Antidepressants Flashcards
List the relevant classes of antidepressants?
TCA = tricyclic antidepressants
MAOi = monoamine oxidase inhibitor
RIMA = reversible inhibitor monoamine oxidase A (RIMA)
SSRIs
SNRIs (less selective)
NARI = noradrenaline reuptake inhibitor
Other = mianserin, mirtazapine (NS-recept antagonist), agomelatine, vortioxetine, hypericin
List the relevant TCAs
amitriptyline
imipramine
nortriptyline
clomiparmine
dothiepin
doxepin
List the relevant MOAi
phenelzine
tranylcypromine
List the relevant RIMAs
moclobemide
List the relevant SSRIs
fluoxetine
citalopram
escitalopram
fluvoxamine (can cause sedation)
paroxetine
sertraline (preferred in elderly)
List the relevant SNRIs
venlafaxine
desvenlafaxine
duloxetine
List the relevant NARIs
Reboxetine
Is there an antidepressant that is more effective than the rest?
all are approximately equal in efficacy
Individual patient response may vary markedly (consideration for switch)
Dont want to excessive 5HT (seizures)
SSRIs = regarded as 1st line, favourable risk-benefit ratio
Which antidepressants cause the most sedation and anticholinergic effects?
TCAs = amitriptyline, clomipramine, imipramine (but not as much as first two)
Discuss important considerations for antidepressant treatment
Treatment = start low dose, inc gradually over 2-4 wks as tolerated
Symptom improvement = 1-3 wks
Full effect = 6-8 wks
Cont Tx = 4-12 months after single episode of major depression (usually cont 4-9 months to prevent relapse)
What should be considered for treatment resistant depression?
Inadequate dosing
Inadequate durations
Patient non-compliance
List the indications for SNRIs
Depression, anxiety, panic attacks
OCD, PMDD, bulimia nervosa, PTSD
chronic pain syndrome = 5HT in spine > inhibit body brain signal transduction of pain
Discuss MOA of SSRIs
Selectively block neuronal reuptake of 5HT, lesser effect on reuptake of noradrenaline
Affects both central and peripheral 5HT receptors, requires adaptation to work
Discuss ADRs of SSRIs
Nausea, diarrhoea = dose dependent, activation of 5HT4 receptor > inc Ach > inc motility
Agitation = CNS excitation, Insomnia = H1-R stimulation, sedation = H1-R antagonism
drowsiness, tremor, dry mouth, dizziness, headache, sweating
Extrapyramidal reactions (tardive dyskinesia, dystonia)
Hyponatraemia (part of SIADH) = 5HT > inc ADH > vasopressin -R response > inc aquaporin > H20 from urine back in to blood
hyperprolactinaemia
Why is SSRI efficacy variable between people?
It is metabolised by CYP2D6 and CYP2C9 CYTp450 enzymes = very polymorphic
Discuss the MOA of TCAs
compete for binding site of amine transporters (NET and SERT) > block uptake of amines
Inhibit 5HT and NA reuptake (equally), lesser effect on DA
Also block = H1, M, alpha-1
Discuss the ADRs of TCAs
H1 block = sedation, weight gain,
M1-R block = dry mouth, blurred vision, mydriasis, dec lacrimation, constipation, reduced GI motility, anticholinergic delirium, prolonged QT
Alpha-1 block = orthostatic hypotension, sinus tachycardia (M-block too), urinary hesitancy/retention
hyponatraemia, seizures, inc IOP = 5HT
gynaecomastia in males, galactorrhoea (inc prolactin?), breast enlargement
Highlight important information about TCA toxicity
70-80% who overdose dont make it to hospital
Main effects = CNS (confusion, mania), heart (cardiac arrhythmia)
Initial effect = excitement, delirium, convulsions (sometimes), coma, resp depression (days)
Pronounced atropine-like effects = flushing, dry mouth/skin, mydriasis (pupil dilation), inhibition of gut and bladder
Discuss the MOA of SNRIs
Inhibit NA, and 5HT reuptake
Does not block M, adrenergic, histamine receptors
Common ADRs of SNRIs
M block = dry mouth, constipation, sweating, blurred vision, mydriasis
Alpha1 block = orthostatic hypotension
5HT = sexual dysfunction (impotence), dec libido, seizures, akathisia, hyperprolactinaemia
SIADH = hyponatraemia
Discuss the MOA of mirtazepine
Tetracylic antidepress
Postsyn block of 5HT2-R and 5HT3-R, presynaptic blocker of central alpha2-adrenergic
Inhibition of alpha2 –> prevents alpha 2 mediated inhibition of NA release
potent H1 antagonist = sedative effect
Discuss ADRs of mirtazepine
Common = inc appetite (H1), weight gain (H1), sedation (H1), peripheral oedema (alpha1B)
Rare = ortho hypotension (alpha1), seizure, mania, nightmares,
What are you non-selective MOAi?
phenelzine
tranylcypromine
What are your irreversible, long acting, non-selective MOAi?
phenelzine, tranylcypromine, isocarboxazid
What are your short acting, reversible MOA-A selective; a RIMA
Moclobemide
It is a better option
What do MAOi do?
Cause rapid, sustained inc in 5HT (most), noreadrenaline and dopamine (least)
Discuss some ADRs of MOAI
A1 block = ortho hypotension
5HT = sleep dist (insomnia, hypersomnia), tremor, twitching, myoclonus, hyperreflexia, weight gain, mania, SIADH
Muscarinic block = dry mouth, constipation, blurred vision
NA/5HT = loss of libido, hypersomnia
Discuss the cheese reaction
Commonly seen with MAOi = severe hypertensive response due to tyramine containing foods
Foods e.g. = cheeses, aged/cured/ pickled meats, overripe vegetables/bananas/raisins/figs
Reaction occurs up to 2 weeks after treatment is discontinued, also due to interactions with other amines
Due to MAOi, MAO is unable to breakdown amine tyromine > inc symp, inc serotinergic, inc dopaminergic
Discuss serotonin toxicity and why it occurs
Occurs due to synaptic [serotonin] inc in CNS due to hyperstimulation of 5HT2A serotonin-R
Occurs with high dose of single drug, when >1 serotonergic agent used, or changing antidepressant with inadequate washout period
What are the symptoms of serotonin toxicity?
Clonus, tremor, incoordination, hyperreflexia
mental state changes (confusion, hypomania, agitation)
shivering, sweating, fever
diarrhoea
