Benzodiazepines

Question 1

What is the mechanism of action of BZ?

Answer 1

They bind to the benzodiazepine binding site on the GABA_A receptor.

GABA MUST BE BOUND FOR BZ TO HAVE AN EFFECT!

BZ causes the ion channel to be open more frequently for longer

Question 2

What is the structure of the GABA receptor?

Answer 2

it is pentomeric - contains 5 subunits spanning the membrane:

• 2 alpha
• 2 beta
• 1 gamma
• Benzodiazepine binding site
• 2 GABA binding sites

Question 3

What is the mechanism of GABA on the GABA receptor. What is required to activate the receptor?

Answer 3

GABA must bind to BOTH GABA binding sites in order to activate the receptor. Binding og GABA activates the ion channel and causes an influx of Cl- ions which hyper polarize the cell and reduce membrane excitability as Ep further from threshold potential.

Question 4

How does increasing the concentration of GABA effect the GABA receptor?

Answer 4

Increases probaility of the channel being open

Question 5

What does GABA stand for? What time of receptor is it?

Answer 5

• Gamma amino butyric acid
• Ligand gated Cl- ion channel

Question 6

What is an agonist?

Answer 6

A chemical that binds to a receptor and triggers change in cell function e.g. muscimol

Question 7

What is an antagonist?

Answer 7

A chemical which binds to the recteptor and blocks the action of an agonist e.g. bicuculline

Question 8

What is an inverse agonist?

Answer 8

A chemical which has the opposite effect of an agonist

Question 9

BZ isn’t an agonist or antagonist, so what is it?

What effects does it have?

Answer 9

A postive allosteric modulator

• Enhances GABA binding
• Enhances effecrs of GABA
• GABA in turn enhances BZ binding

Question 10

What is GABA?

Answer 10

An inhibitory NT endogenously present in the human brain at inhibitory synapses

Question 11

What effects do an anatgonist and inverse agonist have? Examples of each

Answer 11

• Antagonist at BZ binding site. ALSO KNOWN AS NEGATIVE ALLOSTERIC MODULATORS:

Reverses the effect of the BZ (therefore ion channel open as normal) e.g. beta carboline

• Inverse agonist - causes the ion channel to be open less frequently (Shrinks) e.g. flumazenil

Question 12

What are the most common isoforms of the GABA receptor?

Answer 12

• a1, b2, y2
• a2, b3, y2
• a3, b3, y2

Question 13

What is the GABA receptor modulated by?

Answer 13

• BZs
• Barbituates (+ve)
• Zn (-ve)
• ethanol
• Anaesthetics
• neurosteriods

Question 14

What can BZs be used for?

Answer 14

• Axiolytics
• sedatatives
• Muscle relaxtants
• Anti convulsant (AED)

Question 15

Desribe tolerance in relation to BZs

Answer 15

• Decrease in pharmacological effect on repeated administration
• Desensitisation

Question 16

Describe dependance in relation to BZs

Answer 16

• Drug taking becomes complusive
• Euphoria and tranquility with BZs
• Stimulation of the reward pw in limbic system

Question 17

Describe withdrawl in terms of BZs

Answer 17

• Consequence of tolerance
• If BZs suddenly stoppwd the receptor is left desensitised so GABA has less effect
• Produces anxiety, insomnia, depression, muscle tension

These symptoms will continue until BZs replaced or receptors readapt

Question 18

How should people be taken of BZs?

Answer 18

• Transferred to diazepam daily doses
• reduce dose in fortnightly steps of 2 - 2.5mg
• Reduce dose further
• stop