what are the neurotransmitter promoting sleep?
GABA
what are the neurotransmitter promote wakefulness
NE, DA, acetylcholine, histamine, orexin
which stage of the sleep is the restorative sleep?
delta, stage 3-4
what is insomnia?
inability to initiate/maintain sleep, associated with daytime problems (fatique, impaired concentration/memory)
insomnia disorder (DSM-5 criteria)
- at least 1 of the following:
- difficulty with sleep initiation
- difficulty with sleep maintenance
- early morning awakening - sleep compliant is associated with social, occupational, academic, educational, behavioral/functional distress/impairment
- at least 3 nights/week and for at least 3 months
- sleep difficulties happen even with ample opportunity to sleep
- sleep compliant not attributed to/explained by another sleep-wake disorder, adverse effect of medication/substance or co-existing psychiatric illness/medical condition
how can anxiety disorder be classfied?
acute (sleep difficulties for 1 nights - few weeks):
- transisent < 1wk
- short-term < 4wk
chronic >4wk
how is transient acute anxiety disorder manage?
sleep hygiene
usually self-limiting
how is short-term insomnia manage?
short term PRN course of hypnotic for 7-10d, up to 204w
sleep hygiene
how is chronic insomnia manage?
investigate for underlying psychiatric/medical condition –> treat them
sleep hygiene
discourage long-term use of hypnotics
principle of pharmacological therapy for insomnia?
Fast acting Anxiolytics/ Sedatives/ Hypnotics , are intended only as
adjuncts for short term relief of distressful Insomnia/ Anxiety,
- limited to PRN dosing, at lowest effective dose, & short course (1 2 weeks)
- continuous use is harmful if the primary physical/mental issue is not resolved.
what are the non-pharmacological therapy for insomnia?
- Avoid the use of caffeine containing products, nicotine and alcohol especially later in the day.
- Avoid heavy meals within 2 hours of bedtime.
- Avoid drinking fluids after dinner to prevent frequent night time urination.
- Avoid environments that will make you really active after 5pm (i.e. avoid noisy
- Establish a routine for getting ready to go to bed.
- Avoid taking daytime naps. If you have to take them, make sure you do so before 3.00 pm and that
the total napping time does not exceed one hour. - Pursue regular physical activities like walking or gardening but avoid vigorous exercise too close to bedtime.
what are the adjunctive treatment for insomnia?
hypnotics:
- benzodiazepones
- z-hypnotics (zolpidem, zopiclone)
- antihistamine
- melatonin receptor agonist
- lemborexant
MOA for benzodiazepine?
potentiates GABA
side effects for benzodiazepine?
sedation, drowsiness, muscle weakness, ataxia, amnesia
duration of treamtment for benzodiazepines?
short term, limit to 2 weeks PRN at lowest effective dose
MOA for z-hypnotics?
binds to benzodiazepine-binding sites with gamma & a1 subunit –> sedation
side effects for z-hypnotics?
taste distrubance (zopiclone)
less common: nausea, vomiting, dizziness, dry mouth, headache, rarely amnesia, confusion, hallucinations, nightmares, complex sleep behaviours (sleep-walking)
what should you take note for zolpidem?
half dose in females
which hypnotics causes dependence?
z-hypnotics
benzodiazepines
side effects for anti-histamine?
sedation, anticholinergic (dry mouth, constipation)
what is lemborexant MOA?
OX1 & OX2 receptor anatagonism
side effects for lemborexant?
somnolence, nightmare, uncommonly sleep paralysis, hypnagogic, hypnopomic hallucinations
what is the contraindication for lemborexant?
nacrolepsy
what to take note for lemborexant?
it is a moderate to severe CYP3A4 inhibitor/inducer
