administration. The injection should be made as close to the heart as possible and should be followed by a saline flush. The initial dose is 6 mg. If there is no response in 1 or 2 minutes, 12 mg may be tried and repeated once. If a response is going to occur, it should happen as soon as the drug reaches the AV node.
Digoxin
Although its primary indication is HF, digoxin [Lanoxin] is also used to treat supraventricular dysrhythmias. The basic pharmacology of digoxin is discussed in Chapter 48. Consideration here is limited to treatment of dysrhythmias.
Effects on the Heart
Digoxin suppresses dysrhythmias by decreasing conduction through the AV node and by decreasing automaticity in the SA node. The drug decreases AV conduction by (1) a direct depressant effect on the AV node and by (2) acting in the CNS to increase vagal (parasympathetic) impulses to the AV node.
Digoxin decreases automaticity of the SA node by increasing vagal traffic to the node and by decreasing sympathetic traffic. It should be noted that, although digoxin decreases automaticity in the SA node, it can increase automaticity in Purkinje fibers. The latter effect contributes to dysrhythmias caused by digoxin.
Effects on the ECG
By slowing AV conduction, digoxin prolongs the PR interval. The QT interval may be shortened, reflecting accelerated repolarization of the ventricles.
Depression of the ST segment is common. The T wave may be depressed or even inverted. There is little or no change in the QRS complex.
Adverse Effects and Interactions
The major adverse effect is cardiotoxicity (dysrhythmias). Risk is increased by hypokalemia, which can result from concurrent therapy with diuretics (thiazides and loop diuretics). Accordingly, it is essential that potassium levels be kept within the normal range (3.5 to 5 mEq/L). The most common adverse effects are GI disturbances (anorexia, nausea, vomiting, abdominal discomfort).
CNS responses (fatigue, visual disturbances) are also relatively common.
Antidysrhythmic Uses
Digoxin is used only for supraventricular dysrhythmias. The drug is inactive against ventricular dysrhythmias.
Atrial Fibrillation and Atrial Flutter. Digoxin can be used to slow ventricular rate in patients with atrial fibrillation and atrial flutter. Ventricular rate is decreased by reducing the number of atrial impulses that pass through the AV node.
Supraventricular Tachycardia. Digoxin may be employed acutely and chronically to treat SVT. Acute therapy is used to abolish the dysrhythmia.
Chronic therapy is used to prevent its return. Digoxin suppresses SVT by increasing cardiac vagal tone and by decreasing sympathetic tone.
Dosage and Administration
Oral therapy is generally preferred. The initial dosage is 1 to 1.5 mg administered in three or four doses over 24 hours. The maintenance dosage is 0.125 to 0.5 mg/day. This dose should be decreased in patients with renal impairment.
Verapamil for intravenous use is supplied in solution (5 mg/2 mL). The initial dose is 5 to 10 mg injected slowly (over 2 to 3 minutes). If the dys- rhythmia persists, an additional 10 mg may be administered in 30 minutes.
An IV infusion (0.375 mg/min) can be used for maintenance. Intravenous verapamil can cause serious cardiovascular effects. Accordingly, blood pressure and the ECG should be monitored, and equipment for resuscitation should be immediately available.
Verapamil for oral use is available in immediate- and sustained-release tablets. The maintenance dosage is 40 to 120 mg 3 or 4 times a day.
Diltiazem. Like verapamil, diltiazem may be given IV or PO. Intravenous therapy is preferred for initial treatment, and oral therapy is used for maintenance.
Intravenous therapy is initiated with an IV bolus (0.25 mg/kg). If the response is inadequate, a second bolus (0.35 mg/kg) may be administered in 15 minutes. If appropriate, initial therapy may be followed with a continuous IV infusion (up to 24 hours’ duration) at a rate of 5 to 15 mg/hr.
Diltiazem for oral use is available in immediate-release and extended-release tablets. Maintenance dosing is 360 to 480 mg daily taken in four divided doses.
OTHER ANTIDYSRHYTHMIC DRUGS Adenosine
Adenosine [Adenocard], a naturally occurring nucleotide, is a drug of choice for terminating paroxysmal SVT. Adenosine has an extremely short half-life and thus must be administered IV. Adverse effects are minimal because adenosine is rapidly cleared from the blood.
Effects on the Heart and ECG
Adenosine decreases automaticity in the SA node and greatly slows conduction through the AV node. The most prominent ECG change is prolongation of the PR interval, brought on by delayed AV conduction. Adenosine works in part by inhibit- ing cyclic AMP–induced calcium influx, thereby suppressing calcium-dependent action potentials in the SA and AV nodes.
Therapeutic Use
Adenosine is approved only for termination of paroxysmal SVT, including Wolff-Parkinson-White syndrome. The drug is not active against atrial fibrillation, atrial flutter, or ventricular dysrhythmias.
Pharmacokinetics
Adenosine has an extremely short half-life (estimated at 1.5 to 10 seconds), owing primarily to rapid uptake by cells and partly to deactivation by circulating adenosine deaminase.
Because of its rapid clearance, adenosine must be administered by IV bolus, as close to the heart as possible.
Adverse Effects
Adverse effects are short lived, lasting less than 1 minute. The most common are sinus bradycardia, dyspnea (from broncho- constriction), hypotension and facial flushing (from vasodilation), and chest discomfort (perhaps from stimulation of pain receptors in the heart).
KEY POINTS
■ Dysrhythmias result from alteration of the electrical impulses that regulate cardiac rhythm. Antidysrhythmic drugs control rhythm by correcting or compensating for these alterations.
■ In the healthy heart, the SA node is the pacemaker.
■ Impulses originating in the SA node must travel through the AV node to reach the ventricles. Impulses arriving at the AV node are delayed before going on to excite the ventricles.
■ The His-Purkinje system conducts impulses rapidly throughout the ventricles, thereby causing all parts of the ventricles to contract in near synchrony.
■ The heart employs two kinds of action potentials: fast potentials and slow potentials.
■ Fast potentials occur in the His-Purkinje system, atrial muscle, and ventricular muscle.
■ Slow potentials occur in the SA node and AV node.
■ Phase 0 of fast potentials (depolarization) is generated by rapid influx of sodium. Because depolarization is fast, these potentials conduct rapidly.
■ During phase 2 of fast potentials, calcium enters myocardial cells, thereby promoting contraction.
■ Phase 3 of fast potentials (repolarization) is generated by rapid extrusion of potassium.
■ Phase 0 of slow potentials (depolarization) is caused by slow influx of calcium. Because depolarization is slow, these potentials conduct slowly.
■ Spontaneous phase 4 depolarization—of fast or slow potentials—gives cells automaticity.
■ Spontaneous phase 4 depolarization of cells in the SA node normally determines heart rate.
■ The P wave of an ECG is caused by depolarization of the atria.
■ The QRS complex is caused by depolarization of the ventricles. Widening of the QRS complex indicates slowed conduction through the ventricles.
■ The T wave is caused by repolarization of the ventricles.
■ The PR interval represents the time between onset of the P wave and onset of the QRS complex. PR prolongation indicates delayed AV conduction.
■ The QT interval represents the time between onset of the QRS complex and completion of the T wave. QT prolonga- tion indicates delayed ventricular repolarization.
■ Dysrhythmias arise from disturbances of impulse formation (automaticity) or impulse conduction.
■ Reentrant dysrhythmias result from a localized, self- sustaining circuit capable of repetitive cardiac stimulation.
■ Tachydysrhythmias can be divided into two major groups:
supraventricular tachydysrhythmias and ventricular tachy- dysrhythmias. In general, ventricular tachydysrhythmias disrupt cardiac pumping more than do supraventricular tachydysrhythmias.
■ Treatment of supraventricular tachydysrhythmias is often directed at blocking impulse conduction through the AV node, rather than at eliminating the dysrhythmia.
■ Treatment of ventricular dysrhythmias is usually directed at eliminating the dysrhythmia.
■ All antidysrhythmic drugs are also prodysrhythmic (proar- rhythmic). That is, they all can worsen existing dysrhythmias and generate new ones.
■ Class I antidysrhythmic drugs block cardiac sodium chan- nels and thereby slow impulse conduction through the atria, ventricles, and His-Purkinje system.
■ Slowing ventricular conduction widens the QRS complex.
■ Quinidine (a class IA drug) blocks sodium channels and delays ventricular repolarization. Delaying ventricular repolarization prolongs the QT interval.
■ Quinidine causes diarrhea and other GI symptoms in 33%
of patients. These effects frequently force drug withdrawal.
■ Quinidine can cause dysrhythmias. Widening of the QRS complex (by 50% or more) and excessive prolongation of the QT interval are warning signs.
■ Quinidine can raise digoxin levels. If the drugs are used together, digoxin dosage must be reduced.
■ Class IB agents differ from class IA agents in two ways:
they accelerate repolarization and have little or no effect on the ECG.
■ Lidocaine (a class IB agent) is used only for ventricular dysrhythmias. The drug is not active against supraventricular dysrhythmias.
■ Lidocaine undergoes rapid inactivation by the liver. As a result, it must be administered by continuous IV infusion.
■ Propranolol and other class II drugs block cardiac beta1
receptors.
■ By blocking cardiac beta1 receptors, propranolol attenuates sympathetic stimulation of the heart and thereby decreases SA nodal automaticity, AV conduction velocity, and myocardial contractility.
■ By decreasing AV conduction velocity, propranolol prolongs the PR interval.
■ The effects of propranolol on the heart result (ultimately) from suppressing calcium entry. Therefore, the cardiac effects of propranolol and the effects of calcium channel blockers are nearly identical.
■ Propranolol is especially useful for treating dysrhythmias caused by excessive sympathetic stimulation of the heart.
■ In patients with supraventricular tachydysrhythmias, propranolol helps by (1) slowing discharge of the SA node and (2) decreasing impulse conduction through the AV node, which prevents the atria from driving the ventricles at an excessive rate.
■ Class III antidysrhythmics block potassium channels and thereby delay repolarization of fast potentials. As a result, they prolong the action potential duration and the effective refractory period. By delaying ventricular repolarization, they prolong the QT interval.
■ Amiodarone (a class III agent) is highly effective against atrial and ventricular dysrhythmias, but can cause multiple serious adverse effects, including damage to the lungs, eyes, liver, and thyroid.
■ Dronedarone, a derivative of amiodarone, is somewhat less toxic than amiodarone, but also less effective. In patients with heart failure or permanent atrial fibrillation, dronedarone doubles the risk of death.
■ Verapamil and diltiazem (class IV antidysrhythmics) block cardiac calcium channels and thereby reduce automaticity of the SA node, slow conduction through the AV node, and decrease myocardial contractility. These effects are identical to those of the beta blockers.
■ By suppressing AV conduction, verapamil and diltiazem prolong the PR interval.
■ Verapamil and diltiazem are used to slow ventricular rate in patients with atrial fibrillation or atrial flutter and to terminate SVT caused by an AV nodal reentrant circuit.
In both cases, benefits derive from suppressing AV nodal conduction.
■ Adenosine is a drug of choice for terminating paroxysmal SVT.
■ Adenosine has a very short half-life (less than 10 seconds) and must be given by IV bolus.
Please visit http://evolve.elsevier.com/Lehne for chapter- specific NCLEX® examination review questions.
Summary of Major Nursing Implications
aSummaries are limited to the major antidysrhythmic drugs.
Summaries for beta blockers (propranolol, acebutolol, and esmolol), phenytoin, calcium channel blockers (verapamil and diltiazem), and digoxin appear in Chapters 18, 24, 45, and 48, respectively.
QUINIDINE
Preadministration Assessment Therapeutic Goal
The usual goal is long-term suppression of atrial and ven- tricular dysrhythmias.
Baseline Data
Obtain a baseline ECG and laboratory evaluation of liver function. Determine blood pressure.
Identifying High-Risk Patients
Quinidine is contraindicated for patients with a history of hypersensitivity to quinidine or other cinchona alkaloids and for patients with complete heart block, digoxin toxicity, or conduction disturbances associated with marked QRS widening and QT prolongation.
Exercise caution in patients with partial AV block, HF, hypotensive states, and hepatic dysfunction.
Implementation: Administration Routes
Usual Route. Oral.
Rare Routes. IM and IV.
Administration
Advise patients to take quinidine with meals. Warn them not to crush or chew sustained-release formulations.
Dosage size depends on the particular quinidine salt being used: 200 mg of quinidine sulfate is equivalent to 275 mg of quinidine gluconate.
Ongoing Evaluation and Interventions Evaluating Therapeutic Effects
Monitor for beneficial changes in the ECG. Plasma drug levels should be kept between 2 and 5 mcg/mL.
Minimizing Adverse Effects
Diarrhea. Diarrhea and other GI disturbances occur in one-third of patients and frequently force drug withdrawal.
Inform patients that they can reduce GI effects by taking quinidine with meals.
Cinchonism. Inform patients about symptoms of cincho- nism (tinnitus, headache, nausea, vertigo, disturbed vision), and instruct them to notify the prescriber if these develop.
Cardiotoxicity. Monitor the ECG for signs of cardiotoxic- ity, especially widening of the QRS complex (by 50% or more) and excessive prolongation of the QT interval. Monitor pulses for significant changes in rate or regularity. If signs of cardiotoxicity develop, withhold quinidine and notify the prescriber.
Arterial Embolism. Embolism may occur during therapy of atrial fibrillation. Risk is reduced by treatment with an anticoagulant (e.g., warfarin, dabigatran). Observe for signs of thromboembolism (e.g., sudden chest pain, dyspnea), and report these immediately.
Minimizing Adverse Interactions
Digoxin. Quinidine can double digoxin levels. When these drugs are combined, digoxin dosage should be reduced.
Monitor patients for digoxin toxicity (dysrhythmias).
PROCAINAMIDE
Preadministration Assessment Therapeutic Goal
Procainamide is indicated for acute and long-term management of ventricular and supraventricular dysrhythmias. Because procainamide can be toxic with long-term use, quinidine is preferred to procainamide for chronic suppression.
Baseline Data
Obtain a baseline ECG, complete blood count, and laboratory evaluations of liver and kidney function. Determine blood pressure.
Identifying High-Risk Patients
Procainamide is contraindicated for patients with systemic lupus erythematosus (SLE), complete AV block, and second-
Continued
degree or third-degree AV block in the absence of an elec- tronic pacemaker, and patients with a history of procaine allergy.
Exercise caution in patients with hepatic or renal dysfunction.
Implementation: Administration Routes
Oral, IM, IV.
Administration
Instruct patients to administer procainamide at evenly spaced intervals around-the-clock. Warn patients not to crush or chew sustained-release formulations.
When switching from IV procainamide to oral procain- amide, allow 3 hours to elapse between stopping the infusion and giving the first oral dose.
Give IM injections deep into the gluteal muscle.
Ongoing Evaluation and Interventions Evaluating Therapeutic Effects
Monitor the ECG for beneficial changes. Plasma drug levels should be kept between 3 and 10 mcg/mL.
Minimizing Adverse Effects
SLE-like Syndrome. Prolonged therapy can produce a syndrome resembling SLE. Inform patients about manifesta- tions of SLE (joint pain and inflammation; hepatomegaly;
unexplained fever; soreness of the mouth, throat, or gums), and instruct them to notify the prescriber if these develop.
If SLE is diagnosed, procainamide should be discontinued.
If discontinuation is impossible, signs and symptoms can be controlled with a nonsteroidal anti-inflammatory drug (e.g., aspirin) or a glucocorticoid. The ANA titer should be measured periodically, and if it rises, procainamide withdrawal should be considered.
Blood Dyscrasias. Procainamide can cause agranulocy- tosis, thrombocytopenia, and neutropenia. Deaths have occurred. Obtain complete blood counts weekly during the first 3 months of treatment and periodically thereafter. Instruct patients to inform the prescriber at the first sign of infection (fever, chills, sore throat), bruising, or bleeding. If subsequent blood counts indicate hematologic disturbance, discontinue procainamide immediately.
Cardiotoxicity. Procainamide can cause dysrhythmias.
Monitor pulses for changes in rate or regularity. Monitor the ECG for excessive QRS widening (greater than 50%) and for PR prolongation. If these occur, withhold procainamide and notify the prescriber.
Arterial Embolism. Embolism may occur during therapy of atrial fibrillation. Risk is reduced by treatment with an anticoagulant (e.g., warfarin, dabigatran). Observe for signs of thromboembolism (e.g., sudden chest pain, dyspnea), and report these immediately.
LIDOCAINE
Preadministration Assessment Therapeutic Goal
Acute management of ventricular dysrhythmias.
Baseline Data
Obtain a baseline ECG and determine blood pressure.
Identifying High-Risk Patients
Lidocaine is contraindicated for patients with Stokes-Adams syndrome, Wolff-Parkinson-White syndrome, and severe degrees of SA, AV, or intraventricular block in the absence of electronic pacing.
Exercise caution in patients with hepatic dysfunction or impaired hepatic blood flow.
Implementation: Administration Routes
Usual. IV.
Emergencies. IM.
Administration
Intravenous. Make certain the lidocaine preparation is labeled for IV use (i.e., is devoid of preservatives and catechol- amines). Dilute concentrated preparations with 5% dextrose in water.
The initial dose is 50 to 100 mg (1 mg/kg) infused at a rate of 25 to 50 mg/min. For maintenance, monitor the ECG and adjust the infusion rate on the basis of cardiac response.
The usual rate is 1 to 4 mg/min.
Intramuscular. Reserve for emergencies. The usual dose is 300 mg injected into the deltoid muscle. Switch to IV lidocaine as soon as possible.
Ongoing Evaluation and Interventions Evaluating Therapeutic Effects
Continuous ECG monitoring is required. Plasma drug levels should be kept between 1.5 and 5 mcg/mL.
Minimizing Adverse Effects
Excessive doses can cause convulsions and respiratory arrest.
Equipment for resuscitation should be available. Seizures can be managed with diazepam.
AMIODARONE
Preadministration Assessment Therapeutic Goal
Oral Therapy. Long-term treatment of (1) atrial fibrillation and (2) life-threatening recurrent ventricular fibrillation or recurrent hemodynamically unstable ventricular tachycardia in patients who have not responded to safer drugs.
Intravenous Therapy. Initial treatment of recurrent ventricular fibrillation, shock-resistant ventricular fibrillation,
Summary of Major Nursing Implications
a—cont’d
aPatient education information is highlighted as blue text.
recurrent hemodynamically unstable ventricular tachycardia, atrial fibrillation, and AV nodal reentrant tachycardia.
Baseline Data
Obtain a baseline ECG, eye examination, and chest x-ray, along with potassium and magnesium levels, and tests for thyroid, pulmonary, and liver function.
Identifying High-Risk Patients
Amiodarone is contraindicated for patients with severe sinus node dysfunction or second- or third-degree AV block, and for women who are pregnant or breast-feeding.
Exercise caution in patients with thyroid disorders, hypokalemia, or hypomagnesemia.
Implementation: Administration Routes
Oral. Used for maintenance therapy of atrial and ven- tricular dysrhythmias.
Intravenous. Used for acute therapy of atrial and ven- tricular dysrhythmias.
Administration and Dosage
Oral. Initiate treatment in a hospital. High doses are used initially (800 to 1600 mg/day for 1 to 3 weeks). The usual maintenance dosage is 400 mg/day.
Intravenous. Administer by continuous IV infusion, starting with a rapid infusion rate and later reducing the rate for maintenance. Intravenous treatment may last from 2 days to 3 weeks.
Ongoing Evaluation and Interventions Evaluating Therapeutic Effects
Monitor for beneficial changes in the ECG.
Minimizing Adverse Effects
Pulmonary Toxicity. Amiodarone can cause potentially fatal lung damage (hypersensitivity pneumonitis, interstitial/
alveolar pneumonitis, and pulmonary fibrosis). Obtain a baseline chest x-ray and pulmonary function test, and monitor pulmonary function throughout treatment. Inform patients about signs of lung injury (dyspnea, cough, chest pain), and instruct them to report these immediately. Treatment consists of withdrawing amiodarone and providing supportive care, sometimes including glucocorticoids.
Cardiotoxicity. Amiodarone can cause HF and atrial and ventricular dysrhythmias. Patients with pre-existing heart failure must not use the drug. Warn patients about signs of HF (e.g., shortness of breath, reduced exercise tolerance, fatigue, tachycardia, weight gain), and instruct them to report these immediately.
Liver Toxicity. Amiodarone can injure the liver. Obtain tests of liver function at baseline and periodically during treatment. If circulating liver enzymes exceed 3 times the normal level, amiodarone should be withdrawn. Inform
patients about signs and symptoms of liver injury (e.g., anorexia, nausea, vomiting, malaise, fatigue, itching, jaundice, dark urine), and instruct them to report them immediately.
Thyroid Toxicity. Amiodarone can cause hypothyroidism and hyperthyroidism. Obtain tests of thyroid function at baseline and periodically during treatment. Treat hypothyroid- ism with thyroid hormone supplements. Treat hyperthyroidism with an antithyroid drug (e.g., methimazole) or thyroidectomy.
Stopping amiodarone should be considered.
Toxicity in Pregnancy and Breast-Feeding. Amiodarone can harm the developing fetus and breast-feeding infant. Warn
patients to avoid pregnancy and breast-feeding while using amiodarone and for several months after stopping.
Ophthalmic Effects. Amiodarone has been associated with optic neuropathy and optic neuritis, sometimes progressing to blindness. Obtain ophthalmic tests, including funduscopy and a slit-lamp examination, at baseline and periodically during treatment. Advise patients to report reductions in visual acuity or peripheral vision. If optic neuropathy or neuritis is diagnosed, discontinuing amiodarone should be considered.
Virtually all patients develop corneal microdeposits. In most cases, the deposits have no effect on vision and thus only rarely lead to the discontinuation of amiodarone.
Dermatologic Effects. Photosensitivity reactions are common. Advise patients to avoid sunlamps and to wear sunscreen and protective clothing when outdoors. With prolonged sun exposure, skin may develop a bluish-gray discoloration, which typically resolves a few months after amiodarone is stopped.
Minimizing Adverse Interactions
Amiodarone is subject to significant interactions with many drugs. Interactions of special concern are presented here.
Drugs Whose Levels Can Be Increased by Amioda- rone. Amiodarone can increase levels of several drugs, including quinidine, procainamide, phenytoin, digoxin, dil- tiazem, warfarin, cyclosporine, and three statins: lovastatin, simvastatin, and atorvastatin. Dosages of these agents often require reduction.
Drugs That Can Reduce Amiodarone Levels. Amio- darone levels can be reduced by cholestyramine (which decreases amiodarone absorption) and by agents that induce CYP3A4 (e.g., St. John’s wort, rifampin). Monitor to ensure that amiodarone is still effective.
Drugs That Can Increase the Risk of Dysrhyth- mias. The risk of severe dysrhythmias is increased by diuretics (because they can reduce levels of potassium and magnesium) and by drugs that prolong the QT interval.
Drugs That Can Cause Bradycardia. Combining amio- darone with a beta blocker, verapamil, or diltiazem can lead to excessive slowing of heart rate.
Grapefruit Juice. Grapefruit juice inhibits CYP3A4 and can raise levels of amiodarone. Toxicity can result. Advise
patients to avoid grapefruit juice.