2-16 Anti-Depressants Flashcards
Name the MAOI’s (4)
- Phenelzine
- Isocarboxazid
- Tranylcypromine
- Selegiline
Name the TCA’s (6)
- Amitriptyline
- Nortriptyline
- Doxepin
- Imipramine
- Desipramine
- Clomipramine
“AND IDC (i dont care)”
Name the SSRI’s (6) (Selective Serotonin Reuptake Inhibitors)
- Fluoxetine
- Fluvozamine
- Citalopram
- Sertraline
- Escitalopram
- Paroxetine
Name the SNRI’s (Selective Norepinephrine Reuptake Inhibitors) (3)
- Duloxetine
- Venlavaxine
- Desvenlafaxine
I pop SNRI’s and watch DVD’s
MAO-A vs MAO-B (which is primary?)
- What does MAO-A do?
- What does MAO-B do?
- What function do they have in common?
- MAO-A: metabolizes catecholamine (NE, Epi), 5HT (Key type)
- MAO-B: metabolizes trace amines
- MAO-A/B: both metabolize tyramine and DA
Name the irreversible MAOIs (3)
What does it mean for them to be irreversible?
- Phenelzine
- Tranylcypromine
- Selegiline
Once bound to MAO, enzyme must be replaced (takes 10-14 days)
Reversible MAOI’s (1) How is it used here in the US?
How does their duration of action compare to irreversible MAOI’s
There is only meclobemide and it is not used in the US. It shows a shorter duration than irreversible MAO-I’s
Key MAO AE’s (2)
- What happens and why?
- Potential clinical consequences?
HTN Crisis: “Cheese reaction” : Foods w/ high amounts of tyramine (aged cheeses, wines, cured meats) because they are normally metabolized by live MAO’s and if not metabolized serves as a pressor.
Must be careful if patient is on rec. drugs or already hypertensive (risk of ruptured aneurysm, stroke, etc.)
Serotonin Syndrome: MAO’s +SSRI’s/SNRI (or TCA’s)
Increased reflexes, myoclonus, autonomic dysfunction etc.
How can selegiline be administered in order to minimize the “cheese reaction”?
Via transdermal patch
What is the therapeutic site of action for TCA’s and in general, how do TCA’s differ from each other?
All TCAs block the reuptake pumps of both 5-HT and NE thus preventing their reuptake. Different TCAs differ in the magnitude of the re-uptake blockade of these amines.
- What is a T_ertiary TCA?_
- Name them (2)
- Compare how well they block 5-HT and NE
- TCAs w/ 2 methyl groups of N
- Imipramine and Amitriptyline
- Equally block 5-HT and NE reuptake
- What is a Secondary TCA?
- Name them (2)
- Compare how well they block 5-HT and NE
- TCA having 1 methyl group on N
- Despramine and Nortriptyline
- Preferentially blocks NE re-uptake vs 5-HT
What is unique about the TCAs Clomipramine and Doxepin?
They are both tertiary TCAs but act like secondary.
TCA Pharmacokinetics
- Lipid solubility, protein binding, and volume of distribution (high or low?)
- Is absorption rapid or slow?
- T 1/2
- High lipid solubility, high protein binding, large Vd
- Rapid absorption: serum concentrations peak w/in a few hours
- T 1/2 = 8-36 hrs
Prominent TCA side-effects are due to their blocking actions on which receptors (3)? What are the key SE’s for blocking of each receptor?
- H1 histamine receptors: sedation, weight gain
- M1 muscarinic receptors: sedation, confusion
- a1 adrenergic receptors: sedation, orthostatic hypotension, dizziness
- SNRIs: sexual dysfunction (due to increased serotonin) and HTN and Diaphoresis (due to increased NE)
Put the following (5) effects in order of least to greatest, in terms of the concentration of TCA needed to bring about the particular effect:
CNS toxicity, peripheral Ach receptor blockade, Antidepressant efficacy, CVS toxicity, Histamine receptor blockade
- Histamine receptor blockade
- Peripheral Ach receptor blockade
- Antidepressant efficacy
- CNS toxicity
- CVS toxicity
What (2) populations must you be careful with when prescribing TCAs?
- Elderly- more sensitive to TCA side effects so minimize prescribing them
- Pts w/ substance abuse issues- TCAs have an additive effect w/ CNS depressants (like alcohol, barbituates, opiates, and benzos)
How large is the therapeutic window for TCAs?
Describe the clinical presentation of TCA overdose based on the receptors/ channels effected (4).
- Narrow therapeutic window
- Effects of overdose on…
- a1-adrenergic receptors: hypotension, respiratory depression
- M1 muscarinic receptors: confusion/delirium/altered mental status; respiratory depression
- H1 histamine receptors: confusion/delirium/ AMS; respiratory depression
- Blocks sodium channels in myocardium membranes: quinidine-like effects (prolonged action potential/ QRS interval); cardiac conduction defects and severe arrhythmias
Which SSRI has a half-life longer than the others? Which has the smallest level of protein binding?
Longest half-life: Fluoxetine (1-4d) and its metabolite (7-15d) is signficantly longer than the others
Least protein binding: Escitalopram
Which SSRI is the least selective for 5-HT? Which has the highest affinity for 5-HT?
least: Fluoxetine
most: paroxetine
- What (2) SSRIs use CYP2D6 for metabolism?
- Which SSRI is the most likely of all SSRIs to have drug-drug interactions and why?
- Paroxetine and Fluvoxamine both use CYP2D6
- Fluvoxamine is the most likely to have DDI becomes it inhibits a number of CYP enzymes (1A2, 2C19, 2D6, and 3A4)
What are the (5) potential adverse effects of SSRIs?
- GI
- Anxiety
- CNS issues
- Sexual Dysfunction
- SSRI Discontinuation Syndrome: (dizziness, nausea, HA, insomnia, restlessness, unstable gait, brain “zaps”
Which type of SSRI is most likely to lead to an SSRI discontinuation syndrome?
Most likely w/ short acting SSRIs.
Paroxetine > (effexor/pristiq)>> fluvoxamine > sertraline > citalopram >> fluoxetine
Relative to their antidepressant effect, SSRI adverse effects often occur when?
AEs often occur prior to the onset of antidepressant efficacy
- Which SNRI has the greatest level of protein binding?
- Which (2) SNRIs are most likely to cause discontinuation syndrome?
- Duloxetine (Cymbalta) has the greatest level of protein binding
- Venlafaxine and desvenlafaxine are most likely to lead to discontinuation syndrome (they have the shortest half-lives)
- What is the relationship between Venlafaxine and Desvenlafaxine?
- How does this relationship impact metabolism of Desvenlafaxine?
- How are the other SNRIs metabolized?
- Desvenlafaxine is the metabolite of venlafaxine.
- Because it is a metabolite, desvenlafaxine only goes through phase II metabolism.
- Venlaxine and Duloxetine both are CYP2D6 substrates.
- SNRI Side Effects are dependent on what?
- What are the SEs? (3 main categories)
- Dose dependent SEs
- Same as SSRI SEs + Increased BP and Diaphoresis
Name the (2) atypical antidepressants
Mirtazapine and Bupropion
Mirtazapine
- MOA
- SEs
- Protein binding
- MOA: Noradrenergic and serotonin a2 adrenergic receptro antagonist (blocks presynaptic autoreceptors on NE and 5HT neurons)
- SEs: Because it also blocks histamine, you can see wt gain, dry mouth, and sedation
- Highly protein bound (85%)
How are the sedation effects of Mirtazapine related to dose?
Counterintuitively, while highly sedating at low doses, Mirtazapine is less sedating at high doses and can actually even be stimulating
Buproprion
- MOA
- Metabolism
- Protein binding
- MOA: NE and DA reuptake inhiitor (NDRI)
- Strong CYP2d6 inhibitor
- Highly protein bound (85%)
Buproprion SEs (4)
- SEIZURES (at high doses)
- Dry mouth
- Nausea
- Insomnia
No risk of weight gain, sexual dysfunction, etc.
Nefazodone
- MOA
- SEs (1)
- MOA: Blocks 5-HT reuptake
- SE: Mild sedation
Vilazodone
- MOA
- SEs (1)
- MOA: Blocks 5HT reuptake (partial agonist of 5-HT1A receptors)
- SEs: GI (N/V/D) and Insomnia
Vortioxetine
- MOA (4)
- SEs (1)
- MOA:
- Blocks 5HT reuptake
- Agonist at 5-HT1A
- Partial agonist at 5-HT1B
- Antagonist at: 5-HT3 & 5-HT7
- SEs: GI (Nausea > vomiting/diarrhea)
- What do you have to consider when switching from one MAOI to another?
- What do you have to consider when switiching from any other antidepressant to an MAOI?
- When moving from one irreversible MAOI to another, you need to wait for neurons to regenerate MAO enzymes (usually 10-14 day).
- When moving from any other antidepressant to an MAOI, you need to wait 5 half-lives before starting the MAOI
