Antidepressant Drugs Flashcards
What is the paradox of antidepressants?
SEs can start immediately but the therapeutic effects can take weeks
What is the action of MAO inhibitors?
Leads to increased serotonin, dopamine and norepinephrine due to decreased breakdown from the inhibition of MAO.
MAO-A
Metabolizes catecholamines (NE, Epi), 5HT
MAO-B
Metabolizes trace amines and 5HT
Hypertensive Crisis
Tyramine is not degraded while a pt is on an MAO and so it builds up and acts as a pressor and increases BP.
Serotonin Syndrome
Due to a combination of MAO-I and SSRIs that leads to a build up of serotonin that increases its activity leading to increased activity and reflexes.
What are the tertiary tricyclic antidepressants (TCAs) more selective for?
Serotonin and NE are equally selected for
What are the secondary TCAs more selective for?
Norepinephrine
Who should TCAs be avoided in?
- Elderly
- Con-current with CNS Depressants
Where do TCAs act?
All TCAs block the re‐uptake pumps of both 5‐HT and NE thus preventing their re‐uptake.
What are the general SEs of SSRIs?
- GI effects
- Sexual dysfunction
- CNS effects
- SSRI discontinuation syndrome
SSRI Discontinuation Syndrome
Dizziness and nausea that is due to withdrawal and is more likely with short actin SSRIs like paroxetine and fluvoxamine.
Why are there no nausea sexual dysfunction or insomnia as SE from mirtazapine?
It also blocks the other serotonin receptors like 5HT2A/2C/3 which prevents these SEs.
What is the major SE of bupropion?
Can increase risk of seizures at high doses
After stopping an MAOI to switch to another drug, why is there a wait period?
Waiting for the regeneration of the MAO enzyme in the case of irreversible inhibitors. With reversible inhibitors, less time is needed to wait.
When switching from another antidepressant to a MAOI, what is the wait period for?
Wait around a week to wait out the half lives of the drug in the system to flush out. Fluoxetine requires a bit longer of a wait period due to its long half life.
What antidepressant drugs are most likely to cause interactions with other drugs from inhibition of CYP450 systems?
- Fluoxetine
- Fluvoxamine
What are the irreversible MAOIs?
- Phenelzine
- Selegiline
- Tranylcypromine
- Isocarboxazid
What is the half life of MAOI like?
Short - 2-4 hours
What drug combination with MAOI can lead to hypertensive crisis?
- Alpha1 agonists
- NE reuptake blockers
What is a reversible MAO-I?
Moclobemide - not available in the US
Tricyclic Antidepressant MOA
All TCAs block the re‐uptake pumps of both 5‐HT and NE thus preventing their re‐uptake.
What are the tertiary TCAs and what do they act on?
Imipramine and Amitriptyline ‐ produces a comparable blockade of both 5‐HT and NE reuptake.
What are the secondary TCAs and what do they act on?
Desipramine and Nortriptyline - preferentially blocks NE over 5-HT
What are tertiary TCAs metabolized to?
Secondary TCAs
TCA SE
1) H‐1 histamine receptors: excessive sedation, fatigue, weight gain
2) M‐1 muscarinic receptors: confusion & memory dysfunction, excessive sedation, fatigue
3) NE alpha‐1 receptors: postural (orthostatic) hypotension, excessive sedation
TCA Contraindications
- Elderly pts
- Alcoholics
SSRI MOA
Selectively block 5-HT reuptake channels
Which SSRI has the longest half life?
Fluoxetine
Which of the SSRIs has the shortest half lives?
- Paroxetine
- Fluvoxamine
SSRI SE
a) GI‐ decreased appetite, nausea, diarrhea, constipation, dry mouth
b) Anxiety during 1st week of use; (paroxetine in particular)
c) CNS‐insomnia, sedation, headache, dizziness
d) Sexual dysfunction‐loss of libido, impotence, anorgasmia
What is an example of a SNRI?
Venlafaxine
SNRI SE
- Diaphoresis
- Increase in BP that is dependent upon dose
Mirtazapine MOA
Blockade of both noradrenergic and serotonergic nerve terminal’s presynaptic alpha2 receptors which causes increased NE and 5‐HT neurotransmission.
Buproprion MOA
NE and DOPA reuptake inhibitor
Buproprion SE
- can cause dry mouth, nausea, insomnia
- increased seizure risk
Nefazodone MOA
5‐HT2A serotonin receptor antagonist and 5‐HT reuptake inhibitor
What is a SE that nefazodone does not have that makes if favorable?
NO sexual function SE
Nefazodone SE
- Nausea
- Dry Mouth
- Increased Appetite
Vilazodone and Vortioxetine MOA
Serotonin re‐ uptake blockade and serotonin 1A receptor partial agonist
Vilazodone SE
- GI
- Insomnia
- NO weight gain or sexual dysfunction
Vortioxetine SE
- GI
- Some sexual dysfunction at high doses
- NO weight gain
