Antiarrhythmic Drugs: A Practical Guide, Second Edition

185 Pages·2007·1.5 MB·English

by  Richard N. Fogoros(auth.)

Antiarrhythmic
Drugs
A practical guide
SECOND EDITION
Richard N. Fogoros, M.D.
Pittsburgh,PA
(cid:1)C 2007RichardFogoros
PublishedbyBlackwellPublishing
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Firstpublished1997
Secondedition2007
1 2007
ISBN:978-1-4051-6351-4
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Fogoros,RichardN.
AntiarrhythmicDrugs:apracticalguide/RichardN.Fogoros.–2nded.
p.;cm.
Includesbibliographicalreferencesandindex.
ISBN978-1-4051-6351-4(alk.paper)
1.Myocardialdepressants. 2.Arrhythmia–Chemotherapy. I.Title.
[DNLM:1.Anti-ArrhythmiaAgents. 2.Arrhythmia–drugtherapy.
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2007005643
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Contents
Preface,v
Aknowledgments,viii
Part 1 Basic principles
Chapter1 Mechanismsofcardiactachyarrhythmias,3
Chapter2 Introductiontoantiarrhythmicdrugs,36
Part 2 Clinical features of
antiarrhythmic drugs
Chapter3 ClassIantiarrhythmicdrugs,55
Chapter4 ClassIIantiarrhythmicdrugs;
beta-blockingagents,80
Chapter5 ClassIIIantiarrhythmicdrugs,86
Chapter6 ClassIVdrugs:calcium-blockingagents,102
Chapter7 Unclassifiedantiarrhythmicagents,107
Chapter8 Investigationalantiarrhythmicdrugs,112
Chapter9 Commonadverseeventswith
antiarrhythmicdrugs,117
Part 3 Antiarrhythmic drugs in the treatment
of cardiac arrhythmias
Chapter10 Basicprinciplesofusingantiarrhythmicdrugs,133
Chapter11 Treatmentofsupraventriculartachyarrhythmias,138
iii
iv Contents
Chapter12 Treatmentofventriculararrhythmias,151
Chapter13 Treatmentofarrhythmiasinpregnancy,164
Index,169
Preface
Physiciansoncefounditconvenienttothinkofcardiacarrhythmias
as a sort of “itch” of the heart and of antiarrhythmic drugs as a
soothing balm that, applied in sufficient quantities, would relieve
theitch.Duringthepastseveraldecades,however,pioneeringwork
has revealed many of the complexities of cardiac arrhythmias and
of the drugs used to treat them. To the dismay of most reasonable
people,theold,convenientviewpointfinallyprovedutterlyfalse.
Indeed,inthedecadesincethefirsteditionofthisbookappeared,
thewidespreadnotionthatantiarrhythmicdrugsareasalveforthe
irritated heart has been, appropriately, completely reversed. Every
clinicianworthhisorhersaltnowrealizesthatantiarrhythmicdrugs
areamongthemosttoxicsubstancesusedinmedicine,theyareas
likely as not to provoke even more dangerous arrhythmias, and,
indeed,theuseofmostofthesedrugsinmostclinicalsituationshas
beenassociatedwithanincrease(andnotadecrease)inmortality.
Thisnewfoundrespectfor(ifnotfearof)antiarrhythmicdrugshas
beenaccompaniedbythecomfortingmurmursofanelitearmyof
electrophysiologists,assuringlessadeptcliniciansthat,really,there
isnoreasontoworryaboutthesenastysubstancesanymore.After
all(theysay),whatwithimplantabledefibrillators,radiofrequency
ablation, and other emerging technologies (that, by the way, only
wearequalifiedtoadminister),theantiarrhythmicdrugasaserious
clinicaltoolhasbecomenearlyobsolete.
Itiscertainlytruethattheuseofantiarrhythmicdrugshasbeen
considerably curtailed over the past decade or so and that other
emerging treatments have led to significantly improved outcomes
formanypatientswithcardiacarrhythmias.Butneitherthewidely
acknowledgedshortcomingsofthesedrugsnorthedisseminationof
new technologies has eliminated the usefulness of antiarrhythmic
drugsorobviatedtheneedtoapplythem,whenappropriate,inthe
treatmentofpatientswithcardiacarrhythmias.
Consider that implantable defibrillators, while in clinical use for
over 25 years, are still indicated for only a tiny proportion of pa-
tientswhoareatincreasedriskofarrhythmicdeathandareactually
v
vi Preface
implantedinonlyasmallproportionofthese.Untilthesedevicesare
madefarcheaper,easiertoimplant,andmorereliablethantheyare
today (changes that would require dramatic—and thus unlikely—
alterationsinthebusinessmodelsofboththecompaniesthatmake
themandthedoctorswhoimplantthem),theywillneverbeusedin
thevastmajorityofpatientswhoareatriskofarrhythmicdeath.And
considerthatablationtechniquestocureatrialfibrillation—thear-
rhythmiathatproducesthegreatestcumulativemorbidityacrossthe
population—havefailed,despiteprolongedanddedicatedefforts,to
becomesufficientlyeffectiveorsafeforwidespreaduse.Andfinally,
considerthatwithadeeperunderstandingofcellularelectrophysiol-
ogy,drugcompaniesarenowbeginningto“tailor”newcompounds
that might be more effective and less toxic than those in current
use, and that some future generation of antiarrhythmic drugs—
possiblyevensomeoftheinvestigationaldrugsdiscussedherein—
mayofferaveryattractivealternativetocertainexpensiveorrisky
technologies.
Itremainsimportant,therefore,foranyhealth-careprofessional
caring for patients who are at risk of developing cardiac arrhyth-
mias (and not just the electrophysiologists) to understand some-
thingaboutantiarrhythmicdrugs.Accordingly,thisbookisintended
fornonexperts—thepractitioners,trainees,andstudents—whoare
mostoftencalledupontomakedecisionsregardingactualpatients
withcardiacarrhythmias.Thebookattemptstosetoutaframework
forunderstandingantiarrhythmicdrugs:howtheywork,whatthey
actuallydotoimprove(orworsen)thecardiacrhythm,andthefac-
torsonemustconsiderindecidingwhenandhowtousethem.Such
aframework,itishoped,willnotonlyserveasaguidepostinmaking
clinicaldecisions,butwillalsoprovideabasisforinterpretingnew
information that comes to light on antiarrhythmic drugs and their
placeinthetreatmentofcardiacarrhythmias.
The book is divided into three parts. Part 1 is an introduction to
basic principles—the mechanism of cardiac arrhythmias and how
antiarrhythmic drugs work. Part 2 discusses the clinically relevant
featuresofthedrugsthemselves,includingemerginginvestigational
drugsthatappeartoshowpromise.Part3drawsonthisbasicinfor-
mationtoexplorethetreatmentofspecificcardiacarrhythmiasand
emphasizes the current roll of antiarrhythmic drugs in managing
thesearrhythmias.
Throughout this book, basic principles are emphasized. Accord-
ingly, when a choice had to be made between simplicity and
Preface vii
complexity, simplicity prevailed in almost every case. The author
recognizesthatsomecolleaguesmaynotagreewithanapproachthat
risksoversimplificationofaninherentlycomplextopic.Itisanap-
proach,however,thatreflectsadeep-seatedbelief—bykeepingthe
basicssimple,thespecifics(clinicalcasesandscientificreports)can
bemorereadilyweighed,categorized,absorbed,andimplemented.
Acknowledgments
TheauthorthanksGinaAlmond,PublisheratBlackwellPublishing,
for asking me to consider writing a second edition to this book,
and Fiona Pattison, Senior Development Editor at Blackwell, for
helping to shepherd me through the process of actually doing so.
Theirexpertiseandencouragementismuchappreciated.Theauthor
alsothanksAnne,Emily,andJoeFogorosforonceagainoverlooking
thetemporaryinattentivenessthatalwaysseemstoaccompanysuch
endeavors.
viii
Part 1
Basic principles
CHAPTER 1
Mechanisms of cardiac
tachyarrhythmias
Usingantiarrhythmicdrugssafelyisdifficult.Indeed,itisnearlyim-
possible without a firm understanding of the basic mechanisms of
cardiactachyarrhythmiasandthebasicconceptsofhowantiarrhyth-
mic drugs work. Part 1 of this book covers these basics. Chapter 1
reviews the normal electrical system of the heart and the mecha-
nisms and clinical features of the major cardiac tachyarrhythmias.
Chapter2examinestheprinciplesofhowantiarrhythmicdrugsaf-
fectarrhythmias.
The electrical system of the heart
On a very fundamental level, the heart is an electrical organ. The
electricalsignalsgeneratedbytheheartnotonlycausemusclecon-
traction (by controlling the flux of calcium ions across the cardiac
cell membrane) but also organize the sequence of muscle contrac-
tion with each heartbeat, thus optimizing the pumping action of
theheart.Inaddition,andespeciallypertinenttothesubjectofthis
book,thepatternandtimingofthecardiacelectricalsignalsdeter-
minetheheartrhythm.Thus,awell-functioningelectricalsystemis
vitalforadequatecardiacperformance.
Anatomy
Theheart’selectricalimpulseoriginatesinthesinoatrial(SA)node,
high in the right atrium near the superior vena cava (Figure 1.1).
From the SA node, the impulse spreads radially across both atria.
When it reaches the atrioventricular (AV) groove, the impulse en-
counters the fibrous “skeleton” of the heart, which separates the
atriafromtheventricles.Thefibrousskeletoniselectricallyinert,and
thereforestopstheelectricalimpulse.Theonlywayfortheimpulse
3