Katzung & Trevor's Pharmacology Examination and Board Review, 9th Edition

Chapter 14. Antiarrhythmic Drugs

Antiarrhythmic Drugs: Introduction

Cardiac arrhythmias commonly occur in the presence of preexisting heart disease. They are the most common cause of death in patients with a myocardial infarction or terminal heart failure. They are also the most serious manifestation of digitalis toxicity and are often associated with anesthesia, hyperthyroidism, and electrolyte disorders. The drugs used for arrhythmias fall into five major groups or classes, but most have very low therapeutic indices and when feasible, nondrug therapies (cardioversion, pacemakers, implanted defibrillators) are used.

High-Yield Terms to Learn

Abnormal automaticity Pacemaker activity that originates anywhere other than in the sinoatrial node Abnormal conduction Conduction of an impulse that does not follow the path defined in Figure 14-1 or reenters tissue previously excited Atrial, ventricular fibrillation (AF, VF) Arrhythmias involving rapid reentry and chaotic movement of impulses through the tissue of the atria or ventricles. Ventricular, but not atrial, fibrillation is fatal if not terminated within a few minutes Group (class) 1, 2, 3, and 4 drugs A method for classifying antiarrhythmic drugs, sometimes called the Singh-Vaughan Williams classification; based loosely on the channel or receptor affected Reentrant arrhythmias Arrhythmias of abnormal conduction; they involve the repetitive movement of an impulse through tissue previously excited by the same impulse Effective refractory period The time that must pass after the upstroke of a conducted impulse in a part of the heart before a new action potential can be propagated in that cell or tissue Selective depression The ability of certain drugs to selectively depress areas of excitable membrane that are most susceptible, leaving other areas relatively unaffected Supraventricular tachycardia (SVT) A reentrant arrhythmia that travels through the AV node; it may also be conducted through atrial tissue as part of the reentrant circuit Ventricular tachycardia (VT) A very common arrhythmia, often associated with myocardial infarction; ventricular tachycardia may involve abnormal automaticity or abnormal conduction, usually impairs cardiac output, and may deteriorate into ventricular fibrillation; for these reasons it requires prompt management


What Is an Arrhythmia?

Normal electrical cardiac function (normal sinus rhythm, NSR) is dependent on generation of an impulse in the normal sinoatrial (SA) node pacemaker and its conduction through the atrial muscle, through the atrioventricular (AV) node, through the Purkinje conduction system, to the ventricular muscle (Figure 14-1). Normal pacemaking and conduction require normal action potentials (dependent on sodium, calcium, and potassium channel activity) under appropriate autonomic control. Arrhythmias (also called dysrhythmias) are therefore defined by exclusion, that is, any rhythm that is not normal sinus rhythm is an arrhythmia.


Schematic representation of the heart and normal cardiac electrical activity (intracellular recordings from areas indicated and ECG). The ECG is the body surface manifestation of the depolarization and repolarization waves of the heart. The P wave is generated by atrial depolarization, the QRS by ventricular muscle depolarization, and the T wave by ventricular repolarization. The PR interval is a measure of conduction time from atrium to ventricle through the atrioventricular (AV) node, and the QRS duration indicates the time required for all of the ventricular cells to be activated (ie, the intraventricular conduction time). The QT interval reflects the duration of the ventricular action potential. SA, sinoatrial.

(Reproduced, with permission, from Katzung BG, editor: Basic & Clinical Pharmacology, 11th ed. McGraw-Hill, 2009: Fig. 14-1.)

Arrhythmogenic Mechanisms

Abnormal automaticity and abnormal (reentrant) conduction are the 2 major mechanisms for arrhythmias. A few of the clinically important arrhythmias are atrial flutter, atrial fibrillation (AF), atrioventricular nodal reentry(a common type of supraventricular tachycardia [SVT]), premature ventricular beats (PVBs), ventricular tachycardia (VT), and ventricular fibrillation (VF). Examples of electrocardiographic (ECG) recordings of normal sinus rhythm and some of these common arrhythmias are shown in Figure 14-2. Torsade de pointes is a ventricular arrhythmia of great pharmacologic importance because it is often induced by antiarrhythmic and other drugs that change the shape of the action potential and prolong the QT interval. It has the ECG morphology of a polymorphic ventricular tachycardia, often displaying waxing and waning QRS amplitude. Torsade is also associated with long QT syndrome, a heritable abnormal prolongation of the QT interval caused by mutations in the IK or INa channel proteins.


Typical ECGs of normal sinus rhythm and some common arrhythmias. Major waves (P, Q, R, S, and T) are labeled in each electrocardiographic record except in panel 5, in which electrical activity is completely disorganized and none of these deflections are recognizable.

(Modified and reproduced, with permission, from Goldman MJ: Principles of Clinical Electrocardiography, 11th ed. McGraw-Hill, 1982.)

Normal Electrical Activity in the Cardiac Cell

The cellular action potentials shown in Figure 14-1 are the result of ion fluxes through voltage-gated channels and carrier mechanisms. These processes are diagrammed in Figure 14-3. In most parts of the heart, sodium current (INa) dominates the upstroke (phase 0) of the action potential (AP) and is the most important determinant of its conduction velocity. After a very brief activation, the sodium current enters a more prolonged period of inactivation. In the calcium-dependent AV node, calcium current (ICa) dominates the upstroke and the AP conduction velocity. The plateau of the AP (phase 2) is dominated by calcium current (ICa) and one or more potassium-repolarizing currents (referred to as a class as IK). At the end of the plateau, IK causes rapid repolarization (phase 3).


Components of the membrane action potential (AP) in a typical Purkinje or ventricular cardiac cell. The deflections of the AP, designated as phases 0-3, are generated by several ionic currents. The actions of the sodium pump and sodium-calcium exchanger are mainly involved in maintaining ionic steady state during repetitive activity. Note that small but significant currents occur during diastole (phase 4) in addition to the pump and exchanger activity. In non-pacemaker cells, the outward potassium current during phase 4 is sufficient to maintain a stable negative resting potential as shown by the solid line at the right end of the tracing. In pacemaker cells, however, the potassium current is smaller and the depolarizing currents (sodium, calcium, or both) during phase 4 are large enough to gradually depolarize the cell during diastole (dashed line). ATP, adenosine triphosphate.

The refractory period of most cardiac cells (the sodium-dependent cells) is a function of how rapidly sodium channels recover from inactivation. Recovery from inactivation depends on both the membrane potential, which varies with repolarization time and the extracellular potassium concentration, and on the actions of drugs that bind to the sodium channel (ie, sodium channel blockers). The carrier processes (sodium pump and sodium-calcium exchanger) contribute little to the shape of the AP (but they are critical for the maintenance of the ion gradients on which the sodium, calcium, and potassium currents depend). Antiarrhythmic drugs act on 1 or more of the 3 major currents (INa, ICa, IK) or on the  adrenoceptors that modulate these currents. Similarly, in the calcium-dependent AV node, the duration of refractoriness is dependent on the rate of recovery from inactivation of the calcium channels.

Drug Classification

The antiarrhythmic agents are usually classified using a system loosely based on the channel or receptor involved. As indicated by the figure on the first page of this chapter, this system specifies 4 groups or classes, usually denoted by the numerals 1 through 4, plus a miscellaneous group (Table 14-1 and Drug Summary Table).

·                  1. Sodium channel blockers

·                  2. Beta-adrenoceptor blockers

·                  3. Potassium channel blockers

·                  4. Calcium channel blockers

TABLE 14-1 Properties of the prototype antiarrhythmic drugs.

Drug Group PR Interval QRS Duration QT Interval Procainamide, disopyramide, quinidine 1A  or a

  Lidocaine, mexiletine 1B — —b

— Flecainide 1C  (slight)  — Propranolol, esmolol 2  — — Amiodarone 3, 1A, 2, 4    Ibutilide, dofetilide 3 — —  Sotalol 3, 2  —  Verapamil 4  — — Adenosine Misc  — —

aPR interval may decrease owing to antimuscarinic action or increase owing to channel-blocking action.

bLidocaine, mexiletine, and some other group 1B drugs slow conduction through ischemic, depolarized ventricular cells but not in normal tissue.

The miscellaneous group includes adenosine, potassium ion, and magnesium ion.

Group 1 Antiarrhythmics (Local Anesthetics)


The group 1 drugs are further subdivided on the basis of their effects on AP duration (Figure 14-4). Group 1A agents (prototype procainamide ) prolong the AP. Group 1B drugs (prototype lidocaine ) shorten the AP in some cardiac tissues. Group 1C drugs (prototype flecainide ) have no effect on AP duration.


Schematic diagram of the effects of group 1 agents. Note that all group 1 drugs reduce both phase 0 and phase 4 sodium currents (wavylines) in susceptible cells. Group 1A drugs also reduce phase 3 potassium current (IK) and prolong the action potential (AP) duration. This results in significant prolongation of the effective refractory period (ERP). Group 1B and group 1C drugs have different (or no) effects on potassium current and thus shorten or have no effect on the AP duration. However, all group 1 drugs prolong the ERP by slowing recovery of sodium channels from inactivation.

Mechanism of Action

All group 1 drugs slow or block conduction in ischemic and depolarized cells and slow or abolish abnormal pacemakers wherever these processes depend on sodium channels. The most selective agents (those in group 1B) have significant effects on sodium channels in ischemic tissue, but negligible effects on channels in normal cells. In contrast, less selective group 1 drugs (groups 1A and 1C) cause some reduction of INa even in normal cells.

Useful sodium channel-blocking drugs bind to their receptors much more readily when the channel is open or inactivated than when it is fully repolarized and recovered from its previous activity. Ion channels in arrhythmic, abnormal tissue spend more time in the open or inactivated states than do channels in normal tissue. Therefore, these antiarrhythmic drugs block channels in abnormal tissue more effectively than channels in normal tissue. As a result, antiarrhythmic sodium channel blockers are use dependent or state dependent in their action (ie, they selectively depress tissue that is frequently depolarizing, eg, during a fast tachycardia; or tissue that is relatively depolarized during rest, eg, by hypoxia). The effects of the major group 1 drugs are summarized in Table 14-1 and in Figure 14-4.

Drugs with Group 1A Action

Procainamide is a group 1A prototype. Other drugs with group 1A actions include quinidine and disopyramide. Amiodarone , often classified in group 3, also has typical group 1A actions. These drugs affect both atrial and ventricular arrhythmias. They block INa, and therefore slow conduction velocity in the atria, Purkinje fibers, and ventricular cells. At high doses they also slow AV conduction. The reduction in ventricular conduction results in increased QRS duration in the ECG. In addition, the 1A drugs block IK and slow repolarization. Therefore, they increase AP duration and the effective refractory period (ERP) in addition to slowing conduction velocity and ectopic pacemakers. The increase in AP duration generates an increase in QT interval (Table 14-1). Amiodarone has similar effects on sodium current (INa block) and has the greatest AP-prolonging effect (IK block).

Drugs with Group 1B Actions

Lidocaine is the prototype 1B drug and is used exclusively by the IV or IM routes. Mexiletine is an orally active 1B agent. Lidocaine selectively affects ischemic or depolarized Purkinje and ventricular tissue and has little effect on atrial tissue; the drug reduces AP duration in some cells, but because it slows recovery of sodium channels from inactivation it does not shorten (and may even prolong) the effective refractory period. Mexiletine has similar effects. Because these agents have little effect on normal cardiac cells, they have little effect on the ECG (Table 14-1). Phenytoin , an anticonvulsant and not a true local anesthetic, is sometimes classified with the group 1B antiarrhythmic agents because it can be used to reverse digitalis-induced arrhythmias. It resembles lidocaine in lacking significant effects on the normal ECG.

Drugs with Group 1C Action

Flecainide is the prototype drug with group 1C actions. Other members of this group are used outside the United States and may be available in this country in special circumstances. These drugs have no effect on ventricular AP duration or the QT interval. They are powerful depressants of sodium current, however, and can markedly slow conduction velocity in atrial and ventricular cells. They increase the QRS duration of the ECG.

Pharmacokinetics, Clinical Uses, and Toxicities

Pharmacokinetics of the major drugs are listed in the Drug Summary Table at the end of the chapter.

Group 1A Drugs

Procainamide can be used in all types of arrhythmias: atrial and ventricular arrhythmias are most responsive. Quinidine and disopyramide have similar effects but are used much less frequently. Procainamide is also commonly used in arrhythmias during the acute phase of myocardial infarction.

Procainamide may cause hypotension (especially when used parenterally) and a reversible syndrome similar to lupus erythematosus. Quinidine causes cinchonism (headache, vertigo, tinnitus); cardiac depression; gastrointestinal upset; and autoimmune reactions (eg, thrombocytopenic purpura). As noted in Chapter 13, quinidine reduces the clearance of digoxin and may increase the serum concentration of the glycoside significantly. Disopyramide has marked antimuscarinic effects and may precipitate heart failure. All group 1A drugs may precipitate new arrhythmias. Torsade de pointes is particularly associated with quinidine and other drugs that prolong AP duration (except amiodarone). The toxicities of amiodarone are discussed in the following text.

Hyperkalemia usually exacerbates the cardiac toxicity of group 1 drugs. Treatment of overdose with these agents is often carried out with sodium lactate (to reverse drug-induced arrhythmias) and pressor sympathomimetics (to reverse drug-induced hypotension) if indicated.

Group 1B Drugs

Lidocaine is useful in acute ischemic ventricular arrhythmias, for example, after myocardial infarction. Atrial arrhythmias are not responsive unless caused by digitalis. Mexiletine has similar actions and is given orally. Lidocaine is usually given intravenously, but intramuscular administration is also possible. It is never given orally because it has a very high first-pass effect and its metabolites are potentially cardiotoxic.

Lidocaine and mexiletine occasionally cause typical local anesthetic toxicity (ie, central nervous system [CNS] stimulation, including convulsions); cardiovascular depression (usually minor); and allergy (usually rashes but may extend to anaphylaxis). These drugs may also precipitate arrhythmias, but this is much less common than with group 1A drugs. Hyperkalemia increases cardiac toxicity.

Group 1C Drugs

Flecainide is effective in both atrial and ventricular arrhythmias but is approved only for refractory ventricular tachycardias and for certain intractable supraventricular arrhythmias. Flecainide and its congeners are more likely than other antiarrhythmic drugs to exacerbate or precipitate arrhythmias (proarrhythmic effect). This toxicity was dramatically demonstrated by the Cardiac Arrhythmia Suppression Trial (CAST), a large clinical trial of the prophylactic use of group 1C drugs in myocardial infarction survivors. The trial results showed that group 1C drugs caused greater mortality than placebo. For this reason, the group 1C drugs are now restricted to use in persistent arrhythmias that fail to respond to other drugs. Group 1C drugs also cause local anesthetic-like CNS toxicity. Hyperkalemia increases the cardiac toxicity of these agents.

Group 2 Antiarrhythmics (Beta Blockers)

Prototypes, Mechanisms, and Effects

Beta blockers are discussed in more detail in Chapter 10. Propranolol and esmolol are prototypic antiarrhythmic  blockers. Their mechanism in arrhythmias is primarily cardiac -adrenoceptor blockade and reduction in cAMP, which results in the reduction of both sodium and calcium currents and the suppression of abnormal pacemakers. The AV node is particularly sensitive to  blockers and the PR interval is usually prolonged by group 2 drugs (Table 14-1). Under some conditions, these drugs may have some direct local anesthetic (sodium channel-blocking) effect in the heart, but this is probably rare at the concentrations achieved clinically. Sotalol and amiodarone, generally classified as group 3 drugs, also have group 2 -blocking effects.

Clinical Uses and Toxicities

Esmolol, a very short-acting  blocker for intravenous administration, is used exclusively in acute arrhythmias. Propranolol, metoprolol, and timolol are commonly used as prophylactic drugs in patients who have had a myocardial infarction. These drugs provide a protective effect for 2 yrs or longer after the infarct.

The toxicities of  blockers are the same in patients with arrhythmias as in patients with other conditions (Chapter 10 and Drug Summary Table). While patients with arrhythmias are often more prone to -blocker-induced depression of cardiac output than are patients with normal hearts, it should be noted that judicious use of these drugs reduces progression of chronic heart failure (Chapter 13) and reduces the incidence of potentially fatal arrhythmias in this condition.

Skill Keeper: Characteristics of  Blockers

(See Chapter 10)

Describe the important subgroups of  blockers and their major pharmacokinetic and pharmacodynamic features. The Skill Keeper Answer appears at the end of the chapter.

Group 3 Antiarrhythmics (Potassium IK Channel Blockers)


Dofetilide and ibutilide are typical group 3 drugs. Sotalol is a chiral compound (ie, it has 2 optical isomers). One isomer is an effective  blocker, and both isomers contribute to the antiarrhythmic action. The clinical preparation contains both isomers. Amiodarone is usually classified as a group 3 drug because it blocks the same K channels and markedly prolongs AP duration as well as blocking sodium channels. Dronedarone is a new drug, similar to amiodarone but less efficacious and less toxic.

Mechanism and Effects

The hallmark of group 3 drugs is prolongation of the AP duration. This AP prolongation is caused by blockade of IK potassium channels that are responsible for the repolarization of the AP (Figure 14-5). AP prolongation results in an increase in effective refractory period and reduces the ability of the heart to respond to rapid tachycardias. Sotalol, ibutilide, dofetilide, and amiodarone (and group 1A drugs; see prior discussion) produce this effect on most cardiac cells; the action of these drugs is, therefore, apparent in the ECG as an increase in QT interval (Table 14-1).


Schematic diagram of the effects of group 3 agents. All group 3 drugs prolong the AP duration in susceptible cardiac cells by reducing the outward (repolarizing) phase 3 potassium current (IK, wavy lines). The main effect is to prolong the effective refractory period (ERP). Note that the phase 4 diastolic potassium current (IK1) is not affected by these drugs.

Clinical Uses and Toxicities

Sotalol is available by the oral route (Drug Summary Table). It may precipitate torsade de pointes arrhythmia as well as signs of excessive blockade such as sinus bradycardia and asthma. Ibutilide and dofetilide are recommended for atrial flutter and fibrillation. Their most important toxicity is induction of torsade de pointes. The toxicities of group 1A drugs (which share the IK potassium channel-blocking action of group 3 agents) are discussed with the group IA drugs.

Amiodarone: A Special Case

Amiodarone is useful in most types of arrhythmias and is considered the most efficacious of all antiarrhythmic drugs. This may be because it has a broad spectrum: It blocks sodium, calcium, and potassium channels and adrenoceptors. Because of its toxicities, however, amiodarone is approved for use mainly in arrhythmias that are resistant to other drugs. Nevertheless, it is used very extensively, off label, in a wide variety of arrhythmias because of its superior efficacy.

Amiodarone causes microcrystalline deposits in the cornea and skin, thyroid dysfunction (hyper- or hypothyroidism), paresthesias, tremor, and pulmonary fibrosis. Amiodarone rarely causes new arrhythmias, perhaps because it blocks calcium channels and  receptors as well as sodium and potassium channels. Dronedarone , an amiodarone analog that may be less toxic, has recently been approved. Like amiodarone, it acts on sodium, potassium, and calcium channels but at present it is approved only for the treatment of atrial fibrillation or flutter.

Group 4 Antiarrhythmics (Calcium Channel Blockers)


Verapamil is the prototype. Diltiazem is also an effective antiarrhythmic drug. Nifedipine and the other dihydropyridines are not useful as antiarrhythmics, probably because they decrease arterial pressure enough to evoke a compensatory sympathetic discharge to the heart. The latter effect facilitates rather than suppresses arrhythmias.

Mechanism and Effects

Verapamil and diltiazem are effective in arrhythmias that must traverse calcium-dependent cardiac tissue (eg, the AV node). These agents cause a state- and use-dependent selective depression of calcium current in tissues that require the participation of L-type calcium channels (Figure 14-6). AV conduction velocity is decreased and effective refractory period increased by these drugs. PR interval is consistently increased (Table 14-1).


Schematic diagram of the effects of group 4 drugs in a calcium-dependent cardiac cell in the AV node (note that the AP upstroke in this figure is due mainly to calcium current). Group 4 drugs reduce inward calcium current during the AP and during phase 4 (wavy lines). As a result, conduction velocity is slowed in the AV node and refractoriness is prolonged. Pacemaker depolarization during phase 4 is slowed as well if caused by excessive calcium current. ERP, effective refractory period.

Clinical Use and Toxicities

Calcium channel blockers are effective for converting AV nodal reentry (also known as nodal tachycardia) to normal sinus rhythm. Their major use is in the prevention of these nodal arrhythmias in patients prone to recurrence. These drugs are orally active; and also available for parenteral use (see Drug Summary Table). The most important toxicity of these drugs is excessive pharmacologic effect, because cardiac contractility, AV conduction, and blood pressure can be significantly depressed. These agents should be avoided in ventricular tachycardias. See Chapter 12 for additional discussion of toxicity. Amiodarone has moderate calcium channel-blocking activity.

Miscellaneous Antiarrhythmic Drugs


Adenosine is a normal component of the body, but when it is given in high doses (6-12 mg) as an intravenous bolus, the drug markedly slows or completely blocks conduction in the atrioventricular node (Table 14-1), probably by hyperpolarizing this tissue (through increased IK1) and by reducing calcium current. Adenosine is extremely effective in abolishing AV nodal arrhythmias, and because of its very low toxicity it has become the drug of choice for this arrhythmia. Adenosine has an extremely short duration of action (about 15 s). Toxicity includes flushing and hypotension, but because of their short duration these effects do not limit the use of the drug. Transient chest pain and dyspnea (probably due to bronchoconstriction) may also occur.

Potassium Ion

Potassium depresses ectopic pacemakers, including those caused by digitalis toxicity. Hypokalemia is associated with an increased incidence of arrhythmias, especially in patients receiving digitalis. Conversely, excessive potassium levels depress conduction and can cause reentry arrhythmias. Therefore, when treating arrhythmias, serum potassium should be measured and normalized if abnormal.

Magnesium Ion

Magnesium appears to have similar depressant effects as potassium on digitalis-induced arrhythmias. Magnesium also appears to be effective in some cases of torsade de pointes arrhythmia.

Nonpharmacologic Treatment of Arrhythmias

It should be noted that electrical methods of treatment of arrhythmias have become very important. These methods include (1) external defibrillation, (2) implanted defibrillators, (3) implanted pacemakers, and (4) radiofrequency ablation of arrhythmogenic foci via a catheter.

Skill Keeper Answer: Characteristics of  Blockers

(See Chapter 10)

The major subgroups of  blockers and their pharmacologic features are conveniently listed in a table:

-Blocker Subgroup, Features Examples Nonselective Propranolol and timolol are typical 1-selective

Atenolol, acebutolol, and metoprolol are typical; possibly less hazardous in asthmatic patients Partial agonist Acebutolol and pindolol are typical; possibly less hazardous in asthmatic patients Lacking local anesthetic effect Timolol is the prototype; important for use in glaucoma Low lipid solubility Atenolol is the prototype; may reduce CNS toxicity Very short and long acting Esmolol (an ester) is the shortest acting and used only IV; nadolol is the longest acting Combined  and  blockade Carvedilol, labetalol


When you complete this chapter, you should be able to:

 Describe the distinguishing electrophysiologic and ECG effects of the 4 major groups of antiarrhythmic drugs and adenosine.

 List 2 or 3 of the most important drugs in each of the 4 groups.

 List the major toxicities of those drugs.

 Describe the mechanism of selective depression by local anesthetic antiarrhythmic agents.

 Explain how hyperkalemia, hypokalemia, or an antiarrhythmic drug can cause an arrhythmia.

Drug Summary Table: Antiarrhythmic Drugs

Subclass Mechanism of Action Clinical Applications Pharmacokinetics Toxicities, Interactions Group 1A Procainamide Use- and state-dependent block of INa channels; some block of IK channels. Slowed conduction velocity and pacemaker activity; prolonged action potential duration and refractory period

Atrial and ventricular arrhythmias, especially after myocardial infarction Oral and parenteral; oral slow-release forms available Duration: 2-3 h Increased arrhythmias, hypotension, lupus-like syndrome Disopyramide: Similar to procainamide but longer duration of action; toxicity includes antimuscarinic effects and heart failure Quinidine: Similar to procainamide but toxicity includes cinchonism (tinnitus, headache, gastrointestinal disturbance) and thrombocytopenia Group 1B Lidocaine Highly selective use and state-dependent INa block; minimal effect in normal tissue; no effect on IK

Ventricular arrhythmias post-myocardial infarction and digoxin-induced arrhythmias IV and IM Duration: 1-2 h Central nervous system (CNS) sedation or excitation Mexiletine: Similar to lidocaine but oral activity and longer duration of action Group 1C Flecainide Selective use and state-dependent block of INa; slowed conduction velocity and pacemaker activity

Refractory arrhythmias Oral Duration: 20 h Increased arrhythmias; CNS excitation Group 2 Propranolol Block of  receptors; slowed pacemaker activity Postmyocardial infarction as prophylaxis against sudden death ventricular fibrillation; thyrotoxicosis Oral, parenteral Duration: 4-6 h Bronchospasm; cardiac depression, atrioventricular (AV) block, hypotension (see Chapter 10) Esmolol: Selective 1-receptor blockade; IV only, 10-min duration. Used in perioperative and thyrotoxicosis arrhythmias

Group 3 Amiodarone Strong IK block produces marked prolongation of action potential and refractory period. Group 1 activity slows conduction velocity; groups 2 and 4 activity confer additional antiarrhythmic activity

Refractory arrhythmias; used off-label in many arrhythmias (broad spectrum of therapeutic action) Oral, parenteral Half-life and duration of action: 1-10 wk Thyroid abnormalities, deposits in skin and cornea, pulmonary fibrosis, optic neuritis Sotalol IK block and -adrenoceptor block

Ventricular arrhythmias and atrial fibrillation Oral Duration: 7 h Dose-related torsade de pointes; cardiac depression Ibutilide Selective IK block; prolonged action potential and QT interval

Treatment of acute atrial fibrillation Ibutilide is IV only Duration: 6 h Torsade de pointes Dofetilide Like ibutilide Treatment and prophylaxis of atrial fibrillation Oral Duration: 7 h Torsade de pointes Group 4 Verapamil State and use-dependent ICa block slows conduction in AV node and pacemaker activity; PR interval prolongation

AV nodal arrhythmias, especially in prophylaxis Oral, parenteral Duration: 7 h Cardiac depression; constipation, hypotension Diltiazem Like verapamil Rate control in atrial fibrillation Oral, parenteral Duration: 6 h Like verapamil Miscellaneous Adenosine Increase in diastolic IK of AV node that causes marked hyperpolarization and conduction block; reduced ICa

Acute nodal tachycardias IV only Duration: 10-15 s Flushing, bronchospasm, chest pain, headache Potassium ion Increase in all K currents, decreased automaticity, decreased digitalis toxicity Digitalis toxicity and other arrhythmias if serum K is low Oral or IV Both hypokalemia and hyperkalemia are associated with arrhythmogenesis. Severe hyperkalemia causes cardiac arrest Magnesium ion Poorly understood, possible increase in Na+/K+ ATPase activity

Digitalis arrhythmias and other arrhythmias if serum Mg is low IV Muscle weakness, severe hypermagnesemia can cause respiratory paralysis

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