Articles: acetaminophen.
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Drug metabolism reviews · Feb 2012
ReviewOxidant stress, mitochondria, and cell death mechanisms in drug-induced liver injury: lessons learned from acetaminophen hepatotoxicity.
Hepatotoxicity is a serious problem during drug development and for the use of many established drugs. For example, acetaminophen overdose is currently the most frequent cause of acute liver failure in the United States and Great Britain. Evaluation of the mechanisms of drug-induced liver injury indicates that mitochondria are critical targets for drug toxicity, either directly or indirectly through the formation of reactive metabolites. ⋯ Drug toxicity can also induce an inflammatory response with the formation of reactive oxygen species by Kupffer cells and neutrophils. If not properly detoxified, these extracellularly generated oxidants can diffuse into hepatocytes and trigger mitochondrial dysfunction and oxidant stress, which then induces MPT and necrotic cell death. This review addresses the formation of oxidants and the defense mechanisms available for cells and applies this knowledge to better understand mechanisms of drug hepatotoxicity, especially acetaminophen-induced liver injury.
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Randomized Controlled Trial Multicenter Study
Efficacy of oxycodone/paracetamol for patients with bone-cancer pain: a multicenter, randomized, double-blinded, placebo-controlled trial.
Bone-cancer pain is a common and refractory cancer pain. Opioids, on their own, do not control this type of pain well enough, and co-analgesics are necessary. ⋯ Patients with bone-cancer pain, already on opioids, obtain clinically important, additional pain-control, with regular oxycodone/paracetamol dosing.
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Unintended hepatic injury associated with the use of paracetamol (acetaminophen)-containing products has been growing. ⋯ Hepatic injury associated with paracetamol use is increasing significantly faster than population, paracetamol product sales and poison centre use. This suggests a growing portion of consumers is self-dosing paracetamol beyond the toxic threshold. This is true for paracetamol with and without opioids, but the increase in hepatic injury is greater when paracetamol is taken with an opioid. This disproportionate rise is greatest with misuse and abuse of paracetamol products in combination with opioids. Increasing self-dosage of the opioid combination products for the opioid effect is likely to result in more cases of toxic exposure to paracetamol. In contrast, cases of exposure to paracetamol-containing cough and cold products are underrepresented among those injured. In the absence of opioid-containing products, consumption of more than one paracetamol-containing product did not contribute to injury. Efforts to modulate unintentional paracetamol-related hepatic injury should consider these associations.
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Br J Clin Pharmacol · Feb 2012
Staggered overdose pattern and delay to hospital presentation are associated with adverse outcomes following paracetamol-induced hepatotoxicity.
Paracetamol (acetaminophen) poisoning remains the major cause of severe acute hepatotoxicity in the UK. In this large single centre cohort study we examined the clinical impact of staggered overdoses and delayed presentation following paracetamol overdose. ⋯ Both delayed presentation and staggered overdose pattern are associated with adverse outcomes following paracetamol overdose. These patients are at increased risk of developing multi-organ failure and should be considered for early transfer to specialist liver centres.
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An intravenous formulation of acetaminophen was introduced to the United States in 2011. Experience from Europe indicates that serious dosing errors are likely to occur. Most events have involved a 10-fold dosing error in small children caused by calculating the dosage in milligrams, but then administering the solution in milliliters. ⋯ A serum acetaminophen concentration should be drawn 4 hours after the infusion was started or as soon thereafter as possible. If the serum acetaminophen concentration plots above the treatment line on the Rumack-Matthew nomogram, treatment with acetylcysteine should be initiated. Health care providers are encouraged to contact their regional poison center (1-800-222-1222) so that dosing errors will be reported, and the experience with this new product can be accumulated.