China
Africa
Explore chapters and articles related to this topic
Critical care, neurology and analgesia
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
The doses in Table 1 have been calculated to maintain a target trough serum paracetamol concentration of 10 mg/L [9]. Doses in adults are limited by concerns about hepatotoxicity. For patients more than 20% overweight, ideal bodyweight should be used. Children prefer elixir to capsules or tablets. It is important to note that elixir formulation is available in different formulation strengths when prescribing the dose by volume. Proprietary cough and cold medications containing paracetamol are also available. Concurrent use of such medications can result in inadvertent paracetamol toxicity. The relative bioavailability of rectal formulations is reduced out of the neonatal period and dose can be modestly increased (20–30%). Dose is reduced in premature neonates (e.g. 24 mg/kg/day and 45 mg/kg/day at 30 weeks and 34 weeks post conception age, respectively) [17].
Acute liver failure
Published in Louisa Baxter, Neel Sharma, Ian Mann, The Junior Doctor’s Guide to Gastroenterology, 2018
Louisa Baxter, Neel Sharma, Ian Mann, Ian Sanderson
Drugs (e.g. paracetamol). This is the commonest cause of liver failure in the UK. Ingestion of > 10 g paracetamol/24 hours, and of smaller doses in patients with alcoholic liver disease, may be hepatotoxic. Hepatotoxic drug effects may be dose related (those that will occur in most patients given a sufficiently high dose) or idiosyncratic drug reactions (unusual or unpredictable reactions), which usually occur within 6 months of starting the medication. As paracetamol is such a common aetiological factor, you should be familiar with the features of severe paracetamol toxicity, which are as follows:
General toxicology
Published in Timbrell John, Study Toxicology Through Questions, 2017
Q9. The plasma half-life of paracetamol in patients with liver damage due to overdosage is over twice that in normal human subjects after a therapeutic dose. Interpret this information in the light of what is known about paracetamol toxicity. Describe how data obtained in animal studies led to the formulation of an antidote.
Protective effects of resveratrol and avocado oil against paracetamol-induced hepatotoxicity in rats
Published in Drug and Chemical Toxicology, 2022
Erdi Onur Gokkaya, Sukriye Yesilot, Meltem Ozgocmen, Rahime Aslankoc, Cigdem Aydin Acar
Paracetamol, which is also known as acetaminophen, is a powerful analgesic and antipyretic drug. It is among those drugs that are affordable, easily accessible, and available without a prescription. Paracetamol is considered to be very safe when used in therapeutic doses, in addition to being associated with few side effects, which has led to its widespread use worldwide. However, the risk of paracetamol toxicity is acknowledged to be high due to the drug’s widespread use, high safety profile, and easy availability without a prescription. Moreover, paracetamol overdose has been reported to result in severe hepatotoxicity in experimental animals and humans (Lewis and Paloucek 1991, McGill et al.2012, Jaeschke et al.2013, Ingawale et al.2014, Brune et al.2015).
Evidence of drug-induced hepatotoxicity in the Maghrebian population
Published in Drug and Chemical Toxicology, 2022
Mohammed Bourhia, Riaz Ullah, Ali S. Alqahtani, Samir Ibenmoussa
Paracetamol was reported to have side effects on the liver with 3.09% in total cases of drug-induced liver damage. The secondary effect of paracetamol on the liver is induced in a dose-dependent manner upon massive ingestion (doses higher than 125 mg/kg in adults and 100 mg/kg in children). Paracetamol is predicted to induce major clinical symptoms in the liver such as cytolytic icterus and hepatocellular insufficiency upon 2–3 days of administration in patients massively use alcohol or adversely affected by malnutrition and even those concomitantly intake of cytochromatic inducer (Claridge et al.2010). Paracetamol toxicity is considered as one of the most important causes of poisoning worldwide. It is known to induce toxicity when taken in highly repeated doses. Paracetamol is responsible for approximately half of the confirmed cases with liver failure in the United States and remains the principal cause of liver transplantation (Tittarelli et al.2017). However, other data reported no adverse effects of paracetamol on the health of volunteers concomitantly consuming 1–3 units of alcohol and 4 g of paracetamol per day (no change in ALT and AST; Heard et al.2007).
Effect of carvedilol versus propranolol on acute and chronic liver toxicity in rats
Published in Drug and Chemical Toxicology, 2021
Randle et al. (2008) demonstrated that paracetamol-induced toxicity was accompanied by perturbation of the hepatic microcirculation. Histopathological analysis revealed that toxic livers were congested, with a profound accumulation of erythrocytes within the sinusoids. They reported that microcirculatory stasis and RBC accumulation within the sinusoids may be due to catecholamine-induced constriction of the hepatic central veins. The hepatoprotective effect of carvedilol in the present study could be attributed to prevention of such a microcirculatory dysfunction, through its alpha-blocking effects, observed through the lack of liver congestion, analyzed by histology. Randle et al. (2008) reported that the maintenance of hepatic microcirculation in the presence of a continuing toxic insult may be critical to halting the progression of paracetamol toxicity. The delivery of oxygen, amino acids, cofactors and substrates to the liver would aid GSH replenishment, the maintenance of mitochondrial function and energy production to facilitate repair and regeneration, consistent with findings of the present study. This would suggest that prevention of hepatic microvascular constriction is critical for preventing toxicity.