Anxiety Flashcards
Suprachiasmatic nucleus
Hypothalamus
Controls 24h circadian rhythm
Neurones here increase activity during the light phase, and decrease it during the night phase
Melatonin
Increased during dark (sleep) phase
Wakefulness
Cholinergic system (pedunculopontine and laterodorsal tegmental nuclei) Monoaminergic projections (locus coeruleus, raphe nuclei, tuberomammillary nucleus) Dopamine Noradrenaline Serotonin Histamine ACh Orexin
Sleep
GABA and galanin neurones (ventrolateral preoptic nucleus)
Melatonin
Adenosine
Sleep cycles
Each cycle lasts approx. 90 mins
Cycles not identical in ratio NREM/REM sleep
REM
rapid eye movement phase
NREM
non-rapid eye movement phase
SWS
slow wave sleep (NREM-3 and 4)
How to assess sleep stages
Polysomnography
Normal wakefulness EEG
Beta waves
13-30 Hz
Awake + relaxed EEG
Alpha waves
8-12Hz
Stage 1 NREM EEG
Theta waves
3.5-7.5Hz
Stage 2 NREM EEG
Theta waves with sleep spindles and K complex
Stage 3 + 4 NREM EEG
Delta waves
Less than 3.5Hz
Stage 3- less than 50%
Stage 4- more than 50%
Types of Insomnia
Transient- jet lag
Short-term- bereavement, stress
Chronic- 3 weeks +
Ideal drug for insomnia
Benzodiazepines (short-acting)
Z drugs
Short term use Insomnia
Lorazepam
Temazepam
Long term use Insomnia
Eszopiclone
Extended release Zolpidem
Benzodiazepines SE
Change in sleep patterns Daytime sedation Rebound insomnia Tolerance Dependence
Orexin system
Orexin (hypocretin)= peptide produced in hypothalamus
Orexin A
Orexin B
Effects mediated by Orexin 1 + 2 receptors
Regulates arousal, appetite, wakefulness
Orexin deficiency
Narcolepsy- excessive sleepiness, increased frequency of falling asleep in daytime
Suvorexant
Dual orexin receptor antagonist
Used to treat insomnia
Types of anxiety disorders
Panic disorder Agoraphobia Social phobia Simple phobia Obsessive compulsive disorder Post-traumatic stress disorder Generalised anxiety disorder
Structures involved in anxiety
Amygdala Insula Anterior cingulate Prefrontal cortex Thalamus HPA axis abnormalities Monoaminergic systems GABAergic systems
Genetics + anxiety
5HT transmission involved in genetic risk for anxiety disorders
Genes + panic disorder
COMT CCK CCKb receptor Adenosine A2 receptor MAOa 5HT2 receptor
KF1
If don’t have it, increased fear/anxiety
Benzodiazepines
Clonazepam
Lorazepam
5HT1a agonists
Buspirone
Ipsapirone
SSRIs
Fluoxetine
Escitalopram
SNRIs
Venlafaxine
Duloxetine
Beta adrenoreceptor antagonists
Propanolol
Barbiturates problems
Drug dependence Tolerance Induction liver microsomal enzymes Fatal toxicity in overdose- resp. depression Speech drowsiness Withdrawal syndrome
Benzodiazepine MOA
GABAa receptor
Positive allosteric modulators
Potentiates GABA-induced hyperpolarisation
Flumazenil
Antagonist of benzodiazepines
Used in benzodiazepine overdose
Short half life
Generalised anxiety disorder treatment
Buspirone
Venlafaxine, duloxetine (SNRI)
Fluoxetine, escitalopram (SSRI)
Risperidone, quetiapine, olanzapine (APD)
Benzodiazepine complications in elderly
Psychomotor impairment Risk of falls Daytime drowsiness Intoxication Amnesia Depression
Z drug targets
Alpha subunits of GABAa receptors
Zaleplon + zolpidem bind to alpha 1 subunit- hypnotic role
Alpha 3 subunit- linked to anxiolytic effects
