Excerpt from Toxicity, Antidysrhythmic

Synonyms, Key Words, and Related Terms: antidysrhythmic drug toxicity, antidysrhythmic drug poisoning, antidysrhythmic drug exposure, class I drugs, sodium channel blockers, class II drugs, beta-adrenergic blockers, class III drugs, potassium channel blockers, class IV drugs, calcium channel blockers, antiarrhythmic exposures

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Background: Antidysrhythmic drugs have and will continue to have a significant role in decreasing the incidence of sudden cardiac death. Unfortunately, antidysrhythmic drugs also can be prodysrhythmic at both therapeutic and toxic drug concentrations. Because of the desire to find agents with potent antidysrhythmic action and low toxic profiles, the number of antidysrhythmic drugs has increased in the last few years.

Treating patients who are taking antidysrhythmic drugs and presenting with cardiac abnormalities is challenging for the ED physician. Whether the cardiac and extracardiac symptoms are the result of the patient's underlying cardiac condition or secondary to the antidysrhythmic agent being used is always a question. A thorough knowledge of this class of drugs is necessary for differentiating drug toxicity from primary disease.

This article briefly discusses the major antidysrhythmic drugs, with specific attention to their toxic effects. For each major drug, the following categories are outlined:

Antiarrhythmic class
Indications
Therapeutic doses
Metabolism
Therapeutic blood levels
Drug-drug interactions
Cardiac toxicity
Other toxicity
Treatment of toxicity

Pathophysiology: Even with the increase of antiarrhythmic drug types, the classification system of Singh and Vaughan Williams that originated in 1970 is still relevant.

Class I drugs are sodium channel blockers.
Class II drugs are beta-adrenergic blockers.
Class III drugs are potassium channel blockers.
Class IV drugs are calcium channel blockers.

Many agents do not have a pure electrophysiologic action.

Class I - Sodium channel blockers

All Class I agents block fast sodium channels and reduce the rate of rise of the action potential (phase 0) in certain cells. They inhibit depolarization of neuronal cells, thereby producing local anesthesia. They inhibit depolarization in atrial, ventricular, and Purkinje myocytes, thereby decreasing conduction velocity and automaticity. Class I agents are further categorized as A, B, or C subclasses, based on the degree of sodium channel blockade and effects on repolarization. Class IA agents prolong action potential duration and produce moderate slowing of cardiac conduction; prolongation of action potential duration occurs from blockade of outward rectifying potassium channels. Class IB agents shorten action potential duration and selectively depress cardiac conduction in ischemic cells. Class IC agents have little effect on action potential duration but markedly depress cardiac conduction (potent sodium channel blockers).

Class II - Beta-adrenergic blockers

Class II agents indirectly blockade calcium channel opening by attenuating adrenergic activation. These agents block the proarrhythmic effects of catecholamines.

Class III - Potassium channel blockers

Class III agents prolong refractoriness and delay repolarization by blocking potassium channels (phase 2, phase 3); they have little direct effect on sodium channels.

Class IV - Calcium channel blockers

Class IV agents slow sinoatrial node pacemaker cell and atrioventricular conduction by direct blockade of L-type voltage-gated calcium channels.

Frequency:

In the US: In 1998, a total of 1098 antiarrhythmic exposures were reported to US poison control centers, of which 26 (2.4%) resulted in major toxicity and 6 (0.5%) resulted in fatality.

Sex: Both sexes are affected equally; however, with sotalol, some studies have found that females have a higher risk for dysrhythmia (especially for torsade de pointes).

Age: Older patients, in general, have a higher risk for the development of dysrhythmias than younger patients. Drug-drug int .....