Paediatric drugs
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Review Comparative Study
Risks and benefits of nonsteroidal anti-inflammatory drugs in children: a comparison with paracetamol.
Nonsteroidal anti-inflammatory drugs (NSAIDs) possess antipyretic, analgesic and anti-inflammatory effects. They are frequently used in children and have numerous therapeutic indications, the most common ones being fever, postoperative pain and inflammatory disorders, such as juvenile idiopathic arthritis (JIA) and Kawasaki disease. Their major mechanism of action is through inhibition of prostaglandin biosynthesis by blockade of cyclo-oxygenase (COX). ⋯ Pharmacokinetic studies are needed to characterise the disposition of NSAIDs in very young infants in order to use them rationally. To date, no studies have been published on the disposition, tolerability and efficacy of specific COX-2 inhibitors in children. Further clinical experience with these agents in adults is warranted before undergoing trials with specific COX-2 inhibitors in children.
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Topiramate is an antiepileptic drug (AED) which appears to have a broad range of antiseizure activity in humans. A previous overview focused primarily on results of trials of topiramate in adults with epilepsy, and this review highlights the use of topiramate in children. Clinical trials have shown that topiramate is effective when used adjunctively in children with refractory partial-onset seizures and generalised tonic-clonic seizures. The drug significantly reduced seizure frequency compared with placebo in children with partial-onset epilepsy after 16 weeks of double-blind adjunctive treatment (33.1 vs 10.5%); the frequency of secondarily generalised seizures was also markedly reduced. During a nonblind extension of this trial, the mean dosage was titrated from 4.8 to 9 mg/kg/day and further reductions in the frequency of seizures were observed (71% compared with prestudy levels). In 2 mixed adult/paediatric populations with primary generalised tonic-clonic seizures, topiramate (target dosage 5.2 to 9.3 mg/kg/day) reduced the seizure rate compared with those receiving placebo. This difference was significant in one trial (56.7 vs 9%) but not in another (57.1 vs 33.2%). A subanalysis of the paediatric patients found that the favourable effect of topiramate on seizure rates was not age-related. Topiramate (median average dosage 5.1 mg/kg/day) was also found to be useful as adjunctive therapy in the management of Lennox-Gastaut syndrome and significantly reduced the mean frequency of drop attacks by 14.8% compared with an increase of 5.1% with placebo. Further gains in seizure control were made in a nonblind extension of this trial where the mean topiramate dosage was 10 mg/kg/day. Nine of 11 patients in 1 pilot trial of children with otherwise intractable West syndrome, and 5 of 10 in another, achieved a > or =50% reduction in seizure rate with topiramate (target dosage up to 24 mg/kg/day). In an 18-month extension of the former trial (mean dosage 29 mg/kg/day) a > or =50% reduction in seizures was maintained in 7 of 11 children. Adverse events associated with adjunctive topiramate therapy in children were predominantly neuropsychiatric and generally mild to moderate in severity. Behavioural and cognitive problems do occur and are a limiting factor in some children. Also, weight loss can be problematical in some individuals. Withdrawal rates were low in the controlled trials (4.8%), but appear to be more frequent in noncomparative and post-marketing studies. ⋯ Well controlled studies have demonstrated that topiramate is an effective agent for the adjunctive therapy of partial and generalised tonic-clonic seizures in children. Treatment-limiting adverse events do occur, but these may be managed by slow titration. Although comparative studies with the other newer AEDs used in adjuntive therapy are required, topiramate is an important extension to the range of drugs that may be used to treat refractory epilepsy in children.
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Painful procedures are frequently required during treatment of children in the emergency department and are very stressful for the children, their parents and healthcare providers. Pharmacological methods to safely provide almost painless local anaesthesia, analgesia and anxiolysis have been increasingly studied in children. With knowledge of these methods, and patience, the emergency care provider can greatly reduce the distress often associated with emergency care of children. ⋯ Topical creams such as lidocaine/ prilocaine (EMLA) or tetracaine, iontophoresed lidocaine, or buffered lidocaine subcutaneously injected with fine needles can make intravenous catheter placement virtually 'painless'. When anxiety is significant, and mild to moderate analgesia/ anxiolysis/amnesia is needed, nitrous oxide can be administered if the proper delivery devices are available. Alternatively, when intensely painful fracture reduction, burn debridement, or abscess drainage is necessary, well tolerated and effective deep sedation can be achieved with careful use of midazolam and either ketamine or fentanyl.
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Intrathecal chemotherapy with antineoplastic agents is mainly utilised in children with leukaemia and lymphoma, and in selected brain tumours. In these diseases, intrathecal use is restricted to methotrexate (MTX), cytosine arabinoside (Ara-C) and corticosteroids. A number of other agents are, at the present time, under evaluation. ⋯ However, the development of this new approach is currently under evaluation in larger clinical studies. Neurological adverse effects may be expected with intrathecal chemotherapy and are increased by high dose systemic therapy, concomitant cranial radiotherapy or meningeal infiltration by neoplastic cells. Inadvertant intrathecal administration of antineoplastic agents that are indicated for systemic administration only, is dangerous and may result in a fatal outcome.
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Status epilepticus (SE) is a condition characterised by frequent and prolonged epileptic seizures which frequently develop in the immature brain. Fever, metabolic disorders and subtherapeutic concentrations of antiepileptic drugs are the most common factors precipitating SE in children. Progressive neuronal damage occurs if convulsive SE persists for more than 30 minutes, with neurological, epileptic and cognitive sequelae. ⋯ Phenytoin remains an excellent agent because of its long duration of action, but it is not active in nonconvulsive SE. Fosphenytoin, a phenytoin prodrug, represents a significant advance in the treatment of children with convulsive SE. Intravenous phenytoin and intramuscular phenobarbital (phenobarbitone) are generally used in neonatal SE; other agents are rarely used.