Anxiolytics and hypnotics

Question 1

What is the main ascending tract associated with GABA transmission in the brain?

Answer 1

Nigrostriatal

Question 2

Describe the descending GABA pathways in the brain

Answer 2

Mostly localised control neurons

Question 3

Recall the subunits of the GABA receptor

Answer 3

1. Cl- channel protein
2. GABA modulin - links GABA and BDZ receptor proteins
   Receptor proteins for:
3. GABA
4. BARBs
5. BDZs

Question 4

How does binding of BARBs to the BARB receptor protein of the GABAR affect GABA receptor activity?

Answer 4

1. Enhances GABA action by increasing affinity of GABA binding
2. At high concentrations, increases DURATION of Cl- channel opening

Question 5

How does binding of BDZs to the BDZ receptor protein of the GABAR affect GABA receptor activity?

Answer 5

1. Increases affinity of GABARP for GABA

2. Increases FREQUENCY of opening of Cl- channel

Question 6

How does binding of GABAs to the GABA receptor protein of the GABAR affect BARBRP and BDZRPs?

Answer 6

1. No effect on the BARBRP

2. Reciprocally activates the BDZRP

Question 7

Where is GABA modulin found and what is its funcion?

Answer 7

Joining the GABARP and the BDZRP

Opens the Cl- channel

Question 8

What sort of action do BARBs and BDZs show at the GABA receptor?

Answer 8

Allosteric only

Question 9

Compare the selectivity of GABAR agonists and the consequence of this

Answer 9

BARBs = less selective than BDZs as they have effects on other membranes
This is why BARBs have an anaesthetic effect and a low margin of safety

Question 10

Where can GABA be metabolised?

Answer 10

Glia

Post-synaptic terminals

Question 11

Recall the reactions and enzymes involved in GABA metabolism

Answer 11

GABA –> SSA –> succinic acid
Enzyme 1 = GABA-transaminase
Enzyme 2 = SSA-dehydrogenase

Question 12

Recall 2 drugs capable of inhibiting GABA metabolism

Answer 12

Vigabatrin

Sodium valporate

Question 13

Where are the enzymes that metabolise GABA produced?

Answer 13

Mitochondria

Question 14

Recall an example of a barbiturate drug

Answer 14

Amobarbital

Question 15

Recall 3 uses of amobarbital

Answer 15

1. Sedative
2. Hypnotic
3. In severe intractable insomnia

Question 16

What is the main distinguishing factor between BDZ drugs?

Answer 16

They all have similar MOA and potency so distinguish base upon PK

Question 17

Recall the options for administration of BDZs and a reason why one of these might be rpeferable

Answer 17

Oral or IV

When administered IV, may lead to prolonged seizures (status epilepticus)

Question 18

Describe 3 aspects of general BDZ distribution in the body

Answer 18

Extensive FPM
Strongly binds plasma proteins
High lipophilicity

Question 19

How are BDZ drugs usually classified?

Answer 19

Long or short acting

Question 20

What might make a BDZ long-acting?

Answer 20

• Slow metabolism

- Metabolites are active

Question 21

Recall 2 examples for each of long- and short-acting BDZs

Answer 21

Long: diazepam, nordiazepam
Short: oxazepam. temazepam

Question 22

Which class of BDZs are preferable for use as anxiolytics?

Answer 22

Long-acting

Question 23

Which class of BDZs are preferable for use as sedatives?

Answer 23

Short-acting

Question 24

Recall 3 advantages of BDZ drug use over BARBs

Answer 24

1. Less effect on REM sleep
2. OD is safer
3. Does not induce CYP450

Question 25

Other than BARBs and BDZs, give an example of a drug that may be used as a sedative, its general MOA and an advantage of using it

Answer 25

Zopiclone
Short-acting BDZ agonist
Minimal hangover

Question 26

Recall 4 drugs that may be used as anxiolytics other than BARBs and BDZs

Answer 26

SSRIs
Anti-epileptics
Propanolol
Busiprone

Question 27

Why might propanolol be used in anxiety?

Answer 27

Improves physical symptoms of tachycardia and tremor (does not directly affect anxiety)

Question 28

Recall the MOA of busiprone, and one advantage and disadvantage for its use

Answer 28

MOA: 5HT1A agonist
Ad: fewer side effects
Dis: Slow onset of action

Question 29

What can BARBs be used for clinically that BDZs cannot?

Answer 29

Anaesthetic use

Question 30

Give an example of a BARB drug that may be used for its anaesthetic effect?

Answer 30

Thiopentone

Question 31

Give 4 clinical uses of BARB/BDZ drugs

Answer 31

1. Anticonvulsants
2. Antispastics
3. Anxiolytics
4. Sedatives

Question 32

What is the difference between a sedative and a hypnotic drug?

Answer 32

 Sedative should reduce mental/ physical activity without producing loss of consciousness
 Hypnotics should induce sleep
 Use same drugs for both just at different dosages

Question 33

Summarise the side effect profile of BARB drugs

Answer 33

1. Low margins of safety
2. Alter natural sleep
3. Induce liver enzymes
4. Tolerance/ dependence
5. Potentiate other CNS depressants such as alcohol

Question 34

Recall 4 symptoms of BARB withdrawal

Answer 34

Anxiety
Tremor
Convulsions
Insomnia

Question 35

What might increase the plasma concentration of BDZs and why?

Answer 35

Aspirin and Heparin coadministration

Due to high plasma protein binding