PubMed · 16424402
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Paul M O'Byrne, Ellinor Adelroth. 2006. Beta2 déjà vu.. https://doi.org/10.1378/chest.129.1.3
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PURPOSE: Anaesthetic drugs were selected from the Medicines and Healthcare products Regulatory Agency Drug Analysis Prints in order to determine the number and types of reported reactions and associated mortality. METHODS: The chosen drug groups were the intravenous induction agents, the neuromuscular blocking drugs and neostigmine, the inhalational anaesthetic agents and nitrous oxide, local anaesthetic agents and a selection of analgesics agents, naloxone and midazolam and its antagonist flumazenil. From each drug file, the number and type of reactions were analysed. Mortality was calculated as a percentage of the number of deaths against patient reports. RESULTS: A total of 11,199 reactions were analysed from 6603 patients of whom 620 (9%) died. Few drug records reported reactions from multiple constituent formulations. The majority of reactions were not allergic. The highest mortality was in the inhalational anaesthetic group. Although the greatest number of fatal events was associated with halothane, this drug is no longer used. Nevertheless the percentage remains high because cardiovascular mortality is still being reported. Local anaesthetic use was associated with the smallest percentage mortality (3%). The highest reported number of reactions was associated with the intravenous induction agents and idiosyncratic neurological and peripheral vascular reactions were linked with the use of etomidate. CONCLUSIONS: The reporting of allergic reactions was low. The data demonstrate that induction of anaesthesia presents the highest risk of adverse drug reaction; there is also mortality from newer drugs for example, desflurane, remifentanil as well as from drugs for which there is no alternative, for example, suxamethonium.
PURPOSE: This study was performed to investigate the safety of alkylglycosides administered via the respiratory route and to compare the pulmonary absorption profiles of insulin administered as dry powder inhaler and inhaler solution. METHODS: The safety of a series of alkylglycosides with varying alkyl chain lengths was studied by measuring the enzymatic activities in the bronchoalveolar lavage (BAL) fluid of rat lungs. Pulmonary formulations of insulin plus octylmaltoside were administered either as solution or lyophilized dry powder to anesthetized rats, and absorption of insulin was assessed by measuring plasma insulin and glucose levels. The physical characterization of the dry powder formulation was performed using scanning electron microscope (SEM) and Fourier transform infrared spectrophotometer (FTIR). RESULTS: The BAL analysis showed that there was a gradual increase in the amount of lung injury markers released with the increase in the hydrophobic chain length of alkylglycosides. The pulmonary administration of lyophilized dry powder of insulin plus octylmaltoside or its solution counterpart showed that the bioavailability of powder formulation was about 2-fold higher than that of the formulation administered as solution. The SEM studies showed a subtle difference in the surface morphologies of formulation particles after lyophilization. FTIR data showed minor interactions between the peptide and excipients upon lyophilization. CONCLUSIONS: Of the alkylglycosides tested, octylmaltoside was least toxic in releasing lung injury markers. Octylmaltoside-based dry powder insulin formulations were more efficacious in enhancing pulmonary insulin absorption and reducing plasma glucose levels compared with the formulations administered as a solution.
Our laboratory has characterized spatial patterns of evoked neural activity across the entire glomerular layer of the rat olfactory bulb using primarily aliphatic odorants that differ systematically in functional groups and hydrocarbon structures. To represent more fully the true range of odorant chemistry, we investigated aromatic compounds, which have a more rigid molecular structure than most aliphatic compounds and are particularly salient olfactory stimuli for humans. We first investigated glomerular patterns of 2-deoxyglucose uptake in response to aromatic compounds that differ in the nature and position of their functional groups (e.g., xylenes, trimethylbenzenes, tolualdehydes, benzaldehydes, methyl toluates, and anisaldehydes). We also studied the effects of systematic increases in the number and length of alkyl substituents. We found that most aromatic compounds activated glomeruli in the dorsal part of the bulb. Within this general area, aromatic odorants with oxygen-containing substituents favored activation of more rostral regions, and aromatic hydrocarbons activated more posterior regions. The nature of substituents greatly affected the pattern of glomerular activation, whereas isomers differing in substitution position evoked very similar overall patterns. These relationships between the structure of aromatic compounds and their spatial representation in the bulb are contrasted with our previous findings with aliphatic odorants.