Pharmacology of Antidepressants and Mood Stabilisers Flashcards
which drugs diffuse most effectively across the blood brain barrier
hydrophobic/lipophilic
need to diffuse through the fatty barrier
what do psychiatric drugs need to pass through to be effective
blood brain barrier
clinical uses of antidepressants
Moderate to severe depression Dysthymia Generalised anxiety disorder Panic disorder, OCT, PTSD Premenstrual dysphoric disorder Bulimia nervosa Neuropathic pain
what are the types of antidepressants
Monoamine oxidase inhibitors
Monoamine reuptake inhibitors
- tricyclics
- SSRI (selective serotonin reuptake inhibitor)
- noradrenaline reuptake inhibitor
what are monoamines
dopamine
noradrenaline
seratonin (5HT)
(serotonin and noradrenaline are the ones antidepressants effect most)
what is the monoamine hypothesis
depression results from a functional defect of monoamine transmitters
(especially serotonin and noradrenaline)
drugs which deplete monoamine stores cause low mood
where does serotonin originate/travel
rostral area of the midbrain - then projects around the cortex
what does serotonin (5HT) impact
mood sleep feeding behaviour sensory perception
what is the base monoamine (where they originate from)
tryptophan
how is serotonin produced
tryptophan -converted by tryptophan hydroxyls to 5 OH Tryptophan -L-AA decarboxylase converts it to 5HT
what does noradrenaline impact
arousal
emotion
how ado monoamine oxidase inhibitors work (MAO inhibitor)
inhibit monoamine oxidase enzyme which breaks down neurotransmitter into metabolites
examples of MAO inhibitors
Phenelzine
Moclobemide
which MAO inhibitor is reversible
moclobemide
which MAO inhibitor is irreversible
Phenelzine
side effects of monoamine oxidase inhibitors
- ‘Cheese reaction’ - hypertensive crisis (caused by inhibition of monoamine oxidase enzyme in gut preventing breakdown od dietary tyramine)
- potentiates effects of other drugs by decreasing their metabolism
- insomnia
- postural hypotension
- peripheral oedema
what kind of symptoms are caused by tricyclics
anticholingeric side effects
what kind of anti depression would you NOT give to someone with an ischaemic heart disease history
Tricyclics - they are cardiotoxic
what kind of anti depression would you NOT give to someone with an ischaemic heart disease history
Tricyclics - they are cardiotoxic - cause tachycardia, arrhythmia, postural hypotension
what are some examples of tricyclics
Impiramine
Dosulepin
Amitriptyline
Lofepramine
how do tricyclics work
block noradrenaline transporter taking noradrenaline back to the presynaptic neurone to be reuptaken so it stays in the synapse
how do SSRIs work
blocks serotonin transporter taking serotonin back to the presynaptic neurone to be reuptaken so it stays in the synapse
examples of SSRIs
Fluoxetine
Citalopram/escitalopram
Setraline
Paroxetine
Side effects of SSRIs
nausea headache sweating/vivid dreams worsened anxiety sexual dysfunction hyponatraemia (in elderly) transient increase in self-harm/suicidal ideation in young people effects come back when you stop them too
what are other monoamine reuptake inhibitors
SNRIs
venlafaxine, duloxetine
how do SNRIs and dual reuptake inhibitors work
block reuptake of monoamines into presynaptic terminals
similar side effects to SSRIs
lack major receptor blocker actions so more limited range of side effects than tricyclics
what is mirtazapine
atypical antidepressant
- blocks post-synaptic serotonin receptors
- blocks seretenergic side effects if given with SSRIs
side effects or mirtazapine
weight gain + sedation
what is the most effective antidepressant
isn’t one - all similar clinical efficiency
depends what causes the least side effects in different people
only effective in moderate-severe depression
whats the aims of bipolar disorder treatments
Reduce mood in mania
Raise mood in depression
long term - stabilise mood and prevent recurrence of mania and depression
what side effects suggests lithium levels are in a toxic range
ataxia
how is lithium metabolised
it isn’t bc its an element and elements are not metabolism
excreted in urine as lithium
what happens to lithium levels in dehydration
they are increased (Na and lithium are indistinguishable to renal tubules)
how does lithium work
mood stabiliser
blocks phosphatidylinostitol pathways or inhibits glycogen synthesis
side effects of lithium
dry mouth/strange taste polydipsia & polyuria tremor hypothyroidism long term reduced renal function nephrogenic diabetes insidious weight gain
toxic effects of lithium
vomiting diarrhoea ataxia/coarse tremor drowsiness convulsions coma
which mood stabiliser do you do NOT give to women trying to get pregnant
Valporic acid
(an anticonvulsant as a mood stabiliser) - mode of action unclear- may block overactive pathways
side effects of anticonvulsants
valproate & carbamazepine - - drowsiness, ataxia, cardiovascular effects, induced liver enzymes
valporate- teratogenicity
lamotrigine - very small risk of Stevens Johnson syndrome
