D3 Benzodiazepines

Question 1

what are BDZ used for

• what are they blocked by?
• for BDZ to exhibit its effects what is required?

Answer 1

enhance presynaptic inhibiton in spinal cord

• blocked by bicuculiine
• normal levels of GABA

Question 2

where does BDZ bind?

• what does binding modulate
• Classical BDZs are classed as what?

Answer 2

Benzodiazepine receptor = a specific BDZ binding site on the α-subunit of the GABAA receptor complex

• modulates the binding of GABA to its site
• modulates the opening of the Cl- ion channel
• Classical BDZs are classed as agonists at the BDZ site: enhance the inhibitory effects of GABA

Question 3

Consequences of BDZ binding
- what do BDZ enhance

what is this like compared to barbiturates

Answer 3

BDZs enhance the ability of activated GABA receptors to open

• increased frequency of opening
• no change in channel conductance
• no change in mean duration of opening

Barbiturates

• no change in frequency of opening
• no change in channel conductance
• increased mean duration of opening

Question 4

what do BDZ and GABA facilitate for one another

Answer 4

both facilitate binding to each other for their receptor

- GABA increases affinity of BDZ for its binding site as does BDZ increase affinity for GABA binding site

Question 5

what are Endozepines

describe Diazepam binding inhibitor

Answer 5

Endogenouscompounds withBDZlike effects

• acyl-CoA-binding protein
• binds medium- and long-chain acyl-CoA esters
• acts as an intracellular carrier of acyl-CoA esters
• displaces BDZ and Z-drugs from GABAA complex

Question 6

Describe Oleamide

and what is the uncertainty

Answer 6

Endozepines
- derived from the fatty acid oleic acid
- accumulate in thecerebrospinal fluidduringsleep deprivation
- induces sleep in animals
- interacts with multipleneurotransmittersystems (including cannabinoid and BDZ)
((Uncertain if there really is an endogenous ligand))

Question 7

what are Z drugs

• what is there chemical structure like
• give examples

Answer 7

Nonbenzodiazepine agonists of benzodiazepine receptor
(chemically unrelated to BDZ)
- Zolpidem, zopiclone, zaleplon, and eszopiclone
Clinical properties and therapeutic uses similar to BDZ

Question 8

what are some side effects of benzodiazepines

Answer 8

In ascending dose, they cause:

• an increase in seizure threshold
• euphoria, or intense feelings of pleasure
• anxiety-relief (anxiolysis)
• relaxation (sedation)
• sleepiness (hypnosis)
• unconsciousness (anaesthesia)
• death (rarely as sole agent)

Question 9

Benzodiazepine metabolism
where metabolized & by what 
what needs to be factored into duration effect of drug 
where excreted
range of half lives

Answer 9

Metabolised in liver
- by CYP3A4 and/or CYP2C19
- but not inducers of liver enzymes
Many primary metabolites are also BDZ agonists
- needs to be factored into duration of drug effect
Many undergo glucuronidation
Excreted primarily via the kidneys & faeces
Very wide range of plasma half-lives
- from 1 hour to 5 days

Question 10

half life and clinical use

Answer 10

Long half-life (30 – 60 hours)
= anticonvulsants
Intermediate half-life (10 – 20 hours) = used as anxiolytics
Short half-life (under 10 hours) - used as hypnotics, minimises daytime sedation (hangover effect), shorter for problems getting to sleep, longer for problems staying asleep
Very short half-life (1 – 3 hours) = used and IV anaesthetic

Question 11

Describe Flumazenil

Answer 11

Pure antagonist of BDZ and Z-drugs
Short half-life
used for diagnosis/ treatment of BDZ poisoning
reversal of anaesthesia/ sedation produced by a BDZ, treatment of hepatic encephalopathy

Question 12

Z-drugs versus benzodiazepines

Answer 12

Z-drugs 
- used as hypnotics
- Considered more effective than BDZ
- Considered safer than BDZ
Produce less tolerance
Produce less habituation
- reduced withdrawal problem