Treatment of Paracetamol (Acetaminophen) Poisoning With N-Acetylcysteine

Prescott, L. F.; Ballantyne, Anna; Proudfoot, A. T.; Park, Jay J; Adriaenssens, Peter

doi:10.1016/s0140-6736(77)90612-2

Cited by 389 publications

(223 citation statements)

References 9 publications

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“…22 The dosage regimen for intravenous NAC was originally chosen in order to give the highest tolerable dose for a short period in the hope of reversing the events leading to hepatic necrosis at a critical stage. 23 The regimen, although of proven value in the treatment of paracetamol poisoning, is unlikely to be the optimal one, particularly in patients with preexisting liver disease. Our study indicates that reevaluation of the current dosage regimen for NAC is required in patients with cirrhosis and vigilance for adverse effects is required in such patients receiving NAC therapy.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of N‐acetylcysteine are altered in patients with chronic liver disease

Jones

Jarvie

Simpson

et al. 1997

Aliment Pharmacol Ther

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Background: The threshold plasma paracetamol concentration at which N‐acetylcysteine (NAC) treatment is recommended to treat paracetamol poisoning in a patient with induced liver enzymes (for example, with chronic liver disease or taking anticonvulsant drugs) is 50% lower than in a patient without induced liver enzymes. More patients with chronic liver disease might therefore be expected to be exposed to NAC treatment than previously. In addition, there is increasing use of NAC in patients with chronic liver disease for multiorgan failure or hepatorenal syndrome. Little is known of NAC's pharmacokinetic properties in patients with cirrhosis. Aim: The aim was to determine if the pharmacokinetics of NAC are altered by chronic liver disease. Subjects and methods: NAC was given intravenously in a dose of 600 mg over 3 min to nine patients with biopsy‐proven cirrhosis (Child's grade; 1 A, 4 B, 4 C; aetiology: 7 alcohol‐related, 1 primary biliary cirrhosis, 1 secondary biliary stenosis) and six healthy matched controls. Venous blood was taken at 20, 40, 60 and 90 min then at 2, 3, 4, 6, 8 and 10 h after NAC administration. Serum NAC was estimated by HPLC. The data were normalized to a standard body weight of 70 kg. Results: The area under the serum concentration–time curve was increased (152.34 mg/L.h ± 50.38 s.d.) in cirrhotics compared with normal controls; (93.86 mg/L.h ± 9.60 s.d.) (P < 0.05). The clearance of NAC was reduced in patients with chronic liver disease (4.52 L/h ± 1.87 s.d.) compared with controls (6.47 L/h ± 0.78; P < 0.01). Conclusions: Increased vigilance for untoward anaphylactoid reactions is necessary in cirrhotics as they may have higher plasma NAC concentrations. Further studies to determine the optimum dosage regimen in such patients are required.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of N‐acetylcysteine are altered in patients with chronic liver disease

Jones

Jarvie

Simpson

et al. 1997

Aliment Pharmacol Ther

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show abstract

“…The use of oral Lmethionine has been recommended, but again, did not always prevent severe liver damage (Crome, Vale, Volans, Widdop & Goulding, 1976). In 1974 we suggested that N-acetylcysteine might be effective, and this was subsequently confirmed in animal studies (Piperno & Berssenbruegge, 1976) and in man (Prescott, Park, Ballantyne, Adriaenssens & Proudfoot, 1977;Prescott, 1978b aqueous sterile solution and lacks the unpleasant side effects of cysteamine. The results of early treatment of severe paracetamol poisoning with intraveneous Nacetylcysteine are shown in Figures 1 and 2.…”

Section: Paracetamolpoisoning and Acute Hepatic Necrosismentioning

confidence: 99%

The third Lilly Prize Lecture. University of London, January, 1979. The nephrotoxicity and hepatotoxicity of antipyretic analgesics.

Prescott¹

1979

Brit J Clinical Pharma

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“…In 1977, Prescott et al 2 described the treatment of 15 patients with acetaminophen poisoning with i.v. acetylcysteine using a sterile 20% aqueous solution, suggesting that oral administration may improve the drug's efficacy, "since most of the dose should pass through the liver."…”

mentioning

confidence: 99%

“…51 Orally administered acetylcysteine undergoes a first-pass effect so that the entire dose passes through the liver, resulting in high concentrations and the potential for hepatotoxicity. 2 This may be advantageous in poisoned patients who present within 8-10 hours postingestion.…”

mentioning

confidence: 99%

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Comparison of oral and i.v. acetylcysteine in the treatment of acetaminophen poisoning

Kanter

2006

American Journal of Health-System Pharmacy

101

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Treatment of Paracetamol (Acetaminophen) Poisoning With N-Acetylcysteine

Cited by 389 publications

References 9 publications

Pharmacokinetics of N‐acetylcysteine are altered in patients with chronic liver disease

Pharmacokinetics of N‐acetylcysteine are altered in patients with chronic liver disease

The third Lilly Prize Lecture. University of London, January, 1979. The nephrotoxicity and hepatotoxicity of antipyretic analgesics.

Comparison of oral and i.v. acetylcysteine in the treatment of acetaminophen poisoning

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