Non-Dihydropyridine Calcium Channel Blockers: Verapamil and Diltiazem
Non-dihydropyridine calcium channel blockers (CCBs) are a distinct class of calcium antagonists that includes verapamil (phenylethylamine) and diltiazem (benzothiazepine), which have significant effects on cardiac conduction and contractility in addition to their vasodilatory properties. 1, 2
Pharmacological Properties
Mechanism of Action
- Bind to different sites on the L-type calcium channel α1-subunit compared to dihydropyridines 1
- Block calcium influx into vascular smooth muscle and cardiac cells
- Less selective for vascular tissue than dihydropyridines 1
- Significant effects on:
- Sinoatrial (SA) node function
- Atrioventricular (AV) nodal conduction
- Myocardial contractility
Key Differences from Dihydropyridines
| Property | Non-Dihydropyridines (Verapamil, Diltiazem) | Dihydropyridines (e.g., Amlodipine, Nifedipine) |
|---|---|---|
| Cardiac Effects | Strong negative chronotropic and dromotropic effects | Minimal direct effects on cardiac conduction |
| Vasodilation | Moderate | Potent peripheral vasodilation |
| Heart Rate | Decrease | May cause reflex tachycardia |
| AV Node | Significant slowing of conduction | Minimal effect on AV conduction |
Clinical Applications
Primary Indications
- Hypertension - Particularly effective when rate control is also desired 1
- Rate control in atrial fibrillation/flutter - Due to AV nodal blocking effects 1, 2
- Angina pectoris - Both stable and vasospastic variants 1
- Supraventricular tachycardias - Particularly effective for AV nodal reentrant tachycardias 3
Specific Clinical Scenarios
- Unstable angina/NSTEMI: Recommended when beta-blockers are contraindicated 1
- Vasospastic angina: Effective due to coronary vasodilatory properties 1, 3
- Hypertension with tachycardia: Preferred over dihydropyridines due to heart rate-lowering effects 2
Important Precautions and Contraindications
Major Precautions
- Heart failure: Use with caution due to negative inotropic effects 1
- Conduction disorders: May worsen AV block or sinus node dysfunction 3
- Combination with beta-blockers: Requires careful monitoring due to additive negative chronotropic and dromotropic effects 1, 4
Drug Interactions
- Inhibit cytochrome P450 3A4 and P-glycoprotein, affecting levels of many medications 2
- Can increase levels of direct oral anticoagulants, potentially increasing bleeding risk 1, 2
- Additive effects with other negative chronotropic agents (e.g., ivabradine) 2
Management of Overdose or Toxicity
Symptoms of Toxicity
- Profound bradycardia
- Hypotension
- High-degree AV block
- Cardiogenic shock
Treatment Approaches for Toxicity
- Calcium administration (reasonable first-line) 1
- Vasopressors for hypotension 1
- Atropine for significant bradycardia 1
- High-dose insulin for refractory hypotension 1
- Electrical pacing for refractory bradycardia 1
- VA-ECMO for cardiogenic shock refractory to pharmacological interventions 1
Clinical Pearls
- Non-dihydropyridine CCBs should not be used in patients with heart failure with reduced ejection fraction due to their negative inotropic effects 1
- When treating atrial fibrillation, non-dihydropyridines are effective for rate control while dihydropyridines are not 2
- Verapamil has stronger negative inotropic effects than diltiazem 5
- Caution is required when combining non-dihydropyridine CCBs with beta-blockers due to risk of profound bradycardia or heart block 4
Non-dihydropyridine calcium channel blockers represent an important class of cardiovascular medications with distinct pharmacological properties that make them particularly valuable for specific clinical scenarios requiring both vasodilation and control of heart rate.