2, synthesis of acetaminophen with benzene as raw material.
- Paracetamol is produced in different ways. Say all this and discuss a specific way of making paracetamol.
- Why is acetaminophen absorbed more quickly in liquid preparations than in solid ones?
- Do you think paracetamol poisoning and the paracetamol tragedy have the same cause? Explain both. Is there an antidote to paracetamol toxicity?
Overdoses account for about 40% of acute liver failure in the United States and The United Kingdom
Half of hospital admissions for acetaminophen overdose (150 mg/kg) were unintentional
The average ingested dose leading to liver failure was 24 g.
Nephrotoxicity occurs in 1-2% of patients with acetaminophen overdose
If toxicity is suspected, do not delay NAC (N-acetylcysteine). The mechanisms of action of the antidotes include increased glutathione storage and binding to NAPQI, antioxidant effect, anti-inflammatory effect, and increased microvascular perfusion of NO production
Serum acetaminophen concentration as plotted on rumack-Matthew standard chart
Stage 1: (0-24 hours) : asymptomatic, anorexia, N/V, discomfort, subclinical elevation of serum transaminase
Stage 2: (18-72 hours) : right upper abdominal pain, anorexia, increased N/V, transaminase levels
Stage III (72-96 hours) : central lobular necrosis, jaundice, coagulopathy, hepatic encephalopathy, renal failure, fulminant hepatitis, death
Stage IV (96 hours to 3 weeks) : Complete resolution of symptoms and organ failure
Stomach decontamination: within 4 hours after ingestion (charcoal 1g/kg PO)
NAC is given intravenously (150 mg/kg over 15 minutes, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours) or orally (140 mg/kg, then 70 mg/kg Q4 x 17 doses) within 8 hours of ingestion
Support measures
Perioperative morbidity was increased in patients with increased liver function tests
The better prognosis in the pediatric population under 5 years of age after acetaminophen poisoning may be related to increased volume
Asthma may develop in patients who use acetaminophen for a long time.
Avoid anesthesia techniques (i.e., halothane) that impair liver/kidney blood flow
Delay elective surgery and follow liver and renal function tests to optimize the timing of surgical intervention
Long-term use of acetaminophen 2° to Htn in women may alter the autoregulation curve of hemodynamic organ perfusion homeostasis
Increased potential clotting of anticoagulants (e.g., warafin, nsaids)
