Antidepressants

Question 1

What was the original purpose of iproniazid?

Answer 1

Chemotherapy for tuberculosis-patients reported feelings of euphoria - it had a stimulant effect

Question 2

Name 3 common side effects of iproniazid

Answer 2

Mood elevation, weight gain, increased sociability

Question 3

Name 3 rarer side effects of iproniazid

Answer 3

Psychomotor agitation, hypersexuality and psychoses

Question 4

What was iproniazid typically referred to as?

Answer 4

A psychic energiser

Question 5

Who introduced the term antidepressant

Answer 5

Max lurie

Question 6

What were tricyclics first used for

Answer 6

Do treat schizophrenics - but it had no effect

Question 7

Name a tricyclic

Answer 7

Imipramine

Question 8

How do tricyclics work

Answer 8

Block the reuptake of serotonin and noradrenaline into the presynaptic neuron

Question 9

Which are safer: Mao inhibitors or tricyclics

Answer 9

Tricyclics

Question 10

What evidence did Ashcroft and Eccleston (1960) contribute towards the monoamine hypothesis

Answer 10

Autopsy studies of suicide victims and CSF in depressed patients: low serotonin, 5ht, or metabolite 5-HIAA concentrations

Question 11

Who discovered mono amine reap take was blocked by tricyclics

Answer 11

Axelrod

Question 12

Who dismissed the role of serotonin, focusing on the noradrenaline hypothesis of depression

Answer 12

.Schildkraut

Question 13

What does the monoamine hypothesis propose

Answer 13

Depression is associated with deficiency of monoamine neurotransmitters, particularly noradrenaline and serotonin

Question 14

name some of the serious side effects of MAOi

• why are there serious side effects associated

Answer 14

liver damage and blood control issues

• because they are non-specific - can also act in the periphery as well as centrally.

Question 15

people using MAOi need to make dietary changes, why?

Answer 15

dietary tyramine is an indirect noradrenaline agonist found in mature cheeses, red wines, pickled herring and yeast.

• when MAO-A is inhibited as little as 10 mg of dietary tyramine can increase BP

Question 16

what causes the associated side effects of tricyclic use

name 2 side effects

Answer 16

antagonist of muscarinic acetylcholine or cholinergic receptors in the PNS = dry mouth, impaired muscular control, tachycardia, constipation

Question 17

name the two main enzymes responsible for the destruction of noradrenaline

Answer 17

monoamineoxidase
catechol-O-methyl-transferase (COMT)

Question 18

it is important that appropriate antidepressants are prescribed for the right patient (each has specific effects), what is the specific effects of these:
- MAOIs
- trimipramine
- clomipramine

Answer 18

MAOIs = enhance drive
Trimipramine = sedative effects
clomipramine = mood and emotion

Question 19

what was the name of the first SSRI

Answer 19

zelmid

Question 20

what was later found about zelmid

Answer 20

found to cause Guillain-barre syndrome
= immediately removed from the market

Question 21

name a well known SSRI

Answer 21

prozac

Question 22

how do SSRIs work

Answer 22

they inhibit the reuptake of serotonin into the pre-synaptic neuron = more serotonin left in the synaptic cleft

Question 23

prozac has been praised for having less severe side effects, name two of them:

Answer 23

nausea
sexual dysfunction

Question 24

what are the main problems with the monoamine hypothesis

Answer 24

1. time lag between administration and depressive symptom relief
2. inconsistent findings regarding produced noradrenaline and serotonin in depressed patients = suggests the issue is at the receptor level.

Question 25

SNRIs are a new treatment, what is it?

Answer 25

serotonin-noradrenaline reuptake inhibitors

Question 26

name a SNRI

Answer 26

venflaxine

Question 27

what are SARIs (new treatment), name one

Answer 27

serotonin antagonist and reuptake inhibitors - such as trazodone.

Question 28

what are the main effects of trazodone, what does this mean when administering it to treat depression

Answer 28

hypnotic with sedative effects - as it is hypnotic at low doses, to have an antidepressant effect it must be administered at high doses

Question 29

how does trazodone create a antidepressant effect

Answer 29

blocks the serotonin transporter.

Question 30

when patients do not respond to SSRIs, what are they given

Answer 30

Quetiapine

Question 31

what receptors does Quetiapine have an affinity to which make it useful in the treatment of schizophrenia, bi-polar depression and depression

Answer 31

D2 5-HT2A H1 alpha 1 5-HT1A

Question 32

mirtazapine is known as Californian rocket fuel - how does it work

Answer 32

serotonergic and noradrenergic antidepressant with no MAO inhibiton

Question 33

explain the study ran by Tranter et al. 2002

Answer 33

healthy volunteers to compare the effects of sertraline (SSRI) and reboxetine (SNRI) large individual differences in response to drugs - some healthy people developed suicidal ideation and emotional blunting.

Question 34

name 2 dangerous side effects of SSRIs

Answer 34

akathisia (agitation) suicidal ideation

Question 35

how many more times are SSRIs selective for serotonin reuptake inhibition than for noradrenaline reuptake inhibition?

Answer 35

10 x

Question 36

why is it that SSRIs have multiple pharmacological actions - which explain the differences in efficacy between different patients

Answer 36

they bind to a large number of other receptors and enzymes that can contribute to their overall clinical effect

Question 37

what does sertraline do?

Answer 37

dopamine-re uptake inhibition

Question 38

how does sertraline work?

Answer 38

binds with high affinity to the sigma receptor - which is involved in multiple cellular functions, biological processes and diseases.

Question 39

how does paroxetine work?

Answer 39

muscarinic/ cholinergic antagonist noradrenaline reuptake inhibition cytochrome p450 enzymes: 2D6 and 3A4 inhibition

Question 40

what does cytochrome p450 do?

Answer 40

role in drug metabolism

Question 41

why is it important that paroxetine inhibits cytochrome p450 enzymes?

Answer 41

the drug will stay for longer in the system - as it inhibits the enzymes involved in metabolism

Question 42

when was it brought to attention that antidepressants may trigger suicide

Answer 42

1958

Question 43

which type of antidepressants is more likely to cause problems?

Answer 43

activating antidepressants more likely to cause problems over sedating antidepressants

Question 44

which class of drugs is most associated with suicide attempts

Answer 44

monoamine oxidase inhibitors

Question 45

which symptoms does desipramine and nortripytline clear up first, and before what

Answer 45

alleviates depressive psychomotor retardation before it clears up suicidal ideation

Question 46

which drug is the most drive enhancing

Answer 46

MAOis

Question 47

describe the case study finding high suicide rates in fluoxetine treatments

Answer 47

5 females and 1 male depressed patients free of recent suicidal ideation developed intense violent suicidal preoccupation after 2-7 wks of fluoxetine treatment

Question 48

what are the 2 controversial side effects of SSRIs

Answer 48

akathisia suicidal agitation

Question 49

which drug has received lots of negative press from the FDA

Answer 49

paroxetine (Paxil)

Question 50

what is an assessment of causality

Answer 50

challenge, de-challenge, and re-challenge

Question 51

what evidence is there for a dose response relationship between drugs and outcomes

Answer 51

akathisia and suicidal thinking disappeared upon the discontinuation of fluoxetine

Question 52

what is said to be the cause of suicidal ideation

Answer 52

the akathisia which is reported from drug use

Question 53

name 4 side effects of sertraline that stopped a trial within one week in Leeds in the 1980s

Answer 53

apprehension, insomnia, movement disorders, akathisia

Question 54

describe the neurotransmitter receptor sensitivity hypothesis for depression

Answer 54

depression is caused by abnormal upregulation of receptors. elevating neurotransmitter levels through the use of antidepressants leads to long term down regulation of receptors this explains why there is a time lag between administration and clinical effects.