Psychiatric Disorder: Depression, Lecture part II
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Explain the molecular events of week ~3 and 4 of antidepressant tx that may explain the lag time in clinical effectiveness?
As tx continues, the autoreceptors get downregulated, leading to the desired increased level of NT--> therapeutic response via more postsynaptic receptor activation
Explain the molecular events of the first ~1 and 2 weeks of antidepressant tx that may explain the lag time in clinical effectiveness?
Initially, NT release will bind to the autoreceptors causing a slight decrease in monoamine levels. This can lead to more depression, or in children, aggression.
How does Aripiprazole work?
D2 partial agonist, 5HT1A partial agonist and a 5HT2 antagonist. Used as combo therapy w/ other antidepressants.
What class of drugs is Aripiprazole (Abilify)?
an Antipsychotic used as an antidepressant
Why was Nefazadone taken off the martket?
What are the main side effects of Nefazadone and Trazadone?
Postural hypotension, sedation (both due to a1). Trazadone causes priaprism
How do Nefazadone (Serzone) and Trazadone (Desyrel) work?
Block 5HT autoreceptors, block 5HT transporter and weak a1 and h1 antagonist
What are the side effects of Mirtazapine?
Drowsiness, increase TG and cholesterol, stimulates appetite/weight gain- good for elderly patients w/ insomnia and weight loss
What does Mirtazapine, a tetracyclic antidepressant, antagonize? What is it's overall effect to NT levels?
Blocks H1, A2, 5HT2 (A + C, autoreceptors), and NE transporter. Overall effect is to increase 5HT and NE levels.
What are the side effects of Buproprion?
Nausea, insomnia, jitteriness, decreases appepite and causes weight lose (bupropion for big people)
What other drugs do patients use Buproprion with?
Combo therapy with SSRI because Bupropion only blocks DA and NE transporters
Which two transporters does Bupropion (Wellbutrin) inhibit?
DA and NE.
List the Atypical Antidepressants using mnemonic: "My
Atpical Treatment Begins Now"
Mirtazapine (Remeron), Aripiprazole (Abilify), Trazadone (Desyrl), Bupropion (wellbutrin), Nefazadone (Serzone)
What class of antidepressant is Bupropion (Wellbutrin)
Atypical Antidepressant/2nd Gen w/ SSRI and SNRI
At high doses, what can venlafaxine induce?
What are the side effects of SNRI?
similar to SSRI, also causes HTN in the case of venlafaxine
What is the active metabolite of venlafaxine?
At low to mid doses, Venlafaxine (effector) blocks _____, and at higher doses, the inhibition of ________ increases.
5HT, NE transporters
Which of the 3 SNRI's is a true SNRI? What does it mean to be a "true" SNRI?
Duloxetine is a true SNRI because it inhibits both 5HT and NE reuptake pumps regardless of dose used. (similar to TCA MOA)
List the SNRI using VOD mnemonic
- Venlafaxine (Effexor)
- O-desmethyl venlafaxine (Pristiq)
- Duloxetine (cymbalta)
When can GI discomfort caused by SSRI occur?
Anywhere from @ onset (1-2hr post admin.) or when steady state levels are reached.
What side effects can you exp. Taking SSRI?
Most commonly: GI disturbances (N/V/pain), constipation and diarrhea. GI effects go away with continued use. Also, sexual function is effected: reduced libido, delayed orgasm , and delays premature ejaculation
Do SSRI's have a safer side effect profile compared to MAOI and TCA? And yes, give one reason why MAOI and TCA would be less safe?
Yes, SSRI is safer than MAOI and TCA. MAOI can cause tyramine toxicity (tyramine in lots of foods), and TCA can antagonize many receptors
Besides the Raphe Nucleus, where can you find serotonin?
List the SSRI using this mnemonic:
"SSRI Constantly Force Emotions From People"
Sertraline (Zoloft), Citalopram (Celexa), Fluoxetine (Prozac), Esicitalopram (Lexapro), Flovoxamine (Luvox), Paroxetine (Paxil)
Which SSRI increases energy levels/is the most activating?
Should you treat a depressed patient with high energy levels with Fluoxetine? Why or why not?
No, because some SSRI, such as fluoxetine have "activating effects," which facilitate/increase energy/induce jitters
What are the 2nd generation Antidepressants?
SSRI, SNRI and atypical antidepressants
What are the antiadrenergic side effects?
Postural hypotension, reflex tachycardia, drowsiness
What are the anticholinergic side effects of TCA?
Opposite of dumbbells: constipation, urinary retention, blurry vision, tachycardia, N/V, dry mouth, confusion
What are the histaminergic side effects of TCA?
Drowsiness, Weight gain and confusion
List the receptors that TCA antagaonizes.
Histaminergic, Adrenergic, Muscinaric and Dopaminergic
Why are TCA known as "dirty drugs?"
Binds to many receptors leading to many side effects
What is TCA MOA?
- the reuptake transport pump of 5HT and NE
List the TCA's using the mnemonic: "I Don’t Need A Prescription TCA"
Imipramine (Deprimin), Desipramine (Norpramin), Nortriptyline (Aventyl), Amtriptyline (Elavil), Protrityline (vivactil), Trimipramine (Surmontil).
-triptyline and pramine
Why do patients on MAOI need to monitor their diet?
Tyramine toxicity- lots of tyramine in food (dairy, meat, bread and cereal + grain, veggie and fruit, and others. Mainly things with yeast in it.
What AA is tyramine derived from? And what enzyme is required to make tyramine
Tyrosine; tyrosine decarboxylase
What are the side effects of MAOI?
Insomnia, weight gain, HTN, Tyramine Toxicity ***
List the MAOI's.
- Selegiline (Deprenyl-oral; Emsam Patch)
- Tranylcypromine (Parnate)
- Phenelzine (Nardil)
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