Anti Depressant Drugs - Segars Flashcards
What are the symptoms of withdrawal syndrome?
FINISH
- flu-like
- insomnia
- nausea
- imbalance
- sensory disturbance
- hyperarousal
what is the monoamine theory of depression?
agents block 5HT and/or NE re-uptake by pre-synaptic transporters (SERT, NET)
what are the “other” antidepressant indications Segars wants us to know?
- nicotine withdrawal
- enuresis (can’t control urination)
- diabetic peripheral neuropathy, fibromyalgia, and chronic MSK pani
- stress incontinence
what med used for nicotine withdrawal?
bupropion
what med used for enuresis?
impramine
what med used for diabetic peripheral neuropathy, fibromyalgia, chronic MSK pain and stress incontinence?
duloxetine
- citalopram
- escitalopram
- fluxotine
- paroxetine
- sertraline
- vilazodone
- vortioxetine
serotonin-selective reuptake inhibitors
- amitriptyline
- clomipramine
- doxepin
- imipramine
tertiary amines
- amoxapine
- nortriptyline
- desipramine
secondary amines
- TCA’s
- descenlafaxine
- duloxetine
- venlafaxine
- levomilnacipran
serotonin-norepinephrine reuptake inhibitors
buproprion MOA?
noradrenergic-dopamine reuptake inhibitor
- mirtazapine
- nefazodone
- trazodone
serotonin-noradrenergic receptor antagonist
- isocarboxazid
- phenelzine
- selegiline
- tranylcypromine
monoamine oxidase inhibitors
amoxapine MOA?
SNRI and dopamine antagonist
what is the first line drug class prescribed for depression?
SSRI’s
what is the additional MOA of vilazodone?
also a partial agonist of 5HT-1A
what is the additional MOA of vortioxetine?
- partial agonist on 5HT-1B
- full agonist on 5HT-1A
- full agonist on 5HT-1D,3,7
what drug class has much less impact on histamine, muscarinic and adrenergic receptors - and fewer side effects/risk than TCA's?
SSRI’s
what side effect is a concern with all categories of anti depressants?
acute withdrawal reactions
what are the most serious side effects of SSRI’s?
serotonin syndrome:
- sweating
- hyperreflexia
- akathisia
also suicidal thoughts/tendencies
when is there an increased risk of serotonin syndrome?
when SSRI’s are given concurrently with other serotonin-affecting agents
which SSRI has the most CYP450 drug-drug interactions?
fluoxetine (broad and strong inhibitor) - KNOW this one
which SSRI’s have the least CYP450 drug-drug interactions?
vortioxetine, escitalopram
which SSRI’s have low/mild CYP450 drug-drug interactions?
citalopram, sertraline, vilazodone
what is amitriptyline metabolized into?
nortriptyline (tertiary -> secondary amine)
what is imipramine metabolized into?
desipramine (tertiary -> secondary amine)
what other receptors do TCA’s block?
- histamine (H1)
- muscarinic (cholinergic)
- alpha 1 adrenergic
what are the 3 key system-based side effects of TCA’s?
- cardiovascular (alpha): tachycardia, orthostatic hypotension, dysrhythmias
- anticholinergic: dry mouth, urinary retention/constipation, blurred vision
- CNS (histamine): sedation/fatigue, dizziness/seizures
what are the 3 C’s of a TCA overdose?
- coma
- cardiotoxicity (conduction abnormalities) -> “quinidine-like” effect
- convulsions
what two SARA’s act like SSRI’s AND selectively block post-synaptic a1 receptors on NE neurons and post-synaptic 5HT receptors?
- trazodone
- nefazodone
which SARA blocks pre-synaptic a2 receptors on NE and 5HT neurons AND blocks post-synaptic 5HT-2/3 receptors?
mirtazapine
- no SERT-NE activity
- also H1 blockage (sedation)
what are the side effects of SARA’s?
- CNS sedation (mostly trazodone/mirtazapine)
- orthostatic hypotension (mostly trazodone)
- weight gain (mostly mirtazapine)
what is the worst/most worrisome side effect of bupropion (NDRI)?
seizures
- can also cause insomnia
all MAOI’s are non-selective for A/B except for which?
selegiline is B selective
which is there a 2 week wash-out period for MAOI’s?
all oral agents are considered irreversible
- they increase levels of monoamines in neuronal vesicles and increase amounts of NE. 5HT and DA released
NOTE: fluoxetine has a FIVE week washout period!
what is the major concern with MAOI’s?
risk of hypertensive crisis
- MAOI’s inhibit MAO-A, which is necessary in GI for tyramine metabolism
- increased tyramine in diet (fermented foods) can induce significant catecholamine release and HTN crisis
what are the sx of hypertensive crisis?
- severe headache
- nausea/vomiting
- sweating/severe anxiety
- nosebleeds
- tachycardia
- chest pain
- changes in vision
- SOA
- confusion
what is esketamine?
a miscellaneous antidepressant
- NMDA-receptor (glutamate) antag
when is esketamine indicated?
treatment-resistant depression in conjunction with ongoing antidepressant therapy
what is brexanolone?
a miscellaneous antidepressant
- GABA-A receptor positive allosteric modulator
NOTE: 60 hr IV administration by authorized physician only! but single dose lasts up to 30 days!
what are the two classes of mood stabilizers?
- anti-seizure agents
- miscellaneous
- carbamazepine
- lamotrigine
- divalproex/valproic acid
anti-seizure agents, used as mood stabilizer
- exact MOA unknown
litium
miscellaneous mood stabilizer
what are the actions of lithium?
alters brain structure, neurotransmitter modulation, and intracellular changes
what is the only mood stabilizer with neuro-protective effects?
lithium
NOTE: is a monovalent ion, handled by kidneys similar to Na/K. Li competes with Na for kidney reabsorption
what is the MOA of lithium?
inhibits DA neurotransmission, by interfering with activity of both stimulatory and inhibitory proteins (Gs and Gi), keeping them inactive
- lithium also increases GABA levels in CSF by promoting neurotransmission (NT)
NOTE: in mania, dopamine NT is increased. in depression, dopamine NT is decreased
what are the main side effect of lithium?
polyuria/polydipsia
- causes clinical nephrogenic diabetes insipidus
what are the drug-drug interactions with lithium?
- diuretics (preferential Na loss and Li reabs)
- ACEI’s
- NSAID’s
what are the indications for lithium?
- acute and maintenance treatment of mania/bipolar I disorder
- augmentation in unipolar depressive pts with inadequate response
what are the indications for valproic acid/divalproex?
acute bipolar I (with or without psychotic features)
what is lamotrigine used for?
maintenance of bipolar I and II
what is carbamazepine used for?
acute and maintenance treatment of acute mania and mixed episodes (bipolar I)
which mood stabilizer is a major CYP450 inducer?
carbamazepine
