Anxiety and Anxiolytics

Question 1

What is anxiety

Answer 1

1. Anxiety is a normal, physiological response to threatening situations that serves a protective function
2. Anxiety is pathological when there is a bias to interpret non-threatening situations as threatening
3. The concern about the stressor is out of proportion to the realistic threat and can occur without exposure to an external stressor = pathological anxiety

Question 2

What are the different types of anxiety disorders

Answer 2

1. Simple/Specific phobias
2. Social phobia/ Social anxiety disorder (SAD)
   3 Panic disorder (PD)
3. Posttraumatic stress disorder (PTSD)
4. Generalized anxiety disorder (GAD)
5. Obsessive compulsive disorder (OCD)
6. (Premenstrual dysphoric disorder (PMDD))

Question 3

What are the common core elements of anxiety disorders

Answer 3

1. Negative cognition
2. Physiology
3. Avoidance

Question 4

What is the negative cognition

Answer 4

1. Bias to interpret unthreatening situations as threatening

2. Context/memory/ reinforcement

Question 5

What are the Physiological symptoms: autonomic activation

Answer 5

1. Racing heart
2. Palpitations
3. Restlessness
4. Sweating
5. increased blood pressure

Question 6

What are the Defence/ Avoidance behaviours caused by

Answer 6

1. Activation of aminergic pathways

Question 7

What parts of the brain are involved in anxiety disorders

Answer 7

1. Cortex – negative cognition
2. Hippocampus – memory
3. Amygdala – fear perception
4. Hypothalamus – stress responsiveness
5. Basal ganglia/cerebellum – movement control

Question 8

How is the hypothalamus involved in the stress response

Answer 8

1. The Hypothalamic–pituitary–adrenal axis maintains stress responsiveness through release of ACTH from pituitary which acts on adrenal gland to release cortisol and adrenaline
2. Hypothalamus responds to sensory amygdala and hippocampal inputs to adjust the balance of sympathetic/ parasympathetic output

Question 9

What is normal response to threat

Answer 9

1. threatening stimulus
2. stress/fear response, innate or learned
3. defence/ avoidance behaviours
4. autonomic activation ‘fight or flight’
   - noradrenaline- arousal/alertness increased vigilance
5. HPA
   - corticosteroid secretion – metabolic effects
6. negative emotions- (aggression anger)

Question 10

What is the Conscious learned behavior in response to threat controlled by

Answer 10

1. Thalamus (Sensory relay station)
   - Recognition and concept
2. Prefrontal Cortex (integrates emotions with decision making)
   - Is fear response required
3. Hippocampus (Context, Memory)

Question 11

What is the Innate fear response in response to threat controlled by

Answer 11

1. Amygdala (“fear centre”)
   - Amine NTs => Alertness, attention, vigilance
   - Periaquaductal grey
   - Defence/Avoidance behaviour
2. Hypothalamus
   - HPA activation: cortisol/adrenaline
   - Autonomic activation:
   - ‘fight or flight’

Question 12

Why are amine systems important?

Answer 12

1. 5-HT (serotonin) pathways
   - Mood and well being may be depressed
2. Noradrenaline pathways
   - Alertness and attention are increased

Question 13

Describe the Aetiology of anxiety disorders

Answer 13

1. Largely unknown
2. Abnormal regulation of brain areas involved in stress/fear
3. Underactivity of 5HT system?
4. Overactivity of NA system?
5. Disruption in level of GABA inhibition?
   - reduced expression of GABAA-receptors
   - reduced function/regulation of GABAA-receptors by benzodiazepines
   - reduced function/regulation of GABAA-receptors by neurosteroids
6. Genetic and environmental factors play a role

Question 14

What are some pharmacotherapy treatments for anxiety disorders

Answer 14

1. b-blockers – target autonomic symptoms
2. Benzodiazepines*
3. Antidepressants (SSRIs)
4. Buspirone (partial agonist at 5-HT1A receptors)
5. Specific NICE guidance for different anxiety disorders

Question 15

What are the different evidence-based psychological interventions

Answer 15

1. Low intensity interventions e.g. self-help approaches
2. High intensity interventions e.g. CBT for social anxiety disorder
3. Stepped-care approach (NICE guidance)

Question 16

Describe β-adrenoreceptor blockers

Answer 16

1. Treat the symptoms of anxiety
2. Reduce the sympathetic manifestations of stress/fear response
3. No effect on affective components
4. Useful in treating phobias
5. Evidence for use in curing phobias
6. Effects on memory consolidation – evidence for use in eliminating PTSD

Question 17

What are some Anxiolytic drugs that target 5-HT systems

Answer 17

1. Buspirone- Partial agonist at 5-HT1A receptors
   - More difficult to use than benzodiazepine
2. Antidepressants
   - SSRIs - selective serotonin reuptake inhibitors (fluoxetine, citalopram)
   - Combined noradrenaline and 5HT uptake blockers (venflaxine, duloxetine)
3. Mood elevators
4. Preferred choice for GAD, panic disorders and PTSD- SSRIs
5. Delayed clinical response (3-4 weeks)

Question 18

Describe GABA A receptors

Answer 18

1. Functional GABAA receptors are pentameric combinations of different subunits arranged to form the integral chloride ion channel
2. Most prevalent receptor in mammalian brain consists of two α, two β and one γ-subunit
3. GABA binds between α and β-subunits – so 2 molecules to activate receptor

Question 19

How do benzodiazepines work

Answer 19

1. Benzodiazepines bind to an allosteric site on the GABAA receptor
2. Benzodiazepines bind at the interface between α/γ-subunits and affect chloride ion conductance to regulate GABAergic inhibition

Question 20

Describe the structure of benzodiazepines

Answer 20

1. The core of all BZ ligands is a benzene ring joined to a 7-membered 1,4-diazepine ring
2. R side groups influence the properties:
3. AFFINITY of the BZ to bind the receptor – ability to bind
4. INTRINSIC EFFICACY of BZ to produce a functional effect
5. BZ AGONISTS have 100% intrinsic efficacy
6. BZ INVERSE AGONISTS bind to the site but produce the opposite effect and are said to have negative intrinsic efficacy.
7. BZ ANTAGONISTS bind to the BZ site but are unable to activate the receptor (intrinsic efficacy = 0)
8. other properties such as lipophilicity, water solubility etc.

Question 21

What are side effects of benzodiazepines

Answer 21

1. Memory loss- Useful pre-meds for anaesthesia
2. Sedation - Useful pre-meds for anaesthesia
3. Abuse potential - Flunitrazepam (Rohypnol) is a BZ agonist, Temazepam use in opioid addicts
4. Addictive - Some people develop tolerance/physical dependence with long-term BZ use
5. Withdrawal syndrome - Characterized by irritability, cognitive impairment, insomnia, dysphoria, hypersensitive to light/sound

Question 22

What is the spectrum of clinical uses of benzodiazipine

Answer 22

1. Anxiolytic- calm- Diazepam, lorazepam
2. Sedative- drowsy
3. Hypnotic- asleep

Question 23

What effect does alcohol have on the CNS

Answer 23

1. Alcohol is a CNS depressant
2. Apparent stimulatory effects result from depression of inhibitory control mechanisms in the brain
3. Characteristic dose dependent response: euphoria, impaired thought processes, decreased mechanical efficiency