Antidepressin Flashcards
Trazodone
Nefazodone
5-HT2 antagonists
Trazodone
- Hypnotic
- structure has a trizolo moiety
3.
Nefazodone
major depressin of disorder
2. received an FDA black box in 2001
Bupropion
Unicyclic aminoketone structure
- CNS activatin properties like amphetamine
- mid-1990s
- not related to sexual side effects.
Mirtazapine
Tetracyclic
Amoxapine
Maprotiline
tetracyclic
amoxapine is the N-methylated metabolic of loxapine
share structural similarities and side effects comparable to the TCAs.
not used as much.
Monoamine oxidase inhibitors MAOIs
get therapeutic effects
introduced in 1990s.
not used as much.
toxicity and lethal effect and drug interactions
Phenelzine
Tranylcypromine
MAOIs
-treatment of depression ureponsive to other antidepressants
Selegiline
MAOI
used to treat Parkinson
Hydazine derivative
Pheneylzine
Isocarboxazid
Non-hydrazines
Tranylcypromine and Selegiline
Moclobemide
Some agents have substantial CNS effects
Vilazodone
Vortioxetine
Multimodal serotonergic compounds
- SERT inhibitors
- BOTH HAVE RAPID ONSET
- both have partial agonist effects on 5-HT1A
vortioxetine has partial agonist at 5-HT1A, 5-HT1B and antagonist at 5-HT3, 5-HT7
Both are approved for MDD
possibly fewer side effects.
Fluoxetine
very different from other SSRI drugs.
- metabolized to an active product Norfluoxetine:
- have a methyl group within it.
- have the LONGEST HALF-LIFE. need to be very careful in terms of MAOI
- has to be discontinued 4 weeks or longer.
- minimizes the risk of serotonin syndrome.
Fluoxetine
Paroxetine
potent inhibitors of the CYP2D6
Fluvoxamine
inhibitor of CYP3A4
Citalopram
Escitalopram
Sertraline
Only modest CYP interactions
not too much
Vebkafaxine
Desvenlafaxine
HL~1 hr. once a day dosing
both have the lowest protein binding
-Desvenlafaxine is extreted 45% unchanged in the urine (conjugated), venlafaxine is 4-8% unchanged in the urine.
Duoloxetine
extensive oxidative metabolism
CYP2D6 and CYP1A2
hepatic impairment significantly alters duoloxetine levels unlike desvenlafaxine
Milnacipran
Levomilnacipran
twice daily
well absorbed
Tricyclic antidepressants
well absorbed
long half-lives
does only daily at NIGHT because of their sedating effects
extensive metabolism:
TCA levels can affect fluoxetine.
substrate of the CYP2D6 system. genetic polymorphism for CYP2D6
*Desipramine and Nortriptyline
5-HT2 antagonists
Trazodone Nefazodone -rapidly absorbed -hepatic metabolism -limited bioavailability because of extensive metabolism -often a single night dose, low dose
Nefazodone is a potent inhibitor of CYP3A4
Bupropion
- mean protein binding 85%
- extensive hepatic metabolic
- three active metabolites including hydroxybuptopion
- Biphasic, first phase 1h, second ~14hs
Amoxapine
dopamine receptor 2 (D2) blocker with antipsychotic effects.
Maprotiline
well absorbed orally
Mirtazapine
Half-life 20-40 hours
Monoamine oxidase inhibitors
different MAOIs are metabolized via different pathways
-tend to have extentsive first-pass effects
-may substantially decrease bioavailability
——————–
alternative routes of administration are being developed
selegiline is available in both transdermal and sublingual form
Mechanism of action
.
SERT
transmembrane
in axon terminals
12 transmemb region??
-transport Na+, Cl- and serotonin into the cell and bind to intracellular K+ results in return of the transporter to its original conformation
-serotonin released inside cell
-binding to the serotonin transporter causes tonic inhibition of the dopamine system
Drugs that block both serotonin and norepinephrine transporters
Newer agents: venlafaxine duloexetine --------- Older group: tricyclic antidepressants are termed TCAs
Venlafaxine
weak inhibitor of NET
Desvenlafaxine
Duloxetine
Milnacipran
more balanced inhibitors of both SERT and NET
SNRIs
don’t bind to histamines receptors!
-lack potent antihistamine, a-drenergic blocking and anticholinergic effects
Milnacipran
Levomilnacipran
generally more potent NET than SERT inhibitors
TCAs
bind to a lot of different receptors
potent to SERT
—————-
Imipramine has more serotonin effects initially
-Can have later balanced effects with more NET inhibition
———–
common adverse effects:
5-HT2 antagonists
Nefazodone
Trazodone
Mechanism of action:
blockade of the 5-HT2a receptor
Nefazodone
.MCPP is always at very low concentrations
can cause agonist adverse effects????
Trazodone
.
Tetracyclic & unicyclic antidepressants
.
Bupropion
.
Mirtazapine
.
MAOIs
Mechanism of action: Forms: MAOIs classification: Irreversible, nonselective MAOIs Reversible and selective inhibitors of MAO-A Irreversible MAO-B specific agents
MAOIs
Mechanism of action: Forms: MAOIs classification: Irreversible, nonselective MAOIs Reversible and selective inhibitors of MAO-A Irreversible MAO-B specific agents
Irreversible, nonselective MAOIs
.
Reversible and selective inhibitors of MAO-A
.
Irreversible MAO-B specific agents
.
Multimodal serotonergic compounds
Vilazodone
Vortioxetine
Vilazodone
SERT inhibitor and 5-HT1A receptor partial agonist
Vortioxetine
SERT inhibitor, partial agonist (5-HT1a and 5-HT1b) and antagonist (5-HT3, 5-HT7)
