Poisoning paracetamol

A medical journal reported that patients suffering from paracetamol poisoning should be nursed at 30° 0°. In the next issue, it said that this refened to the angle in bed, not the temperature [7]. 

Paracetamol overdose is most likely to cause hepatic necrosis and to a lesser extent renal necrosis. Hepatic necrosis is maximal within 3-4 hours of ingestion and may lead to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema and death. Acetylcysteine tends to protect the liver if given within 10-12 hours of paracetamol poisoning. The maximum adult dose of paracetamol is 4 g in 24 hours. 

Buckley, N.A. and Srinivasan, J. (2002) Should a lower treatment line be used when treating paracetamol poisoning in patients with chronic alcoholism a case for. Drug Safety, 25 (9), 619-624. 

Acetaminophen (paracetamol) poisoning is common in Western countries and is increasing elsewhere. Single doses as low as 7.5 g in adults or 150 mg/kg in a child can cause severe toxicity. Very occasionally, lower doses cause harm. Mortality, from hepatic or occasionally renal failure, is related to blood concentration and the time between ingestion and the initiation of antidotal treatment. Even severely poisoned patients may be asymptomatic, although nausea and vomiting are fairly common. 

Bridger S, Flenderson K, Glucksman E, Ellis AJ, Henry JA, Williams R. Deaths from low dose paracetamol poisoning. BMJ 1998 316(7146) 1724-5. 

Minton NA, Henry JA, Frankel RJ. Fatal paracetamol poisoning in an epileptic. Hum Toxicol 1988 7 33-34. 

Schmidt LE, Dalhoff K. Concomitant overdosing of other drugs in patients with paracetamol poisoning. Br J Clin Pharmacol 2002 53(5) 535 11. 

These protective agents prevent damage to organs and tissues, but if there are too many toxic molecules they are soon overwhelmed, and damage and destruction can follow. As we shall see in the next chapter, this is what happens in paracetamol poisoning following an overdose. 

Acetylcysteine is used intravenously as an antidote for severe paracetamol poisoning, in which it acts as a thiol donor. 

Smith JM, Roberts WO, Hall SM, White TA, Gilbertson AA. Late treatment of paracetamol poisoning with mercaptamine. BMJ 1978 l(6109) 331-3. 

Drugs that induce liver microsomal enzymes, such as phenobarbital, phenytoin, carbamazepine, rifampicin, and isoniazid, can make paracetamol poisoning more severe (104,105). In patients taking such drugs the serum paracetamol concentration should be doubled before consulting the usual treatment nomogram. 

Thomas SH, Homer JE, Chew K, Connolly J, Dorani B, Bevan L, Bhattacharyya S, Bramble MG, Han KH, Rodgers A, Sen B, Tesfayohannes B, Wynne H, Bateman DN. Paracetamol poisoning in the north east of England presentation, early management and outcome. Hum Exp Toxicol 1997 16(9) 495-500. 

Law R. Severity of overdose after restriction of paracetamol availability. Why hasn t strategy for minimising paracetamol poisoning been enacted BMJ 2001 322(7285) 554. 

UK National Poisons Information Service. National guidelines management of acute paracetamol poisoning. Paracetamol Information Centre in collaboration with the British Association for Accident and Emergency Medicine. 1995. 

There are no regulatory exposure standards or guidelines for NAC. Acute doses of 140 mg kg are recommended for the initial loading dose in humans (i.e., for paracetamol poisoning) and 1330 mg kg can be tolerated by humans over a 72 h period. 

Parvolex ) is used a MUCOLYTIC agent, which reduces the viscosity of sputum, so can be used as an expectorant in patients with disorders of the upper respiratory airways, such as chronic asthma and bronchitis. It is also used orally to treat abdominal complications associated with cystic fibrosis, and locally in the eye to increase lacrimation and mucus secretion. It is also used intravenously as an antidote in paracetamol poisoning. 

Flanagan RJ, Mant TGK. Coma and metaboHc acidosis in severe acute paracetamol poisoning. Human Toxicol 1986 5 179-82. 

Paracetamol poisoning is particularly dangerous as the toxic level may not be greatly above the therapeutic level. Also, symptoms of overdose may not appear for 2 days or more, allowing unwitting overdosage to continue. 

Buckley NA, Whyte IM, O Connell DL, DawsonAHJ. Oralorintravenous N-acetylcysteine Which is the treatment of choice for acetaminophen (paracetamol) poisoning J Toxicol CUn Toxicol 1999 37 759-767. 

Paracetamol poisoning provides a useful human model to compare the effectiveness of plasma GST with aminotransferase measurements because in such patients there is often a wide spectrum of the severity of liver damage encountered. In addition, damage to the liver initially occurs in the centrilobular hepatocytes, where phase I drug metabolizing enzymes produce the toxic metabolite (J3). 

Ro. 17. Plasma GST B and B2 subunits and ALT activities in patients with paracetamol poisoning. The upper (a) figure shows enzyme levels in patients treated successfully with Af-acetylcysteine following the admission (first) blood sample and the lower (b) figure the enzyme levels in patients admitted too late after the overdose for effective treatment with Af-acetylcysteine. All data are expressed as multiples of the upper reference limit. 

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