Depression Medchem Flashcards
what are common features to identify tricyclic antidepressants (TCAs)?
triple ring formation
not aromatic (no double bonds on middle ring)
what do TCAs have at C3 that increases their activity?
monohalogenation
the side chain of TCAs do not exceed how many atoms?
4
TCAs with tertiary amine groups can be expected to be more ______ and stronger ______
sedating (greater H1 antagonism), anticholinergics (M1 antagonism)
what is the major route of metabolism for TCAs? minor route?
major: Cyp2D6
minor: Cyp2C19
Imipramine undergoes what metabolism? what are the 2 active metabolites?
N-demethylation
Desipramine and 2-hydroxydesipramine
halogenation of TCAs makes them more potent inhibitors of?
5-HT reuptake
what drug class is Imipramine?
TCA
what drug class is amitriptyline?
TCA
amitriptyline undergoes what metabolism? what is the active metabolite?
N-demethylation
nortriptyline
which TCA is used as a mixture of Z/E isomers?
Doxepin
what drug class is doxepin?
TCA
what is the active metabolite of doxepin?
N-desmethyldoxepin
why do we make anti-itch creams containing doxepin?
it has anti H1 activity
why can doxepin be found in a sleep aid drug?
due to its H1 antagonism
which TCA is more selective for inhibiting NET over SERT?
Maprotiline
what drug class is maprotiline?
TCA
what is the mechanism of action of MAOIs?
catalyze the oxidative deamination of beta-arylethyl amines such as NE, DA, 5-HT, and tyramine
what are the 2 characteristics of traditional MAOIs?
- mechanism-based irreversible inhibitors
- lack selectivity between MAO-A and MAO-B
what drug class is tranylcypromine?
traditional MAOI
what drug class is phenelzine?
traditional MAOI
what route of metabolism does phenelzine inhibit?
Cyp2B6
what drug class is isocarboxazid?
traditional MAOI prodrug
what is the name of the active version of isocarboxazid? drug class?
benzylhydrazine
also a traditional MAOI
what drug class is selegiline?
MAO-B inhibitor
what drug formulation does selegiline come in?
transderm patch
what drug class is fluoxetine?
SSRI
what characteristic do all SSRIs have?
an electron withdrawing group consisting of halogens
what route of metabolism does fluoxetine undergo? what is the active metabolite?
what’s significant about fluoxetine’s half-life?
N-demethylation into Norfluoxetine
has a very long half-life, 4-16 days
which two routes of metabolism do fluoxetine/norfluoxetine inhibit?
Cyp2D6 and 2C19
how long does the pt need to wait after stopping MAOI therapy to start fluoxetine therapy?
2 weeks
how long does the pt need to wait after stopping fluoxetine therapy to start MAOI therapy?
5 weeks
which SSRI is used as a single 1S,4S, enantiomer?
sertraline
what drug class is sertraline?
SSRI
what is the active metabolite of sertraline?
N-desmethylsertraline
what route of metabolism does sertraline inhibit?
Cyp2D6
which SSRI is used as the 3S,4R enantiomer?
paroxetine
what drug class is paroxetine?
SSRI
what route of metabolism does sertraline undergo? what is its inactive metabolite?
Cyp2D6 into catechol metabolite
paroxetine is a potent irreversible inhibitor of what route of metabolism?
2D6
what drug class is fluvoxamine?
SSRI
what is the active metabolite of fluvoxamine?
there is none
which 2 routes of metabolism does fluvoxamine inhibit?
Cyp1A2 and 2C19
which SSRI has the most selectivity for SERT?
citalopram
what drug class is citalopram?
SSRI
what is the single active S enantiomer of citalopram?
escitalopram
what is the active metabolite of citalopram?
desmethylcitalopram
what drug class is trazodone?
serotonin modulator and stimulator
what metabolizes trazodone? what is the active metabolite? what is the drug classification of the metabolite?
Cyp3A4
m-chlorophenylpiprazine
5HT2A partial agonist
what drug class is nefazodone?
serotonin modulator and stimulator
what metabolizes nefazodone? the two active metabolites?
Cyp3A4
m-chlorophenylpiprazine and alpha-hydroxynefazodone
both nefazodone and alpha-hydroxynefazodone are inhibitors of what route of metabolism?
cyp3A4
what drug class is vilazodone?
serotonin modulator and stimulator
what metabolism does vilazodone undergo?
Cyp3A4 N-dealkhylation
what drug class is vortioxetine?
serotonin modulator and stimulator
what route of metabolism does vortioxetine undergo?
Cyp2D6
what drug class is venlafaxine?
SNRI
what metabolite is formed when venlafaxine undergoes Cyp3A4 metabolism? active or inactive?
N-desmethylvenlafaxine
inactive
what metabolite is formed when venlafaxine undergoes Cyp2D6 O-demethylation metabolism? active or inactive?
desvenlafaxine
active
what is the major route of metabolism of desvenlafaxine?
minor route?
which is active/inactive?
glucuronidation
3A4 N-demethylation
neither are active
what drug class is duloxetine?
SNRI
duloxetine is metabolized by Cyp1A2 and 2D6, what is the specific target of their metabolism? what else metabolizes duloxetine? active or inactive?
napthalene ring hydroxylation
glucuronidation
inactive
duloxetine is an inhibitor of what route of metabolism?
2D6
what drug class is levomilnacipran?
SNRI
which SNRI is used as the single 1S,2R enantiomer?
levomilnacipran
what is the metabolic route of levomilnacipran?
active or inactive?
3A4-mediated N-deethylation
inactive
bupropion undergoes hydroxylation via which enzyme? what is the metabolite formed? active or inactive?
Cyp2B6
hydroxybupropion
active
bupropion undergoes reduction into what metabolite? active or inactive?
threo and erythro hydroxybupropion
active
bupropion and hydroxybupropion are inhibitors of what enzyme?
2D6
what distinguishes mirtazapine from TCAs despite having very similar structuring?
the basic nitrogen is closer to the tricyclic ring system than in TCAs
what dosage form does esketamine come in?
nasal spray
what are the main routes of metabolism of esketamine?
2B6 and 3A4 N-demethylation
drug class of esketamine?
NMDA receptor antagonist
drug class of phencyclidine?
NMDA receptor antagonist
