Sleep Disorders and their treatment Flashcards
what is stage 1 in the sleep cycle ?
light sleep, transition from alpha waves at 8-12 Hz to theta waves at 4-7Hz
what is stage 2 of the sleep cycle ?
this is unconscious sleep, sleep spindles occur at 12-16Hz
what are stages 3 and 4 of the sleep cycle ?
these are sometimes considered the same stage
deep sleep, slow wave sleep, delta waves of 0.5-4Hz
how many sleep cycles do you go through each night and describe the events in sleep cycles ?
4-5 cycles, each lasting about 1.5-2 hours
the cycles have more non-REM sleep earlier in the night
the time spent in stage 2 and REM increases through the night
how can sleep patterns be disturbed ?
disturbed by sleep disorders, medication and drugs of abuse
patterns also change with age
what NT are involved in maintaining wakefulness?
noradrenaline serotonin dopamine histamine acetylcholine orexin
what NT are involved in promoting sleep ?
melatonin
GABA
adenosine
what happens with the release of orexin when your awake and when your asleep?
when your awake it is released at the TMN- tuberomamillary nucleus
when your asleep it is not released
what is happening when you are in the awake state ?
the ventrolateral preoptic nucleus has GABAergic neurons that are under tonic inhibition by noradrenaline
what happens in endogenous NREM sleep?
noradrenergic neurones in the locus coeruleus are inhibited by GABA
this in turn releases the tonic noradrenergic inhibition of the ventrolateral preoptic nucleus
what happens when the VLPO is released from inhibition ?
it enables the VLPO to release GABA onto the TMN
this inhibits the release of the arousal promoting histamine into the cortex
this induces loss of consciousness
what are the other pathways involved in NREM sleep ?
VLPO projects to all the monoaminergic cholinergic and orexinergic arousal nuclei such as tmn, LC, DR, PPTg, LDTg, PeF
these project to the cortex where they release arousal promoting neurotransmitters to promote wakefulness
what can be measuredd to assess sleep ?
sleep onset latency total sleep time sleep efficiency wake time after sleep onset (WASO) number of awakenings sleep quality
what is a subjective tool used to assess sleep measurements ?
sleep diary
what objective tools can be used to assess sleep measurements ?
MULTIPLE SLEEP LATENCY TEST
- assess daytime sleepiness by measuring the time it takes for patients to fall asleep (daytime nap)
POLYSOMNOGRAPHY
- typically used during an overnight sleep study
- electrodes continuouslu record eeg, REMs and muscle tone
WRIST ACTIGRAPHY
- used adjunctively with other objective data
- records movements of the wrist to determine time spent sleeping
what is important to record when carrying out a polysomnography ?
blood oxygen levels because some patients can stop breathing briefly during their sleep - this normally occurs in the elderly
what are some examples of sleep disorders ?
insomnia circadian rhythm disorders narcolepsy parasomnias obstructive sleep apnoea syndrome
what are circadian rhythm disorders ?
jet-lag
shift-work disorder
advanced and delayed sleep phase syndromes
what are parasomnias ?
sleep walking night terrors bruxism - grinding of teeth restless leg syndrome periodic leg movement disorder
what happens to our circadian rhythm when we are placed in a cave or special apartment without clocks or time cues ?
people tended to go to bed an hour later and get up an hour later each day
what does melatonin do ?
it promotes sleep
how many people suffer from insomnia ?
it is a significant problem which is being increasingly recognised
10-30% of the population suffer from it
50% of insomnia patients have reduced daytime fucntioning - inability to concentrate, reduced energy, memory problems, work hazard
what is primary insomnia ?
symptoms present for greater than 1 month
no associated mental or physical disorder
it is also known as chronic insomnia
what is transient insomnia ?
associated with specific events- acute periods of stress or anxiety
how is insomnia associated with depression and anxiety ?
insomnia is one of a number of symptoms caused due to depression and anxiety disorders
therefore do you treat the mental disorder or the symptoms
what are non-pharmacological treatments for sleep disorders ?
SLEEP HYGIENE- be active during the day to try and tire yourself out
COGNITIVE BEHAVIOURAL THERAPY- therapy involves training people into good habits
what pharmacological treatments can be used to treat sleep disorders ?
for insomnia
- benzodiazepines and z drugs ( zolpidem, zaleplon, zopiclone)
- chloral hydrate, chlromethiazole, antihistamines and melatonin
for narcolepsy
- sodium oxybate (GHB), modafinil
how can REM sleep be dtermined ?
by putting an electrode net to the your eye- it is when you are dreaming
what agents are involved in promoting sleep ?
GABA agonists and GABA allosteric modulators
melatonin agonists
5-HT2 antagonists
orexin anatgonists
what agents are involved in promoting wakefulness ?
adenosine antagonists - caffeine
dopamine stimulants
what agents cause sedation ?
GABA agonists and allosteric modulators
noradrenergic alpha-1 antagonists
histamine H-1 antagonists
muscarinic antagonists
what do all classical benzodiazepines have ?
all have hypnotic action
what dictates the usefulness of benzodiazepines ?
their duration of action
- do not want daytime sleepiness
short half life benzodiazepines are recommended such as temazepam - 9hrs
what are the concerns associated with dependence of benzodiazepines?
there is more chance with short half life- this datta is limited with respect to hypnotic actions
have to limit use to short term use
PRN- pro re nata- taken when needed
what effects were seen on sleep quality when benzodiazepines were taken ?
improvements were seen during the 24 week test period but it was followed by a rebound worsening of sleep
what are z drugs ?
theses are non-benzodiazepines that act at specific subset of GABAa receptors
what are some examples of Z drugs ?
zolpidem
zopiclone
zalepton
eszopiclones
what receptors do zolpidem, zopiclone and zaleplon primarily act at ?
alpha1/beta2/gamma2 subunit GABAa receptors
what does eszopiclone primarily act at ?
GABAa receptors made up of alpha2/beta2/gamma2, alpha3/beta2/gamma2 subunits
act to a lesser extent at alpha1/beta2/gamma2
what is more recommended BZs or Z drugs ?
BZs is recommeneded by nice
what are the pharmacokinetics of BZs and Z drugs ?
generally they have similar times to reach tmax, becayse 1-2hours
he half life of the BZs is longer copared to the z drugs
what does chloral hydrate and chlormethiazole do ?
they are older drugs and are no longer recommended
GABAa receptor modulators
activate GABAa receptors at high doses and therefore they are not safe
what do antihistamines do ?
e.g. promethazine
over the counter medication
little hypnotic effects, mainly sedative
tolerance and next day sedation are issues
what does melatonin do ?
it is used in short term insomnia for people over 55 yrs
what does sodium oxybate do ?
(gamma-hydroxybutyrae- GHB)
GABA analogue but has an unknown mechanism of action
street drug (GHB, liquid ecstasy)
useful in narcolepsy with cataplexy
what does modafinil do ?
useful for daytime sleepiness associated with narcolepsy
unknown mechanism of action
