Flashcards in Anxiolytics and Hypnotics Deck (49)
What are the four main proteins that make up the GABA-A receptor?
GABA receptor protein
Benzodiazepine receptor protein
Barbiturate receptor protein
Chloride channel protein
What protein links the GABA receptor proteins and the benzodiazepine receptor protein?
Name a competitive antagonist of the GABA receptor protein.
Name a competitive antagonist of the benzodiazepine receptor protein.
What are the two main effects of benzodiazepines that facilitate GABA neurotransmission?
They facilitate the GABA-mediated opening of the chloride channel
They facilitate the binding of GABA to its receptor protein (increase the affinity of GABA to the GABA binding site) – this is reciprocated
What are the three main effects of barbiturates that facilitate GABA neurotransmission?
They enhance the normal physiological action of GABA
They enhance GABA binding to the GABA receptor protein
At higher concentrations, barbiturates can have a direct action on the chloride channel
What is the key difference in the mechanism of action of barbiturates and benzodiazepines?
Benzodiazepines – increase the frequency of chloride channel opening
Barbiturates – increase the duration of chloride channel opening
What is the relative difference in selectivity between barbiturates and benzodiazepines?
Barbiturates are LESS selective
This may explain why barbiturates induce surgical anaesthesia and why barbiturates are less safe than benzodiazepines
NOTE: barbiturates also reduce excitatory transmission
Name a barbiturate that is used as an anaesthetic.
Thiopentone- only barbiturates can be anaesthetics
Name three barbiturates and benzodiazepines that are used as anti-convulsants.
Name a benzodiazepine that is used as an anti-spastic.
What are two other clinical uses of benzodiazepines and barbiturates?
Remove anxiety without impairing mental or physical activity
Reduce mental and physical activity without producing loss of consciousness
What structure is common to all barbiturates?
Six-membered ring (4 carbons and 2 nitrogens)
Barbiturates have been largely superseded by benzodiazepines. Which barbiturate is still used relatively commonly?
Amobarbital- for insomnia
What are the unwanted effects of barbiturates?
Low safety margin (overdose can be lethal)
Alters natural sleep (reduced REM)
Potentiate the action of other CNS depressants (e.g. alcohol)
What structure is common to all benzodiazepines?
They are tricyclic
What are the three key benzodiazepines?
What is the difference between all the benzodiazepines that are in clinical use?
Describe the administration of benzodiazepines.
Well absorbed per orally
Peak plasma concentration after about 1 hour
When would you give IV benzodiazepines?
Treatment of status epilepticus
Describe the distribution of benzodiazepines.
Bind strongly to plasma proteins
Highly lipid soluble
Describe the metabolism of benzodiazepines.
Extensively metabolised in the liver
Describe the excretion of benzodiazepines.
Excreted in the urine as glucuronide conjugates
Describe the duration of action of benzodiazepines.
Varies a lot
This allows classification as short-acting and long-acting benzodiazepines
What makes long-acting benzodiazepines have a long duration of action?
They have slower metabolism
They generate active metabolites
Name two short-acting benzodiazepines.