SNRIs (Anti-Depressants)

Question 1

What are the 4 SNRIs?

Answer 1

Venlafaxine, Desvenlafaxine, Duloxetine, Milnacipran.

Question 2

What do SNRI’s stand for?

Answer 2

Serotonin-Norepinephrine Reuptake inhibitors

Question 3

How are Venlafaxine and Desvenlafaxine related? How are they metabolized

Answer 3

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).

Question 4

Whats special about excretion of desvenlafaxine and what do we need to watch out for?

Answer 4

45% of the drug will be unchanged so we need to adjust for renally impaired.

Question 5

How is Duloxetine metabolized?

Answer 5

By 2D6 and 1A2, thus hepatic impairment will increase the levels of this drug.

Question 6

How is Milnacipran metabolized?

Answer 6

Via glucoronidation, 55% unchanged drug renally excreted so same problem as desvenlafaxine.

Question 7

How do SSRIs and SNRIs compare in terms of CYP inhibition?

Answer 7

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.

Question 8

Which SNRI’s inhibit SERT more than NET?

Answer 8

Velnafaxine, desvelnafaxine and duloxetine.

Question 9

Which SNRI inhibit NET more than SERT?

Answer 9

Milnacipran.

Question 10

Which SNRI also inhibits dopamine transporter DAT?

Answer 10

Venlafaxine and desvenlafaxine (but des is weak).

Question 11

Indication of Venlafaxine?

Answer 11

MDD, anxiety disorders, neuropathic pain, perimenopausal symptoms.

Question 12

Indications of Desvenlafaxine?

Answer 12

MDD

Question 13

Indications of Duloxetine?

Answer 13

MDD, anxiety disorders, pain (neuropathic, fibromyalgia, chronic MSK pain).

Question 14

Milnacipran Indications?

Answer 14

Management of fibromyalgia.

Question 15

Which SNRI is FDA indicated for pain control?

Answer 15

Duloxetine.

Question 16

Class AE’s of SNRIs?

Answer 16

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).

Question 17

Which SNRI have low incidence of CV problems?

Answer 17

Duloxetine.

Question 18

Which 2 SNRI’s are known to have possible hepatotoxicity?

Answer 18

Duloxetine and Milnacipran, so dont give to alcoholics or people with liver disease/liver impairment, jaundice, etc.

Question 19

Which SNRI are we worried about in terms of overdose?

Answer 19

Venlafaxine, where cardiotox is seen (more than other SNRIs and defn more than SSRIs).

Question 20

Preggo + SNRI’s?

Answer 20

Category C.

Question 21

Peds and SNRIs?

Answer 21

Not FDA approved, but off label use of Venlafaxine for ADHD.

Question 22

Which SNRI is used off label for ADHD in kids?

Answer 22

Venlafaxine.

Question 23

Problems with SNRIs and geriatics?

Answer 23

Low anticholinergic activity, minimal sedation and hypotention properties.