Antidepressants Flashcards
monoamine hypothesis
reserpine used for HTN found to cause depression - depleted DA, 5HT, NE
iproniazid/isoniazid - lift depression - inhibit MAO
“depression d/t lowered monoamine NT in synapses - achieve tx via restoring monoamine levels”
isocarboxazid
MAOI
phenelzine
MAOI
traylcypromine
MAOI
selegiline
MAOI
MAOI MOA
mitochondrial enzyme MAO is inhibited = inactivates excess NE, DA, and 5HT that may leak out – they escape degradation
MAO-A: metabolizes NE and 5HT
MAO-B: metabolizes DA and tyramine
antidepressant effect correlates with MAO-A inhibition
hydrazine derivative MAOI
phenelzine
isocarboxazid
non-hydrazine derivative MAOI
tranylcypromine
selegiline
which MAOIs bind irreversibly and nonselectively to MAO-A and MAO-B
phenelzine
isocarboxazid
tranylcypromine
which MAOI only binds MAO-B
selegiline
which MAOI is approved for early tx parkinsons
selegiline
MAOI use
rarely used b/c of AE
used when other tx’s are ineffective
MAOI AE
drowsiness
orthostatic hypotension
weight gain
muscle pain
- serotonin syndrome: hyperthermia, muscle rigidity, myoclonus
- MAOI + serotinergic drug
- cheese reaction
- tyramine causes release of catecholamines = tachycardia, HTN, arrhythmias, seizures
(also seen with sympathomimetic drugs - pseudoephedrine and phenylpropanoloamine)
which MAOI is less likely to cause tyramine induced HTN crisis
selegiline transdermal patch
tx of cheese reaction
phentolamine
prazosin
amitriptyline
TCA
clomipramine
tCA
desipramine
TCA
imipramine
TCA
nortriptyline
TCA
TCA MOA
block SERT and NET = increased MA in cleft
TCA AE
blockade of alpha (orthostatic hypotension, reflex tachy)
- muscarinic (blurred vision, xerostomia, urinary retention) - histamine (sedation, weight gain)
- cardiac fast sodium channels (arrhythmias)
TCA OD tx
sodium bicarbonate - reverse conduction block
citalopram
SSRI
escitalopram
SSRI
fluoxetine
SSRI
fluvoxamine
SSRI
paroxetine
SSRI
sertraline
SSRI
SSRI MOA
specific inhibition of serotonin reuptake
- little activity at alpha, M, and H1 receptors
DOC depression
SSRI
SSRI AE
inc serotinergic activity =
GI upset weight gain (paroxetine) decreased sexual function/interest
SSRI interactions
fluoxetine + paroxetine (inhibit CYP2D6)
Fluvoxamine (inhibit CYP1A2, CYP2C19, CYP3A4)
citalopram, escitalopram, sertraline (low potential for interactions)
(if question tells you person taking multiple medications for HTN, DM, gout etc - give low potential drug)
SSRI OD
seizures
low likely for fatalities
venlafaxine
SNRI
duloxetine
SNRI
SNRI OA
block serotonin and NE reuptake
lack H1, M, and a1 blockade**
venlafaxine
potent inhibitor of 5HT uptake
higher doses inhibit NE uptake
also weakly inhibits DA reuptake
duloxetine
inhbits serotonin and NE reuptake at all doses
bupropion
NDRI
- inhibits NE and DA uptake - increases their release
no sexual dysfunction b/c lacks 5HT component
buproprion OD
seizures
nefazodone
5HT2 antagonist/reuptake inhibitor SARIs
**severe hepatotoxicity - no longer prescribed
trazodone
5HT2 antagonist/reuptake inhibitors SARIs - also inhibits alpha 1 and H1
-extremely sedating and good hypnotic (MAIN USE = hypnotic)
SARIs function
stimulation of 5H2 causes anxiety - so blocking prevents that and may cause sexual dysfunction
combo of 5HT reuptake and 5HT2 antagonist
weak SERT and NET antagonists, strong antagonist at 5HT2
mirtazapine
NASSA = antagonist of central presynaptic alpha 2 receptors - inc release of NE and 5HT
antagonist at 5HT1 and 5HT3
H1 antagonist - *sedation and weight gain
anti-depressant discontinuation syndrome
associated with SSRI discontinuation (most commonly prescribed)
- anxiety, dizzy, HA, lethargy, flu sxs
- electric shock sensations
- insomnia
- n/v/d
which drugs are most likely to cause discontinuation syndrome
paroxetine
venlafaxine
most common with short half life drugs
(least likely with fluoxetine b/c long half life)
which TCAs have greater effects on serotonin
amitriptyline
clomipramine
imipramine
also greater orthostatic hypotension and antimuscarinic effects
which TCAs have stronger NET effects - (greater adrenergic)
2ndary amines: desipramine, nortriptyline
less sedation, anti- muscarinic effects, orthostatic hypotension
which antidepressant is most commonly used as a hypnotic
trazodone
DOC for depression
SSRI
depression adjuncts
atypical antipsychotic
anxiety disorder DOC
SSRI
buproprion is less effective than others
chronic pain use
TCAs and SNRIs (drugs blcoking NE and 5HT reuptake)
SSRIs are not effective
bulimia tx
antidepressants - but not helpful for anorexia
premenstrual dysphoric disorder
SSRIs
smoking cessation tx
bupropion
bipolar contraindication with anti-depressants
may precipitate mania - must screen pts for biopolar disorder
DOC bipolar disorder
lithium
lithium MOA
“inositol depletion theory”
G protein linked receptors to Gq – PLC = cleaves PIP2 = DAG + IP3
IP3 -> IP2 -> IP1 -> inositol
lithium blocks inositol polyphosphatase and monophosphatase = blocking regeneration of inositol - whole cascade stopped
inhibition of central adrenergic, muscarinic, serotonergic transmission
NON-COMPETITIVE = only active receptors on neurons are affected
lithium AE
tremor sedation ataxia seizure wt gain hypothyroidism leukocytosis alopecia nephrogenic diabetes insipidus
tx lithium tremor
propanolol or atenolol
tx nephrogenic DI assoc with lithium
discontinue lithium if possible
–> amiloride otherwise
also thiazides and NSAIDs
lithium intoxication sxs
vomiting diarrhea coarse tremor ataxia coma
lithium in pregnancy
congenital cardiac anomalies
category D
what tests to do in someone taking lithium
serum lithium concentrations
thyroid function
renal function
lithium interactions
dec renal clearance by: thiazides NSAIDs ACE-I ARBs
lithium alternatives
carbamazepine (check CBCs)
valproate (LFT and CBC monitored)
