Ivabradine is used in heart failure with preserved ejection fraction and as add-on to beta-blockers in stable angina. Its mechanism of heart rate reduction involves:

• A Blockade of L-type voltage-gated calcium channels in the SA node
• B Enhancement of acetylcholine release from vagal nerve terminals innervating the SA node
• C Blockade of beta-1 adrenoceptors in the SA node reducing cAMP-mediated pacemaker acceleration
• D Inhibition of the hyperpolarization-activated cyclic nucleotide-gated (HCN) If current in SA node pacemaker cells ✓

Explanation

Ivabradine selectively blocks the funny current (If) carried by HCN channels in sinoatrial node pacemaker cells. This current mediates the spontaneous slow depolarization (phase 4) that drives heart rate. By blocking HCN channels, ivabradine reduces the rate of spontaneous depolarization, slowing heart rate without affecting myocardial contractility, conduction velocity, or blood pressure. This makes it useful when beta-blockers are contraindicated.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.