0071643192.pdf

TOXICOLOGY

Nonsteroidal Anti-Inflammatory Drugs

NSAIDs inhibit the enzyme cyclooxygenase, causing decreased prostaglandin

formation. Prostaglandins have a variety of functions including mediating

pain and inflammation, maintaining the gastric mucosa, and regulating blood

flow in the kidneys. Ibuprofen is the most common NSAID seen in overdose.

MECHANISM/TOXICITY

■ Gastrointestinal irritation (nausea and vomiting) caused by disruption of

the gastric mucosa

■ Large overdoses result in systemic effects from unclear mechanism.

■ Renal insufficiency and GI bleeding are rarein acute overdose.

SYMPTOMS/EXAM

■ Abdominal pain, N/V

■ Altered mental status, seizure, metabolic acidosis

DIAGNOSIS

■ Based primarily on history and physical exam

TREATMENT

■ Supportive and symptomatic therapy

Iron

■ For any given iron compound, it is the amount of elemental iron that

determines its toxicity.

MECHANISM/TOXICITY

■ Direct corrosive effecton gastrointestinal tract

■ Toxicity from free circulating iron→cellular uncoupling of oxidative

phosphorylation and production of free radicals →anaerobic metabolism

and multiorgan failure.

SYMPTOMS/EXAM

Classically described as five phases of toxicity (see Table 6.24), as follows:

TABLE 6.23. Indications for Hemodialysis in Salicylate Toxicity

Level >100 mg/dL (acute ingestions)

Altered mental status

Renal failure

Severe persistent acid-base disturbance

Pulmonary edema

Failure to respond to intensive treatment

A key feature of iron toxicity is

the uncoupling of oxidative

phosphorylation→anaerobic

metabolism.