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Poisoning Due to Calcium Antagonists

Experience with Verapamil, Diltiazem and Nifedipine

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Summary

The calcium antagonists are a heterogeneous class of drugs which block the inward movement of calcium into cells through ‘slow channels’ from extracellular sites. By inhibiting phase 0 depolarisation in cardiac pacemaker cells and phase 2 plateau in myocardium, and by depressing calcium ion flux in smooth muscle cells of blood vessels, these agents may exert profound effects on the cardiovascular system, particularly in susceptible individuals or in overdose. Sinus node depression, impaired atrioventricular (AV) conduction, depressed myocardial contractility, and peripheral vasodilatation may result.

Pharmacokinetic features of calcium antagonists include rapid and complete absorption from the gastrointestinal tract, with extensive first-pass hepatic metabolism yielding generally low bio-availability. The volume of distribution is generally large and protein binding is high. Elimination is almost entirely by the liver. Impaired renal function does not affect pharmacokinetics.

Verapamil is the most potent inhibitor of cardiac conduction and contractility, with diltiazem also showing such effects. Nifedipine is the most potent vasodilator, but only occasionally impairs the sinus node or AV conduction. Significant pharmacodynamic effects are common during combination therapy with calcium antagonists, especially verapamil and β-blockers. Verapamil may significantly elevate serum digoxin concentrations and may exert additive negative effects on chronotropism and dromotropism when this combination is used.

Overdoses of calcium entry blockers are becoming more frequent and reflect an extension of the known pharmacodynamic profile of these agents. Typical features include confusion or lethargy, hypotension, sinus node depression and cardiac conduction defects. Onset of symptoms may be delayed if a sustained release preparation is ingested.

Management of calcium antagonist overdose includes gut decontamination with lavage and activated charcoal. All symptomatic patients and patients with a history of ingesting a sustained release preparation should be admitted for ECG monitoring. If bradycardia and/or conduction defects contribute to hypotension, atropine or isoprenaline (isoproterenol) may accelerate the ventricular rate. Transvenous pacing may be required. Depressed myocardial contractility usually responds well to calcium chloride or calcium gluconate administration, but further inotropic support may be required. Peripheral vasodilatation should be managed with intravenous fluids and a pressor agent such as dopamine or norepinephrine (noradrenaline).

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  1. Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, and San Francisco Bay Area Regional Poison Control Center, San Francisco General Hospital Medical Center, University of California, 1001 Potrero Avenue, Building 30, Room 3220, San Francisco, California, 94110, USA

    Paul D. Pearigen &  Neal L. Benowitz

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Pearigen, P.D., Benowitz, N.L. Poisoning Due to Calcium Antagonists. Drug-Safety 6, 408–430 (1991). https://doi.org/10.2165/00002018-199106060-00003

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