Pharmacology of anxiety + sleep disorders Flashcards
what are the clinical uses of hypnotics and anxiolytics?
induction of sleep
relief of anxiety
sedation + amnesia (before medical procedure)
control of withdrawal states in addiction (e.g. delirium tremens)
muscle relaxation
severe behavioural disturbance
describe the 2 process model of the sleep-wake cycle.
- Circadian alerting signal - changes in hormones (cortisol + melatonin) either increase or decrease alertness
- homeostatic sleep drive - increases throughout the day and reduces at night
What is the role of the suprachiasmatic nucleus (SCN) in terms of the sleep-wake cycle?
This is found in the hypothalamus
It controls the 24-hour circadian rhythm
Neurones in the SCN increase activity in the light phase and reduce activity in the dark phase
*there is an increase in melatonin in the dark/sleep phase
What neurotransmitter/chemical systems and which brain structures are involved in wakefulness?
Cholinergic system:
- pedunculo pontine + lateral dorsal tegmental nuclei
Monoaminergic projections:
- locus coeruleus
- raphe nuclei
- tuberomamillary nucleus
What neurotransmitter/chemical systems and which brain structures are involved in sleep?
GABA + galanin neurones:
- ventrolateral preoptic nucleus
Which neurotransmitters maintain wakefulness?
noradrenaline dopamine serotonin histamine acetylcholine orexin
Which neurotransmitters promote sleep?
GABA
melatonin
adenosine
What do REM, NREM, and SWS stand for?
REM = rapid eye movement NREM = non-rapid eye movement SWS = slow wave sleep (NREM 3+4)
How long does a sleep cycle last?
90 minutes
What waves are associated with:
- Awake
- Stage 1 (awake + relaxed)
- Stage 2 (Stage 1 NREM)
- Stage 3 (Stage 2 NREM)
- Stage 4 (SWS)
- REM
And what are the frequencies of each wave?
- Awake:
beta waves
13-30 Hz - Stage 1 (awake + relaxed)
alpha waves
8-12 Hz - Stage 2 (Stage 1 NREM)
theta waves
3.5 - 7.5 Hz - Stage 3 (Stage 2 NREM)
theta waves with sleep spindles + k complexes
12 - 14 Hz - Stage 4 (SWS)
delta waves
<3.5 Hz - REM
random, fast with sawtooth waves
low voltage
Name the different types of insomnia.
transient (e.g. jet lag)
short-term ( associated with illness, bereavement and stress)
chronic - lasts >3 weeks
What types of drugs are used to treat insomnia? Give examples of short-term and long-term use drugs?
benzodiazepines + Z-drugs
Short-term use: lorazepam + tenazepam
Long-term use: eszopiclone
+ extended release = zolpidem (for chronic insomnia)
What are some of the unwanted effects of benzodiazepines?
- changes in sleep patterns (suppress deep sleep + REM sleep)
- daytime sedation
- rebound insomnia
- tolerance
- dependence
What is the benefit of using pregabalin to treat insomnia?
No disruption of sleep patterns
No tolerance
Where is orexin produced? What forms does it come in? What is its function?
Produced in the hypothalamus
Comes in two forms: orexin A + B
effects are mediated by OX1 and OX2 receptors –> allows regulation of arousal, appetite and wakefulness
What is narcolepsy? What is it the result of?
Condition when a person falls asleep when in relaxing surroundings
Caused by a deficiency in orexin
What is Suvorexant? What condition is it used in? What are the advantages of using this drug?
Dual orexin receptor (1+2) receptor antagonist
Used for insomnia
No amnesia, no dependence + abuse, no rebound insomnia, no resp, depression, no orthostasis or anticholinergic effects
What brain structures and neurotransmitters are involved in anxiety?
Amygdala, insula, ACC, thalamus
Abnormalities in HPA axis
Monoaminergic systems
GABAergic systems
what functional difference is commonly seen in people with anxiety?
hyperactivity of the limbic structures (i.e. amygdala) and the inability of higher cortical structures to control this
Which genes have been associated with panic disorder?
COMT CCK CCKb receptor Adenosine A2 receptor Monoamine oxidase A 5-HT2 receptor
What gene is thought to be an anxiety suppressor?
KF-1 ubiquitin ligase
Name the different classes of anxiolytics and give examples for each one.
Benzodiazepines:
- lorazepam
- alprazolam
- clonazepam
- diazepam
5-HT1a agonist/partial agonist:
- buspirone
- ipsapirone
SSRIs:
- fluoxetine
- escitalopram
- paroxetine
SNRIs:
- venlafaxine
- duloxetine
Beta-adrenoreceptor antagonist:
- propanolol
What drug can be used on benzodiazepine overdose? What is the MOA of this drug?
Flumazenil
It competitively inhibits bezodiazepines/ acts as an antagonist at the benzodiazepine binding site
What are the cellular targets for z-drugs?
alpha subunits of the GABAa receptors
alpha 1 subunit = hypnotic effect
alpha 3 subunit = anxiolytic effect
