Serotonin Receptor Antagonists (5-HT2 Antagonists) (Anti-depressants)

Question 1

What are the 4 major drugs of this group?

Answer 1

Trazodone, nefazodone, Mirtazapine, Mianserin.

Question 2

Whats noteworthy about the PK of this class of 5-HT antagonists?

Answer 2

Extensive first pass metabolism, primarily renal excretion.

Question 3

Metabolism of Trazodone? Nefazodone?

Answer 3

3A4 for both but nefazodone also has 2D6 and gets converted into 3 active metabolites including mCPP (which is also the metabolite of trazodone).

Question 4

What’s special about the active metabolite mCPP>

Answer 4

It’s a strong 3A4 inhibitor.

Question 5

Metabolism of Mirtazapine? Significant PK?

Answer 5

1A2, 2D6, 3A4. Half life is 20-40 hours and prolonged in pt’s with moderate or severe hepatic or renal impairment (75/25 urine/feces excretion).

Question 6

Dosing of Trazodone and nefazodone?

Answer 6

At least x2 a day.

Question 7

MOA of Trazodone?

Answer 7

Blocks 5-HT2AR and alpha 1 AR for the most potent effects. Additionally it hits 5-HT2C, SERT, and H1 receptors, but less potent effects.

Question 8

MOA of Nefazodone?

Answer 8

Blocks 5-HT2 receptors, alpha 1 ARs w/ moderate affinity, SERT and NET with weak affinity. Of note, no antihistamine and anticholinergic effects due to negligable affinity to those receptors.

Question 9

MOA of Mirtazapine and mianserin?

Answer 9

Potent blocking of H1, 5-HT2A, 2C and 5-HT3 receptors, Agonist of alpha 2 receptors.

Question 10

Describe the 5-HT1, 2 and 3 types of receptors. Excitation of 5-HT3 does what?

Answer 10

5-HT1 are Gi inhibitory receptors, HT2 are the Gq excitatory receptors and HT3 are the ionotropic receptors that allow ions to go through. Stimulating HT3 stimulates nausea and vomitting.

Question 11

Therapeutic uses of Trazodone?

Answer 11

Not very effacacious with treating depression, but good for treating insomnia alone or with SSRI’s.

Question 12

Whats attractive about Nefazodone?

Answer 12

In adition to negligable antihistamine and anticholinergic effects, it has reduced sexual side effects.

Question 13

Tx of Mirtazapine and mianserin?

Answer 13

For tx of depression, esp increased effect if used with SSRI’s.

Question 14

Adverse effects of Trazodone?

Answer 14

Sedation, orthostatic hypotension and Priaprism.

Question 15

AEs of Nefazodone?

Answer 15

Orthostatic hypotension, prioprism, hepatotox.

Question 16

AE’s of Mirtazapine and Mianserin?

Answer 16

Sedation, increased appetite, weight gain, agranulocytosis (rare but serious).