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Nervous System: Unit IV > Pharmacology of Depression > Flashcards

Flashcards in Pharmacology of Depression Deck (12)
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1

Catecholamine hypothesis of depression

  • Initial observation that reserpine depleted brain NE-5HT and induced depression formed the hypothesis of the connection
  • additional support came from observation that drugs effective in treating depression shared the common feature of enhancing availability of NE-5HT at postsynaptic receptor (i.e., via block of reuptake, block of metabolism, or increase in release).

2

Limitations of the catecholamine hypothesis

  • biogenic amine theory does not totally explain etiology of depression.
  • Mood elevating effects take 2-3 weeks for onset, but effects on amines occur immediately and some newer agents have little no effect on amine reuptake.
  • Direct evidence in support of the monoamine theory is still largely lacking.

3

Tricyclic antidepressants: MOA, SE, considerations in drug choice

  • MOA: Block 5HT reuptake, and NE to some extent
  • SE

    • Sedation: lassitude, fatigue, sleepiness.

    • Antimuscarinic effects: blurred vision, dry mouth, urinary hesitancy, fuzzy thinking.

      • Higher doses → narrow angle glaucoma aggregation, urinary retention, delirium. ...

  • Considerations

  • Poor SE profile, not commonly used.
  • Can give depressed pt easy way to kill self with overdose.

4

Selective Serotonin Reuptake Inhibitors (SSRIs): MOA, SE, considerations in drug choice

  • MOA: Block 5HT reuptake
  • SE
    • Sedative action.
    • Delayed: weight gain, sexual dysfunctin, cognitive blunting.
    • Acute: n/v, activation insomina (common), restlessness.
    • Withdrawal symptoms: Flulike
  • Considerations
    • Low likelihood of fatality with overdose
    • Inhibits CYP450

5

Buproprion: MOA, SE

  • MOA: Block NE/DA reuptake
  • SE: tremor, insomnia, anxiety, seizure at high doses

6

Venlafaxine: MOA, SE

  • MOA: Block 5HT/NE reuptake
  • SE
    • HTN, anxiety
    • Rapid appearance of withdrawal symptoms

7

Trazadone: MOA, SE, considerations in drug choice

  • MOA: Mixed postsynaptic antag + SRI
  • SE
    • Drowsiness - major sedative
  • Considerations
    • OD: minor problems only

8

MAOi's: MOA, SE, considerations in drug choic

  • MOA: Block NE/5HT/DA degredation
  • SE
    • Postural Hypotension, sedation, CNS stimulatin, liver damage, Seizure + shock + hyperthermia in overdose
  • Considerations
    • Look out for drug drug interactions - hypertensive crisis.

9

ECT: MOA, SE

  • MOA: increases synthesis of NE, 5HT
  • SE: memory loss

10

Mood stabilizers: MOA, use

  • MOA: blocks VSSC
  • Use:
    • blocks bipolar strom, supersensitivity and kindling

11

Mood stabilizers (Lithium): MOA, SE, use, considerations in drug choice

  • MOA: enhance 5HT, diminish NE and DA
  • SE: Fine tremor, GI upset, muscle weakness, weight gain, polyuria, polydipsia
  • Use: Effective for ↓ of manic and depressive episodes
  • Considerations: Drug drug interactions - diuretics and NSAIDs increase Li plasma levels
    • Na+ and Lilevels are inversely related (compete for absorption)

12

 Mood stabilizer examples

  • VSSC blocker
    • Valproic
    • Carbamazepime
  • Lithium