Barbiturates and Benzodiazepines

Question 1

Which compounds fuse to form barbituric acid?

Answer 1

Malonic acid and urea

Question 2

What are all barbiturates derived from?

Answer 2

Barbituric acid

Question 3

What are the three main classes of barbiturates?

Answer 3

Long-acting, short-acting and very-short-acting

Question 4

Which receptor do barbiturates act on?

Answer 4

GABAa

Question 5

What are the effects of barbiturates?

Answer 5

Antioxylitic, sedative, relaxant, analgesics and anticonulsant

Question 6

What are some issues with barbiturates?

Answer 6

Pharmacological tolerance and behavioural dependence

Question 7

Name very-short-acting barbiturates

Answer 7

Thiopentone and Sodium Pentothal

Question 8

Name short-acting barbiturates

Answer 8

Pentobarbitone

Question 9

Name long-acting barbiturates

Answer 9

Barbitone and Phenobarbitone

Question 10

What are the two classes of benzodiazepines

Answer 10

Short and long-acting

Question 11

What makes a short-acting BZ?

Answer 11

The metabolite of the drug is inactive

Question 12

What makes a long-acting BZ?

Answer 12

Only the metabolite is active

Question 13

What are some effects of BZs?

Answer 13

Antioxylitic, sedative, relaxant and anticonvulsant

Question 14

Which is used clinically more commonly out of barbiturates and BZs?

Answer 14

BZs have a (relative to barbiturates) high therapeutic index

Question 15

What are some key issues with BZs?

Answer 15

Tolerance and behavioural and physiological dependence

Question 16

5HTa agonists are useful in treating what?

Answer 16

anxiety

Question 17

What are some benefits of using 5HTa agonists as anxiolytics over BZs?

Answer 17

They are less effective but result in fewer side effects (little drowsiness, nausea, headache, restlessness)

Question 18

Name a 5HTa agonist

Answer 18

Azapirone

Question 19

Name a 5HTa partial agonist

Answer 19

Buspirone

Question 20

What do barbiturates and BZs bind to?

Answer 20

An allosteric site on GABAa and GABAb

Question 21

What do the drugs do when they bind to GABAa allosteric site?

Answer 21

They increase the frequency of the GABA Cl-channel opening

Question 22

What do drugs do when they bind to GABAb?

Answer 22

Via GPCR Gi, they inhibit AC and facilitate GABA channels opening

Question 23

Where is the BZ binding site on GABA channels?

Answer 23

Between the alpha-1 and gamma-2 subunits

Question 24

Where is the barbiturate binding site on GABA channels?

Answer 24

On the top and between alpha-1 and beta-2/3 subunits

Question 25

Where is the GABA binding site?

Answer 25

Between the alpha-1 and beta-2/3 subunits, but closer to the membrane

Question 26

Do drugs show GABA subunit selectivity?

Answer 26

Yes. This makes them desirable drug targets

Question 27

Drugs targeting alpha-1 subunit usually result in which effects?

Answer 27

Sedative effects

Question 28

Drugs targeting alpha-2 subunit usually result in which effects?

Answer 28

Anxiolytic effects

Question 29

How do BZs most commonly affect the GABA channels?

Answer 29

Increase frequency of opening

Question 30

How do barbiturates most commonly affect the GABA channels?

Answer 30

Increase the open time of the channel

Question 31

How does propofol affect GABAergic transmission?

Answer 31

It enhances by acting on allosteric sites and acting directly on the main binding site

Question 32

Name a BZ agonist drug

Answer 32

Diazepam

Question 33

Name a BZ partial agonist drug

Answer 33

Ro 15-1788

Question 34

Name a BZ competitive antagonist

Answer 34

Flumazenil

Question 35

Name a BZ partial inverse agonist

Answer 35

FG 7142

Question 36

Name a BZ inverse agonist

Answer 36

Beta-carbolines

Question 37

How does a BZ agonist induce an effect in the precoupled ON state?

Answer 37

Increases GABA receptors affinity which increases the open time of the Cl- channel, which increases the intrinsic agonist

Question 38

How does a BZ inverse agonist induce an effect in the unprecoupled state?

Answer 38

Keeps a receptor in the 'off' state which reduces the intrinsic efficacy