Pharmacology of Mood Stabilisers

Question 1

what drugs most effectively diffuse across blood brain barrier?

Answer 1

hydrophobic / lipophillic

water soluble = dont get through BBB

Question 2

what are clinical uses for antidepressant drugs?

Answer 2

depression (mod - severe)
dysthymia 
GAD
panic disorder, OCD, PTSD
premenstrual dysphoric disorder
bulimia nervosa 
neuropathic pain

Question 3

what are three main types of antidepressant drugs?

Answer 3

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

Question 4

what are four different kinds of monoamine reuptake inhibitors?

Answer 4

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

Question 5

give 3 examples of monoamine neurotransmitters?

Answer 5

noradrenaline
5-HT
dopamine

Question 6

give 3 examples of monoamine reuptake inhibitors?

Answer 6

phenelzine
imipramine
fluoxetine

Question 7

what area of cortex does 5-HT control mood, sleep, feeding behaviour and sensory perception?

Answer 7

rostral

Question 8

what area of cortex does 5-HT control analgesia?

Answer 8

caudal raphe

Question 9

what converts the following reactions?

a) tryptophan -> 5-OH-tryptophan
b) 5-OH-tryptophan -> 5-HT

Answer 9

a) tryptophan hydroxylase

b) L-AA decarbocylase

Question 10

what areas of cortex does noradrenalin control arousal and emotion?

Answer 10

local ceeruleus

Question 11

what converts the following reactions?

a) tyrosine -> DOPA
b) DOPA -> DA
c) DA -> NA

Answer 11

a) tyrosine hydroxylase
b) L-AA decarboxylase
c) DA B-hydroxylase

Question 12

what is the mode of action of monoamine oxidase inhibitors?

Answer 12

irreversible (phenelzine) or reversible (moclobemide) inhibitors of MAO-A and B (these normally break down neurotransmitter)

Question 13

what are side effects of monoamine oxidase inhibitors?

Answer 13

cheese reaction / hypertensive crisis

potentiates effects of other drugs (barbiturates) by decreasing metabolism

insomnia

postural hypotension

peripheral oedema

Question 14

how do monoamine oxidase inhibitors cause this “cheese reaction” / hypertensive crisis?

Answer 14

inhibit MAO-A in gut preventing breakdown of dietary tyramine (can’t eat cheese if on these)

Question 15

what should be avoided in 57 year old man with ischaemic HD who has become depressed following MI?

Answer 15

tricyclics (imipramine) - these are cardiotoxic

Question 16

give examples of tricyclic antidepressants?

Answer 16

imipramine
dosulepin
amitriptyline
lofepramine

Question 17

what is mode of action of tricyclic antidepressants?

Answer 17

block the reuptake of monoamines (mainly norarenaline and 5-HT) into presynaptic terminals

Question 18

what are common side effects of tricyclics?

Answer 18

anticholinergic - blurred vision, dry mouth, constipation, urinary retention

sedation

weight gain

CV - postural hypotension, tachycardia, arrhythmias

cardiotoxic in overdose

Question 19

what are examples of selective serotonin reuptake inhibitors?

Answer 19

fluoxetine
citalopram / escitalopram
sertraline

Question 20

what is mode of action of SSRI?

Answer 20

selectively inhibit reuptake of serotonin (5-HT) from synaptic cleft

Question 21

what are common side effects of SSRIs?

Answer 21

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

Question 22

do SSRIs have discontinuation effects?

Answer 22

yes but these are self limiting

Question 23

give examples of other monoamine reuptake inhibitors (dual reuptake or SNRIs)

Answer 23

venlafaxine

duloxetine

Question 24

what is mode of action of other monoamine reuptake inhibitors?

Answer 24

block the reuptake of monoamines (noradrenaline and 5-HT) into presynaptic terminals

Question 25

what are side effects of other monoamine reuptake inhibitors?

Answer 25

similar to SSRIs | lack major receptor blocking actions so more limited range of side effects than tricyclics

Question 26

give examples of an atypical antidepressant drug (mixed receptors effects)?

Answer 26

mirtazapine (blocks a2, 5-HT2 and 5-HT3)

Question 27

what are side effects of atypical antidepressants?

Answer 27

weight gain and sedation

Question 28

what is benefit of mirtazapine if given with SSRIs?

Answer 28

can block serotenergic side effects

Question 29

what is example of dopamine uptake inhibitor which only available in USA?

Answer 29

bupropion

Question 30

what is the aim of acute BPAD treatment?

Answer 30

reduce mood in episodes of mania | raise mood in episodes of depression

Question 31

what is the aim of long term BPAD treatment?

Answer 31

to stabilise mood and prevent recurrence of both mania and depression (prophylaxis)

Question 32

lithium is normally given in what form?

Answer 32

lithium carbonate note - different forms have different bioavailablity so be careful about doses if salt has changed

Question 33

what is the thought mode of action of lithium?

Answer 33

may block phosphatidylinositol pathway (second messenger system) or inhibit glycogen synthase kinase 3B

Question 34

why must 12 hour post-dose blood levels be monitored?

Answer 34

due to narrow therapeutic index

Question 35

how is lithium metabolised?

Answer 35

it is an element - it is not metabolised

Question 36

what will the effect of dehydration be on lithium levels?

Answer 36

they will be increased

Question 37

what are the side effects of lithium?

Answer 37

``` dry mouth / strange taste polydipsia and polyuria tremor hypothyroidism long term reduced renal function nephrogenic diabetes insipidus weight gain ```

Question 38

what are toxic effects of lithium?

Answer 38

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

Question 39

what mood stabiliser should be absolutely avoided in pregnant bipolar woman?

Answer 39

valproic acid - do not even give in childbearing age

Question 40

what types of anticonvulsants can be used as mood stabilisers?

Answer 40

valproic acid lamotrigine carbamazepine

Question 41

is the mode of action of anticonvulsants as mood stabilisers clear?

Answer 41

no - perhaps block overactive pathways

Question 42

what are side effects of valproate and carbamazepine?

Answer 42

drowsiness ataxia cardiovascular effects induces liver enzymes

Question 43

what is main side effect of valproate?

Answer 43

teratogenicity (neural tube defects)

Question 44

what does lamotrigine have a very small risk of?

Answer 44

stevens-johnson syndrome

Question 45

which antipsychotics can be used as mood stabilisers?

Answer 45

quetiapine aripiprazole olanzapine lurasidone

Question 46

what is mode of action of antipsychotics as mood stabilisers?

Answer 46

dopamine antagonism + 5-HT antagonism

Question 47

what are side effects of antipsychotics?

Answer 47

sedation, weight gain, metabolic syndrome | extra-pyramidial side effects (aripiprazole)