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    PowerPoint Slides English Spanish Translation

    Common Pharmacologic Interactions in Palliative Care Video Transcript

    Interacciones farmacolgicas comunes en los cuidados paliativos Transcripcin del video

    Professional Oncology Education Common Pharmacologic Interactions in Palliative Care Time: 33:41

    Educacin Oncolgica Profesional Interacciones farmacolgicas comunes en los cuidados paliativos Duracin: 33:41

    Holly M. Holmes, M.D. Associate Professor Department of General Internal Medicine The University of Texas MD Anderson Cancer Center

    Dra. Holly M. Holmes Profesora Asociada Departamento de Medicina Interna General MD Anderson Cancer Center de la Universidad de Texas

    Hi. My name is Holly Holmes, and Im an Associate Professor in the Department of General Internal Medicine at The University of Texas MD Anderson Cancer Center. I am going to talk about common pharmacologic interactions in palliative care.

    Hola, mi nombre es Holly Holmes y soy profesora asociada del Departamento de Medicina Interna General en el MD Anderson Cancer Center de la Universidad de Texas. Hoy hablar de las interacciones farmacolgicas ms comunes en los cuidados paliativos.

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    First, I want to mention that I have no financial relationships, arrangements, or affiliations. And this presentation will not include discussion of investigational or off-label use of any product. I would like to acknowledge the use of my slides from Dr. Mary Lynn McPherson who is a Professor in Pharmacy at The University of Maryland.

    En primer lugar, quiero mencionar que no tengo relaciones financieras, acuerdos o afiliaciones. Esta presentacin no incluir ninguna discusin del uso experimental o con fines de investigacin de ningn producto. Me gustara agradecer el uso de las diapositivas a la Dra. Mary Lynn McPherson, quien es profesora de Farmacia en la Universidad de Maryland.

    Upon completing this module, participants will be able to define the cytochrome P450 system and identify what is a substrate, an inhibitor, and an inducer; understand the role of cytochrome P450 enzymes in drug interactions; and identify clinically relevant drug interactions that involve medications commonly used in palliative care.

    Al completar este mdulo, los participantes podrn definir el sistema del citocromo P450 e identificar qu es un sustrato, un inhibidor y un inductor; comprender la funcin de las enzimas del citocromo P450 en las interacciones entre medicamentos; e identificar las interacciones clnicamente relevantes entre medicamentos que involucran los que comnmente se utilizan en cuidados paliativos.

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    We are really going to be focusing mostly on pharmacokinetic interactions in this lecture. That includes absorption, distribution, metabolism, and excretion. But were going to be focusing mostly on metabolism. And pharmacokinetic really pertains to what the body does to a drug. We will also talk a little bit about pharmacodynamic interactions and thats what the drug does to the body. So the action of the drug once it reaches its target or receptor in the body. And were really not going to talk at all about pharmaceutical interactions, but those are important interactions related to the preparation of a drug including inactive components, solvents, etc.

    En esta disertacin nos concentraremos en las interacciones farmacocinticas, que incluyen absorcin, distribucin, metabolismo y excrecin, pero principalmente en el metabolismo. La farmacocintica se refiere al efecto del organismo sobre un frmaco. Tambin hablar brevemente de las interacciones farmacodinmicas, que son los efectos de los frmacos sobre el organismo, es decir, la accin del medicamento una vez que alcanza su objetivo o receptor en el organismo. No me referir a las interacciones farmacuticas, aunque son importantes porque estn relacionadas con la preparacin de un medicamento, incluidos sus componentes inactivos, disolventes, etc.

    So drug metabolism in the liver is characterized by two phases of enzymatic reactions. And the purpose of these reactions is to make the drug more water soluble to facilitate its elimination from the body. Phase I or biotransformation interactions involve oxidation, hydroxylation, reduction, and hydrolysis. And these are the ones were going to be focusing on with the cytochrome P450 enzyme system. It involves chemical modification to add a functional group after which the drug could either be eliminated or further metabolized in Phase II reactions. Phase II reactions involve conjugation where a functional group is added. Those functional groups could involve acetylation, glucuronidation, sulfation, methylation, and after that happens the drug gets eliminated.

    El metabolismo del medicamento en el hgado se caracteriza por dos fases de reacciones enzimticas. El propsito de estas reacciones es hacer el medicamento ms soluble en agua a fin de facilitar su eliminacin del organismo. La fase I o interacciones de biotransformacin incluyen oxidacin, hidroxilacin, reduccin e hidrlisis. Nos concentraremos en estas en referencia al sistema enzimtico del citocromo P450. La biotransformacin incluye una modificacin qumica a fin de agregar un grupo funcional para que el medicamento pueda ser eliminado o metabolizado ulteriormente en las reacciones de la fase II. Estas reacciones incluyen la conjugacin, en donde se aade un grupo funcional. Los grupos funcionales son acetilacin, glucuronidacin, sulfatacin y metilacin. Despus de estas reacciones, el medicamento es eliminado.

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    Cytochrome P450 is a super family of enzymes that is the terminal oxidase of this whole oxidation system for Phase I drug reactions. These enzymes are part of a cascade that shuttles electrons from molecular oxygen to a drug to oxidize the drugs. Cytochrome means colored cell and the enzymes --- Cytochrome P450 enzymes contain iron which gives the liver its red color. The P450 refers to the fact that Cytochrome P450 enzymes absorb a very characteristic wave length, 450 nanometers of UV light, when exposed to carbon monoxide. You dont really need to know that for drug interactions but it is interesting. So as shown in the figure the enzymes function in the cascade of oxidation reduction --- reduction reactions that depends on ox --- oxygen being present as well as NADPH and Cytochrome reductase. And at the end the drug has a hydroxylated group in this example.

    El citocromo P450 es una superfamilia de enzimas que es la oxidasa terminal de este sistema de oxidacin para las reacciones entre medicamentos en la fase I. Estas enzimas son parte de una cascada que transporta electrones de oxgeno molecular a un medicamento para oxidarlo. Citocromo significa clula coloreada y las enzimas del citocromo P450 contienen hierro, que otorga al hgado su color rojo. P450 se refiere al hecho de que las enzimas de este citocromo absorben una longitud de onda muy caracterstica luz UV de 450 nanmetros cuando son expuestas al monxido de carbono. No necesitamos saber esto para comprender la interaccin entre medicamentos, pero es interesante. Tal como se muestra en la figura, las enzimas funcionan en la cascada de reacciones de oxidacin y reduccin que dependen de la presencia de oxgeno, as como de NADPH y citocromo reductasa. En este ejemplo, al finalizar el proceso, el medicamento tiene un grupo hidroxilado.

    So as I mentioned, the P450 system is a very large, diverse super family of those iron containing proteins. And its found in anything from mammals, birds, fish, sea squirts, sea urchins, all the way to bacteria and archaea. So even the most --- the most simple single cellular organisms have cytochrome P450 enzymes. The P450 system is the bulk of drug metabolizing enzymes. So most drugs are metabolized through this system. But the P450 enzymes are also used to make cholesterol, steroids, and other lipids like prostacyclins or thromboxane A2.

    Como ya mencion, el sistema P450 es una amplia y diversa superfamilia de protenas que contienen hierro. Se encuentra en cualquier organismo, desde mamferos, aves, peces, ascidias y erizos de mar hasta bacterias y arqueas. Incluso los organismos celulares individuales ms simples tienen enzimas del citocromo P450. El sistema P450 constituye la mayor parte de las enzimas que metabolizan medicamentos. Esto quiere decir que la mayora de los medicamentos se metabolizan a travs de este sistema. Las enzimas P450 tambin se utilizan para sintetizar colesterol, esteroides y otros lpidos como prostaciclinas y tromboxano A2.

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    Cytochrome P450s were named by molecular biologists and protein chemists. Their name really does not have a functional implication. The enzymes are named according to families that are defined primarily by the similarity in their amino acid sequence. So for example, to look at the naming for cytochrome P450 2D6. Cytochrome CYP is the root in --- implying that its a cytochrome P450 enzyme, 2 is the genetic family, D is the genetic sub-family, 6 is the specific gene and all of the isoenzymes in the same family have at least 40% structural similarity. And then the same sub-family have 60% structural similarity. But again the amino acid sequence and structural similarity has no functional implication. So for example, cytochrome P450 2C19 is the principal enzyme that metabolizes omeprazole and it is very closely related to 2C9 but 2C9 has no activity to metabolize omeprazole.

    Los citocromos P450 fueron denominados por bilogos moleculares y qumicos de protenas, y su nombre no tiene ninguna implicacin funcional. Las enzimas reciben sus nombres de acuerdo a las familias, que son definidas principalmente por la similitud en su secuencia de aminocidos. Por ejemplo, analicemos la nomenclatura del citocromo P450 2D6. El citocromo CYP es la raz, lo qu