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Year 4 - Toxicology > 17 - Antidepressants > Flashcards

17 - Antidepressants Flashcards

1
Q

What are MAOIs? How long is their wash-out period?

A
  • Irreversible inhibitors of MAO A and B

- 2 weeks before new enzyme is synthesized

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2
Q

How many phases of MAOI overdose?

A

4

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3
Q

Phase 1 of MAOI overdose

A
  • Asymptomatic (latent) period
  • Up to 6-12 h
  • Monitor for 24h post-ingestion
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4
Q

Phase 2 of MAOI overdose

A
  • Neuromuscular excitation and sympathetic hyperactivity
  • Hypertension, hyperreflexia, hyperthermia
  • Tremor, myoclonus, seizures, agitation, rigidity
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5
Q

Phase 3 of MAOI overdose

A
  • CNS depression and possible CV collapse

- Hypotension

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6
Q

Phase 4 of MAOI overdose

A

Secondary complications for survivors

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7
Q

MAOI overdose tx

A
  • Severe hypertension -> tx w/ short-acting antihypertensive
  • Arrhythmias -> standard anti-arrhythmic
  • Hypotension -> direct acting vasopressors (not indirect); start low
  • Charcoal
  • Hyperthermia -> treat aggressively
  • Rigidity -> BZDs, dantrolene (muscle relaxant) to prevent rhabdomyolysis
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8
Q

Foods to avoid w/ MAOIs

A
  • Cheese (all aged)
  • Alcoholic beverages -> red wine, sherry, cognac, beer
  • Fish -> smoked, caviar
  • Meat -> fermented, salami, some sausage
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9
Q

Describe the MAOI-cheese reaction

A
  • Hypertensive crisis from indirect acting amines
    • Direct acting don’t require MAO for their metabolism
    • Catabolized by COMT
  • Tyramine = indirect acting amine
  • Peripheral effects as it doesn’t cross BBB
  • Causes NE release from peripheral noradrenergic neurons
  • Normally, little absorbed
    • Dietary amine metabolized by GI MAO-A
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10
Q

What do TCAs block in the brain?

A
  • Block serotonin and NE reuptake

- Block histamine, muscarinic, and alpha-adrenergic receptors

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11
Q

Cardiac effects of TCAs at usual doses

A
  • Hypertension, tachycardia
  • Slowed cardiac conduction
  • Antiarrhythmic properties
  • Orthostatic hypotension
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12
Q

Px at high risk for TCA cardiac adverse events

A
  • Elderly
  • CV disease
  • Drug interactions (increased levels)
  • Overdose cases
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13
Q

Central anticholinergic effects of TCAs

A
  • Agitation
  • Hallucinations
  • Confusion
  • Sedation
  • Coma, seizures
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14
Q

Peripheral anticholinergic effects of TCAs

A
  • Hypertension, tachycardia, hyperthermia
  • Mydriasis
  • Dry, flushed skin
  • Decreased GI motility
  • Urinary retention
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15
Q

CV effects of TCAs at toxic doses

A
  • Intraventricular conduction delay (QRS prolongation)
  • Sinus tachycardia
  • Ventricular arrhythmias
  • Hypotension
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16
Q

CNS effects of TCAs at toxic doses

A
  • Coma
  • Delirium
  • Myoclonus
  • Seizures
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17
Q

Other effects of TCAs at toxic doses

A
  • Hyperthermia
  • Ileus
  • Urinary retention
18
Q

Risk factors that increase risk of TCA toxicity

A
  • Pre-existing heart condition
  • Electrolyte abnormalities
  • Hepatic insufficiency
  • Stimulant drug use
  • Multiple drugs that increase QT interval
  • Increased dose
19
Q

TCA overdose – general management

A
  • *Treat symptomatically
  • Airway if needed, IV-line, cardiac monitoring, EKG
  • Decreased LOC => O2, dextrose, naloxone, thiamine, ABGs
  • Stomach lavage
  • Charcoal 50-100 g + cathartic
  • Usually 10-20 mg/kg is considered life-threatening (limit Rx to 1 g if suicidal)
  • Sx from as little as 3-4 times daily dose
20
Q

What is the most common cause of death in TCA overdose?

A

Refractory hypotension (due to vasodilation or impaired cardiac contractility)

21
Q

Tx of TCA induced orthostatic hypotension

A
  • Intravascular volume expansion
  • Sodium bicarbonate, vasopressors (NE) or inotropes (dopamine)
  • Correct hyperthermia, acidosis, seizures
22
Q

Tx of TCA induced CNS toxicity

A
  • Confusion, agitation, hallucinations -> supportive therapy and BZDs
  • Coma, myoclonus -> coma usually resolves in 24 h
  • Seizures -> usually brief but often occur immediately before cardiac arrest
    • Acidemia from seizures may predispose to arrhythmias
    • Usually responsive to IV BZDs (midazolam infusion)
    • Refractory -> barbiturates or propofol
    • Phenytoin no longer recommended (b/c proarrhythmic w/ limited efficacy)
23
Q

What is the most common mechanism of TCA associated death?

A

Myocardial depression, ventricular tachycardia, or ventricular fibrillation

24
Q

What is a predictor of arrhythmias?

A

QRS duration > 0.10 s

25
Q

____ can reduce arrhythmias and hypotension caused by TCAs

A

Sodium bicarbonate

26
Q

Can anti-arrhythmics be given to TCA-induced arrhythmias?

A

No, b/c pro-arrhythmic

27
Q

What can be used to treat TCA cardiotoxicity?

A

Lipid emulsion b/c TCAs are highly lipophilic

28
Q

TCA overdose – length of tx

A
  • Anti-cholinergic effects after a large ingestion may result in slow absorption
  • Asymptomatic w/ normal ECG x 6 h w/ only tx GI decontamination -> not likely to develop toxic effects
  • If symptomatic w/ altered mental status, seizures, or cardiac dysrhythmias -> monitor in ICU x 12-24 h after all sx resolved and all supportive interventions are d/c
  • If parameters remain normal then psychiatry to evaluate
29
Q

Venlafaxine safety

A
  • In general, safety profile good
  • Recent data indicated that may not be as safe as SSRIs; closer to TCAs
  • Rare reports of conduction disturbances
  • Potentially may increase QRS; pro-arrhythmic in overdose or poor metabolizers
  • Blood pressure increases
    • Dose dependent response
    • Usually reversible upon d/c
    • Risk greater w/ increased age
30
Q

Symptoms of venlafaxine overdose?

A
  • Overdoses reported –> seizures, hypotension, sinus tachycardia
  • Serotonin syndrome
    • Drug interactions w/ serotonergic agents (MAOIs, SSRIs)
31
Q

When is venlafaxine contraindicated?

A
  • Relatively contraindicated in px w/ high risk of overdoses and/ or pre-existing seizures and cardiac disease
  • Watch in subjects who are poor CYP2D6 metabolizers, or concomitant drugs that inhibit CYP2D6
32
Q

Desvenlafaxine safety

A
  • Minor effects w/ mild hypertension and tachycardia

- Risk of seizures or serotonin toxicity is low

33
Q

Signs and symptoms of duloxetine overdose

A
  • Somnolence
  • Serotonin syndrome
  • Seizures
  • Vomiting
34
Q

SSRIs toxic effects and tx

A
  • Tremor, sinus tachycardia, N/V/D, seizures, serotonin syndrome
  • Mild bradycardia may occur in OD
  • Lower incidence of mortality vs. TCAs
  • Tx = charcoal + supportive care
35
Q

Causes of serotonin syndrome

A
  • Drugs that inhibit breakdown of 5-HT -> MAOIs
  • Drugs that block re-uptake of 5-HT -> SSRIs, venlafaxine, trazodone, clomipramine, dextromethorphan, meperidine, pentazocine, cocaine
  • Drugs that are 5-HT precursors or agonists -> lithium, buspirone, L-tryptophan, LSD, psilocybin
  • Drugs that enhance 5-HT release -> MDMA
36
Q

Tx of serotonin syndrome

A
  • Supportive care
  • Neuromuscular sx -> BZDs
  • Increased temp -> Tylenol, cooling blankets
  • Severe rigidity -> dantrolene
  • Severe sx -> cyproheptadine 4 mg PO q4h; 5-HT antagonism; watch anticholinergic and antihistaminic properties
37
Q

Cognitive sx of serotonin syndrome

A
  • Agitation

- Mental status changes (confusion, hypomania)

38
Q

Autonomic dysfunction sx of serotonin syndrome

A
  • Diaphoresis
  • Diarrhea
  • Fever
  • Shivering
39
Q

Neuromuscular sx of serotonin syndrome

A
  • Incoordination
  • Myoclonus
  • Tremor
  • Hyperreflexia
40
Q

Citalopram and cardiac toxicity

A
  • Dose related QT prolongation
  • High risk in metabolic disturbance and pre-existing cardiac disease
  • Potential increased risk of Torsades de Pointes
  • Maximum dose = 40 mg/day
    • 20 mg in elderly or hepatic impairment
41
Q

Bupropion safety

A
  • May cause sinus tachycardia but not usually associated w/ conduction abnormalities
  • Study in depressed cardiac px -> no significant effect on heart (conduction, arrhythmias, hypotension, pulse)
  • XL product = delayed onset seizures
    • Must monitor for longer time
42
Q

Mirtazapine safety

A
  • Increased 5-HT and NE + serotonin blocker
  • Mild-moderate anticholinergic
  • Antihistamine effects
  • *Watch for serotonergic and anticholinergic effects in overdose
  • Case series -> no cardiac effects, no QTc prolongation

Year 4 - Toxicology (22 decks)

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