Class of 2012 Abstract / Objectives: To evaluate the literature with respect to drug-drug interactions of the hydroxymethylglutaryl CoA reductase inhibitors atorvastatin, fluvastatin, lovastatin, pitavastitin, pravastatin, simvastatin, and rosuvastatin with warfarin. Methods: This descriptive retrospective study identified articles reporting on each drug-drug interaction from the online databases PubMed (1970 – February 2012) and the drug compendia Micromedex and Facts & Comparisons. The studies included in this investigation were primary literature reports, written in English with human subjects. All studies included were evaluated using the van Roon 5-point quality of evidence scale developed in the Netherlands to assess drug-drug interactions. This scale rates the study type from lowest to highest quality, from zero to four. Case-reports were evaluated using the Drug Interaction Probability Scale (DIPS). The DIPS tool uses 10 questions to evaluate the probability that an adverse event is caused by a drug-drug interaction. Results: Twenty studies met the inclusion criteria. One study involved atorvastatin, four for fluvastatin, three for lovastatin, 2 for pitavastatin, 1 for pravastatin, 5 for rosuvastatin, and 6 for simvastatin. The mean van Roon quality of evidence score was 2.1+/- 0.74, the mean score for atorvastatin, pitavastatin, and pravastatin was 3, with the mean score of fluvastatin, lovastatin, rosuvastatin, and simvastatin was 2. 70% of the literature reviewed were case-reports or letters. Conclusions: The studies and reports supporting HMG-CoA reductase inhibitors and warfarin drug-drug interactions are most commonly case- reports and are of low quality and quantity.

A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfillment of the requirements for the degree of Doctor of Philosophy / Alzheimer’s disease (AD) is the most prevalent and progressive neurodegenerative disorder (ND). It is characterized by a progressive decline of cognitive function, complete loss of memory, deterioration of visual capacity and the inability to function independently. According to the World Health Organization (WHO) it is estimated that about 26 million people suffer with AD worldwide. Although the etiology of AD is not fully understood, the aggregation of β-amyloidal (A) peptides that are associated with the formation of extracellular neurotoxin senile plaques and neurofibrillary tangles comprising hyperphosphorylated tau proteins have been recognized as the primary constituents that play a crucial role in AD. Several potential neurotherapeutic agents that can improve the management of AD such as metal chelators and alkaloid drugs have been approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). Metal chelators [e.g. histidine, Ethylenediaminetetraacetic acid (EDTA) and zinc acetate (ZnAc)] are the main therapy used for modulating Aβ peptide aggregation with biological metals (such as zinc and copper ions) which is associated with promoting neurotoxicity in AD. While alkaloid drugs, such as donepezil, galantamine and rivastigmine, are used to inhibit the enzyme acetylcholinesterase (AChE); memantine is used to block the N-methyl-D-aspartate (NMDA) receptors associated with pathological activation. Despite the availability of these indispensable drugs, the clinical utility of these drugs is hampered by their poor retention and difficulty in bypassing the highly restrictive Blood Brain Barrier (BBB). Therefore this study aimed at developing novel nanoliposomes (NLPs) surface-engineered with chelating and synthetic peptides that are capable of crossing the BBB thus improving delivery efficacy and modulating the extracellular neurotoxicity associated with β-Amyloid aggregates of AD. Furthermore, since this system was designed for a chronic condition, a temporary depot-based polymeric system was integrated for further enhancement of the liposomal half-life, storage and prolonged drug delivery over a period of 50 days. The surface-engineered NLPs produced were spherical in shape, 100-149±28nm ~ size, with a zeta potential range of -9.59 to -37.3mV and a polydispersity index (PdI) of 0.02-0.2. A Box-Behnken experimental design was employed for maximizing the ligand coupling efficiency (40-78%) and drug entrapment efficiency (DEE) that ranged from 42-79%. The optimized peptide-based ligand NLP formulation showed sustained drug release (30% of drug released within 48 hours). Chelating ligands on the surface of NLPs showed 50-68% modulation of neurotoxicity on PC12 neuronal cells induced by ZnAβ (1-42) or CuAβ (1-42) aggregates. When drug-loaded functionalized NLPs were embedded within the temporal hydrophilic hydrogel network/scaffold as an implantable nano-enabled bio-robotic intracranial device (BICD), the physicomechanical and physicochemical dynamics showed improvement of liposomal structure such as the stability, and homogeneity in distribution of the liposomes within the internal core of the hydrogel networks and post-lyophilized scaffold. In vitro studies in simulated cerebrospinal fluid (CSF) showed prolonged release behavior of the drug-loaded functionalized NLPs from the BICD with 50-70% released over 50 days. Scanning Electron Microscopy (SEM) and confocal microscopy confirmed intact liposomal structures within the temporal polymeric scaffold/depot post-fixation and post-lyophilization. Ex vivo studies confirmed cell proliferation and a low level of lactate dehydrogenase (LDH), which is associated with cell membrane damage/injury, after PC12 neuronal cells were exposed to the BICD. In addition, when PC12 neuronal cells were exposed to the BICD high accumulation of galantamine (GAL) into these PC12 neuronal cells was observed post-cultivation. This outcome indicated that the released drug-loaded functionalized NLPs from the BICD were still in their intact form and capable of serving as bio-robotic markers for the delivery of GAL into the neuronal cells in response to AD. Furthermore, intracellular activity validated that the synthetic peptide has the potency for targeted delivery of the drug-loaded NLPs post-release of the BICD in ex vivo studies. Overall, results from this study revealed that the BICD device had superior cytocompatibility and may be suitable for application as a prolonged and targeted delivery system for GAL into neuronal cells to treat AD.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Master of Medicine in the branch of Anaesthesiology Johannesburg, 2013 / Background: Microbial contamination of multi-dose vials is one of the mechanisms by which transmission of pathogens to patients can occur in anaesthesia. Common practice at Chris Hani Baragwanath Academic Hospital (CHBAH) is to use boluses of a self-prepared, multi-dose phenylephrine solution (referred to as the solutions) to treat hypotension, due to the vasodilatory effects of a spinal anaesthetic, in stable patients undergoing a caesarean section. Aims: The aims of this study were to determine if there was microbial contamination of the solutions used at CHBAH and to evaluate if appropriate labelling and aspiration practices were adhered to with regard to the solutions A sample was collected and the labelling data was documented from the solutions found in the obsteric theatres at CHBAH over a period of three months. The samples were sent to a laboratory for microbial investigation. Microbial contamination was identified in seven of 110 (6.36%) samples collected from the solutions. The name of the solution was indicated on all 110 (100%) containers and the concentration of the solution was indicated on 106 (96.36%) containers. The date the solution was prepared was indicated on 82 (74.55%) containers and the time the solution was prepared was indicated on 63 (57.27%) containers. Only nine (8.18%) of the healthcare workers that prepared the solutions confirmed it by placing a signature on the container. Labelling data was written directly on all 110 (100%) containers and a spike device was used in 71 (64.54%) containers. This study demonstrated microbial contamination of the solutions and that safe injection practices were not adhered to when intravenous medications were prepared and administered. This is important at CHBAH since a large proportion of South African patients are immunocompromised and susceptible to opportunistic infections. Inappropriate labelling of medications is a cause of medication administration errors and this may have serious legal implications for the anaesthetist.

No description available.

Thesis (M.Pharm.)--University of the Witwatersrand, Faculty of Health Sciences, 2011.

It has commonly been argued that drugs have been securitized, however relatively little in-depth analysis has been carried out on this subject. This thesis addresses this gap in the literature by using a combination of Foucault’s concept of the dispositif and a sociological interpretation of securitization theory to examine how drugs have become constructed as existentially threatening to humankind and the state by the United Nations (UN) and the United States of America (US). The two securitizations analysed here -the 1961 United Nations Single Convention on Narcotic Drugs (Single Convention) and US President Reagan’s 1986 National Security Decision Directive 221 (NSDD-221) -took place within the wider historical context of a control-oriented dispositif, it is argued,but also re-shaped the international drug control system and the drug control dispositif in profound ways. The thesis concludes that the drug control dispositif has continued to evolve through time and across space, and that the securitization of drugs by the US and UN has limited the range of options available within international and domestic drug policies, often exacerbating the harms to humans and the state –the very referent objects that these securitizations aim to protect. Discourse analysis of archival documents from the British National Archives, the US National Archives and the Ronald Reagan Presidential Library and Museum,and process-tracing of media sources are used to examine the ways in which drugs became securitized and how these securitizations affected the drug control dispositif. In order to understand the context in which the securitization(s) of drugs occurred, this thesis firstly identifies the various forms of control that were used during the nineteenth and early twentieth centuries. It then analyses how the Single Convention and NSDD-221 established drugs as being threatening to humankind and the state through securitizing speech acts and non-discursive practices and how these securitizations re-oriented the drug control dispositif towards a prohibitionist paradigm. Finally, this thesis explores how various discourses and practices are challenging the ‘drugs as a threat’ discourse but still sit firmly within the drug control dispositif.

Thesis (M.S.)--Naval Postgraduate School, 2002. / Thesis advisor(s):David R. Henderson, Douglas Moses. Includes bibliographical references (p. 123-132). Also available online.

No description available.

Thesis (M. Soc. Sc.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.

Thesis (J.C.L.)--Catholic University of America, 2003. / Includes bibliographical references (leaves 47-52).