Is diltiazem a dihydropyridine (calcium channel blocker)?

Diltiazem is Not a Dihydropyridine Calcium Channel Blocker

No, diltiazem is not a dihydropyridine calcium channel blocker. Diltiazem is classified as a benzothiazepine calcium channel blocker, which is structurally and pharmacologically distinct from dihydropyridines. 1

Classification of Calcium Channel Blockers

Calcium channel blockers are divided into three distinct chemical and pharmacological classes:

1. Dihydropyridines:

   • Examples: amlodipine, felodipine, nifedipine, nisoldipine
   • Highly selective for vascular L-type calcium channels
   • Primarily cause peripheral vasodilation
   • Minimal direct effects on cardiac conduction

2. Benzothiazepines:

   • Example: diltiazem
   • Chemically identified as 1,5-Benzothiazepin-4(5H)-one derivative 2
   • Intermediate selectivity between vascular and cardiac tissue

3. Phenylethylamines:

   • Example: verapamil
   • Similar cardiac effects to diltiazem

Pharmacological Differences Between Classes

Diltiazem (Benzothiazepine) Properties:

• Less selective for vasculature than dihydropyridines 1
• More pronounced effects on myocardial contractility
• Significant effects on cardiac pacemaker and atrioventricular conduction cells
• Produces negative inotropic and chronotropic effects
• Reduces heart rate, particularly at elevated baseline rates 3
• Prolongs AH conduction time and AV node refractory periods 2

Dihydropyridine Properties:

• High selectivity for vascular L-type channels 1
• Primarily cause peripheral vasodilation
• Often cause reflex tachycardia (especially short-acting agents)
• Minimal direct effects on cardiac conduction
• Common side effects include peripheral edema, headache, and flushing 4

Clinical Implications of the Difference

The classification difference has important clinical implications:

1. Heart Rate Effects:

   • Diltiazem decreases heart rate, especially when elevated 3
   • Dihydropyridines may increase heart rate or leave it unchanged 4

2. Cardiac Conduction:

   • Diltiazem significantly affects AV nodal conduction
   • Can be used for rate control in atrial fibrillation 1
   • Should not be combined with ivabradine due to risk of severe bradycardia 1

3. Drug Interactions:

   • Diltiazem inhibits cytochrome P450 3A4 and P-glycoprotein 1
   • Can increase levels of many medications, including direct oral anticoagulants

4. Combination Therapy:

   • Combining diltiazem with beta-blockers requires caution due to additive negative chronotropic effects 1
   • Dihydropyridines can be more safely combined with beta-blockers

Therapeutic Considerations

When selecting a calcium channel blocker, the classification difference matters:

• For hypertension with tachycardia: Diltiazem may be preferred over dihydropyridines
• For vasospastic angina: Both classes are effective 1
• For atrial fibrillation rate control: Diltiazem is useful, dihydropyridines are not
• For patients with heart failure: Both should generally be avoided, but dihydropyridines are sometimes better tolerated 5

The risk-benefit ratio of diltiazem appears to be closer to that of diuretics and beta-blockers and may be better than that of dihydropyridines in some clinical scenarios 6.