Antidepressants Flashcards
Describe the monoamine deficiency hypothesis
Current antidepressants either block reuptake or inhibit enzyme that breaks down NTs
Describe the dysregulation hypothesis
Failure of homeostatic regulation of NT systems
Describe the hypothalamic-pituitary stress model
Chronic stress and increased cortisol may cause disruption in neuronal function
What drugs act on
5HT transporter
Selective serotonin reuptake inhibitors (SSRI)
What drugs act on
5HT, NE transporter
Serotonin norepinephrine reuptake inhibitors (SNRI)
Tricyclics antidepressants (TCAs)
What drugs act on
5HT, NE, DA transporter
Monoamine oxidase inhibitor (MAOI)
What drugs act on
NE, DA transporter
Bupropion
What drugs act on miscellaneous sites of action?
Nefazodone
Trazodone
Mirtazapine
Vilazodone
Vortioxetine
What are activities of
5HT1A partial agonist
Anxiolytic
Antidepressants
What are activities of
5HT2A antagonist
Anxiolytic
Sleep restoring
What are activities of
5HT2C antagonist
Anxiolytic
What are activities of
Serotonin transporter inhibition
Antidepressant
Anxiolytic
What is the MOA of SSRIs?
What one other action does (only) paroxetine have?
Block pre-synaptic reuptake of serotonin
Paroxetine: blocks post-synaptic muscarinic receptor
What agents are examples of SSRIs?
Fluoxetine
Sertraline
Paroxetine
Fluvoxamine
Citalopram
Escitalopram
What are examples of SNRIs?
Venlafaxine
Duloxetine
Desvenlafaxine
Levomilnacipran
What is the MOA of SNRIs?
Block pre-synaptic 5HT and NE reuptake
*no blockade of alpha1, muscarinic, or histamine receptors
Differentiate venlafaxine dose-related effects
<150 = mostly 5HT action
> 150 = dual 5HT and NE
Which SNRI has higher binding affinity to NE and 5HT reuptake transporters and increases these neurotransmitters at initial doses?
Duloxetine
What is the MOA of TCAs?
Block pre-synaptic reuptake of serotonin and NE
Differentiate between tertiary and secondary amines
Tertiary = more AEs
List examples of TCAs
Tertiary =
+Amitriptyline
+Imipramine
+Clomipramine
Secondary =
- Nortriptyline
- Desipramine
List examples of MAOIs
Phenelzine
Tranylcypromine
Selegiline
What are the MOA of MOAIs?
Bind to MAO irreversibly and destroy its function
Differentiate between monoamine oxidase A and B
MOA A =
Metabolizes NE, 5HT (involved in depression)
MOA B =
Metabolizes dopamine
(Involved in Parkinson’s disease)
What do nefazodone and trazodone do?
Block \+presynaptic 5HT reuptake \+postsynpatic 5HT2 receptor \+postsynpatic alpha1 receptor \+postynaptic histamine receptor
What does bupropion do?
Blocks reuptake of NE and DA
What does mirtazapine do?
Blocks alpha2 autoreceptor
(Causes inc. NE, 5HT)
Blocks postsynaptic 5HT2A Stimulates 5HT1A Blocks post 5HT2C Blocks 5HT3 Blocks H1
What does vortioxetine do?
Indicated for major depression
What AEs are caused by
ACh blockade
Anorexia
Blurry vision
Constipation/confusion
Dry mouth
Sedation, stasis of urine
What AEs are caused by
H1 blockade
Sedation
Dizziness
Confusion
Weight gain
What AEs are caused by
Alpha1 blockade
Orthostatic hypotension
Reflex tachycardia
Dizziness
Sexual dysfunction
Inc. urinary outflow
Which class of antidepressants are worst for anticholinergic effects?
TCAs
Followed by MAOIs
What class of antidepressants are worst for antihistamine effects?
TCAs
Followed by mirtazapine
Which class of antidepressants are worst for alpha1 blockade effects?
TCAs
Trazodone
Nefazodone
What antidepressant AEs is the receptor involved in
5HT
GI (N/V/D)
Platelet dysfunction
What antidepressant AEs is the receptor involved in
5HT2A stimulation
CNS (disturbed sleep)
Sexual dysfunction
What antidepressant AEs is the receptor involved in
5HT2C blockade
Weight gain
What antidepressant AEs is the receptor involved in
5HT3 blockade
No nausea
No GI upset
What antidepressant AEs is the receptor involved in
NE, DA reuptake blockade
Inc. BP/HR
Inc. energy/anxiety/jitteriness
What class of antidepressants are the worst for GI effects?
MAOIs
Followed by TCAs
Why are SSRIs associated with increase in bleeding episodes?
Serotonin potentiates platelet activation
Which antidepressants have the highest risk for seizures?
TCAs
Bupropion
What are miscellaneous AEs associated with antidepressants?
Osteoporosis QT prolongation (citalopram)
Conduction abnormalities
(TCAs highest risk)
Inc. BP/HR - NE/DA drugs
Withdrawal syndrome Sweating SIADH, hyponatremia Weight gain Hepatitis
Compare different antidepressant classes regarding their potential to cause a “hypertensive crisis”
TCAs
SNRIs
Bupropion
Which drugs have the worse withdrawals?
Short acting agents
Paroxetine
Venlafaxine
Fluvoxamine
Which side effect are you most likely to see first with SSRI?
Insomnia
Compare and contrast serotonin syndrome vs. neuroleptic malignant syndrome
Serotonin
+drug = pro-serotonergic
+<12 hrs to develop
+hyperactive bowel sounds
Neuroleptic
+drug = dopamine antagonist
+1-3 days to develop
+rigidity present in muscles
Describe DDIs with MAOIs
Do not use w/in 5 weeks of D/C fluoxetine
Do not use w/in 2 weeks of DC other SSRI, TCA, MAOI
Wait 2 weeks after D/C MAOIs to switch to another antidepressants
If you had a patient complaining of significant nausea,
Which receptor activity would you need in your antidepressant?
5HT3 antagonist
Which drug should be avoided in a patient with significant cardiac history and abnormal EKG findings?
Citalopram
Imipramine
Amitriptyline
A patient who has previously responded to clomipramine for an anxiety condition is requiring a change in medication
Which drug has similar MOA?
Venlafaxine
A 38 YO male with a long h/o alcohol abuse is diagnosed with depression
Which agent would be least desirable to initiate?
Duloxetine
What is the MOA of duloxetine?
5HT and NE reuptake inhibitor
Which antidepressant is least preferred in an elderly patient with glaucoma?
Amitriptyline (TCA)
