Pharmacology of Mood Disorders

Question 1

Clinical uses of anti depressants

Answer 1

a) Dysthymia - persistent depression
b) Panic disorder, OCD, PTSD
c) Depression (moderate/severe)
d) Generalised anxiety disorder
e) Bulimia nervosa
f) Neuropathic pain

Question 2

List the classes of anti- depressants

Answer 2

MAO-I 
Tricyclic antidepressants
SSRI
SSNRI
Others

Question 3

Examples of MAO-I

Answer 3

Phenelezine (irreversible inhibition)

Moclobemide (reversible inhibition)

Question 4

MOA of MAO-I

Answer 4

Inhibitors of monoamine oxidase - mitochondrial enzyme responsible for breakdown of monoamine neurotransmitters

Prevents breakdown of these transmitters thereby increasing their availability

Question 5

Side effects of MAO-I

Answer 5

1. “cheese reaction”/ hypertensive crisis
2. Postural hypotension
3. Peripheral oedema
4. Insomnia

Question 6

Examples of Tricyclic antidepressants (TCA)

Answer 6

Imipramine
Dosulepine
Amitryptiline
Lofepramine

Question 7

MOA of TCA

Answer 7

Blocks reuptake of monoamines into presynaptic terminals

Mainly NA and 5-HT

Leads to increased concentration of the amines in synaptic cleft in both the CNS and periphery

Question 8

Pharmacokinetics of TCA

Answer 8

Good oral absorption

Highly protein bound

Metabolised by liver

Metabolites excreted in urine (1-2 wks)

Question 9

Side effects of TCA

Answer 9

1. Anticholinergic: dry mouth, blurred vision, urine retention, constipation, dizziness
2. Sedation, confusion, weakness
3. Weight gain and increased appetite
4. Cardiovascular: Postural hypotension, sweating, palps
   CARDIOTOXICITY IN OVERDOSE

Question 10

Examples of SSRI

Answer 10

sertraline
fluoxetine
Citalopram/escitalopram

Question 11

MOA of SSRI

Answer 11

Selective inhibition of serotonin uptake (5-HT) from synaptic cleft

Question 12

Tricyclic antidepressants are the first line drugs for depression - True or False?

Answer 12

False -

SSRIs are the first line drugs as:

a) no cardiotoxicity
b) safe in elderly

Question 13

Examples of SNRI

Answer 13

Venlafaxine

Duloxetine

Question 14

MOA of SNRI

Answer 14

Block reuptake of NA and serotonin from synaptic cleft

Question 15

Side effects of SNRI

Answer 15

Similar to SSRI

Lack major receptor blcoking actions (ex. anticholinergic)

Question 16

List the atypical antidepressants (MOA + SE)

Answer 16

MIRTAZAPINE
MOA: Blocks 2, 5-HT2 & 5-HT3 - increasing release of 5-HT and NA in brain - antidepressant effect
SE: weight gain, sedation

BUPROPION
MOA: inhibition of dopamine uptake
SE: insomnia, agitation, dry mouth

Question 17

Which drugs are used as mood stabilisers in treatment of Bipolar Disorder?

Answer 17

1. LITHIUM CARBONATE
2. Antipsychotics
3. Anti-convulsants

Question 18

Which drug needs consistent monitoring when administered? Why?

Answer 18

Lithium - narrow therapeutic window

Question 19

MOA of lithium

Answer 19

May block phosphatidylinositol pathway
OR inhibit glycogen synthase kinase 3B
OR modulate NO signalining

Question 20

Pharmacokinetics of lithium

Answer 20

well absorbed orally (slow)

Neither protein bound nor metabolised

Handled in Kidney

• reabsorption in PCT
• Rapid urinary excretion (10-12 hrs)

Higher levels in older people and those with renal insufficiency

Question 21

SE of Lithium

Answer 21

Dry mouth/strange taste
Tremors
Polydipsia and polyuria
Hypothyroidism
Long term reduced renal function
Nephrogenic DI 
Weight gain

Question 22

Toxic effects of lithium

Answer 22

Vomiting
Diarrhea 
Ataxia/coarse tremor
Drowsiness/altered conscious level
Convulsions
Coma

Question 23

List the anticonvulsants used as mood stabilisers

Answer 23

lamotrigine

carbamazepine

Question 24

MOA of anticonvulsants

Answer 24

unclear

perhaps potentiate GABA transmission thus blocking overactive pathways

Question 25

SE of anticonvulsant

Answer 25

drowsiness, ataxia, CV effects, induction of liver enzymes VALPROATE - teratogenictiy LAMOTRIGINE - Steven Johnson Mary syndrome

Question 26

List the antipsychotics used as mood stabilisers

Answer 26

Quetiapine Aripiprazole Olanzapine Lurasidone

Question 27

MOA of antispychotic

Answer 27

Dopamine + 5-HT antagonism

Question 28

SE of antipsychotic

Answer 28

sedation weight gain metabolic syndrome extrapyramidal effects (aripiprazole)

Question 29

``` Which of the following neurotransmitters is NOT a monoamine A. Dopamine B. Glutamate C. Noradrenaline D. 5-Hydroxytryptophan (5-HT ```

Answer 29

B. Glutamate

Question 30

Which of the following side-effects is MORE likely to be caused by an SSRI antidepressant than by a Tricyclic? ``` A. Blurred vision B. Constipation C. Dry Mouth D. Nausea E. Urinary Retention ```

Answer 30

D. Nausea

Question 31

Which of the following antidepressants should be avoided in a 57year old man with Ischaemic Heart Disease who has become depressed following an MI 2 months ago? ``` A. Citalopram B. Fluoxetine C. Imipramine D. Mirtazapine E. Sertraline ```

Answer 31

C. Imipramine is a TCA - cardiotoxic and easier to cause mortality with overdose

Question 32

Which of the following side-effects would suggest Lithium levels in the toxic range ``` A. Ataxia B. Hypothyroidism C. Nausea D. Polyuria E. Tremor ```

Answer 32

A. Ataxia - symptom of toxicity

Question 33

A 27 year old woman is diagnosed with Bipolar Disorder. She says that she hopes to get pregnant some time in the foreseeable future. Which mood stabiliser is absolutely to be avoided? ``` A. Aripiprazole B. Lamotrigine C. Lithium D. Quetiapine E. Valproic Acid ```

Answer 33

E. | Teratogenic

Question 34

Side effects of SSRI

Answer 34

Nausea Headache Worsened anxiety Increase in self-harm / suicidal ideation in <25 years Sweating / vivid dreams Sexual dysfunction Hyponatraemia (in elderly) Discontinuation effects - unsteadiness, increased mood change, restlessness, difficulty sleeping, GI symptoms, paraesthesia