Pharmacology of Depression Flashcards
What is the mechanism of action of sertraline?
- Inhibition of serotonin reuptake; accumulation of serotonin
- which plays a role in regulation of mood, personality and wakefulness
What is the drug target of sertraline?
serotonin transporter
What are the main side effects of sertraline?
- GI effects (nausea, diarrhoea)
- sexual dysfunction
- anxiety
- insomnia
What is the other minor effect of sertraline?
mild inhibition of the dopamine transporter
What is the process of discontinuing sertraline?
gradually decreased over time
What is the possible side effects of sertraline at high doses?
partial inhibition of CYP2D6
What is the primary mechanism of action of citalopram?
Inhibition of serotonin reuptake; accumulation of serotonin
What is the drug target of citalopram?
Serotonin transporter
What are the main side effects of citalopram?
- GI effects (nausea, diarrhoea)
- sexual dysfunction
- anxiety
- insomnia
What are the other minor effects of citalopram?
mild antagonism of muscarinic and histamine (H1) receptors)
What is citalopram metabolised by?
CYP2C19
What is the process of discontinuing citalopram?
gradually decreased over time
What is the primary mechanism of action of Fluoxetine?
Inhibition of serotonin reuptake; accumulation of serotonin
What is the drug target of Fluoxetine?
Serotonin transporter
What are the main side effects of Fluoxetine?
- GI effects (nausea, diarrhoea)
- sexual dysfunction
- anxiety
- insomnia
What are the other minor effects of Fluoxetine?
- Mild antagonism of 5HT2A and 5HT2C receptors
- Complete inhibition of CYP2D6 and significant inhibition of CYP2C19
What drug contraindicates with Fluoxetine?
Warfarin
What is the mechanism of action of Venlafaxine?
Inhibitor of serotonin reuptake, and a less potent inhibitor of norepinephrine reuptake
(noradrenalin - regulation of emotions and cognition)
What is the drug target of Venlafaxine?
Serotonin and Noradrenalin transporter
What are the main side effects of Venlafaxine?
- GI effects (nausea, diarrhoea)
- sexual dysfunction
- anxiety
- insomnia
- hypertension (at higher doses)
- prolonged QT interval
What is the process of discontinuing Venlafaxine?
gradual decrease over time
What is the primary mechanism of action of Mirtazapine?
- 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.
What are the drug targets of Mirtazapine?
- alpha-2 receptor
- 5-HT2 receptor
What are the main side effects of Mirtazapine?
- weight gain
- sedation
What are the less common side effects of Mirtazapine?
- Low probability of sexual dysfunction.
- May exacerbate REM sleep behaviour disorder
What are the disadvantages of taking Mirtazapine?
- low selectivity
- highest affinity is to H1 receptors > sedation (not therapeutic objective)
Why should you avoid taking erythromycin and citalopram simultaneously?
- both prolong the Q-T interval
What, other than drugs can increase the Q-T interval?
- increasing age
- female
- CVD
- certain metabolic disorders (hypokalaemia)
What causes the plateau when studying the effectiveness of SSRIs?
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.
What are the main drug targets of Venlafaxine?
- serotonin transporter
- noradrenaline transporter
What are the main drug targets of Mirtazapine?
- alpha 2 receptor
- H1 receptor
- 5-HT2 receptor
- 5-HT3 receptor
Why is there a washout period when changing anti-depressants?
risk of:
- drug-drug interactions
- serotonin syndrome
- withdrawal symptoms
- relapse
What is the impact of Mirtazapine on sleep?
- suppresses REM sleep
- increases sleep continuity and duration due to: anti-histaminergic effects
Why does blood pressure need to be measured when administering Venlafaxine?
- 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
What receptor does Mirtazapine have the highest affinity for, and what is the effect?
Histamine (H1) receptor
- sedation
What is the effect of Mirtazapine at low doses?
- higher affinity for histamine receptors over serotonergic receptors
- preferentially blocks the histamine receptor, therefore increased sleep and sedation
What happens at high doses of Mirtazapine?
antihistamine effect is offset by increased noradrenergic transmission, reducing the sedating effect.
