pharmacological treatmentIBSWord格式.docx

pharmacological treatmentIBSWord格式.docx

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TOPICHIGHLIGHTS

WJG20thAnniversarySpecialIssues（4）:

Irritablebowelsyndrome

Recentadvancesinpharmacologicaltreatmentofirritablebowelsyndrome

LazarakiGetal.PharmacologicaltreatmentofIBS

GeorgiaLazaraki,GrigorisChatzimavroudis,PanagiotisKatsinelos

GeorgiaLazaraki,GrigorisChatzimavroudis,PanagiotisKatsinelos,DepartmentofEndoscopyandMotilityUnit,G.GennimatasGeneralHospital,SchoolofMedicine,AristotleUniversityofThessaloniki,54635Thessaloniki,Greece

Authorcontributions:

LazarakiGmainlydraftedandwrotethemanuscript;

ChatzimavroudisGisinvolvedinwritingandeditingthemanuscript;

KatsinelosPisresponsiblefordraftingandcriticalapprovalofthemanuscript.

Correspondenceto:

Panagiotis 

Katsinelos,MD,PhD,AssistantProfessorofGastroenterology,DepartmentofEndoscopyandMotilityUnit,G.GennimatasGeneralHospital,SchoolofMedicine,AristotleUniversityofThessaloniki,EthnikisAminis41,54635Thessaloniki,Greece.gchatzimav@yahoo.gr

Telephone:

+30-2310-963341Fax:

+30-2310-963341

Received:

October1,2013Revised:

March13,2014

Accepted:

June20,2014

Publishedonline:

Abstract

Irritablebowelsyndrome（IBS）isahighlyprevalentfunctionaldisorderthatreducespatients’qualityoflife.Itisachronicdisordercharacterizedbyabdominalpainordiscomfortassociatedwithdisordereddefecationintheabsenceofidentifiablestructuralorbiochemicalabnormalities.IBSimposesasignificanteconomicburdentothehealthcaresystem.Alterationinneurohumoralmechanismsandpsychologicalfactors,bacterialovergrowth,geneticfactors,gutmotility,visceralhypersensitivity,andimmunesystemfactorsarecurrentlybelievedtoinfluencethepathogenesisofIBS.ItispossiblethatthereisaninteractionofoneormoreoftheseetiologicfactorsleadingtoheterogeneoussymptomsofIBS.IBStreatmentispredicateduponthepatient’smostbothersomesymptoms.Despitethewiderangeofmedicationsandthehighprevalenceofthedisease,todatenocompletelyeffectiveremedyisavailable.ThisarticlereviewstheliteraturefromJanuary2008toJuly2013onthesubjectofIBSperipherallyactingpharmacologicaltreatment.DrugsarecategorizedaccordingtotheiradministrationforIBS-C,IBS-DorabdominalpainpredominantIBS.

©

2014BaishidengPublishingGroupInc.Allrightsreserved.

Keywords:

Irritablebowelsyndrome;

Irritablebowelsyndromeconstipation;

Irritablebowelsyndrome-diarrhea;

Constipation;

Diarrhea;

Irritablebowelsyndrometreatment;

Irritablebowelsyndrome-pain

Coretip:

Irritablebowelsyndrome（IBS）isahighlyprevalentfunctionaldisorderthatreducespatients’qualityoflifeandimposesasignificanteconomicburdentothehealthcaresystem.ThisarticleextensivelyreviewstheliteraturefromJanuary2008toJuly2013onthesubjectofIBSperipherallyactingpharmacologicaltreatment.PathophysiologybackgroundandmodeofactioninIBSofeachsubstancearealsodiscussed.

LazarakiG,ChatzimavroudisG,KatsinelosP.Recentadvancesinpharmacologicaltreatmentofirritablebowelsyndrome.WorldJGastroenterol2014;

Inpress

INTRODUCTION

Irritablebowelsyndrome（IBS）isahighlyprevalent（10%-20%oftheUnitedStatesadultpopulation）[1]functionaldisorderthatreducespatients’qualityoflife.IBSisdefinedintheRomeIIIcriteriaasachronicdisordercharacterizedbyabdominalpainordiscomfortassociatedwithdisordereddefecation[eitherconstipation（IBS-C）,diarrhea（IBS-D）,ormixed/alternatingsymptomsofconstipationanddiarrhea（IBS-M）][2].Symptomsshouldbeginatleast6mobeforeandabdominalpainordiscomfortshouldbepresentatleast3dpermonthfor3moduringlast6moandshouldbeassociatedwithtwoormoreofthefollowing:

improvementwithdefecation,onsetassociatedwithachangeinstoolfrequencyand/orchangeinstoolform.BloatingandabdominaldistentionarealsofrequentlyreportedbyIBSpatientsreflectingsensitivitytonormalamountsofintestinalgas.Bydefinition,nodiseasethatcouldexplainthesymptomsshouldbepresent[2].

IBSrepresentsimportantcostsforthehealthcaresystem.Oneshouldlookcarefullyforalertsigns[i.e.,anemia,unintentionalweightloss,gastrointestinal（GI）bleeding,nausea/vomiting,familyhistoryofcancer]ofaseriousunderlyingdisordertodifferentiatefunctionalsymptomsfromorganicdisorders.Thus,foryoungerpatientswhomeetcriteriaforIBSwithnormalphysicalexaminationandno“redflags”,anextensivelaboratoryworkupshouldnotbeconsidered[3].

ItislikelythatthedefinitionofIBSrepresentanauspiceofdifferentconditions/diseasestatesforwhichwelackspecificbiomarkers.Alterationinneurohumoralmechanismsandpsychologicalfactors,bacterialovergrowth,geneticfactors,gutmotility,visceralhypersensitivity,andimmunesystemfactorsarecurrentlybelievedtoinfluencethepathogenesisofIBS[4-6].ItispossiblethatthereisaninteractionofoneormoreoftheseetiologicfactorsleadingtoheterogeneoussymptomsofIBS.

SinceIBSisnotasinglediseaseentity,butratherlikelyconsistsofseveraldifferentdiseasestates,IBStreatmentispredicateduponthepatient’smostbothersomesymptoms.Specifically,ourtreatmentstrategyseemstotargetconstipation,diarrhea,bloatingorpain[7].Awiderangeofmedications[prokinetiks,antispasmodics,sedatives,tranquilizers,laxatives,fecalbulkingagents,probioticsandantibiotics]alongwithlifestyleanddietmodificationshavebeenproposedforthishighlyprevalentcondition;

howevertodatethereisnodefiniteeffectivecureforthisstate[7].

Inthepresentreview,wereporttheresultsofoursearchinPubMed,Scopus,andGoogleScholardatabasesfromJanuary2008toJuly2013onthesubjectofIBSperipherallyactingpharmacologicaltreatment.MeSHterms“irritablebowelsyndrometreatment”and“IBStreatment”wereusedassearchterms.English-writtenarticlesonlywereincluded.Datafrommetanalysisandclinicalstudieswereincluded.Abstracts,casereports,comments/reviews,invitrostudies,animalstudiesandpharmacogeneticstudieswereexcludedfromthereview.Thesearchresultedin1018papersafteromissionofduplicatearticles;

finally86paperswereincludedafteromissionofnon-relevantarticles.FlowgramofthesearchispresentedinFigure1.DrugsarecategorizedaccordingtotheiradministrationforIBS-C,IBS-DorabdominalpainpredominantIBS.

IBS-C

TheevaluatedstudiesineachcategoryarereportedinTable1.Belowisalistofavailabletreatmentmethodsbasedonthefindings.

Laxatives

SeveralclinicalobservationshavereportedadecreaseinbowelmotilityandaprolongedtransittimeinpatientswithIBS-Ccomparedwithcontrols[8,9].Also,someIBS-Mpatientsreportanalternationinbowelhabitswithextendedperiodswithsmall,hardbowelmovementsornobowelmovementfollowedbyperiodswithloosestools.Osmoticagents,stimulants,andstoolsoftenersareallcomprisedinthecategoryoflaxatives.Polyethyleneglycol（PEG）istheonlylaxativethathasbeenevaluatedinthetreatmentofIBS.Thefirststudypublishedin2006assessedtheeffectsofPEG3350inpatientswithIBS-C（RomeIIcriteria）[10].Meanbowelmovementfrequencywassignificantlyincreased;

however,therewasnochangeinmeanpainlevelforthegroupwiththePEGtherapy.Inthelast5years2newstudiesevaluatedtheefficacyofPEGinIBS-C.Thefirststudy[11],arandomized,double-blind,placebo-controlledtrialusedfastingandpostprandial（PP）perceptionofrectaldistensionasmeasurements.Symptomswerealsorecorded.FourtytwopatientswithIBS-C（RomeIIcriteria）andwithapainthresholdof<

32mmHgparticipated.PatientsreceivedeitheroralPEG,3.45gt.i.d.orallyfor30dorplacebo.PEGimprovedconsistencyoffaeces.Both,PEGandplaceboincreasedbowelmovementsperweek（P<

0.001）,andrelievedsymptomswithoutsignificantside-effects.However,therewerenotsignificantdifferencesinfastingandPPrectaltoneandthresholdsforfirstsensation,gassensation,urgetodefecate,andpainbetweenPEGandplacebo.TheinvestigatorsconcludedthatchangesinrectaltoneandsensationwerenotrelatedtoPEG3350andplaceboeffects.PatientswithIBS-CgainedsomerelieffromtheirsymptomsbothwithPEGandplacebo.Inthesecondstudy[12],followinga14-drun-inperiodwithoutstudymedication,139adultpatientswithIBS-CwererandomizedtoreceivePEG3350+Eorplacebofor28days.Theprimaryendpointwasthemeannumberofspontaneousbowelmovementsperdayinthelasttreatmentweek.Inbothgroupstherewasanincreaseinmeanbowelmovementfrequencycomparedtorun-in.Thedifferencebetweenthegroupsinweek4from4.40（PEG3350+E）to3.11（placebo）wasstatisticallysignificant（95%Cl:

1.17-1.95;

P<

0.0001）.However,althoughmeanseverityscoreforabdominaldiscomfort/painwassignificantlyreducedcomparedwithrun-inwithPEG3350+E,therewasnodifferencevsplacebo.Spontaneousbowelmovements（SBMs）,responderrates,stoolconsistency,andseverityofstrainingalsoshowedsuperiorimprovementinthePEG3350+Egroupoverplacebointhefourthweek.TheauthorsconcludedthatPEG3350+Ewassuperiortoplaceboforreliefofconstipationbutresultedinnoimprovementtoabdominaldiscomfort/paincomparedtoplaceboinspiteofthepresenceofastatisticalsignificantimprovementinabdominaldiscomfort/painthatwasobservedcomparedwithbaseline.

Guanylatecyclase-creceptoragonists

Linaclotideisaguanylinpeptide.Guanylinpeptidesareafamilyofpeptideswithsimilarstructuretotheheat-stab