What are the indications for Diltiazem and its effects on heart rate (hr) and blood pressure (bp)?

Diltiazem Indications, Effects on Heart Rate and Blood Pressure

Diltiazem is primarily indicated for hypertension, angina pectoris, atrial fibrillation/flutter with rapid ventricular response, and supraventricular tachycardia, with its main therapeutic effects being reduction of heart rate and blood pressure through calcium channel blockade. 1, 2, 3

Primary Indications

• Hypertension: First-line or alternative treatment for mild to moderate hypertension 3, 4
• Angina:
  • Stable angina pectoris
  • Variant (Prinzmetal's) angina
  • Unstable angina 3
• Arrhythmias:
  • Supraventricular tachycardia (SVT)
  • Atrial fibrillation/flutter with rapid ventricular response 5, 1

Effects on Heart Rate

Diltiazem produces significant heart rate-lowering effects through:

• Inhibition of calcium influx during cardiac membrane depolarization 2
• Decreased sinoatrial and atrioventricular conduction 2
• Prolongation of AH interval and AV node functional/effective refractory periods 2

The heart rate-lowering effect is proportional to baseline heart rate:

• Significant reduction in patients with elevated baseline HR (≥74 beats/min)
• Greater effect at higher initial rates (≥85 beats/min)
• Minimal effect on normal or low baseline heart rates (<74 beats/min) 6

This creates a "regulating effect" where diltiazem reduces tachycardia without causing excessive bradycardia, making it particularly useful for rate control in atrial fibrillation/flutter 6.

Effects on Blood Pressure

Diltiazem lowers blood pressure through:

• Coronary and peripheral vasodilation
• Reduction in peripheral vascular resistance
• Decreased cardiac contractility (negative inotropic effect) 2, 4

The blood pressure-lowering effect is dose-dependent, with:

• Systolic and diastolic BP reductions occurring at therapeutic doses
• Hypotension (SBP <90 mmHg) occurring in approximately 9.7% of patients receiving IV diltiazem 7

Dosing Considerations

• Oral immediate-release: 30 mg every 6 hours or 60 mg every 8 hours
• Oral extended-release: 120-360 mg once daily (median effective dose: 300 mg/day) 1
• IV administration: 0.25 mg/kg over 2 minutes, followed by infusion at 5-15 mg/hour for acute rate control 5

Important Contraindications

Diltiazem is contraindicated in:

1. Pre-excitation syndromes (e.g., WPW syndrome with atrial fibrillation/flutter)
2. Decompensated heart failure
3. Severe left ventricular dysfunction
4. AV block greater than first degree (without pacemaker)
5. Sick sinus syndrome
6. Cardiogenic shock 5, 1

Drug Interactions

Diltiazem is a moderate CYP3A4 inhibitor, which can lead to significant interactions with:

• Direct oral anticoagulants (increased bleeding risk)
• P-glycoprotein substrates
• Multiple other cardiovascular and non-cardiovascular drugs 5, 1

Clinical Pearls

1. When beta-blockers are contraindicated for angina, diltiazem can be substituted, but not if LV dysfunction is present 5

2. The combination of beta-blockers and diltiazem should be used with caution due to increased risk of bradyarrhythmias and heart failure 5

3. Diltiazem can be used in combination with beta-blockers for patients with atrial fibrillation who don't respond adequately to single-agent treatment, particularly when heart rate remains >110-120 beats/min 5

4. Patients should be monitored for bradycardia, hypotension, and signs of worsening heart failure, especially in elderly patients or those with pre-existing cardiac dysfunction 1

5. Unlike dihydropyridine calcium channel blockers, diltiazem decreases heart rate rather than increasing it, which may be beneficial in patients with angina or post-myocardial infarction 6