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Antidepressants Flashcards

1
Q

What are the characteristics of depressive syndromes?

A

-characterized by presence of depressed mood

or

-loss of interest for most of the day (nearly every day for at least 2 weeks for major depression)

+

-associated clinical symptoms

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2
Q

What are the associated clinical symptoms of depressive syndromes?

A
  • loss of energy
  • disturbed sleep
  • disturbed appetite
  • cognitive symptoms
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3
Q

Where do norepinephrine secreting neurons primarily originate from?

A
  • locus ceruleus
  • lateral tegmental areas
  • project widely to almost all areas of brain and spinal cord
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4
Q

Where do serotonergic neurons reside?

A
  • raphé nuclei in brainstem

- diffusely make contact with all areas of brain

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5
Q

When was the first tricyclic antidepressants (TCA) introduced?

A

Imipramine

-1950s

Strong efficacy in treatment of psychotic depression

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6
Q

Name the tertiary amines.

A
  • imipramine
  • amitriptyline
  • clomipramine
  • doxepin
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7
Q

Name the secondary amines.

A

Desipramine

-metabolite of imipramine

Nortriptyline

-metabolite of amitriptyline

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8
Q

Describe the structure of TCAs.

A

Tricyclic structure

-two benzene rings on either side of a seven member ring

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9
Q

What are the categories of TCA side effects?

A
  • cardiac
  • anticholinergic effects
  • adrenergic
  • histamine
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10
Q

Describe TCA cardiac effects.

A

Prolonged QT interval (QTc is corrected for heart rate)

  • slowing of intracardiac conduction by inhibiting sodium channels
  • may be associated with torsades de pointes (potentially fatal ventricular arrhythmia)

Avoid in patients with recent MI

May be associated with increase in CV disease
-even in those not known to have cardiac history prior to initiation

1 to 2 week supply may be fatal in overdose

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11
Q

Describe TCA anticholinergic effects.

A

Muscarinic acetylcholine receptor antagonism

  • dry mouth
  • urinary retention
  • constipation
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12
Q

Describe TCA adrenergic effects.

A

Peripheral α-1 adrenergic antagonism

-orthostatic hypotension

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12
Q

Describe TCA histamine effects.

A

Histamine (H1) receptor antagonism

  • sedation
  • possible weight gain
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13
Q

What is required before starting a TCA?

A

ECG

-to rule out any existing conduction abnormalities before starting therapy

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14
Q

In what patients should TCAs be avoided?

A

Patients with recent MI

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15
Q

What may TCAs be associated with?

A

Increase in CV disease

-even in those not known to have cardiac history prior to initiation

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16
Q

Describe TCA use for pain syndromes.

A

Mild to moderate analgesic effect in treatment of chronic pain syndromes

  • includes migraines
  • independent of effect on mood
  • efficacy starts at lower doses
  • response seen earlier than with depression
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16
Q

Why are TCAs dangerous in overdose?

A

1 to 2 week supply may be fatal in overdose

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17
Q

Which TCAs are particularly effective for pain syndromes?

A
  • amitriptyline
  • clomipramine
  • seem more effective than SSRIs
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18
Q

What is monoamine oxidase?

A

Enzyme

  • metabolizes monoamines (serotonin, NE, dopamine)
  • enzyme has two isomers
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19
Q

What is MAO-A?

A
  • found in brain and intestines
  • metabolizes serotonin, NE, dopamine
  • MAO-A inhibition required for antidepressant effect
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20
Q

What is MAO-B?

A
  • found in brain and platelets

- primarily metabolizes dopamine

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21
Q

What was the first available MAOI?

A

Iproniazide

  • anti-TB drug
  • discovered in 1950s
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22
Q

What are the currently available MAOIs?

A
  • tranylcypromine
  • phenelzine
  • isocarboxazid

Transdermal selegiline
-antiparkinsonian MAO-B selective agent (non-selective at higher doses)

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24
What are MAOIs particularly effective for?
For patients with depressive syndromes also meeting criteria for atypical features (two of the following four): - hyperphagia - hypersomnia - heavy leaden feeling in the limbs - severe sensitivity to criticism or rejection
25
What substance do MAOIs have a dangerous interaction with?
Tyramine-containing foods - aged cheeses - red wines
26
Describe the MAOI-tyramine interaction.
Can lead to adrenergic (hypertensive) crisis (increased sympathetic flow) - severe hypertension - headache - increased risk of stroke / cerebral hemorrhage - serotonergic side effects possible - orthostatic hypotension
27
With what medications should MAOIs not be combined with?
Medications containing sympathomimetic properties - decongestants - amphetamines - epinephrine (often added to local anesthetics as vasoconstrictor)
28
When combined with what drugs, can MAOIs cause serotonin syndrome?
Serotonergic drugs -potentially fatal
29
What are the initial symptoms of serotonin syndrome?
A
30
What are latter symptoms of serotonin syndrome?
May lead to - delirium - seizures - coma - death
31
What is the serotonin syndrome triad?
- mental status changes - alterations in muscular tone - autonomic hyperactivity - not all may occur simultaneously
32
How is serotonin syndrome managed?
- hospitalization | - serotonin antagonists
33
What is the washout period needed between MAOIs and other serotonergic drugs?
-2 week washout period
34
What is the washout period needed between MAOIs and vortioxetine?
-3 week washout period
35
What is the washout period needed between MAOIs and fluoxetine?
- 5 week washout period after stopping fluoxetine | - norfluoxetine has long half life
36
What drugs have serotonergic activity?
- SSRIs/SNRIs - TCAs - buspirone - triptans - cyclobenzaprine - dextromethorphan
37
What opiates have serotonergic activity?
- meperidine - methadone - tramadol
38
What are possible mild early side effects of SSRIs (that can be minimized by starting the SSRI at a low dose and increasing the dose gradually)?
- GI upset - sweating - headaches - jitteriness - sedation
39
What may continuation of SSRIs be associated with?
Reversible sexual side effects (in 2-73% of patients) - delayed ejaculation - decreased libido - ED
40
What are some medical risks of SSRIs?
- anticoagulant effects (greater risk of bleeding syndromes) - worsening osteoporosis; increased risk of falls in elderly; 2-fold increase risk of fractures - may lead to hyponatremia - cataract formation
41
Which SSRI is associated with significant weight gain?
Paroxetine To a lesser extent, citalopram
42
What adverse effect is citalopram associated with?
Dose related QTc prolongation
43
Which SSRIs are LEAST likely to inhibit hepatic enzymes?
- citalopram - escitalopram - followed by sertraline
44
In what situation may SSRIs be less effective or ineffective compared to placebo?
Treatment of depression with concomitant alcohol abuse or dependence
45
What is a risk of using SSRIs in patients with a vulnerability to bipolar disorder?
- can induce mania in the short term - overall mood instability in the long term - younger depressed patients may be incorrectly diagnosed with unipolar depression (may exhibit manic symptoms later)
46
What has SSRI use been associated with in kids, adolescents, and young adults up to 25yo?
Increased risk of treatment emergent suicidality -may be due to increased agitation or activation as a side effect or mixed manic symptoms
47
What side effects of TCAs are the SNRIs expected not to have with a similar efficacy?
- anticholinergic - antihistaminic - hypotensive - significant cardiac effects
48
How does venlafaxine act at lower doses?
Less than 150mg -primarily serotonergic
49
What side effect does venlafaxine have at higher doses?
Mild to moderate dose related hypertension
50
What are some advantages of Pristiq over the parent compound?
- once daily starting dose is the target dose | - metabolism is independent of liver cytochrome enzymes
51
How does duloxetine act throughout its entire dosage range?
Dual action -may increase blood pressure but less pronounced effect
52
How does duloxetine compare to the SSRIs and venlafaxine as an antidepressant?
Less tolerable overall without any advantages in efficacy
53
Describe duloxetine use for pain syndromes?
- does NOT have a clinically significant effect on pain symptoms in most depressed patients - is effective and has FDA approval for diabetic neuropathy pain and fibromyalgia
54
How is levomilnacipran compare to the SNRIs?
Significantly greater selectivity for norepinephrine reuptake inhibition
55
How does bupropion work?
Dopamine reuptake inhibition -may also inhibit NE reuptake
56
Describe bupropion's side effect profile.
- can have mild stimulant like properties - can decrease appetite - non sedating - shortening of QT interval
57
What two side effects that bupropion does NOT have are the most common reasons for non adherence?
- sexual side effects | - weight gain
58
What is a major side effect of bupropion?
Can lower seizure threshold
59
What are conditions that can increase seizure risk?
- eating disorders | - active withdrawal from alcohol / BDZ
60
What drugs may increase bupropion levels?
2D6 inhibitors - paroxetine - fluoxetine
61
Which antidepressant is LEAST likely to cause mania in bipolar patients?
Bupropion
62
How does bupropion compare to SSRIs for anxiety symptoms in depressed patients?
Comparable benefit
63
What is the MOA of mirtazapine?
Antagonist at alpha-2-adrenergic autoreceptors - causes an increase in NE and serotonin release - blocks certain serotonergic post synaptic receptors
64
What effects does mirtazapine have?
- can improve appetite (5HT3 and H1 antagonism) - sleep (through H1 antagonism) - can be helpful in acutely depressed with poor oral intake and insomnia
65
What is nefazodone's MOA?
Post synaptic 5HT2 antagonist -weak serotonin and NE reuptake inhibition

Psychopharmacology (1 decks)

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