Adverse drug reactions are a significant burden on industry and healthcare providers. They account for approximately 5 % of hospital admissions and are a considerable cause of morbidity and mortality in patients. While it is widely considered that an individual's susceptibility to idiosyncratic reactions is caused by a variety of factors; ADRs are thought to be linked to the formation and accumulation of reactive drug metabolites rather than the parent drug. Of the patients administered carbamazepine 30-50 % are subject to the development of some form of adverse drug reaction. Carbamazepine is metabolized extensively in vivo and hypersensitivity reactions have been hypothetically linked to the formation of chemically reactive arene oxide or iminoquinone metabolites. In order to understand the mechanisms behind such ADRs it is important to synthesize a variety of chemical probes to observe changes in pharmacokinetic and pharmacodynamic properties of the compounds. The overall theme of this thesis is the synthesis and the examination of the structure-metabolism relationships for halogenated analogues of carbamazepine. It is divided into three main sections; a general introduction introduces the reader to the basics of drug metabolism from how drugs are metabolized to the implications of halogen substitution on the metabolism of drugs. It next covers the synthetic strategies employed in the formation of halogenated carbamazepine analogues before ending on a discussion of the key findings of the structure-metabolism relationships that may be derived from in vitro investigations
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:569773 |
| Date | January 2011 |
| Creators | Elliott, Emma-Claire |
| Publisher | University of Liverpool |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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