NR566 iWEEK i3 iCHAPTER i16, i28, i36, i39, i40
Angiotensin iconverting ienzyme iinhibitors i(ACEI)
● Slow ior iinhibit ithe iangiotensin iconverting ienzyme ito ithen idecrease ihow imuch
iangiotensin iII iis iproduced, ithus ilowering iblood ipressure.
● Most icommon iACE iInhibitors iis ilisinopril.
● Most iwell-known icomplication iof ilisinopril iis icoughing, iwhich icomes ifrom ithe iincreased
iproduction iof ibradykinin iand isubstance iP iafter ilisinopril iinterrupts ithe irenin-angiotensin-
ialdosterone isystem. iSome ipatients iexperience ithis iside ieffect iimmediately, ibut ia icough
ican iappear iany itime. iThe inext istep iin imanagement iis ito iwithdraw ilisinopril iand isee iif ithe
ipatient iimproves.
● ACE iinhibitors idecrease iproteinuria iin ithose iwith ichronic ikidney idisease
● With ithe iearliest isigns iof idiabetic inephrophathy isuch ias imicroalbuminuria, ilisinopril iis
irecommended. iLisinopril ireduces ithe iprogression iof ithis icomplication iindependent iof
iblood ipressure icontrol. iAdding ian iACE iinhibitor ifor ipatients iwith iknown ichronic ikidney
idisease icommonly iresults iin iincreased iserum icreatinine. iThe iimprovement iin iproteinuria
ihappens idespite ithis ieffect. iFor ithis ireason, iit iis iacceptable ito ihave iup ito ia i30% iincrease
iin iserum icreatinine iwith idiscontinuation iof ithe iACE iinhibitor. iAlthough icreatinines
iincrease, iGFR iimproves ilong-term.
● Beta-blockers iare ino ilonger irecommended ifor ifirst-line itreatment. iIn ipatients>18 iyearsiof
iage iwith ichronic ikidney idisease, iinitial ior iadd-on itherapy ishould iconsist iof ian iACE
iinhibitor ior iARB, iregardless iof ipatient's irace ior idiabetes istatus. iGuidelines ifor iACE
iinhibitors istate ithat idiscontinuation ishould ionly ibe iconsidered ifor ipatients iwith
iprogression iand/or isignificant ideterioration iin irenal ifunction ifor ipatients iwith
ihyperkalemia.
● ACE iinhibitors iare iPregnancy iClass iD idrugs iand iare icontraindicated iin ipregnancy.
iACE/ARB/direct irenin iinhibitors iare icontraindicated ibecause ithey i are iassociated iwith
ifetal irenal iabnormalities iin ithe ilatter ihalf iof ipregnancy iwith icardiac iabnormalities iin ithe
ifirst itrimester. iNitroprusside iis ithe iagent iof ilast iresort iin ian iemergency idue ito ipossible
icyanide ipoisoning
● ACEIs iimprove ioxygenation ito iheart imuscle iand idecrease iinappropriate iremodeling iof
iheart imuscle iafter imyocardial iinfarction i(MI) ior iwith iheart ifailure i(HF). iTheir imild iand
iusually itransient iadverse ieffects iand itheir iease iof idosing imake ithem
Pharmacodynamics:
● Inhibition iof iACE iactivity iresults iin idecreased iproduction iof iboth iangiotensin iII i(AT iII)
iand ialdosterone.
● AT iII ihas imultiple iroles iin ithe icardiovascular isystem.
○ It iincreases ivasomotor itone iby idirect istimulation iof ivascular ismooth imuscle
icontraction iand ithrough ithe iinhibition iof iendothelial initric ioxide iand iprostaglandin
irelease, iraising iBP iand idecreasing iblood iflow ithrough iarteries, iincluding ithe
icoronary iarteries.
○ AT iII iincreases iintravascular ivolume ithrough iits istimulation iof isodium iand iwater
iretention i(with ialdosterone), ishifting iof ithe ipressure-natriuresis irelationship, iand
ialtering iglomerular ihemodynamics. iIt iis ialso iproduced iin iresponse ito itissue
, injury. iThis ilatter iaction iresults iin istimulation iof ismooth imuscle icell iand ifibroblast
iproliferation iwith ithickening iof ithe ivessel iwall i(remodeling). iThis iaction,
icombined iwith iits iinhibition iof ithe iendothelium's iability ito iresist imonocyte iand
iplatelet iadhesion, ipromotes iintravascular iinflammation iand iclotting iand
icontributes ito ithe iatherosclerotic iprocess.
○ AT iII ialso icauses iremodeling iin ithe iheart, iresulting iin ihypertrophy iand ifibrosis iof
imyocardial itissue iafter iischemic iinjury ior iin iresponse ito ipersistent iafterload. iThisiis
ia iprimary imechanism iin iHF.
○ ACE irole iin ithe ikinin-kallikrein-bradykinin isystem:
■ Bradykinin iin ilow idoses icauses idilation iof ivessels iand iacts iwith
iprostaglandin ito iproduce i pain iand icause iextravascular i smooth imuscle
icontraction, iincreased ivascular ipermeability, iand iincreased ileukocyte
ichemostaxis. iBradykinin ihas ia iprimary irole iin iinflammation. iACE
ifacilitates ithe ibreakdown iof ibradykinin iinto iinactive ifragments, ithus
ireducing ithese iactions. iHigh ilevels iof ibradykinin iare ithought ito ibe ia
ifactor iin ithe icough iassociated iwith iACEI iuse.
○ ACEIs iand iARBs ido inot iaffect icardiac ioutput iand iso ido inot iproduce ireflex
itachycardia. iDRIs idirectly iimpact irenin ilevels iwith isubsequent iAT iI iand iAT iII
ireductions. iThe isuppression iof iAT iII ilevels iactually itriggers ia ifeedback
imechanism ithat iincreases irenin iproduction. iThe idrug ieffect iis imore ithan
iadequate ito ioffset ithis irise.
○ ACEI iare ireno-protective ifor iindividuals iwith iproteinuria ibut iis inot ias iprotective iin
irenal ipatients iwithout iproteinuria. iThe ieffectiveness iof iACEIs iin ipreventing
idiabetic inephropathy iprobably iresults ifrom idecreased iglomerular iefferent
iarteriolar iresistance iand ia ireduction iin iintraglomerular icapillary ipressure, iwhich
icauses iimproved irenal ihemodynamics, idiminished iproteinuria, iretarded
iglomerular ihypertrophy, iand ia islower irate iof idecline iin iglomerular ifiltration irate
i(GFR). iThese idrugs ido inot iaffect iglucose imetabolism ior iraise iserum ilipid ilevels,
ibut ithey ido iimprove iinsulin isensitivity; iall iof ithese iare iimportant iissues iin itype i2
idiabetes imellitus. iARBs ido inot iprevent idiabetic inephropathy ibut ido isuppress ithe
irate iof iprogression. iDRIs iin idiabetic i(DM) ipatients iwho ialready ihave inephropathy
ido inot ipreserve irenal ifunction. iDRIs iare inot ito ibe iused iin idiabetic ipatients iwith
irenal ifunction iof iless ithan i60 imL/min.
○ ACEI; icaptopril; ibetter iwhen itaken ion ian iempty istomach;
○ ARB; ilosartan; ifirst ipass imetabolism; ino iregard ito ifood
○ Alsikiren; iDRI; ipoorly iabsorbed, iabsorption iworse iwhen itaken iwith ihigh ifat imeal;
○ Captopril iis ithe ionly ishort-acting iACEI; ihalf-life iless ithan i2 ihours; imust itake i2-3
idoses idaily, iand iit itakes i2-3 idays ito ibuild iup isteady ilevels. iAll iother iACEI’s itake
ilonger ito ibuild iup ilevels, ibut ican ibe itaken ionce idaily.
Contraindications i& iPrecautions
● Absolute i contraindications i to iACEI, iARB, i DRI:
○ bilateral irenal iartery istenosis: iincreased ivascular ipressure iand ivasoconstriction
iappear ito ibe irequired ito isufficiently iovercome ithe istenotic iblood iflow ito iperfuseithe
ikidney. iThe ivasodilating ieffect iof ithese imeds iprevents ithe ikidney ifrom
, maintaining iits iperfusion, iand iischemic irenal ifailure imay idevelop. iUse icaution iin
irenal idisease iand ielderly
○ Angioedema
○ pregnancy.
● Hypovolemic ior ihyponatremic istates ialso irequire icaution.
● Adequate ihydration iis irequired ito imaintain ian iappropriate iGFR iand imust ibe iadequate
before istarting ithese idrugs ito iprevent irenal idysfunction.
● Hyperkalemia i contraindicates i use ibecause i reduced i aldosterone i secretion i may i worsen
ithis ielectrolyte iimbalance. iHyperkalemia irisk iincreases ifor ipatients iwith ichronic iheart
ifailure i(HF) ibecause iof ithe ireduced iblood iflow ito ithe ikidneys. iCheck iserum ipotassium
ilevel ibefore itreatment i& iwithin ione iweek.
Adverse iDrug iReactions
● Angioedema: iincrease iin ibradykinin ilevel iassociated iwith iinhibition iof iACE. iUsually
ioccurs iwith ifirst idose ior iwithin ifirst imonth. iImmediately istop iACEI ior iDRI. iARBS idon’t
ieffect ibradykin iso ithey ishouldnt icause iangioedema.
● hypotension i(dizziness, iheadache, ifatigue, iorthostatic ihypotension).
● Tachyphylaxis; iwith icontinued itherapy.
● dry, ihacking icough ithat iusually ioccurs iin ithe ifirst iweek iof itherapy. iThis iis ia iclass
iphenomenon, ibut ichanging ito ia inewer-generation iACEI ihas ibeen iassociated iwith iless
icough. iBecause ithe iaction iof ibradykinin imay ibe iresponsible ifor ithe iadverse ireactions iof
icough, ichanging ito ian iARB iprovides ibenefits isimilar ito ithose iof ithe iACEI iwith iless
ilikelihood iof icough. iDRIs isometimes iproduce ithis icough.
● Less icommon iadverse ireactions iwith iACEIs iinclude ia irash ithat iis imost icommon iwith
icaptopril iand ineutropenia ithat iincreases iwith ihigh idoses, irenal iimpairment, iand
iconcomitant icollagen idiseases. iEnalipril, iquinapril, iand iramipril ican icause
iphotosensitivity ireactions. iValsartan iis ithe ionly iARB inoted ito ialso ido ithis
Drug iInteractions
● ACEI, ilithium ilevels. iMonitor imore iclosely
● Captopril; idiuretics
● Losartan; ihyperkalemia
● Antacids; idecreased iabsorption iof iACEI; iincreased irisk ifor idix ior ilithium itoxicity
Clinical iUse
● ACEIs, iARBs, i and i DRIs i act i on i the i RAA isystem i to i reduce i pressure i by i decreasing
isodium iand iwater iretention i(aldosterone iaction), iby idecreasing ivasoconstriction
i(angiotensin idirect iaction), iand iby iincreasing ivasodilation i(bradykinin iaction).
● ACEIs iand iARBs iare ithe idrugs iof ichoice ifor ipatients iwho iare iyounger iand iwhite iand ifor
ipatients iwith idiabetes, iHF, ior iMI, ifor iwhom ithey iare imost ieffective iand ihave ithe ilowest
iincidence iof iadverse ireactions.
● Generally inot ias ieffective ifor iblack ipatients
● Black/Asian ihave ihigher irisk iof iangioedema iand icough
● Stop idiuretics i2-3 idays ibefore istarting itreatment, ito iallow ifor iadequate ihydration
● Start ilow iand igo islow
● Angina i → i imbalance i between i myocardial i oxygen i supply i (MOS) i and
imyocardial i oxygen i demand i (MOD). i ACEIs i affect i both i the i MOS i and i the i MOD
, sides iof ithe iequation. iTheir iprevention iof iformation iof iAT iII idecreases
iperipheral-vascular iresistance i(PVR) iand, ithereby, iMOD; idecreases ithe
ithickening iof icoronary iartery iwalls, iresulting iin iincreased iMOS; iand
idecreases ithe ithickening iof iventricular iwalls, iresulting iin idecreased iMOD.
iTheir ireduced isecretion iof ialdosterone idecreases ithe iretention iof isodium iand
iwater, ithereby ireducing iextracellular ifluid i(ECF) ivolume iand ipreload.
● ACEIs iare irecommended ifor iall isymptomatic ipatients iwith ichronic istable iangina ito
prevent iMI ior ideath iand ito ireduce isymptoms
● They iare ialso irecommended ito ilimit icoronary iartery idisease i(CAD) ipatients iwho ialso
ihave idiabetes ior ileft iventricular i(LV) idysfunction.
● Post-MI
○ Survivors iof iacute iMI ihave ia irisk ifor isubsequent imorbidity iand imortality ithat iis
1.5 ito i15 itimes igreater ithan ithat iof ithe igeneral ipopulation.
○ A icombination iof ian iACEI, ia inon-ISA ibeta iblocker i(BB), iantiplatelet itherapy, iand
ilipid-lowering itherapy iafter iMI iis iappropriate.
○ The ireduced imorbidity iand imortality iowing ito ithe iuse iof iACEIs iresults ifrom:
ireduced iAT iII i after i myocardial i injury, i prevention i of i ventricular i remodeling i in
inoninfarcted imyocytes, ialteration iof iventricular imass, iand ipositive ihemodynamic
ieffects ion iBP iand ifluid iand ielectrolyte ibalance.
○ ACEIs, iwith ior iwithout iARBs, ishould ibe istarted iearly iafter iMI iin istable ihigh-risk
ipatients i(anterior iMI, iprevious iMI, iKillip iclass iII). iThey ishould ibe icontinued
iindefinitely ifor iall ipatients iwith iLV idysfunction i(ejection ifractions iless ithan i40%) ior
isymptoms iof iHF iand iused ias ineeded ito imanage iBP ior isymptoms iin iall iother
ipatients.
● Heart iFailure
○ CAD iis ithe iunderlying icause iin iabout itwo-thirds iof ipatients iwith iLV idysfunction,
iwhich ibegins iwith isome iinjury ito ithe imyocardium iand iprogresses ieven iin ithe
iabsence iof iadditional imyocardial iinsults. iThe iprincipal imechanism irelates ito
iremodeling.
○ ACEIs iand iARBs iare iuseful iin itreating iheart ifailure irelated ito iCAD, iprimarily ifor
itheir irole iin ireducing iremodeling. iAnother iunderlying icause ifor iHF iis ichronic
iHTN. iACEIs i and iARBs i are i also i effective i in i treating i this i underlying i cause. i DRIs
ido inot icarry ian iindication ifor iHF.
○ ACEIs iare irecommended ifor itreatment iof iheart ifailure ifor ipatients iwith ia ihistoryiof
iatherosclerotic ivascular i disease, idiabetes imellitus, ior iHTN. iThey ihave ibeen
ishown ito iimprove isymptoms, idecrease imorbidity, iand iincrease ilife iexpectancy.
iBecause ithey iare ithe ionly idrugs ithat iaddress iall iof ithe ipathological imechanisms
ithat iproduce iHF, ithey iare iappropriate ifor iall isubsets iof ipatients iunless ithese
ipatients ihave ian iabsolute icontraindication. iThey iare ialso iuseful ifor ipreventing
ithe idevelopment iof iHF iin ipatients iwith iventricular idysfunction ibut ino iovert
isymptoms. iACEIs iare isuperior ito iall iother idrugs iand idrug icombinations iused ito
itreat iHF. iThey ishould ibe istarted iimmediately iwithout iwaiting ifor isymptoms ito
ibecome iovert.
○ For isymptomatic iHF, ithe idose iis iabout ihalf ithat iused ifor iHTN. iStart ilow iand igo
Angiotensin iconverting ienzyme iinhibitors i(ACEI)
● Slow ior iinhibit ithe iangiotensin iconverting ienzyme ito ithen idecrease ihow imuch
iangiotensin iII iis iproduced, ithus ilowering iblood ipressure.
● Most icommon iACE iInhibitors iis ilisinopril.
● Most iwell-known icomplication iof ilisinopril iis icoughing, iwhich icomes ifrom ithe iincreased
iproduction iof ibradykinin iand isubstance iP iafter ilisinopril iinterrupts ithe irenin-angiotensin-
ialdosterone isystem. iSome ipatients iexperience ithis iside ieffect iimmediately, ibut ia icough
ican iappear iany itime. iThe inext istep iin imanagement iis ito iwithdraw ilisinopril iand isee iif ithe
ipatient iimproves.
● ACE iinhibitors idecrease iproteinuria iin ithose iwith ichronic ikidney idisease
● With ithe iearliest isigns iof idiabetic inephrophathy isuch ias imicroalbuminuria, ilisinopril iis
irecommended. iLisinopril ireduces ithe iprogression iof ithis icomplication iindependent iof
iblood ipressure icontrol. iAdding ian iACE iinhibitor ifor ipatients iwith iknown ichronic ikidney
idisease icommonly iresults iin iincreased iserum icreatinine. iThe iimprovement iin iproteinuria
ihappens idespite ithis ieffect. iFor ithis ireason, iit iis iacceptable ito ihave iup ito ia i30% iincrease
iin iserum icreatinine iwith idiscontinuation iof ithe iACE iinhibitor. iAlthough icreatinines
iincrease, iGFR iimproves ilong-term.
● Beta-blockers iare ino ilonger irecommended ifor ifirst-line itreatment. iIn ipatients>18 iyearsiof
iage iwith ichronic ikidney idisease, iinitial ior iadd-on itherapy ishould iconsist iof ian iACE
iinhibitor ior iARB, iregardless iof ipatient's irace ior idiabetes istatus. iGuidelines ifor iACE
iinhibitors istate ithat idiscontinuation ishould ionly ibe iconsidered ifor ipatients iwith
iprogression iand/or isignificant ideterioration iin irenal ifunction ifor ipatients iwith
ihyperkalemia.
● ACE iinhibitors iare iPregnancy iClass iD idrugs iand iare icontraindicated iin ipregnancy.
iACE/ARB/direct irenin iinhibitors iare icontraindicated ibecause ithey i are iassociated iwith
ifetal irenal iabnormalities iin ithe ilatter ihalf iof ipregnancy iwith icardiac iabnormalities iin ithe
ifirst itrimester. iNitroprusside iis ithe iagent iof ilast iresort iin ian iemergency idue ito ipossible
icyanide ipoisoning
● ACEIs iimprove ioxygenation ito iheart imuscle iand idecrease iinappropriate iremodeling iof
iheart imuscle iafter imyocardial iinfarction i(MI) ior iwith iheart ifailure i(HF). iTheir imild iand
iusually itransient iadverse ieffects iand itheir iease iof idosing imake ithem
Pharmacodynamics:
● Inhibition iof iACE iactivity iresults iin idecreased iproduction iof iboth iangiotensin iII i(AT iII)
iand ialdosterone.
● AT iII ihas imultiple iroles iin ithe icardiovascular isystem.
○ It iincreases ivasomotor itone iby idirect istimulation iof ivascular ismooth imuscle
icontraction iand ithrough ithe iinhibition iof iendothelial initric ioxide iand iprostaglandin
irelease, iraising iBP iand idecreasing iblood iflow ithrough iarteries, iincluding ithe
icoronary iarteries.
○ AT iII iincreases iintravascular ivolume ithrough iits istimulation iof isodium iand iwater
iretention i(with ialdosterone), ishifting iof ithe ipressure-natriuresis irelationship, iand
ialtering iglomerular ihemodynamics. iIt iis ialso iproduced iin iresponse ito itissue
, injury. iThis ilatter iaction iresults iin istimulation iof ismooth imuscle icell iand ifibroblast
iproliferation iwith ithickening iof ithe ivessel iwall i(remodeling). iThis iaction,
icombined iwith iits iinhibition iof ithe iendothelium's iability ito iresist imonocyte iand
iplatelet iadhesion, ipromotes iintravascular iinflammation iand iclotting iand
icontributes ito ithe iatherosclerotic iprocess.
○ AT iII ialso icauses iremodeling iin ithe iheart, iresulting iin ihypertrophy iand ifibrosis iof
imyocardial itissue iafter iischemic iinjury ior iin iresponse ito ipersistent iafterload. iThisiis
ia iprimary imechanism iin iHF.
○ ACE irole iin ithe ikinin-kallikrein-bradykinin isystem:
■ Bradykinin iin ilow idoses icauses idilation iof ivessels iand iacts iwith
iprostaglandin ito iproduce i pain iand icause iextravascular i smooth imuscle
icontraction, iincreased ivascular ipermeability, iand iincreased ileukocyte
ichemostaxis. iBradykinin ihas ia iprimary irole iin iinflammation. iACE
ifacilitates ithe ibreakdown iof ibradykinin iinto iinactive ifragments, ithus
ireducing ithese iactions. iHigh ilevels iof ibradykinin iare ithought ito ibe ia
ifactor iin ithe icough iassociated iwith iACEI iuse.
○ ACEIs iand iARBs ido inot iaffect icardiac ioutput iand iso ido inot iproduce ireflex
itachycardia. iDRIs idirectly iimpact irenin ilevels iwith isubsequent iAT iI iand iAT iII
ireductions. iThe isuppression iof iAT iII ilevels iactually itriggers ia ifeedback
imechanism ithat iincreases irenin iproduction. iThe idrug ieffect iis imore ithan
iadequate ito ioffset ithis irise.
○ ACEI iare ireno-protective ifor iindividuals iwith iproteinuria ibut iis inot ias iprotective iin
irenal ipatients iwithout iproteinuria. iThe ieffectiveness iof iACEIs iin ipreventing
idiabetic inephropathy iprobably iresults ifrom idecreased iglomerular iefferent
iarteriolar iresistance iand ia ireduction iin iintraglomerular icapillary ipressure, iwhich
icauses iimproved irenal ihemodynamics, idiminished iproteinuria, iretarded
iglomerular ihypertrophy, iand ia islower irate iof idecline iin iglomerular ifiltration irate
i(GFR). iThese idrugs ido inot iaffect iglucose imetabolism ior iraise iserum ilipid ilevels,
ibut ithey ido iimprove iinsulin isensitivity; iall iof ithese iare iimportant iissues iin itype i2
idiabetes imellitus. iARBs ido inot iprevent idiabetic inephropathy ibut ido isuppress ithe
irate iof iprogression. iDRIs iin idiabetic i(DM) ipatients iwho ialready ihave inephropathy
ido inot ipreserve irenal ifunction. iDRIs iare inot ito ibe iused iin idiabetic ipatients iwith
irenal ifunction iof iless ithan i60 imL/min.
○ ACEI; icaptopril; ibetter iwhen itaken ion ian iempty istomach;
○ ARB; ilosartan; ifirst ipass imetabolism; ino iregard ito ifood
○ Alsikiren; iDRI; ipoorly iabsorbed, iabsorption iworse iwhen itaken iwith ihigh ifat imeal;
○ Captopril iis ithe ionly ishort-acting iACEI; ihalf-life iless ithan i2 ihours; imust itake i2-3
idoses idaily, iand iit itakes i2-3 idays ito ibuild iup isteady ilevels. iAll iother iACEI’s itake
ilonger ito ibuild iup ilevels, ibut ican ibe itaken ionce idaily.
Contraindications i& iPrecautions
● Absolute i contraindications i to iACEI, iARB, i DRI:
○ bilateral irenal iartery istenosis: iincreased ivascular ipressure iand ivasoconstriction
iappear ito ibe irequired ito isufficiently iovercome ithe istenotic iblood iflow ito iperfuseithe
ikidney. iThe ivasodilating ieffect iof ithese imeds iprevents ithe ikidney ifrom
, maintaining iits iperfusion, iand iischemic irenal ifailure imay idevelop. iUse icaution iin
irenal idisease iand ielderly
○ Angioedema
○ pregnancy.
● Hypovolemic ior ihyponatremic istates ialso irequire icaution.
● Adequate ihydration iis irequired ito imaintain ian iappropriate iGFR iand imust ibe iadequate
before istarting ithese idrugs ito iprevent irenal idysfunction.
● Hyperkalemia i contraindicates i use ibecause i reduced i aldosterone i secretion i may i worsen
ithis ielectrolyte iimbalance. iHyperkalemia irisk iincreases ifor ipatients iwith ichronic iheart
ifailure i(HF) ibecause iof ithe ireduced iblood iflow ito ithe ikidneys. iCheck iserum ipotassium
ilevel ibefore itreatment i& iwithin ione iweek.
Adverse iDrug iReactions
● Angioedema: iincrease iin ibradykinin ilevel iassociated iwith iinhibition iof iACE. iUsually
ioccurs iwith ifirst idose ior iwithin ifirst imonth. iImmediately istop iACEI ior iDRI. iARBS idon’t
ieffect ibradykin iso ithey ishouldnt icause iangioedema.
● hypotension i(dizziness, iheadache, ifatigue, iorthostatic ihypotension).
● Tachyphylaxis; iwith icontinued itherapy.
● dry, ihacking icough ithat iusually ioccurs iin ithe ifirst iweek iof itherapy. iThis iis ia iclass
iphenomenon, ibut ichanging ito ia inewer-generation iACEI ihas ibeen iassociated iwith iless
icough. iBecause ithe iaction iof ibradykinin imay ibe iresponsible ifor ithe iadverse ireactions iof
icough, ichanging ito ian iARB iprovides ibenefits isimilar ito ithose iof ithe iACEI iwith iless
ilikelihood iof icough. iDRIs isometimes iproduce ithis icough.
● Less icommon iadverse ireactions iwith iACEIs iinclude ia irash ithat iis imost icommon iwith
icaptopril iand ineutropenia ithat iincreases iwith ihigh idoses, irenal iimpairment, iand
iconcomitant icollagen idiseases. iEnalipril, iquinapril, iand iramipril ican icause
iphotosensitivity ireactions. iValsartan iis ithe ionly iARB inoted ito ialso ido ithis
Drug iInteractions
● ACEI, ilithium ilevels. iMonitor imore iclosely
● Captopril; idiuretics
● Losartan; ihyperkalemia
● Antacids; idecreased iabsorption iof iACEI; iincreased irisk ifor idix ior ilithium itoxicity
Clinical iUse
● ACEIs, iARBs, i and i DRIs i act i on i the i RAA isystem i to i reduce i pressure i by i decreasing
isodium iand iwater iretention i(aldosterone iaction), iby idecreasing ivasoconstriction
i(angiotensin idirect iaction), iand iby iincreasing ivasodilation i(bradykinin iaction).
● ACEIs iand iARBs iare ithe idrugs iof ichoice ifor ipatients iwho iare iyounger iand iwhite iand ifor
ipatients iwith idiabetes, iHF, ior iMI, ifor iwhom ithey iare imost ieffective iand ihave ithe ilowest
iincidence iof iadverse ireactions.
● Generally inot ias ieffective ifor iblack ipatients
● Black/Asian ihave ihigher irisk iof iangioedema iand icough
● Stop idiuretics i2-3 idays ibefore istarting itreatment, ito iallow ifor iadequate ihydration
● Start ilow iand igo islow
● Angina i → i imbalance i between i myocardial i oxygen i supply i (MOS) i and
imyocardial i oxygen i demand i (MOD). i ACEIs i affect i both i the i MOS i and i the i MOD
, sides iof ithe iequation. iTheir iprevention iof iformation iof iAT iII idecreases
iperipheral-vascular iresistance i(PVR) iand, ithereby, iMOD; idecreases ithe
ithickening iof icoronary iartery iwalls, iresulting iin iincreased iMOS; iand
idecreases ithe ithickening iof iventricular iwalls, iresulting iin idecreased iMOD.
iTheir ireduced isecretion iof ialdosterone idecreases ithe iretention iof isodium iand
iwater, ithereby ireducing iextracellular ifluid i(ECF) ivolume iand ipreload.
● ACEIs iare irecommended ifor iall isymptomatic ipatients iwith ichronic istable iangina ito
prevent iMI ior ideath iand ito ireduce isymptoms
● They iare ialso irecommended ito ilimit icoronary iartery idisease i(CAD) ipatients iwho ialso
ihave idiabetes ior ileft iventricular i(LV) idysfunction.
● Post-MI
○ Survivors iof iacute iMI ihave ia irisk ifor isubsequent imorbidity iand imortality ithat iis
1.5 ito i15 itimes igreater ithan ithat iof ithe igeneral ipopulation.
○ A icombination iof ian iACEI, ia inon-ISA ibeta iblocker i(BB), iantiplatelet itherapy, iand
ilipid-lowering itherapy iafter iMI iis iappropriate.
○ The ireduced imorbidity iand imortality iowing ito ithe iuse iof iACEIs iresults ifrom:
ireduced iAT iII i after i myocardial i injury, i prevention i of i ventricular i remodeling i in
inoninfarcted imyocytes, ialteration iof iventricular imass, iand ipositive ihemodynamic
ieffects ion iBP iand ifluid iand ielectrolyte ibalance.
○ ACEIs, iwith ior iwithout iARBs, ishould ibe istarted iearly iafter iMI iin istable ihigh-risk
ipatients i(anterior iMI, iprevious iMI, iKillip iclass iII). iThey ishould ibe icontinued
iindefinitely ifor iall ipatients iwith iLV idysfunction i(ejection ifractions iless ithan i40%) ior
isymptoms iof iHF iand iused ias ineeded ito imanage iBP ior isymptoms iin iall iother
ipatients.
● Heart iFailure
○ CAD iis ithe iunderlying icause iin iabout itwo-thirds iof ipatients iwith iLV idysfunction,
iwhich ibegins iwith isome iinjury ito ithe imyocardium iand iprogresses ieven iin ithe
iabsence iof iadditional imyocardial iinsults. iThe iprincipal imechanism irelates ito
iremodeling.
○ ACEIs iand iARBs iare iuseful iin itreating iheart ifailure irelated ito iCAD, iprimarily ifor
itheir irole iin ireducing iremodeling. iAnother iunderlying icause ifor iHF iis ichronic
iHTN. iACEIs i and iARBs i are i also i effective i in i treating i this i underlying i cause. i DRIs
ido inot icarry ian iindication ifor iHF.
○ ACEIs iare irecommended ifor itreatment iof iheart ifailure ifor ipatients iwith ia ihistoryiof
iatherosclerotic ivascular i disease, idiabetes imellitus, ior iHTN. iThey ihave ibeen
ishown ito iimprove isymptoms, idecrease imorbidity, iand iincrease ilife iexpectancy.
iBecause ithey iare ithe ionly idrugs ithat iaddress iall iof ithe ipathological imechanisms
ithat iproduce iHF, ithey iare iappropriate ifor iall isubsets iof ipatients iunless ithese
ipatients ihave ian iabsolute icontraindication. iThey iare ialso iuseful ifor ipreventing
ithe idevelopment iof iHF iin ipatients iwith iventricular idysfunction ibut ino iovert
isymptoms. iACEIs iare isuperior ito iall iother idrugs iand idrug icombinations iused ito
itreat iHF. iThey ishould ibe istarted iimmediately iwithout iwaiting ifor isymptoms ito
ibecome iovert.
○ For isymptomatic iHF, ithe idose iis iabout ihalf ithat iused ifor iHTN. iStart ilow iand igo
