5/20/2017 CVPharmacology|CardioinhibitoryDrugs

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CardioinhibitoryDrugs

TherapeuticUseandRationale
TherapeuticUsesof
CardioinhibitoryDrugs
Hypertension
Angina
Arrhythmias
Heartfailure(blockersonly)

Cardioinhibitorydrugsdepresscardiacfunctionbydecreasingheartrate(chronotropy)andmyocardial
contractility(inotropy),whichdecreasescardiacoutputandarterialpressure.Thesecardiacchangesreducethe
workoftheheartandmyocardialoxygenconsumption.Themechanismsofactionofthesedrugsalsoleadto
depressedelectricalconduction(dromotropy)withintheheart.Someofthesedrugsmayalsoimpairrelaxation
(lusitropy).

Themechanicalandmetaboliceffectsofthesedrugsmakethemverysuitablefortreatinghypertension,angina
causedbycoronaryarterydisease,andmyocardialinfarction.Furthermore,theireffectsonelectricalactivity
makethemgoodcandidatesforthetreatmentofcardiacarrhythmias.Finally,somecardioinhibitors,notably
certainbetablockers,areusedinthetreatmentofheartfailure.

Hypertension

Hypertensionisdefinedasanarterialsystolicpressuregreaterthan140mmHgand/oradiastolicpressure
greaterthan90mmHg.Hypertensioncanbecausedbyeitheranincreaseincardiacoutputorbyanincreasein
systemicvascularresistance.Itisnotuncommonforhypertensiontobecausedbyelevationsinboth.Since
cardiacoutputistheproductofheartrateandstrokevolume,cardioinhibitorydrugsthatreduceeitherorboth
willdecreasecardiacoutputandtherebydecreasearterialpressure.

Anginaandmyocardialinfarction
Cardioinhibitors,byreducingheartrate,contractility,andarterialpressure,reducetheworkoftheheartandthe
oxygendemandoftheheart.Byreducingoxygendemand,theoxygensupply/demandratioisimproved,which
canrelieveapatientofanginalpainthatiscausedbyareductionintheoxygensupply/demandratiodueto
coronaryarterydisease.Furthermore,cardioinhibitorsthatblockbetaadrenoceptorshavebeenfoundtobevery
importantinthetreatmentofmyocardialinfarction.Theirbenefitisderivednotonlyfromimprovingthe
oxygensupply/demandratio,butalsofromtheirabilitytoinhibitsubsequentcardiacremodeling.

http://cvpharmacology.com/cardioinhibitory/Cardioinhibitory 3/5
5/20/2017 CVPharmacology|CardioinhibitoryDrugs

Arrhythmias
Becausecardioinhibitorsalterpacemakeractivityandelectricalconductionwithintheheart,theyareusefulfor
treatingarrhythmiascausedbybothabnormalautomaticityandabnormalconduction.

Heartfailure

Althoughitseemscounterintuitivethatcardioinhibitorswouldbeusedinheartfailurethatoccursbecauseofa
functionallydepressedmyocardium,clinicalstudieshaveshownveryconclusivelythatsomecardioinhibitors
(i.e.,specificbetablockers)significantlyimprovecardiacfunctionincertaintypesofheartfailure.Furthermore,
theyhavebeenshowntoreducedeleteriouscardiacremodelingthatoccursinchronicheartfailure.Their
benefitmaybederivedfromtheirblockadeofexcessivesympatheticinfluencesontheheart,whichareknown
tobeharmfultothefailingheart.

DrugClassesandGeneralMechanismsofAction
ThreeClassesof
CardioinhibitoryDrugs
Betablockers
Calciumchannelblockers
Centrallyactingsympatholytics

Cardioinhibitorsusedinclinicalpracticecanbedividedintothreemechanisticclasses:betaadrenoceptor
antagonists(betablockers),calciumchannelblockers,andcentrallyactingsympatholytics.

Betablockers

Betablockersbindtobetaadrenoceptorslocatedincardiacnodaltissue,theconductingsystem,andcontracting
myocytes.Thehearthasbothbeta1(1)andbeta2(2)adrenoceptors,althoughthepredominantreceptortype
innumberandfunctionis1.Thesereceptorsprimarilybindnorepinephrinethatisreleasedfromsympathetic
adrenergicnerves.Additionally,theybindnorepinephrineandepinephrinethatcirculatesintheblood.Beta
blockerspreventthenormalligand(norepinephrineorepinephrine)frombindingtothebetaadrenoceptorby
competingforthebindingsite.Becausethereisgenerallysomelevelofsympathetictoneontheheart,beta
blockersareabletoreducesympatheticinfluencesthatnormallystimulatechronotropy,inotropy,dromotropy
andlusitropy.Thesedrugshaveanevengreatereffectwhenthereiselevatedsympatheticactivity.Beta
blockersthatareusedclinicallyareeithernonselective(1/2)blockers,orrelativelyselective1blockers.
Somebetablockershaveadditionalmechanismsofactionbesidesbetablockade.Betablockersareusedfor
treatinghypertension,angina,myocardialinfarctionandarrhythmias.

http://cvpharmacology.com/cardioinhibitory/Cardioinhibitory 4/5
5/20/2017 CVPharmacology|CardioinhibitoryDrugs

Calciumchannelblockers
Calciumchannelblockers(CCBs)bindtoLtypecalciumchannelslocatedoncardiacmyocytesandcardiac
nodaltissue(sinoatrialandatrioventricularnodes).Thesechannelsareresponsibleforregulatingtheinfluxof
calciumintocardiomyocytes,whichinturnstimulatescardiacmyocytecontraction.Incardiacnodaltissue,L
typecalciumchannelsplayanimportantroleinpacemakercurrentsandinphase0oftheactionpotentials.
Therefore,byblockingcalciumentryintothecell,CCBsdecreasemyocardialforcegeneration(negative
inotropy),decreasedheartrate(negativechronotropy),anddecreaseconductionvelocitywithintheheart
(negativedromotropyparticularlyattheatrioventricularnode).CCBsareusedintreatinghypertension,angina
andarrhythmias.

Centrallyactingsympatholytics

Centrallyactingsympatholyticsblocksympatheticactivitybybindingtoandactivatingalpha2(2)
adrenoceptorslocatedoncardioregulatorycellswithinthemedullaofthebrain.Thisreducessympathetic
outflowtotheheart,therebydecreasingcardiacoutputbydecreasingheartrateandcontractility.Thesedrugs
areonlyusedfortreatinghypertension.

Clickbelowonadrugclassformoredetails:

Betaadrenoceptorantagonists(betablockers)
Calciumchannelblockers(CCBs)
Centrallyactingsympatholytics

Notethatallthesedrugshaveactionsbesidescardiacinhibition,andthereforearealsoclassifiedunderother
drugmechanismclasses.

Revised06/17/08

DISCLAIMER:Thesematerialsareforeducationalpurposesonly,andarenotasourceofmedicaldecision
makingadvice.

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