Anxiety Flashcards
When is anxiety pathological?
When there is a bias to interpret non-threatening situations as life threatening.
Concern about stressor is out of proportion to the realistic threat and can occur without exposure to an external stressor
Core elements of anxiety disorders
Negative cognition
Physiological symptoms - autonomic activation
Defence/Avoidance behaviours
Negative cognition
Bias to interpret unthreatening situations are threatening
Context/memory/reinforcement
Physiological symptoms of anxiety
Racing heart/palpitations
Restlessness
Sweating
Increased blood pressure
etc
Pathways in Defence/Avoidance behaviours
Activation of aminergic pathways
Neuroanatomy involved in anxiety
Cortex
Hippocampus
Amygdala
Hypothalamus
Basal ganglia/cerebellum
Cortex and anxiety
Negative cognition
Hippocampus and anxiety
Memory and context
Uses input from prefrontal cortex
Amygdala and anxiety
Fear perception
Thalamus relays sensory information to prefrontal cortex and amygdala
Hypothalamus and anxiety
Stress responsiveness
Maintained through release of ACTH and cortisol
Responds to sensory amygdala and hippocampal outputs to adjust output
Basal ganglia/cerebellum and anxiety
Movement control
5HT pathways in anxiety
Hypothalamus –> Temporal lobe –> Raphe nuclei
Neocortex –> Basal ganglia –> thalamus –> cerebellum
If these are affected, mood and wellbeing may be depressed
Noradrenaline pathways in anxiety
Hypothalamus –> temporal lobe –> locus coeruleus
Neocortex –> thalamus –> cerebellum
These can increase alertness and attention - hypervigilance
GABA and anxiety
Reduced expression of GABAA-receptors
Reduced function/regulation of GABAA-receptors by benzodiazepines
Reduced function/regulation of GABAA-receptors by neurosteroids
Pharmacotherapy for anxiety
b-blockers: target autonomic symptoms
Benzodiazepines
Antidepressants: SSRIs
Buspirone: partial agonist at 5HT 1A receptors
β-adrenoreceptor blockers
Treat the symptoms of anxiety
Reduce the sympathetic manifestations of the stress/fear responses
Treatment, not cure
Effects on memory consolidation
Antidepressants for anxiety
SSRIs - fluoxetine, citalopram
Combined NA and 5HT uptake blockers - venflaxanine, duloxetine
SSRIs now preferred choice for GAD, panic disorders and PTSD
SSRIs have a delayed clinical response (3-4 weeks)
Main treatment for anxiety
Benzodiazepines
Structure of benzodiazepines
Benzene ring fused to a seven membered diazepine ring.
Method of Action of Benzodiazepines
Binds with specific modulatory site on GABA A receptor
Enhances GABA activity
Opening of Cl- channels
Hyperpolarisation of cells
Depression of CNS
R side groups influence the _ of benzodiazepines
Affinity of the BZ to bind the GABA receptor
Intrinsic efficacy of BZ to produce a functional effect
BZ inverse agonists
Bind to the BZ site but produce the opposite effect.
Said to have negative intrinsic efficacy
BZ antagonists
Bind to the BZ site but are unable to activate the receptor
Intrinsic efficacy = 0
Intrinsic efficacy of BZ agonists
100%
Benzodiazepine is a CNS _
Depressant
Effects of Benzodiazepines on the CNS
Anxiolytic
Sedation and induction of sleep
Muscle relaxation
Anticonvulsant
Anterograde amnesia
Decrease dose of anaesthetic
Effect of Benzodiazepines on PNS
Neuromuscular blockade (paralysis) in high doses
Coronary vasodilation at lower doses
Adverse effects of normal dose of benzodiazepines
Dry mouth, Light headache, Confusion, Ataxia, Impair driving skill
Adverse effects of acute overdose of benzodiazepine
Prolonged sleep
Other adverse effects of benzodiazepines
Tolerance and dependency
Decrease libido
Abuse potential
Benzodiazepines as hypnotics
Can be used, but there are problems with tolerance and dependence
Rebound insomnia also a concern
