Antiarrhythmic Drugs: A Practical Guide, 2nd edition

186 Pages·2007·1.11 MB·English

by  Richard N.

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