What class of drugs cause reflex tachycardia?

Last updated: June 2, 2021

Summary

Calcium channel blockers (CCBs) are drugs that bind to and block L-type calcium channels, which are the predominant calcium channels in the myocardium and vascular smooth muscles. By blocking these channels, CCBs cause peripheral arterial vasodilation (leading to a drop in blood pressure) and myocardial depression (leading to negative chronotropic, inotropic, and dromotropic effects on the myocardium). CCBs are classified into two major groups according to the main site of action: Dihydropyridines (e.g., nifedipine, amlodipine) are potent vasodilators, and nondihydropyridines (e.g., verapamil) are potent myocardial depressants. Diltiazem, a common nondihydropyridine, has moderate vasodilatory and myocardial depressant effects. Nondihydropyridines are also categorized as class IV antiarrhythmic drugs and are used in the treatment of supraventricular arrhythmias. The most common indications for CCB use are arterial hypertension and stable angina. The main side effects of dihydropyridines are caused by vasodilation (e.g., headache, peripheral edema); those of nondihydropyridines are caused by myocardial depression (e.g., bradyarrhythmias, atrioventricular block). CCBs are contraindicated in patients with preexisting cardiac conduction disorders, symptomatic hypotension, and/or acute coronary syndrome.

Overview

Pharmacodynamics

• CCBs bind to and block L-type calcium channels in cardiac and vascular smooth muscle cells; → decreased frequency of Ca2+ channel opening in response to cell membrane depolarization; → decreased transmembrane Ca2+ current
• Effects of decreased Ca2+ influx
  • Vascular smooth muscle relaxation; → vasodilation → decreased peripheral vascular resistance → decreased afterload → decreased blood pressure
  • Decreased cardiac muscle contractility (negative inotropicaction) → decreased cardiac output → decreased blood pressure
  • Decreased SA node discharge rate (negative chronotropic action); → decreased heart rate (bradycardia) →decreased cardiac output→ decreased blood pressure
  • Decreased AV node conduction (negative dromotropic action) → termination of supraventricular arrhythmias
• Dihydropyridines act mainly on vascular smooth muscle. The order of potency is nifedipine/amlodipine followed by the nondihydropyridines verapamil and diltiazem.
• Nondihydropyridines act mainly on the heart. The order of potency is verapamil > diltiazem > amlodipine/nifedipine.

Dihydropyridine CCBs (nifedipine and amlodipine) primarily act on vascular smooth muscles. Nondihydropyridine CCBs (verapamil > diltiazem) primarily act on the heart.

Verapamil mainly acts on Ventricles and Amlodipine mainly acts on Arteries.

Indications

All CCBs [4]

• Arterial hypertension (esp. amlodipine )
• Stable angina: for patients with contraindications for beta blockers or who are not responsive to beta blockers
• Vasospastic angina (Prinzmetal angina)
• Achalasia
• Diffuse esophageal spasm

Dihydropyridines

• Raynaud phenomenon (e.g., nifedipine, felodipine)
• Subarachnoid hemorrhage; (e.g., nimodipine; , nicardipine) to prevent secondary vasospasm
• Tocolysis
• Gestational hypertension
• Hypertensive urgency/hypertensive emergency (e.g., nicardipine, clevidipine)
• Thromboangiitis obliterans

Nondihydropyridines

• Supraventricular arrhythmias (verapamil and diltiazem ;)
  • Supraventricular tachycardia
  • Atrial fibrillation, atrial flutter
• Cardiomyopathy (hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy)
• Migraine
• Verapamil: cluster headache

Short-acting CCBs (e.g., nifedipine) are not indicated for monotherapy of angina because they cause hypotension and secondary reflex tachycardia, which can worsen cardiac ischemia.

Adverse effects

Dihydropyridines [5][6]

• Effects due to vasodilation
  • Peripheral edema (esp. amlodipine)
  • Headaches, dizziness
  • Facial flushing, feeling of warmth
  • Reflex tachycardia: a condition of tachycardia secondary to a decrease in blood pressure (esp. nifedipine)
• Gingival hyperplasia

Nondihydropyridines [6]

• Benzothiazepines: similar to those of the other CCB classes, but milder
• Phenylalkylamines
  • Reduced contractility
  • Bradycardia
  • AV block [8]
  • Gingival hyperplasia
  • Verapamil
    • Constipation
    • Hyperprolactinemia [9]

We list the most important adverse effects. The selection is not exhaustive.

Contraindications

Overdose/intoxication

Patients are usually symptomatic but those who present early or have only consumed a small quantity of CCBs may be asymptomatic.

Laboratory tests [18]

ECG [20]

May show any of the following associated arrhythmias:

Approach

Patients with CCB overdose require continuous cardiac monitoring because they can develop severe cardiovascular complications and deteriorate quickly.

Hemodynamically unstable patients

Management is complicated and specialists should be involved early. A combination of therapies is frequently required and should be tailored to the predominant symptoms.

Patients on high-dose insulin infusions must have glucose regularly monitored.

Refractory overdose

Decontamination

Consider in all patients who present within the following time frames or who have taken sustained or extended-release preparations.

References

Which drugs cause reflex tachycardia?

What causes reflex tachycardia?

Which drug often causes tachycardia?

Which antihypertensive can cause reflex tachycardia?