Paracetamol Poisoning
Acute Paracetamol Poisoning
Introduction
Acute paracetamol poisoning is a potentially serious condition that occurs when a person takes an excessive amount of paracetamol, also known as acetaminophen. The purpose of this article is to provide a comprehensive overview of acute paracetamol poisoning, including its definition, common causes, signs and symptoms, diagnosis, treatment options, prevention strategies, and the importance of seeking immediate medical attention.
It occurs most commonly in small children who has low hepatic glucuronide conjugating ability. if a large dose (>150mg/kg or >10 gm in an adult ) is taken, serious toxicity can occur. Mortality is common with a dose of>250 mg/kg.
Sign & Symptom
Initially, acute paracetamol poisoning may not cause any noticeable symptoms. However, as the condition progresses, individuals may experience followings:-
nausea,
vomiting,
abdominal pain,
Liver tenderness,
loss of appetite.
In severe cases, jaundice, confusion and even liver failure can occur.
After 12-18 hours, centilobular hepatic necrosi occurs, which may be accompained by renal tubular necrosis and hypoglycemia, that may progress to coma. Jaundice starts after 2 days. Further course of disease depends on no of tablet(dose) taken. Fulminating hepatic failure occurs if plasma levels are >200 mcg/ml at 4 hours and 30 mcg/ml at 15 hours and death may occur. if the levels are lower, recovery starts with proper treatment. Early recognition of these symptoms is important for early intervention and successful treatment.
Mechanism of toxicity
The mechanism of toxicity of paracetamol mainly involves its metabolite known as N-acetyl-p-benzoquinone imine (NAPQI). Paracetamol is generally safe when used in therapeutic doses, but overdosage can affect the body’s ability to metabolize it, leading to liver damage or even liver failure.
Here is a step-by-step mechanism of poisoning for paracetamol:
1. Metabolism:
When paracetamol is consumed, it undergoes metabolism in the liver mainly by two routes: glucuronidation and sulfation. These pathways convert paracetamol into inactive and water-soluble metabolites that can be readily eliminated from the body.
2. Formation of NAPQI:
In cases of paracetamol overdose, the glucuronidation and sulfation pathways become saturated, and a significant amount of paracetamol is metabolized via a different pathway called the cytochrome P450 system, specifically the enzyme CYP2E1. This pathway leads to the formation of NAPQI, a highly reactive and toxic compound.
3. Glutathione Deficiency:
Under normal conditions, NAPQI rapidly detoxifies by binding to an endogenous antioxidant called glutathione, forming a non-toxic compound. However, during a paracetamol overdose, the excessive production of NAPQI overwhelms the available glutathione stores in the liver.
4. Liver damage:
When glutathione is depleted, NAPQI can bind to cellular proteins within the liver, particularly in the mitochondria. This binding triggers a cascade of events including oxidative stress, mitochondrial dysfunction and activation of inflammatory processes. These processes can lead to hepatocellular damage and necrosis (cell death) in the liver.
5. Systemic Effects:
As liver damage progresses, released cellular components, such as liver enzymes, may enter the bloodstream, potentially causing additional organ damage and systemic effects. If left untreated, severe liver damage can lead to liver failure, which can be life-threatening.
Early recognition and prompt treatment are important in cases of paracetamol overdose. Typical treatment includes administration of an antidote called N-acetylcysteine (NAC), which replenishes depleted glutathione stores and helps neutralize NAPQI.
It is important to note that paracetamol can be safe and effective when used as directed. However, exceeding the recommended dose or combining it with other medicines containing paracetamol may increase the risk of toxicity. If you have any concerns or questions about drug safety, always follow the recommended dosage and consult a healthcare professional.
Diagnosis:-
Diagnosis of acute paracetamol poisoning involves a combination of physical examination and laboratory tests. During the physical exam, health care professionals assess a patient’s vital signs and evaluate the severity of symptoms. Blood tests, including liver function tests, help determine the extent of liver damage due to overdose and guide the appropriate course of treatment.
Treatment:
The primary goal of treating acute paracetamol poisoning is to stabilize the patient and provide supportive care. If patient has been brought early to medical facility, vomiting should be induced or gastric lavage should be done. Activate charcoal should be given to stop further absorption of paracetamol. supportive care includes ensuring proper ventilation, managing any complications, and correcting fluid and electrolyte imbalances. Additionally, specific antidotes such as N-acetylcysteine (NAC) may be administered to counteract the toxic effects of paracetamol on the liver. NAC 150mg/kg should be infused iv over 15 min, followed by same dose iv over next 20 hours. if ingestion treatment interval is >16 hours, it practically ineffective.
Redressal
Preventing acute paracetamol poisoning starts with safe use guidelines. It is essential to adhere to the recommended dosage and avoid exceeding the maximum daily limit. Patients should be aware of possible side effects and interactions with other drugs. It is advised to consult healthcare professionals or read the medicine label for exact dosage instructions and guidance.
Conclusion:
Preventing acute paracetamol poisoning starts with safe use guidelines. It is essential to adhere to the recommended dosage and avoid exceeding the maximum daily limit. Patients should be aware of possible side effects and interactions with other drugs. It is advised to consult healthcare professionals or read the medicine label for exact dosage instructions and guidance.
Please note that although this article has been written to the best of my ability and knowledge, it is always recommended to consult healthcare professionals or medical sources for accurate and personalized information regarding paracetamol poisoning or any other medical condition.
Related Drugs:
Acetylcysteine has long been recognized as an effective antidote via oral or intravenous administration, reducing the risk and severity of acute liver injury if administered adequately within 16 hours of paracetamol overdose.
The diagnosis of acetaminophen poisoning is usually confirmed through diagnostic tests, including acetaminophen levels, electrolytes, kidney function tests, amylase, lipase, liver function tests, complete blood count, and coagulation factors.
>150mg/kg of body weight is considered for paracetamol poisoning.