Anxiety

Question 1

what are anxiolytics?

Answer 1

drugs used to allay (alleviate) anxiety

Question 2

what are anxiogenics?

Answer 2

drugs that induce anxiety for use in labs

Question 3

what are allosteric modulators?

Answer 3

enhance effects of agonist

Question 4

what is ‘eustress’?

Answer 4

acute stress
physiological stress = bodies response to external pressure

Question 5

define anxiety

Answer 5

psychological response to a perceived threat, very closely linked to fear (which is the psychological response to REAL threat)

Question 6

what is the fight or flight response?

Answer 6

normal stress response to acute pressure (completely normal as should subside after stimulus has gone)

Question 7

what is distress?

Answer 7

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

Question 8

what are the symptoms of distress?

Answer 8

generalised muscle ache/ headache, memory impairment
insomnia
depression
anxiety increase

Question 9

when is anxiety classified as anxiety disorder?

Answer 9

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

Question 10

what is the lifetime prevalence of anxiety (Wittchen and Jacobi 2005)

Answer 10

21% life time prevalence
2:1 ration female :male
often comorbid

Question 11

outline generalised anxiety disorder

Answer 11

excessive and persistent anxiety/worry > 6 months
fear of future events, personal safety
often present with SOMATIC complaints like heachache or stomach ache

Question 12

outline obsessive compulsive disorder

Answer 12

obsessive repetitive thoughts which are often negative counteracted by compulsive behaviours (rituals) providing temporary relief e.g redoing and checking

Question 13

outline panic disorder with/without agoraphobia

Answer 13

sudden unexpected panic attacks - intense recurrent fear of dying/illness
palpitations, tremor, dizziness
fear of certain place can result in phobic avoidance = agoraphobia

Question 14

outline phobic disorders

Answer 14

excessive fear disproportionate to specific situation
generally predictable = phobic avoidance
social phobia = excessive fear of social situations, fear of being negatively scrutinised/humiliated

Question 15

outline post traumatic stress disorder

Answer 15

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

Question 16

what is the biological basis of anxiety disorders?

Answer 16

CNS, HPA axis and autonomic nervous system all connected and feedback to each other to coordinate response

Question 17

how do we know this is what happens

Answer 17

knowledge form classical lesion studies in combination with behaviour and more recently imaging brain areas which are activated by fear

Question 18

what brain area is mainly involved in the stress response?

Answer 18

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)

Question 19

what is an example of why we know the amygdala is involved in the stress response

Answer 19

a study of people with PTSD - when they were shown a feared image fMRI showed higher amygdala activity.
and elevated levels of CRF.

Question 20

are the levels of noradrenaline in people with anxiety disorders always elevated?

Answer 20

no, only when they are stimulated or exposed to fear.

Question 21

how would you summarise what is affected to cause anxiety disorder biologically?

Answer 21

noradrenergic neurotransmission
- an increase of noradrenaline when in situation of perceived threat

Question 22

outline GABAergic dysfunction in anxiety disorders

Answer 22

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

Question 23

why does GABAergic dysfunction arise in anxiety disorder?

Answer 23

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?

Question 24

outline serotonergic dysfunction in anxiety disorders

Answer 24

people with anxiety have dysfunctional 5HT receptors - lower expression of them

Question 25

what is the source of serotonin in the brain

Answer 25

raphe nucleus

Question 26

why do people with anxiety have dysfunctional 5Ht receptors?

Answer 26

chronic stress/glucocorticoid in animals causes decrease in serotonin receptor
in contrast: remove adrenals (stress hormone site) = increase in serotonin receptor expression

Question 27

so what does long stress mean for serotonergic receptors in the brain?

Answer 27

the receptors change and 5Ht receptors are inhibitory which means an increase in excitatory neurotransmission in the brain

Question 28

what are common side effects of anxiolytics with chronic use?

Answer 28

tolerance and dependance

Question 29

are anxiolytics still prescribed

Answer 29

they shouldnt be as are grouped with sedatives and hypnotics but they are still important

Question 30

what does the therapeutic effect of anxiolytics depends on?

Answer 30

the dose given - lower doses cause anxiolysis but higher doses cause sedation and even hypnosis so not good

Question 31

outline alcohol as an anxiolytic

Answer 31

self medication
non specific CNS depressant
rapid effect = high solubility and blood alcohol concentration

Question 32

outline barbiturates as anxiolytics

Answer 32

popular in 60s
effective but small therapeutic window
easy to overdose
effects were potentiated by alcohol
should not be used for anxiety

Question 33

outline benzodiazepines

Answer 33

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

Question 34

outline the therapeutic use of benzodiazepines

Answer 34

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

Question 35

what are some acute side effects of benzodiazepines?

Answer 35

unwanted sedation/drowsiness
amnesia
reduced cognition
reduce motor coordination
potentiated by alcohol
decrease in REM sleep

Question 36

what are some chronic side effects of benzodiazepines

Answer 36

tolerance
dependance
withdrawl symptoms

Question 37

what are the pharmacokinetics of benzodiazepines? - examples

Answer 37

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

Question 38

why does valium have such a long half life?

Answer 38

metabolised into active metabolites so prolongs effect

Question 39

what receptors do anxiolytics act on?

Answer 39

GABAA
they are allosteric modulators of the receptor

Question 40

outline a GABAA receptor

Answer 40

pentameric ion channel which increases Cl- permeability and hyperpolarises to inhibit neurone

Question 40

why does anxiolytics acting on GABAA receptors alleviate anxiety?

Answer 40

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

Question 41

is GABAAergic CNS depression selective? what does this mean?

Answer 41

non selective CNS depression
wide therapeutic range but many side effects

Question 42

why is GABAAergic CNS depression non-selective?

Answer 42

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

Question 43

why are chronic side effects like tolerance and withdrawl cause by GABAA receptors with drug use

Answer 43

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

Question 44

what are examples of anxiolytics and what do they act on?

Answer 44

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

Question 45

how do anxiolytics act?

Answer 45

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

Question 46

why does chronic antidepressant use actually not relieve anxiety?

Answer 46

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

Question 47

so what is 5-HT2c serotonin neurotransmission like?

Answer 47

anxiogenic
causes initial increase in anxiety