Anti-depressants & Mood Stabilizers (TCAs & Atypicals)

Question 1

Definition of depression?

Answer 1

Affective disorder w/ emotional, cognitive, behavioral, somatic regulation

Question 2

Definition of depression?

Answer 2

Affective disorder w/ emotional, cognitive, behavioral, somatic regulation

Question 3

Core syndrome?

Answer 3

Persistent emotion, guilt, untreatable physical symptoms

Question 4

Pathophys of depression?

Answer 4

Decrease of monoamines (NE & serotonin)

Question 5

When do anti-depressants take clinical effect?

Answer 5

Takes weeks

Question 6

BBW for all anti-depressants & mood disorders?

Answer 6

<24 y/o you should monitor changes in depression, suicidal thinking, unusual behavior

Question 7

What is reactive or secondary depression? What are its symptoms? What is its tx?

Answer 7

it is secondary to loss, drugs, alcohol, other psychiatric disorders. Symptoms: Core syndrome. Tx: remits spontaneously + responds to Rx

Question 8

What is major depressive disorder? Symptoms? Tx?

Answer 8

Recurrent. Symptoms: core syndrome + vital signs. Tx: anti-depressants + ECT

Question 9

What is bipolar disorder (manic depression)? Symptoms? Tx?

Answer 9

Mania + depression episodes. Symptoms: increased elation, irritable, less sleep needed, grandiose notions, increased talking. Tx: mood stabilizers + anti-depressants

Question 10

What are the issues with pharmacogenomics?

Answer 10

ABC (MDR1/P-gp) @ BBB –> decreased access to brain

Question 11

What drugs are substrates for MDR1?

Answer 11

Citalopram, Paroxetine, Amitriptyline, Venlafaxine

Question 12

Non-substrates for MDR1?

Answer 12

Mirtazapine, fluoxetine

Question 13

What are the TCAs?

Answer 13

Amitriphyline, Imipramine, Nortriptyline

Question 14

What do the TCAs treat?

Answer 14

• Major depression
• Bedwetting (Imipramine)
• OCD (Clomipramine)

Question 15

MOA of TCAs?

Answer 15

decrease reuptake of 5HT and NE into presynaptic terminals –> increased actions of neuroTx + change receptor profile with treatment

Question 16

What else do the TCAs do?

Answer 16

block ACh, 5-HT, histamine receptors (these are the basis of ADEs)

Question 17

Are the TCAs highly lipid soluble?

Answer 17

Yes, the get into the brain and into fat

Question 18

Are the TCAs protein bound?

Answer 18

Yes, they have a high volume of distribution and a long half life

Question 19

Describe the metabolism of TCAs?

Answer 19

Tertiary amines –> secondary amines via demethylation (imipramine –> desipramine; amitriptyline –> nortriptyline)
-Metabolized via CYP2D6

Question 20

What are the acute effects of TCAs?

Answer 20

drowsy + decreased cognition

Question 21

chronic effects of TCAs?

Answer 21

increased cognition; NOT euphoria

Question 22

DDIs w/ TCAs?

Answer 22

EtOH, other sedatives; TCAs block clonidine

Question 23

ADEs of TCAs?

Answer 23

1. Orthostatic hypoTN (antagonism of alpha-adrenergic receptors)
2. Anti-DUMBBELLS + CI Glaucoma (antagonism of ACh receptors)
3. Sedations (antagonism of histamine + alpha adrenergic receptors)
4. Metabolic/Endocrine: gain weight + sexual disturbance

Question 24

TCAs have a low TI. What does OD cause?

Answer 24

Arrhythmia, cardiac failure, CHF

• Acidosis, delirium, seizure
• FA says Tri-C’s: Coma, Convulsions, Cardiotoxicity

Question 25

What are the atypical anti-depressants?

Answer 25

Amoxamine, Maprotiline, Trazadone/Nefazodone, Mirtazepine, Bupropion, Venlafaxine, Duloxetine *BoopMir MapTraz & Amox VenDul

Question 26

Atypical anti-depressants treat?

Answer 26

Major depression

Question 27

Amoxapine MOA?

Answer 27

Basically a TCA that is a dopamine antagonist

Question 28

Amoxamine ADE?

Answer 28

DA antagonism --> extrapyramidal effects (Parkinsonism)

Question 29

Maprotiline MOA?

Answer 29

SNRI

Question 30

Maprotiline ADE?

Answer 30

seizures, sedation, orthostatic hypoTN

Question 31

Trazodone, Nefazodone use?

Answer 31

used for depression assc w/ anxiety + sleep disturbance

Question 32

Traz, Nefaz MOA?

Answer 32

SSRI

Question 33

Traz, Nefaz PK? ADE?

Answer 33

CYP3A4 inhibitor; short half life. Nefazodone has been largely discontinued due to hepatotoxicity * FA: sedation, nausea, priapism, ortho hypoTN * *Called Trazabone (priapism)

Question 34

Mirtazepine MOA?

Answer 34

alpha 2 receptor antagonist --> increased release of 5HT + NE

Question 35

Mirtazepine ADE?

Answer 35

Antagonizes 5HT-2 recpetors; sedation (anti-histaminergic); weight gain. Less GI & sexual disturbance than SSRIs

Question 36

Bupropion is also used for?

Answer 36

Smoking cessation; formulated for slow release

Question 37

Bupropion MOA?

Answer 37

weak DA, 5HT, NE reuptake inhibitor; metabolites = SNRI

Question 38

Bupropion ADE?

Answer 38

increases monoamines --> restlessness, anxiety, seizures

Question 39

Venlafaxine MOA?

Answer 39

SSRI + SNRI w/ no antihistamine, anti-ACh, anti-adrenergic properties (avoid TCA ADEs)

Question 40

Venlafaxine ADE?

Answer 40

small sustained HTN

Question 41

Duloxetine MOA? A unique thing about it?

Answer 41

SNRI; it is the most potent SNRI available

Question 42

PK of duloxetine?

Answer 42

50% bioavailability; 95% protein bound; CYP2D6 metabolized

Question 43

Vilazodone MOA?

Answer 43

potent 5HT1a partial agonist and SSRI