TCA Toxicity


TCAs are associated with life-threatening CNS and cardiovascular toxicity. Safer medications, such as SSRIs, have decreased the use of TCAs for depression, and they are now more commonly used at lower doses for treatment of chronic pain syndromes, migraine prophylaxis, and enuresis.
Examples include:

MECHANISM/TOXICITY

Histamine receptor blockade  → CNS excitation/Coma
Muscarinic receptor inhibition
(anticholinergic effects)
→ Dry, flushed skin
→ Mydriasis
→ Hyperthermia
→ Seizures
→ Tachycardia
→ Urinary retention
→ CNS excitation ↔ coma
Alpha-Adrenergic receptor blockade → Reflex tachycardia
→ Orthostatic hypotension
→ Miosis
GABA receptor antagonism → seizures
Na channel blockade → prolongation of phase 0 (rapid depolarization) → Quinidine-like effects.
 -- Worsened by acidosis (respiratory or metabolic))

QRS widening
→ Decreased contractility
→ Hypotension

K+ channel antagonism QT prolongation
Inhibition of amine uptake Initial hypertension
CNS excitation ↔ coma

SYMPTOMS/EXAM

DIFFERENTIAL DIAGNOSIS

DIAGNOSIS

ED Care

  1. Supportive care
  2. Obtain IV Access & initiate cardiac rhythm & ECG monitoring.
  3. Activated charcol  1g PO. This may be preceded by gastric lavage in pt presenting < 1hr after a large ingestion (> 1g ingestion).
  4. IV fluid boluses for hypotension. If no response, administer NaHCO3 1-2 mEq/kg IV Bolus, repeated until the pt improves or until pH 7.50-7.55. A continuous IV infusion (150 mEq added to 1L of D5W) may be used at rate of 2-3 ml/kg/h.
  5. Norepinephrine (levophed) for hypotension unresponsive to fluid and sodium bicarbonate
  6. Treat conduction disturbances & ventricular dysrhytmias with NaHCO3. Synchronized cardioversion may be indicated for unstable pt.
  7. Seizures: Benzodiazepines

Disposition

  1. Pt who remain asymptomatic after 6 hr do not need admission for toxicologic reasons. Admit symptomatic pt to monitored bed or ICU
  2. Avoid:
  Receptor Activity    
Agent a1 b1 b2 DA  
Effects
Indication
Phenylephrine
40-180 mcg/min
+++ 0 0 0 SVR ↑↑
CO ↔/↑
Sepsis,
Neurogenic shock
(Levophed)
Norepinephrine
1-30 mcg/min
+++ ++ 0 0 SVR ↑↑
CO ↔↓↑
Sepsis
Epinephrine +++ +++ ++ 0 CO ↑↑
SVR ↓ (L)
SVR ↔/↑ (H)
Anaphylaxis,
ACLS,
Sepsis
Dopamine (mcg/kg/min)
Low-dose (0.5-2) 0 + 0 ++ CO ↑
SVR ↑↓
Sepsis,
Cardiogenic shock
Mid-dose(5-10) + ++ 0 ++ CO ↑
High-dose(10-20) ++ ++ 0 ++ SVR ↑↑
Doubutamine
2.5-20 mcg/kg/min
0/+ +++ ++ 0 CO ↑
SVR ↓
Cardiogenic shock
Isoproterenol
2-10 mcg/min
0 +++ +++ 0 CO ↑
SVR ↓
Cardiogenic shock w/
bradycardia
Vasopressin
(Adjunct)
0.01-0.04 U/min
        V2 receptors Vasoconstriction
Augments catecholamine

COMPLICATIONS