0071643192.pdf

TOXICOLOGY

SYMPTOMS/EXAM

■ The classic triad includes CNS depression, respiratory depression, and pin-
point pupils.
■ Pinpoint pupils may not be seen with propoxyphene (Darvon), penta-
zocine (Talwin), meperidine (Demerol).
■ Bradycardia, hypotension
■ Hypothermia
■ Muscle flaccidity
■ Noncardiogenic pulmonary edema
■ Seizures: After exposure to propoxyphene or meperidine
■ Wide complex dysrhythmias: Associated with Na++channel blockade after
propoxyphene overdose

DIAGNOSIS

■ Clinical diagnosis based on exposure history and physical exam
■ Reversal of symptoms by naloxone

TREATMENT

■ Support ventilation, as needed
■ Antidote = naloxone (Narcan).
■ Pure antagonist at opiate receptor
■ Sodium bicarbonate for wide complex dysrhythmias (propoxyphene)
■ Seizures are typically self-limited.

COMPLICATIONS

■ Aspiration
■ Rhabdomyolysis: From prolonged immobilization

OVER-THE-COUNTER MEDICATIONS

Acetaminophen

Acetaminophen ingestions are typically divided into acute overdoses (single
ingestion) and repeated supra-therapeutic ingestions (chronic exposure). A
single ingestion of greater than 150 mg/kg (children) or 7.5 g (adults) should
be considered toxic.

MECHANISM/TOXICITY

■ Acetaminophen is primarily metabolized by the liver.
■ In therapeutic doses, about 90% of acetaminophen is conjugated with glu-
curonide or sulfate to nontoxic metabolites, while about 5% is oxidized by
cytochrome P-450 to a toxic metabolite, N-acetyl-p-benzoquinoneimine
(NAPQI).
■ Hepatic stores of glutathionerapidly combine with NAPQI to form non-
toxic metabolites.
■ In APAP overdose, normal glucuronide and sulfate conjugation is over-
whelmed and a large amount of NAPQI is produced.
■ When NAPQI formation exceeds glutathione stores, free NAPQI binds to
cellular proteins causing hepatotoxicity (centrilobular or zone III).
■ High-risk patients: Patients with decreased glutathione stores (alcoholics,
malnourished) and those on cytochrome P-450–inducing medications (INH,
anticonvulsants) may have increased risk of hepatotoxicity.

Opiate toxidrome = CNS

depression, respiratory

depression, and pinpoint

pupils.

Naloxone is only indicated for

reversal of hypoventilation

and is not useful in the

intubated patient.

In acetaminophen toxicity,

glutathione stores become

depleted, allowing NAPQI

(toxic metabolite) to

accumulate.