Introduction
See also
- electrical control of the heart
- supraventricular tachycardias
- wide complex tachycardias
Organized electrical activity of the heart plays a significant role in cardiac function, and disruption of this activity in the form of arrhythmias may result in clinical symptoms or even death. These arrhythmias may be too fast – tachyarrhythmias – or to slow – bradyarrhythmias. They may be caused by ischemia, electrolyte abnormalities, sympathetic load, and medications, among other causes.
Antiarrhythmic drugs are used for acute and long term control of arrhythmias, and work to reduce abnormal impulse control in two main ways. They may impact the ion channels for sodium, potassium, and calcium that regulate the heartbeat. They may also modify the neuronal control of the heart, particularly the beta adrenergic innervation of the sympathetic nervous system.
Unfortunately, while antiarrhythmic drugs are meant to bring normalcy to the heart beat, on occasion, the opposite may occur, and they may in fact cause life-threatening arrhythmias. This is particularly true for the sodium channel blocking drugs.
Classification
There are many ways to classify antiarrhythmic medications, and none are universally accepted. However, one of the most common, to be used here, is the Vaughan-Williams classification, which is organized according to the mechanism of action. These classes include:
- class I: sodium channel blockers
- class II: beta receptor blockers
- class III: action potential prolonging medications
- class IV: calcium channel blockers
- class V: digoxin, adenosine, magnesium
Class I – Sodium Channel Blockade
Class I medications, which block sodium channels, are further subdivided into three categories, based on their effects.
Class Ia medications slow the rise of phase 0 of the action potential, therefore slowing conduction velocity. They also prolong the ventricular refractory period, as well as slow the depolarization of phase 4 of pacemaker cells. Class Ia medications include:
- quinidine
- procainamide
- disopyramide
Class Ib medications slow the conduction, and shorten the action potential, of healthy tissue. Class Ib medications include:
- lidocaine
- phenytoin
Class Ic medications slow the rise of phase 0 of the action potential, as well as shorten the refractory period of Purkinje fibres. Class Ic medications include:
- flecainide
- propafenone
While not used frequently in the emergency setting, these medications play an important role in rate management for chronic tachyarrhythmias in certain circumstances. There are also instances where these medications are indicated over more commonly used agents. For example, in the patient with Wolff-Parkinson-White (WPW), certain rate control medications may be contraindicated as they could provoke complete AV nodal blockade. Instead, the clinician may consider procainamide as a rate control medication.
Class II – Beta blockers
Beta blockers reduce arrhythmias in two main ways:
- by blocking beta1 receptors, they decrease the chronotropic and ionotropic response of cardiac tissues to sympathetic stimulation
- Membrane stabilization through blockade of sodium channels (at higher doses)
The effect of beta blockers include:
- Prolongation of the PR interval
- Increase action pulse duration
- work by increasing refractory period
- leads to two-way block
Examples of class II beta blockers include:
- propranolol
- metoprolol (beta1 selective)
- atenolol
- Acebutalol (beta1 selective)
- carvedilol
- bisoprolol
- Esmolol (short acting)
These medications are used very commonly both in emergency and primary care settings. In the context of coronary artery disease, congestive heart failure and chronic rapid arrhythmias there are benefits of beta-blockers for both heart rate control and mortality. Additionally, in those with rapid tachycardia or hypertension, one may consider small boluses of a beta blocker, commonly metoprolol, to achieve rate or pressure control under continuous monitoring.
Beta blockade may be dangerous when used with other AV nodal blocking drugs. They may also be dangerous during uncompensated heart failure, as well as asthma, given the risk of brochospasm. For the latter, beta1 selective drugs are much preferred.
Class III – Potassium Channel Efflux
Class III drugs prolong the action potentials in many ways.
Amiodarone is one of the most commonly used drugs of this class, acting on sodium, potassium, and calcium channels, and with alpha- and beta-adrenergic blocking capacity. These effects combine to inhibit ectopic pacemaker activity. It comes with many substantial side effects. Short term use of amiodarone can include bradycardia, QT prolongation, GI distress, as well as phlebitis if given intravenously. Longer term effects can include photosensitivity, neuropathy, hepatic fibrosis, pulmonary fibrosis, hypothyroidism, and hyperthyroidism.
Other Class III drugs include:
- sotalol (inhibits K channel function, as well as providing beta blockade)
- Dronedarone
- ibutilide (blocks K efflux and activates Na influx)
- dofetilide (blocks K efflux)
Amiodarone may be used to terminate ventricular tachycardia or ventricular fibrillation, particularly during ACLS care. Given its side effects, it should be used beyond this by clinicians with expertise in managing cardiac arrhythmias.
Likewise, other class III medications also pose serious risk of adverse effects, and should only be used by experts. Conditions that may ne managed include atrial fibrillation or flutter, as well as ventricular arrhythmias.
Class IV – Calcium channel blockers
Calcium channel blockers are negative inotropes, blocking Ca2+ influx into vascular smooth muscle cells and cardiomyocytes. These drugs slow the heart rate by reducing AV node conduction velocity and increasing the refractory period. They also result in
- coronary/peripheral vasodilation
- decreased contractility
- decreased afterload
- decreased vasospasms
Calcium channel blockers (CCBs) may be found in two classes.
Dihydropyridines, including amlodipine and nifedipine, have minimal effect on cardiac tissues and are not used in managing arrhythmias.
The non-dihydropyridines include verapamil and diltiazem, and are commonly used to treat arrhythmias.
Non-dihydropyridine CCBs – verapamil and diltiazem – are most commonly used to treat supraventricular arrhythmias, particularly those that result from increased automaticity. Atrial fibrillation with a rapid ventricular response also responds well to these drugs.
However, they may worsen ventricular tachycardias.
CCBs may worsen heart failure, and caution should be used in situations of poor left ventricular function.
Class V – Other
Many drugs that affect cardiac rhythm may not be classified in the above categories, and hence are grouped in the ‘other’ category. These drugs include:
Digoxin is a cardiac glycoside used to increase cardiac contractility. It works to inhibit the cardiac Na-K ATPase, increasing sodium concentrations inside the cell. The Na/Ca exchanger increases intracellular [Ca], leading to increased contraction and therefore cardiac output.
It is used for control of atrial fibrillation and flutter, including situations where congestive heart failure has occurred.
With a narrow therapeutic index, digoxin is one of the few drugs whose levels can, and should, be monitored. It can cause arrhythmias and AV block, potentially leading to cardiac arrest, as well as hypokalemia.Toxicity can also cause visual changes and neuropsychiatric manifestations.
Adenosine is an endogenous nucleoside that acts as a signal molecule. Large doses of IV adenosine activate the A1 receptor in the SA and AV node. This results in hyperpolarization through an influx of K, with a reduction of Ca influx following. A profound, transient heart block results.
The ability of adenosine to cause heart block means it is commonly used to terminate supraventricular tachycardias. It may also be used to temporarily slow the heart rate, allowing for more accurate diagnosis of an unclear rhythm
It has rapid onset of action and half life, lasting only seconds. It can cause symptoms of angina and shortness of breath, and patients should be warned of these disconcerting but temporary sensations. It can also lead to bronchospasm, and care should be taken with patients with asthma or COPD.
Magnesium is an electolyte found throughout the body, with widespread effects. Within the heart, magnesium slows the SA node rate by stabilizing the cell membrane.
Magnesium may be used as an anti-arrhythmic in cases of polymorphic ventricular tachycardia, or torsades de pointes. It may also be used by some in circumstances of pulseless VT or ventricular fibrillation, especially with a history of hypomagnesemia.
Magnesium is normally loaded into an IV bag and administered over a number of minutes.