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Basic&ClinicalPharmacology,13e>

CHAPTER62:DrugsUsedintheTreatmentof
GastrointestinalDiseases

KennethR.McQuaid

ANTIDIARRHEALAGENTS

Antidiarrhealagentsmaybeusedsafelyinpatientswithmildtomoderateacutediarrhea.However,

theseagentsshouldnotbeusedinpatientswithbloodydiarrhea,highfever,orsystemictoxicity

becauseoftheriskofworseningtheunderlyingcondition.Theyshouldbediscontinuedinpatients

whosediarrheaisworseningdespitetherapy.Antidiarrhealsarealsousedtocontrolchronicdiarrhea

causedbysuchconditionsasIBSorinflammatoryboweldisease(IBD).

OPIOIDAGONISTS

Aspreviouslynoted,opioidshavesignificantconstipatingeffects(seeChapter31).Theyincrease

colonicphasicsegmentingactivitythroughinhibitionofpresynapticcholinergicnervesinthe

submucosalandmyentericplexusesandleadtoincreasedcolonictransittimeandfecalwater

absorption.Theyalsodecreasemasscolonicmovementsandthegastrocolicreflex.Althoughall

opioidshaveantidiarrhealeffects,centralnervoussystemeffectsandpotentialforaddictionlimitthe

usefulnessofmost.

Loperamideisanonprescriptionopioidagonistthatdoesnotcrossthebloodbrainbarrierandhasno
analgesicpropertiesorpotentialforaddiction.Tolerancetolongtermusehasnotbeenreported.Itis

typicallyadministeredindosesof2mgtakenonetofourtimesdaily.Diphenoxylateisaprescription

opioidagonistthathasnoanalgesicpropertiesinstandarddoses;however,higherdoseshavecentral

nervoussystemeffects,andprolongedusecanleadtoopioiddependence.Commercialpreparations

commonlycontainsmallamountsofatropinetodiscourageoverdosage(2.5mgdiphenoxylatewith

0.025mgatropine).Theanticholinergicpropertiesofatropinemaycontributetotheantidiarrheal

action.

COLLOIDALBISMUTHCOMPOUNDS

SeethesectionunderMucosalProtectiveAgentsinearliertext.

BILESALTBINDINGRESINS

Conjugatedbilesaltsarenormallyabsorbedintheterminalileum.Diseaseoftheterminalileum(eg,

Crohnsdisease)orsurgicalresectionleadstomalabsorptionofbilesalts,whichmaycausecolonic

secretorydiarrhea.Thebilesaltbindingresinscholestyramine,colestipol,orcolesevelam,may

decreasediarrheacausedbyexcessfecalbileacids(seeChapter35).Theseproductscomeina

varietyofpowderandpillformulationsthatmaybetakenonetothreetimesdailybeforemeals.

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Adverseeffectsincludebloating,flatulence,constipation,andfecalimpaction.Inpatientswith

diminishedcirculatingbileacidpools,furtherremovalofbileacidsmayleadtoanexacerbationoffat

malabsorption.Cholestyramineandcolestipolbindanumberofdrugsandreducetheirabsorption;

hence,theyshouldnotbegivenwithin2hoursofotherdrugs.Colesevelamdoesnotappeartohave

significanteffectsonabsorptionofotherdrugs.

OCTREOTIDE

Somatostatinisa14aminoacidpeptidethatisreleasedinthegastrointestinaltractandpancreas
fromparacrinecells,Dcells,andentericnervesaswellasfromthehypothalamus(seeChapter37).

Somatostatinisakeyregulatorypeptidethathasmanyphysiologiceffects:

1. Itinhibitsthesecretionofnumeroushormonesandtransmitters,includinggastrin,

cholecystokinin,glucagon,growthhormone,insulin,secretin,pancreaticpolypeptide,vasoactive

intestinalpeptide,and5HT.

2. Itreducesintestinalfluidsecretionandpancreaticsecretion.

3. Itslowsgastrointestinalmotilityandinhibitsgallbladdercontraction.

4. Itreducesportalandsplanchnicbloodflow.

5. Itinhibitssecretionofsomeanteriorpituitaryhormones.

Theclinicalusefulnessofsomatostatinislimitedbyitsshorthalflifeinthecirculation(3minutes)

whenitisadministeredbyintravenousinjection.Octreotideisasyntheticoctapeptidewithactions

similartosomatostatin.Whenadministeredintravenously,ithasaserumhalflifeof1.5hours.Italso

maybeadministeredbysubcutaneousinjection,resultingina6to12hourdurationofaction.A

longeractingformulationisavailableforoncemonthlydepotintramuscularinjection.

ClinicalUses

1.Inhibitionofendocrinetumoreffects

Twogastrointestinalneuroendocrinetumors(carcinoid,VIPoma)causesecretorydiarrheaand

systemicsymptomssuchasflushingandwheezing.Forpatientswithadvancedsymptomatictumors

thatcannotbecompletelyremovedbysurgery,octreotidedecreasessecretorydiarrheaandsystemic

symptomsthroughinhibitionofhormonalsecretionandmayslowtumorprogression.

2.Othercausesofdiarrhea

Octreotideinhibitsintestinalsecretionandhasdoserelatedeffectsonbowelmotility.Inlowdoses(50

mcgsubcutaneously),itstimulatesmotility,whereasathigherdoses(eg,100250mcg

subcutaneously),itinhibitsmotility.Octreotideiseffectiveinhigherdosesforthetreatmentofdiarrhea

duetovagotomyordumpingsyndromeaswellasfordiarrheacausedbyshortbowelsyndromeor

AIDS.Octreotidehasbeenusedinlowdoses(50mcgsubcutaneously)tostimulatesmallbowel

motilityinpatientswithsmallbowelbacterialovergrowthorintestinalpseudoobstructionsecondaryto

scleroderma.

3.Otheruses

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Becauseitinhibitspancreaticsecretion,octreotidemaybeofvalueinpatientswithpancreaticfistula.

Theroleofoctreotideinthetreatmentofpituitarytumors(eg,acromegaly)isdiscussedinChapter37.

Octreotideissometimesusedingastrointestinalbleeding(seebelow).

AdverseEffects

Impairedpancreaticsecretionmaycausesteatorrhea,whichcanleadtofatsolublevitamindeficiency.

Alterationsingastrointestinalmotilitycausenausea,abdominalpain,flatulence,anddiarrhea.

Becauseofinhibitionofgallbladdercontractilityandalterationsinfatabsorption,longtermuseof

octreotidecancauseformationofsludgeorgallstonesinover50%ofpatients,whichrarelyresultsin

thedevelopmentofacutecholecystitis.Becauseoctreotidealtersthebalanceamonginsulin,

glucagon,andgrowthhormone,hyperglycemiaor,lessfrequently,hypoglycemia(usuallymild)can

occur.Prolongedtreatmentwithoctreotidemayresultinhypothyroidism.Octreotidealsocancause

bradycardia.

Copyright2017McGrawHillEducation.Allrightsreserved.

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