M5 L6: Drug Treatment of Affective Disorders Flashcards
learn the list of abbreviations if time permits! on slideshow
- 5-HT: 5-hydroxytryptamine (Serotonin)
- AC: Adenylyl Cyclase enzyme
- AGO: Agonist
- ANT: Antagonist
- BDNF: Brain-Derived Neurotrophic Factor
- CYP: Cytochrome P450
- DA: Dopamine (3,4-
dihydroxyphenethylamine) - DAG: Diacylglycerol
- DAT: Dopamine Transporter
- ED: Erectile Dysfunction
- H: Histamine
- HPA: Hypothalamic Pituitary Axis
- IP3: Inositol Trisphosphate
- MAO: Monoamine Oxidase
- MAOIs: Monoamine Oxidase Inhibitors
- m-cpp: meta-Chlorophenylpiperazine
- MDD: Major Depressive Disorder
- NaSSAs: Noradrenergic and Specific
Serotonergic Antidepressants - NE: Norepinephrine
- NET: Norepinephrine Transporter
- SERT: Serotonin Transporter
- SNRIs: Serotonin-Norepinephrine Reuptake
Inhibitors - SSRIs: Selective Serotonin Reuptake
Inhibitors - TeCAs: Tetracyclic Antidepressants
- TCAs: Tricyclic Antidepressants
what are affective (mood) disorders
- group of conditions where the main feature is disturbances in the person’s mood
(depression, bipolar, anxiety, substance-induced, secondary to general med condition)
the neurotrophic hypothesis
- suggests there is a loss of neurotrophic support
- this loss is associated with a decrease in brain-derived neurotrophic factor (BDNF)
the monoamine hypothesis
suggests a decrease in the amount or function of cortical and limbic monoamines, including serotonin, NE, and dopamine
what are types of antidepressants
- SSRIs
- SNRIs
- TCAs
- 5-HT receptor antagonists/modulators
- norepinephrine-dopamine reuptake inhibitors (NDRIs)
- monoamine oxidase inhibitors (MAOIs)
- tetracyclic antidepressants (TeCAs) - (NaSSA)
draw out the table on the slide show about all the different antidepressants
SSRIs
ex:
mech:
effect:
CYP involved:
adverse effect:
remarks:
ex: fluoxetine (prozac)
mech: block presynaptic SERT
effect: increases 5-HT activity
CYP involved: decreases 2D6
adverse effect: safe ED
remarks: most widely used
SNRIs
ex:
mech:
effect:
CYP involved:
adverse effect:
remarks:
ex: venlafaxine (effexor)
mech: block presynaptic SET and NET
effect: increased 5-HT and NE activity
CYP involved: decreased 2D6
adverse effect: anticholinergic effect, antihistamine effect
remarks: n/a
TCAs
ex:
mech:
effect:
CYP involved:
adverse effect:
remarks:
ex: imipramine (tofranil)
mech: block presynaptic SERT and NET
effect: increase 5-HT and Ne activity
CYP involved: metabolized by 2D6
adverse effect: anticholinergic effect, antihistamine effect
remarks: most widely used until SSRIs came along
5-HT R ANT
ex:
mech:
effect:
CYP involved:
adverse effect:
remarks:
ex: trazodone (desyrel)
mech: 5-HT2a R ANT (postsynaptic) 5-HT1a R AGO (partial)
effect: decrease glutamate in cortex
CYP involved: metabolized by 3A4
adverse effect: hypotension, dysrhythmia
remarks: active metabolite m-cpp**
NDRIs
ex:
mech:
effect:
CYP involved:
adverse effect:
remarks:
ex: bupropion (wellbutrin)
mech: block presynaptic NET and DAT
effect: increase NE and DA activity
CYP involved: decreased 2D6
adverse effect: hypotension, dysrhythmia, insomnia
remarks: 3 active metabolites
MAOIs
ex:
mech:
effect:
CYP involved:
adverse effect:
remarks:
ex: phenelzine (nardil)
mech: block MAO A and B (irreversible)
effect: increased in 5-HT and NE activity
CYP involved: metabolized by 1A2, 3A4, and 2C19
adverse effect: hypertensive crisis w tyramine**
remarks: rarely used now
TeCAs
ex:
mech:
effect:
CYP involved:
adverse effect:
remarks:
ex: mirtazapine (remeron)
mech: block presynaptic alpha2 receptors + 5-HT2&3 & H1 receptors
effect: increased NE, 5-HT, and decreased H activity
CYP involved: metabolized by 1A2, 3A4, and 2D6
adverse effect: sedation, weight gain
remarks: aka NaSSAs
what is the first line of treatment for antidepressants?
SSRI**
SNRI, NDRI, or NaSSA
what are MAOIs drug interactions
- SSRIs, SNRIs, TCAs -> serotonin syndrome
- tyramine containing food -> malignant hypertension -> CVS or AMI
