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• W2033929142 abstract "The use of medicines in children is an area of increasing after this syndrome was noted, pharmacokinetic studiesinterest [1]. Many medicines are being used outside the showed that newborn infants had impaired metabolismterms of their product licence [2] thereby increasing of chloramphenicol and that a reduction of the dosagethe risk of drug toxicity. Clinicians need to ensure not from 100 mgkg−1daily to 50 mg kg−1daily preventedonly that toxicity is kept to a minimum but also that the development of this syndrome [12].children arenot denied theuse ofappropriate medicines.This can only be achieved by the scientific study of drugtoxicity in children and is ideally carried out byprospective studies of drug surveillance. This involvesspecifically monitoring for drug toxicity, either in Toxicity in youngchildrenrelation to particular drugs [3,4] or selected patientgroups [5,6].Drug use in children may be accompanied Althoughtheseinitialstudies described clinicalproblemsby problems not seen in adults, or cause adverse drug in newborn infants, and the preterm infant in particular,reactions that are more frequent than in adults. An problems with other drugs have highlighted theexampleofthisismetoclopramide whichcausesdystonia enhanced toxicity of some medicines in children.in teenagers and Parkinsonism in the elderly [7]. Hepatotoxicity in association with the anticonvulsantsodium valproate was initially reported in 1979 [13].Subsequently more than 100 patients died, the majorityof whom were children. A retrospective review [14] of37 patients who died in the USA, showed that thoseAntibiotictoxicity inneonates patients at greatest risk fell into one of three categories:(i) age under 3 years; (ii) receiving other anticonvuls-Infectionshavealwaysbeena majorprobleminneonates ants as well as valproate; (iii) developmental delay.with significant mortality and morbidity. The introduc- Subsequent changes in prescribing habits resulted in ation of antibiotic therapy resulted in major clinical dramatic reduction in the number of deaths due toadvances [8]. However, antibiotic therapy also pro- sodium valproate [15]. The mechanism of valproateduced particular clinical problems. Silverman et al. hepatotoxicity is not fully understood but is thought toreported considerably higher mortality in neonates relate to abnormal metabolism [16]. Other anticonvul-receiving a combination of penicillin and sulphisoxazole sants result in enzyme induction and, therefore, enhancethan those receiving oxytetracycline [9]. There was a certain metabolic pathways resulting in the formationsignificantly higher incidence of kernicterus, both clini- of toxic intermediate metabolites. These pathways maycally(opisthotonos,spasticity,seizures, oculogyricmove- be more prominent in children under the age of 3 yearsments) and pathologically (yellow staining of the brain) and it is important to realise that drug metabolism inin the children who died following penicillin and the children differs from that of adults.sulphonamide. Subsequently, others have shown that The other drug causing hepatotoxicity specifically insulphonamides are highly protein bound and displace children was aspirin. The use of salicylates in childrenbilirubin from albumin [10]. As the preterm infant is with a mild viral infection resulted in a greater risk ofusually jaundiced, the sulphonamide displaced bilirubin developing Reye’s syndrome—a life threatening illnessfrom albumin and this is thought to increase the associated with drowsiness, coma, hypoglycaemia, seiz-incidence of kernicterus. ures and liver failure. Epidemiological work confirmedNewborninfants receivingchloramphenicoldeveloped the association between salicylate ingestion and theabdominaldistension,vomiting, cyanosis,cardiovascular development of Reye’s syndrome [17], although thecollapse, irregular respiration and subsequent death possible association had been postulated 15 years[11]. This was termed the grey baby syndrome. Shortly previously [18]. Starko et al. [17] studied children" @default.
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• W2033929142 date "1996-10-01" @default.
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• W2033929142 title "Drug toxicity and surveillance in children" @default.
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