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Date of Award

2007

Document Type

Dissertation - Pacific Access Restricted

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Pharmaceutical and Chemical Sciences

First Advisor

Patrick Catania

First Committee Member

Sian Carr-Lopez

Second Committee Member

Susan Blalock

Third Committee Member

William Kehoe

Fourth Committee Member

Timothy Smith

Abstract

According to the American Diabetes Association (ADA), over 21 million individuals in the United States have diabetes mellitus. Of those affected by the disease, most (between 90-95%) have the type 2 variety. It is estimated that nearly three-fourths of individuals with diabetes also suffer from hypertension. Hypertension is an insidious disease that can have devastating long-term consequences. Hypertension in patients with diabetes contributes to approximately 75% of all diabetes-related complications. Thus, the comorbidities of type 2 diabetes and hypertension are identified as being responsible for a myriad of vascular problems in affected patients. According to both the JNC 7 Report and the ADA guidelines, patients with diabetes and hypertension have demonstrated observable clinical benefit from use of the following antihypertensive drug classes: diuretics, beta-blockers, ACE Inhibitors, angiotensin-receptor blockers, and calcium-channel blockers. However, despite identification of the negative relationship between arterial hypertension/type 2 diabetes and vascular complications, uncertainty remains as to which pharmacological treatment would best prevent the frequent and costly complications in patients with these comorbidities. A Markov model utilizing both 1 st and 2 nd order Monte Carlo simulation was created to simulate the effects of each recommended drug class on the complications of stroke, myocardial infarction, the microvascular complication of nephropathy, and patient mortality. The present research was conducted with the belief that appropriate selection of an antihypertensive agent for the treatment of high blood pressure in patients with type 2 diabetes will minimize the occurrence of important cardiovascular and microvascular complications, thereby reducing the economic toll and increasing the life expectancy of patients plagued by these two disease states. The findings of the present work illustrate the cost and effectiveness of each therapeutic class of agents advocated for use in patients with type 2 diabetes and hypertension. Furthermore, the value of ACE Inhibitors compared to the other four drug classes espoused for use in this patient population clearly emerged. Ideally, the results of the current work will have the added benefit of partially eliminating the subjective value judgments that clinicians are required to make when deciding which pharmacotherapeutic alternative to initiate in a patient with both clinical conditions.

Pages

233

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