Anxiolytics and Hypnotics

Question 1

What are anxiolytics and hypnotics used to treat?

Answer 1

A- anxiety.

H- insomnia

Question 2

Give psychological and physical symptoms of anxiety.

Answer 2

Psychological- nervousness, fear, foreboding.

Physical- sweating, sleeplessness and palpitations.

Question 3

Give the 5 treatments for anxiolytics and hypnotics?

Answer 3

barbiturates, benzodiazepines and Z drugs, 5HT1a receptor agonists, B adrenoceptor antagonists histamines,

Question 4

How do barbiturates work?

Answer 4

Act as a GABAa positive allosteric receptor modulator.

Question 5

What are GABAa receptors and what do they do?

Answer 5

Ligand gates receptors which have multiple binding sites. GABA binds- receptor opens and Cl ions flow into the cell causing hyper polarisation, this acts an inhibitory stimulus preventing AP firing.

Question 6

Where are most GABAa receptors found?

Answer 6

Post synaptic neurones.

Question 7

What is the structure of GABAa receptors?

Answer 7

Pentameric structure - most common, 2 alpha, 2 beta and a gamma.

Question 8

What other substances bind to GABAa? (name 4)

Answer 8

Benzodiazepines, channel blockers (picrotoxin) channel modulators (GA) and allosteric modulators (barbiturates).

Question 9

Function of barbiturates?

Answer 9

PAM- increase GABAa efficacy for GABA- binds for longer keeping the channel open for longer - enhances the functional response of the GABA receptor.

Question 10

Why are barbiturates dirty?

Answer 10

They bind to other sites- high concentrations act as a direct agonist, block nACh receptors and block Ca dependant NT release.

Question 11

What are benzodiazepines?

Answer 11

Positive allosteric modulators- although have their own binding site.

Question 12

How to BZDs work?

Answer 12

They stabilise the GABA binding site, keeping the receptor in the form GABA can bind to rather than the receptor oscillating between forms. Increase GABA binding.

Question 13

Where to the BZDs bind on the receptor?

Answer 13

To the alpha gama interface (only on alpha 1,2,3,5 as they have a histamine residue to bind to)

Question 14

Name a competitive antagonist of BZDs

Answer 14

flumenazil- only used in severe ODs as it has bad side effects.

Question 15

What are Z drugs?

Answer 15

Similar to BZDs, positie allosteric modulator that acts on the GABAa receptor at the BZD binding site causing a similar response. however they are structurally different.

Question 16

How can BZDs and barbiturates cause addiction and withdrawal symptoms?

Answer 16

They increase GABA stimulation, in response there is an increase in glutamate receptors and simulation in order to balance excitation and inhibition. A withdrawal of BZDs or barbiturates will mean massive glutamate stimulation and no GABA- unbalances, causes withdrawal symptoms (seizures and addiction).

Question 17

How to 5HT1a receptor agonists work? (example)

Answer 17

5HT1 receptors are metatropic auto inhibitory that decrease the release of serotonin. Agonists such as buspirone increase their action.

Question 18

What do 5HT1a receptor agonists do?

Answer 18

Decrease serotonergic drive

Question 19

How do B adrenoceptor antagonists work? (example)

Answer 19

Na binds to beta adrenoceptors, B adrenoceptor antagonists block the NA binding sites preventing the action NA.
Propanolol

Question 20

What do B adrenoceptor antagonists do?

Answer 20

Block B receptors and decrease peripheral symptoms of anxiety. (stop renin release, prevent tachycardia)

Question 21

How do antihistamines work?

Answer 21

they antagonise CNS H1 receptors which are responsible for wakefulness - therefore make people drowsy. Use as a hypnotic only.