CPTP 3.3 - Antidepressents

Question 1

Name four mono-amines?

Answer 1

Dopamine
5-H-T (serotonin)
Norepinepherine
Histamine

Question 2

What is the mono-amine theory of depression?

Answer 2

Depression caused by a deficit in central mono-amine neurotransmission

Question 3

In 5-H-T (serotonin) biosynthesis what is the starting molecule?

Answer 3

Tryptophan (neutral amino acid)

Question 4

Describe 5-H-T (serotonin) biosynthesis?

Answer 4

Tryptophan converted into 5-H-T-P (via tryptophan hydroxylase)
5-H-T-P converted into 5-H-T (via amino acid decarboxylase)

Question 5

Name the molecule that transports 5-H-T into vesicles within the pre-synaptic neurone?

Answer 5

VMAT2

Question 6

Name the two pre-synaptic receptors that autoregulate and induce negative feedback?

Answer 6

5HT1A somatodendritic auto-receptors

5HT1B

Question 7

How are 5-H-T actions terminated?

Answer 7

Re-uptake into the pre-synaptic neurone via SERT

1. 5-H-T is repacked into vesicles by VMAT2
2. 5-H-T is metabolised by monoamine oxidase (MAO) - into 5H1AA metabolite

Question 8

How do Tri-cyclic antidepressants work?

Answer 8

Block the re-uptake of 5-H-T = increased duration and concentration at the synaptic cleft –> more therapeutic effects

Question 9

Name the TCA within the student formulary?

Answer 9

Amytriptyline

Question 10

Why do TCAs have bad side effect profiles?

Answer 10

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

Question 11

Name the SSRI within the student formulary and also name the SSRI with the largest selectivity?

Answer 11

Fluoxetine

Citralopram

Question 12

Name an SNRI?

Answer 12

Venlaxafine

Question 13

Name an NARI?

Answer 13

Reboxetine

Question 14

Name a Dopa re-uptake inhibitor?

Answer 14

Buproprion

Question 15

What are the two isoforms of monoamine oxidase?

Answer 15

MAO-A - breaks down 5HT and Nor-Epi

MAO-B - breaks down dopa

Question 16

What is meclopemide and what are its limitations?

Answer 16

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

Question 17

What is serotonin syndrome?

Answer 17

Blockade of re-uptake and metabolism is XS and this may lead to hyperthermia/hypertensive crisis/confusion

Question 18

Name the monoamine oxidase inhibitor within the student formulary?

Answer 18

Phenelzine

Question 19

Name an atypical antidepressant?

Answer 19

Mitazapine

Question 20

Where is 5HT mainly synthesised and projected from within the brain?

Answer 20

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

Question 21

Where is nor-Epi mainly synthesised and projected from within the brain?

Answer 21

Locus coreuleus - contains nor-Epi cell bodies