What is the difference between dihydropyridine (DHP) and non-dihydropyridine calcium channel blockers?

Dihydropyridine vs Non-Dihydropyridine Calcium Channel Blockers

Dihydropyridines (DHPs) are highly selective for vascular smooth muscle causing pronounced vasodilation without significant cardiac effects, while non-dihydropyridines (non-DHPs) have less vascular selectivity but exert significant negative chronotropic, dromotropic, and inotropic effects on the heart. 1

Mechanism and Binding Sites

• Both classes bind to the α1-subunit of the L-type calcium channel but at different binding sites, which explains their distinct clinical effects 1
• DHPs are highly selective for vascular L-type calcium channels, producing pronounced coronary and systemic vasodilation 2
• Non-DHPs have less selective effects on vasculature and more pronounced effects on myocardial contractility and cardiac conduction 2, 3
• All calcium channel blockers inhibit calcium ion influx into vascular smooth muscle and cardiac muscle cells, reducing intracellular calcium availability for muscle contraction 1

Cardiovascular Effects

Dihydropyridines:

• Primarily reduce afterload through peripheral arterial vasodilation 1
• Do not significantly affect heart rate with chronic dosing 4
• Do not alter sinoatrial nodal function or atrioventricular conduction 4
• Negative inotropic effects can be detected in vitro but not seen in intact animals at therapeutic doses 4

Non-Dihydropyridines:

• Reduce both afterload and heart rate 1
• Have significant negative chronotropic, dromotropic, and inotropic effects on the heart 3
• Prolong the effective refractory period within the AV node and slow AV conduction in a rate-related manner 5
• May predispose to high-degree atrioventricular block when given with other agents that depress AV node function (e.g., β-blockers) 1, 3

Clinical Applications

Both Classes:

• Effective for hypertension and angina 1
• Particularly effective in treating angina due to coronary spasm (Prinzmetal's variant) 1, 4

Non-DHPs Specifically:

• Used for rate control in atrial fibrillation and supraventricular tachycardias 1
• Recommended for ischemic symptoms when beta blockers are not successful, contraindicated, or cause unacceptable side effects 3

Renal and Proteinuric Effects

Non-DHPs have substantially greater antiproteinuric effects than DHPs, translating into greater slowing of kidney disease progression in patients with proteinuria >300 mg/day. 6, 1

• DHPs are less efficacious than ACE inhibitors, ARBs, and non-DHPs in reducing albuminuria in diabetic kidney disease 6, 1
• In diabetic kidney disease, DHPs should not be used without concurrent RAS inhibition 6, 1
• Non-DHPs, along with ACE inhibitors and ARBs, have a greater antiproteinuric effect than other antihypertensive classes in hypertensive patients with diabetic kidney disease 6

Safety Considerations and Contraindications

Non-DHPs:

• Should not be combined with ivabradine due to risk of severe bradycardia 1, 2
• Should be avoided in patients with significant left ventricular dysfunction or heart failure 1, 3
• Should not be used in patients with pulmonary edema or severe LV dysfunction 2
• Have important drug interactions with digoxin, cyclosporine, and certain statins metabolized by CYP3A4 3

DHPs:

• Rapid-release, short-acting DHPs should be avoided without concomitant beta-blockade 1, 2
• High doses often cause peripheral edema, headache, flushing, and tachycardia 7
• Leg edema is a common side effect 2

Drug Interactions

• Non-DHPs (diltiazem and verapamil) are moderate to weak inhibitors of CYP3A4 and can increase exposure to statins such as simvastatin, lovastatin, and atorvastatin 3
• Co-administration of diltiazem with amlodipine resulted in a 60% increase in amlodipine systemic exposure 4