Antiarrhythmic drugs are chemical substances designed to change the electrical properties of the heart muscle and the conduction system so that (it is hoped) abnormal circuits are suppressed. The drugs act on all cells within the heart but may have different effects on diseased cells than they have on healthy cells. In individuals with heart disease, these differences in effects may be beneficial by suppressing the firing of groups of cells in abnormal circuits or by changing the length of time required for recovery from firing so that the circuit can no longer exist. The problem is that the changes in conduction properties induced by the drugs may also cause new circuits to be activated. This latter property is called proarrhythmia and has been observed to cause dangerous or even fatal arrhythmias to occur in individuals with structural heart disease who previously exhibited no such arrhythmias. This side effect, as do all side effects, varies greatly from patient to patient in terms of likelihood of occurrence and severity.
Beta-Blockers (class II) and Calcium Channel Blockers (class IV)
The antiarrhythmic drugs differ widely in their proarrhythmic potential and in their ability to suppress arrhythmias. Beta blockers (such as metoprolol, atenolol, propranolol, and bisoprolol) and calcium channel blockers (such as verapamil and diltiazem) have proven over time to be quite safe. Beta blockers act by decreasing the sensitivity of cells to adrenaline-like substances. They have long been used in the treatment of SVT and in the slowing of the ventricular rate in atrial fibrillation. More recent studies have suggested that beta blockers may also be quite useful in the suppression of VT and VF as well and may significantly decrease the risk of sudden death in individuals with coronary artery disease. Beta blockers are thought to be completely free of dangerous proarrhythmic risk, although beta blockers may actually increase the frequency of SVT in patients who take them to suppress SVT. The side effects of beta blockers include slowing of the heart rate, lowering of the blood pressure, and causing a feeling of mild depression or apathy at first that resolves with continued use.
Calcium blockers such as verapamil and diltiazem act by altering the cellular metabolism of calcium. Verapamil and diltiazem are used to treat some forms of SVT and VT and to slow the ventricular rate in atrial fibrillation. They were originally developed as blood pressure medications, and their side effects include slowing of the heart rate and lowering of the blood pressure. Both also dilate blood vessels and may cause swelling and fluid retention. Verapamil and diltiazem carry no risk of dangerous proarrhythmia but can make SVT more frequent.
The remaining antiarrhythmic medications are medications that have the highest risk of dangerous proarrhythmia, especially for patients with structural heart disease. Included in this group are quinidine, procainamide, disopyramide, flecainide, moricizine, and sotalol. These drugs may be used for the control of SVT or, in very controlled situations, VT. Beside the risk of dangerous proarrhythmia, side effects may include nausea, diarrhea, fatigue, skin rash, arthritis, or other drug-specific problems.
Sodium Channel Blockers
Quinidine, procainamide, disopyramide, flecainide, and moricizine are antiarrhythmic medications that have been used for many years in the United States. Their primary activity in the heart is to slow impulse conduction and thereby prevent potential reentrant circuits from activating. A metabolic by-product of procainamide, N-acetyl procainamide, also has antiarrhythmic activity. Flecainide and moricizine have been proven directly to increase the death rate in patients with coronary artery disease who take them, while it has been suggested from combined analysis of small studies that quinidine may also have proarrhythmic effects. It is not certain whether this hazard also extends to individuals without structural heart disease, but these drugs must always be used with caution.
Potassium Channel Blockers (class III)
Amiodarone and sotalol are drugs that work by prolonging the recovery time of cardiac cells after they have carried an impulse. In doing this, circuits may not be able to cause arrhythmias at all or may only be able to accommodate slower arrhythmias. Sotalol, which is also a beta blocker, has shown less proarrhythmic risk than quinidine or flecainide thus far, and its principal side effects (other than proarrhythmia) are the same as those caused by other beta blockers.
Amiodarone is generally considered to be the most powerful of the antiarrhythmic drugs. Amiodarone exhibits properties of all the other antiarrhythmic drugs, but nevertheless it appears to have a very low risk of proarrhythmia. Its potential side effects can affect almost any organ system because of its tendency to accumulate in body tissues. The most common side effects include sun sensitivity, thyroid problems, tremors, heart rate slowing, and balance problems. The most feared side effects are a chemical hepatitis and lung inflammation, both of which can usually be detected by routine screening before they become serious. The side effects of amiodarone generally wear off after the drug is stopped.