Anxiolytics and Hypnotics Flashcards
(24 cards)
How many subunits form a GABAAR and what is their arrangement?
5
A2B2Y
Where does GABA bind to GABAAR?
Between A and B (two sites)
What is the effect of GABA binding to GABAAR?
Opens Cl- channel
Where do benzodiazepines bind to GABAAR?
Between A and Y
What is the effect of benzodiazepine binding to GABAAR?
Increased Cl- channel opening frequency
Do benzodiazepines open Cl- channel without simultaneous GABA binding to GABAAR?
No
What is the effect of B-carboline binding to GABAAR benzodiazepine binding site?
Prevents GABA binding from opening Cl- channel
Closes channel if GABA already bound
What are the effects of B-carboline?
Anxiety
Insomnia
Name a benzodiazepine antagonist
Flumazenil
What are the effects of benzodiazepines?
Sedation Anxiolysis Hypnosis Muscle relaxation Anti-convulsant
What are uses of short-acting benzodiazepines?
Amnesics
Hyponotics
What are uses of long-acting benzodiazepines?
Anxiolytics
Anti-convulsants
Where do Z drugs act?
Benzodiazepine binding site on GABAARs
What are the effects of Z drugs?
Anxiolysis
Sedation
Hypnosis
What are the side effects of benzodiazepines?
Confusion
Drowsiness
Muscle incoordination
What are the factors affecting benzodiazepine tolerance?
Receptor occupancy
Dose duration
Number of surface receptors
What are the effects of benzodiazepine dependence?
Anxiety
Tremor
Appetite loss
Insomnia
What are the names of the natural anxiolytics in the brain?
Neurosteroids (e.g. allopregnanolone)
Diazepam binding inhibitor protein (e.g. endozepine)
Serotonergic system
What is the effect of 5HT1ARs?
Inhibitory
What is the effect of buspirone?
5HT1AR partial agonist
Acute: binds presynaptic 5HT1ARs - less presynaptic 5HT release - less inhibition of postsynaptic neuron
Chronic: desensitises presynaptic 5HT1ARs - more presynaptic 5HT release - more inhibition of postsynaptic neuron
Name a B-adrenoceptor antagonist and its use
Propranolol
Acts on PNS to treat physical signs of anxiety
Name 3 barbiturates and their uses
Thiopental - anaesthesia
Secobarbital - insomnia
Phenobarbitone - epilepsy
What are the problems with barbiturates?
Cause respiratory depression
No antidote
How do barbiturates act on GABAARs?
Binding with GABA: channel open for longer - potentiation
Barbiturate binding alone: directly opens channel
