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PortalHypertensionMedication
Author:JesusCarale,MDChiefEditor:BSAnand,MDmore...
Updated:Nov07,2015

MedicationSummary
Thegoalsofpharmacotherapyaretoreducemortalityandmorbidity,andprevent
complicationsassociatedwithacutebleedingrelatedtoportalhypertension.Two
maincategoriesofdrugs,vasoconstrictorsandvasodilators,areused.
Themainadvantagestousingvasoactiveagentsincludetheabilityofthesedrugs
totreatvaricealbleedingintheemergencydepartment,lowerportalpressure,and
offertheendoscopistaclearerviewofvaricesbecauseoflessactivebleeding.
Vasoactiveagentsrepresentanidealtreatmentforsourcesofportalhypertensive
bleedingotherthanesophagealvarices(eg,gastricvarices>2cmbelowthe
gastroesophagealjunctionorportalhypertensivegastropathy). [8,15]
Thevasoconstrictorssomatostatinandoctreotideareusedtotreatacutebleedingin
patientswithportalhypertensionbeforeperformingendoscopy. [45,49]Intravenous
infusionsofoctreotidewilllowerportalbloodpressureandcanpreventrebleeding
duringthepatient'sinitialhospitalization.Vasodilatorssuchasisosorbide

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mononitrate(ISMN)reduceintrahepaticvascularresistancewithoutdecreasing
peripheralorportalcollateralresistance.
Betablockers,whichincludepropranolol,nadolol,andtimolol,areusedtoprovide
primaryandsecondaryprophylaxis.Betablockerslowercardiacoutput(viablockade
ofbeta1adrenoreceptors)andcausesplanchnicvasoconstriction(viablockadeof
vasodilatoryadrenoreceptorsofthesplanchniccirculation),reducingportaland
collateralbloodflow.

SomatostatinAnalogs
ClassSummary
Somatostatin,anorphandrug,isanaturallyoccurringtetradecapeptideisolated
fromthehypothalamusandfrompancreaticandentericepithelialcells.Through
vasoconstriction,somatostatindiminishesbloodflowtotheportalsystem,thus
decreasingvaricealbleeding.Ithaseffectssimilartothoseofvasopressinbutdoes
notcausecoronaryvasoconstriction.Somatostatinhasaninitialhalflifeof13
minutesandisrapidlyclearedfromthecirculation.
Somatostatinanalogsinhibitthesecretionofhormonesinvolvedinvasodilation.
Octreotideisasyntheticoctapeptide.Comparedwithsomatostatin,octreotidehas
similarpharmacologicactionswithgreaterpotencyandlongerdurationofaction.In
theUS,octreotideisusedofflabelforthemanagementofvaricealhemorrhage. [45]
Viewfulldruginformation

Octreotide(Sandostatin)
Octreotide,asyntheticoctapeptide,actsprimarilyonsomatostatinreceptor
subtypesIIandV.Itinhibitsgrowthhormonesecretionandhasamultitudeofother
endocrineandnonendocrineeffects,includingtheinhibitionofglucagon,vasoactive
intestinalpeptide,andGIpeptides.Octreotidehasgreaterpotencyandalonger
durationofactionthansomatostatin.

BetaBlockers,Nonselective
ClassSummary
Nonselectivebetablockingagentsdecreasehepaticarterialandportalvenous
perfusion.Betaadrenergicblockersmayblocktheeffectofvasodilators,decrease
plateletadhesivenessandaggregation,andincreasethereleaseofoxygento
tissues.
Nonselectivebetablockershavebeenshowntopreventbleedinginmorethan50%
ofpatientswithmediumorlargevarices. [8]Theseagentsexertamoderateeffecton
thereductionofportalflow,andsmallereffectsontheincreaseinportalresistance
anddecreaseonportalpressure.
Propranololisusedofflabelforprimaryprophylaxisincombinationwith
endoscopicvaricealligation(EVL)foresophagealvarices.Thisagentisalso
indicatedforsecondaryprophylaxisforesophagealvarices.
Viewfulldruginformation

Propranolol(Inderal,InnoPranXL)
Propranololisanoncardioselectivebetablockerthatreducesportalpressure
throughthereductionofportalandcollateralbloodflow.Itcompeteswith
adrenergicneurotransmitters(eg,catecholamines)atsympatheticreceptorsites.
Similartoatenololandmetoprolol,propranololblockssympatheticstimulation
mediatedbybeta1adrenergicreceptorsintheheartandvascularsmoothmuscles.
Viewfulldruginformation

Nadolol(Corgard)
Nadololisanoncardioselectivebetablockerthatreducesportalpressurethrough
thereductionofportalandcollateralbloodflow.
Viewfulldruginformation

Timolol
Timololisanoncardioselectivebetablockerthatreducesportalpressurethroughthe
reductionofportalandcollateralbloodflow.

VasopressinRelated
ClassSummary
Vasoconstrictorsreduceportalbloodflowand/orincreaseresistancetovariceal
bloodflowinsidethevarices.Therefore,thesedrugsreducebloodflowinthe
gastroesophagealcollateralsbecauseoftheirvasoactiveeffectsonthesplanchnic

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vascularsystem.Whenusedincombinationwithnitrates,theefficacyandsafetyof
vasoconstrictorshavebeenshowntoimprove.However,theirusemaybelimitedas
theriskofadverseeventsishigherwithcombinationtherapy.
IntheUS,vasopressinisusedofflabelforthemanagementofacutevariceal
bleeding.
TerlipressiniswidelyusedinEuropebuthasnotreceivedFDAapprovalforusein
theUnitedStates.Thisisasyntheticanalogueofvasopressin.Itistheonly
pharmacologicagentshowntoreducemortalityfromvaricealbleeding.Terlipressin
haslongerbiologicactivitythanvasopressin.Itsignificantlyreducesportaland
varicealpressureandazygosflow.Thedrugisbeneficialwhencombinedwith
sclerotherapy.Terlipressinalsohastheadvantageofpreservingrenalfunction,
whichisaparticularlyimportantfeatureinpatientswithcirrhosis.
Viewfulldruginformation

Vasopressin(Pitressin)
Vasopressinhasvasopressorandantidiuretichormone(ADH)activity.Itincreases
waterresorptionatthedistalrenaltubularepithelium(ADHeffect)andpromotes
smoothmusclecontractionthroughoutthevascularbedoftherenaltubular
epithelium(vasopressoreffects).However,vasoconstrictionisalsoincreasedin
splanchnic,portal,coronary,cerebral,peripheral,pulmonary,andintrahepatic
vessels.Vasopressindecreasesportalpressureinportalhypertension.
Anotableadverseeffectofthisagentiscoronaryarteryconstriction,whichmay
disposepatientswithcoronaryarterydiseasetocardiacischemia.Thiscanbe
preventedwiththeconcurrentuseofnitrates.Vasopressinisrarelyused.

Vasodilators
ClassSummary
Vasodilatorshavebeenshowntoexertasmalleffectonthereductionofportalflow,
anincreaseinportalresistance,anddecreaseonportalpressure.Theseagents
reduceintrahepaticvascularresistancewithoutdecreasingperipheralorportal
collateralresistance.
Nitrates,however,technicallyworkbydecreasingresistance.Theydecreaseportal
flowbydecreasingmeanarterialpressure.Oralnitroglycerinisusedofflabelforthe
managementofvaricealbleeding.
Viewfulldruginformation

NitroglycerinPO(NitroBid,Nitrostat,NitroTime)
Nitroglycerincausesrelaxationofvascularsmoothmusclebystimulating
intracellularcyclicguanosinemonophosphateproduction.Theresultisadecreasein
bloodpressure.

ContributorInformationandDisclosures
Author
JesusCarale,MDConsultingGastroenterologist,ArkansasValleyRegionalMedicalCenter,LaJunta,Colorado
JesusCarale,MDisamemberofthefollowingmedicalsocieties:AmericanGastroenterologicalAssociation
Disclosure:Nothingtodisclose.
Coauthor(s)
SamyAAzer,MD,PhD,MPHProfessorofMedicalEducation,ChairofMedicalEducationResearchand
DevelopmentUnit,FacultyofMedicine,UniversitiTeknologiMARA,MalaysiaVisitingProfessorofMedical
Education,FacultyofMedicine,UniversityofToyama,JapanFormerSeniorLecturerinMedicalEducation,
FacultyEducationUnit,FacultyofMedicine,DentistryandHealthSciences,UniversityofMelbourneand
UniversityofSydney,Australia
SamyAAzer,MD,PhD,MPHisamemberofthefollowingmedicalsocieties:NewYorkAcademyofSciences,
SigmaXi,AssociationforPsychologicalScience,GastroenterologicalSocietyofAustralia,AmericanCollegeof
Gastroenterology,RoyalSocietyofMedicine
Disclosure:Nothingtodisclose.
ParitMekaroonkamol,MDResidentPhysician,DepartmentofInternalMedicine,AlbertEinsteinMedical
Center
ParitMekaroonkamol,MDisamemberofthefollowingmedicalsocieties:AmericanCollegeofPhysicians,
AmericanGastroenterologicalAssociation,PennsylvaniaMedicalSociety
Disclosure:Nothingtodisclose.
ChiefEditor
BSAnand,MDProfessor,DepartmentofInternalMedicine,DivisionofGastroenterology,BaylorCollegeof
Medicine
BSAnand,MDisamemberofthefollowingmedicalsocieties:AmericanAssociationfortheStudyofLiver

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Diseases,AmericanCollegeofGastroenterology,AmericanGastroenterologicalAssociation,AmericanSociety
forGastrointestinalEndoscopy
Disclosure:Nothingtodisclose.
Acknowledgements
SamyAAzer,MD,PhD,MPHProfessorofMedicalEducationandHeadofCurriculumDevelopmentUnit,King
SaudUniversity,Riyadh,SaudiArabiaVisitingProfessorofMedicalEducation,FacultyofMedicine,University
ofToyama,JapanformerProfessorofMedicalEducation,ChairofMedicalEducationResearchand
DevelopmentUnit,FacultyofMedicine,UniversitiTeknologiMARA,MalaysiaformerConsultanttotheVictorian
PostgraduateMedicalFoundation,Melbourne,AustraliaformerSeniorLecturerinMedicalEducation,Faculty
EducationUnit,FacultyofMedicine,DentistryandHealthSciences,UniversityofMelbourneandUniversityof
Sydney,Australia
SamyAAzer,MD,PhD,MPHisamemberofthefollowingmedicalsocieties:AmericanCollegeof
Gastroenterology,AssociationforPsychologicalScience,GastroenterologicalSocietyofAustralia,NewYork
AcademyofSciences,RoyalSocietyofMedicine,andSigmaXi
Disclosure:Nothingtodisclose.
SimmyBank,MDChair,Professor,DepartmentofInternalMedicine,DivisionofGastroenterology,LongIsland
JewishHospital,AlbertEinsteinCollegeofMedicine
Disclosure:Nothingtodisclose.
SandeepMukherjee,MB,BCh,MPH,FRCPCAssociateProfessor,DepartmentofInternalMedicine,Section
ofGastroenterologyandHepatology,UniversityofNebraskaMedicalCenterConsultingStaff,Sectionof
GastroenterologyandHepatology,VeteranAffairsMedicalCenter
SandeepMukherjee,MB,BCh,MPH,FRCPCisamemberofthefollowingmedicalsocieties:RoyalCollegeof
PhysiciansandSurgeonsofCanada
Disclosure:MerckHonorariaSpeakingandteachingIkariaPharmaceuticalsHonorariaBoardmembership
AnnOuyang,MBBSProfessor,DepartmentofInternalMedicine,PennsylvaniaStateUniversityCollegeof
MedicineAttendingPhysician,DivisionofGastroenterologyandHepatology,MiltonSHersheyMedicalCenter
Disclosure:Nothingtodisclose.
WaqarAQureshi,MDAssociateProfessorofMedicine,ChiefofEndoscopy,DepartmentofInternalMedicine,
DivisionofGastroenterology,BaylorCollegeofMedicineandVeteransAffairsMedicalCenter
WaqarAQureshi,MDisamemberofthefollowingmedicalsocieties:AmericanCollegeofGastroenterology,
AmericanCollegeofPhysicians,AmericanGastroenterologicalAssociation,andAmericanSocietyfor
GastrointestinalEndoscopy
Disclosure:Nothingtodisclose.
FranciscoTalavera,PharmD,PhDAdjunctAssistantProfessor,UniversityofNebraskaMedicalCenterCollege
ofPharmacyEditorinChief,MedscapeDrugReference
Disclosure:MedscapeReferenceSalaryEmployment
NoelWilliams,MDProfessorEmeritus,DepartmentofMedicine,DalhousieUniversity,Halifax,NovaScotia,
CanadaProfessor,DepartmentofInternalMedicine,DivisionofGastroenterology,UniversityofAlberta,
Edmonton,Alberta,Canada
NoelWilliams,MDisamemberofthefollowingmedicalsocieties:RoyalCollegeofPhysiciansandSurgeonsof
Canada
Disclosure:Nothingtodisclose.

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