Is diltiazem a dihydropyridine (calcium channel blocker)?

Diltiazem Classification: Non-Dihydropyridine Calcium Channel Blocker

No, diltiazem is not a dihydropyridine calcium channel blocker. Diltiazem is classified as a non-dihydropyridine calcium channel blocker, specifically belonging to the benzothiazepine class. 1

Classification of Calcium Channel Blockers

Calcium channel blockers are divided into two main structural and functional categories:

1. Dihydropyridines:

   • Examples: amlodipine, felodipine, nifedipine, and nisoldipine
   • Characteristics:
     • High selectivity for vascular L-type calcium channels
     • Potent peripheral vasodilation
     • Minimal direct effects on cardiac conduction
     • May cause reflex tachycardia (especially short-acting forms)

2. Non-dihydropyridines:

   • Benzothiazepines (diltiazem)
   • Phenylalkylamines (verapamil)
   • Characteristics:
     • Less selective for vasculature than dihydropyridines
     • More pronounced effects on myocardial contractility
     • Significant effects on cardiac pacemaker and AV conduction
     • Negative inotropic and chronotropic effects 1, 2

Pharmacological Differences Between Diltiazem and Dihydropyridines

Diltiazem has a distinct pharmacological profile compared to dihydropyridines:

• Cardiac Effects: Diltiazem has significant negative chronotropic (heart rate) and dromotropic (conduction) effects, particularly on the AV node 2, 3
• Vasodilation: Diltiazem produces moderate vasodilation, whereas dihydropyridines cause potent peripheral vasodilation 4
• Heart Rate Response: Dihydropyridines may cause reflex tachycardia, while diltiazem typically decreases heart rate 5
• Side Effect Profile: Peripheral edema is less common with diltiazem (3.1%) compared to dihydropyridines (12.3%) 2

Clinical Implications of Diltiazem's Classification

The non-dihydropyridine classification of diltiazem has important clinical implications:

• Atrial Fibrillation: Diltiazem is effective for rate control in atrial fibrillation due to its AV nodal effects 2, 3
• Drug Interactions: Diltiazem inhibits cytochrome P450 3A4 and P-glycoprotein, potentially affecting metabolism of other drugs including direct oral anticoagulants 1
• Combination Therapy: Caution is needed when combining diltiazem with beta-blockers or ivabradine due to risk of severe bradycardia 1
• Heart Failure: Diltiazem should be avoided in heart failure with reduced ejection fraction due to its negative inotropic effects 2

Mechanism of Action

Both diltiazem and dihydropyridines block L-type calcium channels, but they bind to different sites on the channel:

• Diltiazem preferentially blocks inactivated cardiac calcium channels 6
• This state-dependent binding contributes to its unique pharmacological profile that differs from dihydropyridines 6

Understanding the correct classification of diltiazem as a non-dihydropyridine calcium channel blocker is essential for appropriate clinical decision-making, particularly when considering drug combinations and specific clinical scenarios.