ANTI-DEPRESSANTS

Question 1

SSRI examples

Answer 1

1. Fluoxetine (x50 fold)
2. Citalopram (x1000 fold)

Fluoxetine more widely prescribed

Question 2

ADR of MAO inhibitors

Answer 2

1. Postural HYPOtension (due to blocked production of NA at cervical neurons leading to sympathetic block)
2. Insomnia, restlessness (due to increase NA at CNS)
3. DDI w 5-HT stimulating drugs (SSRI & SNRI)
4. FDI w food rich in monoamines

Question 3

ADR of MAO inhibitors

Answer 3

1. Postural HYPOtension (due to blocked production of NA at cervical neurons leading to sympathetic block)
2. Insomnia, restlessness (due to increase NA at CNS)
3. DDI w 5-HT stimulating drugs (SSRI & SNRI)
   eg pethidine
4. FDI w food rich in monoamines

Question 4

TCA examples (NET & SERT)

Answer 4

1. Imipramine
2. Amitriptyline
3. Nortriptyline

Question 5

TCA examples (NET)

NET = NorEPINEPHRINE

Answer 5

Desipramine

Question 6

NARI examples

Answer 6

1. Reboxetine

2. Maprotiline (earlier NARI similar ADR as TCA)

Question 7

SNRI (5-HT & NorADRENALINE) examples

Answer 7

1. Venlafaxine
2. Desvenlafaxine
3. Duloxetine

Question 8

DDI risk for Serotonin Syndrome

Answer 8

1. MAO-A inhibitors
2. SSRI
3. SNRI

Question 9

ADR of TCA

Answer 9

1. Sedation (due to H1 receptor antagonist)
2. Postural hypotension (due alpha-adrenergic antagonism)
3. Dry mouth, constipation & blurred vision etc (due to muscarinic receptors antagonist)
4. DDI (high plasma protein binding & hepatic metabolism)

1&2 esp at start of treatment

Question 10

Mechanism of “cheese” reaction w MAOi

Answer 10

1. MAOi blocked MAO degradation of tyramine in liver & intestines -> increase tyramine (sympathomimetic)
2. Reuptake of tyramine and preferential storage into vesicles > NA -> increase release of NA into synapse (sympathomimetic)

Question 11

ADR of SSRI

Answer 11

1. Sedation
2. Postural hypotension
3. Dry mouth, blurred vision & constipation
4. Nausea
5. Insomnia
6. Sexual dysfunction
7. DDI w 5-HT stimulating drugs (MAOi & SNRI)

• 1,2&3 less than TCA
• Citalopram still has some histamine receptor antagonism leading to sedation

Question 12

ADR of NARI

Answer 12

1. Dry mouth, constipation & blurred vision
2. Insomnia (due to increase NA in CNS)
3. Tachycardia (due to increase NA in heart)

Question 13

ADR of SNRI (5)

Answer 13

less than TCA

1. Nausea
2. Insomnia
3. Sexual dysfunction
4. Serotonin Syndrome when combine w other serotoninergic agents & MAOi
5. Withdrawal effects may be more common & stronger than SSRI & TCA

(( similar to SSRI ))

Question 14

Advantages of SNRI (3)

Answer 14

1. Faster than other anti-depressant
2. Good for treatment-resistant patients
3. Fewer SE than TCA

Question 15

Advantages of SSRI

Answer 15

1. Reduced SE & safety
2. Increased tolerability
3. Increased efficacy

Question 16

Other anti-depressants (5)

Answer 16

1. Mirtazapine
2. Buproprion
3. Agomelatine
4. Ketamine
5. Vortioxetine

Question 17

Mechanism of action of Mirtazapine (NaSSA)

Answer 17

• Norepinephrine & selective 5-HT receptor agonist

- BUT 5-HT2c receptor antagonist & alpha2 adrenergic receptor antagonist

Question 18

Mechanism of action of Buproprion (NDRI)

Answer 18

Norepinephrine & dopamine reuptake inhibitor

Question 19

Mechanism of action of Agomelatine

Answer 19

MT1 & MT2 melatonin receptor agonist

• helps in sleep disorder
• BUT 5-HT2c receptor antagonist

Question 20

Mechanism of action of Ketamine

Answer 20

• Glutamate NMDA rceptor antagonist

- anaesthetic properties (IV GA)

Question 21

Mechanism of action of Vortioxetine

Answer 21

• Multimodal 5-HT receptor effects
• Full agonist of 5-HT1a receptor
• Partial agonist of 5-HT1b receptor
• Agonist of 5-HT1d, 5-HT3 & 5-HT7 receptor
• also increase neurotransmitters (acetylcholines, histamines, dopamine, norepinephrine & 5-HT) in pre-frontal cortex & hippocampus of brain

Question 22

ADR of Vortioxetine

Answer 22

Suicidal ideations in children & teens

Question 23

Advantage of Vortioxetine

Answer 23

1. Pro-cognitive

2. Good for treatment-resistant patients

Question 24

MAO inhibitors examples

Answer 24

Irreversible, non-selective - phenelzine
Reversible, MAO-A i - moclobemide
MAO-B i - selegiline (Jumex) (anti-parkinson)

Question 25

2 major types of depression

Answer 25

1. Unipolar depression 2. Bipolar depression or Affective disorder - alternate between depression and mania

Question 26

Unipolar Depression causes

Answer 26

1. Reactive Depression - 75% of cases - associated with life events 2. Endogenous Depression - 25% of cases - familial pattern -> genetic predisposition - not directly related to external stress

Question 27

Bipolar Depression cause

Answer 27

- strongly familial

Question 28

Monoamine Theory

Answer 28

- reserpine (5-HT and NA inhibition) lead to depressed mood - hypothesis mainly formulated for NA only but later shifted to 5-HT - monoamine theory alone is unable to explain the pharmacological actions of anti-depressants - monoamines are important but there are a complex interactions with other neurotransmitter systems as well

Question 29

Types of MAO enzymes

Answer 29

MAO-A - breaks down 5-HT mainly MAO-B - breaks down NA and dopamine mainly

Question 30

Major limitations on the use of MAOi

Answer 30

FDI with food rich in monoamines | - Cheese Reaction

Question 31

How to reduce the risk of Cheese Reaction with MAOi

Answer 31

Use reversible & selective MAO-A inhibitor | eg Moclobemide

Question 32

Cheese Reaction signs and symptoms

Answer 32

1. Acute HTN 2. Severe throbbing headache 3. Intracranial haemorrhage

Question 33

Nortriptyline

Answer 33

- 2nd gen TCA - milder SE compared to amitriptyline & imipramine hence improve compliance

Question 34

Cheese Reaction = Serotonergic Syndrome ?

Answer 34

No. Cheese reaction due to FDI of MAOi with food rich in monoamines (eg tyramine) Serotonin Syndrome due to DDI w serotonin enhancing drugs

Question 35

1st drug class developed specifically as anti-depressant

Answer 35

SSRI

Question 36

Drugs to treat sexual dysfunction from SSRI

Answer 36

Cyproheptadine or other 5-HT2 blockers

Question 37

Serotonin Syndrome signs and symptoms (4)

Answer 37

1. Tremor 2. Hyperthermia 3. Cardiovascular collapse 4. Acute HTN