What are the uses and dosages of nondihydropyridine (non-DHP) calcium channel blockers, such as verapamil (calcium channel blocker) and diltiazem (calcium channel blocker), in clinical practice?

Nondihydropyridine Calcium Channel Blockers: Uses and Dosages

Nondihydropyridine calcium channel blockers (verapamil and diltiazem) are primarily used for managing supraventricular tachycardias, rate control in atrial fibrillation/flutter, and as alternative antihypertensive/antianginal agents when beta blockers are contraindicated or ineffective. 1

Mechanism of Action

• Nondihydropyridine calcium channel blockers (non-DHPs) inhibit calcium influx through slow channels in cardiac and vascular smooth muscle cells 2, 3
• Unlike dihydropyridines (e.g., nifedipine, amlodipine), non-DHPs have significant effects on:
  • AV node conduction (slowing)
  • Sinus node function (decreased automaticity)
  • Myocardial contractility (negative inotropic effect) 1, 4
• This pharmacological profile makes them particularly useful for arrhythmia management and rate control 1

Clinical Uses

1. Supraventricular Tachyarrhythmias

• Paroxysmal Supraventricular Tachycardia (PSVT)

  • Used when adenosine or vagal maneuvers fail to convert PSVT or when PSVT recurs 1
  • Effective for terminating reentry PSVTs that depend on AV nodal conduction 1

• Atrial Fibrillation/Flutter

  • Effective for ventricular rate control in patients with atrial fibrillation or flutter 1
  • Particularly useful for long-term rate control due to longer duration of action compared to adenosine 1

2. Hypertension

• Alternative to Beta Blockers

  • When beta blockers are contraindicated (e.g., asthma, COPD) 1
  • Extended-release forms may be considered instead of beta blockers (Class IIb recommendation) 1

• Combination Therapy

  • Can be used as add-on therapy when other agents (beta blockers, nitrates) have been fully used 1

3. Angina

• Coronary Artery Spasm (Vasospastic/Prinzmetal's Angina)

  • Effective in preventing coronary artery spasm 3
  • Dilate both epicardial and subendocardial coronary arteries 3

• Exertional Angina

  • Reduce myocardial oxygen demand through decreased afterload, contractility, and heart rate 3
  • Can be used when beta blockers are contraindicated or cause unacceptable side effects 1

4. Unstable Angina/NSTEMI

• First-line therapy when beta blockers are contraindicated 1
• Should be used with caution in patients with heart failure or LV dysfunction 1

Dosing Guidelines

Verapamil

IV Administration (for acute management):

• Initial dose: 2.5-5 mg IV bolus over 2 minutes (3 minutes in older patients) 1
• Repeat dosing: If no response, 5-10 mg every 15-30 minutes to a total dose of 20-30 mg 1
• Alternative regimen: 5 mg bolus every 15 minutes to a total dose of 30 mg 1

Oral Administration:

• Immediate release: 80-160 mg three times daily 1
• Slow/extended release: 120-480 mg once daily 1

Diltiazem

IV Administration (for acute management):

• Initial dose: 15-20 mg (0.25 mg/kg) IV over 2 minutes 1
• Additional dose: If needed, 20-25 mg (0.35 mg/kg) IV after 15 minutes 1
• Maintenance infusion: 5-15 mg/hour, titrated to heart rate 1

Oral Administration:

• For angina: Starting with 30 mg four times daily, gradually increase to 180-360 mg/day in divided doses 3
• Extended release: 120-360 mg once daily 1

Contraindications and Precautions

• Avoid in patients with:

  • Severe left ventricular dysfunction or heart failure 1
  • Cardiogenic shock 1
  • AV block greater than first degree (without pacemaker) 1
  • Sick sinus syndrome 3
  • Pre-excited atrial fibrillation or flutter (risk of accelerated ventricular response) 1

• Use with caution in:

  • Patients receiving other drugs with SA/AV nodal blocking properties 1
  • Hepatic or renal dysfunction 1
  • Elderly patients (consider lower initial doses) 1

Side Effects

• Hypotension 1
• Bradycardia 1
• Worsening heart failure in patients with pre-existing ventricular dysfunction 1
• Constipation (particularly with verapamil) 5
• Edema 1
• Headache, dizziness 6

Clinical Pearls

• Never use immediate-release dihydropyridine CCBs (e.g., nifedipine) without concomitant beta blockade due to increased risk of adverse events 1
• Non-DHPs are preferred over dihydropyridines for rate control in atrial arrhythmias due to their direct effects on AV nodal conduction 1
• Verapamil has more potent negative inotropic effects than diltiazem, making diltiazem potentially safer in patients with borderline LV function 5, 4
• When using for rate control in atrial fibrillation, monitor for excessive bradycardia 1
• Non-DHPs can be used for tachyarrhythmias in patients with cocaine-induced sympathetic overstimulation, whereas beta blockers are relatively contraindicated in this setting 1