L1 Antidepressants

Question 1

5-HT is broken down mainly by

Answer 1

MAO-A

Question 2

Noradrenaline is broken down mainly by

Answer 2

MAO-A and MAO-B

Question 3

Dopamine is broken down mainly by

Answer 3

MAO-A and MAO-b

Question 4

What is the type of MAOi used in Parkinson’s disease?

Answer 4

MAO-B

Question 5

Phenelzine is: (2)

Answer 5

1. non-selective for MAO-A vs MAO-B

- and irreversible MAOi

Question 6

ADR of MAOis

Answer 6

1. postural hypotension - dopamine as inhibitory neurotransmitter, cervical block
2. restlessness or insomnia - CNS stimulation
3. should not be combined with other drugs with seretoninergic function eg. pethidine - myoclonus, hyperexcitability, loss of consciousness, increased muscular tone

Question 7

Significant drug-food interaction related to the use of MAOIs (also its major limitation)

Answer 7

the ‘cheese’ reaction

- cheeses and concentrated yeast products eg. marmites

Question 8

Tyramine has a high affinity for

Answer 8

NA transporters

Question 9

TCAs were initially produced as

Answer 9

potential antipsychotic drugs in 1949, but found to be ineffective in schizophrenia

Question 10

Examples of non-selective TCAs

Answer 10

imipramine, amitriptyline, nortriptyline

Question 11

Example of NET-selective TCA

Answer 11

desipramine

Question 12

Which one of the non-selective TCAs has the mildest side effect profile?

Answer 12

nortriptyline

Question 13

ADR of TCAs (4)

Answer 13

1. sedation - H1 antagonism, tolerance can be developed in 1-2weeks
2. postural hypotension - a-adrenoceptor sympathetic block
3. dry mouth, blurred vision, constipation - muscarinic receptor antagonism
4. ddi - rely on hepatic metabolism

Question 14

Which is the first drug class to be developed for the purpose of antidepressant treatment?

Answer 14

SSRIs

Question 15

What is the mostly widely prescribed antidepressant currently?

Answer 15

Fluoxetine

Question 16

3 key advantages of SSRIs

Answer 16

1. low affinity for alpha-adrenoceptors
2. low affinity for muscarinic cholinergic receptors
3. lack of effect at histamine receptors

Question 17

Which SSRIs still retain some level of sedation?

Answer 17

citalopram - still has some histamine receptor antagonism

Question 18

adr of SSRIs

Answer 18

nausea, insomnia, sexual dysfunction

Question 19

What drugs can be given to prevent SSRTI-induced sexual dysfunction?

Answer 19

cyproheptadine or other 5HT2 blockers

Question 20

What is the current first line therapy used for depression?

Answer 20

SSRIs, but it is not perfect:

• only 2/3 achieve remission
• adverse effects, esp at the start
• discontinuation can be a problem in some

Question 21

Maprotiline

Answer 21

an earlier NARI, had TCA-like adverse effects due to alpha-adrenoceptor and histamine receptor effects and occasionally caused seizures

Question 22

Examples of SNRIs in clinical use

Answer 22

venlafaxine, desvenlafaxine (synthetic metabolite of venlafaxine), and duloxetine

Question 23

Withdrawal effects is more common and stronger for SSRIs/TCAs/SNRIs?

Answer 23

SNRIs

Question 24

Example of a NDRI

Answer 24

bupropion

Question 25

Example of an anesthetic, currently evaluated for rapid-onset antidepressant effect

Answer 25

Ketamine, a glutamate NMDA receptor antagonist

Question 26

Example of a NaSSA

Answer 26

mirtazapine, adrenergic a2 autoreceptor antagonist + 5HT2c receptor antagonist

Question 27

Aglomelatine

Answer 27

agonist of MT1 and MT2 receptors, also has antagonist at 5HT2c receptors - also helps in sleep disorders - less TCA/SSRI-associated adr

Question 28

Vortioxetine

Answer 28

multimodal serotonergic antidepressant + additional receptor affinities

Question 29

Vortioxetine is generally used in

Answer 29

patients resistant to other antidepressants, pro cognitive effects too, appear to work well with children and young adults

Question 30

Close monitoring required in initial stages of vortioxetine use due to

Answer 30

increased risk of suicidal thoughts or actions in childrens and teens

Question 31

Does fluoxetine or citalopram has a higher selectivity for 5-HT?

Answer 31

50-fold vs 1000-fold, citalopram

Question 32

Does TCA and SSRI bind to the same site?

Answer 32

Yes | - SSRI has greater 5-HT reuptake selectivity though, fewer adverse effects

Question 33

Adverse effects of TCAs lead to

Answer 33

prescription of subtherapeutic doses - improved adverse side effect profile of SSRIs lead to better compliance and so prescription of more adequate doses, better efficacy

Question 34

Symptoms of serotonin syndrome

Answer 34

tremor, hyperthermia, cardiovascular collapse

Question 35

Why is SSRis safer in overdose?

Answer 35

low affinity for alpha-adrenoreceptors: lack of cardiovascular effects (postural hypotension, bradycardia)

Question 36

NARI

Answer 36

reboxetine, maprotiline

Question 37

ADR of SNRI

Answer 37

- similar to SSRI: nausea, insomnia, sexual dysfunction - 'serotonin syndrome' when combined with other serotoninergic drugs and MAOis - withdrawal effects may be more common and stronger than for SSRIs and TCAs

Question 38

Which of the following has the fewest adr? TCAs/SSRIs/NARIs

Answer 38

NARI

Question 39

Does venlafaxine have the same structure as TCA?

Answer 39

NO, fewer adr than TCAs

Question 40

Adv of velnlafaxine

Answer 40

- different structure to TCAs and fewer side effects | - claimed to work slightly faster, 2-4weeks, work better in treatment-resistant patients

Question 41

ADR of reboxetine

Answer 41

- dry mouth, constipation - insomnia: noradrenergic activity on CNS - tachycardia: increased NA availability