Anti-Depressants

Question 1

Two Primary Types of Depression Classification

Differentiation?

Answer 1

MDD or Unipolar

Bipolar - has manic episodes

Key is MANIC EPISODES

Question 2

Chemical Anti-Depressant Important Considerations (3)

Answer 2

Ineffective in 30% of patient population

Therapeutic response takes weeks to months

Side effects can limit dosing - elderly are more likely to experience adverse effects

Question 3

Two Hypotheses of Depression

Answer 3

Monoamine/Biogenic Amine

Neurotrophic

Question 4

Monoamine/Biogenic Amine Hypothesis

Answer 4

Depression may be related to DEFICIENCY OF 5-HT, NE, and DA

Question 5

Neurotrophic Hypothesis

Answer 5

Loss of NEUROTROPHIC GROWTH FACTORS

BDNF - “brain fertilizer”

Question 6

MAOI Mechanism of Action

Answer 6

block MAO enzyme (MAO a or b)

increases synaptic availability of NE AND 5-HT

Question 7

MAO-A targets

MAO-B targets

Answer 7

A - Tyramine, NE, 5-HT, DA

B - DA

Question 8

Phenelzine

Answer 8

MAO-A and B inhibitor

irreversible

WORSE SIDE EFFECT PROFILE

Question 9

Tranylcypromine

Answer 9

MAO-A and B inhibitor

Irreversible

WORSE SIDE EFFECT PROFILE

Question 10

Selegiline

Dose dependent uses?

Answer 10

MAO-B Inhibitor (low dose)
Non-selective (High dose)

Low dose - Parkinsons

High dose - Antidepressant

Question 11

MAOI Most common side effects

Answer 11

ORTHOSTATIC HYPOTENSION - alpha-1 receptor inhibition in brainstem

WEIGHT GAIN

Irreversible MAOi’s have HIGHEST RATE OF SEXUAL DYSFUNCTION

Question 12

Food Interactions

Answer 12

Tyramine

HYPERTENSIVE CRISIS

Question 13

Tricyclic Antidepressant Important clinical use

Answer 13

CHRONIC PAIN CONDITIONS

tricyclic - three ring structure

Question 14

Tricyclic Antidepressant MOA

Answer 14

block reuptake of 5-HT AND NE

inhibits SERT and NET

Question 15

Imipramine - drug type? MOA? Important characteristic?

Answer 15

inhibits SERT and NET

PROTOTYPE TCA

has some anti-cholinergic effect

Used to treat enuresis

Question 16

Desipramine - drug type? MOA? Important characteristic?

Answer 16

TCA

inhibits SERT and NET

More effective at treating neuropathic pain

Question 17

Amitriptyline - drug type? MOA? Important characteristic?

Answer 17

TCA

inhibits SERT and NET

Sedative effects

Question 18

Side Effects of TCA’s

Answer 18

Hip breakers in elderly patients - ORTHOSTATIC HYPOTENSIONS

DELIRIUM in elderly more pronounced

CARDIAC TOXICITY

OVERDOSE - convulsions, coma, cardiac arrythmias

Question 19

TCA Drug Interactions

Answer 19

Do not use with MAOI’S OR SSRI’S

Question 20

6 Available SSRI’s

Answer 20

Fluoxetine
Sertraline
Paroxetine
Citalopram
Escitalopram
Fluvoxamine

Question 21

SSRI’s MOA

Answer 21

selectively inhibit SERT and block reuptake of 5-HT into presynaptic terminal

Question 22

SSRI’s Side Effects

Answer 22

Short term - NAUSEA, GI UPSET, DIARRHEA

Long term - SEXUAL DYSFUNCTION

LOW RISK OF OVERDOSE

Question 23

SSRI’s Drug Interaction

Answer 23

SEROTONIN SYNDROME if used with other anti-depressants

Question 24

Serotonin Syndrome

Answer 24

Rare side effect d/t LONG HALF LIFE

Need to ALLOW TIME FOR DRUGS TO CLEAR BEFORE MAKING SWITCHES

Question 25

Fluoxetine and Serotonin Syndrome avoidance

Answer 25

Discontinued for 4-5 WEEKS prior to using other anti-depressants (others are 2 weeks)

Question 26

Discontinuation Syndrome

Answer 26

discontinuation of SHORT HALF-LIFE SSRI's Dizziness, paresthesias, anxiety only occurs in some patients

Question 27

Venlafaxine - drug type? MOA? Clinical?

Answer 27

SNRI inhibit BOTH SERT AND NET severe depression

Question 28

Duloxetine - drug type? MOA? Clinical?

Answer 28

SNRI inhibits BOTH SERT AND NET increasing use for CHRONIC PAIN

Question 29

Trazodone - drug type? MOA? Clinical? Side effect?

Answer 29

Atypical anti-depressant BLOCKS 5-HT2 AND H1 unlabeled hypnotic Priapism - prolonged painful erections - peripheral alpha-1 block

Question 30

Bupropion - drug type? MOA? Clinical?

Answer 30

Atypical Antidepressant BLOCKS NE AND DA REUPTAKE SMOKING CESSATION

Question 31

Mirtazapine - drug type? MOA?

Answer 31

atypical antidepressant Blocks pre-synaptic alpha-2 - increases 5-HT and NE release

Question 32

Anti-depressant Treatment Considerations

Answer 32

2-4 weeks for therapeutic effect SHOULD NOT COMBINE DIFFERENT CLASSES

Question 33

Pharmacokinetic Considerations

Answer 33

most INHIBIT CYP ISOENZYMES - 2D6 and 3A4 Never combine TCA'S AND SSRI'S --> SEROTONIN SYNDROME AND TCA TOXICITY

Question 34

Bipolar Disorder Treatment Main drug? Drugs used to treat acute mania?

Answer 34

Lithium - mood stabilizing agent - MAINTENANCE Valproic acid and Carbamazepine - anti-convulsants

Question 35

Lithium Side Effects

Answer 35

Tremor Hypothyroidism Nephrogenic diabetes insipidus Skin reactions

Question 36

Lithium Drug Interactions

Answer 36

THIAZIDES AND LOOP DIURETICS diminishes Li clearance - can cause toxicity