Paracetamol and salicylates are widely used analgesics and antipyretics, but overdose with either drug can cause life-threatening toxicity. Paracetamol poisoning leads primarily to hepatic injury, while salicylate overdose results in metabolic disturbances and multi-organ complications. Early recognition and appropriate management are essential to prevent morbidity and mortality.
Paracetamol (Acetaminophen) Poisoning
Paracetamol is safe at therapeutic doses but can cause severe hepatotoxicity when taken in overdose. Toxicity occurs when the normal metabolic pathways become saturated, leading to the accumulation of a toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI).
Toxic Dose
- Adults: >150 mg/kg
- Children: >200 mg/kg
- Chronic toxicity may occur with repeated supratherapeutic doses
Mechanism of Toxicity
Most paracetamol is conjugated with sulfate and glucuronide. In overdose, excess drug is metabolized via the CYP450 system to NAPQI. Glutathione normally detoxifies NAPQI, but when depleted, hepatocellular injury occurs.
Clinical Stages of Paracetamol Poisoning
Stage I (0–24 hours)
- Nausea, vomiting
- Malaise
- Often asymptomatic despite ongoing hepatic injury
Stage II (24–72 hours)
- Right upper quadrant pain
- Elevated liver enzymes (AST, ALT)
- Prolonged PT/INR
- Hepatic tenderness
Stage III (72–96 hours)
- Peak hepatotoxicity
- Jaundice
- Coagulopathy
- Hypoglycemia and metabolic acidosis
- Acute hepatic failure
Stage IV (4 days–2 weeks)
- Recovery in survivors
- Possible need for liver transplantation in severe cases
Diagnosis
- Serum paracetamol level at 4 hours post-ingestion
- Use of Rumack–Matthew nomogram for risk assessment
- Liver function tests
- Renal function and coagulation profile
Management
N-acetylcysteine (NAC)
NAC replenishes glutathione stores and neutralizes NAPQI. It is most effective within 8 hours of ingestion but can be beneficial even in late presentations.
Indications:
- Paracetamol level above treatment line on nomogram
- Unknown ingestion time
- Severe hepatic injury regardless of time
Supportive Care
- IV fluids
- Treat nausea and vomiting
- Manage hypoglycemia and coagulopathy
Severe Cases
- Referral to liver transplant center
- Monitor for encephalopathy
Salicylate (Aspirin) Poisoning
Salicylates, including aspirin, can cause multi-system toxicity in overdose due to their effects on metabolism, respiration, and the central nervous system.
Toxic Dose
- 150 mg/kg: mild toxicity
- 300 mg/kg: severe toxicity
- >500 mg/kg: potentially lethal
Mechanism of Toxicity
- Uncouples oxidative phosphorylation
- Stimulates respiratory center, causing respiratory alkalosis
- Accumulation of organic acids leads to metabolic acidosis
- Direct CNS and GI irritation
Clinical Features
Early Symptoms
- Tinnitus
- Vertigo
- Nausea and vomiting
- Hyperventilation
Progressive Symptoms
- Fever
- Dehydration
- Metabolic acidosis
- Confusion and agitation
- Seizures
- Pulmonary edema
Investigations
- Serum salicylate level
- Arterial blood gases
- Electrolytes
- Blood glucose (may be low or high)
Management
1. Supportive Care
- Airway and ventilation support
- Correct dehydration
2. Activated Charcoal
Useful within 1–2 hours of ingestion; may repeat dose in sustained-release formulations.
3. Urinary Alkalinization
IV sodium bicarbonate enhances salicylate excretion by increasing urine pH.
Indications:
- Moderate to severe toxicity
- Metabolic acidosis
- Rising salicylate levels
4. Hemodialysis
The most effective method of salicylate removal.
Indications include:
- Serum salicylate level >100 mg/dL
- Severe acidosis
- Renal failure
- Pulmonary edema
- Altered mental status
Detailed Notes:
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PATH: PHARMD/ PHARMD NOTES/ PHARMD FOURTH YEAR NOTES/ CLINICAL TOXICOLOGY/ PARACETAMOL AND SALICYLATES.