erable variations in potency. The majority of clinical

• Cardiovascular toxicity (specifica lly refractory hypotension) is the leading cause of morbidity and morta lity in

cycl ic antidepressant overdose.

• Hypertonic sodium bicarbonate should be given in

1 -2 mEq/kg boluses to reverse the wide-complex

dysrhythmias commonly encountered with cyclic

antidepressant poison ing.

findings associated with CA poisoning can be attributed to

;:::1 of the following pharmacologic actions:

• Competitive inhibition of acetylcholine at central and

peripheral muscarinic (but not nicotinic) receptors

• Inhibition of a-adrenergic receptors

• Inhibition of norepinephrine and serotonin uptake

• Sodium channel blockade

• Antagonism of GABA-A receptors

Although it is the inhibition of norepinephrine and

serotonin uptake that is believed to account for the antidepressant effects of these agents, the alternative actions just

listed account for the significant toxicity associated with

CA overdose, with sodium channel blockade being the

most important factor contributing to patient mortality.

CLINICAL PRESENTATION

� History

Patients commonly present to the emergency department

with minimal clinical findings only to develop life-threatening cardiovascular and central nervous system (CNS)

manifestations within the timespan of a few hours.

255

CHAPTER 60

Co-ingestants are not uncommon in patients with CA

overdoses, and this possibility must always be investigated.

Attempt to determine the exact amount of drug

ingested, as the cyclic antidepressants have a rather narrow

therapeutic window, and small excursions beyond the

usual therapeutic range (2-4 mg/kg) may result in significant toxicity. Acute ingestions of more than 1 0-20 mg/kg

will cause significant cardiovascular and CNS disturbances

owing to the blockade of cardiac sodium channels and

inhibition of CNS GABA-A receptors, respectively. Toxicity

in children has been reported with ingestions as low as

5 mg/kg.

� Physical Examination

The clinical presentation of CA toxicity varies widely from

mild anti-muscarinic signs and symptoms to severe

Table 60-1 Clinical manifestations of toxicity

resulting from cyclic antidepressants.

Cardiovascular Toxicity

Conduction Delays

PR interval, QTc interval, and QRS complex prolongation

Terminal right access deviation (S in lead I and R in aVR)

Atrioventricular block

Dysrhythmias

Sinus tachycardia

Supraventricular tachycardia

Wide·complex tachycardia

Sinus tachycardia with rate·dependent aberrancy

Ventricular tachycardia

Torsades de pointes

Bradycardia

Ventricular fibril lation

Asystole

Hypotension

Central Nervous System Toxicity

Altered mental status

Delirium

Psychosis

Lethargy

Coma

Myoclonus

Seizures

Anticholinergic Toxicity

Altered mental status

Hyperthermia

Urinary retention

Paralytic ileus

Pulmonary Toxicity

Acute lung·injury aspiration

Repri nted with permission from Flomenbaum N, Goldfrank L,