Anti-depressants

What the monoamine theory of depression?

The pathophysiological basis of depression is **depletion** in the levels of **serotonin**, **noradrenaline**, and/or **dopamine** in the central nervous system.

What are the 3 modes of treatment of depression?

Enhance monoaminergic activity in central synapses:

1\.Inhibit monoamine reuptake

2\.Inhibit enzymatic degradation

3\.Block presynaptic autoreceptors

Types of antidepressants available?

TCAs - Tricyclic antidepressants

SNRIs- **S**erotonin and **N**oradrenaline **R**euptake **I**nhibition

SSRIs- selective serotonin reuptake inhibitors

MAOI- monoamine oxidase inhibitors

Benzodiazepines

NaSSA/ alpha 2 antagonist

Example of a TCA?

==Clomipramine==

Amitriptyline

What are TCAs given for?

* Depressive disorder
* Phobic or obsessional states

What is the MOA of TCAs?

serotonin and/or noradrenaline reuptake inhibition

What are the ADR of TCAs?

* overdose → block Na+ channels → cardiac arrest
* ==**Weight gain**==
* ==**Sexual dysfunction**==
* ==**Depersonalisation**==

Example of a SSRI?

Citalopram

What are SSRIs given for?

* Depressive disorder
* Panic + anxiety

What is the MOA of SSRIs?

Blocks SERT (serotonin re-uptake tranposters)

Serotonin will remain in the synaptic cleft for longer

Leads to repeated activation of 5-HT receptors (post)

What are the ADR of SSRIs?

==QT interval prolongation==

GI disturbances

==sexual dysfunction==

==sleep disorders==

What are the contraindications of SSRIs?

If poorly controlled epileptic or pre-existing long QT interval, or manic

Example of a SNRIs?

Reboxetine

What are SNRIs given for?

major depression

What is the MOA of SNRIs?

Mostly blocks noradrenaline but also some blocking of serotonin

What are the ADR of SNRIs?

==Palpitations==

==Sexual dysfunction==

==Decreased appetite==

Nausea

dry mouth

dizziness

excessive sweating

 

 

Example of a MOAs?

Moclobemide

What are MOAs given for?

Depressive disorder

Social anxiety

What is an example of MAO-A I?

Moclobemide

What is the MOA of MAO-A I?

Inhibit **monoamine oxidase A**, preventing breakdown of **5HT** and **NA**

A **selective** (reversible) **monoamine oxidase inhibitor** which can p**revent MAO-mediated clearance of serotonin, noradrenaline and dopamine** from synaptic clefts

What are the ADR of MAO-A I?

Confused states (agitation), dizziness, dry mouth, **CHEESE CRISIS**

What is the hypertensive cheese crisis?

What is a contraindication of MAO-A I?

**If thyrotoxicosis, if bipolar**

What is an example of f MAO-B I?

Selegiline

A type of Parkinson’s drug

What is the MOA of MAO-B I?

Inhibit **monoamine oxidase B**, preventing breakdown of **dopamine**

A **selective** (reversible) **monoamine oxidase inhibitor** which can p**revent MAO-mediated clearance of serotonin, noradrenaline and dopamine** from synaptic clefts

What are the ADR of MAO-B I?

Confused states (agitation), dizziness, dry mouth

General MAOIs ADRs?

Irritability

Sleep disorder

Nausea + vomiting

Example of a NaSSA/ alpha 2 antagonist?

Mirtazapine

What is the MOA of NaSSAs?

NaSSAs **bind** to and **inhibit both noradrenaline a2-autoreceptors** and **noradrenaline a2-heteroeceptors.**

This action **prevents** the **negative feedback** effect of synaptic noradrenaline on 5-HT and noradrenaline neurotransmission, **sustaining neurotransmission**.

NaSSAs also **block 5-HT2 and 5-HT3** receptors on the post-synaptic membrane, which causes **enhanced 5-HT1 mediated neurotransmission**.

What are the ADR of NaSSA?

**5HT3 antagonist:** increased **appetite**

**H1** (histamine) **antagonist**: **drowsiness**, ***weight*** gain

What are the serotonin receptors?

5-HT1: Gi/Go-protein coupled

5-HT3: Ligand-gated Na+ and K+ channels

5-HT2: Gq/G11-protein coupled

5-HT4: Gs-protein coupled

What is serotonin syndrome?

Increased 5HT activity in the CNS

Caused by drug overdose or **interaction between two 5HT-enhancing drugs** (more common)

What can cause serotonin syndrome?

It's usually triggered when you take an SSRI or SNRI in combination with another medicine (or substance) that also raises serotonin levels, such as another antidepressant or St John's wort.

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Avoid sympathomimetic and dopaminergic drugs (monoamine overload)

Symptoms of serotonin syndrome?

* **Mental state**: anxiety, agitation, disorientation
* **Autonomic (SNS) symptoms**: diaphoresis, raised HR/RR/BP/temp, vomiting/ diarrhoea/ increased bowel sounds; dilated pupils
* **Neuromuscular**: tremor, rigidity, hyperreflexia, bilateral Babinksi