Sleep and Hypnotics

Question 1

What is sleep?

Answer 1

A readily reversible state of reduced responsiveness to and interaction with the environment

Question 2

Hierarchy of awakeness

Answer 2

Alertness > sedation > hypnosis > obtundation > stupor > coma > death

Question 3

Obtundation

Answer 3

Only painful stimuli will make you conscious again

Question 4

Sleep is important for…

Answer 4

Restoration
Homeostasis
Memory consolidation

Question 5

Electroencephalogram

Answer 5

Used to record brain activity
Activity of populations of neurons measured using amplitudes
Reveals synchrony of neuronal activity
Frequencies = how fast neurons are firing

Question 6

δ waves

Answer 6

Deep dreamless sleep
< 4Hz

Question 7

θ waves

Answer 7

Light sleep, dreaming, mental imagery, mediation, memory
4-7 Hz

Question 8

α waves

Answer 8

Conscious relaxation, mental visualisation
8-13 Hz

Question 9

β waves

Answer 9

Awake, alert, concentration, cognition, motor activity, navigation
> 14Hz

Question 10

γ waves

Answer 10

Memory encoding and recall, attention, predictions, cognitive processing

Question 11

REM

Answer 11

Rapid eye movement
Occurs for about 20 mins at a time
Associated with dreaming
β waves

Question 12

Non-REM

Answer 12

Other 4 stages
Stages last for 60-90 minutes total.
Cycle repeats 4-6 times
Stage 4 and stage 3 are lost throughout the night

Question 13

Awake

Answer 13

α and β waves

Question 14

Stage 1 sleep

Answer 14

θ waves
Transitional, lasts 5 mins
Starting to fall asleep
Nerve cells start to become synchronised

Question 15

Stage 2 sleep

Answer 15

Spindles
K-complexes
5-15 minutes
Deeper sleep

Question 16

Stage 3 sleep

Answer 16

δ waves
5-25 mins
All movements are absent
Restorative sleep

Question 17

Stage 4 sleep

Answer 17

δ waves
20-40 mins
Deep sleep
Large amplitude
Slow waveform

Question 18

Autonomic activity in sleep

Answer 18

Sympathetic dominates during REM
Non-REM is a rest period - parasympathetic

Question 19

Important areas for controlling sleep

Answer 19

Reticular activating system
Thalamus

Question 20

Reticular activating system

Answer 20

A group of nuclei in the brainstem
Brain stem lesions result in coma and sleep
Brain stem stimulation induces wakefulness

Question 21

Thalamus and sleep

Answer 21

Thalamic stimulation induces sleep
Thalamus decouples the cortex from the rest of the brain so that it can rest
Thalamo-cortical input controls sleep

Question 22

Mechanism of sleep

Answer 22

Ascending RAS (neurotransmitters)
Increased firing of these neurons = awakening
Decreased firing of these neurons = falling asleep

Question 23

Ascending reticular activating system

Answer 23

• Locus coeruleus – noradrenaline
• Raphe nuclei – serotonin
• Brainstem/forebrain – acetylcholine
• Midbrain – histamine

Question 24

Increased firing of RAS = awakening

Answer 24

• Orexin neurons in hypothalamus increases firing of RAS and histamine
• Thalamus generates non-rhythmic activity
• Cortex entrained into fast waking activity.

Question 25

Decreased firing of RAS = falling asleep

Answer 25

RAS/histamine inhibited by GABA/galanin neurons in the hypothalamus

Question 26

REM-on cells are...

Answer 26

Cholinergic Neurons in brainstem

Question 27

REM-off cells are...

Answer 27

Serotoninergic and noradrenergic Brain stem neurons

Question 28

What drives the change to REM or active sleep?

Answer 28

Switching on of acetylcholine

Question 29

Sleep disorders

Answer 29

Transient insomnia Short term insomnia Chronic insomnia Fatal familiar insomnia (rare prion disease)

Question 30

Insomnia

Answer 30

Difficulty going to sleep Difficulty staying asleep Waking up feeling as if you didn't sleep

Question 31

What are hypnotics

Answer 31

Drugs used to induce and maintain sleep Should be used short term and intermittently Aims to shorten time to sleep and length of sleep without supressing the cycle.

Question 32

Benzodiazepines as hypnotics

Answer 32

Problems with tolerance and dependence, and rebound insomnia Long and short acting depends on the metabolism of the drug

Question 33

Non-benzodiazepines as hypnotics

Answer 33

z drugs May have sub-unit specificity Potentially fewer side effects

Question 34

Barbiturates and barbiturate-like hypnotics

Answer 34

Rarely used now, now mainly used by vets to put animals down Not as safe in overdose as benzodiazepines

Question 35

Orexin antagonists as hypnotics

Answer 35

Orexin switches on the RAS So supressing it can be hypnotic

Question 36

Histamine H1antagonists or inverse agonists as hypnotics

Answer 36

These are over the counter sleep remedies

Question 37

Gamma hydroxybutyrate as hypnotic

Answer 37

Naturally occurring May be a GABAB-agonist or metabolised to GABA

Question 38

Melatonin receptor agonists as hypnotics

Answer 38

May reset disturbed circadian rhythms

Question 39

Narcolepsy

Answer 39

Pathological increase in sleep, (opposite to insomnia) Sudden onset of sleep episodes and loss of motor control (cataplexy) May involve reduced numbers of orexin neurones – loss of RAS activation

Question 40

Treatment of narcolepsy

Answer 40

Stimulant drugs e.g. methylphenidate, modafinil, amphetamine-related Antidepressants - SSRIs, SNRIs, TCAs Sodium oxybate – (GHB) Orexin agonists?