Differences Between Dihydropyridine and Non-dihydropyridine Calcium Channel Blockers
Dihydropyridine calcium channel blockers (DHPs) are highly selective for vascular L-type calcium channels causing pronounced vasodilation, while non-dihydropyridine CCBs (non-DHPs) have less vascular selectivity but more pronounced effects on cardiac conduction and contractility. 1, 2
Mechanism of Action
Both classes work by inhibiting calcium influx through L-type calcium channels, but with important differences:
- Both DHPs and non-DHPs bind to the α1-subunit of the L-type calcium channel, but at different binding sites 1
- All CCBs inhibit calcium ion influx into vascular smooth muscle and cardiac muscle cells, reducing intracellular calcium availability for muscle contraction 2, 3
- This inhibition leads to arterial vasodilation, decreased peripheral vascular resistance, and reduced blood pressure 2
Pharmacological Differences
Dihydropyridine CCBs (e.g., amlodipine, nifedipine)
- Highly selective for vascular smooth muscle with minimal effects on cardiac tissue 1
- Cause pronounced coronary and peripheral vasodilation 2
- Minimal negative inotropic effects on the heart 1
- May cause reflex tachycardia, especially with short-acting formulations 1, 4
- Primarily used for hypertension and angina 5
- Examples: amlodipine, nifedipine, felodipine, nisoldipine 1
Non-dihydropyridine CCBs
- Less selective for vascular tissue with more pronounced effects on cardiac tissue 1
- Include phenylalkylamines (verapamil) and benzothiazepines (diltiazem) 1, 6
- Significant negative chronotropic, dromotropic, and inotropic effects 1, 6
- Greater effects on sinoatrial and atrioventricular nodal conducting tissue 1
- May cause heart rate slowing and atrioventricular block 1
- Used for hypertension, angina, and certain arrhythmias 6, 5
Clinical Effects and Applications
Cardiovascular Effects
- DHPs primarily reduce afterload through vasodilation 1, 2
- Non-DHPs reduce both afterload and heart rate 1, 6
- Non-DHPs may predispose to high-degree atrioventricular block when given with other agents that depress AV node (e.g., β-blockers) 1
- Both classes are effective for hypertension and angina 1, 5
- Non-DHPs are also used for rate control in atrial fibrillation and supraventricular tachycardias 6
Renal Effects
- Non-DHPs have substantially greater antiproteinuric effects than DHPs 1
- Non-DHPs show greater slowing of kidney disease progression in patients with proteinuria >300 mg/day 1
- DHPs are less efficacious than ACE inhibitors, ARBs, and non-DHPs in reducing albuminuria in diabetic kidney disease 1
- In diabetic kidney disease, DHPs should not be used without concurrent RAS inhibition 1
Side Effect Profiles
Dihydropyridine CCBs
- Peripheral edema (common) 1, 4
- Headache, dizziness, flushing 1, 4
- Potential for reflex tachycardia, especially with short-acting formulations 1
- Less constipation than with non-DHPs 4
Non-dihydropyridine CCBs
- Constipation (especially with verapamil in elderly patients) 1, 4
- Bradycardia and heart block 1, 6
- Negative inotropic effects may worsen heart failure 1
- Important drug interactions with digoxin, cyclosporine 4
Clinical Considerations and Cautions
- Non-DHPs should not be combined with ivabradine due to risk of severe bradycardia 1, 6
- Non-DHPs should be avoided in patients with significant left ventricular dysfunction 6
- DHPs are particularly effective in treating angina due to coronary spasm (Prinzmetal's variant) 1
- Rapid-release, short-acting DHPs should be avoided without concomitant beta-blockade 2
- Both classes are effective across all patient groups regardless of sex, race/ethnicity, age, and dietary sodium intake 4