gotta go? urinary incontinence in the elderly

1

GottaGo?UrinaryIncontinence

intheElderly

Stephanie Sibicky,PharmD, BCGP, BCPS

NortheasternUniversityBouvéCollegeofHealthSciences|SchoolofPharmacy

ClinicalPharmacist– IntegratedTeachingUnitBrighamandWomen’sHospital

Objectives• Discuss theetiologyand pathophysiology of urinaryincontinence (UI).

• Evaluatepharmacologic and non-pharmacologic treatmentoptions for urinaryincontinence.

• Createpatient-specific recommendations forthetreatmentof urinaryincontinence based onavailableefficacy andsafetydata.

Epidemiology

0%

20%

40%

60%

80%

CommunityregularUI

CommunityanyUI

CommunityanyUI

Communityfrailoracutehospital

Nursinghome

%prevalence

♂♀

2.5Xmorecommon inwomen

Adapted from Essentials ofClinicalGeriatrics ,2013.

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Consequences ofIncontinence

MedicalRiskofcystitis,urosepsis,

pressure sores,perineal rashes,

sleepdisturbances,

dehydration, falls

PsychosocialEmbarrassment,

isolation,depression,

predispositiontoinstitutionalization

EconomicCostofsupplies,medications,homehealthaide/care at

home,nursingfacility

TheAgingUrinaryTractPhysiologic Change ResultsIn…

↓bladder elasticity Lesscapacityforvolume

↑residualvolume Incompleteemptying

↑nocturnalsodiumandfluidexcretion Nighttimeawakeningtourinate

↑urethralresistance(men) Weakstream,difficultyurinating

↓urethral resistance(women, ↓estrogen) Urgency,goingtoomuch

Weakened pelvicfloormuscles Increasedpressureonthebladder

↑involuntarybladdercontractions Urgency,gottogoNOW!

Allcontribute,butnonealoneprecipitates incontinence

Anatomy&Pathophysiology

Ureters

DetrusorMuscle

ExternalSphincter

InternalSphincter

ParasympatheticNervousSystemSympathetic

NervousSystem(α-adrenergic)

BladderNeck

SomaticNervousSystem

Capacity ≈300ml

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Pathophysiology:StoragePhase

Ureters

ExternalSphincter

InternalSphincter



BladderNeck


InhibitorySignal fromCortex

CONTRACTION(Closed) CONTRACTION

(Closed)

BladderFilling

DetrusorMuscle

RELAXATIONβ3

Pathophysiology:VoidingPhase

Ureters

DetrusorMuscle

ExternalSphincter

InternalSphincter



BladderNeck


InhibitorySignal fromCortexCONTRACTION

MICTURITION

RELAXATION(Open) RELAXATION

(Open)

AChM3

Pathophysiology:Summary

Picture credit: http:/ /sketchymedicine.com/2011/10/neural-control-of-micturitio n/

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Evaluation&DiagnosisHISTORY

• Symptoms (onset, type,frequency, timing)

• Bladder record• Comorbidities,lifestyle,

medications, environment• Patient perception of

incontinence

PHYSICAL

• Mobilityissues• Gynecologicalandurological

evaluation• Tests

– Catheterizationorbladderultrasound (residualvolumes)

– Cystoscopyandflowstudies– Urinarystress test– UAandurinecultures– Bloodchemistries– Renal function– Postprandialglucose

GoalsofTherapy• Minimizesignsandsymptomsmostbothersometothepatient1. Non-pharmacologictechniques2. Medications3. Surgicalintervention

• Setrealistic expectations– Totaleliminationofsymptomsmaynotbefeasible– Communicatemostcommonsideeffects– Balancepatientgoals,expectations,andrisks

Classification:Acute/Transient• Recentonset• Associatedwithacutemedicalproblem– Heartfailure– Acuteconfusionoralteredmentalstatus– Surgicalprocedures

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ReversibleCauses• Delirium or Dementia• Infections• Atrophic vaginitis,urethritis, atonic bladder• Psychologicalor Pharmaceuticals• Endocrine (diabetes, hypothyroidism) or Excessiveurine output/fluid intake

• Restrictedmobility or Retention• Stoolimpaction

Medication-InducedIncontinence

ACE(angiotens ion–convertingenzyme);NSAIDs(non-steroidalantiinflammatorydrugs)

Stress• α-blockers • Atypicalantipsychotics• ACE inhibitors

Urge• Antidepressants • Hormonereplacement• 5HT4-agonists• Directorindirectparasympathomimetics(cholinesteraseinhibitors)

Overflow• Anticholinergics • α-agonists• Antiparkinson drugs • Opioids• β-blockers • Calciumchannelblockers

Functional• H1-antagonists • Opioids• Antipsychotics • Alcohol• Benzodiazepines

IncreaseUrine

Production

• Diuretics • Thiazolidinedione• Lithium • Musclerelaxants• NSAIDs • Alcohol

TreatmentofAcute/TransientUI• Identifyandtreatunderlying cause• Treatsymptomsandpatientneeds• Remove,reduce,substitute offendingmedication• Attendtosurgicalcomplication, impaction, etc.• Improvemoodandmentalstatus• Antibiotics forinfection orvaginitis

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CaseBW• BWisa72-year-oldfemalewhopresentstotheclinic complaining ofincreasedfrequency (every2hours), urgency,andmoderateleakage

• PMHincludes diabetes,uncontrolledhypertension, osteoporosis, andhypothyroidism

• Medicationsinclude metformin, HCTZ,amlodipine, calcium +vitaminD,andlevothyroxine

• Whenaskingherabout OTCuse,shementionsneedingtotakeMiralaxdaily

CaseBW,cont.Afterremovingthepotential acutecausesofUI,BWcontinues tohavesymptoms.Shementionsthatshehasleakagewhenshesneezesandoftenneedsto“racetotheladiesroom”throughout theday.

HowwouldyouclassifyBW’sincontinence?

a) Urgeb) Stressc) Overflowd) Mixed

Classification:Chronic/PersistentUrge Stress Overflow Functional

Cause Detrusormuscleoveractivity

Weakenedpelvicfloormuscles

Bladderdistension duetoobstruction(BPH,fecalimpaction)

Underlyingphysicalormental

impairmentimpactingability

totoilet

CommonSymptoms

Urgencywithorwithout

incontinence,frequency,nocturia orenuresis

Incontinencewithcoughing,

sneezing,laughing,exercise,

activitiesthatincreaseabdominalpressure,frequency

Incompletevoiding,

frequency,urgency,hesitancy,abdominalfullness,straining

Incontinence–looks likeurge

Mixed =usuallycombinationofurgeandstress incontinence

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UrgeUrinaryIncontinence(UUI)• Involuntaryvoidingpreceded byabriefwarning• Causes:– Detrusormuscleinstability(involuntarycontraction)

– Twohypotheses• Neurogenic• Myogenic

• Overactivebladder(OAB)– Syndromeincludingurgency,frequency,andnocturia

–Withorwithout urgeincontinencePicture credit: http:/ /sketchymedicine.com/2012/02/stress -urge-overflow-and-mixed-incontinence/

UUITreatmentStrategy• Identifyandmitigateanyreversiblecauses

• Non-pharmacologic– Lifestyle(e.g.,diet,behavior)– Surgical

• Pharmacologic– Expectationof4-6weekresponse– Ifnoresponse,canswitchtoanotheragentinsameclass

• Diet(monitoring fluid,caffeine,bladder irritants)• Exerciseandweight loss• Smokingcessation• Schedulingregimens:– Timedvoiding– Bladdertrainingandscheduling

• Musclerehabilitation:– Pelvicfloormuscleexercises(e.g.,Kegelexercises)– Biofeedback,electricalstimulation– Acupuncture

• External urinecollection(menonly)• Surgery

Non-pharmacologic TreatmentofUUI

Subak LLetal.NEJM. 2009;360(5):481-90.Dallosso HM et al.BJU Int. 2003;92(1):69-77.

Dumoulin C etal.Cochrane Database SystRev. 2014; May 14;(5):CD005654.

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Non-pharmacologic TreatmentofUUI

• Urinary prosthesis(women)– Drawsurineoutofthebladderandblocksurineflowout

– Insertedbyphysician,thenbypatientorcaregiver

– Replaceevery29days– Useremotecontroltovoid– Informationalvideos:http://vesiflo.com/videos/

Picture credit: http:/ /www.thedailynarrative.com/wp-content/uploads/2014/10/20141014-FG30001014F DA- H.jpg?33 fdec /

UUITreatmentTargets

Ureters

DetrusorMuscle

ExternalSphincter

InternalSphincter



BladderNeck


InhibitorySignal fromCortexCONTRACTION

MICTURITION

RELAXATION(Open) RELAXATION

(Open)

AChM3

β3

UUITreatmentTargets:Non-selectiveReceptor Anatomical Location ResultofAntagonism

M1Brain Cognitiveimpairment

GItract Constipation,drymouth

M2

Brain Cognitiveimpairment

Heart Tachycardia

Urinary tract Bladderrelaxation, sphincterclosing

M3

Urinary tract Bladder relaxation,sphincter closing


Ophthalmologic Mydriasis

M4 Brain Balance impairment

Adapted from Zimmerman K,2015.

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UUITreatment:Anticholinergics• Reducecholinergic transmissiontobladder,inhibit involuntarydetrusor contraction, increasebladder capacity,decreasefrequencyofurination

• Sideeffects:drymouth, visualdisturbances,constipation, dryskin

• Precautions – arrhythmias, cardiovasculardisease,GImotilityissues,dementia, andelderly

• Contraindications – GIobstruction, closedandnarrowangleglaucoma

UUITreatment:Efficacy• Anticholinergics haveamodestbenefit overplacebo– Reductionin0.6episodes/day– 50%ofpatientsstillunhappyorfrustratedwithsymptomsaftertreatment

• 60-70%ofwomendiscontinue within 6months• Similarefficacybetweenagentsalthough limitedhead-to-head trialsbetweenagents

• Extended-release agentshavelowerratesofadverseeffectsthanimmediatereleaseagents

ShamilyanTet al.AnnIntern Med.2012;156(12):861.AHRQ 2012. Availableathttp:/ /effectivehealthcare.ahrq.gov/ehc/products/169/1021/CER36_Urinary-

Incontinence_execsumm.pdf

Non-selectiveAnticholinergicsMedication Formulations AdverseEffects AdditionalCommentsOxybutynin IRtablets(Ditropan®) MOST Referencestandard

GradualdoseescalationERtablets(DitropanXL®) BettertoleratedthanIRPatch(Oxytrol®) OTCforwomenonly

Bypasses1stpassGel(Gelnique®) Bypasses1stpass

Tolterodine IRtablets(Detrol®) CYP2D6 >CYP3A4metabolismRenaldoseadjustments

ERcapsules (Detrol®LA) BettertoleratedthanIRFesoterodine ERtablets(Toviaz®) Adjustmentsforrenal

impairmentand3A4inhibitorsTrospium IRtablets (Sanctura®) Dose adjustmentforCrCl<30

ml/minERtablets (SancturaXR®)

LEASTBettertoleratedthanIRAvoidin renalimpairment

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UUITreatmentTargets:SelectiveReceptor Anatomical Location ResultofAntagonism

M1Brain Cognitiveimpairment


M2

Brain Cognitiveimpairment

Heart Tachycardia

Urinary tract Bladderrelaxation, sphincterclosing

M3

Urinary tract Bladder relaxation,sphincter closing


Ophthalmologic Mydriasis

M4 Brain Balance impairment

SelectiveAnticholinergicsSolifenacin

• IRtablets (Vesicare®)• M3selectivity > M2• Efficacy

– Non-inferior tooxybutynin IR– Superior to tolterodine IR

• Side effects:– Less thanoxybutynin and

tolterodine– More thandarifenacin

• Maximum 5mg/day– Renal impairment (CrCl<30)– Moderate andseverehepatic

impairment

Darifenacin• ERtablets (Enablex®)• Truly selective forM3• Efficacy

– Non-inferior tooxybutynin IR– Moreeffective than

tolterodine IRat12weeks• Lessside effects than

oxybutynin• Norenal doseadjustment• Hepatic impairment

– Moderate –max7.5mg/day– Notevaluated in severe

Mirabegron: β-agonist• ERtablet(Myrbetriq®)• Reducesbladder contractions viarelaxation ofdetrusor musclethrough β3-agonism

• Efficacyin4-8weeks,reduction in0.5episodes/dayat50mgdose

• Maximum25mg/dayifCrCl<30ml/min• Sideeffects:hypertension, nasopharyngitis, UTI,constipation, tachycardia,headache

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OtherPharmacologicTreatment• Tricyclic Antidepressants (e.g.,imipramine)– Increasesbladdercapacityandoutletresistance,anticholinergicproperties

– Sideeffects:weakness,fatigue,posturalhypotension,hipfractures

• Botox® (onabotulinumtoxinA)–Muscleparalyticwheninjectedintodetrusormuscle– ApprovedJanuary2013– Injectedinto20sitesviaurethraevery12weeks– Decreases1.6-1.9episodes/day

CaseBW,cont.Besidesnon-pharmacologic options, which

treatmentforurgeUIwouldbemostappropriateforBW?

a) Mirabegronb) OxybutyninIRc) Darifenacind) TolterodineLA

StressUrinaryIncontinence(SUI)• Involuntaryleakageduetoincreasedintra-abdominalpressure thatovercomesurethralresistance

• Causes–Weakpelvicfloormuscles– Sphincterincompetence– Trauma/damage tourethra–Women>>>Men

Picture credit: http:/ /sketchymedicine.com/2012/02/stress -urge-overflow-and-mixed-incontinence/

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StressUrinary Incontinence Triggers

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Non-Pharmacologic Treatment forSUI

Pelvicfloormuscletraining Pessaries

Bladder

Uterus

Picture credit: http:/ /1qghdw20tywd2qc5uw1w82ap-wpengine.netdna-ss l.com/wp-conten t/uploads/2016/09/vagina.jpg;http:/ /2nznub4x5d61ra4q12fyu67t.wpengine.netdna -cdn.com/ img/54645e rt.jpg

http:/ /www.seekwellness .com/mystore/products_pictures/stepfree%20weights .jpghttp:/ /mciverclinic.com/ images/uploads/pessary.jpg

PharmacologicTreatmentforSUI• Noagent isFDAapprovedforthetreatment ofSUIintheUnitedStates

• Duloxetine(Cymbalta®)– Serotoninandnorepinephrinereuptakeinhibitor

• Involvedincontrolofurethralsmoothmuscleincatsandrats• Facilitatespathwaybetween bladderandsympatheticnervoussystem• Increasessphinctertoneduringstoragephase

– Off-label inUSduetotosuicidalideation,indicatedinUK– Sideeffects(diminishwithtime):nausea,drymouth– Olderadultsunderrepresentedinstudies

GOALIncreasecontractionandtoneof

urethralsphincter

Cardozo Letal.Curr Med Res Opin.2010;26(2):253-61.

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PharmacologicTreatmentforSUI• α-Adrenergicagonists– Pseudoephedrine,phenylephrine– Cautioninelderlyduetosideeffects– Contraindicatedinhypertensionorobstruction

• Topicalestrogen(creams,vaginaltablets,rings)– SUI+vaginitisorurethritisduetoestrogendeficiency

– NOsystemictherapy– Usedincombinationwithα-agonists

• ImipramineMalallahMA et al.IntUrogynecolJ. 2015;26(4):477-85.

CodyJD et al.Cochrane DatabaseSystRev.2012 Oct17;10:CD001405.

MixedUrinaryIncontinence

URGE

STRESS


TreatmentofMixedUI• Initialtherapydependsonpredominatesymptoms

• Canusecombination oftreatmentstrategiesforUUIandSUIintheabsenceofobstruction– Pelvicfloormuscletrainingandbladdertraining– Behavioralinterventions–Medications

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OverflowUrinary Incontinence (OUI)

• Volumeofurineinbladder overcomes closingpressure

• Symptoms:– Diminishedstream– Strainingtovoid– Senseofincompleteemptying

• Causes:– Neurogenicbladder– Atonicbladder– Obstruction(BPH,strictures,neuropathy,impaction)

‒ Interruptedflow‒ Hesitancy


TreatmentofOUINon-pharmacologic

• Obstruction removal(surgery)

• Bladder training andvoidingschedule

• Catheterization– Self-catheterization 3-4x/day– Surgicallyplaced

Pharmacologic

• Bethanechol (Urecholine®)– Cholinomimetic– SEs:muscle cramping,

diarrhea– Cancause life threatening

ADE inasthmaorheartdisease

• αA1-receptor antagonists– Locatedinbladder neck,

urethra, andperiurethraltissues

– TreatmentofBPH inmen– Use inwomen forthis reason

FunctionalIncontinence• Personisunableorunwilling toreachthetoilet• Causes:–Musculoskeletaldisorders/weakness– Disabilities,visionloss– Cognitiveimpairment– Physicalrestraints– Psychologicalimpairments– Environment–Medications(e.g.,sedatives,neuroleptics)

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TreatmentforFunctionalUI• Scheduledorprompted toileting• Removalofbarriers andobstacles• Physicaltherapy• Assistivedevices– Bedsidecommode– Urinals– Elevatedtoiletseats

CaseBW,cont.Afterremovingthepotential acutecausesofUI,BWcontinues tohavesymptoms.Shementionsthatshehasleakagewhenshesneezesandoftenneedsto“racetotheladiesroom”throughout theday.

HowwouldyouclassifyBW’sincontinence?

a) Urgeb) Stressc) Overflowd) Mixed

ChoosingPharmacologicTherapy

MosthavesimilarefficaciesNewisnot

alwaysbetter!!!

Considersymptoms,

comorbidities,drug

interactions,sideeffects,etc.

Formularyrestrictionandinsurancecoverage

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TreatmentApproachinElderly• Determine ifthereisanotherunderlying cause• Anticholinergics areon2015BeersCriteria tobeavoidedinelderlywith dementiaorcognitiveimpairment

• Startlowandgoslow– Doseadjustforrenalandhepaticimpairment– Titrationbasedonsideeffectsandtolerability

• Trialofoneagentforupto2months• Consider switchtoanother agentifnoimprovementandtreatmentisstillnecessary

JAm Geriatr Soc63:2227–2246, 2015.

CounselingTips• Reduceintakeoffluidduring theday,especiallyintheevening(after6pm)

• Avoidcaffeinatedbeverages• Minimizetheuseofartificial sweeteners,acidicandspicyfoods

• Letyourpharmacist knowaboutnewmedicationsyouaretakingtoseeiftheycontribute toyoursymptoms

CaseBW,cont.Fourweeksafterstartingdarifenacin, BWreturns totheclinic becausethismedication isnot working.Shehasseencommercialsforanewmedicationcalled“Mybearstricks”andasksifthisisabetteroptions.Herblood pressuretodayis122/78.

Howwouldyouproceed?

a) Checkwithherinsurancefirsttoseeifitiscoveredb) Counselherthataneffectcantakeupto2monthsc) Recommendaswitchtosolifenacininstead

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TakeHomePoints• UIisaprevalentcondition withthepotential tohaveasignificantimpactonolderadults

• TreatmentforUIshould include non-pharmacologic approachesbeforeinitiatingpharmacologic agents

• Efficacy,adverseevents,andpatientpreferenceneedtobeconsidered whendevelopingatreatmentplan

• Pharmacistscanmonitor forefficacyandhelpmitigateadverseeffectsforpatientswithUI

References• Subak LL,Wing R,West DS, et al. PRIDE Investigators. Weight loss totreat urinary

incontinence inoverweight and obese women. NEngl J Med. 2009Jan29;360(5) :481-90.doi: 10.1056/NEJMoa0806375.

• Dallosso HM,McGrother CW, Matthews RJ,et al. Leicestershire MRC Incontinence StudyGroup. The association of dietand otherlifestyle factorswithoveractive bladder and stressincontinence: a longitudinal studyinwomen. BJUInt. 2003Jul;92(1) :69-77.

• Dumoulin C,Hay-Smith EJ, Mac Habée-Séguin G. Pelvic f loormuscle training versus notreatment, orinactive controltreatments, forurinary incontinence inwomen. CochraneDatabase Syst Rev. 2014May 14;(5) :CD005654.doi:10.1002/14651858.CD005654.pub3.

• Qaseem A, Dallas P,Forciea MA, et al; Clinical Guidelines Committee of the AmericanCollege of Physicians. Nonsurgical management of urinary incontinence inwomen: a clinicalpractice guideline fromthe American College of Physicians. Ann InternMed 2014:161:429-440.

• CodyJD, JacobsML, Richardson K,et al. Oestrogen therapy forurinaryincontinence in post-menopausal women. Cochrane Database Syst Rev. 2012Oct17;10:CD001405.doi:10.1002/14651858.CD001405.pub3.

• Richter HE, BurgioKL, Brubaker L, et al. Pelvic Floor Disorders Network. Continence pessarycompared withbehavioral therapy orcombined therapy forstressincontinence: arandomized controlled trial. Obstet Gynecol. 2010Mar;115(3) :609-17.doi:10.1097/AOG.0b013e3181d055d4.

References• CardozoL, Lange R, VossS, et al. Short- and long-term eff icacy andsafety of duloxetine in

women withpredominant stress urinary incontinence. CurrMed Res Opin. 2010Feb;26(2) :253-61.doi:10.1185/03007990903438295.

• Malallah MA, Al-Shaiji TF. Pharmacological treatment of purestress urinary incontinence: anarrative review. IntUrogynecol J.2015Apr;26(4) :477-85.doi:10.1007/s00192-014-2512-9.Epub2015Jan29.

• ReynoldsWS, McPheeters M, Blume J, etal. Comparative Effectiveness of AnticholinergicTherapy forOveractive Bladder inWomen: A Systematic Review andMeta-Analysis. ObstetGynecol. 2015 Jun;125(6) :1423-32.doi:10.1097/AOG.0000000000000851.

• Shamliyan T, Wyman JF, Ramakrishnan R,et al. Benef its andharms of pharmacologictreatment forurinaryincontinence inwomen: a systematic review. AnnInternMed. 2012Jun;156(12):861-74.

• Effective Health Care Program. Nonsurgical Treatments forUrinary Incontinence inAdultWomen: Diagnosis and Comparative Effectiveness. Agency forHealthcare Research Quality2012.Available at:http://effectivehealthcare.ahrq. gov/ ehc/products/169/1021/CER36_Urinary-Incontinence_execsumm.pdf (Accessed onNovember 19, 2012).

• Solifenacin and darifenacin foroveractive bladder. Obstet Gynecol. 2005Aug;106(2) :401-2.• Campbell SE, Glazener CM, HunterKF, etal. Conservative management for

postprostatectomy urinary incontinence. Cochrane Database Syst Rev. 2012Jan18;1:CD001843.doi:10.1002/14651858.CD001843.pub4.Review.Update in: CochraneDatabase Syst Rev. 2015;1:CD001843.

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QUESTIONS?

Thank [email protected]

GottaGo?UrinaryIncontinence

intheElderly

Stephanie Sibicky,PharmD, BCGP, BCPS

NortheasternUniversityBouvéCollegeofHealthSciences|SchoolofPharmacy

ClinicalPharmacist– IntegratedTeachingUnitBrighamandWomen’sHospital

gotta go? urinary incontinence in the elderly

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