Pharmacology of Depression

Question 1

What is the mechanism of action of sertraline?

Answer 1

• Inhibition of serotonin reuptake; accumulation of serotonin
• which plays a role in regulation of mood, personality and wakefulness

Question 2

What is the drug target of sertraline?

Answer 2

serotonin transporter

Question 3

What are the main side effects of sertraline?

Answer 3

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

Question 4

What is the other minor effect of sertraline?

Answer 4

mild inhibition of the dopamine transporter

Question 5

What is the process of discontinuing sertraline?

Answer 5

gradually decreased over time

Question 6

What is the possible side effects of sertraline at high doses?

Answer 6

partial inhibition of CYP2D6

Question 7

What is the primary mechanism of action of citalopram?

Answer 7

Inhibition of serotonin reuptake; accumulation of serotonin

Question 8

What is the drug target of citalopram?

Answer 8

Serotonin transporter

Question 9

What are the main side effects of citalopram?

Answer 9

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

Question 10

What are the other minor effects of citalopram?

Answer 10

mild antagonism of muscarinic and histamine (H1) receptors)

Question 11

What is citalopram metabolised by?

Answer 11

CYP2C19

Question 12

What is the process of discontinuing citalopram?

Answer 12

gradually decreased over time

Question 13

What is the primary mechanism of action of Fluoxetine?

Answer 13

Inhibition of serotonin reuptake; accumulation of serotonin

Question 14

What is the drug target of Fluoxetine?

Answer 14

Serotonin transporter

Question 15

What are the main side effects of Fluoxetine?

Answer 15

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

Question 16

What are the other minor effects of Fluoxetine?

Answer 16

• Mild antagonism of 5HT2A and 5HT2C receptors

- Complete inhibition of CYP2D6 and significant inhibition of CYP2C19

Question 17

What drug contraindicates with Fluoxetine?

Answer 17

Warfarin

Question 18

What is the mechanism of action of Venlafaxine?

Answer 18

Inhibitor of serotonin reuptake, and a less potent inhibitor of norepinephrine reuptake
(noradrenalin - regulation of emotions and cognition)

Question 19

What is the drug target of Venlafaxine?

Answer 19

Serotonin and Noradrenalin transporter

Question 20

What are the main side effects of Venlafaxine?

Answer 20

• GI effects (nausea, diarrhoea)
• sexual dysfunction
• anxiety
• insomnia
• hypertension (at higher doses)
• prolonged QT interval

Question 21

What is the process of discontinuing Venlafaxine?

Answer 21

gradual decrease over time

Question 22

What is the primary mechanism of action of Mirtazapine?

Answer 22

• Antagonises central pre-synaptic alpha-2-adrenergic receptors (increased release of serotonin and norepinephrine)
• Antagonises central 5HT2 receptors, which leaves 5HT1 receptors unopposed causing anti-depressant effects.

Question 23

What are the drug targets of Mirtazapine?

Answer 23

• alpha-2 receptor

- 5-HT2 receptor

Question 24

What are the main side effects of Mirtazapine?

Answer 24

• weight gain

- sedation

Question 25

What are the less common side effects of Mirtazapine?

Answer 25

• Low probability of sexual dysfunction.

- May exacerbate REM sleep behaviour disorder

Question 26

What are the disadvantages of taking Mirtazapine?

Answer 26

• low selectivity

- highest affinity is to H1 receptors > sedation (not therapeutic objective)

Question 27

Why should you avoid taking erythromycin and citalopram simultaneously?

Answer 27

• both prolong the Q-T interval

Question 28

What, other than drugs can increase the Q-T interval?

Answer 28

• increasing age
• female
• CVD
• certain metabolic disorders (hypokalaemia)

Question 29

What causes the plateau when studying the effectiveness of SSRIs?

Answer 29

there are only a limited amount of sodium reuptake sites, therefore they become fully blocked and maxed out, so an increased dose has no increased therapeutic effect.

Question 30

What are the main drug targets of Venlafaxine?

Answer 30

• serotonin transporter

- noradrenaline transporter

Question 31

What are the main drug targets of Mirtazapine?

Answer 31

• alpha 2 receptor
• H1 receptor
• 5-HT2 receptor
• 5-HT3 receptor

Question 32

Why is there a washout period when changing anti-depressants?

Answer 32

risk of:

• drug-drug interactions
• serotonin syndrome
• withdrawal symptoms
• relapse

Question 33

What is the impact of Mirtazapine on sleep?

Answer 33

• suppresses REM sleep

- increases sleep continuity and duration due to: anti-histaminergic effects

Question 34

Why does blood pressure need to be measured when administering Venlafaxine?

Answer 34

• adrenergic effects of venlafaxine appear with doses administrated more than 150 mg/day
• apparent increase in blood pressure and increased heart rate are observed when the daily dose exceeds 300 mg

Question 35

What receptor does Mirtazapine have the highest affinity for, and what is the effect?

Answer 35

Histamine (H1) receptor

- sedation

Question 36

What is the effect of Mirtazapine at low doses?

Answer 36

• higher affinity for histamine receptors over serotonergic receptors
• preferentially blocks the histamine receptor, therefore increased sleep and sedation

Question 37

What happens at high doses of Mirtazapine?

Answer 37

antihistamine effect is offset by increased noradrenergic transmission, reducing the sedating effect.