Lecture 12 (Anxiolytics)

Question 1

What do you call drugs used to treat anxiety?
and sleep disordors?

Answer 1

-Anxiolytics
-Hypnotics

Question 2

What is anxiety?

Answer 2

Anxiety – anticipatory fear response, which is often independent of external events

Question 3

Name some anxiety disorders? (6)

Answer 3

-Panic disorder, overwhelming fear with marked somatic symptoms
-Social anxiety disorder
-Phobias

-Post-traumatic stress disorder
-Obsessive compulsive disorder

-Generalised anxiety (no clear reason or focus)

Question 4

Name the two animal models of anxiety and describe them? (4)

Answer 4

Elevated plus maze/cross

Elevated cross maze has open and closed size, rodents tend to walk up to closed size due to fear of open side
When you give it anti anxiety drugs the rodents no longer have a preference and are happy to go to open side

Light/Dark Box

Light and dark box, rodents have tenancy to hide in the dark side of the box
When treated with anxiolytic they have no preference and are happy to move to light side

Question 5

What happens when you associate treat with something bad while animal is on anxiolytics?

Answer 5

-With anxiolytic they will go for treat regardless
-When treated with drugs that stop them from feeling the pain, they will still avoid the treat
-Antidepressant also mean that they continue to show fear responses

Question 6

Which receptors are targets for anxiolytics?

Answer 6

GABAa receptors

Question 7

What are the 5 binding sites of GABAa? (5)
and are they allosteric of orthosteric? (5)

Answer 7

GABA - Orthosteric
Ethanol - Allosteric
Benzodiazapene - Allosteric
Barbiturate - Allosteric
Neurosteroids - Allosteric

Question 8

What is the orthosteric binding site responsible for?

Answer 8

Switching one signal/receptor

Question 9

What type of receptors are GABAa?
and what do they mediate?

Answer 9

Ionotropic receptors
Mediate fast inhibitory transmission
(Activation leads to hyper-polarisation and reduction in Excitability)

Question 10

Name an agonist in GABAa for allosteric and orthosteric sites? (2)

Answer 10

Orthosteric - muscimol
Allosteric - diazepam

Question 11

How did scientists identify which subunit is needed to mediate the anxiolytic effects of benzodiazepines?

Answer 11

-Studies in transgenic mice “knock in” mutated in alpha 2 receptor in GABAa
-Benzodiazepines no longer effective

Question 12

What are the physiological effects benzodiazepine agonists? (5)

Answer 12

-Sedation/Anxiolytic
(decreased responsiveness to constant level of stimulation)

-Hypnosis
(latency of sleep onset is decreased, duration stage 2 (non-rem) sleep increased, duration of rem sleep decreased)
(duration of slow-wave (associated with sleep walking and night terrors) sleep decreased)

-Anterograde Amnesia (e.g rohypnol)

-Anti-convulsant (inhibit spread of epileptiform activity)

-Reduction of muscle tone (mediated at level of spinal chord)

Question 13

Which GABAa subunit is in drugs for anxiety and sleep? (2)

Answer 13

-Anti-anxiety drugs involve receptors in alpha 2 subunit
-For sleep-based drugs alpha 1

Question 14

What kind of allosteric receptors are benzodiazepines?

Answer 14

Benzodiazepines are positive allosteric regulators of GABAa receptors

Question 15

What do benzodiazepines do? (2)

Answer 15

-Increase activity of GABAA receptor
-Increase Cl- current across membrane (but only in presence of GABA)

Question 16

What do you call drugs that increase anxiety?

Answer 16

Anxiogenics
(e.g Beta carboline, negative allosteric regulator of GABAa)

Question 17

How do positive and negative allosteric modulators (PAM/NAM) effect GABA?

Answer 17

Positive types increase the response of the receptor by increasing the probability that an agonist will bind to a receptor (i.e. affinity), increasing its ability to activate the receptor (i.e. efficacy), or both.

Negative allosteric modulators have opposite effect and rescue affinity of receptor for agonist at orthosteric site

Question 18

What are adverse effects of Benzodiazepines agonists? (5)

Answer 18

-Tolerance, decreased responsiveness to a drug following continuous exposure
-Misuse
-Physical dependence characterised by withdrawal
-Sleepiness
-Amnesia

Question 19

How can Benzodiazepine agonists have fatal adverse effects?

Answer 19

Can have adverse effects with other CNS depressants such as alcohol

Question 20

What are barbiturates used for?

Answer 20

Sleep drugs

Question 21

What happens with high concentrations of barbiturates?

Answer 21

Barbiturates as you go up in concentrations they behave as agonists at orthosteric sites which can lead to death (e.g used in death penalty)

Question 22

What are other anxiolytics other than benzodiazepines? (3)

Answer 22

-Beta blockers (e.g propanolol)
-Selective Serotonin Re-uptake Inhibitors (SSRIs) (e.g sertraline)
-Buspironne

Question 23

What does drug choice depend on?

Answer 23

Drug choice depends on underlying cause & whether short term or chronic