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.[18]
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
For additional information, see Medscape's Cardiology Resource Center.
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.
Epidemiology
Frequency
United States
In 2009, a total of 1457 antiarrhythmic exposures were reported to US poison control centers, of which 19 (1.3%) resulted in major toxicity and 1 (0.06%) resulted in fatality.[1]
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 interactions are increasing, especially in elderly patients who use multiple antiarrhythmic drugs simultaneously.
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