A.31. Norepinephrine and serotonin receptor antagonist antidepressants. Agomelatine.

Question 1

what is Trazodone?

Answer 1

Serotonin antagonist antidepressant

Question 2

mechanism of action of serotonin antagonist antidepressant ( Trazodone)

Answer 2

1. Inhibition of post-synaptic 5-HT₂ᴀ in the CNS
2. inhibition of serotonin reuptake (SERT)
3. with chronic use–>desensitize pre-synaptic 5-HT₁ᴀ autoreceptors–> ↑ serotonin release

Question 3

what are the indications for giving Trazodone?

Answer 3

major depressive disorders

insomnia (highly sedative) –> “Trazzzodone”

Question 4

Adverse effects of Trazodone?

Answer 4

priapism 
orthostatic hypotension (moderate 𝝰₁ blockade)

Question 5

what is the T1/2 of Trazodone?

Answer 5

short (requires administration 2-3 times a day)

Question 6

what is Agomelatine

Answer 6

agonist MT₁ and MT₂ receptors in the suprachiasmatic nucleus (melatonin receptors)

Question 7

what does Agomelatine do?

Answer 7

5-HT₂ and 5-HT₃ receptor inhibition

Question 8

a side effect of Agomelatine

Answer 8

weight gain

Question 9

what is Agomelatin used for?

Answer 9

major depressive disorders

Question 10

what is Tianeptine?

Answer 10

atypical antidepressant
AMPA-R modulator
μ-opioid receptor

Question 11

what is Tianeptine used for?

Answer 11

major depressive disorders

anxiety

Question 12

what is Lithium?

Answer 12

ion, mood stabilizer

for bipolar disorder (manic-depressive disease)

Question 13

What is the mechanism of lithium?

Answer 13

unknown

enters through Na channels–> accumulates intracellularly

Question 14

important pharmacokinetic property in lithium

Answer 14

narrow therapeutic index

requires monitoring of plasma levels to establish a safe dosage regimen

Question 15

what drugs ↑ plasma levels of lithium?

Answer 15

NSAID’s
ACE inhibitors
thiazide and loop diuretics (chronic use)

Question 16

what substances ↓ plasma levels

Answer 16

caffeine, theophylline

increases renal clearance

Question 17

clinical use of Lithium

Answer 17

1. acute treatment of bipolar disorders

2. maintenance therapy - ↓ frequency of mood swings (‘mood stabilizer’)

Question 18

what agents are usually required at the beginning of lithium treatment?

Answer 18

antipsychotics and/or benzodiazepines

*due to the slow onset of action of lithium

Question 19

what drugs are used concomitantly during maintenance therapy

Answer 19

antidepressants

Question 20

what are the adverse effects of lithium

Answer 20

flu-like symptoms
GI distress
Neurotoxicity: tremors, seizures
hypothyroidism and goiter (lithium is a deiodinase inhibitor)
nephrogenic diabetes insipidus (late, usually reversible)

Question 21

what can Lithium cause if given in pregnancy?

Answer 21

Ebstein’s anomaly

CI in pregnancy

Question 22

symptoms of acute lithium toxicity

Answer 22

vomiting
hyperreflexia
ataxia
seizures

Question 23

how do we treat acute lithium toxicity?

Answer 23

discontinuation of the agent
hydration
consider hemodialysis

Question 24

other drugs used in bipolar disorders

Answer 24

valproate
carbamazepine
(acute and maintenance therapy)

Olanzapine (acute treatment)

Question 25

drugs that can be used during pregnancy with bipolar disorders

Answer 25

clonazepam

Gabapentin