pharmacology of depression Flashcards
SSRI primary mechanism of action
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.
SSRI primary target
serotonin transporters
Main side effects of SSRIs
GI effects (nausea, diarrhoea), sexual dysfunction, anxiety, insomnia
What does sertraline cause mild inhibition of
dopamine transporter
How must SSRIs be discontinued
gradually
What does sertaline partially inhibit at high doses
Partial inhibition of CYP2D6 at high doses (150 mg).
What does citalopram mildly antagonise
muscarinic and histamine (H1) receptors
Citalopram metabolised by
CYP2C19.
fluoxetine has complete inhibition of what
CYP2D6
fluoxetine has partial inhibition of what
CYP2C19
What other drug should fluoxetine be used cautiously with
warfarin
what type of anti depressant is venlaflaxine
SNRI
Main drug targets of venlaflaxine
serotonin transporter
noradrenaline transporter
Primary mechanism of venlaflaxine
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.
How must venlaflaxine be discontinued
gradually
Side effects of venlaflaxine
GI effects (nausea, diarrhoea), sexual dysfunction, anxiety, insomnia, hypertension (at higher doses)
Mirtazapine mechanism of action
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.
Mirtazapine targets
Alpha-2 receptor
5-HT2 receptor
Side effects of mirtazapine
Low probability of sexual dysfunction. May exacerbate REM sleep behaviour disorder
Weight gain, sedation
Screening tool GPs can use for depression
Patient Health Questionnaire 9
Why should citalopram and erythromycin not be prescribed together
both increase QT interval
Why does SSRI effectiveness plateau eventually
SSRIs block serotonin reuptake but at 1 point all the available serotonoin reuptake transporters are blocked so there’s no point increasing dose
When do the adrenergic effects of venlaflaxine occur
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
Describe mirtazapine drug targets from highest to lowest affinity
Histamine (H1) receptor - sedation
alpha 2 receptor - anti depressant
5HT2 receptor - antagonism
5HT3 receptor - anti emetic
Why is mirtazapine’s sedative effects decreased at high doses
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
Caution when switching anti depressants
Caution is required when switching from one antidepressant to another due to the risk of drug interactions, serotonin syndrome, withdrawal symptoms, or relapse.
Washout required before starting new drug
