Description

Ranolazine is a medication used to treat chronic angina (chest pain). It belongs to a class of drugs known as anti-anginals. It is a unique medication because its mechanism of action is different from other commonly used anti-anginal drugs like beta-blockers, calcium channel blockers, and nitrates. Ranolazine works by targeting specific ion channels in the heart, and importantly, it does so without significantly affecting heart rate or blood pressure.

Indications

Ranolazine is primarily indicated for the treatment of chronic stable angina pectoris. It is typically used:

• As a second-line therapy in combination with other anti-anginal drugs (such as beta-blockers, calcium channel blockers, or nitrates) when those medications alone do not adequately control symptoms.

• For patients who cannot tolerate other anti-anginal medications due to side effects like low heart rate or low blood pressure.

While it is approved for chronic angina, ranolazine is not used to treat acute angina attacks.

Mechanism of Action

Ranolazine’s anti-anginal effects are a result of its unique ability to selectively inhibit the late sodium current (INa​) in cardiac muscle cells.

Inhibition of Late Sodium Current: Under normal conditions, a small, persistent inward sodium current flows into heart cells during the repolarization phase (Phase 3) of the cardiac action potential. In ischemic conditions (when the heart muscle is not getting enough oxygen), this “late” or “persistent” sodium current is significantly increased.

1. Prevention of Calcium Overload: This increased sodium influx leads to an accumulation of intracellular sodium (Na+). This elevated sodium level, in turn, disrupts the function of the sodium-calcium exchanger (NCX), a protein that pumps sodium out of the cell in exchange for calcium (Ca2+) coming in. The disruption of this exchanger leads to an overload of calcium inside the heart muscle cells.
2. Reduced Myocardial Wall Tension: This calcium overload can cause a number of problems, including reduced diastolic relaxation and increased ventricular wall tension, which increases the heart’s oxygen demand and can worsen angina. By inhibiting the late sodium current, ranolazine prevents this chain of events

3. Improved Myocardial Function: The reduction in intracellular sodium and calcium overload improves the relaxation of the heart muscle and reduces ventricular stiffness, which ultimately decreases the heart’s oxygen consumption and improves blood flow. This effect alleviates the symptoms of angina without affecting heart rate or blood pressure.

4. Secondary Effects: By stabilizing the ionic balance in heart cells, ranolazine also has been shown to have antiarrhythmic properties, as it can reduce the electrical instability caused by late sodium current overload.