<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>1137-6627</journal-id>
<journal-title><![CDATA[Anales del Sistema Sanitario de Navarra]]></journal-title>
<abbrev-journal-title><![CDATA[Anales Sis San Navarra]]></abbrev-journal-title>
<issn>1137-6627</issn>
<publisher>
<publisher-name><![CDATA[Gobierno de Navarra. Departamento de Salud]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S1137-66272006000300007</article-id>
<title-group>
<article-title xml:lang="es"><![CDATA[Interacción entre fármacos y plantas medicinales]]></article-title>
<article-title xml:lang="en"><![CDATA[Interaction between medicines and medicinal plants]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Tres]]></surname>
<given-names><![CDATA[J.C.]]></given-names>
</name>
<xref ref-type="aff" rid="A01"/>
</contrib>
</contrib-group>
<aff id="A01">
<institution><![CDATA[,Centro de Farmacovigilancia de Navarra  ]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>08</month>
<year>2006</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>08</month>
<year>2006</year>
</pub-date>
<volume>29</volume>
<numero>2</numero>
<fpage>233</fpage>
<lpage>252</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://scielo.isciii.es/scielo.php?script=sci_arttext&amp;pid=S1137-66272006000300007&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.isciii.es/scielo.php?script=sci_abstract&amp;pid=S1137-66272006000300007&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.isciii.es/scielo.php?script=sci_pdf&amp;pid=S1137-66272006000300007&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="es"><p><![CDATA[En los últimos años, el consumo de plantas medicinales ha experimentado un notable incremento en la sociedad española. Esto ha podido ser debido a que en algunos casos, se ha demostrado su eficacia en el tratamiento de determinadas patologías y a la percepción, errónea, de la inocuidad de estos productos. Las plantas medicinales se comportan como verdaderos fármacos ya que las sustancias químicas que las componen pueden tener una actividad biológica en humanos. Por esta razón, la administración conjunta con "fármacos convencionales" puede producir variaciones en la magnitud de su efecto. Este tipo de interacciones, al igual que las producidas entre dos o más fármacos pueden producirse por mecanismos farmacocinéticos, si afectan a procesos de absorción, distribución, metabolismo y excreción o farmacodinámicos, si afectan al resultado de su acción farmacológica. En la literatura médica son escasos los artículos y notificaciones de casos sobre los efectos adversos e interacciones que afectan a las plantas medicinales, lo que probablemente refleja una infranotificación de estos fenómenos. Si a esto añadimos la falta de datos experimentales y de estudios controlados, la percepción de su prevalencia es difícil o casi imposible. Este trabajo expone, ordenados según se explica más adelante, los hallazgos de una exhaustiva revisión de la literatura médica con el fin de que el lector conozca su existencia, sin entrar en otras consideraciones, como por ejemplo el grado de evidencia, que serán sujeto de próximos trabajos.]]></p></abstract>
<abstract abstract-type="short" xml:lang="en"><p><![CDATA[In recent years there has been a notable increase in the consumption of medicinal plants in Spanish society. This might be due to the fact that in some cases they have shown themselves to be efficient in treating certain pathologies and to the erroneous perception that these products are innocuous. Medicinal plants behave as authentic medicines since the chemical substances of which they are formed can have a biological activity in humans. For this reason, their joint administration with "conventional medicines" can produce variations in the magnitude of the effect. This type of interaction, just like those produced between two or more medicines, can produce pharmacokinetic mechanisms if they affect the processes of absorption, distribution, metabolism and excretion, or pharmacodynamic mechanisms if they affect the result of the pharmacological action. In the medical literature there are few articles and notifications of cases concerning the adverse effects and interactions that affect medicinal plants, which probably reflects an under-notification of these phenomena. If we add to this the lack of experimental data and controlled studies, perception of their prevalence is difficult or nearly impossible. This article sets out, in an order that will be explained later, the findings of an exhaustive review of the medical literature with the aim of making its existence known to the reader, without going into other considerations, such as the degree of evidence for example, which will be the subject of forthcoming articles.]]></p></abstract>
<kwd-group>
<kwd lng="es"><![CDATA[Plantas medicinales]]></kwd>
<kwd lng="es"><![CDATA[Fitoterapia]]></kwd>
<kwd lng="es"><![CDATA[Interacciones]]></kwd>
<kwd lng="es"><![CDATA[Interacciones con fármacos]]></kwd>
<kwd lng="en"><![CDATA[Medicinal plants]]></kwd>
<kwd lng="en"><![CDATA[Herbal medicine]]></kwd>
<kwd lng="en"><![CDATA[Interactions]]></kwd>
<kwd lng="en"><![CDATA[Interactions with medicines]]></kwd>
</kwd-group>
</article-meta>
</front><body><![CDATA[ <p align="right"><font face="Verdana" size="2"><b>REVISIONES</b></font></p>     <p>&nbsp;</p>     <p><font face="Verdana" size="2"><a name="top"></a></font><font face="Verdana" size="4"><b>Interacción entre fármacos y plantas medicinales</b></font></p>     <p><font face="Verdana" size="4"><b>Interaction between medicines and medicinal plants</b></font></p>     <p>&nbsp;</p>     <p>&nbsp;</p>     <p><font face="Verdana" size="2"><b>J.C. Tres</b></font></p>     <p><font face="Verdana" size="2">Centro de Farmacovigilancia de Navarra.</font></p>     <p><font face="Verdana" size="2"><a href="#back">Correspondencia</a></font></p>     <p>&nbsp;</p>     ]]></body>
<body><![CDATA[<p>&nbsp;</p> <hr size="1">     <p><font face="Verdana" size="2"><b>RESUMEN</b></font></p>     <p><font face="Verdana" size="2">En los últimos años, el consumo de plantas medicinales ha experimentado un notable incremento en la sociedad española. Esto ha podido ser debido a que en algunos casos, se ha demostrado su eficacia en el tratamiento de determinadas patologías y a la percepción, errónea, de la inocuidad de estos productos.    <br> Las plantas medicinales se comportan como verdaderos fármacos ya que las sustancias químicas que las componen pueden tener una actividad biológica en humanos. Por esta razón, la administración conjunta con “fármacos convencionales” puede producir variaciones en la magnitud de su efecto. Este tipo de interacciones, al igual que las producidas entre dos o más fármacos pueden producirse por mecanismos farmacocinéticos, si afectan a procesos de absorción, distribución, metabolismo y excreción o farmacodinámicos, si afectan al resultado de su acción farmacológica.    <br> En la literatura médica son escasos los artículos y notificaciones de casos sobre los efectos adversos e interacciones que afectan a las plantas medicinales, lo que probablemente refleja una infranotificación de estos fenómenos. Si a esto añadimos la falta de datos experimentales y de estudios controlados, la percepción de su prevalencia es difícil o casi imposible.    <br> Este trabajo expone, ordenados según se explica más adelante, los hallazgos de una exhaustiva revisión de la literatura médica con el fin de que el lector conozca su existencia, sin entrar en otras consideraciones, como por ejemplo el grado de evidencia, que serán sujeto de próximos trabajos.</font></p>     <p> <font face="Verdana" size="2"><b>Palabras clave. </b>  Plantas medicinales. Fitoterapia. Interacciones. Interacciones con fármacos.</font></p> <hr size="1">     <p> <font face="Verdana" size="2"><b>ABSTRACT</b></font></p>     <p> <font face="Verdana" size="2">In recent years there has been a notable increase in the consumption of medicinal plants in Spanish society. This might be due to the fact that in some cases they have shown themselves to be efficient in treating certain pathologies and to the erroneous perception that these products are innocuous.    <br> Medicinal plants behave as authentic medicines since the chemical substances of which they are formed can have a biological activity in humans. For this reason, their joint administration with “conventional medicines” can produce variations in the magnitude of the effect. This type of interaction, just like those produced between two or more medicines, can produce pharmacokinetic mechanisms if they affect the processes of absorption, distribution, metabolism and excretion, or pharmacodynamic mechanisms if they affect the result of the pharmacological       action.    ]]></body>
<body><![CDATA[<br> In the medical literature there are few articles and notifications of cases concerning the adverse effects and interactions that affect medicinal plants, which probably reflects an under-notification of these phenomena. If we add to this the lack of experimental data and controlled studies, perception of their prevalence is difficult or nearly impossible.    <br> This article sets out, in an order that will be explained later, the findings of an exhaustive review of the medical literature with the aim of making its existence known to the reader, without going into other considerations, such as the degree of evidence for example, which will be the subject of forthcoming articles.</font></p>     <p> <b><font face="Verdana" size="2">Key words.</font></b> <font face="Verdana" size="2"> Medicinal plants. Herbal medicine. Interactions. Interactions with medicines.</font></p> <hr size="1">        <p>&nbsp;</p>     <p><b><font face="Verdana" size="3">Introducción</font></b></p>     <p><font face="Verdana" size="2">El consumo de plantas medicinales (hierbas medicinales) o fitoterapia constituye uno de los capítulos más importantes dentro del variado mundo de la medicina alternativa y complementaria. En la práctica supone un segmento no controlado de la terapia farmacológica, dada la posibilidad de efectos terapéuticos, tóxicos o interacciones que pueden causar los principios activos de las plantas y porque su utilización ha crecido espectacularmente en los paises       desarrollados<sup>1-3</sup>.</font></p>     <p>       <font face="Verdana" size="2">       En España, podemos hacernos una idea del consumo de plantas medicinales a través de los resultados publicados tras realizar encuestas a pacientes en el ámbito de atención primaria, donde el 19,6% de los pacientes reconoce su       consumo<sup>4</sup>; consultas externas de digestivo, en donde un 34,7% de las personas encuestadas había consumido alguna vez plantas       medicinales<sup>5</sup>; y en las consultas preanestésicas, con un 35,73% de los pacientes consumiendo algún tipo de planta       medicinal<sup>6</sup>. Esto ha sido debido, en gran parte, a la creencia, en algunos casos demostrada con estudios clínicos, de que algunas plantas como el ajo o el ginkgo pueden ser beneficiosas en el tratamiento de alteraciones cardiovasculares, el hipérico es eficaz en el tratamiento de la depresión no grave, y a la errónea percepción de la inocuidad de estos productos.</font></p>    <p>       <font face="Verdana" size="2">       Con el reconocimiento de estos beneficios aparece el reconocimiento del riesgo, cuyo conocimiento se ve dificultado porque las plantas, crudas o extractadas pueden contener mezclas complejas de sustancias químicas orgánicas que incluyen: ácidos grasos, esteroles, alcaloides, flavonoides, glicósidos, saponinas, taninos y terpenos. Cualquiera de los componentes mencionados puede tener una actividad biológica en humanos. Además, el procesamiento de estas plantas utilizando medios físicos como calentamiento o hervido puede alterar la actividad farmacológica de los constituyentes orgánicos, que también pueden verse afectados en su concentración dependiendo de factores ambientales de cultivo o localización como características del suelo, humedad y temperatura ambiente, altitud, etc. y de la parte del vegetal utilizado (hojas, tallos, flores, raíces, semillas).</font></p>    <p>       <font face="Verdana" size="2">       Por su actividad farmacológica las plantas medicinales podrían interaccionar con fármacos convencionales. Los mecanismos por los que se producen son complejos y, a menudo, hay más de uno implicado. Pueden dividirse en farmacocinéticos o farmacodinámicos, si afectan a procesos de absorción, distribución, metabolismo y excreción, o si afectan al sitio de acción o su acción farmacológica.</font></p>    <p>       <font face="Verdana" size="2">       La mayoría de las interacciones entre plantas y fármacos que afectan a la absorción lo hacen reduciendo los niveles del fármaco, bien sea por alteración del pH digestivo, afectando la motilidad o por la formación de complejos no absorbibles. El desplazamiento de fármacos unidos a proteínas incrementa los valores de fármaco libre, afectando a la distribución en tejidos, siendo de particular importancia en grupos farmacológicos como antiepilépticos, aunque no se han notificado casos clínicos. El metabolismo de fármacos es el mecanismo más importante de interacciones y una buena muestra de ello son los fármacos que ven afectados sus niveles cuando se administran conjuntamente con hipérico, un inductor del citocromo P450.</font></p>    ]]></body>
<body><![CDATA[<p>       <font face="Verdana" size="2">       Pacientes con afecciones renales pueden acumular fármacos que se eliminan por excreción renal y plantas con propiedades diuréticas supuestamente acelerarían la excreción, al igual que las que pueden alterar el pH urinario podrían influir en las concentraciones urinarias de fármacos que son ácidos o bases débiles.</font></p>    <p>       <font face="Verdana" size="2">       Las interacciones farmacodinámicas resultan de efectos aditivos, sinérgicos o antagónicos entre fármacos y plantas con las mismas propiedades farmacológicas. Por ejemplo, plantas con propiedades sedantes, anticoagulantes o hipotensoras podrían incrementar la acción de fármacos con estas características. Aunque la importancia clínica de estas potenciales interacciones todavía no se ha establecido, sí hay varias notificaciones de síndrome serotoninérgico relacionado con antidepresivos e hipérico.</font></p>    <p>       <font face="Verdana" size="2">       Este artículo aborda las interacciones entre fármacos y plantas medicinales ordenando, tanto las revisiones como las notas y casos clínicos que hemos obtenido tras examinar la literatura, en grupos terapéuticos farmacológicos con los consiguientes fármacos más relevantes. Las primeras líneas del texto de cada apartado recogen los datos o casos más contrastados. Finalmente y para hacer más amena la consulta y divulgación hemos elaborado unas tablas que resumen el texto de los principales grupos terapéuticos farmacológicos       (<a href="/img/revistas/asisna/v29n2/revision_t1-7.pdf" target="_blank">Tablas       1-7</a>) y otra más extensa con las plantas medicinales ordenadas alfabéticamente y sus correspondientes interacciones       (<a href="/img/revistas/asisna/v29n2/revision_t8.pdf" target="_blank">Tabla       8</a>).</font></p>    <p>       &nbsp;</p>    <p><b><font face="Verdana" size="3">Métodos</font></b></p>    <p><font face="Verdana" size="2">Se hizo una búsqueda bibliográfica, hasta diciembre de 2004, en las siguientes bases de datos electrónicas o computarizadas:</font></p>    <p>       <font face="Verdana" size="2">       – Iowa Drug Information Service (IDIS)</font></p>    <p>       <font face="Verdana" size="2">       – Micromedex system (Thomson; Drugdex)</font></p>    <p>       <font face="Verdana" size="2">       – Medline vía plataforma WebSpirs</font></p>    <p>       <font face="Verdana" size="2">       – Embase (Evidence Based Medicine) via plataforma WebSpirs</font></p>    ]]></body>
<body><![CDATA[<p>       <font face="Verdana" size="2">       – Indice Médico Español (IME)</font></p>    <p>       <font face="Verdana" size="2">       – Uptodate</font></p>    <p>       <font face="Verdana" size="2">       – The Cochrane Library plus</font></p>    <p>       <font face="Verdana" size="2">       – Clinical Evidence</font></p>    <p>       <font face="Verdana" size="2">       Se consultaron los siguientes textos y documentos de referencia:</font></p>    <p>       <font face="Verdana" size="2">       – Blumenthal M, ed. The Complete Commission E. Monographs. Boston: Integr Medical       Comm, 1998</font></p>    <p>       <font face="Verdana" size="2">       – Gruenwald J, ed. PDR for Herbal Medicines. Medical Economics Company, 2000</font></p>    <p>       <font face="Verdana" size="2">       – Brinker F, ed. Herb contraindications and Drug interactions. Eclectic Medical       Publications, 1998</font></p>    <p>       <font face="Verdana" size="2">       – European Scientific Cooperative on Phytotherapy. Monographs On The Medicinal Uses of Plant Drugs</font></p>    <p>       <font face="Verdana" size="2">       – WHO Monographs on Selected Medicinal Plants</font></p>    ]]></body>
<body><![CDATA[<p>       <font face="Verdana" size="2">       – American Herbal Pharmacopocia Monographs. American Botanical Council</font></p>    <p>       <font face="Verdana" size="2">       – Catálogo de Plantas Medicinales. Consejo General de Colegios Oficiales de Farmacéuticos, 2004</font></p>    <p>       <font face="Verdana" size="2">       – Font de Quer P, ed. Plantas Medicinales. El Dioscoridos renovado. Editorial Labor. Barcelona</font></p>    <p>       <font face="Verdana" size="2">       – Zucchero FJ, Megan MJ, Somuner CD, eds. Evaluations of Drug Interactions. First       Databank, 2001</font></p>    <p>       <font face="Verdana" size="2">       – Stockhey IH, ed. Interacciones farmacológicas. Pharma Editores, 2004</font></p>    <p>       <font face="Verdana" size="2">       Utilizamos los siguientes términos médicos extraídos de MeSH database: <i> herbal medicine, herb, phytotherapy, interactions y drug interactions</i> (traducidos al castellano cuando se utilizó el IME).</font></p>    <p>       <font face="Verdana" size="2">       Se incluyen todos los datos y referencias relativas a interacciones plantas medicinales- fármacos independientemente de que se tratara de casos aislados, series de casos, ensayos clínicos u otros tipos de investigación en humanos, excluyendo (o haciendolos notar específicamente) los experimentos in vitro o con animales. Se exponen a continuación y en las tablas los resultados obtenidos en la búsqueda realizada durante los periodos de tiempo comentados y sin evaluar los niveles de evidencia.</font></p>    <p>       &nbsp;</p>    <p>       <b><font face="Verdana" size="3">Sangre y órganos hematopoyéticos</font></b></p>    <p>       <b><font face="Verdana" size="2">Agentes antitrombóticos</font></b></p>    ]]></body>
<body><![CDATA[<p>       <font face="Verdana" size="2">Hierba de San Juan (<i>Hypericum perforatum</i>): disminución del efecto anticoagulante de warfarina y fenprocumona por inducción del       CYP2C9<sup>7-9</sup>.</font></p>    <p>       <font face="Verdana" size="2">       Varios productos utilizados en la medicina tradicional china (Dong Quai, Danshen, Kangen-Karyn) podrían interaccionar con warfarina produciendo un incremento en el International normalized ratio (en adelante INR). El Kangen-Karyn contiene, entre otras cosas,       <i> Salvia       miltiorrhiza</i><sup>10,11</sup>, lo mismo que el Danshen<sup>12-14</sup>, mientras que el Dong Quai es angélica       (<i>Angelica sinensis</i>), ambas con propiedades anticoagulantes.</font></p>    <p>       <font face="Verdana" size="2">       El consumo de ajo (<i>Allium sativum</i>)<sup>15-18</sup>, jenjibre (<i>Zingiber       officinale</i>)<sup>15,19</sup>, ginkgo (<i>Ginkgo biloba</i>)<sup>15-20</sup> y ginseng (Panax ginseng)<sup>15,21</sup> ha sido relacionado con alteraciones en el INR, generalmente prolongándolo, aunque hay una notificación de reducción del efecto de la warfarina con ginseng       (<i>Panax quinquefolium</i>)<sup>22</sup>.</font></p>    <p>       <font face="Verdana" size="2">       También casos individuales de prolongación de INR con cambronera (<i>Lycium       barbarum</i>)<sup>23</sup>, boldo (<i>Peumus boldus</i>) y alholva (<i>Trigonella       foenun-graecum</i>) en asociación<sup>24</sup>, asociación de calabacera       (<i>Cucurbita pepo</i>) y palma enana o palmito salvaje (<i>Serenoa repens</i>)<sup>25</sup>.</font></p>    <p>       <font face="Verdana" size="2">       Se ha postulado que la zaragatona (<i>Plantago psyllium</i>) e ispagula (<i>Plantago       ovata</i>) podrían inhibir la absorción de       warfarina<sup>26</sup>.</font></p>    <p>       <font face="Verdana" size="2">       Existe una notificación en la literatura de interacción de warfarina con el fruto del mango en grandes       cantidades<sup>27</sup>, lo mismo que con cantidades elevadas de té verde<sup>28</sup>.</font></p>    <p>       <font face="Verdana" size="2">       Aunque no se han descrito interacciones, las plantas que contienen salicilatos como la ulmaria       (<i>Filipendula ulmaria</i>) y sauce (<i>Salix spp.</i>) deberían utilizarse con cuidado en pacientes anticoagulados, lo mismo que algunas plantas como melitoto       (<i>Melitotus officinalis</i>), haba tonca (<i>Dipteryx odoratum</i>) y asperilla       (<i>Galium odoratum</i>) que contienen derivados cumarínicos<sup>29-32</sup>.</font></p>    <p>       <font face="Verdana" size="2">       Existe un potencial efecto aditivo con hierbas que contienen salicilatos y con las que tienen actividad antiplaquetaria como ginseng       (<i>Panax ginseng</i>) o ginkgo (<i>Ginkgo biloba</i>)<sup>31-32</sup>.</font></p>    <p>       <font face="Verdana" size="2">       Teóricamente, la matricaria (<i>Tanacetum parthenium</i>), jengibre (<i>Zingiber       officinale</i>), kava (<i>Piper methysticum</i>) y dong quai, tienen efecto antiplaquetario in       vitro<sup>32</sup>.</font></p>    <p>       <font face="Verdana" size="2">       Se ha descrito un caso de interacción de fluindiona con ajo (<i>Allium       sativum</i>), resultando en un incremento del       INR<sup>33</sup>.</font></p>    ]]></body>
<body><![CDATA[<p>       <font face="Verdana" size="2">       Se ha descrito también un caso de hemorragia ocular en un paciente tratado con aspirina y ginkgo (Ginkgo biloba), aunque este último ha sido relacionado con       hemorragia<sup>34-36</sup>.</font></p>    <p>       &nbsp;</p>    <p><b><font face="Verdana" size="3">Sistema cardiovascular</font></b></p>    <p><b><font face="Verdana" size="2">Terapia cardíaca</font></b></p>    <p><font face="Verdana" size="2">Los laxantes que contienen sen (<i>Cassia senna</i> y otras <i> Cassia spp</i>), cáscara sagrada (<i>Rhamnus purshiana</i>) pueden producir hipokaliemia produciendo toxicidad por       digoxina<sup>29,32</sup>.</font></p>    <p>       <font face="Verdana" size="2">       Hay evidencia clínica de reducción en niveles de digoxina por hipérico       (<i>Hypericum perforatum</i>)<sup>34-37       </sup> y elevación de niveles de digoxina en tratamiento conjunto con ginseng siberiano       (<i>Eleutherococcus senticosus</i>)<sup>38,39</sup>.</font></p>    <p>       <font face="Verdana" size="2">       El espino blanco (<i>Crataegus spp.</i>) tiene efectos similares a los digitálicos, por lo que habría que controlar un posible       sinergismo<sup>40,41</sup>.</font></p>    <p>           <br>       <b><font face="Verdana" size="2">Antihipertensivos</font></b></p>    <p>       <font face="Verdana" size="2">La yohimbina (<i>Pausinystalia yohimbe</i>) puede antagonizar los efectos de guanabenz y metildopa por propiedades antiadrenérgicas       &#945;2<sup>42-46</sup>.</font></p>    ]]></body>
<body><![CDATA[<p>           <br>       <font face="Verdana" size="2"><b>Bloqueantes de canales del calcio</b></font></p>    <p>       <font face="Verdana" size="2">       Se ha notificado la teórica interacción entre nicardipino y ginkgo (<i>Ginkgo       biloba</i>) por inducción del CYP3A2 donde se metabolizan nicardipino, nifedipino y diltiazem, en       ratas<sup>47</sup>.</font></p>    <p>       <font face="Verdana" size="2">       Los antagonistas del calcio son sustratos del P450 isoenzima 3A4 por lo que, teóricamente, podrían ver influenciado su metabolismo por el hipérico<sup>48-50</sup>.</font></p>    <p>           <br>       <b><font face="Verdana" size="2">Agentes que actúan sobre el sistema       Renina-Angiotensina</font></b></p>    <p>       <font face="Verdana" size="2">       Existe potenciación del efecto hipotensivo del lisinopil por el ajo (Allium sativum) y de la tos por aplicación de una crema de capsaicina       (<i>Capsicum spp.</i>)<sup>51,52</sup>.</font></p>    <p>           <br>       <b><font face="Verdana" size="2">Agentes que reducen los lípidos séricos</font></b></p>    <p>       <font face="Verdana" size="2">       La inducción del CYP3A4 hepático e intestinal puede disminuir las concentraciones plasmáticas de simvastatina, que es extensivamente metabolizada en intestino por esta vía. Las concentraciones de pravastatina no se       modificaron<sup>53</sup>.</font></p>    ]]></body>
<body><![CDATA[<p>       &nbsp;</p>    <p><b><font face="Verdana" size="3">Sistema nervioso central</font></b></p>    <p><b><font face="Verdana" size="2">Anestésicos</font></b></p>    <p>       <font face="Verdana" size="2">       En un estudio hospitalario, entre pacientes estudiados y evaluados preoperatoriamente, más de la mitad de ellos consumían suplementos vitamínicos y hierbas medicinales, entre las que se encontraban ajo       (<i>Allium sativum</i>), ginkgo (<i>Ginkgo biloba</i>), hipérico (<i>Hypericum       perforatum</i>), efedra (<i>Ephedra sinnica</i>), equinácea (<i>Echinacea       purpurea</i>) laxantes antraquinónicos y regaliz (<i>Glycyrrhiza gylabra</i>), que podrían interactuar con fármacos utilizados en       anestesia<sup>54</sup>.</font></p>    <p>       <font face="Verdana" size="2">       El efecto de las hierbas medicinales en la respuesta a los anestésicos no ha sido evaluada todavía, por lo que se recomienda suspender su administración dos o tres semanas antes del procedimiento quirúrgico<sup>55</sup>. Los pacientes tomando ginkgo       (<i>Ginkgo biloba</i>), ginseng (<i>Panax ginseng</i>) y ajo (<i>Allium       sativum</i>) deberían abandonar el tratamiento ante la posibilidad de problemas hemorrágicos, aunque el riesgo no está establecido. También el hipérico       (<i>Hypericum perforatum</i>) podría interaccionar con fármacos usados en anestesia y la efedra       (<i>Ephedra sinnica</i>) puede incrementar la presión sanguínea y la frecuencia cardíaca<sup>56</sup>.</font></p>    <p>       <font face="Verdana" size="2">       Asimismo, la medicina tradicional china debería tenerse en cuenta en pacientes que van a recibir medicación anestésica<sup>57</sup>.</font></p>    <p>           <br>       <b><font face="Verdana" size="2">Analgésicos</font></b></p>    <p>       <font face="Verdana" size="2">Pueden encontrarse salicilatos en varias plantas, como por ejemplo en la corteza del sauce       (<i>Salix spp.</i>) y en la ulmaria (<i>Filipendula ulmaria</i>), aunque su potencial de toxicidad parece ser mucho menor que el de la aspirina. Los salicilatos pueden interactuar con trombolitícos y antiagregantes y, aunque no se suele recomendar el ajuste de dosis, deberían hacerse las mismas consideraciones para las hierbas que contienen       salicilatos<sup>58,59</sup>.</font></p>    <p>       <font face="Verdana" size="2">       El tamarindo (<i>Tamarindus indica</i>) puede incrementar la absorción de       aspirina<sup>60</sup>.</font></p>    ]]></body>
<body><![CDATA[<p>       <font face="Verdana" size="2">       Existe una notificación de hemorragia en un paciente que recibía rofecoxib y ginkgo (<i>Ginkgo biloba</i>)<sup>61</sup>.</font></p>    <p>           <br>       <b><font face="Verdana" size="2">Psicolépticos (Ansiolíticos)</font></b></p>    <p>       <font face="Verdana" size="2">Las benzodiacepinas sustratos del P450 3A4 pueden ver inhibido su metabolismo por el hipérico (<i>Hypericum perforatum</i>)<sup>48-50</sup>.</font></p>    <p>       <font face="Verdana" size="2">       Un paciente presentó coma por una posible interacción entre alprazolam y kava (<i>Piper methisticum</i>)<sup>62</sup>.</font></p>    <p>           <br>       <b><font face="Verdana" size="2">Psicolépticos (Antipsicóticos)</font></b></p>    <p>       <font face="Verdana" size="2">       Se han descrito dos casos de crisis en pacientes que tomaban aceite de onagro       (<i>Oenothera biennis</i>), que contiene ácido gamolénico, junto con       flufenacina<sup>63</sup>, ya que ambos disminuyen el umbral convulsivo.</font></p>    <p>       <font face="Verdana" size="2">       Muchas preparaciones de hierbas contienen polifenoles y taninos que podrían interaccionar con fenotiacinas, como en el caso de té y café<sup>64-66,</sup> disminuyendo los niveles plasmáticos y su acción       antipsicótica.</font></p>    <p>       <font face="Verdana" size="2">       Laxantes que contienen ispagula (<i>Plantago ovata</i>) o zaragatona (<i>Plantago       psyllium</i>) podrían disminuir los niveles de litio por disminución de su absorción<sup>67</sup>.</font></p>    ]]></body>
<body><![CDATA[<p>       <font face="Verdana" size="2">       Caso de toxicidad por litio con el uso concomitante de un compuesto diurético conteniendo junípero       (<i>Juniperus communis</i>), buchu (<i>Agathosma betulina</i>) equiseto (<i>Equisetum       arvense</i>), maíz (<i>Zea mays</i>), gayuba (<i>Arctostaphylos uva-ursi</i>), perejil       (<i>Petroselinum crispum</i>), entre       otros<sup>68</sup>.</font></p>    <p>           <br>       <b><font face="Verdana" size="2">Psicoanalépticos (Antidepresivos)</font></b></p>    <p>       <font face="Verdana" size="2">Potenciación del efecto serotoninérgico de los ISRS, por las propiedades serotoninérgicas del hipérico (<i>Hypericum perforatum</i>), habiéndose descrito casos de síndrome serotoninérgico con la planta medicinal sola o asociada a paroxetina, sertralina o       nefazodona<sup>69,70</sup>.</font></p>    <p>       <font face="Verdana" size="2">       Los alcaloides de la rauwolfia producen la liberación y deplección de los depósitos de noradrenalina, reduciendo la transmisión de las terminaciones nerviosas adrenérgicas, produciendo hipotensión y depresión. Si el paciente estaba en tratamiento con inhibidores de la MAO puede haber una liberación súbita de noradrenalina y serotonina con estimulación excesiva de los receptores con hipertensión y estimulación central. Si es absolutamente necesario utilizar inhibidores de la MAO y alcaloides de la rauwolfia, éstos deben administrarse antes que los inhibidores de la       MAO<sup>71</sup>.</font></p>    <p>       <font face="Verdana" size="2">       Existen, al menos, dos casos de insomnio y cefalea por fenelzina junto con ginseng       (<i>Panax ginseng</i>). El mecanismo es desconocido y debe tenerse en cuenta que los inhibidores de la MAO pueden producir estas reacciones por sí       solos<sup>72</sup>.</font></p>    <p>       <font face="Verdana" size="2">       Un caso de manía por fluoxetina al interaccionar con cannabis (<i>Cannabis       sativa</i>), posiblemente debido al efecto inhibidor de la recaptación de serotonina del       tetrahidrocanabinol<sup>73</sup>.</font></p>    <p>       <font face="Verdana" size="2">       Un caso de coma por posible interacción entre trazodona (antidepresivo sedante) y ginkgo       (<i>Ginkgo biloba</i>)<sup>74</sup>.</font></p>    <p>       <font face="Verdana" size="2">       Se han descrito casos de disminución de las concentraciones de amitriptilina achacables al hipérico       (<i>Hypericum perforatum</i>)<sup>75,76</sup>.</font></p>    <p>       <font face="Verdana" size="2">       Existe una comunicación acerca de una interacción beneficiosa de reserpina (derivado de la rauwolfia) y tricíclicos como imipramina y       desipramina<sup>77</sup>, reduciendo los síntomas depresivos.</font></p>    ]]></body>
<body><![CDATA[<p>       <font face="Verdana" size="2">       En estudios clínicos, los antidepresivos tricíclicos pueden incrementar la sensibilidad sobre el sistema nervioso, central y autonómico, de la yohimbina (<i>Pausinystalia yohimbe</i>), con varios casos de hipertensión<sup>78-80</sup>.</font></p>    <p>           <br>       <b><font face="Verdana" size="2">Antiparkinsonianos</font></b></p>    <p>       <font face="Verdana" size="2">El efecto de la levodopa podría verse reducido por la administración de alcaloides de la rauwolfia (como la reserpina) que altera la liberación de       neurotransmisores<sup>81</sup>.</font></p>    <p>       <font face="Verdana" size="2">       La administración de kava (<i>Piper methisticum</i>) puede reducir la eficacia de la levodopa en el tratamiento del Parkinson por su efecto antagónico sobre la       dopamina<sup>82</sup>.</font></p>    <p>       <font face="Verdana" size="2">       Se ha observado interacción entre prociclidina y la nuez de la areca (<i>Areca       catechu</i>), con aparición de un cuadro extrapiramidal en un paciente tratado con       flufenacina<sup>83</sup>.</font></p>    <p>           <br>       <b><font face="Verdana" size="2">Antiepilépticos</font></b></p>    <p>       <font face="Verdana" size="2">       Los aceites de onagro (<i>Oenothera biennis</i>) y de borraja (<i>Borago       officinalis</i>) contienen ácido gamolénico que puede disminuir el umbral convulsivo. Si se administran con fármacos que también actúan en este sentido, como flufenacina, podrían       interactuar<sup>63</sup>.</font></p>    <p>       <font face="Verdana" size="2">       El hipérico (<i>Hypericum perforatum</i>), a través de su acción inductora del citocromo P450, podría interferir en el aclaramiento de algunos antiepilépticos, aunque existe un trabajo en el que no existe interferencia del aclaramiento de carbamacepina por el hipérico       (<i>Hypericum perforatum</i>)<sup>84</sup>.</font></p>    ]]></body>
<body><![CDATA[<p>       <font face="Verdana" size="2">       Plantas con propiedades sedantes como valeriana (<i>Valeriana spp.</i>), pasionaria       (<i>Passiflora spp.</i>) y kava (<i>Piper methysticum</i>) podrían potenciar la medicación antiepiléptica<sup>85-88</sup>.</font></p>    <p>       <font face="Verdana" size="2">       Los estimulantes que contienen cafeína podrían exacerbar la producción de crisis al disminuir el umbral       convulsivo<sup>89</sup>.</font></p>    <p>       <font face="Verdana" size="2">       Los aceites esenciales están presentes en muchas hierbas y especias y contienen compuestos epileptogénicos como cineol, canfor y       fenchona<sup>90,91</sup>.</font></p>    <p>       <font face="Verdana" size="2">       El ginkgo (<i>Ginkgo biloba</i>) puede reducir el umbral convulsivo<sup>92-95</sup>.</font></p>    <p>       &nbsp;</p>    <p><b><font face="Verdana" size="3">Sistema genitourinario y hormonas sexuales</font></b></p>    <p><b><font face="Verdana" size="2">Hormonas sexuales y moduladores del sistema genital</font></b></p>    <p><font face="Verdana" size="2">El hipérico (<i>Hypericum perforatum</i>) debido a su capacidad de producir inducción enzimática y a un incremento en la expresión de la glicoproteína P puede reducir los niveles de anticonceptivos en sangre, por lo que pueden producirse fallos en el efecto contraceptivo y también sangrado       intermenstrual<sup>96-100</sup>.</font></p>    <p><font face="Verdana" size="2">Algunas hierbas utilizadas como reguladores hormonales o como terapia hormonal sustitutiva “natural” podrían estimular el crecimiento del cáncer de mama u oponerse a la acción de los antagonistas competitivos de los estrógenos, como el tamoxifeno. El mecanismo de acción de estas hierbas es a menudo desconocido y en muchos casos, su efecto hormonal no ha sido demostrado, como ocurre con la angélica (<i>Angelica sinensis</i>), agnocasto (<i>Vitex agnuscastus</i>) y serpentaria o cimifuga (<i>Cimifuga racemosa</i>). Por otra parte, hierbas como el trébol rojo (<i>Trifolium pratense</i>) y soja (<i>Glycine max</i>) contienen isoflavonoides estrogénicos, cuyo alto consumo se asocia con una baja incidencia de cáncer de mama. Esta paradoja podría explicarse como resultado de que las isoflavonas se unen a los receptores estrogénicos actuando como agentes de terapia sustitutiva y previniendo la unión de estrógenos endógenos más potentes y actuando, así, como antiestrógenos<sup>101</sup>.</font></p>    <p><font face="Verdana" size="2">Existe una publicación notificando un episodio psicótico en un paciente tratado con testosterona, sertralina e hipérico (<i>Hypericum perforatum</i>)<sup>69</sup>.</font></p>    ]]></body>
<body><![CDATA[<p>&nbsp;</p>    <p><b><font face="Verdana" size="3">Tracto alimentario y metabolismo</font></b></p>    <p><b><font face="Verdana" size="2">Fármacos usados en diabetes</font></b></p>    <p><font face="Verdana" size="2">Una variedad de angélica, la <i> Angelica dahurica</i>, utilizada en la medicina china tradicional, contiene furanocumarinas y podría retrasar la eliminación de tolbutamida por inhibición enzimática<sup>102</sup>.</font></p>    <p>       <font face="Verdana" size="2">       La insulina y los hipoglicemiantes orales podrían interaccionar con las hierbas “estimulantes” como efedra (<i>Ephedra sinnica</i>) y productos que contienen cafeína como la cola o el guaraná, ya que todos estos productos aumentan la glucosa sanguínea<sup>81</sup>.</font></p>    <p>       <font face="Verdana" size="2">       El fruto del melón amargo o karela (<i>Momordica charantia</i>) tiene propiedades hipoglicemiantes por lo que podría interferir en el control de la glucemia por su efecto aditivo con los antidiabéticos<sup>103</sup>.</font></p>    <p>       <font face="Verdana" size="2">       Las dosis de insulina y antidiabéticos orales, podrían necesitar ajustes debido al efecto hipoglicemiante del ginseng       (<i>Panax Ginseng</i>)<sup>104</sup>.</font></p>    <p>       &nbsp;</p>    <p><b><font face="Verdana" size="3">Antiinfecciosos para uso sistémico</font></b></p>    <p><b><font face="Verdana" size="2">Antibacterianos para uso sistémico</font></b></p>    ]]></body>
<body><![CDATA[<p><font face="Verdana" size="2">Se ha publicado un caso de posible interacción entre el hinojo (<i>Foeniculum vulgare</i>) y ciprofloxacino, resultando en una disminución de las concentraciones de este último, en       ratas<sup>105</sup>.</font></p>    <p>       <font face="Verdana" size="2">       El khat, una hierba masticada en África y Yemen podría reducir la absorción de ampicilina y       amoxicilina<sup>106</sup>.</font></p>    <p>       <font face="Verdana" size="2">       Podría producirse una disminución en la absorción de penicilina V con la administración concomitante de goma guar       (<i>Cyamopsis tetragonolobus</i>)<sup>107</sup>.</font></p>    <p>       <font face="Verdana" size="2">       La mayoría de los antibióticos macrólidos son sustratos del citocromo P450, por lo que podrían sufrir inducción enzimática con hipérico (<i>Hypericum perforatum</i>)<sup>49,50</sup>.</font></p>    <p>           <br>       <b><font face="Verdana" size="2">Antivirales de uso sistémico</font></b></p>    <p>       <font face="Verdana" size="2">       Disminución de niveles de indinavir con hipérico (<i>Hypericum       perforatum</i>) por inducción enzimática. Aunque no se ha demostrado con otros antirretrovirales, debería tenerse en cuenta esta interacción para todos los fármacos de este       grupo<sup>9,108</sup>.</font></p>    <p>       <font face="Verdana" size="2">       Los inhibidores de la proteasa, ritonavir y especialmente saquinavir, pueden ver disminuidas sus concentraciones plasmáticas al administrarlos con ajo (<i>Allium sativum</i>)<sup>109-111</sup>.</font></p>    <p>       &nbsp;</p>    <p>       <b><font face="Verdana" size="3">Agentes antineoplásicos e       inmunomduladores</font></b></p>    ]]></body>
<body><![CDATA[<p>       <b><font face="Verdana" size="2">Agentes antineoplásicos</font></b></p>    <p>       <font face="Verdana" size="2">Reducción de niveles de ciclosporina con rechazo de órganos en trasplantados por disminución de niveles en tratamiento concomitante con hipérico (<i>Hypericum perforatum</i>) al inducir su metabolismo vía       CYP3A4<sup>112-117</sup>.</font></p>    <p>       <font face="Verdana" size="2">       Disminución de las concentraciones de tacrolimo<sup>118,119</sup>, por hipérico       (<i>Hypericum perforatum</i>).</font></p>    <p>       <font face="Verdana" size="2">       Un caso de incremento en niveles sanguíneos de ciclosporina en un paciente tratado también con azatioprina, prednisona, diltiacem, nifedipina y uso concomitante de un té de hierba del clavo       (<i>Geum chiloense</i>)<sup>120</sup>.</font></p>    <p>       <font face="Verdana" size="2">       La glicirrizina del regaliz (<i>Glycyrrhiza glabra</i>) puede reducir el aclaramiento de prednisolona en adultos       sanos<sup>121</sup>.</font></p>    <p>       <font face="Verdana" size="2">       La equinacea (<i>Echinacea spp</i>) se utiliza como inmunoestimulante y podría interferir con fármacos inmunosupresores, aunque no hay notificaciones de esta potencial interacción<sup>122</sup>.</font></p>    <p>       <font face="Verdana" size="2">       El hipérico (<i>Hypericum perforatum</i>) podría influir en el metabolismo de algunos citostáticos, como es el caso del       irinotecan<sup>123,124</sup>.</font></p>    <p>       <font face="Verdana" size="2">       Los aceites de onagro (<i>Oenothera biennis</i>) y borraja (<i>Borago officinalis</i>) pueden potenciar la citotoxicidad “in vitro” de paclitaxel y       vinorelbina<sup>125</sup>.</font></p>    <p>       &nbsp;</p>    <p><b><font face="Verdana" size="3">Miscelánea</font></b></p>    ]]></body>
<body><![CDATA[<p><font face="Verdana" size="2">La teofilina se metaboliza a través del CYP1A2 y aunque el hipérico (<i>Hypericum perforatum</i>) induce el CYP3A4, hay un caso descrito de disminución de niveles plasmáticos y otro en el que no existe modificación del       metabolismo<sup>126-128</sup>.</font></p>    <p>       <font face="Verdana" size="2">       La piperina que contienen algunas especies como Piper nigrum y Piper longum, incrementa la biodisponibilidad de algunos fármacos como fenitoína, propranolol y       teofilina<sup>129</sup>.</font></p>    <p>       <font face="Verdana" size="2">       Un paciente que fumó cannabis (<i>Cannabis sativa</i>) mientras estaba tomando sildenafilo, sufrió un infarto de       miocardio<sup>130</sup>.</font></p>    <p>       <font face="Verdana" size="2">       Algunas hierbas como efedra (<i>Ephedra sinnica</i>), yohimba (<i>Pausinystalia       yohimbe</i>) y regaliz (<i>Glycyrrhiza glabra</i>), pueden elevar la presión arterial, incluso cuando se consumen       solas<sup>131,132</sup>, por lo que podrían interferir con la medicación antihipertensiva.</font></p>    <p>       <font face="Verdana" size="2">       El hipérico (<i>Hypericum perforatum</i>) parece afectar la sulfoxidación por el CYP3A4 del omeprazol y también la hidroxilación por el CYP2C19 con la posibilidad de disminuir la concentración hemática<sup>133</sup>.</font></p>    <p>       <font face="Verdana" size="2">       El hipérico (<i>Hypericum perforatum</i>) puede alterar, de forma variable, la farmacocinética de la       fexofenadina<sup>134</sup>.</font></p>    <p>       <font face="Verdana" size="2">       El ginkgo (<i>Ginkgo biloba</i>) podría potenciar el efecto de la papaverina en la terapia de la disfunción eréctil<sup>135</sup>.</font></p>     <p align="center">&nbsp;</p>     <p><b><font face="Verdana" size="3">Bibliografía</font></b></p>    <!-- ref --><p><font face="Verdana" size="2">1. 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J Urol 1989; 141: 188A.</font>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;[&#160;<a href="javascript:void(0);" onclick="javascript: window.open('/scielo.php?script=sci_nlinks&ref=320999&pid=S1137-6627200600030000700135&lng=','','width=640,height=500,resizable=yes,scrollbars=1,menubar=yes,');">Links</a>&#160;]<!-- end-ref --><p>  &nbsp;</p>     <p>  &nbsp;</p>     <p><b><font face="Verdana" size="2"><a name="back"></a><a href="#top"><img border="0" src="/img/revistas/asisna/v29n2/seta.gif" width="15" height="17"></a>Correspondencia:    <br> </font></b> <font face="Verdana" size="2"> Hospital de Navarra    <br> C/ Irunlarrea, 3    <br> 31008 Pamplona    ]]></body>
<body><![CDATA[<br> E-mail: <a href="mailto:jtresbel@cfnavarra.es">jtresbel@cfnavarra.es</a></font></p>     <p> <font face="Verdana" size="2"> Aceptado para su publicación el 13 de marzo de 2006.</font></p>      ]]></body><back>
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