Porfirias agudas y polimorfismos de las enzimas que metabolizan fármacos

Acute porphyrias (AP) are a group of hepathic pathologies characterized by the accumulation of porphyrins and their precursors. They usually manifest at puberty (more\noften in women), and include the New Acute Porphyria (NAP), Acute Intermittent\nPorphyria (AIP), Variegata Porphyria (VP) and the He...

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Autor principal:	Sánchez Temiño, Victoria Emilia
Otros Autores:	Gerez, Esther Noemí
Formato:	Tesis de maestría acceptedVersion
Lenguaje:	Español
Publicado:	Facultad de Farmacia y Bioquímica 2019
Materias:	Porfirias Porfiria Aguda Intermitente Farmacogenética CYP-450 CYP3A4 CYP3A5 AKR1D1 Ciencias de la vida
Acceso en línea:	http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_5946 http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_5946.dir/5946.PDF
Aporte de:	Repositorio Digital de la Universidad de Buenos Aires (UBA) de Universidad de Buenos Aires

id	I28-R145-HWA_5946
record_format	dspace
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-145
collection	Repositorio Digital de la Universidad de Buenos Aires (UBA)
language	Español
orig_language_str_mv	spa
topic	Porfirias Porfiria Aguda Intermitente Farmacogenética CYP-450 CYP3A4 CYP3A5 AKR1D1 Ciencias de la vida
spellingShingle	Porfirias Porfiria Aguda Intermitente Farmacogenética CYP-450 CYP3A4 CYP3A5 AKR1D1 Ciencias de la vida Sánchez Temiño, Victoria Emilia Porfirias agudas y polimorfismos de las enzimas que metabolizan fármacos
topic_facet	Porfirias Porfiria Aguda Intermitente Farmacogenética CYP-450 CYP3A4 CYP3A5 AKR1D1 Ciencias de la vida
description	Acute porphyrias (AP) are a group of hepathic pathologies characterized by the accumulation of porphyrins and their precursors. They usually manifest at puberty (more\noften in women), and include the New Acute Porphyria (NAP), Acute Intermittent\nPorphyria (AIP), Variegata Porphyria (VP) and the Hereditary Copro Porphyria (HCP) (Thunell et al., 2007). All of them have sudden neurovisceral manifestations, which are\ncommonly known as acute attack or crisis, which are often confused with other\npathologies. These attacks are triggered by exposure to different factors such as fasting, stress, hormones and commonly used medications. Many hypotheses try to explain the\nvariability in the prediction of the porphyrinogenicity of drugs, among which is the genetic polymorphism of the CYP-450 enzymes. In the this work we wanted to verify if the difference in the triggering or not of the acute crises in AIP patients was given by some of the most frequent polymorphisms and clinical significant of the enzymes of the CYP3A\nfamily (CYP3A4 * 22 and CYP3A5 * 3), or even by a difference in the expression of them, given by the AKR1D1. Also, the allelic and phenotypic frequencies of the polymorphisms analyzed were determined for argentinian population with and without\nAIP.\nResults: Both allelic frequencies and genotypic frequencies found in the AIP population are very similar to those of the healthy argentinian population. So when analyzed statistically with the X2 test (p <0.05), it was not a surprise founding out that there is no\ntrend of the AIP population to any SNP. Therefore, the genetic polymorphisms analyzed do not explain the interindividual variability that exists in these patients when an acute crises arrise. Another interesting conclusion obtained from this study is that there is a\nsignificant amount of extensive metabolizers compared to poor metabolizers in the\nhealthy argentinian population. This is extremely important when adjusting the dose of numerous drugs that are metabolized by this path, since these patients may be receiving or have received at first a subtherapeutic dose for their threatment.
author2	Gerez, Esther Noemí
author_facet	Gerez, Esther Noemí Sánchez Temiño, Victoria Emilia
format	Tesis de maestría Tesis de maestría acceptedVersion
author	Sánchez Temiño, Victoria Emilia
author_sort	Sánchez Temiño, Victoria Emilia
title	Porfirias agudas y polimorfismos de las enzimas que metabolizan fármacos
title_short	Porfirias agudas y polimorfismos de las enzimas que metabolizan fármacos
title_full	Porfirias agudas y polimorfismos de las enzimas que metabolizan fármacos
title_fullStr	Porfirias agudas y polimorfismos de las enzimas que metabolizan fármacos
title_full_unstemmed	Porfirias agudas y polimorfismos de las enzimas que metabolizan fármacos
title_sort	porfirias agudas y polimorfismos de las enzimas que metabolizan fármacos
publisher	Facultad de Farmacia y Bioquímica
publishDate	2019
url	http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_5946 http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_5946.dir/5946.PDF
work_keys_str_mv	AT sanchezteminovictoriaemilia porfiriasagudasypolimorfismosdelasenzimasquemetabolizanfarmacos
_version_	1766017556250886144
spelling	I28-R145-HWA_59462022-04-12 Acute porphyrias (AP) are a group of hepathic pathologies characterized by the accumulation of porphyrins and their precursors. They usually manifest at puberty (more\noften in women), and include the New Acute Porphyria (NAP), Acute Intermittent\nPorphyria (AIP), Variegata Porphyria (VP) and the Hereditary Copro Porphyria (HCP) (Thunell et al., 2007). All of them have sudden neurovisceral manifestations, which are\ncommonly known as acute attack or crisis, which are often confused with other\npathologies. These attacks are triggered by exposure to different factors such as fasting, stress, hormones and commonly used medications. Many hypotheses try to explain the\nvariability in the prediction of the porphyrinogenicity of drugs, among which is the genetic polymorphism of the CYP-450 enzymes. In the this work we wanted to verify if the difference in the triggering or not of the acute crises in AIP patients was given by some of the most frequent polymorphisms and clinical significant of the enzymes of the CYP3A\nfamily (CYP3A4 * 22 and CYP3A5 * 3), or even by a difference in the expression of them, given by the AKR1D1. Also, the allelic and phenotypic frequencies of the polymorphisms analyzed were determined for argentinian population with and without\nAIP.\nResults: Both allelic frequencies and genotypic frequencies found in the AIP population are very similar to those of the healthy argentinian population. So when analyzed statistically with the X2 test (p <0.05), it was not a surprise founding out that there is no\ntrend of the AIP population to any SNP. Therefore, the genetic polymorphisms analyzed do not explain the interindividual variability that exists in these patients when an acute crises arrise. Another interesting conclusion obtained from this study is that there is a\nsignificant amount of extensive metabolizers compared to poor metabolizers in the\nhealthy argentinian population. This is extremely important when adjusting the dose of numerous drugs that are metabolized by this path, since these patients may be receiving or have received at first a subtherapeutic dose for their threatment. Fil: Sánchez Temiño, Victoria Emilia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Buenos Aires, Argentina Gerez, Esther Noemí Facultad de Farmacia y Bioquímica Rossetti, María Victoria Sánchez Temiño, Victoria Emilia 2019-05-16 Las Porfirias agudas (PA) son un grupo de patologías hepáticas caracterizadas por la acumulación de porfirinas y sus precursores. Suelen manifestarse en la pubertad (más frecuentemente en mujeres), y comprenden la Nueva Porfiria Aguda (NPA), la Porfiria Aguda Intermitente (PAI), la Porfiria Variegata (PV) y la Copro Porfiria Hereditaria\n(CPH) (Thunell et al., 2007). Todas ellas poseen manifestaciones neuroviscerales súbitas,\nlo que comúnmente se conoce como ataque o crisis aguda, que suelen confundirse con\notras patologías. Estos ataques se desencadenan por exposición a diferentes factores como ayuno, estrés, hormonas y medicamentos de uso habitual. Muchas hipótesis tratan de explicar la variabilidad en la predicción de la porfirogenicidad de los fármacos, entre ellas está el polimorfismo genético de las enzimas del CYP-450. En el presente trabajo se quiso comprobar si la diferencia en el desencadenamiento o no de las crisis agudas en los pacientes PAI estaba dada por algunos de los polimorfismos más frecuentes y de mayor\nsignificancia clínica de las enzimas de la familia CYP3A (CYP3A422 y CYP3A53), o por una diferencia en el grado de su expresión, dada por la AKR1D1. Asimismo, se\ndeterminaron las frecuencias alélicas y fenotípicas de los polimorfismos analizados para la población tanto argentina con PAI como sin PAI.\nResultados: Tanto las frecuencias alélicas como las frecuencias genotípicas halladas en la\npoblación con PAI son muy similares a las de la población argentina sana. Por lo que cuando se analizó estadísticamente con la prueba de X2 (p<0.05), no fue una sorpresa que se comprobara que no hay una mayor o menor tendencia de la población PAI a uno u\notro SNP. Por lo que los polimorfismos genéticos analizados no explican la variabilidad interindividual que existe en estos pacientes frente a la manifestación de crisis agudas.\nOtra conclusión interesante que se obtuvo del presente trabajo, es que existe un aumento significativo de metabolizadores rápidos en detrimento de los metabolizadores pobres en\nla población argentina sana. Esto resulta sumamente importante al momento de ajustar la dosis de numerosos fármacos que se metabolizan por esta vía, ya que esos pacientes\npodrían estar recibiendo o haber recibido en sus inicios una dosis subterapéutica. application/pdf Cotignola, Javier Rossetti, Liliana Hocht, Christian Porfirias Porfiria Aguda Intermitente Farmacogenética CYP-450 CYP3A4 CYP3A5 AKR1D1 spa Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/2.5/ar/ Ciencias de la vida Porfirias agudas y polimorfismos de las enzimas que metabolizan fármacos info:eu-repo/semantics/masterThesis info:ar-repo/semantics/tesis de maestría info:eu-repo/semantics/acceptedVersion http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_5946 http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_5946.dir/5946.PDF

Porfirias agudas y polimorfismos de las enzimas que metabolizan fármacos

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