Antidepressants

Question 1

Name two SSRIs

Answer 1

fluoxetine
sertraline

Question 2

Name an SNRI

Answer 2

duloxetine

Question 3

Name two TCAs

Answer 3

amitriptyline
desipramine

Question 4

Name a MAOIs

Answer 4

tranylcypromine

Question 5

Name three “other” antidepressants

Answer 5

bupropion
mirtazapine
trazodone

Question 6

True/false: Antidepressants take a while to work.

Answer 6

TRUE

Blood levels plateau in hours-days, but the therapeutic
benefits are not seen until much later, **often 2- 6 weeks. **

Question 7

Describe the MOA of SSRIS

Answer 7

SSRIs selectively block the serotonin transporter (SERT), inhibiting reuptake of serotonin

What are the TWO NOTS?

Do not affect other amines (such as NE)

Do not act director at neurotransmitter receptors

Question 8

What is the initial adverse effect of SSRIs?

Answer 8

CNS stimulation

Question 9

True/false: SSRIS are metabolized by oxidation by CYP3A4; Phase 2 glucuronidation. Metabolism of some SSRIs produces active metabolites

Answer 9

TRUE

Question 10

What are side effects of SSRIS?

Answer 10

• *CNS stimulation** (insomnia, agitation)
• *GI problems** (nausea, diarrhea, bleeding)
• *Sexual dysfunction** (⇓ libido, anorgasmia)

Most effects can be minimized by starting w/
lower doses; *Generally not true for sexual dysfunction

Question 11

How does the MOA of SSRIs compare to SNRI?

Answer 11

SNRIs block SERT

What are the differences?
• at med/hi doses, they block re-uptake of norepinephrine (NET)

Question 12

What are two unique features of SNRIs?

Answer 12

Unique adverse effect: can
increase BP at high doses

Unique indication: neuropathic pain
(esp. duloxetine)

Question 13

What is serotonin syndrome?

Answer 13

hyperthermia,
muscle rigidity, myoclonus, akathisia, hyperreflexia,
fluctuating vital signs & mental status

Question 14

What is Trazodone’s MOA?

Answer 14

5-HT2A receptor blockade

Also . . . α1 receptor antagonist: sedation; postural hypotension
Active metabolite mCPP: agonist at several 5-HT receptors

Question 15

What are the MOA of mirtazapine?

Answer 15

Potent α2 antagonist: enhances NE release

Potent H1 antagonist: sedation

Weak antagonist at muscarinic and α1 – side effect

Question 16

What is the most prominent adverse effect of mirtazapine?

Answer 16

sedation

Question 17

What is the MOA of Buproprion?

Answer 17

Primary mechanisms: block both DAT
(dopamine) & NET (norepinephrine)
= enhanced DA and NE levels

Question 18

What are the main adverse effects of buproprion?

Answer 18

CNS stimulation and seizures

Question 19

What are TCAs MOA?

Answer 19

Block neuronal reuptake pumps for both 5-HT & NE (SERT & NET)

**2o amines (e.g. desipramine) \>\> _block NET_
3o amines (e.g. amitriptyline) \>\> _block SERT _**

_ALSO_ **muscarinic cholinergic; α1 adrenergic; H1 histamine

Note** 3o amines are metabolized to 2o amines
(e.g. imipramine to desipramine); effect
of 3o amines is block reuptake of both
amines

Question 20

What are initial adverse effects of TCAs?

Answer 20

Drowsiness, autonomic symptoms (dry mouth,
constipation), anxiety, dysphoria, difficulty in
concentration

Question 21

What are other major adverse effects of TCA?

Answer 21

Heart: arrhythmias
Vascular: a1 block - orthostatic hypotension
Autonomic: peripheral anticholinergic - dry mouth, constipation
CNS: brain anticholinergic - sedation
Vegetative: increased appetite, weight gain
Sexual: impotence (anticholinergic); delayed orgasm (a1 block); decreased libido (SERT block)

Question 22

What is the low TI of TCAs due to?

Answer 22

Arrthymias

Tx: supportive; lavage; lidocaine for arrhythmias

Question 23

True/false:** 2o amine**s (e.g. desipramine) have a significantly better side-effect profile and higher therapeutic index than 3o amines (e.g. amitriptyline)

Answer 23

True

Question 24

What is the MOA of MAOIs?

Answer 24

• *Irreversibly and unselectively** inhibit monoamine oxidase (MAO)
• = Increased NE & 5-HT*

Question 25

What is the indication for MAOIs?

Answer 25

atypical depression

Question 26

EXTREMELY High incidence of drug interation with MAOIs

Answer 26

Sympathomimetics \>\> HA, increased BP Tramadol; St. John’s wort; triptans for migraine Meperidine, dextromethorphan \>\> **serotonin syndrome** SSRIs / SNRIs / TCAs / trazodone \>\> serotonin syndrome

Question 27

Overdose in MAOIs

Answer 27

Overdose: not common when taken alone; effects include **agitation, delirium; can lead to hyperthermia, shock, coma, seizures**

Question 28

What ADD should be avoided in pregnancy?

Answer 28

Associated with significant risks; **avoid in pregnancy:** tranylcypromine (hypertension) Associated with **slightly increased risk** of rare fetal malformations: fluoxetine, sertraline Associated with a **possible risk of limb malformation **: amitriptyline

Question 29

What is the only drug that has received FDA approval for use in children with major depressive disorder?

Answer 29

fluoxetine

Question 30

Abuse/tolerance/dependence of ADD.

Answer 30

Abuse = No evidence Tolerance = Develops for most adverse effects, EXCEPT: **o sexual dysfunction w/ SSRIs / SNRIs o cardiac toxicity of TCAs** Dependence / withdrawal = Some exhibit “discontinuation syndrome”

Question 31

What are the 5D's of poor response?

Answer 31

Adequate **_D_**ose? Adequate **_D_**uration? – allow 1-6 weeks Prope**_r D_**iagnosis? Additional **_D_**rugs? **_D_**ifferent (additional) Tx?

Question 32

What is key to the management of mania?

Answer 32

key = **sedation** * antipsychotics * benzos * anticonvulsants * lithium (but lower efficacy, b/c slower)

Question 33

What is the Drug of choice for bipolar maintenance therapy?

Answer 33

lithium

Question 34

What is important to watch with lithium?

Answer 34

**Excreted in urine** (\>95% of dose) o 80% of filtered is **reabsorbed** • Narrow TI dictates blood level monitoring start w/ l**_ow dose for 5 days to achieve steady state_** 10-12 hrs after dose measure blood levels (effective @ **_0.6-1.2 mEq/L)_**

Question 35

Which drugs ↑ Li+ excretion ↓ Li+ blood levels?

Answer 35

Mannitol, acetazolamide, theophylline

Question 36

↑ Na+ excretion causes ↓ Li+ excretion, ↑ Li+ levels, ↑lithium toxicity

Answer 36

**Sodium-depleting diuretics**: o thiazides, furosemide, ethacrynic acid * Dehydration (including w/ exercise) * NSAIDS * ACE inhibitors

Question 37

How much lithium is toxic?

Answer 37

\>2 mEq/L considered toxic

Question 38

Lamotrigine

Answer 38

Combo of lamotrigine and lithium is best. • Side effects: nausea; dizziness; headache; mild rash (**_StevensJohnson _**much less common)

Question 39

What is a major side effect of olanzapine?

Answer 39

weight gain / diabetes type 2 risk are a potential problem with all atypical antipsychotic

Question 40

What are two anticonvulsants used in bipolar disorder?

Answer 40

valproic acid and lamotrigine