NR 566 Midterm Exam Study Guide
i i i i i
Direct iRenin iInhibitors i(DRIs)
• Drug: i Aliskiren i (Tekturna)
• MOA
• Related ito iACEIs iand iARBs ibut iact iuniquely iby idirectly iblocking iof irenin iitself i(not ion
iitsigenesis ior ion ithe iangiotensin icomponents iof ithe iRAAS)
• Directly iimpact irenin ilevels iwith isubsequent iAT iI iand iAT iII ireductions
• The i suppression i of i AT i II i levels i triggers i a i feedback i mechanism i that i increases i renin i production
o i i The idrug ieffect iis imore ithan iadequate ito ioffset ithis irise
• Do inot ipreserve irenal ifunction
• Contraindicated i in i patients i with i renal i function i less i than i 60 i mL/min
• Contraindications: i bilateral irenal iartery istenosis, iangioedema, iand ipregnancy
• Use iwith icaution: iimpaired irenal ifunction iespecially iin iolder iadults
• Use i with i caution: i impaired i renal i function i especially i in i older i adults, i hypovolemic
i orihyponatremic istates
• Contraindicated iin i hyperkalemia: ireduced ialdosterone imay iworsen ithe iimbalance
• Monitoring: iPatients ishould ihave iserum ipotassium ichecked iprior ito iinitiating itherapy iand
iwithin ione iweek ito inote itrends
• ADRs: iangioedema i(can ibe ilife ithreatening)
o i ADRs iare iusually itransient, imild, iand imore icommon iin ilonger iacting iagents
• Drug i interactions:
o minor i issue i with i CYP3A4 i but i greater i ones i in iother i meds iwith i p-glycoprotein
(cyclosporine i and i itraconazole)
o Make ifurosemide i less ieffective
o Additive ihypotension i with i other i antihypertensives, i nitrates, i phenothiazines, i and
i ETOHiingestion
o Due ito iinterference iwith ialdosterone isecretion, iconcurrent iuse iof iK isupplements,
iK-isparing idiuretics, ior icyclosporine imay iresult iin ihyperkalemia
o Antihypertensive i response i is i reduced i by i NSAIDs i r/t i effect i on i prostaglandins
Calcium ichannel iblockers i(CCB)
o Drugs:
o Two imajor iclasses
▪ Type i I i– iNon-dihydropyridines: iaffect i conduction ithrough ithe iAV i node i and
i haveinegative ichronotropic ieffects
▪ Why i it i is iused i in i treating i supraventricular i tachycardia
▪ Diltiazem i(Cardizem), iverapamil i(Calan)
▪ Type iII i– iDihydropyridines: ido inot iaffect iconduction ithrough ithe iAV inode
▪ Nifedipine i(Procardia), iamlodipine i(Norvasc), ifelodipine i(Plendil)
▪ All itype i 2 idrugs i cause ivasodilation i that i result iin i reflex itachycardia
i andipooling iof iperipheral iblood
o Block i L-type i or i long ilasting i calcium i channels
o Predominate i in i cardiac i and i smooth i muscle
o Indications: iangina, iHTN, iand iselected itachyarrhythmias
o Off ilabel iuses: imigraine iHA iprophylaxis, iRaynaud’s isyndrome, icardiomyopathy, iand iesophageal
ispasm
o May i interfere iwith i platelet i aggregation i and i reduce i development iof i lesions
o Pharmacodynamics
o Contraction i is i caused iby i influx iof i Ca
o CCBs idirectly iblock ithe iinflux iof icalcium iat ithe ionset iof ithe icycle
, o Acts i from i the i inner i side i of i the i membrane i and i bind i to i channels i in i depolarized
i membranes,ichanges imode iof ioperation iof ithe ichannel ifrom ifrequent ito irare iopenings
o Results iin idecrease iin itransmembrane iCa icontent iand iprolonged ivascular ismooth imuscle
irelaxation
o The iblocking i actions iof iCCBs i occurs ivia i 3 idifferent ireceptors:
▪ Diphenyl-alkylamine-based i and i benzothiazepine-based i (both i type i 1 i receptors)
▪ Dihydropyridine-based i (type i 2 i receptor)
▪ Type iof ireceptor iinfluences idrug itype
o All iCCBs irelax i arterial ismooth imuscle ibut ihave ilittle i effect i on ivenous ibed
▪ Results iin isignificant ireduction iin iafterload ibut ilimited ieffect ion ipreload
o Cardiac i muscle: i reduction i in i contractility i (negative i inotropism) i and i decreases i in i SA i and
i AViconduction ivelocity ioccur
▪ Greater idegree iof ivasodilation iwith idihydropyridines icauses isufficient
ireflexiincrease iin isympathetic itone ito iovercome ithe inegative i inotropic
ieffects
o CCBs ieffect iof i nodal i conduction idepends iof i if i it idelays islow iCa i channel i recovery
▪ Nifedipine i(Adalat, iProcardia) iand ithe iother idihydropyridines ido inot iaffect ithe irate
iof irecover iof ithese ichannels
▪ At iclinical idoses ithey ido inot iaffect iAV inode iconduction
▪ In icontrast, iverapamil i(Calan, iIsoptin), inot ionly iaffect iopenings iof iCa ichannels
ibutialso idecreases ithe irate iof irecovery
▪ Resulting i in i depression i of i the i SA i node i firing i rate i and i slowing
i AViconduction
▪ Therefore iverapamil iis iused ito itreat iSVT
▪ Verapamil iis ialso ia idirect inegative iinotrope
o Functionally i act i as i vasodilators, i lowering i calcium i (Ca++) i influx i into i smooth i muscles
o Verapamil ihas i strongest i negative iinotropic ieffect i and i should i be iavoided i in i patients
i withiHF
o Using iCCB/ACE icombo idecreased iperipheral iedema iby i50% ivs. ithose ion iCCB ialone
o Pharmacokinetics
o All i CCBs i are i metabolized i by i CYP34A
o Inducers
o Inhibitors
o Pharmacotherapeutics
o Nicardipine: i dosage i reductions i based i on i renal i impairment
o Verapamil: i(Avoid iin iHF)
▪ strongest i negative iinotropic i effect i and ishould i be i avoided i in i HF
▪ This ieffect ican iworsen ithe idisorder
▪ Has ithe istrongest i effect i on i nodal i conduction
▪ Can i significantly i worsen i bradycardia
o Diltiazem: i affects i nodal i conduction i and i can i worsen i or i cause i bradycardia i (less
i thaniverapamil)
o CCBs i are i not i drugs i of i choice i immediately i after i MI
▪ However idiltiazem ihas ishown isome ibenefit iin ireducing imortality iin inon iQ iwave iMI
ifor ia iselected igroup iof ipatients iwho iEF iare iabout i40%
o Contraindicated: i EF i <40% i and i for i all i other i patients i early i after i MI, i type i 1 i CCBs
i areicontraindicated ir/t inegative iinotropic iand ibradycardic ieffects
o Ventricular i dysfunction, i SA i or i AV i nodal i conduction i disturbances, i and i SBPs i below i 90
i should inot ibe itreated iwith itype i1 iCCBs i r/t ihigh irisk ifor iinduction iof iHF iand i significant
ihypotension
o Type i2 idrugs iare iless idependent ion ithe iheart ifor itheir ieffects ibut istill inot idrug iof
ichoiceiafter iMI
o Type i2: iAvoid iin ipatients iwith isignificant iperipheral iedema
▪ Their istrong iperipheral ivasodilating ieffects iresults iin iperipheral ipooling iof iblood
iand imay ilead ito ireflex itachycardia
o Type i2 idrugs: iContraindicated iin iunstable iangina ir/t ipotential ito icause itachycardia
o If inecessary i to i treat i patients i with i peripheral i edema i or itachyarrhythmia i SR i forms
i areipreferred
o Hepatic iimpairment: iall iCCBs ishould ibe iused icautiously iwith idosage ireduction
irecommended ifor imost iagents
o Pregnancy i Category i C: i teratogenic i and i embryotoxic i effects i in i small
i animals:icontraception
, o Verapamil, idiltiazem, inifedipine, iand inicardipine: ifound iin ibreast imilk: ido inot igive ito
iduring imothers
o Safety iand iefficacy iof ithese idrugs ihave inot ibeen iestablished iin ichildren
o ADR
o Dizziness, i HA, i hypotension, i and i syncope
▪ These ilead i to i HF i with i congestion, i SOB, i cough, i and i palpitations
o HF iis iworse iwith iverapamil, idiltiazem, iand inifediple
o GI: idry imouth, iNV, ireflux, iand iconstipation i(especially icommon iwith iverapamil: iincrease
ifiber iand istool isoftener)
o Not icommon: isexual idysfunction iand igynecomastia
o Hyperglycemia i(uncommon)
o Photosensitivity iand ifacial itelangiectasia ican ioccur iwith iamlodipine, inifedipine,
iandid iltiazem
▪ Also i associated i with i hyperpigmentation
o ADRs ireduced iwith iuse iof isustained-release iforms iversus iimmediate irelease
o Drug i interactions:
o CYP3A4 i metabolism i of i all i CCBs
o Additive ihypotension iwith iother iantihypertensive idrugs, initrates, iquinidine, ior iETOH
o NSAIDS imay idecreased iantihypertensive ieffects
o Verapamil, i diltiazem, i and i some i dihydropyridines i have i additive i bradycardia i with i BBs
i oridigoxin
o Digoxin ilevels imay iincrease iwith ir/f itoxicity iwhen iused iwith iverapamil, idiltiazem, ior
inifedipine
o Verapamil i may i decrease i effectiveness i of i rifampin i and i the i effectiveness i of i verapamil
i mayibe idecreased iby iconcurrent iuse iof ivitamin iD iand iCa
o Verapamil: ialters ilithium ilevels: ipick ianother iCCB
o Grapefruit ijuice: iincreased ifree iCCB i(increased idrug ilevels ir/t itoxicity)
o Clinical i Use i and
i DosingiChronic iAngina
• Both itype i 1 iand i 2 idrugs i are ieffective iin itreatment iof istable i and iexertional i angina
• Act i on iboth i sides i of i the i supply-demand i equation:
o peripheral ivasodilation iand inegative iinotropism ireduce ioxygen idemand
o dilation i of i coronary i arteries i increases i oxygen i supply
• Nifedipine, inicardipine, iand iamlodipine iare idrugs iof ichoice
o Nifedipine i(Procardia iXL) iis ithe imost ioften iprescribed
o Combining ithis idrug iwith ipropranolol i is i more ieffective ithan ieither i agent igiven i alone
o BB i suppresses i the i reflex i tachycardia i that i can i occur i with i type i 2 i CCBs
• Nicardipine iis isimilar ito inifedipine ibut iless ilikely ito icause ihypotension i and iLV idysfunction
o Useful ifor ipatients iwith i angina iwho ialso ihave imild iHF ior iborderline iHTN
• Amlodipine iis iwell i tolerated i with iless i venous i pooling i and i minimum i reflex i tachycardia
o Safe ito iuse ifor ipatients iwith isignificant iventricular idysfunction
o Long ihalf ilife
▪ (acts ilike i a isustained i release iform: i less ivenous i pooling, i less ireflex
i tachycardia,iand ionce idaily idosing)
o Amlodipine ican ibe icrushed
o 5 img iinitially
o Doses ihigher ithan i10 img ihave inot idemonstrated iany iincrease iin ibenefit
o Amlodipine i has i been i used i in i combination i with i several i BBs i to i produce
i improvediresponse
• Diltiazem: i less i likely i to i cause i hypotension i and i other i ADRs i associated i with
i peripheralivasodilation ithan inifedipine
o Less i negative i inotropic i activity i than i verapamil
o The ireduction iin i average idaily iheart irate i improves icoronary i artery ifilling itime
i andimyocardial ioxygen isupply
o Good ichoice ifor ipatients iwho ineed ito ireduce itheir iHR
, • Verapamil iis iRx imore ioften ifor iTx iof iarrhythmias ir/t ipotent inegative iinotropic ieffect iand
isignificant islowing iof iAV inode iconduction
o Not iused ifor ipatients iwith icompromised iLV ifunction, ibradycardia, ior iAV iblock
o May i be i chosen i for i patients i with i SVT i with i angina
Vasospastic i (Variant, i Prinzmetal’s) i Angina
• Diltiazem, ilong i acting inifedipine, i and i amlodipine i most iused: iproduce i more icoronary
i arteryivasodilation iand ireduce ivasospasm
Unstable iAngina
• If ivasospasm iis ia icomponent iof ithe iangina, iCCBs imay ibe iused
• Verapamil: idrug iof ichoice
• Type i 2 idrugs i are i contraindicated i in i unstable i angina
Hypertension
• Guidelines i indicate i black i patients i as i a i group i are i more i responsive i to i diuretics i and i CCBs i as
i firstiline imedications ifor ithe itreatment iof iHTN
• Indicated ifor iboth isevere ibp i>160/110 iand inone-severe iHTN i(BP i140 ito i159/90 ito i109)
i in ipregnancy
o i i Nifedipine icapsules iand iperipheral iarterial idilator idrugs iare iuseful ifor iboth idisorders
• Amlodipine: iespecially iuseful ifor iHTN iin ipatients iwith iLV idysfunction iand iCHF
• Long i acting inifedipine, idiltiazem, ior iverapamil i may ibe iused ifor ipatients iwith iCAD
• Long iacting inifedipine: igood ichoice ifor iPVD ir/t ivasodilating ieffect
• For iall iCCBs: iold iadults ishould ibe istarted ion ihalf ithe iusual idose iand iincreases iin idosage
ishould ibe igradual ito ireduce iADRs
SVT iand iAFib
• Type i 1 i CCB i in i selected i supraventricular i tachycardias i because i the i slow i AV i node i conduction
o Verapamil i (80 i to i 120 i mg i PO) i can i terminate i the i rhythm
▪ Conversion itakes iabout ian ihour
o Diltiazem i (40 ito i 80 i mg iorally) i can i also i be i tried
• Verapamil i prophylaxis: i 240 i to i 480 i mg/d i for i PSVT
o Ensure ithat ithe irhythm iis i not iventricular
o Verapamil ican iworsen iventricular irhythm idisturbances ir/t inegative iinotropic
ieffects
• Verapamil iused i as i an ialternative ito idigoxin i to islow i a irapid i ventricular i response i in ithe
itreatment iof iAFIB ir/t idirect ieffect ion iAV inode i(prolongs irefractory iperiod iand iconductio
time)
o Doses ilike iPSVT
• Verapamil iand idigoxin itogether: icheck idig ilevels ioften ican iincrease idig ilevels ir/f itoxicity
• Wolff-Parkinson-White isyndrome
o Ventricular i responses i that i are i dangerously i rapid: i surgical i ablation
Migraine iHA iProphylaxis
• Unlabeled iindication i for iCCBs
• Verapamil: iused i most i often i (240 i to i 480 i mg/d)
• To ifacilitate iadherence iuse iSR iform ifor ionce idaily idosing
• Trial ifor i3 imonths
Raynaud’s iSyndrome
o Unlabeled iindication
o Type i2 iCCBS idrug iof ichoice ir/t iperipheral ivasodilating ieffects iand iplatelet iinhibition
o Nifedipine i10 img iPO iat ithe ioffice ito i assess ieffect ion iBP, iif ino isignificant idrop iin iBP ithen iRx
i 10img iPO iTID
o Dose imay ibe iincreased iby i10 img/d ievery i3 ito i4 idays ito ia imax iof i30 img iTID
o Monitoring ievery i2 ito i4 imonths
o Diltiazem imay ibe itried iif inifedipine idoes inot iwork
o 30 img iQID iand iincreased ievery ithree ito ifour idays iuntil imax iof ifour i120 img idoes idaily
iis ireached
o Felodipine i and iisradipine i are ialso i vasodilators ithat i may ibe itried
Esophageal iSpasm
i i i i i
Direct iRenin iInhibitors i(DRIs)
• Drug: i Aliskiren i (Tekturna)
• MOA
• Related ito iACEIs iand iARBs ibut iact iuniquely iby idirectly iblocking iof irenin iitself i(not ion
iitsigenesis ior ion ithe iangiotensin icomponents iof ithe iRAAS)
• Directly iimpact irenin ilevels iwith isubsequent iAT iI iand iAT iII ireductions
• The i suppression i of i AT i II i levels i triggers i a i feedback i mechanism i that i increases i renin i production
o i i The idrug ieffect iis imore ithan iadequate ito ioffset ithis irise
• Do inot ipreserve irenal ifunction
• Contraindicated i in i patients i with i renal i function i less i than i 60 i mL/min
• Contraindications: i bilateral irenal iartery istenosis, iangioedema, iand ipregnancy
• Use iwith icaution: iimpaired irenal ifunction iespecially iin iolder iadults
• Use i with i caution: i impaired i renal i function i especially i in i older i adults, i hypovolemic
i orihyponatremic istates
• Contraindicated iin i hyperkalemia: ireduced ialdosterone imay iworsen ithe iimbalance
• Monitoring: iPatients ishould ihave iserum ipotassium ichecked iprior ito iinitiating itherapy iand
iwithin ione iweek ito inote itrends
• ADRs: iangioedema i(can ibe ilife ithreatening)
o i ADRs iare iusually itransient, imild, iand imore icommon iin ilonger iacting iagents
• Drug i interactions:
o minor i issue i with i CYP3A4 i but i greater i ones i in iother i meds iwith i p-glycoprotein
(cyclosporine i and i itraconazole)
o Make ifurosemide i less ieffective
o Additive ihypotension i with i other i antihypertensives, i nitrates, i phenothiazines, i and
i ETOHiingestion
o Due ito iinterference iwith ialdosterone isecretion, iconcurrent iuse iof iK isupplements,
iK-isparing idiuretics, ior icyclosporine imay iresult iin ihyperkalemia
o Antihypertensive i response i is i reduced i by i NSAIDs i r/t i effect i on i prostaglandins
Calcium ichannel iblockers i(CCB)
o Drugs:
o Two imajor iclasses
▪ Type i I i– iNon-dihydropyridines: iaffect i conduction ithrough ithe iAV i node i and
i haveinegative ichronotropic ieffects
▪ Why i it i is iused i in i treating i supraventricular i tachycardia
▪ Diltiazem i(Cardizem), iverapamil i(Calan)
▪ Type iII i– iDihydropyridines: ido inot iaffect iconduction ithrough ithe iAV inode
▪ Nifedipine i(Procardia), iamlodipine i(Norvasc), ifelodipine i(Plendil)
▪ All itype i 2 idrugs i cause ivasodilation i that i result iin i reflex itachycardia
i andipooling iof iperipheral iblood
o Block i L-type i or i long ilasting i calcium i channels
o Predominate i in i cardiac i and i smooth i muscle
o Indications: iangina, iHTN, iand iselected itachyarrhythmias
o Off ilabel iuses: imigraine iHA iprophylaxis, iRaynaud’s isyndrome, icardiomyopathy, iand iesophageal
ispasm
o May i interfere iwith i platelet i aggregation i and i reduce i development iof i lesions
o Pharmacodynamics
o Contraction i is i caused iby i influx iof i Ca
o CCBs idirectly iblock ithe iinflux iof icalcium iat ithe ionset iof ithe icycle
, o Acts i from i the i inner i side i of i the i membrane i and i bind i to i channels i in i depolarized
i membranes,ichanges imode iof ioperation iof ithe ichannel ifrom ifrequent ito irare iopenings
o Results iin idecrease iin itransmembrane iCa icontent iand iprolonged ivascular ismooth imuscle
irelaxation
o The iblocking i actions iof iCCBs i occurs ivia i 3 idifferent ireceptors:
▪ Diphenyl-alkylamine-based i and i benzothiazepine-based i (both i type i 1 i receptors)
▪ Dihydropyridine-based i (type i 2 i receptor)
▪ Type iof ireceptor iinfluences idrug itype
o All iCCBs irelax i arterial ismooth imuscle ibut ihave ilittle i effect i on ivenous ibed
▪ Results iin isignificant ireduction iin iafterload ibut ilimited ieffect ion ipreload
o Cardiac i muscle: i reduction i in i contractility i (negative i inotropism) i and i decreases i in i SA i and
i AViconduction ivelocity ioccur
▪ Greater idegree iof ivasodilation iwith idihydropyridines icauses isufficient
ireflexiincrease iin isympathetic itone ito iovercome ithe inegative i inotropic
ieffects
o CCBs ieffect iof i nodal i conduction idepends iof i if i it idelays islow iCa i channel i recovery
▪ Nifedipine i(Adalat, iProcardia) iand ithe iother idihydropyridines ido inot iaffect ithe irate
iof irecover iof ithese ichannels
▪ At iclinical idoses ithey ido inot iaffect iAV inode iconduction
▪ In icontrast, iverapamil i(Calan, iIsoptin), inot ionly iaffect iopenings iof iCa ichannels
ibutialso idecreases ithe irate iof irecovery
▪ Resulting i in i depression i of i the i SA i node i firing i rate i and i slowing
i AViconduction
▪ Therefore iverapamil iis iused ito itreat iSVT
▪ Verapamil iis ialso ia idirect inegative iinotrope
o Functionally i act i as i vasodilators, i lowering i calcium i (Ca++) i influx i into i smooth i muscles
o Verapamil ihas i strongest i negative iinotropic ieffect i and i should i be iavoided i in i patients
i withiHF
o Using iCCB/ACE icombo idecreased iperipheral iedema iby i50% ivs. ithose ion iCCB ialone
o Pharmacokinetics
o All i CCBs i are i metabolized i by i CYP34A
o Inducers
o Inhibitors
o Pharmacotherapeutics
o Nicardipine: i dosage i reductions i based i on i renal i impairment
o Verapamil: i(Avoid iin iHF)
▪ strongest i negative iinotropic i effect i and ishould i be i avoided i in i HF
▪ This ieffect ican iworsen ithe idisorder
▪ Has ithe istrongest i effect i on i nodal i conduction
▪ Can i significantly i worsen i bradycardia
o Diltiazem: i affects i nodal i conduction i and i can i worsen i or i cause i bradycardia i (less
i thaniverapamil)
o CCBs i are i not i drugs i of i choice i immediately i after i MI
▪ However idiltiazem ihas ishown isome ibenefit iin ireducing imortality iin inon iQ iwave iMI
ifor ia iselected igroup iof ipatients iwho iEF iare iabout i40%
o Contraindicated: i EF i <40% i and i for i all i other i patients i early i after i MI, i type i 1 i CCBs
i areicontraindicated ir/t inegative iinotropic iand ibradycardic ieffects
o Ventricular i dysfunction, i SA i or i AV i nodal i conduction i disturbances, i and i SBPs i below i 90
i should inot ibe itreated iwith itype i1 iCCBs i r/t ihigh irisk ifor iinduction iof iHF iand i significant
ihypotension
o Type i2 idrugs iare iless idependent ion ithe iheart ifor itheir ieffects ibut istill inot idrug iof
ichoiceiafter iMI
o Type i2: iAvoid iin ipatients iwith isignificant iperipheral iedema
▪ Their istrong iperipheral ivasodilating ieffects iresults iin iperipheral ipooling iof iblood
iand imay ilead ito ireflex itachycardia
o Type i2 idrugs: iContraindicated iin iunstable iangina ir/t ipotential ito icause itachycardia
o If inecessary i to i treat i patients i with i peripheral i edema i or itachyarrhythmia i SR i forms
i areipreferred
o Hepatic iimpairment: iall iCCBs ishould ibe iused icautiously iwith idosage ireduction
irecommended ifor imost iagents
o Pregnancy i Category i C: i teratogenic i and i embryotoxic i effects i in i small
i animals:icontraception
, o Verapamil, idiltiazem, inifedipine, iand inicardipine: ifound iin ibreast imilk: ido inot igive ito
iduring imothers
o Safety iand iefficacy iof ithese idrugs ihave inot ibeen iestablished iin ichildren
o ADR
o Dizziness, i HA, i hypotension, i and i syncope
▪ These ilead i to i HF i with i congestion, i SOB, i cough, i and i palpitations
o HF iis iworse iwith iverapamil, idiltiazem, iand inifediple
o GI: idry imouth, iNV, ireflux, iand iconstipation i(especially icommon iwith iverapamil: iincrease
ifiber iand istool isoftener)
o Not icommon: isexual idysfunction iand igynecomastia
o Hyperglycemia i(uncommon)
o Photosensitivity iand ifacial itelangiectasia ican ioccur iwith iamlodipine, inifedipine,
iandid iltiazem
▪ Also i associated i with i hyperpigmentation
o ADRs ireduced iwith iuse iof isustained-release iforms iversus iimmediate irelease
o Drug i interactions:
o CYP3A4 i metabolism i of i all i CCBs
o Additive ihypotension iwith iother iantihypertensive idrugs, initrates, iquinidine, ior iETOH
o NSAIDS imay idecreased iantihypertensive ieffects
o Verapamil, i diltiazem, i and i some i dihydropyridines i have i additive i bradycardia i with i BBs
i oridigoxin
o Digoxin ilevels imay iincrease iwith ir/f itoxicity iwhen iused iwith iverapamil, idiltiazem, ior
inifedipine
o Verapamil i may i decrease i effectiveness i of i rifampin i and i the i effectiveness i of i verapamil
i mayibe idecreased iby iconcurrent iuse iof ivitamin iD iand iCa
o Verapamil: ialters ilithium ilevels: ipick ianother iCCB
o Grapefruit ijuice: iincreased ifree iCCB i(increased idrug ilevels ir/t itoxicity)
o Clinical i Use i and
i DosingiChronic iAngina
• Both itype i 1 iand i 2 idrugs i are ieffective iin itreatment iof istable i and iexertional i angina
• Act i on iboth i sides i of i the i supply-demand i equation:
o peripheral ivasodilation iand inegative iinotropism ireduce ioxygen idemand
o dilation i of i coronary i arteries i increases i oxygen i supply
• Nifedipine, inicardipine, iand iamlodipine iare idrugs iof ichoice
o Nifedipine i(Procardia iXL) iis ithe imost ioften iprescribed
o Combining ithis idrug iwith ipropranolol i is i more ieffective ithan ieither i agent igiven i alone
o BB i suppresses i the i reflex i tachycardia i that i can i occur i with i type i 2 i CCBs
• Nicardipine iis isimilar ito inifedipine ibut iless ilikely ito icause ihypotension i and iLV idysfunction
o Useful ifor ipatients iwith i angina iwho ialso ihave imild iHF ior iborderline iHTN
• Amlodipine iis iwell i tolerated i with iless i venous i pooling i and i minimum i reflex i tachycardia
o Safe ito iuse ifor ipatients iwith isignificant iventricular idysfunction
o Long ihalf ilife
▪ (acts ilike i a isustained i release iform: i less ivenous i pooling, i less ireflex
i tachycardia,iand ionce idaily idosing)
o Amlodipine ican ibe icrushed
o 5 img iinitially
o Doses ihigher ithan i10 img ihave inot idemonstrated iany iincrease iin ibenefit
o Amlodipine i has i been i used i in i combination i with i several i BBs i to i produce
i improvediresponse
• Diltiazem: i less i likely i to i cause i hypotension i and i other i ADRs i associated i with
i peripheralivasodilation ithan inifedipine
o Less i negative i inotropic i activity i than i verapamil
o The ireduction iin i average idaily iheart irate i improves icoronary i artery ifilling itime
i andimyocardial ioxygen isupply
o Good ichoice ifor ipatients iwho ineed ito ireduce itheir iHR
, • Verapamil iis iRx imore ioften ifor iTx iof iarrhythmias ir/t ipotent inegative iinotropic ieffect iand
isignificant islowing iof iAV inode iconduction
o Not iused ifor ipatients iwith icompromised iLV ifunction, ibradycardia, ior iAV iblock
o May i be i chosen i for i patients i with i SVT i with i angina
Vasospastic i (Variant, i Prinzmetal’s) i Angina
• Diltiazem, ilong i acting inifedipine, i and i amlodipine i most iused: iproduce i more icoronary
i arteryivasodilation iand ireduce ivasospasm
Unstable iAngina
• If ivasospasm iis ia icomponent iof ithe iangina, iCCBs imay ibe iused
• Verapamil: idrug iof ichoice
• Type i 2 idrugs i are i contraindicated i in i unstable i angina
Hypertension
• Guidelines i indicate i black i patients i as i a i group i are i more i responsive i to i diuretics i and i CCBs i as
i firstiline imedications ifor ithe itreatment iof iHTN
• Indicated ifor iboth isevere ibp i>160/110 iand inone-severe iHTN i(BP i140 ito i159/90 ito i109)
i in ipregnancy
o i i Nifedipine icapsules iand iperipheral iarterial idilator idrugs iare iuseful ifor iboth idisorders
• Amlodipine: iespecially iuseful ifor iHTN iin ipatients iwith iLV idysfunction iand iCHF
• Long i acting inifedipine, idiltiazem, ior iverapamil i may ibe iused ifor ipatients iwith iCAD
• Long iacting inifedipine: igood ichoice ifor iPVD ir/t ivasodilating ieffect
• For iall iCCBs: iold iadults ishould ibe istarted ion ihalf ithe iusual idose iand iincreases iin idosage
ishould ibe igradual ito ireduce iADRs
SVT iand iAFib
• Type i 1 i CCB i in i selected i supraventricular i tachycardias i because i the i slow i AV i node i conduction
o Verapamil i (80 i to i 120 i mg i PO) i can i terminate i the i rhythm
▪ Conversion itakes iabout ian ihour
o Diltiazem i (40 ito i 80 i mg iorally) i can i also i be i tried
• Verapamil i prophylaxis: i 240 i to i 480 i mg/d i for i PSVT
o Ensure ithat ithe irhythm iis i not iventricular
o Verapamil ican iworsen iventricular irhythm idisturbances ir/t inegative iinotropic
ieffects
• Verapamil iused i as i an ialternative ito idigoxin i to islow i a irapid i ventricular i response i in ithe
itreatment iof iAFIB ir/t idirect ieffect ion iAV inode i(prolongs irefractory iperiod iand iconductio
time)
o Doses ilike iPSVT
• Verapamil iand idigoxin itogether: icheck idig ilevels ioften ican iincrease idig ilevels ir/f itoxicity
• Wolff-Parkinson-White isyndrome
o Ventricular i responses i that i are i dangerously i rapid: i surgical i ablation
Migraine iHA iProphylaxis
• Unlabeled iindication i for iCCBs
• Verapamil: iused i most i often i (240 i to i 480 i mg/d)
• To ifacilitate iadherence iuse iSR iform ifor ionce idaily idosing
• Trial ifor i3 imonths
Raynaud’s iSyndrome
o Unlabeled iindication
o Type i2 iCCBS idrug iof ichoice ir/t iperipheral ivasodilating ieffects iand iplatelet iinhibition
o Nifedipine i10 img iPO iat ithe ioffice ito i assess ieffect ion iBP, iif ino isignificant idrop iin iBP ithen iRx
i 10img iPO iTID
o Dose imay ibe iincreased iby i10 img/d ievery i3 ito i4 idays ito ia imax iof i30 img iTID
o Monitoring ievery i2 ito i4 imonths
o Diltiazem imay ibe itried iif inifedipine idoes inot iwork
o 30 img iQID iand iincreased ievery ithree ito ifour idays iuntil imax iof ifour i120 img idoes idaily
iis ireached
o Felodipine i and iisradipine i are ialso i vasodilators ithat i may ibe itried
Esophageal iSpasm
