Anxiolytics

Question 1

What are the psychological and physical symptoms of anxiety?

Answer 1

Psycho: Negative emotions (worry, nervousness, unease), arousal, lack of concentration, insomnia

Physical: tachycardia, shortness of breath, nausea, gastric acid hypersecretion, trembling

Question 2

Describe the biochemical basis of anxiety states.

Answer 2

• Central and peripheral noradrenergic/adrenergic activation ➝ fight or flight response
• Stress response ➝ secretion of cortisol (HPA axis: corticotropin releasing hormone > adrenocorticotropic hormone > cortisol)

Question 3

Describe generalised anxiety disorder.

Answer 3

• excessive, uncontrollable worry about everyday matters
• interferes with daily functioning
• both psycho and physical symptoms
• diagnosed when present for ≥ 6 months
• most common cause of disability in the work place

Question 4

What is the mechanism of action of benzodiazepines?

Answer 4

They bind to the benzodiazepine allosteric site on GABA A receptors and potentiate the binding of GABA, leading to increased freq of Cl- channel opening. This leads to greater influx of Cl- and hyperpolarisation of the cell, reducing neural excitability.

Question 5

List examples of short acting benzos.

Answer 5

Short acting = 3-8h. e.g. midazolam, triazolam

Question 6

List examples of intermediate acting benzos.

Answer 6

Intermediate = 10-20h. e.g. temazepam, alprazolam, clonazepam, lorazepam

Question 7

List examples of long acting benzos.

Answer 7

Long = 1-2 days. e.g. diazepam, flurazepam, chlordiazepoxide

Question 8

Name examples of benzos used as anxiolytics/sedatives, hypnotics and pre-anaesthetics.

Answer 8

• Anxio/sedatives: diazepam, lorazepam
• Hypnotics: diazepam, temazepam, triazolam
• Pre-anaesthetics: diazepam, midazolam

Question 9

Compare the safety profile of benzos and barbiturates.

Answer 9

Both can lead to tolerance and dependency and withdrawal symptoms, benzo < barbs.

Both cause severe respiratory depression in overdose, esp with concurrent use of alcohol. Benzo overdose can be treated with flumazenil, but barb overdose cannot.

Question 10

Side effects of benzos

Answer 10

impaired muscle coordination & drowsiness, confusion, amnesia

Question 11

Which non-benzo works at the same site as benzo but is not effective as anxiolytic?

Answer 11

Zolpidem - primarily used to treat insomnia due to good hypnotic effect

Question 12

Which non-benzo is indicated for GAD but takes longer for anxiolytic effect to occur?

Answer 12

Buspirone - partial agonist of 5HT1A receptor.

• effects take 1-2 weeks
• lack anticonvulsant and muscle relaxant properties

Question 13

How does duration of action affect indication for barbiturates?

Answer 13

Ultra short (20min): IV induction of anaesthesia e.g. thiopental
Short (3-8h): Sedative and hypnotic e.g. pentobarbital, amobarbital
Long (1-2 days): Anticonvulsant e.g. phenobarbital (but LAST LINE DUE TO HIGH RISK OF DEPENDENCE)

Question 14

What is an impt side effect to counsel patients who are taking pregabalin for GAD?

Answer 14

Pregabalin may be associated with emergence or worsening of suicidal thoughts.

Question 15

What is the benefit of using hydroxyzine over BZDs and barbs?

Answer 15

low addictive potential. also helps with itching as it is an antihistamine.

Question 16

MOA of hydroxyzine

Answer 16

Anxiolytic effects due to antagonism of serotonin 5HT2 receptors.

Question 17

When is propranolol used for anxiety?

Answer 17

Treat performance anxiety and social phobias. It reduces physical symptoms associated with adrenergic activation e.g. tachycardia and ↑ RR