CPTP 3.3 - Antidepressents Flashcards
Name four mono-amines?
Dopamine
5-H-T (serotonin)
Norepinepherine
Histamine
What is the mono-amine theory of depression?
Depression caused by a deficit in central mono-amine neurotransmission
In 5-H-T (serotonin) biosynthesis what is the starting molecule?
Tryptophan (neutral amino acid)
Describe 5-H-T (serotonin) biosynthesis?
Tryptophan converted into 5-H-T-P (via tryptophan hydroxylase)
5-H-T-P converted into 5-H-T (via amino acid decarboxylase)
Name the molecule that transports 5-H-T into vesicles within the pre-synaptic neurone?
VMAT2
Name the two pre-synaptic receptors that autoregulate and induce negative feedback?
5HT1A somatodendritic auto-receptors
5HT1B
How are 5-H-T actions terminated?
Re-uptake into the pre-synaptic neurone via SERT
- 5-H-T is repacked into vesicles by VMAT2
- 5-H-T is metabolised by monoamine oxidase (MAO) - into 5H1AA metabolite
How do Tri-cyclic antidepressants work?
Block the re-uptake of 5-H-T = increased duration and concentration at the synaptic cleft –> more therapeutic effects
Name the TCA within the student formulary?
Amytriptyline
Why do TCAs have bad side effect profiles?
They hive affinity for lots of post-synaptic receptors:
M1 receptor ANTAGONISM - dry mouth/blurred vision/constipation/urinary retention
H1 receptor ANTAGONISM - sedation/weight gain
a1 adrenoreceptor ANTAGONISM - postural hypotension
Name the SSRI within the student formulary and also name the SSRI with the largest selectivity?
Fluoxetine
Citralopram
Name an SNRI?
Venlaxafine
Name an NARI?
Reboxetine
Name a Dopa re-uptake inhibitor?
Buproprion
What are the two isoforms of monoamine oxidase?
MAO-A - breaks down 5HT and Nor-Epi
MAO-B - breaks down dopa
What is meclopemide and what are its limitations?
Selective MAO-A inhibitor (MAOI)
Cheese-effect = In gut there are lots of MAO-A which break down dietary amines, blockage will therefore lead to lost of these dietary amines being absorbed into the blood and they can enter the PNS and displace endogenous amines from the sympathetic nervous syster = hypertensive crisis
What is serotonin syndrome?
Blockade of re-uptake and metabolism is XS and this may lead to hyperthermia/hypertensive crisis/confusion
Name the monoamine oxidase inhibitor within the student formulary?
Phenelzine
Name an atypical antidepressant?
Mitazapine
Where is 5HT mainly synthesised and projected from within the brain?
Raphe nucleus - contains 5HT cell bodies
SSRI’s block 5HTT (transporter) in the DORSAL raphe nucleus = Increased 5HT = Increased 5HT1A auto-receptor autro-regulation (needs to be desensitised) = 2 weeks
Where is nor-Epi mainly synthesised and projected from within the brain?
Locus coreuleus - contains nor-Epi cell bodies
