HAVE YOU NOTICED how challenging it is to keep pace with the changing beat of pharmacology? Just as you learn the latest drugs and classifications, new classes are developed and new drugs added to classes. Even drugs that have been on the market a long time can have dosing and indication changes.
Antiarrhythmic drugs, which restore normal rhythm and conduction to the heart, are no exception. In this article, I'll bring you up-to-date on the antiarrhythmics now available.
Class assignments
Most antiarrhythmic drugs used to slow a rapid heart rate are classified according to the Vaughn Williams classification system (see Classifying Antiarrhythmics the Vaughn Williams way). These drugs fall into four general groups in this classification system with each group having several subgroups. Drugs are assigned to classes I through IV according to their effects on the heart's action potential; each class acts on a different phase. For details on cardiac conduction, see Conducting impulses.
Of course, it's not completely straightforward: The classes can be quite confusing because they include some types of drugs that have properties of more than one class; others don't fit into any class at all. Let's break it down, class by class, and review some examples.
Class I
Sodium channel blockers stop the flow of sodium into the cell during the initial phase of the action potential. The blocking action slows the exchange of ions through the sodium-potassium channel, resulting in conduction and repolarization delays.
Drugs in Class I are further broken down into three subcategories:
* Class IA drugs, which moderately block the effect of the sodium channels, reducing conductivity and prolonging repolarization and the action potential
* Class IB drugs, which cause a minimal blocking effect and shorten repolarization
* Class IC drugs, which have marked sodium channel blocking effects and significantly reduce conductivity.
Procainamide, a Class IA drug, is used to convert atrial fibrillation (AF) or flutter to normal sinus rhythm and to control the rate if ventricular function is preserved. Procainamide can also be used for paroxysmal supraventricular tachycardia (PSVT) that's uncontrolled by vagal maneuvers and adenosine, or for stable wide-complex tachycardia of unknown origin, as long as cardiac function is preserved.
Because procainamide may cause dysrhythmias, use it cautiously, especially if the patient has had an acute myocardial infarction (MI), if he's hypokalemic or hypomagnesemic, or if he's receiving other drugs that prolong the QT interval, such as amiodarone or sotalol. Reduce the dosage if he has renal impairment.
Lidocaine, a Class IB drug, may be used to treat hemodynamically stable ventricular tachycardia (VT) or cardiac arrest from VT or ventricular fibrillation (VF). Lidocaine isn't recommended in acute MI to prevent ventricular dysrhythmias.
Flecainide, a Class IC drug, is approved in oral form only in the United States. It's indicated to treat ventricular dysrhythmias and supraventricular tachycardia (SVT) in patients without coronary artery disease (CAD). It's also been found to stop AF, atrial flutter, SVT, and atrioventricular (AV) nodal reentry tachycardia associated with an accessory pathway. Because this drug has negative inotropic effects, it shouldn't be used in patients with impaired left ventricular function.
Propafenone is another Class IC drug that's approved for oral use only in the United States. It's indicated to treat ventricular and supraventricular dysrhythmias.
Don't give propafenone to patients who've had an MI or who have CAD because it's been found to increase the risk of death in patients who've had an MI. Be sure to frequently check digoxin levels and the international normalized ratio when propafenone is taken with digoxin or warfarin, because it can increase digoxin and warfarin levels. Propafenone also has significant negative inotropic effects, so it won't be ordered if left ventricular function is impaired.
Class II
Beta-receptor blockers decrease sinoatrial (SA) nodal automaticity, increase AV nodal refractoriness, and decrease AV nodal conduction velocity. These drugs are used to control ventricular response and to convert the rhythm in PSVT, AF, and atrial flutter. The cardiac conduction effects of beta-blockers are similar to those of the calcium channel blockers diltiazem and verapamil.
Beta-blockers are divided into three categories:
* nonselective beta-adrenergic receptor blockers, including propranolol. These drugs decrease heart rate and contractility but also block beta-receptors in the lungs.
* cardiac selective beta-adrenergic receptor blockers, which include atenolol, metoprolol, and esmolol. They block beta-receptors in the heart only.
* combination alpha-beta receptor blockers, such as labetalol, which block alpha-receptors in the peripheral blood vessels, resulting in vasodilation, and beta-receptors in the heart.
Class III
Potassium channel blockers inhibit the movement of potassium during the third phase of the action potential (cell membrane recovery), prolonging repolarization and the refractory period.
Ibutilide is used to convert recent-onset AF and atrial flutter. Ibutilide prolongs the action potential and increases atrial and ventricular refractoriness.
Be alert for potential adverse reactions when administering ibutilide. Ventricular arrhythmias, such as torsade de pointes, occur in about 3% of patients who receive ibutilide. Patients with significantly impaired left ventricular function are at greatest risk for these dysrhythmias. Monitor the patient's cardiac rhythm during the infusion and for 4 to 6 hours postinfusion.
Amiodarone is an example of a Class III drug that has properties of all four Vaughn Williams classes. Patients may develop hypotension from this drug, so monitor blood pressure frequently. Also watch for compatibility with other drugs being given; amiodarone can prolong the QT interval, so don't use it with other drugs that prolong the QT interval. Amiodarone is given intravenously (I.V.) or orally, depending on the indication. The drug is administered I.V. in emergencies or when the patient can't take it orally. It's used orally in nonemergency situations and for maintenance therapy.
If your patient is on maintenance therapy, tell him to avoid the sun and to use sunblock. Sun exposure will give the skin a blue or grayish tint.
Class IV
Calcium channel blockers inhibit the movement of calcium through the slow calcium channels of the SA and AV nodes. But only two calcium channel blockers affect heart rate by inhibiting the movement of calcium during the second phase of the action potential: diltiazem and verapamil. Calcium channel blockers decrease conduction velocity, increase the refractory period at the SA and AV nodes, and decrease the strength of contraction.
Diltiazem and verapamil are often used to treat rapid AF and atrial flutter. By slowing conduction through the AV node, these drugs decrease ventricular response, reducing myocardial oxygen consumption. These drugs should be used in the presence of second- or third-degree heart block or sick sinus syndrome without a pacemaker, and should be avoided in patients with a history of heart failure. Use them with extreme caution in older adults. Diltiazem and verapamil shouldn't be given to patients with Wolff-Parkinson-White syndrome (a dysrhythmia caused by an extra abnormal electrical pathway in the heart) and AF or atrial flutter.
Unclassified antiarrhythmics
Some antiarrhythmics don't fall into any of the classes mentioned above. Let's take a closer look.
Atropine is typically used to treat symptomatic bradycardias while the patient awaits transcutaneous pacing. It blocks the effects of acetylcholine on the SA and AV nodes, increasing heart rate. If the patient is experiencing myocardial ischemia or hypoxia, remember that atropine increases myocardial oxygen demand.
Atropine should be avoided if the patient is experiencing bradycardia as a result of hypothermia. In that situation, the hypothermic heart may not respond to the drug. In addition, because of reduced drug metabolism, the drug may accumulate to toxic levels.
Atropine can be administered through an endotracheal tube in an emergency when I.V. or intraosseous routes aren't possible.
If the patient doesn't respond to atropine, an epinephrine or dopamine infusion may be considered while the patient awaits pacing or if pacing is ineffective. Dopamine may be used to increase the heart rate.
Both epinephrine and dopamine may cause tachydysrhythmias or excessive vasoconstriction. These drugs should be given through a central venous access device whenever possible to minimize the risk of extravasation.
Digoxin can be used to slow the ventricular rate in patients with AF or atrial flutter. This drug decreases heart rate and conduction velocity through the AV node, and increases cardiac contractility.
Digoxin is often combined with another drug. It isn't indicated for acute treatment of dysrhythmias because building to a therapeutic digoxin level takes time. Monitor the patient for signs and symptoms of digoxin toxicity, including conduction abnormalities, nausea, vomiting, fatigue, generalized muscle weakness, yellow-green halos around images, and blurred vision.
Adenosine, a naturally occurring amino acid found in all body cells, is the treatment of choice for most forms of narrow-complex PSVT. Adenosine slows conduction through the AV node and can interrupt the reentry pathways through the AV node.
Adenosine has an extremely short half-life, less than 10 seconds. Transient effects of adenosine include brief periods of asystole, bradycardia, and ventricular ectopy.
Magnesium sulfate can be another treatment option for ventricular dysrhythmias. Because magnesium is essential for the function of the sodium-potassium pump and cell depolarization, magnesium deficiency is associated with a high incidence of cardiac dysrhythmias.
Ready for steady rhythm
By understanding the mechanisms of action and indications for antiarrhythmic drugs that may be ordered in an emergency, you'll be better prepared to manage your patient's care and help get him back on the beat.
Conducting impulses
The conduction system of the heart, shown below, begins with the heart's natural pacemaker, the sinoatrial (SA) node. When an impulse leaves the SA node, it travels through the atria along Bachmann's bundle and the internodal pathways on its way to the atrioventricular (AV) node. After the impulse passes through the AV node, it travels to the ventricles, first down the bundle of His, then along the bundle branches and, finally, down the Purkinje fibers.
Classifying antiarrhythmics the Vaughn Williams way
Here are examples of the four classes:
Class I: sodium channel blockers
Class IA
* quinidine
* procainamide (Pronestyl)
* disopyramide (Norpace)
Class IB
* lidocaine
* phenytoin (Dilantin)
* mexiletine (Mexitil)
Class IC
* flecainide (Tambocor)
* propafenone (Rythmol)
Class II: beta-receptor blockers
* propranolol (Inderal)
* acebutolol (Sectral)
* esmolol (Brevibloc)
Class III: potassium channel blockers
* amiodarone (Cordarone)
* ibutilide (Corvert)
* dofetilide (Tikosyn)
* sotalol (Betapace)
Class IV: calcium channel blockers
* diltiazem (Cardizem)
* verapamil (Isoptin, Calan)
Other agents
* atropine
* digoxin (Lanoxin)
* adenosine (Adenocard)
* magnesium
Selected references