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Vol. 7. Núm. D.
Novedades en la reducción de la frecuencia cardiaca
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Vol. 7. Núm. D.
Novedades en la reducción de la frecuencia cardiaca
Páginas 32D-45D (Junio 2007)
Novedades en la reducción de la frecuencia cardiaca
Acceso a texto completo
Ivabradina, un bloqueador selectivo de la corriente If. Aspectos farmacológicos y tolerabilidad
Ivabradine: a Selective If Current Inhibitor. Pharmacological Characteristics and Tolerability
Visitas
...
Miguel Vaquero, Ricardo Gómez, Lucía Núñez, Ricardo Caballero, Eva Delpón, Adriana Barana, Juan Tamargo
Autor para correspondencia
jtamargo@med.ucm.es

Correspondencia: Dr. J. Tamargo. Departamento de Farmacología. Facultad de Medicina. Universidad Complutense. Avda. Complutense, s/n. 28040 Madrid. España.
Departamento de Farmacología. Facultad de Medicina. Universidad Complutense. Madrid. España
Información del artículo

La frecuencia cardiaca es el principal determinante de las demandas miocárdicas de O2 y del flujo sanguíneo coronario. La frecuencia cardiaca depende de la actividad eléctrica espontánea de las células marcapasos del nódulo sinoauricular. Estas células presentan una fase de despolarización diastólica que desplaza el potencial de membrana hacia su valor umbral y se inicia un nuevo potencial de acción que se propaga a través del miocardio y produce una respuesta contráctil. La corriente If de entrada de iones Na+ y K+ a través de canales activados por la hiperpolarización y modulados por nucleótidos cíclicos (HCN) es la principal determinante de la inclinación de la fase de lenta despolarización diastólica. Los canales se abren cuando el potencial de membrana se hiperpolariza y se modulan por la concentración celular de adenosinmonofosfato cíclico. La ivabradina es un bloqueador específico de la If. Para ello debe atravesar la membrana y alcanzar su receptor, que se encuentra en la boca intracelular del poro del canal. Como consecuencia, produce una reducción dependiente de la dosis de la frecuencia cardiaca, que reduce las demandas miocárdicas de O2 y aumenta el flujo sanguíneo coronario. Sin embargo, a concentraciones terapéuticas no inhibe otras corrientes iónicas cardiacas, razón por la que no modifica la presión arterial, la contractilidad o las propiedades electrofisiológicas cardiacas. En este artículo se revisa el mecanismo de acción, las propiedades farmacocinéticas y farmacodinámicas y las reacciones adversas y contraindicaciones de la ivabradina.

Palabras clave:
Ivabradina
Frecuencia cardiaca
Angina de pecho
Corriente If
Farmacología cardiaca
Abreviaturas:
ABC
ACh
AMPc
AV
Cmáx
CNBD
ECG
Em
EPOC
HCN
HTA
ICa,L
ICa,T
If
INa
MVO2
SA

The heart rate is the main determinant of both myocardial oxygen demand and coronary blood flow. Heart rate is determined by spontaneous electrical activity in the pacemaker cells of the sinoatrial node. These cells exhibit a diastolic depolarization phase that drives the membrane potential towards the threshold value for initiating a new action potential, which propagates throughout the myocardium and triggers a contractile response. The If current, an inward current of Na+ and K+ ions through hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels, is the main determinant of the slope of the slow diastolic depolarization phase. These channels open in response to membrane hyperpolarization and are modulated by the intracellular cAMP concentration. Ivabradine specifically blocks the If current. To do so, it crosses the membrane and binds to a receptor located on the intracellular side of the channel pore. As a result, ivabradine produces a dose-dependent decrease in heart rate that reduces myocardial oxygen demand and increases coronary blood flow. However, at therapeutic concentrations, it does not affect other cardiac ionic currents, which is why ivabradine does not alter blood pressure, cardiac contractility, or cardiac electrophysiological parameters. This article reviews ivabradine's mechanism of action, pharmacodynamic and pharmacokinetic properties, side effects, and interactions.

Key words:
Ivabradine
Heart rate
Angina pectoris
If current
Cardiac pharmacology
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