Sleep, Attention, & Consciousness Flashcards
Effects of ACh on sleep
Muscarinic agonists and AChEIs activate REM
Antimuscarinic drugs cause drowsiness but decrease REM
Effects of histamine on sleep
Histamine inhibits the REM-ON switch promoting wakefulness
Antihistamines promote drowsiness and sleep
Effects of adenosine on sleep
Accumulation of adenosine signals time to sleep
Adenosine antagonists (caffeine) increases alertness
Mechanism of Benzo action in sleep
Agonists at GABA-A1 receptors in the cortex which mediate sleep, amnestic, and anticonvulsant actions
Benzodiazepines used for sleep + Pharmacokinetics
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
Adverse effects of benzodiazepines in sleep
Daytime sedation
Anterograde amnesia
Rebound insomnia
Psychologic and physical dependence (Schedule IV)
Benzodiazepines vs. Z drugs
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
Treatment of benzodiazepine overdose
Flumazenil
Ramelteon
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
Trazodone
Serotonin antagonist / reuptake inhibitor (SARI)
Uses: Patients with co-morbid substance abuse/depression
Adverse effects: Orthostasis, Priapism
Use of TCADs in insomnia
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
Diphenhydramine
Histaminic and muscarinic antagonist; produces drowsiness
Not indicated for use in insomnia
Characteristics of Z drugs
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
Z Drug Adverse Effects
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
What are the 3 types of ADHD?
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
What is the epidemiology of ADHD?
3-8% of school-aged children
4% of adults
Males > Females
What is the role of psychiatric comorbidity in ADHD?
65% of children with ADHD experience psychiatric comorbidity, including:
Major depression Anxiety / social phobia Oppositional / conduct disorder Antisocial personality disorder Substance abuse
Stimulant treatments for ADHD
Methylphenidate derivatives - Focalin/Ritalin (short acting) vs. Concerta (long acting)
Amphetamine salts - Adderall (short acting)
Non stimulant-based treatment of ADHD
NRIs (Atomoxetine)
NDRIs (Buproprion)
TCADs
Alpha-agonists (Clonidine) - for hyperactivity
Delirium
A state of fluctuating confusion, inattention, and misperceptions (illusions/hallucinations)
Stupor
A sleep-like state from which the patient can be aroused only by vigorous stimuli
Coma - Definition
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
Vegetative State - Definition
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)
Minimally conscious state (MCS)
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
Decerebrate posturing
Upper and lower extremity extension
Suggests lesion of upper brainstem
Worse prognosis than decorticate
Decorticate posturing
Upper extremity flexion with lower extremity extension
Suggests lesion of cerebral hemisphere
Components of brain death
- Unresponsiveness / Deep Coma (GCS = 3)
- No cerebrally modulated motor response to painful stimuli (spinal reflexes may be present; seizures or flexor/extensor posturing may NOT)
- All brainstem reflexes are absent (pupils, corneals, oculovestibular, oculocephalic, gag, cough, respiratory effort)
- Core body temperature of 32.2 (90F)
- Toxicology is non-explanatory
- Adequate BP (SBP > 90) and pulse (>50)
Stage 1 Sleep
Transition phase with EEG similar to wakefulness
Stage 2 Sleep
Light sleep
Accounts for 50% of total sleep
Stages 3 and 4 Sleep
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
REM Sleep
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
Delayed sleep phase syndrome
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
Insomnia - Contributing factors
Predisposing factors: Anxiety, worry, moodiness
Precipitating factors: Anything causing a sleepless night
Perpetuating factors: Catastrophizing about sleep, self-medication with ETOH and drugs
Restless Leg Syndrome
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)
REM Behavior Disorder
Failure of skeletal muscle inhibition during REM leads to acting out dreams
Treatment: Clonazepam, Melatonin
Narcolepsy
EDS followed by cataplexy
Cataplexy = short, sudden episode of lost muscle tone triggered by emotion; varies from slight facial weakness to total collapse
Excessive Daytime Sleepiness - DDx
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
Fatigue - DDx
Low Epworth score due to:
Anxiety
DepressionConditioned / learned insomnia
How do we ‘entrain’ to a 24 hour day?
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
How is sleep and wakefulness regulated by temperature?
Sleep is best on the descending curve of core body temperature; awakening occurs spontaneously 2-3 hours after body temperature begins to rise
Zolpidem
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
Zaleplon
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)
Eszoplicone
Longer half life Z drug agent; relatively safer for long term use without development of tolerance, dependence, or abuse
Which region of the brain is the sleep/wake switch?
Hypothalamus
Which region of the brain is the NREM/REM switch?
Brainstem
Narcolepsy
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
Pathophysiology of Narcolepsy
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
Effects of 5HT and NE on sleep
5HT and NE inhibit the REM-ON switch promoting wakefulness
SSRIs, SNRIs and TCADs suppress REM sleep
Normal sleep pattern
50% Stage 2 Sleep
25% Slow Wave Sleep (NREM Stages 3 and 4)
25% REM
Minimal sleep latency, minimal nocturnal awakenings
