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Calcium channel blockers

Last updated: February 22, 2021

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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 of calcium channel blockers [1]
Agents Effects Side effects Indications
Dihydropyridines [2][3]
  • Short-acting : nifedipine, clevidipine, nimodipine
  • Intermediate-acting : nitrendipine, nicardipine, lercanidipine
  • Long-acting : amlodipine, felodipine
Nondihydropyridines
  • Benzothiazepines: diltiazem
  • Phenylalkylamines: verapamil, gallopamil

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.

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.

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

Nondihydropyridine CCBs should not be combined with beta blockers because CCBs can enhance the negative inotropic, chronotropic, and dromotropic effects of beta blockers.

Phenylalkylamines (e.g., verapamil), which primarily affect the calcium channels of the heart, are contraindicated in cases of heart failure because of their negative effect on myocardial contractility.

We list the most important contraindications. The selection is not exhaustive.

Clinical features [18]

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

Diagnostics [19]

  • Diagnosis is based on clinical observation and a thorough history
    • Determine the time of intake, type, amount, and preparation (extended-release vs. immediate-release) of the drug.
    • Assess for risk of self harm.
  • Any ingestion exceeding the maximum therapeutic dosage is usually clinically relevant.

Laboratory tests [18]

ECG [20]

May show any of the following associated arrhythmias:

Acute management [21]

Approach

  • Assess hemodynamic stability.
    • Pulseless
      • Start CPR (see “Advanced cardiac life support”).
      • Give calcium IV.
      • Consider lipid emulsion therapy and VA-ECMO (see “Management of a refractory overdose of CCB”).
    • Hemodynamically unstable: combination therapy for stabilization (e.g., IV fluids, calcium, atropine, vasopressors)
    • Hemodynamically stable or asymptomatic patients: 24 hours of inpatient observation
  • All patients
    • Consider decontamination.
    • Evaluate for ingestion of other substances (e.g., beta blockers)
    • Contact poison control center.
    • Admit for continuous cardiac monitoring.
    • Frequent blood pressure checks
    • Cardiology consult
    • All potentially intentional overdoses: psychiatry consult

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.

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