[AF] INR elevado

[Ramón Díaz-Alersi]

At 21:05 01/12/2003 +0100, you wrote:
>
>Ramón.
> >El topiramato es un inductor enzimático y, en todo  caso, debería
> >haber aumentado la metabolización del sintrom y disminuído el INR
>
>Si, pero aunque sea un inductor enzimático, no está descrita ninguna
>interacción con acenocumarol (al menos yo la he buscado y no la
>he encontrado)
>
>

No, es cierto. Al menos yo no he encontrado ninguna que implique 
exactamente al acenocumarol y al topiramato. Sí he encontrado esto en una 
revisión de la revista Epilepsia:

>Dicoumarol and warfarin
>
>Dicoumarol is an anticoagulant indicated for the prevention of thrombosis 
>associated with cardiovascular diseases and surgical procedures for 
>vascular disease. Dicoumarol interferes with coagulation by competitively 
>binding to vitamin K, which is essential for the formation of several 
>coagulation factors. Warfarin is an anticoagulant that is therapeutically 
>similar to dicoumarol. Its metabolism is primarily via CYP2C9, although 
>CYP3A4 and CYP1A2 also are involved. Enzyme-inducing AEDs, such as PB, 
>PHT, and CBZ can reduce the anticoagulant effects of both drugs by 
>increasing their metabolism, possibly via an induction of CYP2C9. During 
>polytherapy, care must be taken to maintain appropriate plasma 
>concentrations of dicoumarol/warfarin, as significant changes in plasma 
>concentration could be life-threatening; this is achieved by checking the 
>patient's coagulation function. The effects of discontinuing a 
>concomitantly administered AED also should be considered. This is 
>particularly important if the AED is removed or replaced by one that does 
>not induce hepatic enzymes, because the loss of enzyme induction may lead 
>to haemorrhaging due to elevated dicoumarol/warfarin plasma 
>concentrations. As drug interactions with dicoumarol/warfarin are 
>dependent on the CYP system, the second-generation AEDs that do not induce 
>CYP isoenzymes (e.g., VGB, LTG, TGB, LEV, and GBP) are unlikely to 
>interact with dicoumarol/warfarin. In addition, OXC does not appear to 
>interact with warfarin to any clinically relevant extent.

Lo que me hace pensar que la interacción es posible, aunque el resultado 
sería el contrario al que describes. La cita es de Epilepsia, 2002 
Apr;43(4):365-85. Me parece que el artículo completo es accesible de forma 
gratuita:

http://www.blackwell-synergy.com/links/doi/10.1046/j.1528-1157.2002.13001.x/full/



>A finales de octubre, el paciente padeció una infección respiratoria, según
>me ha contado hoy. Al parecer le trataron con 6 envases de Cefonicid 1 g im.
>No lo había registrado el farmacéutico que me sustituyó un par de días en la
>ficha de paciente ese dato.
>El proceso infeccioso y febril quizás explique la alteración del INR.


No estoy seguro ¿cuánto tiempo duró el episodio? porque tienes dos INR 
excesivamente altos separados por 11 días. Por otro lado, el propio 
Cefonicid puede haber contribuido al descenso en la actividad de 
protrombina, dando lugar a un INR tan elevado:

>Acta Clin Belg. 1990;45(5):327-33.
>
>Coagulation disorders caused by cephalosporins containing 
>methylthiotetrazole side chains
>
>Peetermans W, Verbist L.
>
>Algemeen Inwedige Geneeskunde, Universitaire Ziekenhuizen K.U. Leuven, Belgie.
>
>Treatment with MTT side chain containing cephalosporins can result in a 
>clinically relevant coagulopathy due to a deficiency in active vitamin K 
>dependent clotting factors. This complication is not caused by a decreased 
>production of vitamin K by the intestinal flora, but by an interference 
>with hepatic enzymes which synthetize active clotting factors. The 
>gamma-carboxylation of glutamic acid components of inactive precursor 
>peptides of vitamin K dependent clotting factors is inhibited as well as 
>the reduction of vitamin K2,3 epoxide to active vitamin K. Predisposing 
>factors for the coagulopathy caused by certain MTT side chain containing 
>cephalosporins are a limited supply of vitamin K, impaired liver and renal 
>function and a prolonged treatment.


Saludos.


----------------------------------
Ramón Díaz-Alersi
UCI.- H.U. Puerto Real
11150.-Puerto Real, Cádiz
España.
http://www.uninet.edu
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