SNRIs (Anti-Depressants) Flashcards
What are the 4 SNRIs?
Venlafaxine, Desvenlafaxine, Duloxetine, Milnacipran.
What do SNRI’s stand for?
Serotonin-Norepinephrine Reuptake inhibitors
How are Venlafaxine and Desvenlafaxine related? How are they metabolized
Venlafaxine is metabolized by 2D6 to remove the methyl group and become desvenlafaxine. Desvenlafaxine has minor 3A4 oxidation but mostly metabolized via glucoronidation. They are both renally excreted. Halflife of Desvenlafaxine is almost x2 (11h) of venlafaxine (5h).
Whats special about excretion of desvenlafaxine and what do we need to watch out for?
45% of the drug will be unchanged so we need to adjust for renally impaired.
How is Duloxetine metabolized?
By 2D6 and 1A2, thus hepatic impairment will increase the levels of this drug.
How is Milnacipran metabolized?
Via glucoronidation, 55% unchanged drug renally excreted so same problem as desvenlafaxine.
How do SSRIs and SNRIs compare in terms of CYP inhibition?
SSRIs have a relatively strong CYP inhibition, but SNRIs do not. Venlafaxine/Desvenlafaxine are weak inhibitors, duloxetine is a moderate inhibitor, and milnacipran doesn’t have any CYP inhibition or substrate.
Which SNRI’s inhibit SERT more than NET?
Velnafaxine, desvelnafaxine and duloxetine.
Which SNRI inhibit NET more than SERT?
Milnacipran.
Which SNRI also inhibits dopamine transporter DAT?
Venlafaxine and desvenlafaxine (but des is weak).
Indication of Venlafaxine?
MDD, anxiety disorders, neuropathic pain, perimenopausal symptoms.
Indications of Desvenlafaxine?
MDD
Indications of Duloxetine?
MDD, anxiety disorders, pain (neuropathic, fibromyalgia, chronic MSK pain).
Milnacipran Indications?
Management of fibromyalgia.
Which SNRI is FDA indicated for pain control?
Duloxetine.
Class AE’s of SNRIs?
All the class effects of SSRI’s (the GI, CNS, bleeding, sexual dysfunction, SIADH and withdrawal syndromes). + they have CV dose related problems (HTN, tachycardia).
Which SNRI have low incidence of CV problems?
Duloxetine.
Which 2 SNRI’s are known to have possible hepatotoxicity?
Duloxetine and Milnacipran, so dont give to alcoholics or people with liver disease/liver impairment, jaundice, etc.
Which SNRI are we worried about in terms of overdose?
Venlafaxine, where cardiotox is seen (more than other SNRIs and defn more than SSRIs).
Preggo + SNRI’s?
Category C.
Peds and SNRIs?
Not FDA approved, but off label use of Venlafaxine for ADHD.
Which SNRI is used off label for ADHD in kids?
Venlafaxine.
Problems with SNRIs and geriatics?
Low anticholinergic activity, minimal sedation and hypotention properties.
