Buprenorphine May Not Be as Safe as You Think: A Pediatric Fatality From Unintentional Exposure
ABSTRACT Buprenorphine is a partial μ-opioid receptor agonist that is approved for the treatment of opioid dependency. It is generally believed to be safer than methadone because of its ceiling effect on respiratory depression. As more adults in US households use buprenorphine, an increasing number of children are being exposed. We report a fatal exposure to buprenorphine in a small child that occurred after ingestion of a caretaker's buprenorphine/naloxone. Postmortem toxicology analysis showed free serum concentrations of 52 ng/mL and 39 ng/mL for buprenorphine and norbuprenorphine, respectively. No other drugs were detected. Autopsy did not find signs of injury or trauma. The theoretical safety provided by the ceiling effect in respiratory depression from buprenorphine may not apply to children, and buprenorphine may cause dose-dependent respiratory depression.
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ABSTRACT: Abstract Noroviruses are the leading cause of epidemic gastroenteritis, including foodborne outbreaks, in the United States. Hospitalization and mortality associated with norovirus infection occur most frequently among elderly persons, young children, and immunocompromised patients. Noroviruses belong to the family Caliciviridae and can be grouped into five genogroups (GI through GV), which are further divided into at least 34 genotypes. Human disease primarily is caused by GI and GII noroviruses, with most outbreaks caused by GII.4 strains. During the past decade, new GII.4 strains have emerged every 2-3 years, replacing previously predominant GII.4 strains. Emergence of these new norovirus strains has often, but not always, led to increased outbreak activity. For example, the previously dominant GII.4 New Orleans strain was not associated with increased norovirus outbreak activity in the United States. CDC collects information on norovirus strains associated with outbreaks in the United States through an electronic laboratory surveillance network called CaliciNet. This report documents the recent emergence of a new GII.4 strain, GII.4 Sydney, which caused most (53%) of the norovirus outbreaks reported through CaliciNet during September-December 2012. Continued surveillance will enable further assessment of the public health implications and significance of this new strain.MMWR. Morbidity and mortality weekly report 01/2013; 62.
- BJA British Journal of Anaesthesia 05/2013; 110(5):842. DOI:10.1093/bja/aet082 · 4.35 Impact Factor
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ABSTRACT: In order to describe drug action at a G protein-coupled receptor (GPCR), a full understanding of the pharmacological terms affinity, efficacy and potency is necessary. This is true whether comparing the ability of different agonists to produce a measurable response in a cell or tissue, or whether determining the relative ability of an agonist to activate a single receptor subtype and produce multiple responses. There is a great deal of interest in the μ opioid receptor (MOPr) and the ligands that act at this GPCR, not only because of the clinically important analgesic effects produced by MOPr agonists, but also because of their liability to induce adverse effects such as respiratory depression and dependence. Our understanding of the mechanisms underlying these effects, as well as the ability to develop new, more effective MOPr drugs depends upon the accurate determination of the efficacy with which these ligands induce coupling of MOPr to downstream signalling events. In this review, which is written with the minimum of mathematical content, the basic meaning of terms including efficacy, intrinsic activity and intrinsic efficacy is discussed, along with their relevance to the field of MOPr pharmacology, and in particular in relation to biased agonism at this important GPCR.British Journal of Pharmacology 05/2013; 169(7). DOI:10.1111/bph.12222 · 4.99 Impact Factor