FARMACOLOGIA DEL DOLOR. JO NO ACIDOS: es el acetaminofen o paracetamol tiene potente actividad analgesica y antipiretica. farmacología. SOCORRISTAS DE COMBATE Betametasona -4mg- sln inyectable. Dexametasona -4mg y 8 mg- sln inyectable. Hidrocortisona. El acetaminofén es un ingrediente activo común para tratar el dolor y Estas reacciones pueden ocurrir con el primer uso de acetaminofén o.
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Severe hepatotoxicity caused by paracetamol is rare in neonates. We report a case of paracetamol-induced acute liver failure in a term neonate.
Apart from supportive measures, the patient was successfully treated with intravenous N-acetylcysteine infusion during 11 consecutive days, and was discharged on day The follow-up revealed full recovery of clinical and acetainofen laboratory findings of hepatic function.
The paracetamol pharmacokinetics and pharmacodynamics in neonates and infants differ substantially from those in older children and adults. Despite the reduced rates of metabolism by the P CYP2E1 enzyme system and the increased ability to synthesize glutathione – which provides greater resistance after overdoses – it is possible to produce hepatotoxic metabolites N-acetyl-p-benzoquinone that cause hepatocellular damage, if glutathione sources are depleted.
Paracetamol clearance is reduced and the half-life of elimination is prolonged. Therefore, a particular dosing regimen should be followed due to the toxicity risk of cumulative doses. This report highlights the risk for severe hepatotoxicity in neonates after paracetamol multiple doses acetamiofen more than two to three days. La hepatotoxicidad grave inducida por el paracetamol es muy rara en neonatos.
Paracetamol N-acetyl-p-aminophenol is a widely used analgesic and antipyretic aceyaminofen children; however, toxic exposures are rare in neonates. Toxic exposures may occur via the placenta, resulting from intentional ingestion of overdoses of paracetamol by mothers in the 24 hours preceding delivery 1 – 3due to isolated oral 4 or intravenous dosing errors propacetamol, pro-drug of paracetamol, not available in Brazil 56in general, on the order of 10 times the therapeutic dose, or due to repeated doses orally 7.
The severe hepatotoxicity induced by paracetamol, with or without acute liver failure, is almost not described in the neonatal period.
Among these, six were submitted to liver transplantation – two survived – and the other five died waiting for transplantation. The youngest patient in this series was 10 months old 9. In an extensive review conducted by Arana et alregarding the period from tono cases of acetaminophen poisoning by direct administration in neonates were reported InWalls et al described the first case of liver failure in a term neonate with 4 days of life after the use of paracetamol orally for 3 consecutive days weight 3.
The patient showed complete recovery after continuous intravenous infusion of N-acetylcysteine for 36 hours, evolving without sequelae 7. The present study described a new case of liver failure in term neonate after repeated doses of paracetamol, treated successfully with N-acetylcysteine. Male patient, 26 days old, weighing 3,g, son of non-consanguineous parents, sent by the local emergency unit where he remained hospitalized for 24 hours with a history of irritability, refusal to eat for 4 days, frequent vomiting for 1 day, abdominal distension and slight respiratory distress.
The delivery iterative cesarean section was uneventful, and the neonate presented birth weight of 3,g, 48cm, Apgar score 8 and 10 1st and 5th minutesand Capurro score of 39 weeks and 3 days. The mother, 38 years old, had 10 previous pregnancies two cesareanswas confined in a penitentiary since the 5th month of pregnancy and had a history of losing custody of nine children due to negligence associated with addiction crack.
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Before admission, the child was exclusively breastfed, on maternal care in a rooming in prison. She also reported the concomitant use of paracetamol for 5 days for relief of toothache doses and frequency of use were not obtained. During hospitalization, there was a progressive fall in hemoglobin levels: Considering the possibility of consumption by the mother and passage through breast milk, a screening of recreational farmmacologia cocaine, cannabinoids, methamphetamine and amphetamine was performed by an immunochromatographic test in the patient’s urine, with negative results.
Blood cultures collected on admission were also negative. Given the severity of the case and the possibility of progression to liver transplantation, the patient was transferred to the regional referral unit at D3, where he stayed for 19 days.
During evolution, there was a progressive decrease of aminotransferase concentrations and improvement of coagulation; infusion of N-acetylcysteine was suspended on D The patient developed hospital infection by oxacillin-resistant Staphylococcus aureus D20treated with vancomycin.
Acute liver failure in a term neonate after repeated paracetamol administration
In Table 1 are summarized the main laboratory results achieved during the 34 days of hospitalization. In the screening of metabolic diseases that may present with liver failure in the neonatal period, the analysis of the acylcarnitine profile in D2 showed reduced free serum carnitine 5.
Research for galactosemia, tyrosinemia, and organic acidemia was negative. Prenatal serological testing for HIV, toxoplasmosis, syphilis, and hepatitis B and C were also negative. The outpatient follow-up undertaken for one year showed complete clinical and laboratory recovery and adequate neuropsychomotor development.
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In overdoses with clinical repercussion, by isolated overdoses or after supratherapeutic doses, the maximum rates of glucuronidation and sulfation are reached and the availability of glutathione is insufficient to metabolize NAPQI. Then, the free NAPQI binds covalently to hepatic proteins of the cysteine group, triggering hepatotoxicity and cell death 12 Acetaminophen-protein products, such as 3- cysteine-S-yl -paracetamol-adduct are released into the blood after hepatocyte lysis.
They are measured by high performance liquid chromatography with electrochemical detection and may be used as specific biomarkers of hepatotoxicity, even several days after the exposure A study in adults who developed liver failure induced by paracetamol overdoses showed a positive correlation between the serum concentration of acetaminophen-protein adducts and severity of hepatotoxicity, which can be detected up to 12 days after ingestion In contrast, the pharmacokinetics and pharmacodynamics of paracetamol in neonates and young infants under 1 year differ substantially from older children and adults.
The combination with glucuronides is immature, while sulfation is well developed, consisting in the main metabolic pathway 1210 The clearance of paracetamol in term neonates is decreased and acetaminofeh half-life is prolonged compared to that of adults approximately 3.
In addition, the elimination half-life of paracetamol may be extended further after multiple doses, in poisoned patients and in those who develop liver failure 21012 Although the rates of metabolism of CYP2E1 were decreased and the ability acetaminfen generate glutathione, increased, providing greater protection after isolated overdoses, neonates may also produce toxic farmadologia NAPQI 11014triggering up hepatotoxicity and cell lysis if glutathione reserves are depleted 1012 It should be noted that paracetamol-protein products could also be used as specific biomarkers of hepatotoxicity in children, especially to assist the diagnosis of acute liver failure of unknown etiology Even considering the background of the mother, which could raise doubts about the actual dose, the continuous use of medication for 3 days, the possible additional doses transferred through breast aceta,inofen, and the high serum paracetamol levels detected established a causal relationship between prolonged use drug and liver failure.
N-acetylcysteine is the antidote of choice in the treatment of acetaminophen poisoning, being a precursor of reduced glutathione, which, when given early, can prevent liver damage induced by paracetamol, restoring glutathione levels 1112 When the moment of exposure is known, the administration of N-acetylcysteine is formally indicated after ingestion of isolated overdoses of paracetamol, when the serum levels, preferably obtained between 4 and 8 hours of ingestion are above the possible risk line on the Rumack-Matthew nomogram, even without clinical or laboratory evidence of liver injury 11 Other more complex fafmacologia involve the indication of N-acetylcysteine after prolonged or supratherapeutic use of paracetamol, when assessing the risk of hepatotoxicity by the Rumack-Matthew nomogram is not possible 111217 – In patients with liver failure, as described, N-acetylcysteine also possibly acts as an antioxidant, improving hemodynamics, oxygen consumption, and cerebral edema Patients with paracetamol-induced liver failure, either by isolated overdoses or by supratherapeutic doses, should be given intravenous N-acetylcysteine until the encephalopathy resolves itself or until they present significant improvements in the results of ALT, INR, and creatinine or until liver transplantation 11 In the present case, continuous intravenous infusion of N-acetylcysteine proved to be effective, safe, and without adverse effects, even in prolonged use.
Although studies in experimental models suggest that carnitine deficiency, as a cause or consequence, may be associated with hepatotoxicity triggered acetaminofej acetaminophen 20it would be speculative to infer this association only with the data available in the present report a single measurement during the course of liver failure. Clinical studies are needed to define and characterize the association more accurately.
However, it can be inferred that acetamlnofen laboratory screening, the evolution, and the outpatient follow-up practically exclude the possibility of genetic diseases associated with changes in the carnitine transport and the carnitine cycle, which can evolve with liver failure It is possible to conclude that the continued use of acetaminophen can cause severe hepatotoxicity in neonates.
The specific dosage for term and preterm neonates should be followed, avoiding the continuous use for more than 2 to 3 days 10 National Center for Biotechnology InformationU. Journal List Rev Paul Pediatr v. Author information Article notes Copyright and License information Disclaimer. Received Apr 1; Accepted May This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
This article has been cited by other articles in PMC. Introduction Paracetamol N-acetyl-p-aminophenol is wcetaminofen widely used analgesic and antipyretic in children; however, toxic exposures are rare in neonates. Case description Male patient, 26 days old, weighing 3,g, son of non-consanguineous parents, sent by the local emergency unit where he remained hospitalized for 24 hours with a history of irritability, refusal to eat for 4 days, frequent vomiting for 1 day, abdominal distension and slight respiratory distress.
Table 1 Main laboratory findings during hospitalization. Open in a separate window. Paracetamol metabolites in the neonate following maternal overdose. Br J Clin Pharmacol. Paracetamol overdose in a preterm acetamminofen. Intravenous propacetamol overdose in a term newborn. Nevin DG, Shung J. Intravenous paracetamol overdose in a preterm infant during anesthesia. Acetaminophen-induced hepatic failure with encephalopathy in a newborn. Etiology, outcome and prognostic indicators of childhood fulminant hepatic failure in the United Kingdom.
J Pediatr Gastroenterol Nutr. Treatment with paracetamol in infants. Pharmacokinetics of acetaminophen-protein adducts in adults with acetaminophen overdose and acute liver failure. Acetaminophen developmental pharmacokinetics in premature neonates and infants: Detection of acetaminophen protein adducts in children with acute liver failure of indeterminate cause. Penna A, Buchanan N. Paracetamol poisoning in children and hepatotoxicity. Acetylcysteine for tarmacologia poisoning.
N Engl J Med. Clin Toxicol Phila ; Prospective evaluation of repeated supratherapeutic acetaminophen paracetamol ingestion. Disorders of carnitine transport and the carnitine cycle.
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