Psychopharmacology of Anxiolytics

Question 1

Enumerate structures modulating fear

Answer 1

1. Amygdala
2. Anterior cingulate cortex
3. Orbitofrontal cortex

Question 2

Avoidance, a primarily motor response, is regulated by which structures?

Answer 2

Reciprocal connections between the amygdala and periaqueductal gray (PAG)

Question 3

Which hormone is secreted in the fear response?

Answer 3

Cortisol

Question 4

What are the physiologic responses to fear?

Answer 4

1. Changes in respiration (regulated by parabrachial nucleus)
2. Increases in HR and BP (regulated by connections between amygdala and locus ceruleus)

Question 5

What is re-experiencing?

Answer 5

Traumatic memory stored in the hippocampus triggering the amygdala to initiate a fear response

Question 6

Neurotransmitters involved in symptoms of anxiety and fear associated with malfunctioning of amygdala-centred circuits

Answer 6

1. Serotonin (5HT)
2. GABA
3. Corticotropin releasing factor
4. norepinephrine

Question 7

Structure associated with symptoms of worry

Answer 7

Cortico-striato-thalamic-cortical (CSTC) loop

Question 8

Drug treatments for Anxiety

Answer 8

1. GABAergic anxiolytics/Benzodiazepines
2. Serotonergic anxiolytics
3. Noradrenergic anxiolytics

Question 9

Most widely used anxiolytics

Answer 9

Benzodiazepines

Question 10

Principal inhibitory neurotransmitter

Answer 10

GABA

Question 11

Benzodiazepine mode of action

Answer 11

Enhancement of GABA action at amygdala and prefrontal cortex within CSTC loops

Question 12

Types of GABA receptors

Answer 12

1. GABAa: gatekeepers of chloride channel, allosterically modulated
2. GABAb: Not allosterically modulated, binds exclusively to Baclofen

Question 13

Benzodiazepine receptors

Answer 13

1. Omega 1 (cerebellum: anxiolytic, sedative-hypnotic.)
2. Omega 2: (spinal cord and striatum: muscle relaxant)
3. Omega 3: peripheral

Question 14

Actions of benzodiazepines

Answer 14

1. Anxiolytic
2. Anticonvulsant
3. Muscle relaxation
4. Hypnosis and stupour in high doses

NOT

1. Analgesia
2. Anaesthesia

Question 15

Clinical uses of benzodiazepines

Answer 15

1. Anxiety disorders
2. Muscle relaxation
3. Anticonvulsant
4. Alcohol withdrawal

Question 16

Adverse effects of benzodiazepines

Answer 16

1. Drowsiness
2. Confusio
3. Ataxia
4. Amnesia

Question 17

Benzodiazepines not metabolised in the liver, thus safe to give in liver disease

Answer 17

1. Oxazepam
2. Temazepam
3. Lorazepam

Question 18

Benzodiazepine antagonist given for poisoning, reverses the effect of benzodiazepines

Answer 18

Flumazenil

Question 19

Neurotransmitter innervating the amygdala and CSTC, which regulates fear and worry

Answer 19

Serotonin

Question 20

Serotonergic anxiolytics

Answer 20

1. Buspirone
2. Gepirone
3. Tandospirone

Question 21

Identify:
Serotonin 1A partial agonist, a generalised anxiolytic used as an augmenting agent to antidepressants which does not interact with alcohol, benzodiazepines, or sedatives; has no dependence or withdrawal symptoms even with long term use

Answer 21

Buspirone

Question 22

Clinical uses for Buspirone

Answer 22

1. Chronic and persistent anxiety
2. Comorbid substance abuse
3. Elderly

Question 23

Neurotransmitter with important regulatory output to the amygdala, prefrontal cortex, and thalamus in CSTC circuits

Answer 23

Norepinephrine

Question 24

Noradrenergic anxiolytic that is an alpha 2 agonist (stimulates alpha-2 receptors) effective at decreasing tachycardia, dilated pupils, sweating, and tremors, but not at blocking subjective and emotional aspects of anxiety

Answer 24

Clonidine

Question 25

Anxiolytics useful in cases of social phobia

Answer 25

Beta blockers

Question 26

Novel approaches to treatment of anxiety disorders

Answer 26

1. Fear extinction | 2. Reconsolidation

Question 27

Benzodiazepine advantages

Answer 27

1. Rapid-onset 2. Effective 3. Well-tolerated 4. General anti-anxiety effects 5. Safe in overdose

Question 28

Benzodiazepine disadvantages

Answer 28

1. Withdrawal reaction 2. Sedation 3. Multiple daily dosing may be required 4. Abuse potential 5. Poor antidepressant

Question 29

SSRI advantages

Answer 29

1. Effective 2. Benign side effects 3. No dependence issue 4. Once a day dosing

Question 30

Tricyclic antidepressant (TCA) advantages

Answer 30

1. Single daily dose 2. Antidepressant effect 3. No abuse potential 4. Well-studied 5. Effective 6. Generics available

Question 31

TCA disadvantages

Answer 31

1. Delayed-onset 2. Anticholinergic side effects 3. Postural hypotension 4. Weight gain 5. Dangerous in overdose

Question 32

Pharmacotherapeutic agents for insomnia

Answer 32

1. Nonbenzodiazepine short-acting hypnotics (e.g. Zateplon, Zolpidem, Zopiclone) 2. Benzodiazepines (decrease sleep latency, diminish wakenings, increase duration of sleep) 3. Melatonergic hypnotics 4. Sedative-hypnotic antidepressants 5. Sedating antihistamines 6. OTC agents 7. Older sedative hypnotics e.g. Chloral hydrate