PharmacologyTier 1Medical Sciences concept

Ivabradine - funny channel (If) mechanism

Core concept

Ivabradine selectively inhibits the If ("funny") current in the sinoatrial node pacemaker cells
If is a mixed Na+/K+ inward current active during diastolic (phase 4) depolarisation -- it sets the slope of spontaneous SA node depolarisation and therefore heart rate
Blocking If slows the rate of diastolic depolarisation -> reduces heart rate, with no effect on contractility, blood pressure, or conduction (AV node, His-Purkinje)

Mechanistically distinct from beta-blockers and non-dihydropyridine CCBs, which reduce heart rate and contractility/conduction (negative inotropic and dromotropic effects) -- ivabradine is "pure" heart rate reduction
Requires sinus rhythm to work -- If current is a property of the SA node pacemaker itself, so ivabradine has no rate-controlling effect in atrial fibrillation (does not act on the AV node)
Characteristic adverse effect: visual phosphenes (luminous visual disturbances) -- If-like channels are also present in retinal photoreceptors

Used as an anti-anginal (see separate note) and in HFrEF with sinus rhythm and resting heart rate >=70 bpm despite maximally tolerated beta-blocker -- add-on for further rate reduction without added negative inotropy
Ineffective and not indicated in AF -- a recognised trap given its heart-rate-lowering reputation
Can cause symptomatic bradycardia; contraindicated with strong CYP3A4 inhibitors (levels rise significantly) and in severe hepatic impairment

Contrast with beta-blockers (also reduce SA node rate but via reduced sympathetic/cAMP drive, plus AV nodal and contractility effects) and digoxin (rate control via AV nodal vagal enhancement, works in AF)
Same SA node target as the physiological determinant of heart rate variability and chronotropic competence generally
Ranolazine (late Na current) and ivabradine (If current) are the two anti-anginals that spare haemodynamics (no BP/contractility effect) -- useful when BP will not tolerate more agents

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