Pharmacology of Mood Stabilisers Flashcards
what drugs most effectively diffuse across blood brain barrier?
hydrophobic / lipophillic
water soluble = dont get through BBB
what are clinical uses for antidepressant drugs?
depression (mod - severe) dysthymia GAD panic disorder, OCD, PTSD premenstrual dysphoric disorder bulimia nervosa neuropathic pain
what are three main types of antidepressant drugs?
monoamine oxidase inhibitors
monoamine reuptake inhibitors
atypical drugs (post-synaptic receptor effects)
what are four different kinds of monoamine reuptake inhibitors?
tricyclics
other non selective reuptake inhibitors
selective serotonin reuptake inhibitors
noradrenaline reuptake inhibitors
give 3 examples of monoamine neurotransmitters?
noradrenaline
5-HT
dopamine
give 3 examples of monoamine reuptake inhibitors?
phenelzine
imipramine
fluoxetine
what area of cortex does 5-HT control mood, sleep, feeding behaviour and sensory perception?
rostral
what area of cortex does 5-HT control analgesia?
caudal raphe
what converts the following reactions?
a) tryptophan -> 5-OH-tryptophan
b) 5-OH-tryptophan -> 5-HT
a) tryptophan hydroxylase
b) L-AA decarbocylase
what areas of cortex does noradrenalin control arousal and emotion?
local ceeruleus
what converts the following reactions?
a) tyrosine -> DOPA
b) DOPA -> DA
c) DA -> NA
a) tyrosine hydroxylase
b) L-AA decarboxylase
c) DA B-hydroxylase
what is the mode of action of monoamine oxidase inhibitors?
irreversible (phenelzine) or reversible (moclobemide) inhibitors of MAO-A and B (these normally break down neurotransmitter)
what are side effects of monoamine oxidase inhibitors?
cheese reaction / hypertensive crisis
potentiates effects of other drugs (barbiturates) by decreasing metabolism
insomnia
postural hypotension
peripheral oedema
how do monoamine oxidase inhibitors cause this “cheese reaction” / hypertensive crisis?
inhibit MAO-A in gut preventing breakdown of dietary tyramine (can’t eat cheese if on these)
what should be avoided in 57 year old man with ischaemic HD who has become depressed following MI?
tricyclics (imipramine) - these are cardiotoxic
give examples of tricyclic antidepressants?
imipramine
dosulepin
amitriptyline
lofepramine
what is mode of action of tricyclic antidepressants?
block the reuptake of monoamines (mainly norarenaline and 5-HT) into presynaptic terminals
what are common side effects of tricyclics?
anticholinergic - blurred vision, dry mouth, constipation, urinary retention
sedation
weight gain
CV - postural hypotension, tachycardia, arrhythmias
cardiotoxic in overdose
what are examples of selective serotonin reuptake inhibitors?
fluoxetine
citalopram / escitalopram
sertraline
what is mode of action of SSRI?
selectively inhibit reuptake of serotonin (5-HT) from synaptic cleft
what are common side effects of SSRIs?
nausea headache sweating / vivid dreams worsened anxiety sexual dysfunction hyponatraemia (in elderly) increase in self harm / suicidal ideation
do SSRIs have discontinuation effects?
yes but these are self limiting
give examples of other monoamine reuptake inhibitors (dual reuptake or SNRIs)
venlafaxine
duloxetine
what is mode of action of other monoamine reuptake inhibitors?
block the reuptake of monoamines (noradrenaline and 5-HT) into presynaptic terminals
what are side effects of other monoamine reuptake inhibitors?
similar to SSRIs
lack major receptor blocking actions so more limited range of side effects than tricyclics
give examples of an atypical antidepressant drug (mixed receptors effects)?
mirtazapine (blocks a2, 5-HT2 and 5-HT3)
what are side effects of atypical antidepressants?
weight gain and sedation
what is benefit of mirtazapine if given with SSRIs?
can block serotenergic side effects
what is example of dopamine uptake inhibitor which only available in USA?
bupropion
what is the aim of acute BPAD treatment?
reduce mood in episodes of mania
raise mood in episodes of depression
what is the aim of long term BPAD treatment?
to stabilise mood and prevent recurrence of both mania and depression (prophylaxis)
lithium is normally given in what form?
lithium carbonate
note - different forms have different bioavailablity so be careful about doses if salt has changed
what is the thought mode of action of lithium?
may block phosphatidylinositol pathway (second messenger system) or inhibit glycogen synthase kinase 3B
why must 12 hour post-dose blood levels be monitored?
due to narrow therapeutic index
how is lithium metabolised?
it is an element - it is not metabolised
what will the effect of dehydration be on lithium levels?
they will be increased
what are the side effects of lithium?
dry mouth / strange taste polydipsia and polyuria tremor hypothyroidism long term reduced renal function nephrogenic diabetes insipidus weight gain
what are toxic effects of lithium?
vomiting diarrhoea ataxia / coarse tremor drowsiness convulsions coma
what mood stabiliser should be absolutely avoided in pregnant bipolar woman?
valproic acid - do not even give in childbearing age
what types of anticonvulsants can be used as mood stabilisers?
valproic acid
lamotrigine
carbamazepine
is the mode of action of anticonvulsants as mood stabilisers clear?
no - perhaps block overactive pathways
what are side effects of valproate and carbamazepine?
drowsiness
ataxia
cardiovascular effects
induces liver enzymes
what is main side effect of valproate?
teratogenicity (neural tube defects)
what does lamotrigine have a very small risk of?
stevens-johnson syndrome
which antipsychotics can be used as mood stabilisers?
quetiapine
aripiprazole
olanzapine
lurasidone
what is mode of action of antipsychotics as mood stabilisers?
dopamine antagonism + 5-HT antagonism
what are side effects of antipsychotics?
sedation, weight gain, metabolic syndrome
extra-pyramidial side effects (aripiprazole)
