Drug toxicity and surveillance in children.

The use of medicines in children is an area of increasing after this syndrome was noted, pharmacokinetic studies showed that newborn infants had impaired metabolism interest [1]. Many medicines are being used outside the terms of their product licence [2] thereby increasing of chloramphenicol and that a reduction of the dosage from 100 mg kg−1 daily to 50 mg kg−1 daily prevented the risk of drug toxicity. Clinicians need to ensure not only that toxicity is kept to a minimum but also that the development of this syndrome [12]. children are not denied the use of appropriate medicines. This can only be achieved by the scientific study of drug toxicity in children and is ideally carried out by prospective studies of drug surveillance. This involves Toxicity in young children specifically monitoring for drug toxicity, either in relation to particular drugs [3,4] or selected patient Although these initial studies described clinical problems groups [5,6]. Drug use in children may be accompanied in newborn infants, and the preterm infant in particular, by problems not seen in adults, or cause adverse drug problems with other drugs have highlighted the reactions that are more frequent than in adults. An enhanced toxicity of some medicines in children. example of this is metoclopramide which causes dystonia Hepatotoxicity in association with the anticonvulsant in teenagers and Parkinsonism in the elderly [7]. sodium valproate was initially reported in 1979 [13]. Subsequently more than 100 patients died, the majority of whom were children. A retrospective review [14] of 37 patients who died in the USA, showed that those patients at greatest risk fell into one of three categories: Antibiotic toxicity in neonates (i) age under 3 years; (ii) receiving other anticonvulsants as well as valproate; (iii ) developmental delay. Infections have always been a major problem in neonates with significant mortality and morbidity. The introducSubsequent changes in prescribing habits resulted in a dramatic reduction in the number of deaths due to tion of antibiotic therapy resulted in major clinical advances [8]. However, antibiotic therapy also prosodium valproate [15]. The mechanism of valproate hepatotoxicity is not fully understood but is thought to duced particular clinical problems. Silverman et al. reported considerably higher mortality in neonates relate to abnormal metabolism [16]. Other anticonvulsants result in enzyme induction and, therefore, enhance receiving a combination of penicillin and sulphisoxazole than those receiving oxytetracycline [9]. There was a certain metabolic pathways resulting in the formation of toxic intermediate metabolites. These pathways may significantly higher incidence of kernicterus, both clinically (opisthotonos, spasticity, seizures, oculogyric movebe more prominent in children under the age of 3 years and it is important to realise that drug metabolism in ments) and pathologically (yellow staining of the brain) in the children who died following penicillin and the children differs from that of adults. The other drug causing hepatotoxicity specifically in sulphonamide. Subsequently, others have shown that sulphonamides are highly protein bound and displace children was aspirin. The use of salicylates in children with a mild viral infection resulted in a greater risk of bilirubin from albumin [10]. As the preterm infant is usually jaundiced, the sulphonamide displaced bilirubin developing Reye’s syndrome—a life threatening illness associated with drowsiness, coma, hypoglycaemia, seizfrom albumin and this is thought to increase the incidence of kernicterus. ures and liver failure. Epidemiological work confirmed the association between salicylate ingestion and the Newborn infants receiving chloramphenicol developed abdominal distension, vomiting, cyanosis, cardiovascular development of Reye’s syndrome [17], although the possible association had been postulated 15 years collapse, irregular respiration and subsequent death [11]. This was termed the grey baby syndrome. Shortly previously [18]. Starko et al. [17] studied children