depression pharmacological treatment Flashcards
what 2 receptors do the most effective anti-depressants work on?
5-HT (serotonin) and NA (noradrenaline)
Where are 5HT cell bodies contained in the brain?
in the dorsal and median raphe nuclei
Where are NA cell bodies contained in the brain?
in the Locus coerulus
what determines the synthesis rate of NA and 5HT?
- TPH for 5HT (tryptophan hydroxylase)
2. TH for NA (tyrosine hydroxylase)
what determines the breakdown of 5HT and NA?
MAO (monoamine oxidase)
what determines the release rate of 5HT and NA?
the firing activity of the impulse
what determines the reuptake rate of 5HT and NA?
the transporter activity
what part of 5HT, NA and DOPA does MAO act on?
the NH2 at the end of the chain
where do MAO act?
they break down the monoamine in the cytosol and regulate the vesicle content
How do the monoamine reuptake transporters work?
they transport the monoamines from the synaptic cleft to the presynaptic terminal
how can we increase 5HT and NA neurotransmission?
- reduce their breakdown in the synaptic cleft hence increase their release per impulse
- block their reuptake hence increase their duration and concentration in the synaptic cleft.
- increase the post-synaptic receptor activation.
what are the two main classes of antidepressant drugs?
- inhibitors of monoamine metabolism (so they inhibit monoamine oxidase)
- inhibitors of monoamine reuptake e.g. (SSRIs, SNRIs and TCAs)
what group of MAO are blocked by monoamine oxidase inhibitors (MAOi)?
- Monoamine Oxidase A (MAOAa)
or drugs that block - Monoamine oxidase A and B (MAOA and MAOb)
what are drugs that target just MAOb used for?
used for treating Parkinson’s disease.
give an example of only an MAOb inhibitor?
Selegiline
Give an example of an MAOa and MAOb inhibitor?
Iproniazid
Give an example of a MAOa inhibitor?
Clorgyline
Give an example of a TCA?
amitriptyline
Give an example of a SSRI?
citalopram
give an example of SNRI
duloxetine and venlafaxine
which of these are selective: SSRI, SNRI or TCA
SSRIs
what are the side effects of reuptake inhibitors
GI disturbance sexual dysfunction dry mouth sedation hypotension weight gain skin lashes anaphylaxiss
how do MAOIs bind: reversibly or irreversibly
ireeversibily
what effect do MAOIs have on blood pressure
they lower blood pressure by causing vasoconstriction, hence provoking hyperetensive crisis
what is the downside of taking other antidepressants alongside the depressant your already on
causes serotonin syndrome
what happens in serotonin syndrome
- blocks reuptake transporter and inhbiting MAO would increase 5HT release and there’ll be a build up of serotonin in the synaptic cleft
symptoms of serotonin syndrome
high temp agitation in creased reflexes tremor sweating dilated pupils diarrhoea delirium comvulsions death
what is the first lien antidepressant treatment
SSRIs
last line antidepressant treatment
MAOI
How long should you continue to treat after patient has recovered
6 month - 2 years after recovery
what symptoms are experienced in antidepressant discontinuation syndrome
dizziness, headache, nausea and lethargy
what is used to treat bipolar disorder
lithium
valproate
atypical antipschotics
fluoxetine
what causes bipolar disorder
dpomaine hyperactivity
- antagonists of the dpomaine receptor reduce mania
- reducing dopamine synthesis reduces mania
where are dopamine cell bodies contained
in the ventral tegmental area in the midbrain
how is dopamine released
by tonic and phasic release
how does lithium work
decreases DA release
decreases DA ( and 5HT) receptor signalling
inhbits seconf mess
what is the main use of lithium in Bipolar Disorder
acute mainia and prophylaxsis
what is the recommended plasma lithium levels
0.4-1mmol / L
side effects of lithium
dry mouth or metallic taste in mouth mild shaking or fine tremor of the hand (s) thirst passing mroe urine dizziness mild dizziness weight gain oedema
what does it mean by lithium being teratogenic
interferes with fetal development and causes birth defects
how does sodium valproate work
increases GABA transmission
when do we use valproate
when lithium isn’t tolerated
side effects of valproate
nausea vomiting sedation tremor hair loss weight gain pancreatitis
is valproate teratogenic
yes, causes fetal valproate syndrome, neural tube defects and intellectual impairment
