Anxiety Flashcards
what are anxiolytics?
drugs used to allay (alleviate) anxiety
what are anxiogenics?
drugs that induce anxiety for use in labs
what are allosteric modulators?
enhance effects of agonist
what is ‘eustress’?
acute stress
physiological stress = bodies response to external pressure
define anxiety
psychological response to a perceived threat, very closely linked to fear (which is the psychological response to REAL threat)
what is the fight or flight response?
normal stress response to acute pressure (completely normal as should subside after stimulus has gone)
what is distress?
chronic stress
unrelenting pressure for long periods - usually psychological but can be physical e.g arthiritis
symptoms similar to eustress but exaggerated
anxiety does not subside and it is out of proportion to the stimulus/threat
what are the symptoms of distress?
generalised muscle ache/ headache, memory impairment
insomnia
depression
anxiety increase
when is anxiety classified as anxiety disorder?
when it interferes with everyday life
- core symptoms of fear and avoidance behaviours
- avoidance behaviour allows fear to continue unchallenged i.e prevents person from observing external info that might disconfirm fears
what is the lifetime prevalence of anxiety (Wittchen and Jacobi 2005)
21% life time prevalence
2:1 ration female :male
often comorbid
outline generalised anxiety disorder
excessive and persistent anxiety/worry > 6 months
fear of future events, personal safety
often present with SOMATIC complaints like heachache or stomach ache
outline obsessive compulsive disorder
obsessive repetitive thoughts which are often negative counteracted by compulsive behaviours (rituals) providing temporary relief e.g redoing and checking
outline panic disorder with/without agoraphobia
sudden unexpected panic attacks - intense recurrent fear of dying/illness
palpitations, tremor, dizziness
fear of certain place can result in phobic avoidance = agoraphobia
outline phobic disorders
excessive fear disproportionate to specific situation
generally predictable = phobic avoidance
social phobia = excessive fear of social situations, fear of being negatively scrutinised/humiliated
outline post traumatic stress disorder
onset weeks/months after intense traumatic event
re-experience of trauma fear of dying and flashbacks
triggered by sensory cues so develop avoidance symptoms
hyperarousal with hypervigilance
what is the biological basis of anxiety disorders?
CNS, HPA axis and autonomic nervous system all connected and feedback to each other to coordinate response
how do we know this is what happens
knowledge form classical lesion studies in combination with behaviour and more recently imaging brain areas which are activated by fear
what brain area is mainly involved in the stress response?
the amygdala
receives external info about threat and appraises new stimulus in context of stored emotional memories in the prefrontal/medial cortex and hippocampus ( we have innate fears but most of them we have learnt)
what is an example of why we know the amygdala is involved in the stress response
a study of people with PTSD - when they were shown a feared image fMRI showed higher amygdala activity.
and elevated levels of CRF.
are the levels of noradrenaline in people with anxiety disorders always elevated?
no, only when they are stimulated or exposed to fear.
how would you summarise what is affected to cause anxiety disorder biologically?
noradrenergic neurotransmission
- an increase of noradrenaline when in situation of perceived threat
outline GABAergic dysfunction in anxiety disorders
decreased binding at benzodiazepine site on GABAA receptor/benzodiazepine complex in anxiety disorder
PTSD patients have lower benzodiazepine binding in frontal cortex indicating lower level of GABAA receptor
why does GABAergic dysfunction arise in anxiety disorder?
chronic stress/lots of glucocorticoids decreases inhibitory GABAA receptor expression
adrenalectomy (removal of adrenals) increases GABAA expression
long stress means one would constantly produce cortisol and data indicates GABAA expression might decrease?
outline serotonergic dysfunction in anxiety disorders
people with anxiety have dysfunctional 5HT receptors - lower expression of them
what is the source of serotonin in the brain
raphe nucleus
why do people with anxiety have dysfunctional 5Ht receptors?
chronic stress/glucocorticoid in animals causes decrease in serotonin receptor
in contrast: remove adrenals (stress hormone site) = increase in serotonin receptor expression
so what does long stress mean for serotonergic receptors in the brain?
the receptors change and 5Ht receptors are inhibitory which means an increase in excitatory neurotransmission in the brain
what are common side effects of anxiolytics with chronic use?
tolerance and dependance
are anxiolytics still prescribed
they shouldnt be as are grouped with sedatives and hypnotics but they are still important
what does the therapeutic effect of anxiolytics depends on?
the dose given - lower doses cause anxiolysis but higher doses cause sedation and even hypnosis so not good
outline alcohol as an anxiolytic
self medication
non specific CNS depressant
rapid effect = high solubility and blood alcohol concentration
outline barbiturates as anxiolytics
popular in 60s
effective but small therapeutic window
easy to overdose
effects were potentiated by alcohol
should not be used for anxiety
outline benzodiazepines
Librium discovered in 1957 - sedative and anticonvulsant then rapid development of other drugs e.g Valium which accounted for half of US psychoactive drug prescriptions
outline the therapeutic use of benzodiazepines
short term sedation for surgical procedures
anxiolysis (sedation where person is very relaxed yet awake)
anticonvulsant (suppress neuronal activity in seizure)
hypnosis (induce sleep)
relieves muscle tension
what are some acute side effects of benzodiazepines?
unwanted sedation/drowsiness
amnesia
reduced cognition
reduce motor coordination
potentiated by alcohol
decrease in REM sleep
what are some chronic side effects of benzodiazepines
tolerance
dependance
withdrawl symptoms
what are the pharmacokinetics of benzodiazepines? - examples
sedative MIDOZOLAM - very short half life
hypnotic OXAZEPAM - short half life 8-12 hours
VALIUM anxiolytics - long half life 20-90 hours but cause acute alcohol withdrawal, convulsions
why does valium have such a long half life?
metabolised into active metabolites so prolongs effect
what receptors do anxiolytics act on?
GABAA
they are allosteric modulators of the receptor
outline a GABAA receptor
pentameric ion channel which increases Cl- permeability and hyperpolarises to inhibit neurone
why does anxiolytics acting on GABAA receptors alleviate anxiety?
GABAAergic interneurons in all of brain, release gaba to inhibit neuronal activity.
enhance the inhibition of neurones in brain regions involved in stress response
so lower gabaa receptor expression = decreased anxiety
is GABAAergic CNS depression selective? what does this mean?
non selective CNS depression
wide therapeutic range but many side effects
why is GABAAergic CNS depression non-selective?
humans - 2 alpha, 2 beta 1 gamma subunit
alpha 1 - sedation , alpha 3- anxiolysis , alpha 5 - learning and memory
benzodiazepine and alcohol will act on most GABAA receptors in brain regardless of subunit
why are chronic side effects like tolerance and withdrawl cause by GABAA receptors with drug use
the receptors adapt with chronic use
symptoms go down because GABAA is enhanced by alloesteric modulation but over time decreases expression of GABAA which causees tolerance and dependance issues - need more for same effect
what are examples of anxiolytics and what do they act on?
act on serotonin
SSRIS e.g fluoxetine - well tolerated, used for comorbidity with depression
SNRI’s - venlafaxine - anxiety
tricyclic antidepressants - for panic disorder
Busiprone - 5Ht receptor agonist - diff to others as inhibits 5HT release via activating inhibitory 5HT receptor
how do anxiolytics act?
inhibit 5HT transport by blocking 5HT1a receptor to prevent uptake into pre synaptic cleft terminal - this keeps more 5HT in cleft to activate post synaptic neurones
5-HT 1a receptor specifically
acute use increases this
why does chronic antidepressant use actually not relieve anxiety?
5-Ht2c receptors involved in anxiogenesis (causing anxiety - neurotransmission in amygdala) - knocking this out thought to decrease anxiety but receptor agonist of this will increase anxiety behvaiour
so what is 5-HT2c serotonin neurotransmission like?
anxiogenic
causes initial increase in anxiety
