Antidepressants Flashcards
What was the original purpose of iproniazid?
Chemotherapy for tuberculosis-patients reported feelings of euphoria - it had a stimulant effect
Name 3 common side effects of iproniazid
Mood elevation, weight gain, increased sociability
Name 3 rarer side effects of iproniazid
Psychomotor agitation, hypersexuality and psychoses
What was iproniazid typically referred to as?
A psychic energiser
Who introduced the term antidepressant
Max lurie
What were tricyclics first used for
Do treat schizophrenics - but it had no effect
Name a tricyclic
Imipramine
How do tricyclics work
Block the reuptake of serotonin and noradrenaline into the presynaptic neuron
Which are safer: Mao inhibitors or tricyclics
Tricyclics
What evidence did Ashcroft and Eccleston (1960) contribute towards the monoamine hypothesis
Autopsy studies of suicide victims and CSF in depressed patients: low serotonin, 5ht, or metabolite 5-HIAA concentrations
Who discovered mono amine reap take was blocked by tricyclics
Axelrod
Who dismissed the role of serotonin, focusing on the noradrenaline hypothesis of depression
.Schildkraut
What does the monoamine hypothesis propose
Depression is associated with deficiency of monoamine neurotransmitters, particularly noradrenaline and serotonin
name some of the serious side effects of MAOi
- why are there serious side effects associated
liver damage and blood control issues
- because they are non-specific - can also act in the periphery as well as centrally.
people using MAOi need to make dietary changes, why?
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
what causes the associated side effects of tricyclic use
name 2 side effects
antagonist of muscarinic acetylcholine or cholinergic receptors in the PNS = dry mouth, impaired muscular control, tachycardia, constipation
name the two main enzymes responsible for the destruction of noradrenaline
monoamineoxidase
catechol-O-methyl-transferase (COMT)
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
MAOIs = enhance drive
Trimipramine = sedative effects
clomipramine = mood and emotion
what was the name of the first SSRI
zelmid
what was later found about zelmid
found to cause Guillain-barre syndrome
= immediately removed from the market
name a well known SSRI
prozac
how do SSRIs work
they inhibit the reuptake of serotonin into the pre-synaptic neuron = more serotonin left in the synaptic cleft
prozac has been praised for having less severe side effects, name two of them:
nausea
sexual dysfunction
what are the main problems with the monoamine hypothesis
- time lag between administration and depressive symptom relief
- inconsistent findings regarding produced noradrenaline and serotonin in depressed patients = suggests the issue is at the receptor level.
SNRIs are a new treatment, what is it?
serotonin-noradrenaline reuptake inhibitors
name a SNRI
venflaxine
what are SARIs (new treatment), name one
serotonin antagonist and reuptake inhibitors - such as trazodone.
what are the main effects of trazodone, what does this mean when administering it to treat depression
hypnotic with sedative effects
- as it is hypnotic at low doses, to have an antidepressant effect it must be administered at high doses
how does trazodone create a antidepressant effect
blocks the serotonin transporter.
when patients do not respond to SSRIs, what are they given
Quetiapine
what receptors does Quetiapine have an affinity to which make it useful in the treatment of schizophrenia, bi-polar depression and depression
D2
5-HT2A
H1
alpha 1
5-HT1A
mirtazapine is known as Californian rocket fuel - how does it work
serotonergic and noradrenergic antidepressant with no MAO inhibiton
explain the study ran by Tranter et al. 2002
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.
name 2 dangerous side effects of SSRIs
akathisia (agitation)
suicidal ideation
how many more times are SSRIs selective for serotonin reuptake inhibition than for noradrenaline reuptake inhibition?
10 x
why is it that SSRIs have multiple pharmacological actions - which explain the differences in efficacy between different patients
they bind to a large number of other receptors and enzymes that can contribute to their overall clinical effect
what does sertraline do?
dopamine-re uptake inhibition
how does sertraline work?
binds with high affinity to the sigma receptor - which is involved in multiple cellular functions, biological processes and diseases.
how does paroxetine work?
muscarinic/ cholinergic antagonist
noradrenaline reuptake inhibition
cytochrome p450 enzymes: 2D6 and 3A4 inhibition
what does cytochrome p450 do?
role in drug metabolism
why is it important that paroxetine inhibits cytochrome p450 enzymes?
the drug will stay for longer in the system - as it inhibits the enzymes involved in metabolism
when was it brought to attention that antidepressants may trigger suicide
1958
which type of antidepressants is more likely to cause problems?
activating antidepressants more likely to cause problems over sedating antidepressants
which class of drugs is most associated with suicide attempts
monoamine oxidase inhibitors
which symptoms does desipramine and nortripytline clear up first, and before what
alleviates depressive psychomotor retardation before it clears up suicidal ideation
which drug is the most drive enhancing
MAOis
describe the case study finding high suicide rates in fluoxetine treatments
5 females and 1 male depressed patients free of recent suicidal ideation
developed intense violent suicidal preoccupation after 2-7 wks of fluoxetine treatment
what are the 2 controversial side effects of SSRIs
akathisia
suicidal agitation
which drug has received lots of negative press from the FDA
paroxetine (Paxil)
what is an assessment of causality
challenge, de-challenge, and re-challenge
what evidence is there for a dose response relationship between drugs and outcomes
akathisia and suicidal thinking disappeared upon the discontinuation of fluoxetine
what is said to be the cause of suicidal ideation
the akathisia which is reported from drug use
name 4 side effects of sertraline that stopped a trial within one week in Leeds in the 1980s
apprehension, insomnia, movement disorders, akathisia
describe the neurotransmitter receptor sensitivity hypothesis for depression
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.
