Antidepression drugs

Question 1

Iproniazid mechanism

Answer 1

MOA inhibitor

Question 2

Iproniazid use

Answer 2

AD (no longer used clinically)
Tuberculosis drug - patients aborally happy - evidence for monoamine hypothesis

Question 3

List MOA inhibitors used in depression

Answer 3

Phenelzine
Tranylcypromine
Isocarboxazid
Moclobemide

Question 4

MAOI mechanism

Answer 4

Inhibit MOA in presynaptic mt outer membrane
Increases releasable pool of MAs
Immediate action

Question 5

Name older MOAI drugs

Answer 5

Phenelzine
Tranylcypromine
Isocarboxazid

Question 6

Describe the use of older MOAI drugs

Answer 6

Very effective
Not prescribed much due to lots of interactions (dietary) e.g. cheese reaction

Question 7

What is the cheese reaction and what drug is it found in

Answer 7

Tyramine (dietary MA) cannot be metabolised in the liver by MOA-A as normal when it is inhibited my MOAIs
Tyramine does not cross the BBB but in periphery acts as a false substrate for:
NET (gets taken into presynaptic sympathetic terminals)
VMAT (gets put into vesicles)
It is then released (non-vesicularly) and causes massive activation of sympathetic ns
Hypertensive crisis - stroke and death

Question 8

Newer MAOI

Answer 8

Moclobomide

Question 9

New MAOI mechanism of action

Answer 9

Selective for MAO A
Reversible inhibitor

Question 10

Why are the dietary interactions seen with old MAOIs not seen in new MAOIs

Answer 10

New MAOIs are reversible - tyramine can compete with drug so does get broken down in liver

Question 11

Use of moclobemide

Answer 11

AD
Newer MAOI
Still under prescribed due to prejudice of MAOIs caused by older class MAOIs

Question 12

What is serotonin syndrome and what is is caused by

Answer 12

Interaction of old class MAOIs with SSRIs or tricyclic ADs
Causes huge increase in synaptic serotonin ]Can cause confusion, muscles twitching, seizure, coma, death

Question 13

what are SSRIs

Answer 13

Selective seretonin reuptake inhibitors

Question 14

What are SNRIs

Answer 14

Serotonin/noradrenaline reuptake inhibitors

Question 15

What are NRIs

Answer 15

NA reuptake inhibitors

Question 16

What is the most widely used class of AD

Answer 16

SSRIs

Question 17

Name 4 SSRIs

Answer 17

Citalopram
Paroxetine (Paxil)
Sertraline
Fluoxetine (Prozac)

Question 18

What is citalopram

Answer 18

An SSRI

Question 19

What is Paroxetine/Paxil

Answer 19

An SSRI

Question 20

What is Sertraline

Answer 20

An SSRI

Question 21

What is Fluoxetine/Prozac

Answer 21

AN SSRI

Question 22

Name 2 SNRIs

Answer 22

Venlafaxine
Duloxetine

Question 23

What is venlafaxine

Answer 23

An SNRI

Question 24

What is Duloxetine

Answer 24

An SNRI

Question 25

Name 2 NRIs

Answer 25

Reboxetine Atomoxetine

Question 26

What is reboxetine

Answer 26

An NRI

Question 27

What is atomoxetine

Answer 27

An NRI

Question 28

Other uses of SSRIs/SNRIs/NRIs

Answer 28

anxiety disorders premature ejaculation

Question 29

What are 1st generation ADs

Answer 29

MAOIs Tricyclic ADs

Question 30

What are 2nd generation ADs

Answer 30

SSRIs Some people include SNRIs and NRIs

Question 31

What are 3rd generation ADs

Answer 31

SNRIs NRIs Only some people recognise these as their own generation

Question 32

First SSRI produced

Answer 32

Fluoxetine/Prozac

Question 33

What is the side effect profile of 2nd/3rd generation ADs like and why is it important

Answer 33

Quite benign, low overdose suicide risk (compared to 1st gen) Important as med overdose is common method of suicide attempt

Question 34

Name 3 tricycles ADs

Answer 34

Amitriptyline Nortriptyline Imipramine

Question 35

Tricyclic ADs mechanism

Answer 35

Similar to SNRIs Inhibit SERT and NET Increase synaptic concentration of MAs

Question 36

Why are tricyclic ADs only used for treatment resistant MDD

Answer 36

They have a high suicide mortality on overdose

Question 37

Other uses of tricyclic ADs

Answer 37

Pain Migraine (At lower doses)

Question 38

What is the difference between SNRIs and tricyclic

Answer 38

Side effect profiles Tricyclics have hard to deal with side effects and very dangerous in overdose

Question 39

What is discontinuation syndrome

Answer 39

flu like symptoms when suddenly stop taking Insomnia Motor and cog problems last 1-4 weeks

Question 40

Name newer treatments for depression

Answer 40

Ketamine/esketamine Psychedelics - LSD, psylocibin Agomelatine

Question 41

How is esketamine administered

Answer 41

Nasal spray - sickened in UK

Question 42

How long do AD effects of ketamine/eskatamine take to occur after administration

Answer 42

4 hours

Question 43

Possible risks of ketamine (based on ketamine abuse)

Answer 43

bladder dysfunction and personal lesions - unsure

Question 44

How is discontinuation syndrome combatted

Answer 44

ween off meds rather than cold turkey

Question 45

Which drugs give discontinuation syndrome (worst)

Answer 45

Duloxetine Venlafaxie Also SSRIs citalopram and paroxetine, MAOIs and NaSSAs

Question 46

Name an NaSSA

Answer 46

Mirtazapine

Question 47

Where does Mirtazapine act

Answer 47

Antagonist at alpha 2 adrenoceptors and 5HT2 A and C Antagonist at histamine H1

Question 48

Which receptors doe mirtazapine have highest affinity for/cause most side effects

Answer 48

H1 histamine receptor

Question 49

Benefits of mirtazapine

Answer 49

Generally effective and well tolerated (does not cause sexual dysfunction or nausea Faster onset than others

Question 50

Mirtazapine mechanism

Answer 50

Alpha 2 adrenoceptors for NA - presynaptic autoreceptors (feedback inhibition for nt release) - antagonise so increase release of 5HT or NA 5HT2A/C receptors involved in mood (overactivity = depression and maybe anxiety) - antagonise 5HT3 receptors - antiemetic

Question 51

How do psychedelics act

Answer 51

MA based Act faster than normal ADs

Question 52

How does Agomelatine act

Answer 52

moderately potent antagonist of 5HT2 receptor (influence mood - overactivity of these milked to depression) Melatonin receptor Equivalent effect to SSRIs but may be better tolerated Approved