Antidepressants Flashcards
What monoamines are metabolized by Mao-A vs Mao-B
MAO-A: NE, Epi, Serotonin, Dopamine, tryamine
MAO-B: trace amines, DOPAMINE, 5HT at high concentrations, tyramine
Which irreversible MAO-I binds preferentially to MAO-B?
Selegiline
What are some common side effects of MAO inhibitors?
GI-nausea, constipation, appetite change, Orthostatic hypotension-dizziness Sedation Sleep disturbances Sexual dysfunction Weight gain
Name two irreversible MAO inhibitors
Phenelzine and Tranylcyrpromine
What are two serious adverse effects associated with MAO-I’s
Hypertensive crisis
Serotonin syndrome
Which MAO-I has the lowest risk of a hypertensive crisis?
selegeline: it preferentially inhibits MAO-B.
MAO-A is responsible for metabolism of tyramine by the GI tract
Tyramine is a pressor –> release of NE –> hypertensive crisis
What are the symptoms of serotonin syndrome?
Hyperreflexia
Myoclonus
Autonomic dysfunction (increased bp, increased temp)
Disorientation
How do secondary TCA’s work?
NE > 5HT re-uptake inhibitor
How do tertiary TCA’s work?
NE=5HT re-uptake inhibitor
What are the side effects of TCAs associated with blocking the H1 receptor?
Sedation and weight gain
What are the side effects of TCAs associated with blocking the M1 muscarinic receptors?
sedation, confusion, blurred vision, urinary retention, dry mouth, constipation
What are the side effects of TCAs associated with blocking the alpha-1 adrenergic receptors?
sedation, orthostatic hypotension, dizziness
What are the side effects of TCAs associated with blocking serotonin vs NE re-uptake?
Serotonin: sexual dysfunction
NE: hypertension, sweating
IN order, what are the receptors bound by TCAs (from receptors bound at lowest concentration to receptors bound at highest concentration)
Histamine ACh --Anti-depressant efficacy-- (NE and 5HT) CNS toxicity (about 4x drug efficacy) CVS toxicity (about 5x drug efficacy)
In what age group should TCA’s be avoided?
Elderly- they are more susceptible to the side effects due to decreased renal and hepatic function, and they are also more likely to have polypharmacy- other drug interactions
Describe the therapeutic index of TCAs
The therapeutic index is narrow- avoid giving it to anyone who is at risk for overdosing, as ingestion of a 2 week supply can be lethal
How do TCAs cause cardiac problems?
They block fast Na+ channels in the myocardium –> prolonged action potential, prolonged QRS interval –> cardiac conduction defects and potentially lethal arrhythmias
When does selegiline work as an antidepressant?
At high doses, when it begins to inhibit MAO-A
MAO-I’s combined with what classes of drugs can lead to serotonin syndrome?
Antidepressants, Opioids
Mirtazapine, SNRIs, TCAs, SSRIs
MAO-I’s combined with what classes of drugs can lead to a hypertensive crisis?
Sympathomimetics
Antidepressants (all but SSRIs)
OTC cold remedies
Tertiary TCAs are metabolized to become what?
Secondary TCAs
Imipramine is metabolized to what drug?
Desipramine (a secondary TCA)
Amitriptyline is metabolized to what drug?
Nortriptyline
Why should TCAs be avoided in people that take other CNS depressants (alcohol, barbiturates, opiates, benzodiazepines)?
Because of additive effects that can lead to over-sedation or possible death
Where are TCAs metabolized?
In the liver - CYP450 system
Of the SSRIs, which one has the highest affinity for 5HT, NE and Dopamine receptors compared to when it begins to bind the other histamine, muscarinic etc receptors?
Sertraline
Which of the antidepressants has the longest half-life?
Fluoxetine: it has the longest half-life of all the drugs used in psych
It’s half life (1-4 days) is extended as the active metabolite is 7-15 days!
Important: If fluoxetine interferes with another drug through the CYP450 system, it’s going to take a looonnnggg time to clear out
Which two SSRIs are strong CYP 2D6 inhibitors?
Fluoxetine and Paroxitine
Which two SSRIs have the shortest half-life of the SSRIs? What is the risk of such a short half life?
Paroxetine and Fluvoxamine
Short half life –> most likely to undergo withdrawal symptoms with a missed dose
What’s the difference between citalopram and Escitalopram?
Citalopram = both isomers Escitalopram= pure S isomer (the active compound)
Which SSRI is the prototype?
Fluoxetine – therefore the least 5-HT selective
Which SSRI has the highest affinity for the 5HT transporter?
Paroxetine
How does Paroxetine affect its own metabolism?
Paroxetine slows its own metabolism (as a CYP 2D6 inhibitor)
List the relative receptors bound by Venlafaxine in order
5HT , NE, Dopamine …THEN all the side effects
As a result, side effects are related to serotonin and NE
Are venlafaxine and dualoxetine associated with discontinuation syndrome?
Yes- they both have relatively short half-lives
What is the MOA of mirtazapine?
Blocks both NE and Serotonin alpha-2 autoreceptors
What is the MOA of bupropion?
NE and dopamine re-uptake inhibitor
How does Mirtazapine have no low side effects associated with nausea, sexual dysfunction, insomnia and anxiety?
Mirtazapine also blocks 5-HT2A, 5-HT2C and 5-HT3
What are the major side effects associated with mirtazapine?
Histamine binding –> weight gain, dry mouth, and sedation
What are the effects of bupropion in the liver?
Strong CYP2D6 inhibitor
What is the MOA of nefazodone?
5HT re-uptake inhibitor
5HT-2A receptor antagonist
What are the side effects of nefazodone?
No sexual side effects, sedation
How long does it take cells to regenerate MAOs after stopping MAO-Is?
10-14 days
How long do you have to wait after stopping a RIMA for the effects to wash out?
1 day - RIMAs are reversible
After stopping any antidepressant to switch to an MAO-I, how long do you have to wait?
5 half lives for the drugs to clear (about a week)
