18 - Anxiety and Insomnia Flashcards
What controls nocturnal/diurnal rhythms in the brain
Suprachiasmatic nucleus in the hypothalamus
What occurs to the activity of the SCN neurons in light phase?
They increase their activity
Which hormone increases in the dark phase
Melatonin
Wakefulness cholinergic system
pedunculopontine and laterodorsal tegmental nuclei
Wakefulness monoaminergic projections
locus coeruleus, raphe nuclei, tuberomamillary nucleus
Sleep GABA and galanin neurons
ventrolateral preoptic nucleus
How long is one sleep cycle
90mins
REM
rapid eye movement phase
Eyes still move under lids
NREM
non-rapid eye movement phase
Deep sleep
SWS
Slow Wave Sleep
Includes NREM
Insomnia treatment
Benzodiapines
Z drugs
Examples of Z drugs
Zaleplon, Zolpiedm, Zopiclone
Short term insomnia treatment?
lorazepam, temazepam
Long term insomnia treatment?
eszopiclone and extended release zolpidem
Side effects of Benzodiapines
Change in sleep patterns (suppress deep sleep and REM sleep)
Daytime sedation
Rebound insomnia – Become dependent
Tolerance
Dependence (withdrawal syndrome characterised by anxiety, nausea, muscle cramps, seizures)
Where is Orexin produced
Hypothalamus
What do orexins regulate
arousal, appetite, wakefulness
Narcolepsy
Deficiency in orexins
Excessive sleepiness
Orexin Antagonist
Suvorexant - used to treat insomnia
Structures in the brain involved in Anxiety
Amygdala, insula, anterior cingulate, prefrontal cortex, thalamus
Genetic risk factors for anxiety
5-HT transmission COMT CCK CCKB receptor Adenosine A2 receptors MAOA 5-HT2 receptor
KF-1 ubiquitin ligase
anxiety suppressor (increases after administration of SSRIs)
Anxiolytics
Benzodiapines 5-HT1A agonists B-adrenoceptor antagonists SSRIs Barbiturates (obsolete)
Benzodiapines
clonazepam, alprazolam, diazepam
POSITIVE ALLOSTERIC MODULATORS at the receptor complex of GABAa
Overdose of benzodiazepines
Flumazenil
5-HT1A agonists
buspirone, ipsapirone
B–adrenoceptor antagonists
propranolol
SSRIs
fluoxetine, escitalopram, paroxetine
Why are barbiturates no longer used for anxiety
Fatal overdose toxicity
Major risk of drug dependence
Management of generalised Anxiety Disorder
1) buspirone
2) venlafaxine, duloxetine (SNRI)
3) fluoxetine, escitalopram (SSRI)
4) risperidone, quetiapine, olanzapine (APD)
GABA subunit target for Z drugs
A subunits
zaleplon and zolpidem bind to the α1 subunit – hypnotic role
α3 subunits are linked to anxiolytic effects
