Efeito agudo da galantamina em par??metros hemodin??micos e auton??micos em portadores da s??ndrome metab??lica: estudo cl??nico prospectivo randomizado

• Autor(a) principal: Costa, Fernando Oliveira
• Data de Publicação: 2014
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da Uninove
• Texto Completo: http://bibliotecatede.uninove.br/handle/tede/1152
• topic: s??ndrome metab??lica; via colin??rgica antiinflamat??ria; variabilidade da freq????ncia card??aca; balan??o auton??mico; galantamina; metabolic syndrome; cholinergic anti-inflammatory pathway; heart rate variability; autonomic balance; galantamine; CIENCIAS DA SAUDE

The metabolic syndrome (MetS) consists of a combination of conditions that tend to cluster together, and increase the risk of type 2 diabetes and cardiovascular disease. The components of the metabolic syndrome include central (abdominal) obesity, elevated fasting glucose, dyslipidemia (abnormally high triglycerides and low high-density lipoprotein cholesterol), and elevated blood pressure. MetS is also associated with proinflammatory and prothrombotic states, non-alcoholic liver steatosis, obstructive sleep apnea and reproduction disorders. Although a common unifying physiopathological mechanism is not known, central obesity and inflammation play a major role in MetS and upon each of its components. The MetS has reached epidemic proportions and to date there are no proven pharmacological interventions that simultaneously target all of the components of this syndrome. Inflammation plays an important role in the pathogenesis of the MetS. Recently, it was discovered that inflammation can be regulated by neural, cholinergic mechanisms and a cholinergic drug, the acetylcholinesterase inhibitor galantamine suppresses abnormal inflammation and alleviates MetS pathologies in rodents. The fact that galantamine is an approved drug, used to treat patients with Alzheimer??s disease with a known safety profile, will facilitate its clinical application in another situations. We hypothesize that treatment of subjects with the MetS with galantamine will result in alleviation in the MetS clinical conditions and inflammation. The objective of our study was to initiate an investigation on the safety profile of galantamine in MetS patients, with special attention on autonomic, hemodynamic and cognitive parameters. A randomized, double-blind, prospective study evaluated clinical, autonomic, hemodynamic and cognitive variables of patients with MetS in two moments: before treatment (basal state) and after 28 days of treatment with galantamine 8 mg daily. There was a statistical tendency in reducing systolic blood pressure in the HRV with Finometer?? in patients under galantamine (124.4 ?? 4 vs 119.7 ?? 3.7 mmHg, basal and 28 days values, respectively) and also a reduction in diastolic blood pressure (72.5 ?? 1.3 vs 67.2 ?? 1.7 mmHg, basal and 28 days values, respectively). Paradoxically, an increase in the sympathetic modulation of the heart was observed with the HRV study measuring the LF (nu) value (46.2 ?? 3.8 vs 57.1 ?? 3.4 basal and 28 days, respectively) and a decrease in the parasympathetic modulation HF (nu) value (53.8 ?? 3.8 vs 43.0 ?? 3.4, basal and 28 days, respectively). We did not observe any significant change in cognitive domains. Our conclusion is that treatment with galantamine 8 mg exhibits a safe clinical profile and can be used in MetS patients.