drugs for mood disorders Flashcards
(46 cards)
depression
most common type of the affective disorder - mood and actions are innappropriate to circumstances
unipolar depression
major depression - the mood changes in the same direction
bipolar disorder
(manic depression) - oscillates between depression and mania (excessive enthusiasm and self-confidence, impatience and aggression)
monoamine theory of depression
hypothesized based on clinical effects of drugs that cause or alleviate symptoms of depression and their known neurochemical effects of monoaminergic transmission
a functional deficit of noradrenaline and serotonin in certain brain regions
problem with the monoamine theory
- doesnt differentiate between noradrenaline and serotonin as to which neurotransmitter plays a dominant role
drugs affecting either are equally effective - antidepressatn drugs have immidate neurochemical effect, yet symptom relief is not seen for two weeks, belived that serotonin and noradrenlaine are mediating long term antidepressant effects
imipramine
block noradrenaline and serotonin uptake
depressed schitzophrenics show mood improvement
ipromiazid
monoamine oxidase inhibitor (MAOI)
improved mood of depressed people
reserpine
inhibit noradrenaline and serotonin storage
patients developed depression
time scale of neurotransmission
immediate effects due to release of transmitters and fast synaptic transmission
long term effects due to structural remodelling and degeneration/regeneration
brain-derived neurotrophic factor BDNF
a member of the neurotrophic factor family
CNS development and neuronal plasticity
binds to TrkB (tropomyosin receptor kinase B), which activates three signalling pathways
all three pathways converge on the transcription factor CREB (cAMP response element binding protein) to up-regulate gene expression
how is BDNF produced in the body
prepro-BDNF (a precursor protein) - cleaved into pro-BDNF - further cleaved into mature BDNF
CREB
(cAMP response element binding protein)
up-regulates gene expression
what does BDNF bind
binds to TrkB (tropomyosin receptor kinase B), which activates three signalling pathways
all three pathways converge on the transcription factor CREB
chronic elevated levels of cortisol inhibits the transcriptional activity of of
CREB
chornic elevated levels of corticol is caused by
stress
reduced transcriptional activity of CREB causes
reduced BDNF expression > apoptosis of prefrontal cortex and hippocampus
increased transcriptional activity of CREB promotes
BDNF expression (BDNF binds to TrkB) > neurogenesis of prefrontal cortex and hippocampus
neuroplasticity theory of depression
depression is as a result of extended decreased BDNF levels in the hippocampus/prefrontal cortex
2 theories of cause of depressioon
- monoamine theory
- neuroplasticity theory
evidence for neuroplasticity theory
in animal studies, chronic stress decreased BDNF expression in hippocampus
antidepressant treatment increased BDNF levels in hippocampus
BDNF infusion into hippocapmus produced antidepressant like effects
post mortem analysis in humans shows decreased hippocampal BDNF levels in suicide victims and depressed individuals
selective serotonin reuptake inhibitors
bind to 5-HT transporter - block reuptake of 5-HT - elevate synaptic [5-HT], but
decrease release of 5-HT (due to negative feedback)
desensitisation of somatodendritic 5-HT1a receptor (weeks to develop) and increase in synaptic [5-HT]
4 examples of SSRIs
- fluoxetine (prozac)
- paroxetine
- sertraline
- citalopram
adverse effects associated with SSRIs
better side effect profile - due to no affinity for mAch receptors and histamine H1-receptors
safer than TCAs and MAOIs in overdose
5-HT2 receptor - agitation and insomnia
5-HT3 receptor - nausea
sexual dysfunction
‘serotonin syndrome’ if combined with MAOIs
CYP2D6-mediated drug-drug interactions - co-administration of fluoxetine with drugs that are metabolised by CYP2D6
serotonin syndrome
can occur if SSRIs are combined with MAOIs
