The nonsteroidal anti-inflammatory drugs (NSAIDs) are a chemically diverse group of agents that have similar pharmacologic properties and are widely used for control of pain and inflammation (Table II–39). Overdose by most of the agents in this group usually produces only mild GI upset. However, toxicity may be more severe after overdose with oxyphenbutazone, phenylbutazone, mefenamic acid, piroxicam, or
Table II-39 NSAIDs |Favorite Table|Download (.pdf)
Table II-39 NSAIDs
Maximum Daily Adult Dose (mg)
Chronic use associated with severe liver injury.
(PO or SC)
Approved for use in dogs only.
Acute renal failure.
Massive overdose may cause coma, renal failure, metabolic acidosis, and cardiorespiratory depression.
Large overdoses may cause respiratory depression, coma, and seizures.
High risk for renal failure.
Extensive enterohepatic recirculation.
Removed from US market owing to concern for increased risk for cardiovascular events.
Removed from US market in 2005 owing to concern for increased risk for cardiovascular events and serious skin reactions.
Mechanism of toxicity
NSAIDs produce their pharmacologic and most toxicologic effects by inhibiting the enzyme cyclooxygenase (isoforms COX-1 and COX-2); this results in decreased production of prostaglandins and decreased pain and inflammation. Central nervous system, hemodynamic, pulmonary, and hepatic dysfunction also occurs with some agents, but the relationship to prostaglandin production remains uncertain. Prostaglandins are also involved in maintaining the integrity of the gastric mucosa and regulating renal blood flow; thus, acute or chronic intoxication may affect these organs.
The newest generation of NSAIDs, known as the COX-2 inhibitors (rofecoxib [Vioxx], celecoxib [Celebrex], valdecoxib [Bextra]), selectively inhibits the COX-2 isoform, with no COX-1 inhibition at therapeutic doses. Because COX-1 is involved in GI mucosal protection, the likelihood of GI bleeding is less with these drugs than with conventional NSAIDs.
Pharmacokinetics. NSAIDs are generally well absorbed, and volumes of distribution are relatively small (eg, 0.15 L/kg for ibuprofen). COX-2 inhibitors have larger volumes of distribution (86–91 L in adults for rofecoxib, 400 L for celecoxib). Most of these agents are highly protein-bound, and most are eliminated through hepatic metabolism and renal excretion, with variable half-lives (eg, 1.5–2.5 hours for ibuprofen and 12–17 hours for naproxen; see also Table II–61).
Toxic dose. Human data are insufficient to establish a reliable correlation between amount ingested, ...