Introduction to Paracetamol
Paracetamol, also known as acetaminophen, is a commonly used analgesic and antipyretic medication. It is widely available over-the-counter and is considered safe when used at therapeutic doses. However, it can be toxic in overdose situations, leading to severe health complications, including liver damage.
Mechanism of Action
Paracetamol works primarily by inhibiting the enzyme cyclooxygenase (COX), which is involved in the synthesis of prostaglandins. Prostaglandins are compounds that mediate inflammation, pain, and fever. Unlike non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol does not have significant anti-inflammatory properties. Toxicity and Metabolism
In normal doses, paracetamol is metabolized in the liver via conjugation reactions to form non-toxic metabolites. However, a small fraction is metabolized by the cytochrome P450 enzyme system to form a toxic metabolite called N-acetyl-p-benzoquinone imine (
NAPQI). Under normal circumstances, NAPQI is detoxified by conjugation with glutathione. In overdose situations, glutathione stores are depleted, and NAPQI binds to cellular proteins, leading to
hepatic injury.
Symptoms of Paracetamol Overdose
The symptoms of paracetamol overdose can be divided into four stages: Stage 1 (0-24 hours): Symptoms may include nausea, vomiting, sweating, and general malaise.
Stage 2 (24-72 hours): Patients might experience abdominal pain with elevated liver enzymes, indicating liver damage.
Stage 3 (72-96 hours): This is the most critical phase, where liver function may fail, and symptoms of liver necrosis, renal failure, and encephalopathy can occur.
Stage 4 (4 days to 2 weeks): Recovery phase, where liver function might improve if the patient survives the acute phase.
Diagnosis and Management
Diagnosis of paracetamol overdose is primarily based on patient history and serum paracetamol concentration. The
Rumack-Matthew nomogram is a tool used to assess the risk of hepatic injury following an acute overdose. Treatment involves the administration of
N-acetylcysteine (NAC), a precursor of glutathione, which can mitigate liver damage if given promptly.
Prevention and Public Health Considerations
Preventing paracetamol toxicity involves strict adherence to recommended dosing guidelines and public education on the risks of overdose. Combination products containing paracetamol should be used cautiously, especially among individuals with pre-existing liver disease or those consuming alcohol excessively.
Conclusion
Paracetamol is a widely used medication with a favorable safety profile when used correctly. However, its potential for toxicity underscores the importance of understanding its pharmacokinetics and the management of overdose scenarios. Continued efforts in public health education and careful monitoring of paracetamol use can prevent toxic outcomes and ensure patient safety.
