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Pharmacology II > Antidepressants > Flashcards

Antidepressants Flashcards

1
Q

Name two SSRIs

A

fluoxetine
sertraline

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2
Q

Name an SNRI

A

duloxetine

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3
Q

Name two TCAs

A

amitriptyline
desipramine

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4
Q

Name a MAOIs

A

tranylcypromine

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5
Q

Name three “other” antidepressants

A

bupropion
mirtazapine
trazodone

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6
Q

True/false: Antidepressants take a while to work.

A

TRUE

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

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7
Q

Describe the MOA of SSRIS

A

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

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8
Q

What is the initial adverse effect of SSRIs?

A

CNS stimulation

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9
Q

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

A

TRUE

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10
Q

What are side effects of SSRIS?

A
  • *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

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11
Q

How does the MOA of SSRIs compare to SNRI?

A

SNRIs block SERT

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

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12
Q

What are two unique features of SNRIs?

A

Unique adverse effect: can
increase BP at high doses

Unique indication: neuropathic pain
(esp. duloxetine)

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13
Q

What is serotonin syndrome?

A

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

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14
Q

What is Trazodone’s MOA?

A

5-HT2A receptor blockade

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

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15
Q

What are the MOA of mirtazapine?

A

Potent α2 antagonist: enhances NE release

Potent H1 antagonist: sedation

Weak antagonist at muscarinic and α1 – side effect

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16
Q

What is the most prominent adverse effect of mirtazapine?

A

sedation

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17
Q

What is the MOA of Buproprion?

A

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

18
Q

What are the main adverse effects of buproprion?

A

CNS stimulation and seizures

19
Q

What are TCAs MOA?

A

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

20
Q

What are initial adverse effects of TCAs?

A

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

21
Q

What are other major adverse effects of TCA?

A

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)

22
Q

What is the low TI of TCAs due to?

A

Arrthymias

Tx: supportive; lavage; lidocaine for arrhythmias

23
Q

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)

A

True

24
Q

What is the MOA of MAOIs?

A
  • *Irreversibly and unselectively** inhibit monoamine oxidase (MAO)
  • = Increased NE & 5-HT*
25
Q

What is the indication for MAOIs?

A

atypical depression

26
Q

EXTREMELY High incidence of drug interation with MAOIs

A

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

27
Q

Overdose in MAOIs

A

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

28
Q

What ADD should be avoided in pregnancy?

A

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

29
Q

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

A

fluoxetine

30
Q

Abuse/tolerance/dependence of ADD.

A

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”

31
Q

What are the 5D’s of poor response?

A

Adequate Dose?
Adequate Duration? – allow 1-6 weeks
Proper Diagnosis?
Additional Drugs?
Different (additional) Tx?

32
Q

What is key to the management of mania?

A

key = sedation

  • antipsychotics
  • benzos
  • anticonvulsants
  • lithium (but lower efficacy, b/c slower)
33
Q

What is the Drug of choice for bipolar maintenance therapy?

A

lithium

34
Q

What is important to watch with lithium?

A

Excreted in urine (>95% of dose)
o 80% of filtered is reabsorbed

• Narrow TI dictates blood level monitoring
start w/ low dose for 5 days to achieve steady state
10-12 hrs after dose measure blood levels

(effective @ 0.6-1.2 mEq/L)

35
Q

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

A

Mannitol, acetazolamide, theophylline

36
Q

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

A

Sodium-depleting diuretics:
o thiazides, furosemide, ethacrynic acid

  • Dehydration (including w/ exercise)
  • NSAIDS
  • ACE inhibitors
37
Q

How much lithium is toxic?

A

>2 mEq/L considered toxic

38
Q

Lamotrigine

A

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

39
Q

What is a major side effect of olanzapine?

A

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

40
Q

What are two anticonvulsants used in bipolar disorder?

A

valproic acid and lamotrigine

Pharmacology II (7 decks)

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