Anxiety Flashcards
What differentiates anxiety disorders from each other
most have similar physiological symptoms and behavioural manifestations, but the cognitive component of the disorder (i.e., focus of the apprehension for that disorder) differs
What is an important way of diving anxiety for psychopharmacological perposes and why?
- the immediate physiological response -> fear and panic
- more future oriented things like worry and rumination
Important because the underlying neural circuitry is different -> implications for treatment
What part of neurobiology is important for understanding the more immediate anxiety/fear symptoms?
The amygdala: because it is the fear conditioning and emotion processing centre in the brain
What part of neurobiology is important for understanding the more future oriented worry symptoms?
Cortico-striato-thalamo-cortical ‘loops’
Describe how the amygdala is related to fear?
The amygdala integrates sensory and cognitive information (e.g. fear memories) to determine if we should have a fear response resulting in:
- feelings of fear
- motor response
True or false: When we do fear extinction we are eliminating a pathway in the brain?
False we are creating a new pathway/new learning
The emotional component of fear is related to which circuit (acronyms only said not important to remember names of areas)
amygdala to ACC and OFC
The Avoidance type behaviours of fear are related to which circuit (acronyms only said not important to remember names of areas)
Amygdala and PAG
Fear is related to overactivation of circuits related to which 4 circuits
- Affect
- Avoidance
- Endocrine output
- Autonomic output
The autonomic output of fear is related to
amygdala and LC
The Endocrine output of fear is related to?
amygdala and hypothalamus
Which neurotransmitters are involved in the fear circuits?
- Serotonin (5HT)
- GABA
- glutamate
- Norepinepherine
- Cortocotropin releasing
Worry is related to overactivation of which ciruit?
overactivation in cortico- striato-thalamo-cortical (CSTC) feedback loops originating in the prefrontal cortex
Which neurotransmitters are involved in the worry circuits?
- Serotonin (5HT)
- GABA
- glutamate
- Norepinepherine
- Dopamine
What is the main advantage of bezodiazepines over barbiturates?
What is the problem?
Overdose is rarely fatal unless combined with alcohol or opioids
benzos often combined with drugs and alcohol and are involved in many overdose deaths
What is the difference between the action that barbiturates versus benzodiazepines have on GABA receptors?
benzos increase the frequency of ion channel opening
barbiturates increase the duration of the ion channel opening
What is the consequence of not being able to target only the relevant brain ciruits to increase GABA efficiency in?
We end up reducing it more broadly in the brain which results in side effects:
sedation, increased seizure threshold, cognitive impairment, amnesia, and muscle relaxation
GABA is?
The most common inhibitory neurotransmitter
What vitamin is required to produce GABA
vitamin B6
Which aspects of anxiety does increasing the efficiency of GABA affect?
Both fear and worry components
- it is involved in both circuits
What is GABA made from?
glutamate
what does GABA do
it increases the flow of chloride ions into the post synaptic neuron -> reducing likelihood that the post synaptic neuron will fire (hyperpolarize)
How is GABA’s action terminated
by being taken up by glial cells and converted into to succinate in the mitochondria
What are the subtypes of GABA receptors/what kind are they?
GABAa = ionotropic (ligand gated ion channels) for chloride ions
GABAb = metabotropic receptors
What is the main clinical action of benzodiazepines?
GABA positive allosteric modulator (according to cary)
GABA receptor agonist (book) but also specified that
- BUT Not a direct agonist though because it doesn’t stimulate the same site where GABA would bind
it binds to another site that affects how many choride ions can pass through
Which then increases the inhibitory synaptic action of GABA
What is a GABAa receptor composed of? why are they important?
5 subunits
important because there are many subtypes of receptors depending on the composition of subunits that it is made of
and in theory it is possible to make drugs that would target just one subtype of receptors and potentially have less side effects
How many transmembrane regions do GABAa receptors have?
4
What is an issue with benzos?
that people can develop a physiological tollerance and can create dependency and have a signficant rebound effect when they go off
What is the antidote to bezodiazepines and how does it work?
Flumazenil
- competitive antagonist at the BZ binding site
What are Alpha-2-delta ligands used for?
what is their mechanism of action?
Treating anxiety and insomnia
- show some efficacy in treating SAD and PD
- second line for people who can’t tolerate SSRIs/Benzos because they don’t have a direct effect on 5-HT or GABA
Reduce glutamate release through Binding to presynaptic voltage-sensitive calcium
channels
-reduces the threshold for these calcium channels to open which inhibits neurotrasmitter release
Name 2 Alpha-2-delta ligands
Gabapentin and pregablin
What is the difference between long and short acting benzodiazepines?
Short acting are metabolized into inactive products and extreted whereas long acting are metabolized into an active metabolite first with a long half life (approx 60 hours)
Why should the use of benzodiazepines generally be avoided in the elderly?
Because they have a reduced capacity to metabolize them and their active metabolites which results in a very long half life (7-10 days) and they can result in cognitive dysfunction
What are the main advantages of benzodiazepines?
The major clinical advantages of benzodiazepines are high efficacy, rapid onset of action, and low toxicity.
Are bezos safe during pregancy?
relatively
- no association with malformations when taken in first trimester only
- when taken for whole pregnancy slightly elevated risk
- it does freely cross the placenta and into breastmilk and can result in dependence in the infant
Where are 5HT1a receptors found
pre synaptic (autoreceptors) and post synaptic
buspirone (Buspar) is less effective in?
people who have previously taken bezos
How is Norepinepherine related to anxiety?
NE regulates activity in the amygdala and the prefrontal cortex and thalamus in CSTC circuits
Too much NE from locus coeruleus results in autonomic NS overactivation
what disorder should not be treated with benzos?
PTSD -> can make it worse because of disinhibition
What is first line drug therapy for GAD
First-line drug therapy includes the use of SSRI/SNRI
and non-sedating TCAs
