Polimorfísmos genéticos de COX-1 y eNOS y hemorragias gastrointestinales: interacción con aire: Un estudio de casos y controles

La hemorragia gastrointestinal alta es un cuadro grave que está producido por medicamentos en un porcentaje elevado de los casos. Ciertos fármacos como los antiinflamatorios no esteroideos (AINE), los antiagregantes plaquetarios o los anticoagulantes orales, pueden dar lugar a una hemorragia que exija la hospitalización del paciente y, en ocasiones, provoque la muerte. Además de los fármacos, se han identificado otros factores que se asocian con la hemorragia gastrointestinal; entre ellos estaría la infección por Helicobacter pylori o el consumo de determinadas sustancias como el alcohol, el tabaco o la cafeína.Se admite para la hemorragia gastrointestinal también una susceptibilidad genética que haría que ciertos individuos presentaran esta reacción con una mayor frecuencia al ser expuestos a determinados fármacos. En este estudio se ha explorado la posible asociación entre dos variantes polimórficas del gen que codifica la enzima COX-1 y una en el gen que codifica para la enzima e-NOS, ambas responsables de la producción de sustancias protectoras de la mucosa gastrointestinal (prostaglandinas y óxido nítrico). OBJETIVOS Explorar la posible asociación entre polimorfismos funcionales en el gen de COX-1 (C50T y A-842G) y la hemorragia digestiva. Explorar la posible asociación entre polimorfismos funcionales en el gen de eNOS (a/b situado en el intrón 4) y la hemorragia digestiva. Conocer la distribución de estos polimorfismos en la población española. MÉTODO Se ha llevado a cabo un estudio de casos y controles en cinco hospitales españoles. Se identificaron casos de hemorragia digestiva alta confirmados mediante endoscopia y controles de la misma población emparejados por edad, sexo y tiempo de atención. A todos los individuos del estudio se les realizó una entrevista y se les extrajo una muestra de sangre para estudios genéticos. RESULTADOS Tanto ara el polimorfismo C50T de COX-1 como para el polimorfismo A-842G, la distribución fue del 90% para las variantes normales y del 10% para las variantes polimórficas C/T y T/T, con la misma distribución en casos y controles. Para el polimorfismo de eNOS la distribución fue del 61% para la variante normal (4b/4b) y del 39% para las variantes polimórficas (4b/a, 4a/a, 4b/c), igual distribuidas en casos y controles. Se calculó el riesgo de hemorragia gastrointestinal alta en relación a los polimorfismos estudiados. Las OR ajustadas fueron de 0,69 (IC al 95%, 0,39-1,22) para la variante C50T de COX-1, de 0,77 (IC95%, 0,42-1,45) para la variante A-842G de COX-1 y de 1,21 (IC95%, 0,81-1,82)Departamento de Biología Celular, Histología y Farmacologí

No differences between men and women in adverse drug reactions related to psychotropic drugs: a survey from France, Italy and Spain

Producción CientíficaA large number of studies have suggested that being a woman represents a potential risk factor for the development of adverse drug reactions (ADRs). The aim of this study is to further explore the differences between men and women with regard to reported ADRs, particularly those associated with psychotropic drugs. We used spontaneous reports of suspected ADRs collected by Midi-Pyrénées (France), Veneto (Italy) and Castilla y León (Spain) Regional Pharmacovigilance Centres (January 2007-December 2009). All the reports including a psychotropic medication were selected in a first step; age distribution, seriousness and type of ADRs were compared between men and women. Reports of nonpsychotropic drugs were similarly identified and treated. The absolute number of reports and the proportion, considering population, were higher in women than in men. This was observed for all reports, but was particularly higher for psychotropic drugs (592 vs. 375; P < 0.001) than for nonpsychotropics drugs (5193 vs. 4035; P < 0.001). Antidepressants were the most reported (women, 303; men, 141; P < 0.001); the reporting rates (number of reports divided by exposed patients in the same period, estimated through sales data) for these drugs, however, were not significantly different between women (0.87 cases per 10 000 treated persons per year) and men (0.81 cases per 10 000 treated persons per year). Although there was a higher number of reports of ADRs in women, ADR reporting rates might be similar as highlighted by the case of antidepressants. Antidepressant ADRs in fact were similarly reported in men and in women. Gender differences are sometimes subtle and difficult to explore. International networks, as the one established for this study, do contribute to better analyse problems associated with medications.Junta de Castilla y León. Consejería de Sanidad. Dirección General de Salud Pública e Investigación, Desarrollo e Innovación

Hip fracture rates and bisphosphonate consumption in Spain. An ecologic study

Producción CientíficaIntroduction Bisphosphonates are used worldwide to treat osteoporosis and, thus, to prevent fractures. Though they have been proven in clinical trials to avoid some fractures, their effectiveness in reducing hip fractures is unclear. The aim of the present study was to explore the relationship between bisphosphonate use and hip fracture trends in Spain. Methods For this purpose, an ecologic study spanning 2002 to 2008 was conducted in Spain. Consumption data were obtained from the Spanish Ministry of Health and Social Policy. The number of hip fractures was obtained from hospital discharges; annual hip fracture rates were determined and standardized using the Spanish 2002 population census. A linear regression was performed between fracture rate and use of bisphosphonates; R2 and Pearson correlation coefficient were calculated. Results From 2002 to 2008, dispensed prescriptions of bisphosphonates in Spain increased from 3.28 to 17.66 DDD/1,000 inhabitants per day. In the same period, the crude hip fracture rate increased from 2.85 to 3.02 cases per 1,000 inhabitants older than 50 years; however, when age standardized rates were estimated, the rate declined from 2.85 to 2.79. Analyzed by sex, the standardized rate for men slightly increased from 1.45 to 1.48, while for women the rate significantly dropped from 4.00 to 3.91.Conclusion A small effect of bisphosphonates on hip fracture rates can not be ruled out; however, other factors might partially explain this decline. Assuming this medication was the only cause for hip fracture rate reduction, the elevated medication cost to avoid a single hip fracture makes it necessary to explore less expensive intervention

Heart rhythm risturbances associated with rupatadine: a case series from the Spanish and Portuguese Pharmacovigilance Systems

Producción CientíficaWe searched the Spanish and Portuguese pharmacovigilance databases for spontaneous case reports of heart rhythm disturbances associated with rupatadine and other new H1 antihistamines. Five cases were found involving patients treated with rupatadine (13.9% of all reports relating to this drug). In all five cases, the reaction started after exposure and resolved when the drug was discontinued. In two cases, rupatadine was the only medication being taken by the patient, and no other condition that could explain the heart rhythm disturbances was diagnosed. The reporting odds ratio was 3.2 (95% confidence interval, 1.0-10.5). The reporting rate was 2 cases per 100,000 patients treated per year (95% confidence interval, 0.4-6.0). These results suggest a causal relationship between rupatadine and heart rhythm disturbancesJunta de Castilla y León. Consejería de Sanidad. Dirección General de Salud Pública e Investigación, Desarrollo e Innovación