Pharmacology of depression

Question 1

what are drug options for depression

Answer 1

sertraline, citalopram, fluoxetine, venlafaxine, mirtazapine

Question 2

primary mechanism of sertraline

Answer 2

Inhibition of serotonin reuptake results in an accumulation of serotonin. Serotonin in the central nervous system plays a role in the regulation of mood, personality, and wakefulness.

Question 3

drug target for sertraline

Answer 3

serotonin transporter

Question 4

side effects for sertraline

Answer 4

GI effects (nausea, diarrhoea), sexual dysfunction, anxiety, insomnia

Question 5

what are else does sertraline inhibit

Answer 5

mild inhibition of dopamine transporter
partial inhibition of CYP2D6 at high doses (150mg)

Question 6

if discontinuing sertraline, venlafaxine or citalopram what must you do

Answer 6

dose must be decreased gradually

Question 6

primary mechanism of action of citalopram

Answer 6

Inhibition of serotonin reuptake results in an accumulation of serotonin. Serotonin in the central nervous system plays a role in the regulation of mood, personality, and wakefulness

Question 7

drug target for citalopram

Answer 7

serotonin transporter

Question 8

side effects of citalopram

Answer 8

GI effects (nausea, diarrhoea), sexual dysfunction, anxiety, insomnia

Question 9

citalopram leads to mild antagonism of what

Answer 9

muscarinic and histamine (H1) receptors

Question 10

what is citalopram metabolised by

Answer 10

CYP2C19

Question 11

primary mechanism of fluoxetine

Answer 11

Inhibition of serotonin reuptake results in an accumulation of serotonin. Serotonin in the central nervous system plays a role in the regulation of mood, personality, and wakefulness.

Question 12

drug target of fluoxetine

Answer 12

serotonin transporter

Question 13

side effects of fluoxetine

Answer 13

GI effects (nausea, diarrhoea), sexual dysfunction, anxiety, insomnia

Question 14

what else does fluoxetine act on

Answer 14

Mild antagonism of 5HT2A and 5HT2C receptors

Complete inhibition of CYP2D6 and significant inhibition of CYP2C19 (caution with warfarin)

Question 15

primary mechanism of action of venlafaxine

Answer 15

Venlafaxine is a more potent inhibitor of serotonin reuptake than norepinephrine reuptake.
Noradrenaline in the central nervous system is implicated in the regulation of emotions and cognition.

Question 16

drug target of venlafaxine

Answer 16

serotonin transporter
noradrenaline transporter

Question 17

side effects of venlafaxine

Answer 17

GI effects (nausea, diarrhoea), sexual dysfunction, anxiety, insomnia, hypertension (at higher doses)

Question 18

primary mechanism of action of mirtazapine

Answer 18

Antagonises central presynaptic alpha-2-adrenergic receptors, which causes an increased release of serotonin and norepinephrine.
Antagonises central 5HT2 receptors, which leaves 5HT1 receptors unopposed causing anti-depressant effects.

Question 19

drug target for mirtazapine

Answer 19

Alpha-2 receptor

5-HT2 receptor

Question 20

side effects of mirtazapine

Answer 20

weight gain, sedation
Low probability of sexual dysfunction. May exacerbate REM sleep behaviour disorder

Question 21

what questionnaire can be used to screen for depression

Answer 21

patient health questionnaire 9 (PHQ-9)
the higher the result the more severe the depression

Question 22

3 most commonly prescribed SSRIs are

Answer 22

sertraline
citalopram
fluoxetine

Question 23

why should you avoid use of erythromycin and citalopram together

Answer 23

they both prolong QT interval and it is recommended not to use 2 or more drugs that do this

Question 24

other than drugs what else can predispose to QT prolongation

Answer 24

increasing age, female sex, cardiac disease and some metabolic disturbances (notable hypokalaemia)

Question 25

how severe is the interaction between erythromycin and citalopram

Answer 25

severe

Question 26

how are reduction in depression rates affected as SSRI dose goes up

Answer 26

initially there is an increased reduction in depression and then as dose increases further the reduction in depression decreases

Question 27

how are dropouts due to adverse affects affected by increased SSRI doses

Answer 27

as you increase the dose you increase the dropouts due to adverse effects

Question 28

If we assume that the anti-depressant effects of SSRIs are solely due to their action at the serotonin transporter, how do we explain the plateau in the therapeutic effect?

Answer 28

after a certain dose the serotonin reuptake transporter will be fully blocked and the serotonin in the synapse is maxed out, this means that further dose increase will have no extra effect

Question 29

what is there a risk of when switching anti depressants

Answer 29

drug interaction, serotonin syndrome, withdrawal symptoms, relapse of depression

Question 30

when are the adrenergic effects of venlafaxine observed and what are these

Answer 30

appear with doses more than 150mg a day
apparent increase in BP and HR observed when dose exceeds 300mg

Question 31

what is mirtazipine’s effects on sleep and why

Answer 31

Mirtazapine modestly suppressREMsleep whilst still having a beneficial impact on sleep continuity and duration due to its anti-histaminergic effects

Question 32

order the receptors on which mirtazipine acts on in order of affinity

Answer 32

highest affinity - histamine H1 receptor (with sedative effect) alpha-2 receptor (antidepressant effect), 5HT2 receptor (antidepressant effect), 5HT3 receptor (anti emetic effect)

Question 33

how is the action of mirtazipine different at differing doses

Answer 33

At low doses, mirtazapine preferentially blocks the histamine receptor, since at lower plasma concentrations it has a higher affinity to histamine receptors than to serotonergic receptors. Consequently, there is increased duration of sleep at low plasma concentrations and increased sedation at low doses of mirtazapine. At higher doses, the antihistamine activity is offset by increased noradrenergic transmission, which reduces its sedating effect