Pharmacology of ADs and Mood Stabilisers

Question 1

why are psychiatric drugs often different from other drugs?

Answer 1

need to pass the BBB

Question 2

which type of drugs diffuse across the BBB best?

Answer 2

hydrophobic/lipophilic

BBB is fatty

Question 3

7 uses of antidepressants?

Answer 3

mod-severe depression
dysthymia
generalised anxiety disorder
panic disorder, OCD, PTSD
premenstrual dysphoric disorder
bulimia
neuropathic pain

Question 4

3 groups of antidepressants?

Answer 4

monoamine oxidase inhibitors
monoamine reuptake inhibitors
atypical drugs (post-synaptic receptor effects)

Question 5

types of monoamine reuptake inhibitors?

Answer 5

tricyclics
other non-selective reuptake inhibitors
selective serotonin reuptake inhibitors
noradrenaline reuptake inhibitors

Question 6

examples of monoamines?

Answer 6

noradrenaline
dopamine
5-HT

Question 7

describe the monoamine hypothesis?

Answer 7

depression is due to a lack of monoamine transmitters (mainly serotonin and noradrenaline)
therefore any drug which depletes stores of monoamines can cause low mood
- not strictly true, depression is multifactorial not directly related to monoamines only

Question 8

what does serotonin affect?

Answer 8

mood
sleep
behaviour
sensory perception

Question 9

where does analgesia affect?

Answer 9

caudal raphe

Question 10

describe the serotonin pathway?

Answer 10

trptophan >* 5-OH tryptophan >* 5HT > leaves presynaptic terminal and acts on postsynaptic 5HT receptor > 5HT reuptaken and metabolised to 5-HIAA by MAO enzyme

*tryptophan hydroxylase, then L-AA decarboxylase involved in these steps

Question 11

where is the source of noradrenaline neurones?

Answer 11

locus caeruleus

Question 12

what does noradrenaline affect?

Answer 12

arousal

emotion

Question 13

pathway at noradrenergic synapse?

Answer 13

tyrosine >* DOPA >* DA >* NA > leaves presynaptic terminal and acts on postsynaptic alpha/beta receptor > reuptakes and metabolised to MHPG by MAO enzyme

• = tyrosine hydroxylase
• = L-AA decarboxylase
• = DA beta-hydroxylase

Question 14

how do MAO inhibitors work?

Answer 14

inhibit monoamine oxidase enzyme which breaks down neurotransmitter into metabolites
therefore more neurotransmitter is available and reuptake is inhibited

Question 15

types of MOA inhibitors?

Answer 15

irreversible (phenelzine) or reversible (moclobemide) inhibitors of MOA-A and B

Question 16

side effects of MOA inhibitors?

Answer 16

cheese reaction (tyramine reaction)/hypertensive crisis
potentiates effects of other drugs by decreasing their metabolism (e.g barbiturates)
insomnia
postural hypotension
peripheral oedema

Question 17

tricyclic side effects?

Answer 17

anti-cholinergic effects

• dry mouth
• urinary retention
• etc

Question 18

tricyclic side effects?

Answer 18

anti-cholinergic effects

• dry mouth
• urinary retention
• blurred vision
• sedation
• weight gain
• cardiotoxic (tachycardia etc - so avoid in cardio disease)
• etc

Question 19

SSRI side effect?

Answer 19

nausea
headache
sweating/vivid dreams
worsened anxiety
sexual dysfunction
hyponatraemia (mainly in elderly)
transient increase in self harm/suicidal ideation in <25 years

Question 20

how do tricyclic antidepressants work?

Answer 20

block noradrenaline transporter so less makes it back to the presynaptic neurone to be reuptaken

Question 21

example of tricyclic?

Answer 21

imipramine
dosulepin
amitriptyline
lofepramine

Question 22

how do SSRIs work?

Answer 22

inhibit the reuptake of serotonin

Question 23

examples of SSRIs?

Answer 23

fluoxetine
citalopram/escitalopram
sertraline
paroxetine

Question 24

what are SNRIs and how do they work?

Answer 24

type of monoamine reuptake inhibitors
AKA dual reuptake inhibitors
block the reuptake of monoamines into presynaptic terminals

Question 25

2 examples SNRIs?

Answer 25

venlafaxine | duloxetine

Question 26

side effects of SNRIs?

Answer 26

similar to SSRIs

Question 27

non-selective antidepressants?

Answer 27

amitriptyline imipramine clopiramine

Question 28

5-HT selective antidepressants?

Answer 28

``` venlafaxine paroxetine sertraline fluoxetine citalopram ```

Question 29

examples of atypical antidepressant?

Answer 29

mirtazapine - blocks mixed receptors bupropion - dopamine uptake inhibitor

Question 30

side effects of mirtazapine?

Answer 30

weight gain and sedation

Question 31

aims of acute bipolar treatment?

Answer 31

reduce mood in mania | raise mood in depression

Question 32

long term bipolar treatment?

Answer 32

stabilise mood and prevent recurrence of mania and depression

Question 33

signs of toxic lithium levels?

Answer 33

``` vomiting diarrhoea ataxia/course tremor drowsiness convulsions coma ```

Question 34

lithium side effects?

Answer 34

``` hypothyroid nausea polyuria tremor dry mouth/strange taste long term reduced renal function nephrogenic diabetes insipidus weight gain ```

Question 35

lithium mode of action?

Answer 35

blocks phosphatidylinositol pathway (2nd messager system) or inhibits glycogen synthase kinase

Question 36

how is lithium metabolised?

Answer 36

it isn't - no elements are metabolised - excreted in urine as lithium

Question 37

how are lithium levels affected by dehydration and why?

Answer 37

lithium levels increase | sodium and lithium ions are indistinguishable to renal tubules

Question 38

which mood stabiliser avoided in pregnancy?

Answer 38

valproic acid (mainly - same effects as sodium valproate)

Question 39

how can anticonvulsants help stabilise mood?

Answer 39

unclear | can block overactive pathways

Question 40

side effects of anticonvulsants?

Answer 40

valproate and carbamazepine - drowsiness, ataxia, cardio effects, induces liver enzymes valproate - teratogenic lamotrigine - small steven Johnson syndrome risk

Question 41

4 examples of antipsychotics?

Answer 41

quetiapine aripiprazole olanzapine lurasidone

Question 42

how do antipsychotics work as mood stabilisers?

Answer 42

dopamine antagonists + 5HT antagonists

Question 43

side effects of antipsychotics?

Answer 43

sedation weight gain metabolic syndrome aripiprazole = extra-pyramidal side effects