A.28

Question 1

Norepinephrine and serotonin receptor antagonist antidepressants. Agomelatine. Tianeptine. Agents used for treatment of manic phase of bipolar disorders

Answer 1

Vortioxetin,
Mirtazapine,
Agomelatine,
Lithium

Question 2

Mirtazapine

Answer 2

MOA: selective α2 antagonist, H1-R, 5HT2A/C, 5HT3-R antagonist;
Kinetics: p.o admin., hep.met. by CYT P450,
T1/2=30h;
IND: major depression, PTSD;
Effect&SEs: increased NE synthesis+release (→weight gain), 5HT2C inhibition- stimulation of DA+NE pathways(→anxiolytic effect), 5HT3 inhibition- lack of nausea, vomiting, diarrhea (→antiemetic), H1 inhibition- weak sedative

Question 3

Agomelatine

Answer 3

MOA: MT1/MT2 agonist, NE and DA releaser, 5-HT2B/C antagonist;
IND: major depression;
Contra-IND: dementic patients and patients older than 75y;
SEs: nausea, weight gain, hepatotoxicity, dizziness; Extra: hepatic metabolism by CYP1A2;
T1/2: 1h (dose-x1/day

Question 4

Tianeptine

Answer 4

MOA: AMPA-R modulator (?), enhancer of 5HT reuptake;
Effect: inhibition of stress-induced activation of the HPA-axis (=anxiolytic);
IND: Anxiety, depression, alcohol withdrawal;
SEs: TCA-like SEs but weaker

Question 5

Lithium-carbonate

Answer 5

MOA: mechanism not fully understood.
prevent recycling of inositol→ ↓IP3+DAG→ interfere with actions of Gq/s-coupled receptors→ ↓2nd messengers→ ↓neuronal activity in pathologically overactive circuits→ mood stabilization;
IND: can be used also in unipolar depression (if other drugs didn’t work), acute treatment of bipolar disorders (GOLD STANDARD!),
maintenance therapy→ ↓frequency and magnitude of mood swings (“mood stabilizer”)→ usually an antidepressant/antipsychotic is also required;
ROA: p.o;
Extra: does not bind plasma proteins, can be excreted in breast milk, not metabolized- excreted unchanged in urine, Narrow therapeutic index;
SEs: neurologic- tremor, motor hyperactivity, mental confusion.
Thyroid dysfuntion (→hypothyroidism), polydipsia, polyuria → TSH-Rs uncoupled from its Gs-protein. Teratogenic (→Ebstein’s abnormality→ congenital heart defect), leukocytotsis;
Conta-IND: pregnancy!

Question 6

Vortioxetin

Answer 6

MOA: 5HT-R antagonist, 5HT3A, 5HT7 antagonist, 5HT1A/1B partial agonist;
IND: antidepressants;
Extra: Hepatic metabolism by CYP2D6, fast acting, more expensive;
ROA: p.o (x1/day);
SEs: serotonin syndrome, GI SEs (but well tolerated); T1/2: 66h

Question 7

HPA axis

Answer 7

hypothalamic-pituitary-adrenal axis