Anxiety and anxiolytics Flashcards
What is anxiety?
a normal, physiological response to threatening situations that serves as a protective function
What is pathological anxiety?
concern about stressor is out of proportion to the realistic threat and can occur without exposure to an external stressor
How many people in the UK are affected by anxiety disorders?
8 million
Examples of anxiety disorders?
Specific phobias, social anxiety, panic disorder, PTSD, OCD, Generalised anxiety disorder, premenstrual dysphoric disorder
length of generalised anxiety disorder?
6 months
What are the core symptoms of anxiety disorders?
Negative cognition, physiology (heart racing etc), avoidance behaviour
What is negative cognition?
A bias to interpret unthreatening situations as threatening
Physiological symptoms of anxiety disorders?
Racing heart, restlessness, sweating, increased blood pressure
Part of anxiety disorder that the cortex is involved in?
negative cognition
Part of anxiety disorder that hippocampus the is involved in?
Memory
Part of anxiety disorder that the amygdala is involved in?
fear perception
Part of anxiety disorder that the hypothalamus is involved in?
Stress responsiveness
Part of anxiety disorder that the basal ganglia/cerebellum are involved in?
movement control
What hormone is released upon the perception of stress?
Corticotropin releasing hormone
Which part of the brain releases Corticotropin releasing hormone?
Hypothalamus
Where is Corticotropin releasing hormone released onto?
Pituitary gland
Which stress related hormone is released by the pituitary gland?
Adrenocorticotropic hormone (ACTH)
Where is ACTH released onto?
The adrenal gland
What is produced by the adrenal glands in response to ACTH?
Glucocorticoids, particularly cortisol
Why is cortisol released in response to stress?
To give you the energy for the fight or flight response, as it is responsible for metabolism of glucose and lipids
Where is adrenaline released from in response to stress?
Adrenal glands
Which brain area is first used in the fear response and why?
Thalamus as it deals with sensory stuff
Which brain area is used after the thalamus in the fear response?
Amygdala
Role of amygdala in fear response?
Switching on amine NTs (noradrenaline etc)
Role of periaqueductal grey in fear response?
Innate avoidance behaviour (e.g. stepping back)
Which brain area releases cortisol in response to stress?
Hypothalamus
Where are most anxiety disorders thought to originate?
Prefrontal cortex and hippocampus
Why is noradrenaline released in the fear response?
Need to be hyper aware of your surroundings
Which NTs are implicated in the fear response?
Serotonin and noradrenaline
Role of GABAa networks?
Fast inhibition
Treatments of anxiety disorders?
Beta blockers, benzodiasepines, antidepressants, buspirone
How do beta blockers work?
They block beta adrenergic receptors
What symptoms of anxiety do beta blockers target?
Autonomic systems
SSRI stands for?
Selective serotonin reuptake inhibitors
What specific anxiety type could propranolol (beta blocker) treat?
Phobias
How does propranolol treat phobias?
Give patient drug then expose them to thing they’re scared of
What is propranolol thought to work on?
Hippocampus–> where -ve memories of the thing are removed (positive association forms instead of -ve association)
How does buspirone work?
It is a partial agonist at 5-HT1a receptors (turning up inhibition in those neurons)
How do SSRIs work?
Bind to reuptake transporters, thus boosting levels of serotonin in synapse
What is the preferred treatment for generalized anxiety disorder, PD and PTSD?
Combined noradrenaline and 5HT uptake blockers
WHat are some combined noradrenaline and 5HT uptake blockers?
venflaxine, duloxetine
What do benzodiazepines bind to?
GABAa receptors
Role of GABA?
Inhibitory NT
What can the binding of drugs to allosteric site on GABAa receptors do?
Turn up or down gating of CL- ions in the presence of GABA
What is an inverse agonist?
Something that binds and turns down the receptor
What do benzodiazepine agonists do once bound to GABA?
Turn up the effects of endogenous GABA
Where on the GABAa receptor do benzodiazepines bind?
Alpha gamma interface
General structure of benzodiazapines?
Benzene ring joined to a 7 membered 1,4-diazepine ring (R 1 2 3 5 7 8 are side groups)
What do the R side groups change ab benzodizepine?
Affinity, intrinsic efficacy, lipophilicity, water solubility
Affinity meaning?
How likely something is to bind
Intrinsic efficacy meaning?
The effect of smthn once bound
What is the intrinsic efficacy of a BZ agonist?
+ve (100%)
What is the intrinsic efficacy of BZ inverse agonists?
-ve
What intrinsic efficacy to BZ antagonists have?
0
What is the intrinsic efficacy of partial or full agonists?
near 100%
What are full BZ agonists called?
Positive allosteric modulators
What are full BZ agonists used for?
Anxiolytic
What are inverse agonists used for?
Investigating GABA
Effect of inverse agonists on Cl- flow through GABAa?
Less chloride flux through the channel so less inhibition
Effect of alcohol on the CNS?
Depressant
Effect of alcohol on GABA receptors?
Causes increase inhibition