844 resultados para abuse of drugs


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Goldsmiths'-Kress no. 22183.

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"The directions presented here have been formulated during the growth of the course as presented in the University of Missouri."--Pref.

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Mode of access: Internet.

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Contribution from Forest Service.

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Mode of access: Internet.

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At head of title: Prize essay.

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The salient feature of metals is that unlike organic compounds they do not degrade in the environment and barely move from one environmental matrix to another. Human interventions take these compounds from their stable and non-bioavailable geological matrix into situations of biological accessibility. Studies in the 1970s and the 1980s of metal bioavailability and impacts of metals and metalloids were driven by the process of abatement of lead in the environment. Humans have clear and identifiable sources of exposure from fuels, food and leaded water pipes to lead. Interventions started at that time have dramatically lowered human lead exposure. Attention has now shifted to other metals, in particular, cadmium, which has seen increasing use. It is generally accepted that food crops grown on cadmium containing soils or soils naturally rich in this metal are the major source of exposure to humans other than exposure from smoking of cigarettes. This mini-review gives a summary and commentary on early studies on effects of lead on haem metabolism that provide us the clue to why investigations of the impacts of other toxic heavy metals and metalloids such as cadmium and arsenic on different human cytochrome P450 forms have become of great interest at the current time. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

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Objectives The aim of this work was to investigate the effect of cholesterol on the bilayer loading of drugs and their subsequent release and to investigate fatty alcohols as an alternative bilayer stabiliser to cholesterol. Methods The loading and release rates of four low solubility drugs (diazepam, ibuprofen, midazolam and propofol) incorporated within the bilayer of multilamellar liposomes which contained a range of cholesterol (0–33 mol/mol%) or a fatty alcohol (tetradecanol, hexadecanol and octadecanol) were investigated. The molecular packing of these various systems was also investigated in Langmuir monolayer studies. Key findings Loading and release of drugs within the liposome bilayer was shown to be influenced by their cholesterol content: increasing cholesterol content was shown to reduce drug incorporation and inclusion of cholesterol in the bilayer changed the release profile of propofol from zero-order, for phosphatidyl choline only liposomes, to a first-order model when 11 to 33 total molar % of cholesterol was present in the formulation. At higher bilayer concentrations substitution of cholesterol with tetradecanol was shown to have less of a detrimental impact on bilayer drug loading. However, the presence of cholesterol within the liposome bilayer was shown to reduce drug release compared with fatty alcohols. Monolayer studies undertaken showed that effective mean area per molecule for a 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) : cholesterol mixture deviated by 9% from the predicted area compared with 5% with a similar DSPC : tetradecanol mixture. This evidence, combined with cholesterol being a much more bulky structure, indicated that the condensing influence of tetradecanol was less compared with cholesterol, thus supporting the reduced impact of tetradecanol on drug loading and drug retention. Conclusions Liposomes can be effectively formulated using fatty alcohols as an alternative bilayer stabiliser to cholesterol. The general similarities in the characteristics of liposomes containing fatty alcohols or cholesterol suggest a common behavioural influence for both compounds within the bilayer.

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Targeting of drugs and therapies locally to the esophagus is an important objective in the development of new and more effective dosage forms. Therapies that are retained within the oral cavity for both local and systemic action have been utilized for many years, although delivery to the esophagus has been far less reported. Esophageal disease states, including infections, motility disorders, gastric reflux, and cancers, would all benefit from localized drug delivery. Therefore, research in this area provides significant opportunities. The key limitation to effective drug delivery within the esophagus is sufficient retention at this site coupled with activity profiles to correspond with these retention times; therefore, a suitable formulation needs to provide the drug in a ready-to-work form at the site of action during the rapid transit through this organ. A successfully designed esophageal-targeted system can overcome these obstacles. This review presents a range of dosage form approaches for targeting the esophagus, including bioadhesive liquids and orally retained lozenges, chewing gums, gels, and films, as well as endoscopically delivered therapeutics. The techniques used to measure efficacy both in vitro and in vivo are also discussed. Drug delivery is a growing driver within the pharmaceutical industry and offers benefits both in terms of clinical efficacy, as well as in market positioning, as a means of extending a drug's exclusivity and profitability. Emerging systems that can be used to target the esophagus are reported within this review, as well as the potential of alternative formulations that offer benefits in this exciting area.