Transmitters and Receptors Flashcards
5 places that CNS drugs can act on
- Synthesis
- Storage
- Release
- Inactivation: Re-uptake/Metabolism
- Receptor
Problems with drug in the CNS re: mechanisms:
molecular mechanisms known
therapeutic mechanism not always known.
SSRI, Cocaine and Anti-AChE affect what?
reuptake of NTs
Cocaine and amphetamines affect NA but also:
dopaminergic
serotonergic
Which drug in epilepsy limits excitatory nerve activation?
phenytoin: binds to OPEN sodium channel, decrease Glutamate action
What drug enhances inhibitory input for epilepsy?
benzodiazepines enhance GABA receptor activity
Two NTs implicated for sedation/anxiety?
GABA
Serotonin
3 NTs implicated for anxiety?
serotonin
NA
Neuropeptide Y
NT implicated for Sedation in children
Histamine
Benzodiazepines used in treating what 5 main things:
epilepsy anxiety sleep disorders premedication acute alcohol withdrawal
Beta-adrenoceptor antagonists do what for anxiety?
block physical signs
nothing for CNS though
4 clinically recognized anxiety disorders?
general anxiety
panic disorder
phobia
PTSD
Barbiturates, hypnotic/anxiolytics used much today?
pretty much obsolete
What is Zolpidem?
direct non-benzodiazepine GABA agonist at orthosteric site
What do barbiturates do? why bad?
General depressants toxic: narrow therapeutic window induce liver enzymes abrupt withdrawal = death addictive
2 situations where you anxiolytics/hypnotics are still used?
anaesthetic
anticonvulsant
Why choose benzodiazepines over barbiturates?
wider therapeutic index
less cardioresp depression
less addictive
‘safer’ in overdose
benzodiazepines interact with GABA A or GABA B receptors?
GABA A receptor only
three ways benzodiazepines interact with GABA A receptor?
- modulate orthosteric ligand affinity
- modulate orthosteric ligand efficacy
- modulate receptor activation level
benzodiazepines modulate at which site?
allosteric modulators
diazepam a benzodiazepines does what to the GABA A receptor?
- increase frequency of Cl- channel opening
2. increase sensitivity with no change to maximal response
difference between benzodiazepines and barbituates in terms of receptor channel? how does this affect overdose?
- benzodiazepines: open and close/frequency: hits ceiling, safer
- barbituates: keeps the channel open, can overdose easily
why are allosteric modulators better?3 big ones:
- increase therapeutic window
- positive modulation of ENDOGENOUS agonist, not exogenous
- more receptor subtype selectivity
unwanted side effects of benzodiazepines?
drowsiness
confusion
impaired coordination
disadvantages of benzodiazepines?
interact with alcohol,
antihistamines/barbituates
withdrawal,
dependence
Can you take the same dose of benzodiazepines always?
develop tolerance: need to increase dose
How long is short vs. long acting benzodiazepines?
short: 6-12 hours
Long: >24 hours
Does low potency matter?
only if awkward to administer, low potency does not = inferior drugs
what is pharmacological efficacy?
strength of receptor activation: full vs. partial agonist
what is clinical efficacy?
strength of beneficial effect
benzodiazepines vs. barbituates: 3 big points in terms of efficacy/potency
- both affect GABA receptors
- Benzo: increase channel frequency (increase potency)
- barbituates increase duration of Cl- channel opening (increase efficacy)
What is Buspirone? where does it act?
non benzo anxiolytic: partial agonist at 5HT1 receptors
