Thesis (M.S.)--The University of North Carolina at Greensboro, 2008. / Directed by Paul Davis; submitted to the Dept. of Kinesiology. Title from PDF t.p. (viewed Jul. 20, 2010). Includes bibliographical references (p. 104-112).

Beta blockers are commonly prescribed for the chronic treatment of hypertension, one of the most prolific disease states worldwide. The beta blockers selected for this study include acebutolol hydrochloride, labetalol hydrochloride, metoprolol tartrate oxprenolol hydrochloride and propranolol hydrochloride. All of these compounds have a short elimination half-life, necessitating multiple dose per day regimens and therefore the development of sustained release dosage forms incorporating these agents was considered beneficial in terms of extending the dosing interval, with the aim of improving patient compliance and subsequent therapeutic outcomes. Preformulation studies that were conducted included moisture content analysis by Karl Fischer titration, and DSC, a method used to predict potential interactions between the drugs and tablet excipients. Tablets were manufactured by both wet granulation and direct compression techniques, and the resultant drug release characteristics were evaluated using the USP Apparatus 3(BIO.DIS). A validated isocratic HPLC method, capable of separating the five drug candidates simultaneously, was developed and used for the analysis of drug samples. Tablet quality was assessed using analyses that included the physical assessment of weight, diameter, thickness, hardness and friability, as well as content uniformity of tablets, before and after dissolution testing. Direct compression tablet formulations containing each of the five beta blockers were successfully adapted from a prototype wet granulation matrix tablet containing metoprolol tartrate, and various formulation variables were investigated to establish,their effect on the rate and extent of drug release from these tablets. The grade and quantity of ethylcellulose used in the wet granulation and direct compression formulae influenced the release rate of some drug candidates. In addition, an alternative formulation method, involving freeze-drying of the drug with an ethylcellulose dispersion, was shown to have potential for altering release rates further. Anti-frictional agents, talc and colloidal silicon dioxide, did not affect drug release from these matrices,however, they affected the physical character:istics such as tablet weight and thickness, of the resultant tablets. All of the matrix tablets formulated were shown to release drug according to square root of time kinetics, in a sustained manner over a 22 hour period.

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Controversy exists regarding the effects of beta-blocker medications on functional capacity in cardiac patients and in the effects of disease-related impairments on cardiorespiratory dynamics during exercise testing. Therefore, this study was conducted to examine the exercise responses of 26 subjects (ages 37-66 years) to a graded exercise test. Subjects were divided into three groups based on clinical status: apparently healthy (AH; N=8); cardiacs receiving beta-blockers (C-BB; N=8); cardiacs not receiving beta-blockers (Câ NBB; N=lO). / Master of Science

Made available in DSpace on 2014-07-29T15:25:14Z (GMT). No. of bitstreams: 1 Tese de doutorado Luiza Cristina Lacerda Jacomini.pdf: 1113139 bytes, checksum: 6f7dbdd64a41cff3100ce05df4ddcf61 (MD5) Previous issue date: 2010-08-05 / Lacerda Jacomini, LC. Investigation on dysautonomia, epinephrine and norepinephrine-evoked pain, and effect of beta-blocker in fibromyalgia and systemic lupus erythematosus. 2010, 169 p. Doctoral thesis - Universidade Federal de Goiás, Goiânia. Dysautonomia is a condition in which an altered autonomic function affects the health in an adverse way. The present study aims: to search for the presence of epinephrine and norepinephrine-evoked pain; to evaluate the cardiovascular autonomic function and the effect of propranolol in women with fibromyalgia (FM), systemic lupus erythematosus (SLE) and controls (CTR). For each objective a separate research was developed, including a clinical trial. Epinephrine and norepinephrine-evoked pain were diagnosed when the subcutaneous injections containing these substances (10 micrograms/ 0.1 mL saline solution) induced greater pain than the saline solution did (n=7). Autonomic function was assessed through the standard Ewing tests battery, through heart rate responses to Valsalva maneuver, deep breathing, standing and blood pressure responses to ortostatism and to hand grip (n=7). Functional symptoms related to autonomic manifestations were checked. In a randomized, double-blind, placebo-controlled, crossover clinical trial with 6 women with FM, SLE and CTR, propranolol (80 mg/day po/4 weeks) was added to the usual schedule of prescribed medicines and its effect was examined regarding: pain, fatigue, tender points, blood pressure, heart rate, health related quality of life (SF-36) and fibromyalgia impact questionnaire. Epinephrine-evoked pain was diagnosed in SLE and FM groups and norepinephrine-evoked pain was diagnosed in FM group. Epinephrine and norepinephrine-evoked pain intensity has a trend to be greater in FM patients when compared to healthy CTR. FM and SLE patients had an elevated number of functional symptoms related to autonomic manifestations. Cardiovascular autonomic function was altered in FM and SLE groups. Parasympathetic cardiovascular autonomic function tests were mainly abnormal in SLE patients while in FM patients both, parasympathetic and sympathetic tests were abnormal. Propranolol reduced tender points count and the number of symptoms related to autonomic manifestations in FM group. Four in six patients presented significant improvement in health related quality of life evaluated by SF-36. These results suggest that FM belong to the group of sympathetically maintained pain syndromes. The study demonstrates that FM and SLE patients have cardiovascular autonomic function alterations which can be detected by simple, standardized, non-invasive and inexpensively methodology and that propranolol has a potential benefit in FM treatment. / Lacerda Jacomini, LC. Pesquisa de disautonomia, dor evocada por adrenalina e noradrenalina e efeito de beta-bloqueador na fibromialgia e no lupus eritematoso sistêmico. 2010, 169 p. Tese de doutorado - Universidade Federal de Goiás, Goiânia. Disautonomia é uma condição na qual a função autonômica alterada afeta a saúde de modo adverso. Os objetivos do presente estudo foram: pesquisar a presença de dor evocada por adrenalina (AD) e por noradrenalina (NA), avaliar a função autonômica cardiovascular e o efeito do propranolol, em mulheres com fibromialgia (FM), lupus eritematoso sistêmico (LES) e controles (CTR). Para cada objetivo foi desenvolvida uma etapa de estudo, sendo incluído um ensaio clínico. A dor evocada por AD ou NA foi diagnosticada quando estas substâncias produziram dor maior que soro fisiológico quando injetadas (10 microgramas/ 0,1 mL de soro fisiológico), via subcutânea (n=7). A função autonômica foi testada usando-se a bateria de testes de Ewing (respostas da frequência cardíaca à manobra de Valsalva, respiração profunda e ao ortostatismo e respostas da pressão arterial ao ortostatismo e à preensão sustentada) (n=7). Foram pesquisados sintomas funcionais relacionados às manifestações autonômicas. No ensaio-clínico randomizado, duplo-cego, placebo controlado e cruzado em grupos de 6 mulheres com LES, FM e CTR, o propranolol (80 mg/dia, via oral/4 semanas) foi adicionado ao esquema terapêutico das pacientes e seu efeito avaliado segundo as variáveis: dor, fadiga, tender points, pressão arterial, frequência cardíaca, qualidade de vida e questionário do impacto da FM. A dor evocada por AD ocorreu nos grupos FM e LES comparada ao CTR e, por NA ocorreu no grupo FM. Os escores de dor evocada por AD e por NA, no grupo FM, tiveram uma tendência a serem maiores do que os do grupo CTR. Pacientes com FM e com LES apresentaram elevado número de sintomas funcionais relacionados a manifestações autonômicas. A função autonômica cardiovascular estava alterada no LES e na FM. No grupo LES, os testes de função parassimpática tiveram frequência maior de respostas anormais e no grupo FM estavam alterados tanto os da função parassimpática como da simpática. O propranolol reduziu o número de tender points e de sintomas funcionais relacionados a manifestações autonômicas no grupo FM. Quatro em 6 pacientes do grupo FM apresentaram melhora significativa na qualidade de vida avaliada pelo SF-36. Os resultados sugerem que a FM faz parte do grupo de doenças com dor simpaticamente mantida. O estudo demonstrou que as pacientes com LES e FM têm alterações da função autonômica cardiovascular detectáveis por metodologia simples, padronizada, não invasiva e de baixo custo e que o propranolol tem um benefício potencial no tratamento da FM.

The sympathetic nervous system plays a key role in the regulation of cardiovascular and ventilatory responses during exercise. The regulation of the heart and peripheral circulation by the autonomic nervous system is accomplished by control centers that receive input from mechanical and chemical receptors through the body. Therefore, the changes in sympathetic and parasympathetic activity allow for rapid responses. <p><p>Exercise is associated with increases of ventilation, heart rate and blood pressure. Ventilation increases adaptedly to increased oxygen uptake (VO2) and carbon dioxide output (VCO2) and eventually to limit metabolic acidosis occurring above the ventilatory threshold. Cardiac output increases to meet the contracting muscles’ requirement for flow. The increase in cardiac output occurs through increases in both heart rate and stroke volume and is regulated by feed-forward mechanisms: central command and exercise pressor reflex. <p><p>Skeletal muscle contraction elicits a reflex increase in sympathetic outflow which causes vasoconstriction contributing to the exercise induced rise in blood pressure. This reflex is triggered by stimulation of metabo- and chemoreceptors. Although the precise stimulus is not known, adrenergic receptor signaling is involved in the cardiovascular and respiratory alterations in response to exercise. <p><p>This thesis has been devoted to a better understanding of the functional aspects of sympathetic nervous system activation during dynamic and resistive exercise, with use of β blocker and β2 stimulant interventions The hypotheses were: 1) that β blocker interventions would decrease aerobic exercise capacity by a limitation of maximal cardiac output, but more so the ventilatory responses to exercise because of a decreased chemosensitivity, thereby decreasing dyspnea, and 2) β2 stimulant interventions would slightly increase aerobic exercise capacity by an increase in maximal cardiac output, but also the ventilatory responses because of an increased chemosensitivity, with possible decrease of the ventilatory reserve at exercise and increased dyspnea. Both interventions could affect maximal muscle strength through central effects.<p><p>Ventilatory responses to hyperoxic hypercapnia (central chemoreflex) and to isocapnic hypoxia (peripheral chemoreflex) were confronted to measurements of ventilatory equivalents for oxygen (O2) and carbon dioxide (CO2) during standard cardiopulmonary exercise test (CPET). Resting 5 measurements of muscle sympathetic nervous activity (MSNA) were obtained in different conditions with and without pharmacological interventions. Muscle metaboreflex and muscle stength measurements were also considered. Drugs with β blocker or β2 stimulant properties were administered in range of doses used in clinical practice for the teatment of cardiovascular or rerspiratory conditions. The results show that β blockade with bisoprolol slightly reduced maximal exercise capacity as assessed by a maximal oxygen uptake (VO2max) or maximal workload (Wmax), with a decreased maximal heart rate, without significant effect on ventilation (VE) or MSNA responses to hypercapnia, hyperoxia or to isometric muscle contraction or ischemia. Both VE/VO2 and VE/VCO2 slopes were decreased during CPET, which was attributable to β blockade-related hemodynamic changes. On the other hand, stimulation of β2 receptors with salbutamol did not affect exercise capacity as assessed by VO2max or Wmax in spite of increased peripheral chemosensitivity with increased VE/VCO2 slopes and early lactic acidosis. MSNA burst frequency, muscle metaboreflex and maximal isokinetic muscle strength were not affected by salbutamol. <p><p>Thus, aerobic exercise capacity in healthy subjects is sensitive to sympathetic nervous system modulation by β blocker or β2 stimulant interventions with drugs at doses prescribed in clinical practice. B blocker intervention has a slight limitation of aerobic exercise capacity and a hemodynamic decrease in ventilation, while β2 stimulant intervention has no change in exercise capacity with associated increased ventilatory responses because of increased chemosensitivity, partly related to early lactic acidosis. None of the studied phamacologic interventions affected MSNA or muscle strength measurements. <p><p>We hope that these results might be useful for the understanding of the effects of revalidation to exercise of patients treated with β blocker or β2 stimulant drugs, document the limited ergogenic properties and also side effects of the intake of these substances in healthy exercising subjects.<p> / Doctorat en Sciences de la motricité / info:eu-repo/semantics/nonPublished

Background: Beta blockers are recommended by the American College of Cardiology/American Heart Association Guidelines for high and intermediate-risk cardiac patients undergoing non-cardiac surgery. Beta blockers are a class of drugs that moderate the effects of increased catecholamine levels on the heart by selectively blocking beta receptors in the heart and blood vessels, resulting in a lower heart rate and blood pressure. Beta blocker use perioperatively has been shown to reduce the risk of ischemia and infarction. Purpose: The purpose of this project is to address beta blocker use in a group of anesthesia providers who routinely attend to high-risk and intermediate-risk cardiac patients undergoing non-cardiac surgery in a medium-sized private hospital in suburban South Florida. There are barriers to the implementation of the published guidelines for beta blocker administration, including lack of awareness of the best current practice and a lack of a formal beta blocker protocol at the institutional level. Methods: A simple and inexpensive beta blocker protocol was implemented and evaluated by various means. Beta blocker administration practices were examined and documented prior to and after protocol implementation. Beta blocker usage was examined prior to and after protocol implementation Findings/Implications: It was hypothesized that increased anesthesia provider awareness would lead to increased administration of perioperative beta blockers to high-risk and intermediate-risk cardiac patients undergoing non-cardiac procedures. Although there was a knowledge increase related to the new beta blocker protocol, no change in practice was observed.