L17 Antidepressants

Question 1

emotional symptoms

Answer 1

low mood, negative thought; loss of motivation, indecisiveness; low self-esteem

Question 2

imipramine

Answer 2

block noradrenaline and serotonin uptake → improve mood in depressed schizophrenics

Question 3

Monoamine theory of depression

Answer 3

a functional deficit of noradrenaline and serotonin in certain brain regions
↑ noradrenaline and ↑ 5-HT are equally effective as antidepressants (individual variation)

Question 4

Monoamine theory of depression issue/limits

Answer 4

• pharmaco weeks not hours or minutes

Question 5

BDNF (brain-derived neurotrophic factor)

Answer 5

• CNS development and neuronal plasticity

Question 6

Neuroplasticity BDNF path to CREB

Answer 6

Prepro-bdnf
↓
Pro-bdnf
↓
Mature BDNF
↓Bind to TrkB (tropomypsin rec kinase B)
CREB (cAMP response element
↓
Gene expression

Question 7

Neuroplasticity of depression involves decrease

Answer 7

BDNF levels in hippocampus/prefrontal cortex

Question 8

Activity of CREB

Answer 8

transcriptional activity of CREB
↓
Promotes BDNF expression
↓
Causes neurogenesis in the prefrontal cortex and hippocampus

Question 9

What happens to CREB activity when there is increased stress an cortisol levels

Answer 9

Suppresses he transcription activity of CREB therefore imparing BDNF expression and neurogenesis

Question 10

What does cortisol and stress do to the prefrontal cortex and hippocampus

Answer 10

Can cause apoptosis in neurons

Question 11

selective serotonin reuptake inhibitor (SSRIs)

Answer 11

fluoxetine

Question 12

tricyclic antidepressants (TCAs)

Answer 12

imipramine

Question 13

monoamine oxidase inhibitors (MAOIs)

Answer 13

• phenelzine
• moclobemide

Question 14

Which drug has a fast onset of antidepressant effects

Answer 14

Ketamine

Question 15

fluoxetine simple

Answer 15

• most prescribed antidepressants; first-line treatment
• binds to serotonin transporter and blocks the reuptake of serotonin,

Question 16

Blocking 5-HT reuptake by drugs (fluoxetine) causes

Answer 16

Elevated synaptic [5HT] but decreased release

Question 17

somatodendritic 5-HT1A receptor desensitisation + ↑ synaptic [5-HT] postsynaptic

Answer 17

5-HT1 receptor → antidepressant effects

Question 17

Why does antidepressants take so long (Inhibit serotonin uptake)

Answer 17

Because desensitisation of receptors (5-HTa1) takes long

Question 18

What is fluoxetine metabolised by

Answer 18

CYP2D6

Question 19

What enzyme does fluoxetine inhibit

Answer 19

CYP2D6

Question 20

What is serotonin syndrome

Answer 20

If fluoxetine is taked with another increaser of serotonin but via a different method it will increase via both methods

Question 21

Fluoxetine Side effects

Answer 21

• agitation and insomnia (5 HT2 receptor)
• nausea (5-HT3 receptor)
• sexual dysfunction

Question 22

Better adverse effect profile for Fluoxetine

Answer 22

lack of affinity for muscarinic acetylcholine receptors and histamine H1 receptors

Question 23

Mirtazapine on receptor

Answer 23

a2-adrenoceptors antagonist

Question 24

Mirtazapine as an antagonist

Answer 24

* inhibit alpha-2 adrenoceptors (central presynaptic) and enhance NA and 5-HT release * Antagonist to 5-HT2 and 5-HT3 receptors

Question 25

Mirtazapine side effects

Answer 25

* Histamine H1 antagonism - sedation * Increase appetite and weight gain * headaches

Question 26

Good alternative if adverse effects of SSRIs are problematic

Answer 26

Mirtazapine

Question 27

Tricyclic antidepressants function

Answer 27

bind serotonin and noradrenaline transporters and inhibit reuptake of 5-HT and noradrenaline → synaptic [5-HT] and [noradrenaline] ↑

Question 28

Name 1 Tricyclic antidepressants

Answer 28

imipramine

Question 29

imipramine half life and antagonism

Answer 29

* long half-life - repeated dosing ↑ risk of adverse effects * muscarinic acetylcholine receptor antagonist - dry mouth, blurred vision * histamine H1 receptor antagonist - sedation * not to be combined with monoamine oxidase inhibitor

Question 30

imipramine metabolite from CYP2C19

Answer 30

desipramine (active) both parent and this can be further metabolised by CYP2D6

Question 31

Monoamine oxidase inhibitor drugs

Answer 31

* Phenelzine * Moclobemide

Question 32

Monoamine oxidase inhibitors

Answer 32

inhibit monoamine oxidase type A and/or type B ⟶ cytoplasmic concentrations of monoamines ↑ ⟶ rate of spontaneous leakage of monoamines ↑

Question 33

irreversible MAO-A and MAO-B inhibitor non-selective, long acting

Answer 33

phenelzine* -

Question 34

reversible MAO-A inhibitor Short acting

Answer 34

moclobemide

Question 35

Monoamine oxidase inhibitors effects

Answer 35

* atropine-like effects - dry mouth, blurred vision * other drugs that ↑ serotonin levels * ‘cheese reaction’ (drug-food interaction)

Question 36

MAO inhibition + tyramine ingestine

Answer 36

Hypertension and headache by MAO would have metabolised Tyramine so it doesn't go into circulation but MAO inhibited

Question 37

Ketamine

Answer 37

a non-competitive NMDA receptor antagonist

Question 38

Ketamine dose

Answer 38

one single subanaesthetic dose - rapid (within hours) and sustained (~24 hours), including in individuals with treatment-resistant depression * BDNF release

Question 39

Ketamine spray

Answer 39

nasal spray of Spravato (esketamine, the S-enantiomer) in conjunction with an oral antidepressant for treatment-resistant depression

Question 40

Ketamine as a rapid acting antidepressant

Answer 40

– proposed mechanisms * NMDA receptor inhibition * on GABAergic interneurons (a) * extrasynaptic (b) * synaptic (c) – BDNF translation or release ↑