Anxiolytics

Question 1

What is the biochemical basis of anxiety states?

Answer 1

Central and peripheral noradrenergic/adrenergic activation → fight or flight response
Stress response → hypothalamus pituitary adrenal axis → secretion of stress hormones

Question 2

When is GAD diagnosed?

Answer 2

When psychological and physical symptoms are present for at least 6 months

Question 3

Therapeutic rationale of GAD

Answer 3

Reduce the activation of CNS using CNS depressants (sedation, hypnotic, anxiolytic)

Question 4

Therapeutics to treat GAD

Answer 4

Benzodiazepines
Zolpidem 
Buspirone 
Barbiturates eg phenobarbital
Pregabalin 
Hydroxyzine
Propanolol

Question 5

Benzodiazepines MOA

Answer 5

Potentiate GABA actions by increasing the frequency of GABA-induced channel opening

Question 6

Short acting benzodiazepines

Answer 6

Midazolam, triazolam

For procedural sedation

Question 7

Intermediate acting benzos

Answer 7

Lorazepam, temazepam

Question 8

Long acting benzos

Answer 8

Diazepam

For chronic conditions eg alcohol withdrawal syndrome, refractory seizure

Question 9

Unwanted effects of benzodiazepines

Answer 9

Acute toxicity → respiratory depression esp when used with alcohol; treatment is with flumazenil
Drowsiness, confusion, amnesia
Impaired muscle coordination
Tolerance and dependence

Question 10

Zolpidem MOA and use

Answer 10

Potentiates GABA A mediated chloride ion currents at the same site as benzodiazepines
Good hypnotic effects → used for insomnia

Question 11

Buspirone MOA and use

Answer 11

Serotonin partial agonist + binds to dopamine receptors
Indicated for GAD
Lack anticonvulsant and muscle relaxant properties as they do not work on GABA

Question 12

Barbiturates MOA

Answer 12

Potentiates GABA mediated chloride ion currents (diff site from benzos)
At anesthetic doses, can directly open chloride channels and block sodium channels

Question 13

Long acting, short acting and ultra-short acting barbiturates

Answer 13

Phenobarbital, pentobarbital, amobarbital, thiopental

Question 14

Do benzodiazepines depress CNS stronger than barbiturates?

Answer 14

No, same dose of barbiturate may have more CNS depression compared to same dose of benzodiazepines

Question 15

Pregabalin MOA and uses

Answer 15

GABA analogue, increases synaptic GABA → hyperpolarisation
Also works on voltage gated clacium ion channels
Used for GAD, has anticonvulsant effects
Associated with suicidal thoughts

Question 16

Hydroxyzine

Answer 16

Antihistamine with serotonergic and alpha adrenergic receptor activity
Anxiolytic effects due to antagonism of serotonin 5HT2 receptors
Antihistamine activity → helps with itching

Question 17

Propanolol

Answer 17

Beta adrenergic receptor antagonist
Used for performance anxiety and social phobias
Reduces physical symptoms (tachycardia, muscle tremors) associated with adrenergic activation
Contraindicated in asthma and heart conditions

Question 18

Other antidepressants used as anxiolytics

Answer 18

Mirtazipine
Clomipramine
Fluoxetine, citalopram