Anxiety

Question 1

What tests on humans look at effectiveness of drugs to treat anxiety?

Answer 1

Lie detector test and galvanic skin reactions

Question 2

What excitatory amino acids are involved with anxiety?

Answer 2

Glutamate and aspartate

Question 3

What inhibitory amino acids are involved with anxiety?

Answer 3

GABA and glycine

Question 4

What is the structure of GABAaR?

Answer 4

2a, 2B, Y

Question 5

What are agonists and antagonists at the orthosteric site of GABAaR?

Answer 5

Agonist- muscimol

Antagonist- bicuculline (competitive), picrotoxin (non competitive)

Question 6

what is the orthosteric site?

Answer 6

Primary binding site

Question 7

Beta-carboline

Answer 7

Stabilises the close form of GABAaR, increase memory and learning in animals with unwanted side effects

Question 8

Give examples of agonists and antagonist at allosteric site?

Answer 8

Agonist- Diazepam

Antagonist- flumazenil

Question 9

What can GABAa be regulated by/

Answer 9

Allosteric agonists, barbiturates, neurosteroids, general anaesthetics

Question 10

What do GABAb do?

Answer 10

Activates GIRK (potassium channels) to produce post synaptic inhibition

Question 11

How does GABA open GABAa receptors?

Answer 11

2 GABA bind on a+B subunit interface

Question 12

Where is the allosteric site on GABA?

Answer 12

Interface of a and Y subunit

Question 13

What are GABAa receptors targets for?

Answer 13

Sedatives, anxiolytics, hypnotics, anti-convulsants, neurosteroids, some general anaesthetics

Question 14

How are the subunits that respond to Benzos known?

Answer 14

Animal models- replace a2 gene with mutated/ KO, gives no anxiolytic effects of diazepam

Question 15

What physiological effects does Benzo have?

Answer 15

Sedation, hypnotic, anterograde, anticonvulsant, reduce muscle tone

Question 16

How does Benzo cause sedation?

Answer 16

Decrease responsiveness to constant level of stimulation, occurs with lowest doses

Question 17

How does Benzo cause hypnosis?

Answer 17

Latency of sleep onset decreased, duration of stage 2 sleep increase, duration of rem sleep is decreased duration of slow wave decreased

Question 18

How does Benzo cause anti-convulsant effects?

Answer 18

Prevents development and spread of epileptiform activity

Question 19

How does Benzo cause reduced muscle tone?

Answer 19

By central action of spinal cord

Question 20

What are Benzodiazapines split into and why?

Answer 20

Short, medium and long acting compounds- lipid solubility, drug half life, presence of active metabolites plasma protein binding

Question 21

What does drug half life depend on?

Answer 21

Renal function and enzyme induction

Question 22

What are the main drugs to treat anxiety?

Answer 22

SSRIs, bentos, Buspirone, anti epileptic, atypical antipsychotics, B adrenoceptor antagonist

Question 23

Which Benzos are metabolised to produce active intermediates with long half life?

Answer 23

Diazapam

Question 24

Zolpidem

Answer 24

Short half life, no active metabolites, actions limited to 4 hours, good for insomnia but not generalised anxiety

Question 25

What is the half life of Diazapam?

Answer 25

20-40 hours

Question 26

What are the adverse effects of Benzos?

Answer 26

Sleepiness, impaired psychomotor function, amnesia, additive effects with other CNS depressants, tolerance, misuse, physical dependance

Question 27

What happens with physical dependanc to Benzos?

Answer 27

Withdrawel with increased anxiety, insomnia, CNS excitability, convulsion, more problematic with drugs with short half lives,