Antidepressants Flashcards
what is the monoamine / biogenic amine hypothesis of depression?
deficiency in levels of serotonin, NE, and DA neurotransmission in the synapse
what is the neurotropic hypothesis of depression?
changes in nerve growth factor signaling play a role in cell survival and synaptic plasticity
what is the MOA of TCAs?
- block reuptake of both 5HT and NE by inhibition of SERT and NET respectively
- desensitize presynaptic autoreceptors, further promotes release of 5HT and NE
- reduce central beta adrenergic receptor responsiveness and density
what are the clinical uses of TCAs?
chronic pain, major depression, phobic and panic anxiety states, OCD
what is the side effect profile of TCAs?
- cardiac arrhythmias
2. overdose - convulsions, coma
what is the MOA of MAOIs?
increase synaptic availability of NE and 5HT by blocking catabolism via inhibition of MAO enzymes
what are the clinical uses of MAOIs?
- treatment resistant MDD patients
- atypical depressions
- anxiety states (social, panic)
what is the side effect profile of MAOIs?
orthostatic hypotension and weight gain
what is the MOA of SSRIs?
selectively inhibits SERT and blocks reuptake of 5HT into presynaptic terminal - increases synaptic 5HT
what are the clinical uses of SSRIs?
major depression and other psychiatric disorders
what is the short term side effect profile of SSRIs? long term?
short term - nausea, GI upset, diarrhea
long term - sexual dysfunction
what are the atypical antidepressant classes?
SNRIs, 5HT antagonists, alpha blockers, DA/NE uptake blockers
what is the MOA of lithium?
- prevents recycling of inositol phosphate (mood dampening)
- inhibits release of NE (prevents mania)
what are the clinical uses of lithium?
bipolar disorder - manic and depressive phases
what is the side effect profile of lithium?
tremor, hypothyroidism, nephrogenic diabetes insipidus, skin reactions
what are the MAOI drugs?
- phenelzine
- tranylcypromine
- selegiline
what is the MOA for phenelzine and tranylcypromine?
irreversible non-selective inhibition of both MAOIs (A and B)
what is the MOA for selegiline at low dose? high dose?
low dose - irreversible MAO-B inhibitor
high dose - non-selective MAOI
what is the clinical use of selegiline at low dose? high dose?
low dose - Parkinson’s disease
high dose - antidepressant
what food interaction is important to consider for MAOIs? what is the adverse effect of interaction? what is the MOA?
- tyramine
2. hypertensive crisis - triggers release of catecholamines into synapse
TCAs are potent antagonists of which receptor types?
cholinergic, histaminergic, alpha adrenergic
what are the TCA drugs?
imipramine, desipramine, amitriptyline
what is the main clinical use of imipramine?
- bed wetting
2. TCA
what is the main clinical use of desipramine? what class of drug is this?
- neuropathic pain
2. TCA
what is the main clinical use of amitriptyline?
- sedation
2. TCA
what are the SSRI drugs?
- fluoxetine
- sertraline
- paroxetine
- citalopram
- escitalopram
- fluvoxamine
how does the SSRI MOA differ from the TCA MOA?
SSRIs are selective
what is serotonin syndrome? what are the symptoms? if untreated?
rare side effect of combining SSRIs with other SSRIs, MAOIs, TCAs
lethargy, restlessness, mental confusion
if untreated - hypertension, hyperthermia, hypertonicity, renal failure, death
what are the SNRI drugs?
venlafaxine and duloxetine
what is the MOA of SNRIs?
inhibit serotonin (SERT) and NE (NET) transporters
what is the 5HT antagonist drug?
trazodone
what is the MOA of trazodone? what is the effect?
blocks 5HT (and H1) receptor - sedative but without tolerance or dependence
what is the major side effect of trazodone?
priapism
what is the MOA of bupropion?
blocks NE and DA reuptake and increases presynaptic release of catecholamines
what are the side effects of SNRIs?
similar to TCAs but not as severe
GI, sexual dysfunction, weight gain (serotonergic)
increased BP and HR (noradrenergic)
SSRIs should never be combined with what other drug class? what are the results?
TCAs - serotonin syndrome and TCA toxicity
what are the important drug interactions with lithium? why?
thiazide and loop diuretics - diminishes lithium clearance
