Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used medications for pain, fever, and inflammation. Although generally safe at therapeutic doses, overdose or chronic misuse can lead to significant toxicity. NSAID poisoning affects the gastrointestinal tract, kidneys, central nervous system, and in severe cases, can result in metabolic acidosis and multi-organ complications. Understanding NSAID overdose is essential for clinical toxicology practice.
Common Non-steroidal anti-inflammatory drugs Involved in Poisoning
- Ibuprofen
- Diclofenac
- Naproxen
- Aspirin-like NSAIDs (non-salicylate)
- Indomethacin
- Ketoprofen
Mechanism of Toxicity
NSAIDs primarily inhibit cyclooxygenase (COX-1 and COX-2) enzymes, reducing prostaglandin synthesis. In overdose, inhibition becomes extensive, leading to:
- Gastrointestinal irritation and bleeding
- Reduced renal blood flow and acute kidney injury
- Platelet dysfunction
- Central nervous system depression
Severe toxicity is more common in patients with renal impairment, dehydration, or concurrent drug use.
Toxic Dose
- Ibuprofen: Mild toxicity at >100 mg/kg; severe toxicity at >400 mg/kg
- Diclofenac: Toxic effects at >150 mg/kg
- Naproxen: Long half-life increases risk even at moderate overdoses
Clinical Features of Non-steroidal anti-inflammatory drug Poisoning
Gastrointestinal Symptoms
- Nausea and vomiting
- Epigastric pain
- Gastritis and gastrointestinal bleeding
- Occult or overt melena in severe cases
Central Nervous System Symptoms
- Drowsiness and dizziness
- Headache
- Seizures (rare, mainly with mefenamic acid and indomethacin)
- Coma in severe overdose
Renal Manifestations
- Reduced urine output
- Acute kidney injury
- Electrolyte disturbances
Metabolic and Other Features
- Anion-gap metabolic acidosis
- Hypotension and cardiovascular collapse (rare)
- Hepatotoxicity in massive overdoses
Investigations
- Serum electrolytes
- Renal function tests (BUN, creatinine)
- Liver function tests
- Arterial blood gases for acidosis
- Serum drug levels (rarely useful for NSAIDs)
- Stool occult blood test for GI bleeding
Management
1. Initial Stabilization
- Assess airway, breathing, and circulation
- Monitor vital signs and level of consciousness
2. Gastrointestinal Decontamination
- Activated charcoal within 1–2 hours of ingestion
- Consider repeat dose for sustained-release formulations
3. Symptomatic and Supportive Care
- IV fluids for dehydration and kidney protection
- Antiemetics for persistent vomiting
- Proton pump inhibitors for GI irritation or bleeding
- Monitor urine output closely
4. Management of Complications
Renal Injury
- IV hydration
- Avoid nephrotoxic drugs
- Dialysis in severe renal failure
Seizures
- Benzodiazepines (diazepam or lorazepam)
Metabolic Acidosis
- Sodium bicarbonate for severe acidosis
Gastrointestinal Bleeding
- PPI infusion
- Endoscopic evaluation if needed
When to Admit
- Large intentional overdose
- Persistent vomiting or GI bleeding
- Renal dysfunction or electrolyte abnormalities
- Altered mental status or seizures
- Metabolic acidosis
Prognosis
Most NSAID overdoses are mild and resolve with supportive management. Severe toxicity is uncommon but can occur in massive ingestions or in patients with comorbidities. Early recognition and prompt supportive care greatly improve outcomes.
Detailed Notes:
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PATH: PHARMD/ PHARMD NOTES/ PHARMD FOURTH YEAR NOTES/ CLINICAL TOXICOLOGY/ NON-STEROIDAL ANTI-INFLAMMATORY DRUGS.