Table of Contents
Antiarrhythmic drugs are grouped into five different classes using the Vaughan-Williams classification system (see table below).
|Class 1||Fast sodium channel blockers. In turn, it is classified into three categories, namely:||1a: quinidine, disopyramide, procainamide (prolong repolarization)
1b: mexiletine, lidocaine, phenytoin (shorten repolarization)
1c: moricizine, flecainide, propafenone (no effect on repolarization)
|Class 2||Antagonist at the beta channels – Beta blocker||Timolol, propranolol, esmolol, metoprolol, atenolol|
|Class 3||Potassium channel blocker||amiodarone sotalol, ibutilide, dofetilide|
|Class 4||Slow calcium channel blockers||Verapamil and Diltiazem|
|Class 5||Miscellaneous||Digoxin, Adenosine, Magnesium sulfate, Trimagnesium dicitrate|
Description of the Action Potential
The heart’s action potential can be divided into five phases (0 to 4), beginning and ending with phase 4. Each channel is responsible for a different phase.
Phase 4: The resting phase
- The resting potential of a cardiac muscle is negative due to a constant outward leak of K+ ions.
Phase 0: Depolarization
- Phase 0 begins with a stimulus origin. When the stimulus exceeds the threshold, it leads to depolarization.
- Fast Na+ channels open and Na+ rapidly enters the cell.
- The large Na+ current rapidly depolarizes the membrane from resting (negative) potential to 0 mV and slightly above 0 mV (positive potential)
- Fast Na+ channels then close, as they are time dependent.
- L-type (“long-opening”) Ca2+ channels open and cause a small, steady entry of Ca2+ into the cell.
Phase 1: Early repolarization
- Some K+ channels open.
- An outward flow of K+ returns the positive membrane potential to approximately 0 mV.
Phase 2: The plateau phase
- L-type Ca2+ channels are still open and there is a small, constant, inward entry of Ca2+.
- At the same time, K+ moves out of the cell through its own channels.
- These two countercurrents are electrically balanced, and a plateau is achieved.
Phase 3: Repolarization
- Ca2+ channels are closed.
- The continuous outflow of K+ now exceeds Ca2+ entry.
- This brings the membrane potential back to resting negative potential (phase 4).
The action potential also varies between the different tissues of the heart—for example, the myocardium, conduction tissue, and impulse centers, such as sinoatrial and atrioventricular (AV) nodes.
Classification and Mechanism of Action
Miscellaneous antiarrhythmic agents include:
- Cardiac glycosides (eg, digoxin)
- Magnesium and potassium salts
Digoxin is an important member of the miscellaneous group, along with adenosine.
Mechanism of action
- Digoxin is commonly used to treat two conditions:
- Systolic heart failure
- Supraventricular tachycardia
In the case of supraventricular tachyarrhythmia, digoxin’s mechanism of action is quite different than when used in heart failure. Digoxin causes direct suppression of conduction through the AV node. This blockage increases the resistance for conduction of the impulse along the AV node. An increase in vagal tone also occurs. Thus, the refractory period increases and the conduction velocity decreases.
In cases of heart failure, digoxin inhibits the sodium/potassium ATPase pump in the cells of the myocardium. The inhibition of the sodium/potassium ATPase leads to an increase in the sodium concentration intracellularly, which, in turn, promotes calcium influx via the sodium-calcium exchange pump. The resulting increase in intracellular calcium is the main reason why digoxin is effective in treating heart failure.
Due to its multiple side effects and narrow therapeutic index, however, other drugs are usually used for both conditions.
The most dangerous manifestation of digoxin toxicity is arrhythmia. Other presentations include disturbances in the gastrointestinal tract along with neurological signs such as confusion and weakness. Changes in vision may also occur. Unfortunately, digoxin concentration does not always correlate with toxicity.
Treatment with the digoxin-specific antibody is recommended in all patients with clinically significant manifestations of digoxin toxicity. The other treatment option includes atropine, which helps decrease heart rate.
The concentration of digoxin in the body increases with administration of verapamil, quinidine, and amiodarone, as these medications can cause digoxin toxicity. As well, antacids decrease intestinal absorption and thus decrease the efficacy of digoxin.
Mechanism of action
Adenosine is used in the treatment of paroxysmal supraventricular tachycardia. It decreases conduction along the AV node and prevents the movement of reentry circuits into the heart. The A1 receptor, along with the G0, is believed to inhibit calcium conduction, which occurs in the conduction tissue.
Adenosine is administered intravenously. Its half-life is brief (< 10 seconds).
Drug efficacy is decreased by caffeine and theophylline products. Its toxic effect is enhanced by carbamazepine, digoxin, and dipyridamole.
Adverse and side effects
As with all antiarrhythmic drugs, there is always a risk of arrhythmias with adenosine administration. Other conditions that may occur include atrial premature contraction, atrial fibrillation, and block. Additionally, there is an increased risk of facial flushing, headache, dizziness, disturbances of the gastrointestinal tract and dyspnea, paresthesia, numbness, and discomfort in the extremities.
Magnesium and Potassium Salts
Indication and scope
In a patient with acute myocardial infarction (MI), the occurrence of hypokalemia and hypomagnesemia are risk factors for ventricular arrhythmia. The incidence of ventricular arrhythmia doubles in patients with hypokalemia. A magnesium/potassium supplement acts as a prophylaxis to prevent the occurrence of arrhythmia in patients with MI.
The successful correction of hypokalemia depends on the correction of hypomagnesemia. American College of Cardiology guidelines indicate that magnesium levels should be maintained above 2 mg/dl and potassium levels should be above 4 mg/ml.
Mechanism of action
There are two types of cholinergic receptors: muscarinic and nicotinic. Acetylcholine, which is released from the vagal nerve ending, is responsible for deceleration of the heart, which in turn leads to bradycardia. Bradycardia is itself a significant risk factor for the occurrence of arrhythmia. Atropine acts as a competitive antagonist of acetylcholine at the level of the muscarinic receptors. No effect occurs in the nicotinic receptor.
Adverse and side effects
Side effects include all muscarinic receptor blocker side effects, such as dry mouth and gastrointestinal disturbances.