Causes
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Acetaminophen is primarily metabolized by the liver. Overdose acetaminophen can overwhelm the liver normally functions.
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Production of acetaminophen's toxic metabolite- NAPQI, causes liver damage, necrosis, and failure.
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If the liver is already damaged because of viral or bacterial infection, alcohol abuse, or other illness, there is increased susceptibility of damage from acetaminophen overdose.
Signs and symptoms
End-organ (liver and kidney) toxicity is often delayed 24-48 hours postingestion.
Patients with malnutrition, AIDS, chronic alcohol abuse, are at increased risk for morbidity because of deficient glutathione stores and inadequate detoxification of NAPQI.
Phase 1- (0 – 24 hrs)
Phase 2- (24 – 72 hrs)
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Right upper quadrant abdominal pain
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Anorexia
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Nausea/vomiting
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Right upper quadrant abdominal tenderness
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Tachycardia
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Hypotension
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Continued rise in LFT (serum transaminases) levels
Phase 3 (72- 96 hrs)
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With centrilobular liver necrosis- the intensity and severity abdominal pain increases
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Jaundice
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Increased bleeding manifestation
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Hepatic encephalopathy
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Renal failure
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Fatality
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Tenderness in liver edge
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Gastrointestinal (GI) bleeding
Phase 4 (4 days – 3 wk)
Complete resolution of symptoms and organ failure
Tests and diagnosis
Serum acetaminophen concentration
Serum APAP concentration (N-acetyl-p-aminophenol)
Liver function test
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Transaminases levels- SGOT and SGPT, toxicity is defined as serum SGOT or SGPT levels greater than 1000 IU/L.
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Direct and indirect bilirubin levels
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Serum electrolytes
Renal function test- blood urea and creatinine
Human chorionic gonadotropin (HCG levels) in females of childbearing age
Urinalysis- proteinuria and hematuria in acute tubular necrosis
Arterial blood gas analysis
Treatment
Emergency care
Gastric decontamination
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Activated charcoal is the drug of choice for patients presenting within 1-2 hrs of ingestion
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Activated charcoal avidly adsorbs acetaminophen and should be administered if the patient presents within 1 hour of ingestion
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1 g/kg orally or 10 times the amount of drug ingested
Antidote- N-acetyl-cysteine
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Early administration of N-acetyl-cysteine, within 8 hours of ingestion, is nearly 100% hepato protective.
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It’s the drug of choice for prevention and treatment of acetaminophen-induced hepatotoxicity.
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It can be administered orally after diluting with chilled juice or cola to a 5% solution.
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Can also be given by nasogastric tube, if nausea and vomiting is severe
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When administered IV, dilute in 5% dextrose solution.