Mechanism of Action of Nicorandil
Nicorandil has a dual mechanism of action as both a potassium channel activator and a nitrate donor, making it unique among antianginal medications.
Primary Mechanisms
1. Potassium Channel Activation
- Activates ATP-sensitive potassium (KATP) channels in vascular smooth muscle 1
- This activation leads to:
- Arterial vasodilation
- Reduction in afterload
- Decreased myocardial oxygen demand
- Potential cardioprotective effects through ischemic preconditioning 2
2. Nitrate-like Effects
- Contains a nitrate moiety in its chemical structure 3
- Produces venodilation through nitric oxide (NO) donation 4
- Results in:
- Decreased preload
- Reduced left ventricular end-diastolic pressure
- Decreased myocardial wall tension
Hemodynamic Effects
- Balanced coronary and peripheral vasodilation 2
- Reduction in both preload and afterload 5
- Decreased total peripheral resistance (approximately 19%) 5
- Reduced systolic (34%) and diastolic (21%) blood pressure 5
- Does not impair myocardial contractility or atrioventricular conduction 5
Cardioprotective Properties
- Involvement in myocardial preconditioning 6
- Potential protection against ischemia-reperfusion injury 2
- Reduction in ST-segment elevation during ischemia in patients undergoing coronary angioplasty 2
- Improvement in regional left ventricular wall motion after ischemic damage 2
- Strong spasmolytic activity against coronary vasospasm 5
Mechanism Predominance in Different Conditions
The relative contribution of each mechanism varies depending on:
- Dose of nicorandil administered
- Target tissue/organ
- Underlying pathophysiology 4
For example:
- KATP channel opening predominates in models of myocardial and pulmonary fibrosis
- NO donation is the primary mechanism in hepatic fibrosis and inflammatory bowel diseases 4
Clinical Implications
- Effective antianginal agent at doses of 10-40 mg 5
- Sustained efficacy with no evidence of tolerance development 5
- Equivalent efficacy to beta-blockers and calcium channel blockers in comparative trials 2
- May have additional benefits in patients with vasospastic angina 3
Common Side Effects
- Headache (most common, occurs in approximately one-third of patients) 3
- Usually mild to moderate in intensity
- Tends to diminish with continued treatment
- Can be minimized by starting at a lower dose (5 mg twice daily) 3
- Other potential side effects: facial flushing, hypotension, and rarely, mouth ulcers 2
Nicorandil's unique dual mechanism provides effective angina management while potentially offering additional cardioprotective benefits not seen with other antianginal medications.