Pharmacology of Depression

Question 1

What is the mechanism of action of sertraline?

Answer 1

• Inhibition of serotonin reuptake causing accumulation of serotonin
• sertraline 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 are the other minor effects of sertraline?

Answer 4

• mild inhibition of the dopamine transporter
• partial inhibiton of enzyme involved in metabolising drugs (CYP2D6) at high dosages

Question 5

What is the process of discontinuing sertraline?

Answer 5

gradually decreased over time

Question 6

What is the primary mechanism of action of citalopram?

Answer 6

Inhibition of serotonin reuptake causing accumulation of serotonin

Question 7

What is the drug target of citalopram?

Answer 7

Serotonin transporter

Question 8

What are the main side effects of citalopram?

Answer 8

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

Question 9

What are the other minor effects of citalopram?

Answer 9

mild antagonism of muscarinic and histamine (H1) receptors)

Question 10

What is citalopram metabolised by?

Answer 10

CYP2C19

Question 11

What is the process of discontinuing citalopram?

Answer 11

gradually decreased over time

Question 12

What is the primary mechanism of action of Fluoxetine?

Answer 12

Inhibition of serotonin reuptake; accumulation of serotonin

Question 13

What is the drug target of Fluoxetine?

Answer 13

Serotonin transporter

Question 14

What are the main side effects of Fluoxetine?

Answer 14

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

Question 15

What are the other minor effects of Fluoxetine?

Answer 15

• Mild antagonism of serotonin receptors (5HT2A and 5HT2C)
• Complete inhibition of enzymes which metabolise drugs (CYP2D6 and significant inhibition of CYP2C19)

Question 16

What drug contraindicates with Fluoxetine?

Answer 16

Warfarin

Question 17

What is the mechanism of action of Venlafaxine?

Answer 17

• Inhibitor of serotonin reuptake
• less potent inhibitor of norepinephrine reuptake
  (noradrenaline regulates emotions and cognition)

Question 18

What is the drug target of Venlafaxine?

Answer 18

Serotonin and Noradrenalin transporter

Question 19

What are the main side effects of Venlafaxine?

Answer 19

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

Question 20

What is the process of discontinuing Venlafaxine?

Answer 20

gradual decrease over time

Question 21

What is the primary mechanism of action of Mirtazapine?

Answer 21

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

Question 22

What are the drug targets of Mirtazapine?

Answer 22

• alpha-2 receptor
• 5-HT2 receptor

Question 23

What are the main side effects of Mirtazapine?

Answer 23

• weight gain
• sedation

Question 24

What are the less common side effects of Mirtazapine?

Answer 24

May exacerbate REM sleep behaviour disorder

Question 25

What is an advantage of taking mirtazapine?

Answer 25

Low probability of sexual dysfunction

Question 26

What are the disadvantages of taking Mirtazapine?

Answer 26

- low selectivity - highest affinity is to H1 receptors causing 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 serotonin reuptake sites on the presynaptic neurone, therefore they become fully blocked and maxed out, so an increased dose has no increased therapeutic effect.

Question 30

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

Answer 30

risk of: - drug-drug interactions - serotonin syndrome - withdrawal symptoms - relapse

Question 31

What is the impact of Mirtazapine on sleep?

Answer 31

- suppresses REM sleep - increases sleep continuity and duration due to anti-histaminergic effects

Question 32

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

Answer 32

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

Question 33

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

Answer 33

- Histamine (H1) receptor - sedation

Question 34

What happens at high doses of Mirtazapine?

Answer 34

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