Recent Developments in the Management of Paracetamol (Acetaminophen) Poisoning

Janes, J.; Routledge, PA

doi:10.2165/00002018-199207030-00002

Cited by 59 publications

(42 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To avert this limitation, intracellular cysteine pools are usually elevated by NAC administration. NAC is involved in the rate-limiting step of GSH synthesis, and is a well-known antioxidant with an established high toxicity threshold in vivo (Janes and Routledge, 1992). NAC can cross the cell membrane; therefore, it has a protective effect inside the cell.…”

Section: Discussionmentioning

confidence: 99%

N-Acetyl-l-cysteine protects against δ-aminolevulinic acid-induced 8-hydroxydeoxyguanosine formation

1999

View full text Add to dashboard Cite

5-Aminolevulinic acid (ALA) is a heme precursor that accumulates in acute intermittent porphyria and lead poisoning. It has been shown that ALA induces free radical generation and may cause damage to proteins and DNA. In the present study, the effects of ALA on DNA damage and its prevention by N-acetyl-L-cysteine (NAC) and the antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD) are investigated. Oxidative damage to DNA was quantitated by measuring the increase in 8-hydroxy-2%-deoxyguanosine (oh 8 dG) formation. The time -course study demonstrated that ALA causes a linear increase in oh 8 dG levels in Chinese hamster ovary (CHO) cells. However, direct lead exposure did not cause any measurable increase in oh 8 dG levels. In the presence of either NAC (1 mM) or antioxidant enzymes (10 u/ml SOD and 10 u/ml CAT), oh 8 dG levels returned to the corresponding control levels. This suggests a protective role for NAC and the antioxidant enzymes. To determine the effect of ALA on cell proliferation, cell numbers were counted at the end of 24 h of incubation in the presence and absence of ALA at different concentrations. Results showed that levels of ALA up to 5 mM do not inhibit cell proliferation.

show abstract

Section: Discussionmentioning

confidence: 99%

N-Acetyl-l-cysteine protects against δ-aminolevulinic acid-induced 8-hydroxydeoxyguanosine formation

1999

View full text Add to dashboard Cite

show abstract

“…The formation of NAPQI (measured as the GSH conjugate) by foetal hepatocytes was one-tenth of that compared with the adult level, and sulfation of paracetamol clearly predominated over glucuronidation in the foetus. Early antidotal treatment with N-acetylcysteine appears to improve outcome in cases of paracetamol overdose in pregnancy (Janes & Routledge 1992).…”

Section: Paracetamolmentioning

confidence: 99%

Neonatal Hepatic Drug Elimination

Gow

Ghabrial

Smallwood

et al. 2001

Pharmacology & Toxicology

104

View full text Add to dashboard Cite

After the transition from in utero to newborn life, the neonate becomes solely reliant upon its own drug clearance processes to metabolise xenobiotics. Whilst most studies of neonatal hepatic drug elimination have focussed upon in vitro expression and activities of drug-metabolising enzymes, the rapid physiological changes in the early neonatal period of life also need to be considered. There are dramatic changes in neonatal liver blood flow and hepatic oxygenation due to the loss of the umbilical blood supply, the increasing portal vein blood flow, and the gradual closure of the ductus venosus shunt during the first week of life. These changes which may well affect the capacity of neonatal hepatic drug metabolism. The hepatic expression of cytochromes P450 1A2, 2C, 2D6, 2E1 and 3A4 develop at different rates in the postnatal period, whilst 3A7 expression diminishes. Hepatic glucuronidation in the human neonate is relatively immature at birth, which contrasts with the considerably more mature neonatal hepatic sulfation activity. Limited in vivo studies show that the human neonate can significantly metabolise xenobiotics but clearance is considerably less compared with the older infant and adult. The neonatal population included in pharmacological studies is highly heterogeneous with respect to age, body weight, ductus venosus closure and disease processes, making it difficult to interpret data arising from human neonatal studies. Studies in the perfused foetal and neonatal sheep liver have demonstrated how the oxidative and conjugative hepatic elimination of drugs by the intact organ is significantly increased during the first week of life, highlighting that future studies will need to consider the profound physiological changes that may influence neonatal hepatic drug elimination shortly after birth.The development of clinical pharmacology has resulted in a more rational approach to drug therapy, as well as a deeper understanding of the factors capable of influencing drug disposition, and hence drug effects. Of these factors, age is of great importance. However, substantial differences in drug disposition not only exist between neonates and adults, but also among premature neonates, term neonates, infants and children.During the last two decades drug disposition in the neonatal period has been studied extensively. A major impetus for these studies seems to have been a series of incidents involving illness or death following the administration of drugs at ratios of dose/body weight innocuous in an adult (Craft et al. 1974;Gershanik et al. 1982). These studies have shown that the transition from neonate to childhood is characterised by the ontogeny of all of the processes of drug absorption, distribution, hepatic metabolism and renal excretion, with the development of hepatic drug metabolism being particularly important.The extent to which the neonatal drug-metabolising en-

show abstract

“…Treatment with intravenous acetylcysteine is commonly used in the United Kingdom in patients with acetaminophen (paracetamol) poisoning. The dose depends on the patient's body weight and requires the preparation of at least three separate infusion bags [7]. The dose of acetylcysteine in each bag is different, as is the volume of 5% glucose solution in each infusion (see Table 1).…”

Section: Introductionmentioning

confidence: 99%

Random and systematic medication errors in routine clinical practice: a multicentre study of infusions, using acetylcysteine as an example

Ferner

Langford

Anton

et al. 2001

Brit J Clinical Pharma

View full text Add to dashboard Cite

Aims The nature and incidence of errors in prescribing and giving medicines have previously been estimated by trained observers, or by retrospective analysis of incidents in which patients have come to harm. We have examined prospectively in routine clinical practice the concentrations of intravenous infusions of a drug (acetylcysteine) which is given according to a complicated dosing schedule. Methods We prospectively collected samples before and, where possible, after the infusion of acetylcysteine in 66 anonymous patients requiring treatment for acetaminophen (paracetamol) overdose in four centres in the United Kingdom. We measured the concentration in each infusion bag, and deduced from the weight of the patient the percentage of the anticipated dose that had actually been given. Results The experimentally determined dose was within 10% of the anticipated dose in 68 of 184 individual bags (37%), and within 20% of the anticipated dose in 112 bags (61%). Doses in 17 bags were more than 50% from the anticipated doses. In three patients, values in all three bags appeared to be systematically wrong by 50% or more; in a further seven cases, individual bags differed by 50% or more from the anticipated value. The median difference between pre-and post-infusion samples was 0% [interquartile range x5.2% to +14.6%], but 9% showed a disparity of greater than t50%. Conclusions Our data suggest that there is large random variation in administered dosage of intravenous infusions. Systematic calculation errors occur in about 5% [95% con®dence interval 2, 8%] of cases, and major errors in drawing up in a further 3% [1, 7%], with inadequate mixing in 9% [4, 14%]. While we have no evidence that patients were adversely affected, and while the regime of administration of the drug studied (acetylcysteine) is complicated, these data suggest that the delivered dose often deviates from the intended dose, and that methods of quality control are needed.

show abstract

Recent Developments in the Management of Paracetamol (Acetaminophen) Poisoning

Cited by 59 publications

References 35 publications

N-Acetyl-l-cysteine protects against δ-aminolevulinic acid-induced 8-hydroxydeoxyguanosine formation

N-Acetyl-l-cysteine protects against δ-aminolevulinic acid-induced 8-hydroxydeoxyguanosine formation

Neonatal Hepatic Drug Elimination

Random and systematic medication errors in routine clinical practice: a multicentre study of infusions, using acetylcysteine as an example

Contact Info

Product

Resources

About