Elsevier

Critical Care Clinics

Volume 13, Issue 4, 1 October 1997, Pages 829-848
Critical Care Clinics

POISONING BY SODIUM CHANNEL BLOCKING AGENTS

https://doi.org/10.1016/S0749-0704(05)70371-7Get rights and content

The cell membrane is relatively impermeable to sodium ions (Na+), and cells expend much energy pumping Na+ out of cells to maintain higher extracellular Na+ concentrations and negative resting membrane potentials (about −90 mV in heart muscle). The organized influx of Na+ back into cardiac cells through Na+ channels, however, helps pacemaker cells reach threshold; allows propagation of the action potential through the heart's conduction system and muscle; and triggers calcium influx in myocardium, which in turn initiates myocardial contraction.

Many pharmaceutical agents are administered primarily because of their ability to block Na+ channels, whereas other Na+ channel antagonists are given because of additional pharmacologic effects (Table 1). The ability of agents to block Na+ channels is variously described as a membrane stabilizing effect, a local anesthetic effect, or a quinidine-like effect. Regardless of which name is used, toxicity following large doses of Na+ channel blockers shares a common pathophysiology and results in similar signs and symptoms. Importantly, recent studies indicate that adverse effects resulting from Na+ channel blockade produced by a multitude of agents may respond to therapy with hypertonic sodium bicarbonate.

Section snippets

VOLTAGE-GATED SODIUM CHANNELS AND CARDIAC ACTION POTENTIALS

Sodium channels reside in the cell membrane and comprise several subunits of long polypeptides that span the plasma membrane several times. Numerous subtypes of Na+ channels exist, and are part of a common gene superfamily, explaining their structural similarity.

Sodium channels are generally classified based upon the stimulus that causes them to open. Ligand-gated Na+ channels open (activate) in response to binding of a ligand to the channel. For example, the nicotinic receptor for

MYOCARDIAL TOXICITY FROM SODIUM CHANNEL BLOCKADE

Overdoses with the various Na+ channel blockers listed in Table 1 share several cardiotoxic features that result from Na+ channel blockade. These include intraventricular conduction defects, ventricular arrhythmias, myocardial depression, and bradyrhythmias.

OTHER FEATURES OF POISONING BY SODIUM CHANNEL BLOCKERS

Many Na+ channel blockers possess anticholinergic properties (see Table 1) that produce agitation, coma, and respiratory depression along with urinary retention, tachycardia, anhydrosis, and depressed gastrointestinal motility. Propoxyphene-induced coma reverses with large doses of naloxone. Coma may be seen following massive doses of Na+ channel blockers in the absence of anticholinergic or narcotic properties.

Seizures are not uncommon following overdoses of most Na+ channel blockers. In some

HYPERTONIC SODIUM BICARBONATE AND Na+ CHANNEL BLOCKERS

Most clinicians recognize that the treatment of choice for intraventricular conduction defects, ventricular arrhythmias, and hypotension refractory to fluids resulting from Na+ channel blockade by tricyclic antidepressants is hypertonic sodium bicarbonate. Most physicians, however, do not realize that alkaline hypertonic sodium solutions were shown to be effective for other Na+ channel antagonists first, and that animal studies have since demonstrated hypertonic sodium bicarbonate's efficacy in

Miscellaneous Measures

Severe poisoning by Na+ channel blockers frequently produces coma, convulsions, and respiratory depression. Securing an airway and ensuring adequate ventilation, as always, are first priority. All the specific nuances of caring for each Na+ channel blocker overdose cannot be discussed here because of diverse, additional pharmacologic effects these drugs possess. For example, beta blocker–induced hypotension and bradycardia frequently respond to glucagon. Coma from propoxyphene usually reverses

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    Address reprint requests to Steven C. Curry, MD, Department of Medical Toxicology, 925 East McDowell Road, Second Floor, Phoenix, AZ 85006

    *

    From the Department of Medical Toxicology, Good Samaritan Regional Medical Center; and University of Arizona College of Medicine, Phoenix, Arizona

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