Once the specific arrhythmia is diagnosed, drug therapy is generally the first course of treatment considered. The existing drugs, however, often have limited usefulness-hence the need for newer agents. Because we are a nationally known testing center, our patients often have access to newer drugs not generally available. When patients cannot tolerate drugs due to side effects or the drug is not effective, other forms of treatment become the only realistic alternative.
A wide range of drugs effective in the treatment of cardiac rhythm disturbances are currently available. These pharmacological agents are primarily used in the therapy of fast heart rhythms, or tachycardias, originating from either the upper chambers of the heart (atria) or the lower chambers (ventricles). Specific drug therapy is chosen based on the underlying arrhythmia, dosing schedule, side effects, and the presence of other cardiac, pulmonary, liver, or renal disease.
Quinidine, first described in 1848, is one of the oldest antiarrhythmic drugs. Originally used to treat malaria, its efficacy in treating cardiac rhythm disturbances was later discovered incidentally.
Quinidine is used to treat arrhythmias of both the upper and lower cardiac chambers. It has been used to treat atrial fibrillation, AV nodal reentrant tachycardia, Wolff-Parkinson-White syndrome, premature ventricular complexes, and ventricular tachycardia. Oral dosing of the relatively short-acting formulation quinidine sulfate is usually every 6 hours, while quinidine gluconate is available in a sustained-release preparation that allows dosing every 8 to 12 hours.
The side effect profile of quinidine has severely limited its use. About 1/3 of patients develop abdominal cramping and diarrhea. Rash, changes in hearing and altered vision are not uncommon. Most importantly, quinidine has the potential to cause serious heart rhythm disturbances, necessitating close monitoring during drug initiation.
Procainamide has been in use since the mid 1900’s. Its use and efficacy are similar to that of quinidine. Long-term therapy may effectively control a variety of supraventricular and ventricular arrhythmias. Its use as an oral agent is limited in part by the need for frequent dosing. Standard short-acting preparations need to be dosed every 3-4 hours. Sustained release formulations require every 6-hour dosing.
Like quinidine, procainamide commonly causes gastrointestinal side effects. Additionally, a lupus-like syndrome with fever, joint and muscle pains, rash, lung and liver problems may occur in up to 30% of patients on long-term therapy. Like quinidine, procainamide may also produce serious cardiac rhythm disturbances.
Disopyramide belongs to the same class of drugs as quinidine and procainamide. Disopyramide’s side effect profile is notable for its potential to lessen the strength with which the heart muscle squeezes or contracts. As a result, it has found application not only in the treatment of supraventricular and ventricular arrhythmias, but also in the therapy of neurocardiogenic syncope, a condition triggered by increased contractility in the ventricles. Typical dosing is every 6 to 12 hours.
Significant side effects can occur in 1/3 of patients taking disopyramide, and are particularly bothersome in the elderly. These commonly include dry mouth, blurred vision, constipation, and difficulty with urination.
Flecainide is a relatively well-tolerated agent that is effective in the therapy of many cardiac arrhythmias. It has a convenient dosing schedule, with usual dosing initiated every 12 hours. Side effects including blurred vision, headache, and difficulty with balance necessitate discontinuation in approximately 13% of patients.
The primary drawback of flecainide therapy is the associated risk of life-threatening cardiac rhythm disturbances that may occur when the drug is used in patients with underlying structural heart disease, such as prior myocardial infarction. Serious arrhythmias secondary to flecainide are fortunately rare in patients with normal hearts. Thus, flecainide use is primarily confined to the treatment of supraventricular arrhythmias in patients without other heart disease.
Like flecainide, propafenone is effective against a wide spectrum of supraventricular and ventricular rhythm disturbances. A shorter-acting agent, it must be dosed approximately every 8 hours. Approximately 10-25% of patients develop side effects necessitating drug discontinuation. These may include nausea, dizziness, blurred vision, and a metallic taste. As is the case for flecainide, serious rhythm disturbances may occur when propafenone is used in patients with significant underlying heart disease, but their occurrence is rare in patients with structurally normal hearts treated for supraventricular tachycardia.
Amiodarone is a complex drug, which was initially developed to treat angina pectoris. Its potent antiarrhythmic activity was later incidentally discovered. Amiodarone has several unique properties, including the requirement for a prolonged period of drug loading (weeks to months) prior to full drug efficacy, and a similarly lengthy period of drug elimination from the body following discontinuation of therapy.
Amiodarone is broadly effective in treating rhythm disturbances of both the upper (atria) and lower (ventricular) cardiac chambers. There is recent evidence to support a widespread view that amiodarone may be uniquely effective as an antiarrhythmic drug. Furthermore, the pharmacology of amiodarone permits once daily dosing with chronic therapy, a convenient feature. Given the potential for most of the antiarrhythmic agents to provoke serious rhythm disturbances in patients with underlying heart disease, amiodarone’s track record of relative safety in patients with coronary artery disease and congestive heart failure is a distinct advantage in this patient population.
Despite its effectiveness, amiodarone use is limited by a multitude of relatively frequent potential adverse effects. Often, the occurrence of side effects depends on cumulative drug dose over time. While amiodarone uncommonly promotes tachycardia, it may cause significant slowing of the heart rate. Amiodarone is also associated with a wide range of non-cardiac side effects. Patient’s may experience nervous system side effects, including tremor, headaches, and peripheral neuropathy. Visual problems may also occur, necessitating drug discontinuation. Rashes, particularly in response to sun exposure, are not uncommon, including a blue-grey discoloration of the skin. Thyroid and liver abnormalities commonly occur, necessitating periodic screening with blood work in patients taking amiodarone chronically. Finally, the risk of lung toxicity with amiodarone is of special concern because of its potentially serious nature.
Sotalol is an antiarrhythmic drug belonging to the class of drugs termed Beta-receptor blocking drugs or beta-blockers. In addition to its potent beta-blocking activity, sotalol has other properties, which make it a broadly effective agent for treating supraventricular and ventricular arrhythmias.
Sotalol may be dosed at a convenient interval of every 12 hours. Notably, sotalol is excreted almost exclusively by the kidneys. This necessitates close monitoring and dosing adjustment in patients with kidney dysfunction.
As a member of the beta-blocker family, sotalol may provoke acute spasm of the airways in patients with underlying asthma or chronic obstructive pulmonary disease (COPD). Additionally, sotalol may cause marked heart rate slowing. Like most of the other antiarrhythmic agents, sotalol also has the potential to cause serious rapid rhythm disturbances. This necessitates close monitoring during drug initiation and follow-up.
Dofetilide is one of the most recently released drugs in our armamentarium of antiarrhythmic agents, with current approval for the treatment of atrial fibrillation.
Like sotalol, dofetilide is dosed every 12 hours. With excretion by the kidneys, dosing must be carefully modified if kidney function is impaired.
Although dofetilide has the potential to cause serious cardiac rhythm disturbances, it has relatively few non-cardiac side effects. The risk of promotion of dangerous cardiac arrhythmias may be minimized by close monitoring of the cardiac rhythm during drug initiation, appropriate adjustment of dosage according to renal function, and avoidance of other drugs with the potential for interactions. Notably, current evidence suggests that dofetilide may be a relatively safe agent for use in patients with significant structural abnormalities of the heart, including coronary artery disease and congestive heart failure.
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