Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Neuropharmacology > Anxiety Disorders And Their Treatment(+FXS) > Flashcards

Anxiety Disorders And Their Treatment(+FXS) Flashcards

0
Q

What is FXS?

A

It’s a mental condition which is hereditary and arises on chromosome x

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
1
Q

What are prominent characteristics of FXS?

A

Elongated face
Large or protruding ears
Low muscle tone- particularly in the face

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What causes FXS?

A

Expansion of the CGG trinucleotide repeat affecting the fragile x mental retardation 1 gene -FMR1
Prevents the expression of the fragile x mental retardation protein FMRP- this is needed for normal development

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Which sex is more affected with FXS ?

A

Males

The mutation occurs on the X chromosome and the males only have one X chromosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the “full mutation” for FXS?

A

> 200 CGG
This mutation occurs in the promoter region of the FMR1 gene and causes a methylated promoter region - this shuts down the gene so little or no mRNA is produced so no protein available

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the mGluR theory ?

A

Used to explain many aspects of the clinical symptoms present in patients with FXS and in FMR1 KO mouse

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the clinical symptoms found in FXS patients and FmR1 KO mice ?

A
  • higher density of spines and more immature spines compared to normal
  • electrophysiological deficits in FmR1 mice
  • exaggerated dendritic protein in FmR1 KO nice after activation of mGluR5
  • behavioural phenotype in patients with FXS and FmR1 KO mice
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What does the mGluR theory state ?

A

That AMPA receptor internalisation triggered by group 1 mGluR stimulation is exaggerated in FXS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are AMPA receptors do ?

A

Essential for long term synaptic plasticity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What does FMRP do ?

A

It negatively regulates transcription and reduces internalisation of AMPA receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what is characteristic of neurones from patients with FXS?

A

they have increased internalisation of AMPA receptors in the absence of FMRP - this reduces long term synaptic plasticity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what happens when mGluR5 is activated ?

A

they signal through protein kinase c

leads to activation of SRC family tyrosine kinases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what happens when group 1 mGluRs are activated ?

A

causes the up regulation of protein synthesis and this has been implicated in playing a role in FRMP dependent synaptic plasticity

it is thought that using these receptors as a target, could be a treatment for FXS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what are therapeutic substances for FXS?

A

negative modulators of mGluR5

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what is MPEP and what does it do ?

A

1st negative modulator of mGluR5 - classed as an mGluR5 antagonist
interacts with transmembrane domain 7

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

why is MPEP not used in clinical trials?

A

causes toxicity and had a short half life

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what beneficial effects did MPEP have ?

A

suppressed audiogenic seizures and rescued deficits in prepulse inhibition of acoustic startle in FRM1 KO mice

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what is anxiety ?

A

normal biological process

- apprehension, tension and fearfulness

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what is the difference between normal anxiety and chronic anxiety ?

A

chronic anxiety is debilitating

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

how common are anxiety disorders and what are some different types ?

A 
18% of population in USA have anxiety disorders
general anxiety disorder 
social anxiety disorder 
obsessive compulsive disorder 
panic disorder
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what are the types of symptoms of anxiety disorders ?

A

psychological and somatic (physical)

21
Q

what do the symptoms of anxiety disorders depend on ?

A

depends on the particular anxiety disorder

depends on the individual

22
Q

what are the causes of anxiety disorders ?

A

most often the causes are unknown

PTSD is often a cause though

23
Q

what are some examples of somatic symptoms of anxiety disorders ?

A

tachycardia
sweating
trembling

24
Q

what are some examples of psychological symptoms of anxiety disorders ?

A

worry
panic
exaggerated fear

25
Q

how are anxiety disorders diagnosed?

A

diagnostic and statistical manual of mental disorders, 4th edition

26
Q

what is the pathophysiology underlying anxiety disorders ?

A

unknown however stress is thought to be involved and the levels of catecholamines

27
Q

how does stress contribute to anxiety disorders ?

A

causes a heightened physiological response - normally emotional stress

  • increases catecholamine levels
  • thought that the hypothalamic-pituitary-adrenal axis is implicated because its involved in the release of catecholamines
28
Q

which neurotransmitters are influence the HPA axis and/or involved in the pharmacological treatment of anxiety disorders ?

A

serotonin
GABA
noradrenaline

29
Q

what regions of the brain have been hypothesized to have implications in anxiety disorders ?

A

disturbances in the cerebral cortex - especially the limbic system including the amygdala

30
Q

what are the types of anxiolytics ?

A

benzodiazepines- GABAergic
Beta blockers- noradrenergic
SSRIs/buspirone- Serotonin
SNRIs- serotonin and noradrenaline

31
Q

what do benzodiazepines do ?

A

bind to GABAa receptors
they have a specific binding site on these receptors
it enhances the influx of chloride ions when GABA binds

32
Q

what do GABAa receptors look like ?

A

mutlisubunit receptors - 19 different types

pentameric - combination of alpha beta and gamma subunits- combinations are different in different brain regions

33
Q

where does benzodiazepine bind on GABAa receptors ?

A

binds at the interface between alpha and gamma subunits

34
Q

what happens to the electrophysiological recordings in GABA receptors when a mutation is induced ?

A

the mutation caused the receptor to become insensitive to diazepam
the alpha-2,3,and 5 receptors were rendered insensitive to diazepam when histidine is replaced by arginine at 101

35
Q

what are the actions of benzodiazepines ?

A 
sedative 
hypnotic 
anxiolytic 
anticonvulsant 
muscle relaxant 
amnesic
36
Q

what are some other examples of benzodiazepines ?

A

alprazolam
chlordiazepoxide
lorazepam
oxazepam

37
Q

why are lorazepam and oxazepam useful ?

A

they have a shorter action

good for patients with hepatic impairment

38
Q

what are the pharmacokinetics of benzodiazepines ?

A

normally taken orally
rapidly absorbed
peak concentration after one hour
highly protein bound and highly lipid soluble so sequestered into body fat

39
Q

how are benzodiazepines metabolised?

A

mainly by N-desmethylation - can lead to an active metabolite- desmethyldiazepam - 70 hour half life
phase 2 by glucuronide- the shorting acting ones goes straight to this phase

40
Q

what happens if you overdose on benzodiazepines?

A

generally safe

not lethal- prolonged sleep

41
Q

when can benzodiazepine administration be dangerous ?

A

if they are taken with other CNS depressants

if they are taken with ethanol- respiratory depression

42
Q

what is used to treat a benzodiazepine overdose?

A

flumazenil

- benzodiazepine site antagonist

43
Q

what are the unwanted effects of benzodiazepines ?

A

drowsiness
confusion
amnesia
poor coordination

44
Q

do people suffer from tolerance when taking benzodiazepines?

A

tolerance to anxiolytic effects have been seen in animals but not humans
- more pronounced tolerance to anticonvulsant and sedative effects

45
Q

why are benzodiazepines not used for chronic administration ?

A

dependence
there are marked withdrawal symptoms - anxiety, tremor and dizziness
it is difficult to wean patients off them if they have been used for a long time
withdrawal has to be slow and tapering

46
Q

how do beta blockers work and what do they do ?

A

antagonist of beta-1 and 2 adrenoreceptors
act on autonomic system
they are used to treat the somatic symptoms
they have no effect on psychological effects however the reduction in the somatic symptoms may reduce worry and fear

47
Q

what is buspirone ?

A

serotonin 1a agonist

48
Q

how does buspirone work ?

A

it is a partial agonist
stimulates serotonin 1a receptors at low serotonin levels
inhibits serotonin 1a receptors at high serotonin levels
also binds to D2 and 5HT 2a receptors
they are presumed to alter serotonergic transmission

49
Q

what anxiety disorders can busprione be used to treat and which can it not treat ?

A

used to treat generalised anxiety disorder
cant treat panic disorder or OCD

not thought to show tolerance to therapeutic effects but it does show tolerance to adverse effects
only for acute treatment

50
Q

how do SNRIs work ?

A

they have combined selectively for both serotonergic and noradrenergic uptake mechanisms
e,g venlafaxine

51
Q

when are SSRIs and SNRIs used ?

A

for the management of chronic anxiety - 4or more weeks
can sometimes initally worsen the effects
can be taken with benzodiazepines to relieve the initial worsening of symptoms

Neuropharmacology (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions