Pharmacology of antidepressant drugs and mood stabilisers

Question 1

Give the 8 classes of antidepressant?

and 2 examples of each

Answer 1

MAOI-monoamine oxidase inhibitors
(Phenelzine, Isocarboxazid)

RIMA-reversible monoamine oxidase inhibitor
(Moclobemide)

TCA- tricyclic antidepressant
(Amitriptyline, Clomipramine)

SSRI- selective serotonin reuptake inhibitor
(Fluoxetine, Paroxetine, Citalopram)

SNRI-Serotonin–norepinephrine reuptake inhibitor
(Venlafaxine, Duloxetine)

NARI- noradrenaline reuptake inhibitor
(Reboxetine)

NassA- Noradrenergic and specific serotonergic antidepressant
(Mirtazapine)

Other
(Trazodone, Nefazodone)

Question 2

SSRIs

• give 3 examples
• used in what?
• mechanism of action?
• why is the effect delayed?
• adverse effects?

Answer 2

-Fluoxetine, Paroxetine, Citalopram

-depression
panic disorder
social anxiety 
PTSD
OCD
Chronic pain
eating disorders
stroke recovery
prem ejaculation 

-inhibit the re-uptake of 5-HT and so increase synaptic 5-HT
this stimulates the 5-HT receptors to inhibit firing
the effect takes 2-3 weeks to improve mood
chronic occupancy of the 5-HT receptor causes it to desensitise and there is a return of normal firing

-5-HT1a receptors are auto receptors throughout the CNS, they are inhibitory and so more receptors means greater inhibition

-sexual dysfunction
GI- nausea, dyspepsia, constipation etc
short term anxiety
in young people inc risk of self harm in a few weeks

Question 3

Tricyclic antidepressants

• give 2 examples
• used in what?
• mechanism of action?
• adverse effects?

Answer 3

• Amitriptyline, Clomipramine
• depression & neuropathic pain
• serotonin-norepinephrine reuptake inhibitors (SNRIs) by blocking the serotonin transporter (SERT) and the norepinephrine transporter (NET), so get an elevation of the synaptic concentrations

-drowsiness
dry mouth
blurred vision
constipation
urinary retention
effect on cardiac function and postural hypotension

Question 4

Monoamine oxidase inhibitors

• give 2 examples
• mechanism of action?
• adverse effects?
• management of ^?
• restrictions?

Answer 4

-phenelzine, isocarboxazid

-inhibit monoamine oxidase A&B,
(MAO A metabolises NA, 5-HT and tyramine, MAO B metabolises DA, tyramine and phenylethylamine)
so get increased storage and availability for release of 5-HT and NA

-Tyramine is normally inactivated in the gut by MAO do hypertensive crisis can occur with tyramine containing food and some drugs e.g. cheese, yogurt, yeast extracts
drugs- sympathomimetics
symptoms: flushing, headache, inc BP

• alpha blockade e.g. phentolamine
• Dietary & drug interactions

Question 5

what effects do antidepressants have on dopamine?

Answer 5

some give extrapyramidal SEs

likely that there is antagonism of DA receptors

Question 6

GABA

• what is it?
• function?
• Give the 2 types of GABA receptor and their agonists?

Answer 6

• main inhibitory NT in mammalian brains
• opens ion channels and allows either CL into cell or K out of cell to give negative change in transmembrane potential and hyperpolarization
• GABAa- ligand gated ion channel
  ethanol, benzos, propofol, anaesthetics

GABAb- Gprotien couples receptors
Baclofen, propfol

Question 7

Mood stabilisers

• what are they?
• Give the 3 types of mood stabiliser and examples (3,2,2)

Answer 7

-mostly anti-convulsant drugs
tend to be better at reducing manic episodes than depressive ones

-Anti-convulsant drugs
(carbamazepine, valproate, Lamotrigine)

Atypical
olanzapine, risperidone

Others
Lithium carbonate , nimodipine

Question 8

anti-convulsants

-MOA?

Answer 8

-increase inhibitory NT in the brain but all have different mechanisms

Question 9

Lamotrigine

-MOA?

Answer 9

-blocks Na channels
reduces excitability and cell firing
lamotrigine may also inhibit 5-HT uptake aswell

Question 10

Lithium

• MOA?
• SE?
• monitoring?

Answer 10

-unknown exactly why
inhibition of 5-HT autoreceptors 
increase in anti apoptotic factor Bcl-2
inhibits GSK-3
Depletion of inositol
up regulation of glutamate re-uptake 

-risk of toxicity high
problems with poor adherence

-NEEDS BLOOD MONITORING

Question 11

Antipsychotic drugs

• MOA for first generation and second generation (3) ?
• adverse effects?

Answer 11

-affinity for the D2 receptor, produces DA blockade in the mesolimbic circuits

2nd gen:
inc D2 receptor-binding affinity
inc 5-HT2c, 5-HT2a receptor binding affinity increases efficacy
inc 5-HT1a receptor binding affinity reduces efficacy

-due to DA blockade in the nigrostriatal and tubero-infundibular pathways:
weight gain