Depression Flashcards
Describe the mechanism of action of sertraline (SSRIs)
- Inhibition of serotonin re-uptake results in an accumulation of serotonin.
- mild inhibition of dopamine transporter
What is the target of sertraline?
Serotonin reuptake transporter in pre-synpatic neurones
What are the main side effects of sertraline?
- GI effects (nausea, diarrhoea)
- sexual dysfunction
- anxiety
- insomnia
Why do anti-depressants need to gradually be decreased on discontinuation?
- to reduce withdrawal symptoms
- to prevent relapse of depression
- to reduce risk of drug interactions (liver enzyme metabolism is affected by many drugs)
- to prevent serotonin syndrome
What is serotonin syndrome?
Too much serotonin due to multiple anti-depressants . It can cause….
- confusion
- tachycardia
- loss of muscle co-ordination
What is the mechanism of action for Citalopram (SSRI)?
Inhibition of serotonin reuptake results in an accumulation of serotonin
What is Citalopram’s target?
Serotonin transporter on presynaptic neurones
What are some of the side effects of using Citalopram?
- GI effects (nausea, diarrhoea)
- sexual dysfunction
- anxiety
- insomnia
What other receptors are affected by Citalopram and how are they affected?
- muscarinic receptors
- histamine (H1) receptors
MILD ANTAGONIST (inhibition of function)
What is the Fluoxetine’s mechanism of action (SSRI)?
Inhibition of serotonin reuptake results in an accumulation of serotonin.
What is Fluoxetine’s target?
Serotonin transporter on presynaptic neurones
What are some of the side effects of using Fluoxetine?
- GI effects (nausea, diarrhoea)
- sexual dysfunction
- anxiety
- insomnia
What other receptors are affected by Fluoxetine and how are they affected?
5-HT2A receptors
5-HT2C receptors
MILD ANTAGONIST (inhibition of function)
What enzymes are affected by Fluoxetine and how are they affected?
- Complete inhibition of CYP2D6
- Significant inhibition of CYP2C19
BOTH ARE P450 enzymes.
Describe the mechanism of action of Venlafaxine (SNRI).
Serotonin + norepinephrine re-uptake inhibitor
more so serotonin
What does Venlafaxine target?
- Serotonin re-uptake transporters
- Noradrenaline re-uptake transporters
Both of these transporters are on the pre-synaptic neurones.
What are the side effects of using Venlafaxine?
- GI effects (nausea, diarrhoea)
- sexual dysfunction
- anxiety
- insomnia
- hypertension (at higher doses)
What are the contra-indications of Venlafaxine?
Uncontrolled hypertension
This is because Venlafaxine increases adrenaline, which mediates (increases) BP and HR.
What is the mechanism of action of Mirtazapine?
- Antagonises (inhibits) central presynaptic alpha-2-adrenergic receptors, which causes an increased release of serotonin and norepinephrine.
- Antagonises central 5-HT2 receptors, which leaves 5-HT1 receptors (serotonin binds to these receptors) unopposed, causing anti-depressant effects.
- Antagonises H1 receptors which causes sedation + increased duration of sleep
What receptors does Mirtazapine target?
- a-2 adrenergic receptors
- 5-HT2 receptors
- 5-HT3 receptors
- H1 receptors
What are some of the side effects of Mirtazapine?
- Weight gain
- Sedation
- may exacerbate REM sleep behaviours
- sexual dysfunction is RARE
Mirtazapine has low selectivity (but it’s still effective). Describe its affinity to different target receptors at low doses.
HIGHEST AFFINITY 1. H1 receptor (sedation) 2. Alpha-2 receptor (Anti-depressant) 3. 5-HT2 receptor (Anti-depressant) 4. 5-HT3 receptor (anti-emetic) LOWEST AFFINITY
What happens to the affinity of Mirtazapine to its receptors at higher doses?
Antihistamine effect is offset by increased noradrenergic transmission
(anti-depressant effect > sedative effect)
What is the role of serotonin in the CNS?
Involved in the regulation of mood, personality, and wakefulness.
What is the role of norepinephrine in the CNS?
Involved in the regulation of emotions and cognition.
