0071643192.pdf

TOXICOLOGY

Examples include:

■ Amitriptyline (Elavil)
■ Nortriptyline (Aventyl)
■ Imipramine (Tofranil)

MECHANISM/TOXICITY

TCAs have seven pharmacologic effects that contribute to toxicity, including:

■ Histamine receptor blockade →antihistamine effects.
■ Muscarinic receptor inhibition →anticholinergic effects.
■ α-Adrenergic receptor blockade
■ GABA receptor antagonism →seizures.
■ Na++-channel blockade →prolongation of phase 0 (rapid depolarization)
→quinidine-like effects.
■ Worsened by acidosis (respiratory or metabolic)
■ K+-channel antagonism
■ Inhibition of amine uptake

SYMPTOMS/EXAM

Table 6.5 summarizes the clinical findings in TCA poisonings.

■ Early poisoning →reflex sinus tachycardia and hypertension.
■ Life-threatening toxicity →Na++channel blockade →hypotension with
QRS widening >100 msec.

Life-threatening cardiac

toxicity results from Na++-

channel blockade.

TABLE 6.5. Clinical Findings in TCA Toxicity

PHARMACOLOGICEFFECT SYMPTOMS/EXAM

Antihistamine CNS excitation ↔coma

Anticholinergic Dry, flushed skin

Mydriasis

Hyperthermia

Seizures

Tachycardia

Urinary retention

CNS excitation ↔coma

α-Adrenergic receptor blockade Reflex tachycardia

Orthostatic hypotension

Miosis

GABA receptor blockade Seizures

Na++channel blockade QRS widening

Decreased contractility

Hypotension

K+channel antagonism QT prolongation

Inhibition of amine uptake Initial hypertension

CNS excitation ↔coma

Acidosis worsens Na++

channel blockade.