Pharmacology of ADs and Mood Stabilisers Flashcards
why are psychiatric drugs often different from other drugs?
need to pass the BBB
which type of drugs diffuse across the BBB best?
hydrophobic/lipophilic
BBB is fatty
7 uses of antidepressants?
mod-severe depression dysthymia generalised anxiety disorder panic disorder, OCD, PTSD premenstrual dysphoric disorder bulimia neuropathic pain
3 groups of antidepressants?
monoamine oxidase inhibitors
monoamine reuptake inhibitors
atypical drugs (post-synaptic receptor effects)
types of monoamine reuptake inhibitors?
tricyclics
other non-selective reuptake inhibitors
selective serotonin reuptake inhibitors
noradrenaline reuptake inhibitors
examples of monoamines?
noradrenaline
dopamine
5-HT
describe the monoamine hypothesis?
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
what does serotonin affect?
mood
sleep
behaviour
sensory perception
where does analgesia affect?
caudal raphe
describe the serotonin pathway?
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
where is the source of noradrenaline neurones?
locus caeruleus
what does noradrenaline affect?
arousal
emotion
pathway at noradrenergic synapse?
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
how do MAO inhibitors work?
inhibit monoamine oxidase enzyme which breaks down neurotransmitter into metabolites
therefore more neurotransmitter is available and reuptake is inhibited
types of MOA inhibitors?
irreversible (phenelzine) or reversible (moclobemide) inhibitors of MOA-A and B
side effects of MOA inhibitors?
cheese reaction (tyramine reaction)/hypertensive crisis
potentiates effects of other drugs by decreasing their metabolism (e.g barbiturates)
insomnia
postural hypotension
peripheral oedema
tricyclic side effects?
anti-cholinergic effects
- dry mouth
- urinary retention
- etc
tricyclic side effects?
anti-cholinergic effects
- dry mouth
- urinary retention
- blurred vision
- sedation
- weight gain
- cardiotoxic (tachycardia etc - so avoid in cardio disease)
- etc
SSRI side effect?
nausea headache sweating/vivid dreams worsened anxiety sexual dysfunction hyponatraemia (mainly in elderly) transient increase in self harm/suicidal ideation in <25 years
how do tricyclic antidepressants work?
block noradrenaline transporter so less makes it back to the presynaptic neurone to be reuptaken
example of tricyclic?
imipramine
dosulepin
amitriptyline
lofepramine
how do SSRIs work?
inhibit the reuptake of serotonin
examples of SSRIs?
fluoxetine
citalopram/escitalopram
sertraline
paroxetine
what are SNRIs and how do they work?
type of monoamine reuptake inhibitors
AKA dual reuptake inhibitors
block the reuptake of monoamines into presynaptic terminals
2 examples SNRIs?
venlafaxine
duloxetine
side effects of SNRIs?
similar to SSRIs
non-selective antidepressants?
amitriptyline
imipramine
clopiramine
5-HT selective antidepressants?
venlafaxine paroxetine sertraline fluoxetine citalopram
examples of atypical antidepressant?
mirtazapine
- blocks mixed receptors
bupropion
- dopamine uptake inhibitor
side effects of mirtazapine?
weight gain and sedation
aims of acute bipolar treatment?
reduce mood in mania
raise mood in depression
long term bipolar treatment?
stabilise mood and prevent recurrence of mania and depression
signs of toxic lithium levels?
vomiting diarrhoea ataxia/course tremor drowsiness convulsions coma
lithium side effects?
hypothyroid nausea polyuria tremor dry mouth/strange taste long term reduced renal function nephrogenic diabetes insipidus weight gain
lithium mode of action?
blocks phosphatidylinositol pathway (2nd messager system) or inhibits glycogen synthase kinase
how is lithium metabolised?
it isn’t
- no elements are metabolised
- excreted in urine as lithium
how are lithium levels affected by dehydration and why?
lithium levels increase
sodium and lithium ions are indistinguishable to renal tubules
which mood stabiliser avoided in pregnancy?
valproic acid (mainly - same effects as sodium valproate)
how can anticonvulsants help stabilise mood?
unclear
can block overactive pathways
side effects of anticonvulsants?
valproate and carbamazepine - drowsiness, ataxia, cardio effects, induces liver enzymes
valproate - teratogenic
lamotrigine - small steven Johnson syndrome risk
4 examples of antipsychotics?
quetiapine
aripiprazole
olanzapine
lurasidone
how do antipsychotics work as mood stabilisers?
dopamine antagonists + 5HT antagonists
side effects of antipsychotics?
sedation
weight gain
metabolic syndrome
aripiprazole = extra-pyramidal side effects
