Anxiolytics (Block 4)

Question 1

Anxiety

Answer 1

Normal & essential response to perceived/impending danger (different to fear, which is of a known threat)
Becomes a clinical issue when there’s no reasonable cause and it interferes with normal functioning

Question 2

Examples of anxiety disorders

Answer 2

Generalised anxiety disorder (GAD)
Post-Traumatic Stress Disorder (PTSD)
Panic disorder, with or without agoraphobia

Question 3

Sedative

Answer 3

Reduce alertness
Relieve anxiety & in high doses induce sleep

Question 4

Hypnotics

Answer 4

Induce sleep

Question 5

Anxiolytics

Answer 5

taken to relieve anxiety and stress. Ideal anxiolytics have no sedative effect. Anxiolytic drugs, whether sedative or not, may sometimes be referred to as minor tranquillisers.

Question 6

Historical anxiolytic agents

Answer 6

Belladonna alkaloids (atropine, scopolamine)
Opiates (opium, morphine, diamorphine (heroine))

Question 7

Atropine

Answer 7

Historically used as an anxiolytic agent
General anaesthesia
Atropine is a muscarinic receptor antagonist (GPCR)
So prevents acetylcholine binding
Duration of action= 4 hours

Question 8

Historical agents - Barbiturates

Answer 8

Used a lot in WW1
Sedatives
Harmful side effects
A big step forward for the time

Question 9

Benzodiazepines

Answer 9

Commercially - Valium
Only used in acute cases now but was used very widely before
Tolerance issue, hence decrease in reduction despite success

Question 10

Azapirones

Answer 10

Effectiveness develops over 1-3 weeks
Effective in GAD but not in panic attacks
Licensed for short term treatment in the UK

Question 11

Mechanisms of action - barbiturates

Answer 11

Their sedative and anxiolytic actions are thought to arise from their binding to GABAA receptors, where they potentiate GABAergic signalling.

Question 12

Mechanisms of action - Benzodiazepines

Answer 12

Benzodiazepines act at the benzodiazepine (BDZ) site of GABAA receptors to increase the receptor’s affinity for GABA (thereby increasing the size of responses).

Question 13

Therapeutic selectivity

Answer 13

Some benzodiazepines show therapeutic selectivity. Action at different GABAA receptor subtypes may underlie this.
Eg -> zolpidem is an hypnotic; clonazepam is an anticonvulsant

Question 14

The GABA-A receptor - ligand gated ion channel

Answer 14

Ionotropic receptor, permeable to chloride ions
Action therefore inhibitory
Endogenous agonist is GABA (-aminobutyric acid)
Similar to nicotinic acetylcholine receptors, with five subunits per channel