MYFORTIC NOVARTIS

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    MICOFENOLICO CIDO

    MICOFENOLATO SDICOCON CUBIERTA ENTERICA

    NIDIA A- CALLE REYMERMDICO NEFRLOGA

    HNLNSPNP

    MYFORTIC

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    DROGAS INMUNOSUPRESORAS: LUGARES DE ACCION ENEL MODELO DE TRES SEALES

    n engl j med 351;26 december 23, 2004

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    y AGENTES DIRIGIDOS FRENTE A LA SEAL UNO

    Anticuerpo monoclonal OKT3 se une a una de lassubunidades de 20 kd del complejo CD3 determinando laendocitosis del receptor de las clulas T.

    Anticuerpos policlonales (globulina antitimoctica) se dirigefrente a la molcula CD3 y a una serie de marcadores celulares desuperficie.

    Inhibidores de la calcineurina: Ciclosporina y el Tacrolimus:

    inhiben la actividad fosfatasa de la calcineurina cuando se unen a alas protenas fijadoras de inmunofilina en el citoplasmaproduciendo una inhibicin de la transcripcin del gen de la IL2.

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    y LOSLINFOCITOS REQUIERENNIVELESADECUADOS DELOS

    NUCLETIDOS PURNICOS:GUANOSINA YDEOXIGUANOSINA Y NIVELESREDUCIDOS DE ADENOSINA YDEOXIADENOSINA PARAPROLIFERAR.

    y ESTOSNUCLETIDOSSE

    SINTETIZAN ENLASCLULASHUMANASA TRAVS DE DOSVAS:LA VA DE NOVO Y LA VAALTERNAO DE RESCATE. LOSLINFOCITOS UTILIZANFUNDAMENTALMENTE LA VADE NOVO, LO QUE LES HACESENSIBLESA LA ACCIN DE

    MPA QUE LLEVAR A LADISMINUCIN DE LA SNTESISDE GTP, COMPOMENTEFUNDAMENTALDE LATRASNFORMACIN MITGENADELLINFOCITO

    Nefrologa. Vol. 25. Nm. 3.2005

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    ACIDO MICOFENOLICOy Se aisl por primera vez en 1898 a partir del moho Penicillin

    glaucum, estudiado inicialmente como antibitico.

    y Es un inhibidor reversible de la IMPDH.

    y

    Derivados del ACIDO MICOFENOLICO:MICOFENOLATO MOFETIL

    MICOFENOLATO SDICO CON CUBIERTAENTRICA.

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    Exposicin de MPA en el post-trasplante

    Hale MD et al. Clin PharmacolTher 1998; 64: 672-683.

    4g MMF

    2 g MMF

    1g MMF

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    j Alta variacion entre pacientes

    j La exposicin se corelaciona inversamente con el

    rechazo.

    j La exposicin va en aumento en el postrasplante.

    MPA monitoreo puede ser util por :

    v. Gelder T et al. Transplantation 68: 261-266, 1999Hale M et al. Clin Pharmacol Ther 64: 672-683, 1998

    Pero...La monitorizacin mejoraria los resultados???

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    y 1: INDUCTION THERAPY1.1: We recommend starting a combination of immunosuppressivemedications before, or at the time of, kidney transplantation. (1A)1.2: We recommend including induction therapy with a biologic

    agent as part of the initial immunosuppressive regimen in KTRs.(1A)1.2.1: We recommend that an IL2-RA be the first-lineinduction therapy. (1B)1.2.2: We suggest using a lymphocyte-depleting agent,

    rather than an IL2-RA, for KTRs at high immunologic risk.(2B)

    IL2-RA, interleukin 2 receptor antagonist; KTRs, kidney transplantrecipients.

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    y 2: INITIAL MAINTENANCEIMMUNOSUPPRESSIVE MEDICATIONS2.1: We recommend using a combination of immunosuppressive medications asmaintenance therapy including a

    CNI and an antiproliferative agent, with or without corticosteroids. (1B)2.2: We suggest that tacrolimus be the first-line CNI used. (2A)

    2.2.1: We suggest that tacrolimus or CsA be started before or at the timeof transplantation, rather than delayed until the onset of graft function. (2D

    tacrolimus; 2B CsA)2.3: We suggest that mycophenolate be the first-line antiproliferative agent.(2B)2.4: We suggest that, in patients who are at low immunological risk and whoreceive induction therapy, corticosteroids could be discontinued during the firstweek after transplantation. (2B)

    2.5: We recommend that if mTORi are used, they should not be started untilgraft function is established and surgical wounds are healed. (1B)CNI, calcineurin inhibitor; CsA, cyclosporine A; mTORi, mammalian target of

    rapamycin inhibitor(s).

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    y 3: LONG-TERM MAINTENANCE IMMUNOSUPPRESSIVE

    MEDICATIONS3.1: We suggest using the lowest planned doses ofmaintenance immunosuppressive medications by 24 months aftertransplantation, if there has been no acute rejection. (2C)

    3.2: We suggest that CNIs be continued rather than

    withdrawn. (2B)3.3: If prednisone is being used beyond the first week after

    transplantation, we suggest prednisone be continued rather thanwithdrawn. (2C)

    CNI, calcineurin inhibitor.