

Question 47

Pathophysiology of Narcolepsy

Answer 47

Normally, hypocretin-secreting neurons activate serotonergic, noradrenergic, and histaminergic neurons that inhibit the "REM-ON" switch, promoting wakefulness; loss of hypocretin-secreting cells may disinhibit the REM-ON switch

Question 48

Effects of 5HT and NE on sleep

Answer 48

5HT and NE inhibit the REM-ON switch promoting wakefulness SSRIs, SNRIs and TCADs suppress REM sleep

Question 49

Normal sleep pattern

Answer 49

50% Stage 2 Sleep 25% Slow Wave Sleep (NREM Stages 3 and 4) 25% REM Minimal sleep latency, minimal nocturnal awakenings