Pharmacology of anxiolytic drugs

Question 1

What is the main tract involved in fear

Answer 1

Amygdala-centred circuit

Question 2

What is the main tract involved in worry?

Answer 2

Cortico-striatal-thalamic-cortical circuit

Question 3

What is the function of the amygdala?

Answer 3

Integrates sensor and cognitive information

Question 4

Structure involved in the affect of fear?

Answer 4

Anterior cingulate cortex/orbitofrontal cortex

Question 5

Structure involved in avoidance?

Answer 5

Periaqueductal gray (Fight or flight)

Question 6

Structure involved in cortisol increase in fear?

Answer 6

Hypothalamus

Question 7

Structure involved in increasing BP and HR in fear?

Answer 7

Locus coeruleus

Question 8

Structure involved in re-experiencing of traumatic memories?

Answer 8

Hippocampus

Question 9

What are some neurotransmitters and hormones involve din the amygdala-centred circuits?

Answer 9

• 5-HT
• GABA (Gamma-aminobutyric acid)
• Glutamate
• CRF (Corticotrophin releasing factor)
• Noradrenaline
• Voltage-gated ion channels

Question 10

What is the main inhibitory transmitter of the brain?

Answer 10

GABA

Question 11

What is the function of GABA in anxiety and fear?

Answer 11

GABA reduces the activity of neurones in the amygdala and CSTC circuit, therefore diminishing anxiety and fear levels

Question 12

How does GABA decrease neuronal activity?

Answer 12

GABA binds to GABA binding sites
This causes opening of Cl- channels which hyper polarises the cell, making it harder for the cell to reach it’s threshold for AP

Question 13

What are some drugs that affect the GABA channels?

Answer 13

Benzodiazepines
Barbituates
General anaesthetics
Alcohol

Question 14

What is the MOA of benzodiazepines

Answer 14

Benzodiazepines bind to BDZ binding sites on GABA-A channels, causing it to open, allowing more Cl- to enter and therefore depressing neuronal activity

Question 15

What are the pharmacological effects of benzodiazepines?

Answer 15

reduction in anxiety and aggression, sedation, muscle relaxation, anti-convulsant effect and anterograde amnesia

Question 16

What are some examples of benzodiazepines?

Answer 16

• Lorazepam (Activan)
• Diazepam (Valium)
• Chlordiazepoxide (Librium)
• Alprazolam (Xanax)
• Midazolam
• Clonazepam

Question 17

What are some clinical uses of benzodiazepines?

Answer 17

• Acute treatment of extreme anxiety
• Hypnosis
• Alcohol withdrawal
• Mania
• Delerium
• Rapid tranquilisation
• Premedication before surgery or during minor procedures
• Status epilepticus

Question 18

What drug can be given in cases of benzodiazepine overdose?

Answer 18

Flumazenil (BDZ antagonist)

Question 19

What are some side effects of benzodiazepines?

Answer 19

Paradoxical aggression
Anterograde amnesia
Impaired coordination
Tolerance or dependance

Question 20

What are some withdrawal effects of benzodiazepines?

Answer 20

• Abdominal cramps
• Increased anxiety and panic attacks
• Muscle tension, chest pain, palpitations, sweating and shaking
• Blurred vision
• Depression
• Insomnia, nightmares
• Dizziness and headaches
• Nausea and vomiting

Question 21

What are some possible effects of rapid benzodiazepine withdrawal?

Answer 21

Confusion, psychosis and convulsions

Question 22

How can benzodiazepines cause tolerance?

Answer 22

Chronic treatment with BDZs causes a decrease in GABA receptors and so decreases the bodies response to GABA

Question 23

How should withdrawal of BDZs be performed?

Answer 23

Withdrawing benzodiazepines should be done by switching to the equivalent dose of diazepam and then reducing the dose ever 2-3 weeks, maintaining the dose if withdrawal symptoms occur, until symptoms improve

Question 24

How can SSRIs and SNRIs be used in anxiety?

Answer 24

Serotonin is a key neurotransmitter in the amygdala
Increasing extrecellilar serotonin causes neuroadapidve changes, causing increased neurosteroid synthesis