Ivabradine – the first selective sinus node If channel inhibitor in the treatment of chronic stable angina with normal sinus rhythm.

Ivabradine is currently the only agent shown to clinically lower heart rate with no negative inotropism or effects on conduction and contractility. Lowering heart rate is therefore one of the most important therapeutic approaches in the treatment of stable angina pectoris, which reduces myocardial oxygen demand, simultaneously improving oxygen supply.

Mechanism of action:

Ivabradine acts on the If  ion current, which is highly expressed in the SA node.. If is a mixed Na+–K+ inward current due to hyperpolarization which is modulated by the autonomic nervous system. It is one of the most important ionic currents for regulating pacemaker activity in the sinoatrial (SA) node. Ivabradine selectively inhibits the pacemaker If current in a dose-dependent manner. Blocking this channel reduces pacemaker  activity, reduces the heart rate and enabling more blood to flow to the myocardium.

Dosage:

5 mg and 7.5 mg twice daily (bid) for the treatment of stable angina.

 

Adverse Effects:

Luminous Phenomena –  (by patients described as sensations of enhanced brightness in a fully maintained visual field). This is probably due to blockage of I h ion channels in the retina which are very similar to cardiac If. These symptoms are mild, transient, fully reversible and non-severe.

Bradycardia

Headache

First-degree AV block

Ventricular Extrasystoles

Dizziness and/or blurred vision.

 

Contraindications:

Sick sinus Syndrome, and cannot be used concominantly with inhibitors of CYP 3A4 such as azole anti-fungals (such as ketoconazole), macrolide antibiotics, nefazodone and the anti-HIV drugs nelfinavir and ritonavir.