WEEK 8 - ANXIOLYTICS AND SEDATIVES

Question 1

Anxiety Disorders…Large group of mood disorders including: 6 HN

Answer 1

1. Generalised anxiety disorder
   2 * Panic disorder
   3 * Social anxiety
   4 * Obsessive compulsive disorder
   5 * Trauma and stressor related disorders
   (e.g. PTSD)
   6* Phobias (e.g. agoraphobia)

Question 2

Anxiety Disorders = Generally characterised by recurrent fears or thoughts that are distressing and
interfere with daily life = 4

Answer 2

1 -Panic attacks

2 -Physiological stress responses

3 -Avoidance

4. High prevalence and high comorbidity with other mental health disorders (e.g.
   Depression)

Question 3

Neurobiology of Anxiety =

Answer 3

1. Variety of ‘neuroendocrine’, ‘neurotransmitters’ and brain connections that may contribute to anxiety disorders
2. Symptoms of mood disorders are thought to arise from DISRUPTIONS IN THE BALANCE OF ACTIVITY IN EMOTIONAL PROCESSING CENTRES OF THE BRAIN

Question 4

Neurobiology of Anxiety -Key areas of the brain implicated = 5

Answer 4

1. Prefrontal cortex- Executive functions
2. • Anterior cingulate cortex- Emotional processing, learning and error detection

3 * Limbic system- Emotional processing and memory

4 – Amygdala

5 – Hippocampus

Question 5

Neurobiology of Anxiety = 3

HPA

Answer 5

1. Hypothalamic pituitary axis (HPA)-
2. Neuroendrocrine
   negative feedback loop that regulates levels of stress
   hormones and response
3. -Glucocorticoids and mineralocorticoids

Question 6

Neurobiology of Anxiety =

‘Glucocorticoids are important for a range of cellular processes:’ = 3

Answer 6

-Metabolism,

• stress,
• inflammation, etc

Question 7

Neurobiology of Anxiety:

Glucocorticoid receptors are expressed in nearly all cell
types in the body and brain = 4

Answer 7

-High expression in

• frontal cortex,
• amygdala and
• hippocampus

Question 8

Neurobiology of Anxiety -‘Glucocoricoids can modulate neurotransmitter release’

Answer 8

-GABA, dopamine, serotonin and more

Question 9

Neurobiology of Anxiety = Sex and age differences in stress response

Answer 9

-Males vs females

-Development

Question 10

Sedatives-

Answer 10

Drugs that DEPRESS the CNS to REDUCE ACTIVITY AND ALERTNESS

Question 11

Anxiolytics

Answer 11

Drugs that are used to reduce the symptoms of anxiety

Question 12

Sedatives and Anxiolytics =

Several classes of drugs used that include: 5

Answer 12

1. • Hypnotics
2. • Muscle relaxants
3. • Anti-convulsants
4. • Benzodiazepines
5. • Barbituates

Question 13

what is GABA?

Answer 13

1. Major INHIBITORY NEUROTRANSMITTER in the
   CNS
2. Activation of GABA receptors “inhibit”
   NEURONS, OBSERVED AS INHIBITORY POST-SYNAPTIC POTENTIALS ***
3. GABA(A) CHLORIDE INFLUX CAUSES MEMBRANE ‘HYPERPOLARISATION’
4. GABA(B) POTASSIUM EFFLUX causes
   MEMBRANE ‘HYPER-POLARISATION’

Question 14

2 TYPES OF GABA receptors?

Answer 14

1. ionotropic
   GABA (A)
2. metabotropic
   GABA (B)

Question 15

what is BENZODIAZEPINES…4

Answer 15

1. Wide CLINICAL USE
2. ENHANCE GABAA RECEPTOR FUNCTION in
   the CNS
3. Prolongs the DECAY OF INHIBITORY POST-SYNAPTIC POTENTIALS]
4. Can also INCREASE THE AMPLITUDE OF INHIBITORY POST-SYNAPTIC POTENTIALS IN SOME NEURAL NETWORKS

Question 16

Benzodiazepines and GABAA Receptors…RELATIONSHIP = 4

Answer 16

1. Large heterogeneity in GABA(A) subunit composition
2. 7 subunit families (α,β,γ,ε,θ,ρ,δ)
3. Most GABAA receptors composed of α,β,γ subunits
4. Different combinations of subunits regulates receptor ‘kinetics, affinity for
   GABA, etc.’

Question 16

Benzodiazepines and GABAA Receptors = BINDING SITE RELATIONSHIP

WHAT CAN THEY CAUSE =5

Answer 16

1. Benzodiazepines have a BINDING SITE
   on GABAA receptors
2. Depending on the subunit
   composition, benzodiazepines can
   cause:
   - 3. * Sedation
   - 4. * Amnesia
   - 5. * Anxiolysis
   - 6. * Muscle relaxation
   - 7. * Protection against seizures

Question 17

Benzodiazepines and Anxiety = 4

Answer 17

1. Tolerance and dose dependence occurs with all benzodiazepines
2. Unclear how tolerance develops, but it may be due to a loss in GABAA receptors and/or subunit composition
3. If use is stopped abruptly, patients can experience heightened anxiety and several side effects (headaches, tremors, sleep imbalance, etc)
4. A gradual decrease in benzodiazepine treatment is recommended to avoid withdrawal and side effects

Question 18

Benzodiazepines and Dependence = 3

Answer 18

1. Patients can become DEPENDENT on
   benzodiazepines
2. Often ABUSED IN COMBINATION WITH ‘OPOIDS’ AND ‘ALCOHOL’
3. Can be used ILLICITLY DUE TO ANXIOLYTIC PROPERTIES

Question 19

WHAT ARE Barbiturates? = 2

Answer 19

1. Act on GABAA receptors, INHIBIT GLUTAMATE RELEASE AND NON-NMDA GLUTAMATE RECEPTORS
2. POTENT DEPRESSION on CNS DEPRESSION because of its MULTIMODAL ACTION

Question 20

Anti-epileptic/anti-convulsants = 5

Answer 20

1. Traditional anti-epileptic drugs mainly target 3 channels:
2. • GABA receptors
3. • Sodium channels
4. • Calcium channels
5. Drugs that target GABA transaminase have anxiolytic effects

Question 21

WHAT IS ‘SEROTONIN’ (5-HT) = 5

Answer 21

1. An excitatory amine neurotransmitter
2. Important for mood and eating habits
3. Synthesises from 5-hydroxytrptophan
   (5-HTP) to make 5-hydroxytrptamine
   (5-HT)
4. Implicated in many mental health disorders
5. THE CONCENTRATION OF SEROTONIN IN THE BRAIN IS THOUGHT TO BE DIRECTLY CORRELATED TO LEVELS OF ANXIETY

Question 22

5-HT Receptors = 3

Answer 22

1. 7 subtypes of 5-HT receptors
2. All but 5-HT3 (ion channel) are GPCRs
3. Expressed pre and post-synaptically

Question 23

Azapirones = 4

Answer 23

1. Act on 5-HT1A receptors (pre and postsynaptically)
2. Thought to desensitise pre-synaptic 5-HT1A receptors but down regulate postsynaptic 5-HT1A receptors
3. Activation of the GPCR pathways alters adenylyl cyclase and a potassium channel
4. May not be effective in severe anxiety States

Question 24

AZAPIRONES

Answer 24

1. BUSPIRONE
2. ISPAPIRONE
3. GEPIRONE
4. RECEPTOR = 5HT(1A)
5. TRANSDUCER = Gi
6. LOCALISATION
   - Hippocampus, septum, amygdala, dorsal raphe, cortex
7. Agonist
   - buspirone, lisuride

Question 25

Selective Serotonin Re-uptake Inhibitors (SSRIs) =
5

Answer 25

1. Fluoxetine is a highly active blocker of the serotonin transporter
2. Increases the amount of serotonin at the synapse
3. Fluoexetine lacks affinity for neurotransmitter receptors but also acts on other transporters
4. SSRIs do not have an immediate therapeutic effect
5. Immediate effects of SSRIs are more commonly side effects

Question 26

5-HT Syndrome

Answer 26

5-HT syndrome is a rare but lethal syndrome where too much 5-HT accumulates in the brain stem and spinal cord

Question 27

what is XENON GAS = 4

Answer 27

1. Xenon is an INERT NOBEL gas
2. Typically used as an anaesthetic
3. Inhibits excitatory neurotransmission
4. Shown to have some efficacy in reducing fear-related behaviour and
   memory

Question 28

Xenon Gas = Sub-anaesthetic xenon gas: 5

Answer 28

1 * Inhibits NMDA receptor (competes for binding site)

2 * Inhibits AMPA receptors

3 * Inhibits nicotinic receptors

4 * Inhibits 5-HT3 receptors

5 * Activates potassium channels

Question 29

WHAT IS KAVA? = 6

Answer 29

1. Common drink in south pacific cultures for tribal and ritualistic purposes
2. Contains several bioactive
   substances:
   
   3. • Kavain
   4. • Dihydrokavain
3. Interacts with GABAA receptors
4. Some evidence to suggest inhibition of voltage gated sodium and calcium
   channels