Anti-depressants

What the monoamine theory of depression?

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- Serotonin and Noradrenaline Reuptake Inhibition

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 prevent 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 prevent 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.

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