Creation, validation, and analysis of a novel model for the study of nonadherence in newly diagnosed epileptic rats

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Publication Type dissertation
School or College College of Engineering
Department Bioengineering
Author Thomson, Kyle Edmond
Title Creation, validation, and analysis of a novel model for the study of nonadherence in newly diagnosed epileptic rats
Date 2014-12
Description One in 26 people in America will develop epilepsy at some point in their life. Approximately one-third of patients with epilepsy do not have full control of their seizures on their current antiseizure drug (ASD) regimen. In the past 20 years, 16 new ASDs have been made available to the patient with epilepsy. However, the percentage of pharmacoresistant patients has remained relatively constant. Thus, it is necessary to explore alternative avenues to explain the lack of seizure control in these patients. It is unknown how the practice of nonadherence contributes to the percentage of refractory patients. An animal model of nonadherence would permit the study of nonadherence and its consequences on seizure control. To model nonadherence, a computer-automated system was created to dose animals with antiseizure drugs (ASDs) using a drug-in-food protocol. Two studies were conducted and serve as a first-pass characterization. In the first study, newly-diagnosed epileptic rats were administered carbamazepine (CBZ) at varying levels of adherence. Two groups, one adherent (100%), and one nonadherent (50%), were compared to placebo control (0%). The 50% group displayed similar seizure frequency and severity to the placebo controls, while the 100% adherent group were observed to have fewer seizures overall. This suggesting that taking medication 50% of the time had no measurable effect on seizure control. In the second study, a group of newly diagnosed epileptic rats was subjected to a two-week on (100%), two-week off (0%) and two-week on CBZ (100%) paradigm. Despite numerous seizures after discontinuation of CBZ treatment, animals regained the same level of seizure control when CBZ treatment was reinstituted. Finally, nonadherence can lead to status epilepticus (SE), a severe seizure lasting several minutes. In an effort to aid drug discovery, a new and simple method which results in an unbiased method to assess the duration and severity of the electrographic component of SE was created. This method has been used to quantify the response of electrographic SE to novel investigational compounds. Together, this dissertation aims to aid in the treatment of epilepsy by providing etiologically relevant models of nonadherence and analysis of electrographic SE.
Type Text
Publisher University of Utah
Subject Carbamazepine; Epilepsy; Nonadherence; Status epilepticus
Dissertation Institution University of Utah
Dissertation Name Doctor of Philosophy
Language eng
Rights Management Copyright © Kyle Edmond Thomson 2014
Format Medium application/pdf
Format Extent 1,867,738 bytes
Identifier etd3/id/3331
ARK ark:/87278/s6bg5x7n
Setname ir_etd
Date Created 2015-02-19
Date Modified 2021-05-06
ID 196896
Reference URL
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