Sleep and Hypnotics Flashcards
What is sleep?
A readily reversible state of reduced responsiveness to and interaction with the environment
Hierarchy of awakeness
Alertness > sedation > hypnosis > obtundation > stupor > coma > death
Obtundation
Only painful stimuli will make you conscious again
Sleep is important for…
Restoration
Homeostasis
Memory consolidation
Electroencephalogram
Used to record brain activity
Activity of populations of neurons measured using amplitudes
Reveals synchrony of neuronal activity
Frequencies = how fast neurons are firing
δ waves
Deep dreamless sleep
< 4Hz
θ waves
Light sleep, dreaming, mental imagery, mediation, memory
4-7 Hz
α waves
Conscious relaxation, mental visualisation
8-13 Hz
β waves
Awake, alert, concentration, cognition, motor activity, navigation
> 14Hz
γ waves
Memory encoding and recall, attention, predictions, cognitive processing
REM
Rapid eye movement
Occurs for about 20 mins at a time
Associated with dreaming
β waves
Non-REM
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
Awake
α and β waves
Stage 1 sleep
θ waves
Transitional, lasts 5 mins
Starting to fall asleep
Nerve cells start to become synchronised
Stage 2 sleep
Spindles
K-complexes
5-15 minutes
Deeper sleep
Stage 3 sleep
δ waves
5-25 mins
All movements are absent
Restorative sleep
Stage 4 sleep
δ waves
20-40 mins
Deep sleep
Large amplitude
Slow waveform
Autonomic activity in sleep
Sympathetic dominates during REM
Non-REM is a rest period - parasympathetic
Important areas for controlling sleep
Reticular activating system
Thalamus
Reticular activating system
A group of nuclei in the brainstem
Brain stem lesions result in coma and sleep
Brain stem stimulation induces wakefulness
Thalamus and sleep
Thalamic stimulation induces sleep
Thalamus decouples the cortex from the rest of the brain so that it can rest
Thalamo-cortical input controls sleep
Mechanism of sleep
Ascending RAS (neurotransmitters)
Increased firing of these neurons = awakening
Decreased firing of these neurons = falling asleep
Ascending reticular activating system
- Locus coeruleus – noradrenaline
- Raphe nuclei – serotonin
- Brainstem/forebrain – acetylcholine
- Midbrain – histamine
Increased firing of RAS = awakening
- Orexin neurons in hypothalamus increases firing of RAS and histamine
- Thalamus generates non-rhythmic activity
- Cortex entrained into fast waking activity.
Decreased firing of RAS = falling asleep
RAS/histamine inhibited by GABA/galanin neurons in the hypothalamus
REM-on cells are…
Cholinergic
Neurons in brainstem
REM-off cells are…
Serotoninergic and noradrenergic
Brain stem neurons
What drives the change to REM or active sleep?
Switching on of acetylcholine
Sleep disorders
Transient insomnia
Short term insomnia
Chronic insomnia
Fatal familiar insomnia (rare prion disease)
Insomnia
Difficulty going to sleep
Difficulty staying asleep
Waking up feeling as if you didn’t sleep
What are hypnotics
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.
Benzodiazepines as hypnotics
Problems with tolerance and dependence, and rebound insomnia
Long and short acting depends on the metabolism of the drug
Non-benzodiazepines as hypnotics
z drugs
May have sub-unit specificity
Potentially fewer side effects
Barbiturates and barbiturate-like hypnotics
Rarely used now, now mainly used by vets to put animals down
Not as safe in overdose as benzodiazepines
Orexin antagonists as hypnotics
Orexin switches on the RAS
So supressing it can be hypnotic
Histamine H1antagonists or inverse agonists as hypnotics
These are over the counter sleep remedies
Gamma hydroxybutyrate as hypnotic
Naturally occurring
May be a GABAB-agonist or metabolised to GABA
Melatonin receptor agonists as hypnotics
May reset disturbed circadian rhythms
Narcolepsy
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
Treatment of narcolepsy
Stimulant drugs e.g. methylphenidate, modafinil, amphetamine-related
Antidepressants - SSRIs, SNRIs, TCAs
Sodium oxybate – (GHB)
Orexin agonists?
