Norepinephrine and Serotonin receptor antagonist ADs. AgomelatineTianepine Agents for manic bipolar disorder

Question 1

What are the norepinephrine and serotonin antagonist antidepressants

Answer 1

Mirtazepine and Trazodone (and Nefazodone)
heterocyclic/atypical.

Also called heterocyclic antidepressants

Question 2

Trazodone mechanism and indications

Answer 2

Main actions:

• Inhibits alpha1
• Inhibits 5HT2a

Minor actions:

• Inhibits NET
• Inhibits SET
• Inhibits H1

Indications:
Depression with insomnia - it causes sig sedation.

Question 3

Trazodone SEs and contras

Answer 3

Significant sedation - contraindicated along with any other CNS depressants.

Orthostatic hypotension - contraindicated in elderly

Priaprism - gives you a TrazoBONEr
- making it contraindicated in sickle cell anemia and multiple myeloma, which for some reason increase risk of priaprism.

Other sexual dysfunction

Serotonin syndrome

Rare cases of hepatotoxicity

Question 4

Mirtazepine mechanism and indications

Answer 4

1) Alpha 2 inhibition. Increases NE and 5HT release presynaptically
2) Inhibits 5HT2 and 5HT3
3) Inhibits H1

Indications:

• Used as 1st line for Depression with insomnia.
• Often given in conjuction with Buproprion to balance its arousal effects (not directly, but via its H1 inhibition, while buproprion increases NE)
• Also for depression in patients that have had sexual side effects with other drugs. Has no sexual SEs, no antimuscarinic effects
• Depression with anorexia. It causes weight gain.

Question 5

Mirtzepine SEs

Answer 5

Weight GAIN

Question 6

Agomelatine

Answer 6

AGONIST at MT1 and MT2
Antagonist at 5HT2C

Also increases NE and DA release in cortex.

Atypical antidepressant

Doesn’t cause weight gain or sexual dysfunctions.

Question 7

Tianeptine

Answer 7

Structurally is a TCA

Increases Serotonin uptake or may be a reuptake inhibitor.
Increases DA relase also.
mu opioid receptor agonist.

Inhibits stress induced activation of the HPA axis.

Question 8

Agents to treat manic phase of bipolar

Answer 8

Lithium carbonate

Sodium Valproate
Carbamazepine
Lamotrigine

1st and 2nd gen antipsychotics

Question 9

Dose for lithium?

Answer 9

0.4-1 g/day, orally, Lithium Carbonate.

Blood concentration should be checked to confirm concentration is
0.5-1.0 mEq/L

Toxic plasma level is 1.5-1.7 mEq/L

Question 10

Lithium mechanism

Answer 10

it is UNKNOWN

BUT, may involve:

Inhibition of IP3 signaling pathway

Inhibition of Glycogen synthase kinase 3

Inhibition of other kinase pathways

Question 11

Lithium indications

Answer 11

1st line for bipolar disorder

Is effective in the long term at decreasing BOTH the manic episodes and depressive episodes
-mood stabilizer-

but it is NOT useful in acute manic episodes

Question 12

Lithium side effects

Answer 12

GI irritation, nausea vomitting diarrhea

Chronic:

• Tremor, Ataxia
• Confusion
• Hypothyroidism
• Nephrogenic Diabetes Insipidus
• Increased Aldosterone levels and Edema
• Acne and Folliculitis
• Teratogenic
• Atrialization of the RV - Ebsteins abnormality.

Question 13

Lithium kinetics and interactions

Answer 13

Taken orally, eliminated purely by urinary excretion, no metabolism.

Everything that decreases GFR increases lithium

ACEIs
Loops
Thaizides
Dehydration
NSAIDs