2-Drugs for Depression Flashcards
what are the numbers needed to treat
vary from 2-25
which type of depression sees the best results with antidepressants
Major depressive disorder
what are the monoamine neurotransmitters
serotonin, dopamine, adrenaline and noradrenaline
what is so special about the shape of the monoamines
amine group connected to a ring structure via two carbons
what is the monoamine theory of depression
that it is related to a deficiency in the amount of cortical and limbic serotonin, noradrenaline and dopamind
what is the role of the limbic system
emotion and please
what is the role of the cortex
higher cognitive functioning
what caused the monoamine theory to arise
drugs that depleted monoamines was associated to depression in some patients
what happens when a depressed patient who is responding to antidepressants that boosts serotonin levels is given a diet without tryptophan
and why
they relapse because tryptophan is a precursor of serotonin
what happens when a patient responding to a drug that boosts noradrenaline levels if given a noradrenaline synthesis inhibitor
relapse
cant make noradrenaline so then they can be boosted
which antidepressants boost the monoamine system
all currently available antidepressants
what is the neurotrophic factor theory
that a lack of nerve growth factors are responsible for depression
what are neurotrophic factors
nerve growth factors
what is BDNF
Brain-derived neurotrophic factor
a growth factor protein that is involved in regulation of neural plasticity and neurogenesis
what happens to BDNF levels when you are depressed and what does this cause
levels lower causes a decrease in dendritic connectivity and decreased neurogenesis
how do antidepressants raise BDNF levels
it was not a planned effect, it was a byproduct of the monoamine targets
what does CREB do
a protein that regulates transcription of certain genes by binding to DNA
What is the role of CREB in depression
it may mediate BDNF but we don’t really know if it is affected by antidepressants
what does cortisol do to BDNF levels
lowers BDNF levels
what has the biggest effect in a treated state on CREB
BDNF and Monoamines (causes more BDNF release)
glutamate does other things too
what volume of the brain is most important in neurogenesis
hippocampus
where is decreased levels most found
cerebrospinal fluid
what does electroconvulsive therapy do
increases BDNF and increases neurogenesis in the hippocampus
what happens when you inhibit SERT or NET
serotonin and adrenaline accumulate in the synapse
what are autoreceptors/ what do they do/ where are they
on the presynaptic neuron, negative feedback, prevents further release
what do SERT and NET do
pump 5HT and NE back into the presynaptic inhibitor, reuptake
which drug was the first blockbuster SSRI
prozac/fluoxetine
what is fluoxetine/prozac more selective for
serotonin transporters than noradrenaline transporters
what enzyme metabolizes fluoxetine/prozac
CYP2D6
what is fluoxetine/prozac metabolized into
norfluoxetine
what is the half life of fluoxetine/prozac and why
super long because norfluoxetine has a super long half life, 180h
what is the issue with fluoxetine/prozac and norfluexitine
what does this cause
they are potent inhibitors of CYP2D6
increases half life over time
what kind of drug is fluoxetine/prozac
SSRI
what kind of drug is venlafaxine(effexor)
SNRI
how is SNRI different than SSRI
it is more selective towards NET than SERT (however still more SERT than NET, just less extreme, more balanced)`
what metabolizes venlafaxine(effexor)
CYP2D6
what does venlafaxine(effexor) become after metabolism
desvenlafaxine
half life of venlafaxine(effexor)
8-11 hours (just know its less than fluoxetine/prozac)
what do MAOIs do and how do they work
boost monoamine neurotransmitter levels by inhibiting MAO, the enzyme that metabolises them
what do TCAs do and how do they work
inhibit SERT and NET
which has the most potentially lethal overdose
TCAs, also MAOIs
What are some TCA side effects
antimuscarinic and drowziness because they antagonize H1 receptors (prevents ACh binding)
what is MAO / what does it do
an enzyme that metabolizes monoamine neurotransmitters
do MAOI work pre or post synaptically
PRE
what is the reason that antidepressants take awhile to work? (2 words)
receptor desensitization
what causes receptor desensitization
chronic elevation of serotonin levels desensitizes the autoreceptors, thereby there will be more synaptic levels
this happens with both alpha2 for noradrenaline neuron receptors too
how does BDNF work
changes the expression of genes, thus changing the relative abundance of proteins in various brain regions
why does it take awhile for BDNF to work
because new neurons still need to form and migrate, and BDNF is a protein and can take time to work
which drugs directly target the BDNF system
none
what macromolecule is BDNF
protein
