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~~~~~~~~~~~~~~~~ bZx 2  ;  P+sZCU 4  3@))=c6N3!Rl +; M.+ - =3a a      a  $" &r<dH  $'  2 8- v<B4 g ^  ?++D  -9! +"4    0VE&' +,hb$s#ڿE`"  j"$318]`mK'& j"$[қi:b'Ejb$*@tqeT *jb$ t40c3j$jb$b0#7j"$;W[-L;j"$Qq_}yNqUXj"$ҷbPs_P]tjb$젗.2B@j$j$j2$g -Ǫ]``5j t0e0e    A A5% 8c8c     ?A)BCD|E||S" 3@R ʚ;l8ʚ;g4FdFdv 0 Pp@pP <4!d!d` 0LZ<4dddd` 0LZ <4dddd 0Lg4=d=dv 0.p po0___PPT10 ppZ___PPT9<%hlp#$$$&22222z(? %O =2siLa paroxetina se asocia a un mayor riesgo de muerte por cncer de mama en mujeres tratadas con tamoxifeno"j" fffj$                 ( t Antecedentes   AEl tratamiento con tamoxifeno reduce a la mitad la mortalidad por cncer de mama en mujeres: en estadios tempranos y receptores estrognicos positivos. El citocromo P450 se encuentra implicado en la activacin del tamoxifeno, por lo que es posible que los frmacos que interfieren con ste puedan afectar a su eficacia.H]0P=0P0P]=P d  1 `u Objetivos   {Estudiar si algunos inhibidores selectivos de la recaptacin de la serotonina (ISRS) reducen la efectividad del tamoxifeno.| |>0  " v Diseo (1)  VEstudio de cohortes. Se identificaron los casos de cncer de mama a partir del Ontario Cancer Registry. A partir del Ontario Public Drug Benefit Program, que contiene todos los registros de la medicacin consumida por la poblacin >65 aos de este estado del Canad: Se identificaron todas las mujeres e"66 aos que haban iniciado un tratamiento con tamoxifeno entre 1993 y 2005. Se analiz la medicacin que haban retirado. Z PPO#sPN Dw Diseo (2)  Se incluyeron en la cohorte a las mujeres: cuya adherencia estimada al tratamiento en funcin de la medicacin retirada era e"80% y a las que se les haba prescrito un nico ISRS durante el tratamiento con tamoxifeno. Fecha ndice: aquella en la que se retir por ltima vez el tamoxifeno ms 60 das. Variable de resultado principal: muerte por cncer de mama. Variable de exposicin principal: nmero de das en los que las participantes haban tomado conjuntamente el tamoxifeno y el ISRS.H+0P0P0P+> >   xResultados (2) ConclusionesLos autores concluyen que: el tratamiento con paroxetina en mujeres con cncer de mama tratadas con tamoxifeno se asocia a un mayor riesgo de muerte por esta enfermedad, lo que apoya la hiptesis de que la paroxetina puede reducir los beneficios del tamoxifeno.*ZZP- + ` ! 0Comentario (1)El tamoxifeno ha venido siendo en las ltimas dcadas un tratamiento coadyuvante del cncer de mama con receptores estrognicos positivos, dado que disminuye: la tasa de recurrencias y la mortalidad por cncer de mama y por todas las causas. El tamoxifeno es un profrmaco que se metaboliza a nivel heptico por el citoctromo P450 para generar metabolitos que tienen mayor afinidad por los receptores estrognicos y mayor actividad biolgica. El ms importante de stos es el endoxifeno.BPUPPU e x    K ? eComentario (2)OLas pacientes con cncer de mama presentan a menudo cuadros depresivos que son tratados con ISRS y con inhibidores selectivos de la recaptacin de la noradrenalina (ISRN). Adems, estos frmacos se pueden administrar para aliviar los sofocos producidos por el tratamiento con tamoxifeno. Algunos (fluoxetina, la paroxetina y la venlafaxina) son metabolizados por el citocromo P450, por lo que es a priori posible que interacten con el tamoxifeno. En un estudio previo, la administracin conjunta de paroxetina y tamoxifeno produjo una reduccin de la concentracin de endoxifeno del 56%.PPP      < 6  -  Comentario (3)Los resultados de este estudio son coherentes con estas observaciones. A medida que aumenta el tiempo de tratamiento concomitante con estas dos sustancias aumenta la probabilidad de recidiva del cncer de mama y de morir por la enfermedad. Por lo tanto, en caso de que se precise un tratamiento con ISRS o con ISRN en pacientes con cncer de mama en tratamiento con tamoxifeno es conveniente seleccionar alguno de los que no han mostrado tendencia a aumentar la mortalidad por esta enfermedad.Pn v/4 1kgxy~z{|}~< ` ` ̙33` 333MMM` ff3333f` f` f` 3` >?" dd@(|?" dd@   " @ ` n?" dd@   @@``PR    @ ` ` p>> =(  #  68Z "P<$ 0  k7Haga clic para modificar el estilo de ttulo del patrn8 8i  0] "<$ 0  kHaga clic para modificar el estilo de texto del patrn Segundo nivel Tercer nivel Cuarto nivel Quinto nivel7    l  S .Aapaldia"nP %!0  N''''':' ' '                8 @ @ @H  0޽h ? _1W1___PPT1071.+*x|DI' n= @B D' = @BA?%,( < +O%,( < +D;' =%(D' =%(D' =A@BBBB0B%(E' =4 B`BPB`B?<*%(/%,( < +D' =1:Bvisible*o3>+B#style.visibility<*7%(D' =+4 8?dCB0-#ppt_w/2BCB#ppt_xB*Y3>B ppt_x<*7D' =+4 8?\CB#ppt_yBCB#ppt_yB*Y3>B ppt_y<*7D' =A@BBBB0B%(E' =4 B`BPB`B?<*%( /%,( < +D' =1:Bvisible*o3>+B#style.visibility<*7E%(D' =+4 8?dCB0-#ppt_w/2BCB#ppt_xB*Y3>B ppt_x<*7ED' =+4 8?\CB#ppt_yBCB#ppt_yB*Y3>B ppt_y<*7ED' =A@BBBB0B%(E' =4 B`BPB`B?<*%( /%,( < +D' =1:Bvisible*o3>+B#style.visibility<*ER%(D' =+4 8?dCB0-#ppt_w/2BCB#ppt_xB*Y3>B ppt_x<*ERD' =+4 8?\CB#ppt_yBCB#ppt_yB*Y3>B ppt_y<*ERD' =A@BBBB0B%(E' =4 B`BPB`B?<*%(/%,( < +D' =1:Bvisible*o3>+B#style.visibility<*R_%(D' =+4 8?dCB0-#ppt_w/2BCB#ppt_xB*Y3>B ppt_x<*R_D' =+4 8?\CB#ppt_yBCB#ppt_yB*Y3>B ppt_y<*R_D' =A@BBBB0B%(E' =4 B`BPB`B?<*%(/%,( < +D' =1:Bvisible*o3>+B#style.visibility<*_l%(D' =+4 8?dCB0-#ppt_w/2BCB#ppt_xB*Y3>B ppt_x<*_lD' =+4 8?\CB#ppt_yBCB#ppt_yB*Y3>B ppt_y<*_l+++0 + +D' =4@BBBB%(E' =4 B`BPB`B?<*%(/%,( < +D' =1:Bvisible*o3>+B#style.visibility<*%(D' =+4 8?dCB0-#ppt_w/2BCB#ppt_xB*Y3>B ppt_x<*D' =+4 8?\CB#ppt_yBCB#ppt_yB*Y3>B ppt_y<* +D' =4@BBBB%(E' =4 B`BPB`B?<*%(/%,( < +D' =1:Bvisible*o3>+B#style.visibility<*%(D' =+4 8?dCB0-#ppt_w/2BCB#ppt_xB*Y3>B ppt_x<*D' =+4 8?\CB#ppt_yBCB#ppt_yB*Y3>B ppt_y<* +D' =4@BBBB%(E' =4 B`BPB`B?<*%(/%,( < +D' =1:Bvisible*o3>+B#style.visibility<*%(D' =+4 8?dCB0-#ppt_w/2BCB#ppt_xB*Y3>B ppt_x<*D' =+4 8?\CB#ppt_yBCB#ppt_yB*Y3>B ppt_y<* +D' =4@BBBB%(E' =4 B`BPB`B?<*%(/%,( < +D' =1:Bvisible*o3>+B#style.visibility<*%(D' =+4 8?dCB0-#ppt_w/2BCB#ppt_xB*Y3>B ppt_x<*D' =+4 8?\CB#ppt_yBCB#ppt_yB*Y3>B ppt_y<* +D' =4@BBBB%(E' =4 B`BPB`B?<*%(/%,( < +D' =1:Bvisible*o3>+B#style.visibility<*%(D' =+4 8?dCB0-#ppt_w/2BCB#ppt_xB*Y3>B ppt_x<*D' =+4 8?\CB#ppt_yBCB#ppt_yB*Y3>B ppt_y<* *Diseo predeterminado0 ` +(      0 O3   R*     0D  3  T*  d   c $ ?po  /   0 e @1  kHaga clic para modificar el estilo de texto del patrn Segundo nivel Tercer nivel Cuarto nivel Quinto nivel7    l   6t O   R*     6    T*  H   0whg ? ̙3380___PPT10.0Y  p@@(  @ @ 0Z O3  Z @*  @ 0Z  3 Z B*  @ 6$Z O  Z @*  @ 6   Z B* H @ 0whg ? ̙3380___PPT10.0\Z  ~o  %   0 t P (  t j t BAL jY ?P3 t  f_ж_ж ?8   L8 @ @ @ t  f_ж_ж ? ` `   L8 ` `  ` t <._ж_ж ? K  cKelly CM, Juurlink DN, Gomes T, Duong-Hua M, Pritchard KI, Austin PC, Paszat LF. Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study. BMJ 2010; 340: 693. `> O''''   C8 @ @ @ t HD>_ж_жfff ? @2!0!0 IAP al da [ http://www.apaldia.com/resumenes/resumen.php?idresumen=632 ]J>''''':' ' '                8 @ @ @ t 6A ?  @2!0!0 t 6A ?  @2!0!0  t 6A  ? [ @2!0!0< t c $޽h ? ̙33___PPT10i.]0G+D=' t= @B +~  o  % | f(  |  | # l,_ж_ж ?   L8 @ @ @& |  ft_ж_ж ? <$0  L8 >~> ~ >~< | c $޽h ? ̙330(___PPT10..]0G+[W_D' t= @B DS' = @BA?%,( < +O%,( < +DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*| j%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*| j6%(+8+0+| 0 +;  %  l(     # l_ж_ж ?   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L8 @ @ @&   f8_ж_ж ?<$0  L8 \ \ \<  c $޽h ? ̙33  ___PPT10 ..]0G+FDc ' t= @B D ' = @BA?%,( < +O%,( < +D ' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<* %(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<* a%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<* a%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<* T%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<* T%(+8+0+ 0 + % }u@ p(   &  Bl_ж_ж ?P Resultados (1)(>'(   8 @ @ @  0m  &,$0 oEdad media: 74 aos. Duracin media del tratamiento con tamoxifeno: 4,0 aos. No se detectaron diferencias importantes entre las mujeres que recibieron diferentes ISRS. 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