20.6 Flashcards
(22 cards)
Benzodiazepines ___ GABA activity to reduce excessive neuronal discharge in epilepsy.
Enhance
Phenytoin ___ excitatory (glutamate) nerve fibre activity by ___ Na+ channels, but this only occurs it the channel is ___.
Decrease
Inhibiting Na+ channels
Only if the channel is open because it binds inside the channel!
By binding and enhancing the ___ receptor, benzodiazepines induce sedation, hypnosis or anxiolytic activity!
GABA
Barbiturates are general ___ that produce all levels of CNS ___.
General depressants, produce all levels of CNS depression i.e. mild sedation, surgical anesthesia, coma and death.
Barbiturates are ___ effective, ___ toxic and ___ addictive.
Highly for all!
Barbiturates are NOT ___, but used in controlled environments.
Prescribed
Benzodiazepines c.f. barbiturates have a wider ___ ___ because there is less depression of CV/resp centres and less dependence.
It is also ‘safe in overdose’ because it is an ___ ___
Therapeutic index
Allosteric modulator
Benzodiazepines are ___ modulators!
Allosteric
There are 2 GABA receptor types: GABA A is a ___ ___ ___ channel, and GABA B is a ___-___ ___ receptor.
GABA A is a ligand gated ion channel
GABA B is a G-protein coupled receptor
Benzodiazepines interact with the GABA ___ receptor ONLY.
GABA A ONLY
GABA A is an ionotropic receptor that mediates fast inhibitory potentials, by Cl- influx.
Benzodiazepines bind to ___ sites on the GABA A receptor that cause ___ changes that ___ the affinity of the receptor for GABA, thereby increasing the ___ of the GABA A receptor Cl- channel opening.
Allosteric sites
Conformational changes
Increase affinity -> enhance effect of receptor
Increases FREQUENCY of Cl- channel opening
Compared to benzodiazepines, barbiturates bind to the GABA receptor and increase the ___ that the channel is open for so it increases sensitivity AND maximum response - but benzodiazepines only increase frequency of opening -> increases sensitivity but NOT maximum response.
DURATION that the channel is open
Barbiturates ___ GABA action, but benzodiazepines DO NOT!
Amplify action!
Benzodiazepines only regulate GABA action.
Benzodiazepines increase the affinity of the GABA receptor for its ligand -> increases ___ of opening of channel
Frequency!
There is a physical limit to the frequency of opening of the channel - this is called a ___ effect of benzodiazepines.
Ceiling effect
C.f. barbiturates - there is a higher ceiling of effect because of increased duration of opening.
What are adverse effects of benzodiazepines?
Drowsiness, confusion, impaired coordination.
Describe how benzodiazepines interact with alcohol.
Alcohol binds to GABA receptors and changes their conformation.
This results in loss of allosteric modulation.
Alcohol can amplify the effects of benzodiazepines, leading to depression of cardiovascular and respiratory centres.
What are the disadvantages of benzodiazepines?
Tolerance (so gradually increase dose), withdrawal symptoms (physical AND psychological, so gradual dose reduction), dependence (potential for abuse), and interaction with alcohol, antihistamines and barbiturates.
Benzodiazepines are active ___, but there are differences in duration of action.
Orally
Oxazepam and temazepam are ___ acting benzodiazepines, and clonazepam and diazepam are __ acting.
Short
Long
Definition of pharmacological efficacy
What is the pharmacological efficacy of full agonists, and of partial agonists?
Strength of receptor activation
Full agonists - high efficacy.
Partial agonists - low efficacy.
Benzodiazepines increase the ___ of GABA, but barbiturates increase the ___ of GABA. Why?
Benzodiazepines increase the POTENCY of GABA - increase the frequency of the chloride ion channel opening at the GABA A receptor.
Barbiturates increase the EFFICACY of GABA - increase the duration of chloride ion channel opening at the GABA A receptor.
