Two cases of acute liver injury caused by ingesting small dose of acetoaminophen.

Yasunaga, Mitsuru; Matsuda, Shoshi; Murata, Makoto; Ogino, Michiko; Kado, Yuji; Shinkai, Yasushi; Nawata, H; T, Handa; Noda, Kenichi; Okita, Kiwamu; Takemoto, Tadayoshi

doi:10.2957/kanzo.26.493

Cited by 3 publications

(5 citation statements)

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“…However convincing the numerous reports of liver damage following paracetamol overdosage in chronic alcoholics may be [2–20], they are purely anecdotal and the inescapable fact remains that exactly the same severe and fatal liver damage occurs after overdosage in patients who are not chronic alcoholics. The doses claimed to have been taken by the chronic alcoholics ranged from less than 10 g [6, 17, 18, 103] to more than 30 g [5, 10, 15, 18, 20, 104, 105].…”

Section: Clinical Studiesmentioning

confidence: 99%

“…In the absence of control data these anecdotal case reports in themselves cannot ‘prove’ that therapeutic doses of paracetamol cause liver injury in chronic alcoholics. The fact that there are similar (but sometimes equally suspect) reports of patients who were not chronic alcoholics [7, 18, 40, 41, 58, 103, 123–127] is conveniently overlooked. Indeed, if paracetamol in normal doses is as dangerous in chronic alcoholics as it is claimed, liver damage should be commonplace considering the enormous scale on which the drug is used and the prevalence of alcoholism.…”

Section: Clinical Studiesmentioning

confidence: 99%

“…There have been many reports claiming that the hepatotoxicity of paracetamol (acetaminophen) is increased in chronic alcoholics, and that such individuals not only carry an increased risk of severe and fatal liver damage after acute overdosage [1–20], but that similar serious liver damage may also occur with ‘therapeutic’ use [5, 9, 10, 17, 18, 21–64]. In the original studies of the mechanisms of toxicity, paracetamol was found to cause liver damage through conversion by hepatic cytochrome P450 enzymes to a minor but toxic intermediate metabolite [65–68] and this was subsequently identified as N ‐acetyl‐ p ‐benzoquinoneimine [69, 70].…”

Section: Introductionmentioning

confidence: 99%

“…In the circumstances, it was natural to suspect that there might be similar potentiation of paracetamol hepatotoxicity following overdosage in chronic alcoholics and indeed, this had been suggested in an early study in which the outcome of severe paracetamol poisoning in potentially induced patients appeared to be worse than in similar noninduced patients [1]. Subsequently, many anecdotal reports appeared describing severe and sometimes fatal liver damage in chronic alcoholics taking paracetamol in overdosage [2–20], as well as after its use for therapeutic purposes [5, 9, 10, 17, 18, 21–64].…”

Section: Introductionmentioning

confidence: 99%

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Paracetamol, alcohol and the liver

Prescott

2000

Brit J Clinical Pharma

197

106

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It is claimed that chronic alcoholics are at increased risk of paracetamol (acetaminophen) hepatotoxicity not only following overdosage but also with its therapeutic use. Increased susceptibility is supposed to be due to induction of liver microsomal enzymes by ethanol with increased formation of the toxic metabolite of paracetamol. However, the clinical evidence in support of these claims is anecdotal and the same liver damage after overdosage occurs in patients who are not chronic alcoholics. Many alcoholic patients reported to have liver damage after taking paracetamol with`therapeutic intent' had clearly taken substantial overdoses. No proper clinical studies have been carried out to investigate the alleged paracetamol± alcohol interaction and acute liver damage has never been produced by therapeutic doses of paracetamol given as a challenge to a chronic alcoholic.The paracetamol±alcohol interaction is complex; acute and chronic ethanol have opposite effects. In animals, chronic ethanol causes induction of hepatic microsomal enzymes and increases paracetamol hepatotoxicity as expected (ethanol primarily induces CYP2E1 and this isoform is important in the oxidative metabolism of paracetamol). However, in man, chronic alcohol ingestion causes only modest (about twofold) and short-lived induction of CYP2E1, and there is no corresponding increase (as claimed) in the toxic metabolic activation of paracetamol. The paracetamol±ethanol interaction is not speci®c for any one isoform of cytochrome P450, and it seems that isoenzymes other than CYP2E1 are primarily responsible for the oxidative metabolism of paracetamol in man. Acute ethanol inhibits the microsomal oxidation of paracetamol both in animals and man. This protects against liver damage in animals and there is evidence that it also does so in man. The protective effect disappears when ethanol is eliminated and the relative timing of ethanol and paracetamol intake is critical.In many of the reports where it is alleged that paracetamol hepatotoxicity was enhanced in chronic alcoholics, the reverse should have been the case because alcohol was actually taken at the same time as the paracetamol. Chronic alcoholics are likely to be most vulnerable to the toxic effects of paracetamol during the ®rst few days of withdrawal but maximum therapeutic doses given at this time have no adverse effect on liver function tests. Although the possibility remains that chronic consumption of alcohol does increase the risk of paracetamol hepatotoxicity in man (perhaps by impairing glutathione synthesis), there is insuf®cient evidence to support the alleged major toxic interaction. It is astonishing that clinicians and others have unquestioningly accepted this supposed interaction in man for so long with such scant regard for scienti®c objectivity.

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Section: Clinical Studiesmentioning

confidence: 99%

Section: Clinical Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Paracetamol, alcohol and the liver

Prescott

2000

Brit J Clinical Pharma

197

106

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“…The exposure to paracetamol at the concentration of 66mg/kg body weight has undesirable effects on living organisms like alterations in biochemistry and histopathology in the liver of rats [42] and 5 and 15mg/kg body weight exposure to acetaminophen in the early stages of development affects the neurotransmission associated with the medulla oblongata [43] or it can directly affect the spinal cord [44]. There have been many reports in the past which claim that the hepatotoxicity of paracetamol is highly increased in chronic alcoholics, and such individuals' carry an increased risk of severe and fatal liver damage after acute over dosage [45][46][47][48][49][50][51][52][53][54][55]. The serious liver damage may also occur with 'therapeutic' use of this drug [56][57][58][59][60][61].…”

Section: Environmental Toxicity and Health Risks (Challenges And Thre...mentioning

confidence: 99%

Paracetamol - A Contaminant of High Concern: Existence in Environment and Adverse Effect

Agarwal¹

2022

PDRAJ

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Pharmaceuticals (analgesics and non-steroidal anti inflammatory drugs- NSAIDS) though, a major human scientific development, have undoubtedly lengthened life spans, cured millions from deadly diseases, and made life comfortable and free from pain. This very success has now led to their emergence as rapidly growing environmental pollutants and contaminants. Paracetamol (4’-hudroxyacetanilide, acetaminophen or N-acetyl-p-aminophenol) is amongst the most popular pain killers and widely used analgesic and antipyretic drug which is used for relieving pain and fever as a non prescription drug, worldwide. Such huge consumption all over the world can be expected to result in the contamination of the environment and threat to human health, since residual drugs after usage, easily accumulate in the environment especially aquatic environment through human excreta and industrial effluents produced from paracetamol active ingredients production. Its presence has been found in the environment which has been detected drinking water, waste water and sewage treatment plant effluents. Recent researches focus on adverse effects of paracetamol usage and health hazards in the form of increasing behavioural disorders in offspring. Although chemical oxidation process is done for the treatment of waste water to remove paracetamol but severe reaction conditions, production of secondary pollutants as by products and huge operational expenses associated, leave no choice but to find other methods of treatment. Biodegradation of paracetamol by microorganisms is now being considered as an environment friendly alternative which has bearable cost. The widespread use of paracetamol and the scarcity of parallel and safe alternatives, its impact on the environment and on human health deserves further investigations and researches. The main aim of this review is develop comprehensive understanding on the percolation of paracetamol in environment through uncontrolled usage its toxic effects and proposed metabolic pathways of its biodegradation.

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Should a Lower Treatment Line Be Used When Treating Paracetamol Poisoning in Patients with Chronic Alcoholism?

Dargan

Jones

2002

Drug Safety

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The widespread practice of using a lower plasma paracetamol (acetaminophen) concentration threshold for the treatment of paracetamol poisoning in patients with chronic alcoholism has been introduced on the basis of anecdotal case reports. In animals, acute alcohol loading inhibits toxic metabolic activation of paracetamol whilst chronic alcohol administration results in cytochrome P450 (CYP) 2E1 induction with increased toxic metabolic activation of paracetamol by CYP2E1 and increased hepatotoxicity. However, due to species differences in CYP expression, activity and induction, it is not possible extrapolate the results of these animal studies to clinical situations in humans. Isoenzymes are also responsible for the metabolic activation of paracetamol in humans and human studies to date have not convincingly demonstrated increased toxic metabolic activation of paracetamol in patients with chronic alcoholism. Acute alcohol ingestion at the time of a paracetamol overdose is probably protective and the timing and chronicity of alcohol intake is therefore crucial in the interpretation of the effects of alcohol on paracetamol overdose. One of the problems in the interpretation of the literature to date is that insufficient information is available on the timing of alcohol intake in relation to the ingestion of paracetamol. Whilst it is possible that chronic exposure to excessive amounts of alcohol does predispose patients with paracetamol overdose to hepatotoxicity, a critical review of the literature reveals that the evidence to date does not support this. A prospective, controlled study is required. On the basis of the scientific evidence to date, use of the 100 line for patients with chronic alcoholism, in countries where the 200 line represents the standard treatment line, is unjustified.

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Two cases of acute liver injury caused by ingesting small dose of acetoaminophen.

Cited by 3 publications

References 0 publications

Paracetamol, alcohol and the liver

Paracetamol, alcohol and the liver

Paracetamol - A Contaminant of High Concern: Existence in Environment and Adverse Effect

Should a Lower Treatment Line Be Used When Treating Paracetamol Poisoning in Patients with Chronic Alcoholism?

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