Therapeutic misadventure with paracetamol in children

Shivbalan, So; Sathiyasekeran, Malathi; Thomas, Kuruvilla

doi:10.4103/0253-7613.71894

Cited by 10 publications

(9 citation statements)

References 10 publications

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“…However, there are few reports on the toxicity of acetaminophen in India is available. 6) Therefore the present study was designed to evaluate the sub-acute toxicity of acetaminophen in order to find out no observed effect level, target organ toxicity and reversibility of signs of toxicity after the recovery period in Sprague Dawley (SD) rats.…”

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Sub-acute Toxicity Studies of Acetaminophen in Sprague Dawley Rats

Deecaraman

Vijayalakshmi

et al. 2014

Biological & Pharmaceutical Bulletin

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The aim of the present study was to evaluate the sub-acute oral toxicity of acetaminophen in Sprague Dawley (SD) rats at 250 to 1000 mg/kg body weight (b.wt.). The following observations were noticed during the study. No mortality in male and female rats, at and up to the dose of 1000 mg/kg b.wt. There were abnormal clinical signs observed on female animals at 1000 mg/kg b.wt. dose level. There were no difference in body weight gain and no effect on the daily feed consumption. No toxicologically significant effect on the haematological parameters but liver and kidney related biochemical parameter showed significant difference at 1000 mg/kg b.wt. in females. No toxicologically significant effect on the urinalysis parameters, absolute and relative organ weights and gross pathological alterations; whereas histopathological alterations were observed in female liver at dose level of 1000 mg/kg b.wt. were observed. Based on the findings of this study, the No Observed Adverse Effect Level (NOAEL) of acetaminophen in SD rats, following oral administration at the doses of 250, 500 and 1000 mg/kg on daily basis was found to be 500 mg/kg b.wt.Key words acetaminophen; rat; hematology; biochemistry Acetaminophen (paracetamol) is a widely consumed antipyretic over-the-counter (OTC) drug in India in spite of it was banned in most of the developed countries. Acetaminophen was first evaluated for pharmacologic activity in 1893 by Von Mehring, who discovered its analgesic and antipyretic properties; however, it was not until the work of Brodie in the 1940's that serious consideration was given to its use in humans. 1)Acetaminophen was first introduced as a prescription drug in the United States in 1955 and was approved by the Food and Drug Administration for sale as a non prescription drug in 1960.2) Toxicity from acetaminophen is not from the drug itself but from one of its metabolites, N-acetyl-p-benzoquinoneimine (NAPQ1). Acetaminophen biotransformation involves conjugation with glucoronide and sulphate. A small amount of acetaminophen is metabolised by mixed function oxidase enzymes to form highly reactive compound NAPQ1, which is immediately conjugated with glutathione and subsequently excreted as cysteine and mercapturic conjugates. In overdoses, large amounts of acetaminophen are metabolised by oxidation because of saturation of the sulphate conjugation pathway, 3,4) but once the protective intracellular glutathione stores are depleted hepatic and renal damage may ensue. Hepatotoxicity is the most remarkable feature of acetaminophen overdose.5) Acute overdoses of acetaminophen can cause potentially fatal liver damage and, in rare individuals, a normal dose can do the same; the risk is heightened by alcohol consumption. Acetaminophen toxicity is the foremost cause of acute liver failure. Renal effects of acetaminophen overdose are less commonly seen than hepatic effects. However, renal impairment may be more common than previously recognised. There are extensive toxicity studies on acetaminophen are available. However, ther...

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Sub-acute Toxicity Studies of Acetaminophen in Sprague Dawley Rats

Deecaraman

Vijayalakshmi

et al. 2014

Biological & Pharmaceutical Bulletin

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“…Es por esto que el uso de los antipiréticos deberá estar sustentado en un uso racional, pues no se trata de un medicamento inocuo. Por el contrario, existen múltiples evidencias que cuestionan el uso rutinario de antipiréticos, sustentadas en el riesgo al que se someten los niños debido a su toxicidad (45)(46)(47). Sin embargo, se deben considerar los niños que no toleran el aumento de las demandas metabólicas y los que poseen condiciones específicas de base, como la presencia de enfermedades crónicas o graves, en las que el manejo deberá ser diferencial y enfocado en lograr la normotermia, ya que en ellos las reservas metabólicas se encuentran disminuidas, por tanto se debe mejorar el reconocimiento, la evaluación y el manejo de la fiebre en lo que respecta a enfermedades subyacentes en los niños (48).…”

Section: El Uso De Antipiréticos: Una Rutina En Contravía De La Saludunclassified

La fiebre en el niño: una mirada reflexiva a las prácticas de cuidado

Tobón

2017

Av. enferm.

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Objetivo: Realizar uma análise crítico-reflexiva das práticas de rotina por profissionais de enfermagem e cuidadores familiares, em cuidados para a criança com febre, que permita promover a busca de cuidados baseados em evidências científicas que garanta o bem-estar das crianças. Conclusões: A concepção de febre na criança centrada sobre o medo e os danos, permanece. As ações de cuidados mais comuns tais como banho de esponja e o uso e abuso de antipiréticos são questionados a partir da evidência, mostrando os efeitos deletérios produzidos sobre a saúde das crianças. Cuidar de crianças, após um enfoque individualizado na avaliação, deve procurar conforto, um ambiente fresco e tranquilo, e aumentar a ingestão de líquidos para evitar a desidratação ou outras complicações. Síntese do conteúdo:Descritores: Febre; Criança; Cuidadores; Enfermagem Baseada em Evidências; Cuidado da Criança (fonte: decs, bireme). Objective:To carry out a critical and reflexive analysis of nursing professionals and family caregivers routine practices in feverish child caring, in order to promote the caring based on scientific evidence that assures child well-being.

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“…3 ), which is 10–15 times the recommended dosage [ 78 ], even though idiosyncratic reactions associated to increased activity of the hepatic cytochrome P450 detoxifying system have been reported [ 85 ]. Sustained dosing (>1 day) with >90 mg/kg/day (whereas the recommended dosing 60 mg/kg/day) puts children aged <2 years at high risk for hepatotoxicity [ 81 ]. Case reports describe children presenting with paracetamol toxicity after sustained dosing of 100–367 mg/kg/day [ 81 ].…”

Section: Tolerability and Safetymentioning

confidence: 99%

“…Sustained dosing (>1 day) with >90 mg/kg/day (whereas the recommended dosing 60 mg/kg/day) puts children aged <2 years at high risk for hepatotoxicity [ 81 ]. Case reports describe children presenting with paracetamol toxicity after sustained dosing of 100–367 mg/kg/day [ 81 ]. A recent study conducted in Australia and New Zealand revealed that hepatic failure due to paracetamol ingestion occurred in children mostly as a result of medication errors such as doses in excess of 120 mg/kg/day, double dose, too frequent administration, coadministration of other medicines containing paracetamol or regular paracetamol for up to 24 days [ 82 ].…”

Section: Tolerability and Safetymentioning

confidence: 99%

Recent Advances in Pediatric Use of Oral Paracetamol in Fever and Pain Management

Martino

Chiarugi

2015

Pain Ther

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Paracetamol is a common analgesic and antipyretic drug for management of fever and mild-to-moderate pain in infants and children, and it is considered as first-line therapy for the treatment of both according to international guidelines and recommendations. The mechanism of action of paracetamol is complex and multifactorial, and several aspects of the pharmacology impact its clinical use, especially in the selection of the correct analgesic and antipyretic dose. A systematic literature search was performed by following procedures for transparent reporting of systematic reviews and meta-analyses. To maximize efficacy and avoid delays in effect, use of the appropriate dose of paracetamol is paramount. Older clinical studies using paracetamol at subtherapeutic doses of ≤10 mg/kg generally show that it is less effective than non-steroidal anti-inflammatory drugs (NSAIDs). However, recent evidence shows that when used at dose of 15 mg/kg for fever and pain management, paracetamol is significantly more effective than placebo, and at least as effective as NSAIDs. Paracetamol 15 mg/kg has a tolerability profile similar to that of placebo and NSAIDs such as ibuprofen and ketoprofen used for short-term treatment of fever. However, when used at repetitive doses for consecutive days, paracetamol shows lower risk of adverse events compared to NSAIDs. Also, unlike NSAIDs, paracetamol is indicated for use in children of all ages. Overall, clinical evidence qualifies paracetamol 15 mg/kg a safe and effective option for treatment of pain and fever in children.

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Therapeutic misadventure with paracetamol in children

Cited by 10 publications

References 10 publications

Sub-acute Toxicity Studies of Acetaminophen in Sprague Dawley Rats

Sub-acute Toxicity Studies of Acetaminophen in Sprague Dawley Rats

La fiebre en el niño: una mirada reflexiva a las prácticas de cuidado

Recent Advances in Pediatric Use of Oral Paracetamol in Fever and Pain Management

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