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Flashcards in Know this Antidepressant Agents/ Manic Deck (18):
1

Lithium – Adverse Effects

Related to plasma concentration - narrow therapeutic index**

Fine tremor, GI upset, muscle weakness
Decrease in thyroid function (3-30%); possible weight gain
Polyuria, polydipsia (anti-ADH action) (12%)

Moderate toxicity: Confusion, sedation, lethargy, twitching**

Severe toxicity: Seizures, stupor, coma**

Drug Interaction

Diuretics can decrease renal clearance by 25%***

Increase in lithium levels also seen with NSAIDs

2

Lithium – Pharmacokinetics

Competes with Na+ for reabsorption - Food-Drug Interactions possible

Increase in dietary Na+ --> ↓ Li+ Cp

Na+ restriction --> ↑ Li+ Cp

3

Lithium – Mechanism of Action

Also interference with Gs and Gi (adenylyl cyclase) can lead to side effects

In thyroid --> anti-TSH --> hypothyroidism

In kidney --> anti-ADH --> polyuria-polydipsia

May affect gene regulation for growth factors and neuronal plasticity

4

Lithium – Mechanism of Action

Slow onset (10-21 d) – necessary to accumulate Li+ in cell

Effects greatest on cells with highest level of activity (use-dependence)

Enhance 5HT action and/or diminish NE and DA effect – most favored MOA:

Interference with PIP recycling (Gq protein: IP3 and DAG)

5

Weight Gain

More: TCADs – mirtazapine – paroxetine

Less: fluoxetine – sertraline – venlafaxine

Least: bupropion

6

Sexual Dysfunction

Less with bupropion and mirtazapine

7

Anticholinergic side effects

Concern with TCADs (

8

Arrhythmias

Concern with TCADs (avoid if cardiac disease - ↑ QT)

9

Orthostatic hypotension

Trazodone - TCADs - MAOIs*

10

Hypertension

Venlafaxine-Duloxetine

11

Withdrawal syndrome (flu-like or neurologic symptoms)

Paroxetine and venlafaxine most likely

Fluoxetine least likely

12

Most agents: ______________-

Additive CNS depressant effects when used with other sedatives

13

SSRIs + MAOIs --> serotonin syndrome

Hyperthermia, muscle rigidity, myoclonus

Rapid changes in mental status (confusion / agitation) and vital signs (hypertension and tachycardia)

Also SSRIs + opioids: analgesics [meperidine-tramadol] and antitussive [ dextromethorphan]**

14

SSRI Common Side Effects Acute

Insomnia

Somnolence

Diarrhea

Nausea

15

SSRI Common Side Effects Delayed onset

Sexual dysfunction

Weight gain

Cognitive blunting

Under-appreciated by physicians, but most concerning to patients

16

Summary of Pharmacotherapy for Depression

Generic SSRIs are usually first line

Fluoxetine

17

Summary of Pharmacotherapy for Depression

Equal efficacy

Less weight gain and sexual side effects

Not effective in anxious depression

Bupropion

18

SNRIs (esp. Venlafaxine)

May be more effective

Side effects > SSRIs

HTN, withdrawal symptoms,