Pharmacology of Antidepressants & Mood Stabilisers

Question 1

Are most psychiatric drugs lipophilic or hydrophilic and why?

Answer 1

Must be lipophilic to cross the Blood Brain Barrier

Question 2

What beta blocker can be used for anxiety due to its lipophilic properties?

Answer 2

Propranolol

Question 3

Antidepressants are used for what other mental disorders other than depression?

Answer 3

• Generalised anxiety disorder
• Panic disorder, OCD, PTSD
• Premenstrual dysphoric disorder
• Bulimia nervosa
• Neuropathic pain

Question 4

Glutamate, 5HT, Dopamine and Noradrenaline are all monoamines. TRUE/FALSE?

Answer 4

FALSE - glutamate is NOT a monoamine

Question 5

What nucleus is involved in the Serotonin (5-HT) projection pathway?

Answer 5

Rostral nucleus

Question 6

What nucleus found in the midbrain can be involved in analgesia?

Answer 6

Caudal Raphe

Question 7

How are serotonin and noradrenaline handled after reuptake into the presynaptic neuron?

Answer 7

Either:

• reuptake into vesicles for redistribution into synaptic cleft
• OR metabolised by monoamine oxidase

Question 8

What nucleus in the brain is involved in noradrenaline projection pathways?

Answer 8

Locus coeruleus

Question 9

Give examples of Monoamine oxidase inhibitors which will prevent the break down of neurotransmitters after reuptake from the synaptic cleft.

Answer 9

Phenelzine

Moclobemide

Question 10

What are the main side effects of Monoamine oxidase inhibitors?

Answer 10

• inhibition of MAO in gut prevents breakdown of dietary tyramine => precipitates hypertensive crisis (patients need to avoid specific foods)
• Potentiates effects of other drugs
• Insomnia
• Postural hypotension
• Peripheral oedema

Question 11

Give examples of tricyclic antidepressants

Answer 11

Imipramine
Dosulepin
Amitriptyline
Lofepramine

Question 12

What antcholinergic side effects can tricyclic antidepressants cause?

Answer 12

blurred vision
dry mouth
constipation
urinary retention

Question 13

What is the mechanism of action of tricyclics?

Answer 13

Block re-uptake of 5HT and Noradrenaline into presynaptic terminal

Question 14

What other (NOT anticholinergic) side effects do tricyclic antidepressants cause?

Answer 14

Sedation
Weight gain
Cardiovascular-Postural hypotension, tachycardia, arrhythmias
Cardiotoxic in overdose

Question 15

Give examples of different types of SSRI?

Answer 15

Fluoxetine
Citalopram / Escitalopram
Sertraline
Paroxetine (less commonly used now)

Question 16

What side effects are usually experienced with an SSRI?

Answer 16

Nausea
Headache
Sweating / vivid dreams
Worsened anxiety
Sexual dysfunction
Hyponatraemia (in elderly)
Transient increase in self-harm / suicidal ideation in <25 years
Discontinuation effects

Question 17

Give examples of Dual reuptake inhibitors/SNRIs?

Answer 17

Venlafaxine

Duloxetine

Question 18

Why are SNRIs preferable to tricyclic antidepressants?

Answer 18

Lack major receptor-blocking actions

=> more limited range of side effects than tricyclics

Question 19

Give an example of an atypical antidepressant and its side effects?

Answer 19

Mirtazapine

Causes weight gain + sedation

Question 20

Give an example of a dopamine uptake inhibitor?

Answer 20

Bupropion

used in USA not in UK

Question 21

Why are antidepressants used cautiously in children/ young adults?

Answer 21

due to transient increase in suicidal / aggressive ideas

Question 22

What is the aim of acute vs long term treatments for bipolar disorder?

Answer 22

ACUTE:

• reduce mood in episodes of mania
• raise mood in episodes of depression

LONG TERM:

• stabilise mood
• prevent recurrence of both mania and depression (prophylaxis)

Question 23

What form of salt is lithium usually given with, and why is this clinically relevant?

Answer 23

Usually Lithium CARBONATE

different salts have different bioavailability so be careful about doses if the type of lithium salt is changed

Question 24

Lithium is thought to have what mode(s) of action?

Answer 24

• block phosphatidylinositol pathway (second messenger system)
• inhibit Glycogen Synthase Kinase 3β

act on post-synaptic neuron

Question 25

What side effects can patients experience from a normal therapeutic dose of lithium?

Answer 25

- Dry mouth / strange taste - Polydipsia and polyuria - Tremor - Hypothyroidism - Long term reduced renal function - Nephrogenic diabetes insipidus - Weight gain

Question 26

What side effects would indicate that a patient is lithium toxic?

Answer 26

- Vomiting and Diarrhoea - Ataxia / coarse tremor - Drowsiness/ coma - Convulsions

Question 27

How is lithium excreted?

Answer 27

``` Excreted in the urine Not metabolised (as it is an element) ```

Question 28

Why is dehydration potentially dangerous for patients on lithium?

Answer 28

Renal tubules cant tell difference between Na and Lithium => when dehydrated, kidneys attempt to retain water, causing Na and Li to follow => Lithium retained and levels are higher than they should be

Question 29

What anticonvulsants can be used as long term mood stabiliser treatment?

Answer 29

Valproic acid Lamotrigine Carbamazepine

Question 30

What side effects do the anticonvulsant mood stabilisers have?

Answer 30

Valproate AND carbamazepine: drowsiness, ataxia, cardiovascular effects, induces liver enzymes Valproate: teratogenicity (neural tube defects) Lamotrigine: very small risk of Stevens-Johnson syndrome (SJS)

Question 31

What antipsychotics can be used as mood stabilisers and how do they work?

Answer 31

Quetiapine, Aripiprazole, Olanzapine, Lurasidone Mode of action: Dopamine antagonism + 5-HT antagonism

Question 32

What side effects do mood stabilising antipsychotics have?

Answer 32

sedation weight gain metabolic syndrome extra-pyramidal side-effects (Aripiprazole)