Class of 2005 Abstract / Objective: The purpose of this study was to retrospectively determine if individuals within the SAVAHCS home-based patient population with a diagnosis of diabetes mellitus are receiving an angiotensin-converting-enzyme inhibitor (ACE-I) based on recent evidence supporting its use in these patients. Research Design: A retrospective, chart review of 41 patients with a diagnosis of diabetes mellitus from November 1, 2004 to December 31, 2005. Methodology: This was a retrospective, chart review of all patients within the SAVAHCS home-based population with an active diagnosis of diabetes mellitus. Once the patients were identified, their clinical profiles were extracted from the VISTA computer system. The patients had data regarding age, gender, diabetes type, diagnoses of heart disease and hypertension, type of ACE- Inhibitor prescribed, blood pressure, HgbA1c, and height and weight in order to calculate body mass index (BMI). The patients were classified as either having or not having ACE-Inhibitor therapy. Results: The total number of diabetic patients currently receiving an ACE-Inhibitor was 24 (58.5%). This was significantly lower than the value of 80% predetermined (p=0.0352). Thirty-one patients were also found to have a diagnosis of hypertension (75.6%), with 18 of these patients having a prescription for an ACE-Inhibitor (43.9%). Four patients (9.8%) who were not currently on an ACE- Inhibitor had a documented history of cough induced by the use of these drugs. Clinical Relationships: ACE-Inhibitors are drug agents used to treat hypertension. They have also been shown to be of significant clinical value in diabetic patients, in both renal protective effects as well as to reduce cardiovascular risk, the most common cause of morbidity and mortality in diabetic patients.

Class of 2008 Abstract / Objectives: : The purpose of this paper is to provide greater understanding of ACE inhibitor cough and appropriate treatment options. Methods: A Medline search of key terms from 1975-2008 was conducted and all types of published material were included in this review. The articles were evaluated for relevance and appropriateness for inclusion in this review. Subjects considered appropriate included ACE inhibitor cough treatment, mechanism of action, incidence and prevalence, genetics, cough characteristics, onset and resolution of cough, and others. Whenever possible, original studies were obtained but several reviews were also used. Results: ACE inhibitor cough is typically a dry, non-productive, persistent but benign cough reportedly occurring in anywhere from 0.5%-50% of patients receiving ACE inhibitors, though most studies indicate less than 20%. The mechanism is not completely understood but seems to be related to a complicated mechanism involving pathways caused by ACE inhibition and including bradykinin, C fibers, and prostaglandins. Several treatment options have been successful in resolving or relieving cough, including NSAIDs, baclofen, cromolyn and others. Results, however, are inconsistent. Anti-tussive agents, switching to a different ACE inhibitor, or lowering the dose of the current ACE inhibitor do not seem to be effective. Conclusions: In spite of its benign nature, ACE inhibitor cough is usually bothersome enough to discontinue the medication and therefore can not be ignored. Several treatments have appeared effective, all of which carry the risk of drug interactions and additional side effects, and alternative therapy such as angiotensin receptor blockers seem to be reasonable in indicated patients.

No description available.

Class of 2010 Abstract / OBJECTIVES: To comprehensively review medical literature and report angiotension converting enzyme inhibitors (ACE-­‐I) adverse drug reactions including, incidences, mechanism of action, predisposing conditions, and report prevention and treatments. METHODS: This was a descriptive retrospective study of data related to ACE-­‐I adverse drug reactions other than ACE-­‐I induced cough. It was to review the ADR that accompany with the use of ACE-­‐I. Literature obtained through search engines MEDLINE and OVID SP available through the Arizona Health and Science Library at the University of Arizona. RESULTS: This comprehensive literature review looked at angioneurotic edema, orthostatic hypotension, hyperkalemia, and increased risk of bleeding and anaphylaxis with tPA and to a minor extent Elevated serum creatinine, and Teratogenicity. Angioneurotic edema (angioedema) reports initially estimated an incidence of 0.1 to 0.7%. A comprehensive review suggested the incidence was even lower at 0.1 to 0.2%, but the OCTAVE trial that specifically looked at angioedema as an endpoint estimated an incidence of ~0.7% although the study only had a 24-­‐week follow up. Most patients that discontinued treatment due to angioedema experienced symptom relief within 72 hours. The incidence of orthostatic hypotension from a study that followed patients on lisinopril was only 0.25%;moreover, a meta-­‐analysis by Agusti et al included 51 RCT that reported a relative risk of developing OH on an ACE-­‐I alone was 1.95. Hyperkalemia incidence reporeted varied from 1.1% to 10%; the more recent literature suggests a value near the lower end of this range. Elevated serum creatinine appears to occur early in ACE-­‐I treatment with discontinuation resolving in resolution. ACE-­‐I have been shown to be teratogenic during any trimester and should generally be avoided in pregnancy. There appears to be an increased risk of bleeding and anaphylactoid typer reactions when alteplase and ACE-­‐I are used simultaneously. Muravyov et al reported the viscosity of whole blood and plasma to be decreased after only three weeks of ACE-­‐I administration. CONCLUSIONS: With the continued increasing use of ACE-­‐Is and the drug class' ability to achieve therapeutic outcomes in a wide array of patient populations, it is important to better understand the processes and mechanisms behind the ADRs associated with ACE-­‐I therapy. A basic understanding of incidence rates and physiologic mechanisms will allow clinicians to properly assess the probability of causation and better treat patients who have experienced an ACE-­‐I induced ADR. However, an in-­‐depth level of understanding can help guide clinicians in making decisions that will hopefully decrease the amount of ADRs their patients experience or prevent their patients from developing ACE-­‐I related ADR altogether. It is important to note that, in most of the aforementioned ADR situations, treatment consists of ACE-­‐I discontinuation and avoidance of future exposures.

by Patricia Jane Anderson. / Thesis (M. Phil.)--Chinese University of Hong Kong, 1993. / Includes bibliographical references (leaves 199-215). / List of Figures --- p.i / List of Tables --- p.v / List of Abbreviations --- p.viii / Abstract --- p.1 / Introduction --- p.3 / Chapter Chapter 1 - --- Literature Reviews / Chapter 1.1 --- Pharmacoanthropology and Pharmacogenetics --- p.5 / Chapter 1.1.1 --- Genetic Polymorphisms --- p.7 / Chapter 1.1.2 --- Pharmacogenetics in Asians and Caucasians --- p.13 / Chapter 1.1.2.1 --- ACE-inhibitors in Asians and Caucasians --- p.18 / Chapter 1.2 --- The Renin Angiotensin System --- p.20 / Chapter 1.2.1 --- Discovery of Inhibitors of Angiotensin Converting Enzyme --- p.24 / Chapter 1.3 --- ACE-Inhibiting Drugs --- p.25 / Chapter 1.3.1 --- Pharmacokinetics and Pharmacodynamics of Perindopril --- p.28 / Chapter 1.3.2 --- The Pharmacokinetics and Pharmacodynamics of Cilazapril --- p.32 / Chapter Chapter 2 - --- General Methodology / Chapter 2.1 --- Introduction --- p.38 / Chapter 2.2 --- Subjects --- p.49 / Chapter 2.3 --- Sample Collection --- p.40 / Chapter 2.3.1 --- Blood Samples --- p.40 / Chapter 2.3.2 --- Urine Samples --- p.40 / Chapter 2.4 --- Blood Pressure and Heart Rate Measurements --- p.41 / Chapter 2.5 --- Measurement of Transthoracic Electrical Bioimpedance --- p.41 / Chapter 2.5.1 --- Background --- p.42 / Chapter 2.5.2 --- Practical Details --- p.45 / Chapter 2.6 --- Data Analysis --- p.48 / Chapter 2.6.1. --- Analysis of Pharmacokinetic Parameters --- p.48 / Chapter 2.6.2 --- Analysis of Pharmacodynamic Parameters --- p.59 / Chapter 2.6.3 --- Analysis of Non-Invasive Haemodynamic Monitoring Data --- p.60 / Chapter 2.7 --- Statistical Analysis --- p.64 / Chapter Chapter 3 - --- The Perindopril Study / Chapter 3.1 --- Introduction --- p.67 / Chapter 3.1.1 --- Aims --- p.67 / Chapter 3.2 --- Methodology --- p.68 / Chapter 3.2.1 --- Inclusion Criteria --- p.68 / Chapter 3.2.2 --- Non-Inclusion Criteria --- p.69 / Chapter 3.2.3 --- Study Design --- p.69 / Chapter 3.2.4 --- Blood Sampling --- p.71 / Chapter 3.2.5 --- Urine Sampling --- p.71 / Chapter 3.2.6 --- Blood Pressure and Heart Rate --- p.72 / Chapter 3.2.7 --- Non-invasive Haemodynamic Monitoring --- p.72 / Chapter 3.2.8 --- Analysis of Plasma Samples --- p.73 / Chapter 3.2.9 --- Hormone and Enzyme Assays --- p.74 / Chapter 3.3 --- Data Analysis and Statistical Methods --- p.75 / Chapter 3.3.1 --- Pharmacokinetic Analysis of Plasma --- p.75 / Chapter 3.3.2 --- Pharmacokinetic Analysis of Urine --- p.75 / Chapter 3.3.3 --- Pharmacodynamic Analysis of Hormone Data --- p.75 / Chapter 3.3.4 --- Analysis of Haemodynamic Monitoring Data --- p.76 / Chapter 3.3.5 --- Statistical Analysis --- p.76 / Chapter 3.4 --- Pharmacokinetic Results --- p.77 / Chapter 3.4.1 --- Pharmacokinetics of Perindopril in Plasma --- p.77 / Chapter 3.4.2 --- Pharmacokinetics of Perindopril in Urine --- p.84 / Chapter 3.4.3. --- Pharmacokinetics of Perindoprilat in Plasma --- p.85 / Chapter 3.4.4 --- Pharmacokinetics of Perindoprilat in Urine --- p.89 / Chapter 3.5 --- Pharmacodynamic Results --- p.89 / Chapter 3.5.1 --- Angiotensin Converting Enzyme Inhibition --- p.89 / Chapter 3.5.2 --- Angiotensin I (AI) --- p.102 / Chapter 3.5.3 --- Aldosterone and Plasma Renin Activity (PRA) --- p.102 / Chapter 3.5.4 --- Plasma Protein Binding --- p.102 / Chapter 3.5.5 --- Blood Pressure and Heart Rate --- p.107 / Chapter 3.5.6. --- Safety and Tolerance --- p.108 / Chapter 3.5.7 --- Non-invasive Haemodynamic Monitoring --- p.108 / Chapter 3.6 --- Discussion --- p.120 / Chapter Chapter 4 - --- The Cilazapril Study / Chapter 4.1 --- Introduction --- p.135 / Chapter 4.1.1 --- Aims --- p.135 / Chapter 4.2 --- Methodology --- p.136 / Chapter 4.2.1 --- Inclusion Criteria --- p.136 / Chapter 4.2.2. --- Exclusion Criteria --- p.136 / Chapter 4.2.3 --- Study Design --- p.137 / Chapter 4.2.4 --- Blood Sampling --- p.139 / Chapter 4.2.5 --- Urine Sampling --- p.140 / Chapter 4.2.6 --- Blood Pressure and Heart Rate --- p.140 / Chapter 4.2.7 --- Non-Invasive Haemodynamic Monitoring --- p.140 / Chapter 4.2.8 --- Analysis of Plasma Cilazaprilat Samples --- p.142 / Chapter 4.2.9 --- Hormone and Enzyme Assays --- p.143 / Chapter 4.3 --- Data Analysis and Statistical Methods --- p.143 / Chapter 4.3.1 --- Pharmacokinetic Analysis --- p.143 / Chapter 4.3.2 --- Pharmacodynamic Analysis of Hormone Data --- p.144 / Chapter 4.3.3 --- Analysis of Non-Invasive Haemodynamic Monitoring Data --- p.144 / Chapter 4.3.4 --- Statistical Analysis --- p.146 / Chapter 4.4 --- Pharmacokinetic Results --- p.146 / Chapter 4.4.1 --- Pharmacokinetics of Cilazaprilat in Plasma --- p.146 / Chapter 4.5 --- Pharmacodynamic Results --- p.150 / Chapter 4.5.1 --- Angiotensin Converting Enzyme Inhibition --- p.150 / Chapter 4.5.2 --- Aldosterone and Plasma Renin Activity (PRA) --- p.155 / Chapter 4.5.3 --- Blood Pressure and Heart Rate --- p.155 / Chapter 4.5.4 --- Safety and Tolerance --- p.159 / Chapter 4.5.5 --- Non-Invasive Haemodynamic Monitoring --- p.160 / Chapter 4.6 --- Discussion --- p.182 / Chapter Chapter 5 - --- General Discussion --- p.188 / Appendix --- p.195 / References --- p.199 / Acknowledgements --- p.216

Thesis (M. Phil.)--University of Hong Kong, 2001. / Includes bibliographical references.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Thesis (M. Phil.)--University of Hong Kong, 2007. / Also available in print.

Thesis (Ph.D.) - University of Queensland, 2004. / Includes bibliographical references.

Thesis (M. Med. Sc.)--University of Hong Kong, 2006.