Antiarrhythmic Drugs: A Practical Guide, 2nd edition PDF
Preview Antiarrhythmic Drugs: A Practical Guide, 2nd edition
Antiarrhythmic Drugs A practical guide SECOND EDITION Richard N. Fogoros, M.D. Pittsburgh,PA (cid:1)C 2007RichardFogoros PublishedbyBlackwellPublishing BlackwellFuturaisanimprintofBlackwellPublishing BlackwellPublishing,Inc.,350MainStreet,Malden,Massachusetts02148-5020,USA BlackwellPublishingLtd,9600GarsingtonRoad,OxfordOX42DQ,UK BlackwellScienceAsiaPtyLtd,550SwanstonStreet,Carlton,Victoria3053,Australia Allrightsreserved.Nopartofthispublicationmaybereproducedinanyformorbyany electronicormechanicalmeans,includinginformationstorageandretrievalsystems, withoutpermissioninwritingfromthepublisher,exceptbyareviewerwhomayquote briefpassagesinareview. Firstpublished1997 Secondedition2007 1 2007 ISBN:978-1-4051-6351-4 LibraryofCongressCataloging-in-PublicationData 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. QV150F656a2007] RM347.F642007 616.1(cid:2)28061–dc22 2007005643 AcataloguerecordforthistitleisavailablefromtheBritishLibrary SetinMeridien9.25/12ptbyAptaraInc.,NewDelhi,India PrintedandboundinSingaporebyMarkonoPrintMediaPteLtd CommissioningEditor:GinaAlmond DevelopmentEditor:FionaPattison EditorialAssistant:VictoriaPitman ForfurtherinformationonBlackwellPublishing,visitourwebsite: www.blackwellcardiology.com Thepublisher’spolicyistousepermanentpaperfrommillsthatoperateasustainable forestrypolicy,andwhichhasbeenmanufacturedfrompulpprocessedusingacid-free andelementarychlorine-freepractices.Furthermore,thepublisherensuresthatthetext paperandcoverboardusedhavemetacceptableenvironmentalaccreditationstandards. BlackwellPublishingmakesnorepresentation,expressorimplied,thatthedrugdosages inthisbookarecorrect.Readersmustthereforealwayscheckthatanyproduct mentionedinthispublicationisusedinaccordancewiththeprescribinginformation preparedbythemanufacturers.Theauthorandthepublishersdonotaccept responsibilityorlegalliabilityforanyerrorsinthetextorforthemisuseor misapplicationofmaterialinthisbook. 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
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