Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Drugs And The Brain > Mood Disorders 2 > Flashcards

Mood Disorders 2 Flashcards

You may prefer our related Brainscape-certified flashcards:
The Brain flashcards
1
Q

Monoamine oxidase A

A

present in CNS: role to metabolize 5HT, NA, dopamine
important in periphery- metabolizes Dietary monoamines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Monoamine oxidase B

A

CNS: primarily metabolism of dopamine;

in periphery metabolize Dietary monoamines (but not as important as A)

found in presynaptic nerve terminal, Located on outer mitochondrial membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

inhibiting MAO

A

increases presynaptic MA, boosting MA transmission

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

weakness of MA hypothesis

A

effect on monoamines immediate but takes two weeks to see the clinical effect of anti depressants

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

examples of older MAO inhibitors

A

phenelzine, tranylcypromine, isocarboxazid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

older MAO inhibitors

A

Non selective (A vs B) irreversible inhibitors

Very effective in MDD, bipolar (+ mood stabilizer), anxiety disorders

Doctors very reluctant to prescribe due to large number of interactions

cheese reaction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

cheese reaction

A

Tyramine normally broken down in liver by MAO

When MAO-A inhibited, tyramine from diet can cause big problems!
-cant cross the BBB, but can cause problems in the periphery

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

tyramine

A

Tyramine acts as a false substrate for NET (noradrenaline transporter) so can be taken up into vesicles and displace noradrenaline

That noradrenaline then gets released into the synapse via non-vesicular release

This causes massive activation o the sympathetic nervous system and in turn hypertensive crisis
-this can result in stroke and death

People taking irreversible non-selective inhibitors need to be careful of things in their diet because it could trigger this adverse reaction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what causes serotonin syndrome

A

SSRI or tricyclic AD with MAOI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what is serotonin syndrome?

A

Massive increase in synaptic serotonin

confusion, agitation
muscle twitching, sweating
seizures, arrhythmias, coma (death)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what is the warrior gene

A

a 30 base repeated sequence inn the promoter of monoamine oxidase. Copies vary from 2-5 and affect the expression of MOA-A

alleles that result in low expression (such as the two repeat variant) have been associated with increased risk of violent behaviour
-however this is likely to be dependent on the presence of other risk factors such as childhood trauma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

example of newer MAOI

A

moclobemide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

newer MAOI

A

selective for MAO-A

reversible
-therefore we dont get dietary interactions
-if concentration of tyramine goes up it will be able to compete with the MAO inhibitor for the active site of MAO and we still get the breakdown of MAO

very fewer adverse affects

relatively fast onset

useful in MDD, bipolar (plus mood stabiliser), anxiety disorder

prejudice against MAO inhibitors because of the dangers associate with older drugs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

SSRI meaning

A

selective serotonin reuptake inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

SNRI meaning

A

serotonin/ noradrenaline (norepinephrine) reuptake inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

NRI meaning

A

noradrenaline reuptake inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what are the most widely used anti-depressants (2nd generation AD drugs)

A

SSRIs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

examples of SSRIs

A

citalopram, paroxetine, sertraline, fluoxetine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

first SSRI drug used

A

fluoxetine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

example SNRIs

A

venlafaxine, duloxetine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

examples NRIs

A

reboxetine, atomoxetine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what are NRIs, SNRIs and SSRIs useful for?

A

major depressive disorders, anxiety disorders, premature ejaculation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

risk of suicide in newer MAOIs compared to other drugs

A

much lower risk than TCA and older MAOIs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

2nd/ 3rd generation reuptake inhibitors

A

block the transporter (SERT and NET), increasing synaptic concentrations of the neurotransmitter

have side effects that tend to be short lived and manageable

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

SSRI, SNRI and NRI unwanted effects

A

nausea, anorexia in many
anorexia in some
discontinuation syndrome in all
anorgasmia
increased aggression, suicide ideation and self harm possible in the early stages of treatment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

discontinuation syndrome

A

flu like symptoms if you stop taking the drug suddenly, insomnia, motor and cognitive problems

normally last like 1 to 4 weeks

some people find it very difficult to deal with so doctors suggest that patients taper off the dose

can occur in up to 50% of people

27
Q

anorgasmia

A

lack of sensitivity to sexual stimulation

beneficial effect if you suffer from premature ejaculation (sometimes useful to treat men)

28
Q

why to NICE only recommend the SSRI fluoxetine

A

fluoxetine has a good benefit to risk ratio

drugs increase suicide ideation, which can be dangerous as people may still feel depression in the early stages of treatment but have the energy to follow through on ideation

29
Q

when are 2nd generation MOAIs recommended

A

only after other treatments, like talking therapies, haven’t worked

30
Q

affects of tricyclic antidepressants

A

mAChR: important ANS
H receptors: sedative effects
5HT receptors
alpha1 adrenergic

very dirty drugs

31
Q

when were tricyclic antidepressants

A

developed in 1950s

first line treatment for MDD

32
Q

what have TCA been replaced by

A

largely by SSRIs and SNRIs

33
Q

when are TCAs used

A

sometimes used as a last resort treatment for resistant MDD
used at lower doses to treat difficult difficult to manage pain

34
Q

downsides of TCA

A

many side effects
high suicide mortality in overdose

35
Q

examples of tricyclic antidepressants

A

amitriptyline, nortriptyline, imipramine

36
Q

what are the worst anti depressants for discontinuation syndrome

A

duloxetine and venlafaxine

SSRIs such as citalopram and paroxetine can also produce significant withdrawal symptoms

37
Q

what can discontinuation syndrome be explained by

A

the oppositional tolerance model

38
Q

oppositional tolerance model

A

when a drug perturbates neurotransmitter systems, the brain will down or up regulate components of the system to try and oppose the actions of the drugs

39
Q

why has controversy regarding the efficacy of antidepressants risen

A

partially due to a lack of transparency regarding clinical trials

40
Q

what is needed to get a drug licenced, what are the problems with this system

A

a pharmaceutical only needs to submit 2 or 3 successful trials to the regulator

they may have conducted many other clinical trials which have been unsuccessful in the past. Data from these trials have only rarely been published

Makes it difficult to know how much bias has happened due to lack of reporting of unsuccessful trials

41
Q

what type of drug is NaSSA

A

Noradrenergic and specific serotonergic antidepressant

42
Q

example of a NaSSa

A

mirtazapine

43
Q

actions of mirtazapine

A

Antidepressant actions probably due to actions as an Antagonist of 𝛂2 adrenoceptors and 5HT2A, C receptors

Highly sedating (H1 antagonist)
has highest receptor affinity for H1 histamine receptors and this cause major sedating effect and increased appetite

44
Q

side effects of miratazapine

A

appetite in crease
sedation
discontinuation syndrome

has fewer side effects than many of the other drugs we’ve met

generally very effective and well tolerated

faster onset of action than other AD drugs

45
Q

mirtazapine mechanism

A

Find alpha 2 adrenoreceptors on presynaptic nerve terminals of serotonergic and noradrenergic neurons
-function to inhibit neurotransmitter release via feedback inhibition
-in serotonergic neurons they are responding to noradrenaline that has drifted in from neighbouring noradrenergic terminals

Mirtazapine inhibits these receptors leading to an increased release of monoamines (S or N)

Has an effect on postsynaptic 5HT2a2c receptors
-These receptors seem heavily involved in mood and when they are overactive may contribute to depression and anxiety

Additional effect: can be used to reduce nausea and vomiting
Act as an antagonist of 5HT3 receptor
-ligand gated ion channel, actions here produce antiemetic effects

46
Q

newer treatments for depression

A

esketamine and ketamine, psychedelic drugs and agomelatine

47
Q

esketamine

A

S-enantiomer of ketamine (which is racaemic)

strong antidepressant effects in clinical trials
occurs quickly (4 hrs after dose)

nasal spray recently been licenced in the uk to treat depression

48
Q

ketamine

A

dissociative anaesthetic

strong antidepressant effects in clinical trials
effects occur quickly after administration

administered intravenously

effects of a single doses usually last at least 10 days
-maintenance therapy would presumably involve a dose every two weeks

49
Q

what does ketamine abuse cause?

A

bladder dysfunction
neuronal lesions

50
Q

mechanism of esketamine and ketamine

A

related to their actions as non competitive antagonists of NMDA?

how this links to depression is unclear

51
Q

psychedelic drugs as depression treatment

A

act to resolve depression much quicker than conventional antidepressants
-many see improvements in one week

legal restrictions on lsd, psilocybin and MDMA make it difficult to see how these could be licenced in the UK `

52
Q

agomelatine as a treatment of depression

A

moderately potent agonist of 5HT receptors

main mechanism of action as a melatonin receptor agonist

approved in europe for the use of MDD treatment in 2009

may also give some benefits in anxiety disorders

53
Q

prophylaxis

A

mood stabilising drugs
prevent swinging between depressed and manic mood

54
Q

examples of prophylaxis

A

lithium
anticonvulsant: e.g., lamotrigine and valproate
olanzapine (antipsychotic)

55
Q

managing mania

A

if already on mood stabilising drug then increase its dose

antipsychotic. e.g., olanzapine or quetiapine
-on top of mood stabilising drug or stand alone
-may add lithium or valproate

56
Q

managing depression (bipolar)

A

add olanzapine and fluoxetine, or olanzapine/ quetiapine to existing drugs

if someone is on an antidepressant and they present with mania there is a good chance it was precipitated by the antidepressant. They should be taken off immediately

57
Q

lithium possible mood stabilising mechanism

A

inhibition of teh IP3 pathway
changes neurotropic factors
inhibition of glycogen synthase kinase - 3
modulation of cAMP signalling

58
Q

problems with lithium

A

narrow therapeutic window - need to monitor plasma levels

lots of adverse effects

59
Q

other drugs to treat bipolar

A

NRIs
ketamine
opioids
drugs acting via GTC mechanisms

60
Q

talking therapies for depression

A

group physical activity
cognitive behavioural therapy

CBT for more severe forms of depression

61
Q

electroconvulsive therapies

A

done using anaesthetics and muscle relaxants

can be highly effective and produces a rapid resolution of depression in many patients and can also be used for bipolar disorder and schizophrenia (mainly for catatonia)

62
Q

side effects of ECT

A

most common: memory loss.
-Usually transient, but for some people it can last a long time or even be permanent.

short term effects
nausea and loss of appetite,
a headache
confusion/drowsiness.

longer term cognitive problems such as difficulty concentrating and assimilating new information

blunting of their emotional responses.

63
Q

animal model of depression

A

introducing a young animal into a cage with a dominant older male rat

subjecting the animals to chronic unpredictable mild stress was such as illuminating the cage at night, withholding food and water or tilting the cage.

Measures of depression in these models can be things like loss of interest in pleasurable stimuli such as sweetened water.

placed in a stressful situation from which it cannot escape. For example, being suspended by its tail or placed in a beaker of water from which it cannot escape. These situations can induce a condition called “learnt helplessness” or “behavioural despair”. Essentially, the animal will struggle or swim for a while before it becomes hopeless and passive and accepts the stress.

The time that the animal spends struggling/swimming and the time it spends immobile is a measure of how “depressed” it is.

Drugs And The Brain (9 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions