Paracetamol and Renal Damage

Edwards, O. M.; Edwards, P.; Huskisson, E. C.; Taylor, Ruth

doi:10.1136/bmj.2.5753.87

Cited by 30 publications

(4 citation statements)

References 9 publications

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“…There were no important renal function abnormalities and no evidence of papillary necrosis. A further study with paracetamol (Edwards et al, 1971) reached a similar conclusion. Laakso et al, (1986) observed 1000 patients over a lO-year period and compared them with a matched control population of the same size.…”

Section: Renal Papillary Necrosis (Analgesic Nephropathy)supporting

confidence: 52%

Aspirin, Paracetamol and Non-Steroidal Anti-Inflammatory Drugs

Fowler¹

1987

Medical Toxicology

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Non-steroidal anti-inflammatory drugs (NSAIDs) effectively control the symptoms of many of the rheumatic diseases although they have little effect on the underlying causes. Their effect is mainly on the mediators of the inflammatory process. Unfortunately, these mediators have important physiological roles in the maintenance of health, particularly in the gastrointestinal tract and the kidney, so that their inhibition results in many unwanted reactions of varying severity. The mechanisms underlying these reactions are described. Their occurrence varies, both qualitatively and quantitatively, and an attempt is made to assess these differences, although it may be that they are related directly to differences in dosage and therapeutic efficacy. In addition, immunologically mediated adverse reactions occur. These mechanisms are outlined and related to the clinical picture. There are considerable differences in frequency of reactions between the compounds: in particular there is a wide variation in the rate of dermatological reactions of this type. Agranulocytosis has been particularly associated with the pyrazolone compounds, although it has been reported with most others. Aplastic anaemia, which may not be an immune-mediated reaction, is also thought of as a pyrazolone reaction, but the incidence with indomethacin approaches a similar level. Although all drugs analysed may cause hepatic reactions, these are rare except with the now withdrawn benoxaprofen. Several types of immunologically mediated renal reactions occur and these rarities are also described. Paracetamol does not have any effect on the inflammatory mediators. Anxieties about this substance relates to the parent compound phenacetin and its necrotic effect on the renal papillae. There is extensive literature on this subject concerning not only paracetamol, but also aspirin and other NSAIDs. This is also assessed and summarised. The danger of paracetamol as a direct hepatic toxin in self-poisoning is discussed. Novel NSAIDs are introduced and others withdrawn with frequent and monotonous regularity. Sometimes the reasons have some medical or scientific plausibility, but often they are over-reactions by registration authorities or pharmaceutical companies in response to uninformed media publicity. The problems of the numerically and scientifically accurate collection and assessment of adverse reaction data are legion and as a result useful agents have been lost. Some of these difficulties are described, and some non-drug 'adverse reactions' are described.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Renal Papillary Necrosis (Analgesic Nephropathy)supporting

confidence: 52%

Aspirin, Paracetamol and Non-Steroidal Anti-Inflammatory Drugs

Fowler¹

1987

Medical Toxicology

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“…As with other non-steroidal anti-inflammatory drugs, paracetamol may cause acute renal failure following overdosage (Prescott, 1983), and there has been a single report of reversible acute tubular necrosis attributed to the use of therapeutic doses (Gabriel et al, 1982). There have been very few reports of analgesic nephropathy associated with paracetamol alone (Prescott, 1982;Segasothy et al, 1988) and its cumulative consumption during chronic use in patients with arthritis was not related to impairment of renal function (Edwards et al, 1971). The results of recent epidemiological studies have been conflicting.…”

Section: Effects Ofparacetamol and Indomethacin On The Disposition Ofmentioning

confidence: 99%

The comparative effects of paracetamol and indomethacin on renal function in healthy female volunteers.

Prescott

Mattison

Menzies

et al. 1990

Brit J Clinical Pharma

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1 Renal function was assessed in 10 healthy female volunteers during administration of placebo, paracetamol (acetaminophen) (4.0 g daily) and indomethacin (150 mg daily) for 3 days under conditions of controlled sodium and fluid intake. 2 Paracetamol and indomethacin had no significant effect on the glomerular filtration rate and effective renal plasma flow as measured by the renal clearances of inulin, creatinine and p-aminohippurate (PAH). 3 Compared with placebo, paracetamol reduced the mean urinary excretion of prostaglandin E2 by 43% on the second day and 58% on the third treatment day (P < 0.01). With indomethacin the corresponding reductions were 73 and 80%. Paracetamol and indomethacin had much less effect on the excretion of prostaglandin 6-keto Fia, and a significant decrease was observed only on the third day. 4 The decreased urinary excretion of prostaglandin E2, produced by paracetamol was associated with a reduction in sodium excretion of more than 50% (P < 0.01) and delay in the onset of diuresis following an acute water load. 5 The renal effects of paracetamol and indomethacin appear to differ. Although indomethacin reduced prostaglandin excretion more than paracetamol it had a similar effect on sodium excretion and less initial antidiuretic action. Unlike paracetamol, indomethacin also reduced basal plasma renin activity. 6 Paracetamol reduced the total body clearance of PAH and increased its plasma halflife. This effect could be attributed to inhibition of the acetylation of PAH by paracetamol. 7 In normal use paracetamol does not appear to have the adverse renal effects associated with the non-steroidal anti-inflammatory analgesics and further studies are required to establish the clinical significance of these findings.

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“…In one series of 280 patients who had taken an overdose of paracetamol, isolated renal failure in the absence of severe liver damage was not seen (Lesna et al, 1976). Ingestion of the parent compound, phenacetin, over a long period is a well recognised cause of chronic renal failure, but this has been reported only rarely following chronic ingestion of paracetamol (Krikler, 1967;Edwards et al, 1971).…”

mentioning

confidence: 99%

Frequency of renal impairment in paracetamol overdose compared with other causes of acute liver damage.

Wilkinson¹,

Moodie²,

Arroyo³

et al. 1977

J Clin Pathol

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SUMMARY In an analysis of 160 patients with fulminant hepatic failure, the frequency of renal failure in the patients who had taken an overdose of paracetamol was not significantly higher than in those with hepatic failure due to other causes. The same was found in another group of patients with less severe hepatic damage. In both the latter group and the patients with fulminant hepatic failure, the development of renal failure was closely related to the occurrence of endotoxaemia as detected by the Limulus lysate assay. These findings do not support the concept that an overdose of paracetamol has a specific nephrotoxic effect.

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Paracetamol and Renal Damage

Cited by 30 publications

References 9 publications

Aspirin, Paracetamol and Non-Steroidal Anti-Inflammatory Drugs

Aspirin, Paracetamol and Non-Steroidal Anti-Inflammatory Drugs

The comparative effects of paracetamol and indomethacin on renal function in healthy female volunteers.

Frequency of renal impairment in paracetamol overdose compared with other causes of acute liver damage.

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