Antidepressants

Question 1

Imipramine (TCA)

Answer 1

Mechanism:
Block NE & 5-HT reuptake to prolong the action of NE & 5-HT
- Also block muscarinic, α1, & hist

Use: antidepressant

Toxicity:

• Muscarinic blockade: dry mouth, urinary retention, constipation, cycloplegia
• α1 blockade: orthostatic hypotension, reflex tachycardia
• Hist-1 blockade: sedation
• Weight gain
• Decreased seizure threshold
• Sexual dysfunction

Metabolism:
- Pregnancy category D in first trimester – CV, renal, cleft palate, adrenal hypolasia

Interactions:

Risk for overdose – results in cardiotoxicity. If overdose occurs treat with activated charcoal & gastric lavage with NaHCO3

Question 2

Amitriptyline (TCA)

Answer 2

Mechanism:
Block NE & 5-HT reuptake to prolong the action of NE & 5-HT
- Also block muscarinic, α1, & hist

Use: antidepressant

Toxicity:

• Muscarinic blockade: dry mouth, urinary retention, constipation, cycloplegia
• α1 blockade: orthostatic hypotension, reflex tachycardia
• Hist-1 blockade: sedation
• Weight gain
• Decreased seizure threshold
• Sexual dysfunction

Metabolism:
- Pregnancy category D in first trimester – limb defects

Interactions:

Risk for overdose – results in cardiotoxicity. If overdose occurs treat with activated charcoal & gastric lavage with NaHCO3

Question 3

Fluoxetine

-SSRI

Answer 3

Mechanism: Selectively block 5-HT reuptake

Toxicity:

• Nervousness, insomnia, agitation
• Sexual dysfunction

Metabolism:

• Active metabolites
• Pregnancy category C

Interactions:

• Difficult to overdose due to high therapeutic index
• Inhibits CYP2D6
• Serotonin syndrome when given w/ MAOIs, which increase 5-HT

Question 4

Paroxetine

-SSRI

Answer 4

Mechanism: Selectively block 5-HT reuptake

Toxicity:

• Muscarinic blockade: dry mouth, urinary retention, constipation, cycloplegia
• Hist-1 blockade: sedation
• Sexual dysfunction

Metabolism:
- Pregnancy category D – clubfoot & cutaneous hemangiomas

Interaction:

• Paroxetine inhibits CYP2D6
• Difficult to overdose
• Serotonin syndrome when given w/ MAOIs, which increase 5-HT
• Inhibit NE & DA reuptake at the upper end of their dose ranges – Specificity depends on dose

Question 5

Sertaline

-SSRI

Answer 5

Mechanism: Selectively block 5-HT reuptake

Toxicity: Sexual dysfunction

Metabolism: Pregnancy category C

Interaction:

• Paroxetine inhibits CYP2D6
• Difficult to overdose
• Serotonin syndrome when given w/ MAOIs, which increase 5-HT
• Inhibit NE & DA reuptake at the upper end of their dose ranges – Specificity depends on dose

Question 6

Venlafaxine

Answer 6

Mechanism: Blocks 5-HT & NE reuptake

Toxicity: Pregnancy Category C

Question 7

Bupropion

• atypical antidepressant

Answer 7

Mechanism:
appears to block NE and DA uptake

toxicity: decreased seizure threshold

Pregnancy Category C

Question 8

Mirtazapine

• atypical antidepressant

Answer 8

Mechanism:

• Blocks α2 autoreceptors to inhibit feedback and increase NE release
• Subsequent α1 receptor stimulation leads to 5-HT release

Toxicity:

• Muscarinic blockade: dry mouth, urinary retention, constipation, cycloplegia
• Hist-1 blockade: sedation

Pregnancy Category C

Question 9

Selegiline

• MAO inhibitor

Answer 9

High dose inhibits MAO-A (NE, 5-HT, tyramine) & MAO-B (DA) – increases cytosolic amines in nerve terminals – maximal inhibition occurs in 5-10 days

Use: Administered for depression as a transdermal patch to avoid GI effects (tyramine)

Toxicity:

• CNS excitation – agitation, hallucination, convulsion
• Suppression of REM sleep
• Weight gain
• Sexual dysfunction

Metabolism:

• Metabolized by acetylation, so slow acetylators may exhibit exaggerated effects
• Takes weeks for new enzyme synthesis to return MAO activity to normal
• Pregnancy category C

Interaction:

• Serotonin syndrome with SSRIs
• Tyramine reaction when intestinal MAO-A is inhibited → HTN & stroke