ABSTRACT
The epidemic increase in the incidence of type 2 diabetes mellitus (T2DM) in children and adolescents is presenting enormous challenges to the medical profession. The combination of factors such as obesity, ethnicity, puberty, and genetic predisposition has contributed to the development of T2DM in younger ages. These factors affect the regulatory mechanism of insulin secretion, insulin action, and hepatic gluconeogenesis. In contrast to adults, children appear to have a shorter latency to disease, a more rapid development of symptoms, and an increased ketoacidosis. There are limited therapeutic options to prevent or manage T2DM in children. Although the role of diet and exercise (lifestyle intervention) has not been adequately evaluated in children, they will remain important adjuncts in the prevention and treatment of T2DM. Insulin and metformin are currently the only approved medications for the treatment of T2DM in children. Clinical trials involving other oral agents used in adults are currently being conducted to evaluate their safety and efficacy in children.
ABSTRACT
OBJECTIVES: Intravenous Y-site administration of more than one medication through the same in-line catheter is a common practice used in the management of acute seizures. The objective of this study was to determine the compatibility of valproate sodium (Depacon(®); 2 or 20 mg/mL) with 13 medications that are frequently administered to manage seizures or are given to patients with an acute head injury who are at risk for developing post-traumatic epilepsy. METHODS: The study medications included atracurium, dexamethasone, diazepam, fosphenytoin, lorazepam, magnesium sulfate, mannitol, methyl-prednisolone, midazolam, pentobarbital, phenytoin, ranitidine, and thiopental. Equal volumes of valproate and each of the study drugs were admixed and immediately examined using several physiochemical criteria: Tyndall effect, color and pH change, gas evolution, and particle formation (HIAC/Royco liquid particle counter). Samples were also evaluated using HPLC analysis (C(18) column; methanol/tetrahydrofuran/ phosphate buffer; 44/1/55% v/v, at 1.5 mL/min; 50°C) with UV (190-400 nm) photodiode detection. The valproate peak (220 nm) was quantified by both peak area and height. Samples were analyzed within 5 minutes of admixture and were reassessed at 15 and 30 minutes. RESULTS: With the exception of diazepam, midazolam, and phenytoin, all of the remaining drugs were chemically compatible with valproate, both in 5% Dextrose Injection, USP(D5W) and in 0.9% Sodium Chloride Injection, USP (Normal Saline -NS). None of the compatible medications produced a significant pH change, discernible gas, particle formation, reduced valproate titer by HPLC analysis (coefficient of variability < 1.5%), or the temporal formation of unidentified UV absorbing (190-400 nm) peaks. CONCLUSIONS: Intravenous valproate is compatible with most agents employed in seizure management or used in patients at risk for seizures following head injury and is safe for concurrent Y-site drug administration.
ABSTRACT
ß2-adrenergic receptors (ß2AR) are GTP-binding protein (G-protein) coupled receptors widely distributed in human tissue. Inhaled ß2-agonist drugs exert their primary effect on the ß2AR of bronchial smooth muscles, causing relaxation and bronchial dilatation. Polymorphisms in the ß2AR gene have been identified, which may affect responsiveness to ß2-agonists and disease severity in asthmatics. Nine single nucleotide polymorphisms (SNPs) within the coding region and eight SNPs within in the 5' upstream region of the ß2AR gene have been identified. The two most studied polymorphisms are mutations in the coding region at codon 16, Arg to Gly (Arg16Gly) and at codon 27, Gln to Glu (Gln27Glu). Evidence suggests that carriers of Gly16, as well as carriers of Gln27, are prone to down-regulation of ß2AR. Patients who are homozygous for Arg16 and/or Glu 27 may be more susceptible to tachyplaxis with chronic use of ß2-agonists. Although ß2AR polymorphism is not related to the severity of asthma, patients with nocturnal asthma have higher frequency of Gly16. A polymorphism in the 5' upstream region, 5' leader cistron (5'LC), encodes for a protein that regulates mRNA transcription. The Cys19 polymorphism in the 5'LC is associated with higher expression of ß2AR. More recent studies have focused on combinations of polymorphisms across the gene region (haplotypes). The interaction of multiple SNPs within a haplotype may control ß2AR function resulting in different phenotypic response in patients with asthma. ß2AR polymorphism may have a significant implication in the pathophysiology of asthma and therapeutic response.
