Pharmacologic Treatment For BPH

Dr. Harnold P. Sihaloho, Sp. U

SMF UROLOGY RSUD Dr. Pirngadi Kota Medan

Anatomy of BPH Bladder

Anatomy of BPH

ProstateUrethra Obstructed

Urinary flow

HypertrophiedDetrusor muscle

Kirby RS, et al, eds benign Prostatic Hyperplasia, 5th ed. 1995

Pathophysiology of BPH• Size of the prostate does not always

correlate to symptom severity

• symptom severity depends on :* Ability of prostate capsule to expand* Location of hyperplasia with respect to urethra* Ability of bladder to compensate for the obstruction* Central nervous system influences

Mc Vary K, Medication Management of Benign Prostatic Hyperplasia in the long term care setting, Princeton CME,September 14 2007 WWW. Princetoncme.com

DHT

Nocturia and Frequency Most Nocturia and Frequency Most Common ComplaintsCommon Complaints

Nocturia occurs in 87 % of men over 50+Nocturia occurs in 87 % of men over 50+Frequency occurs in 71 % of men over Frequency occurs in 71 % of men over

50+50+Disrupts lifestyleDisrupts lifestyle Impacts productivityImpacts productivity

Grayhack JT, et al Benign prostatic hyperplasia In :Grayhack JT, et al Benign prostatic hyperplasia In : Gillenwater JJ, et al, eds. Adult and Pediatric Urology. Vol 2, 4 Gillenwater JJ, et al, eds. Adult and Pediatric Urology. Vol 2, 4 thth ed 2002 : ed 2002 :

1401-14701401-1470

Symptoms of LUTS/BPHSymptoms of LUTS/BPH

Obstructive SymptomsObstructive Symptoms Irritative Irritative SymptomsSymptoms

* Hesitancy* Hesitancy * Urgency* Urgency* Weak stream* Weak stream * Frequency* Frequency* Straining to pass urine* Straining to pass urine * Nocturia* Nocturia* Prolenged micturition* Prolenged micturition * Urge incontinence* Urge incontinence* Felling of incomplete Bladder emptying* Felling of incomplete Bladder emptying* Urinary retention* Urinary retention

LUTS/BPH and QualityLUTS/BPH and Quality of Life of Life

The Impact of BPH on the The Impact of BPH on the PatientPatient

Concern Over

Need For Surgery

Symptoms

ConcernOver RiskOf AUR

Bother

Interferenceand Quality

Of lifeConcern

Over Cancer

Mc Vary K, Medication Management of Benign Prostatic Hyperplasia in the long term care setting, Princeton CME,

September 14 2007 WWW. Princetoncme.com

Diagnostic Tests for BPHDiagnostic Tests for BPH AUASI = IPSSAUASI = IPSS DREDRE PSAPSA UrinalysisUrinalysis TRUSTRUS Urinary flow rate *Urinary flow rate * Postvoid residual * Postvoid residual * * Denotes optional testing.* Denotes optional testing. AUASI = American Urological Association Symptom indexAUASI = American Urological Association Symptom index

Mc Vary K, Medication Management of Benign Prostatic Hyperplasia in the Mc Vary K, Medication Management of Benign Prostatic Hyperplasia in the long term care setting, Princeton CME,long term care setting, Princeton CME,

September 14 2007 WWW. Princetoncme.comSeptember 14 2007 WWW. Princetoncme.com

Differential Diagnosis of LUTSDifferential Diagnosis of LUTSProstateProstate

Obstruction ( BPH, BPE, BOO )Obstruction ( BPH, BPE, BOO )BladderBladder

* Detrusor overactivity* Detrusor overactivity* Impaired detrusor contractility* Impaired detrusor contractility* Sphincteric incontinence* Sphincteric incontinence* Polyuria/nocturnal polyuria* Polyuria/nocturnal polyuria

MedicationsMedications* Anthihistamines* Anthihistamines* Antidepressants* Antidepressants

Medical Therapy AlgorithmMedical Therapy AlgorithmPatien

IPSS ≤ 7 IPSS > 7

No or Little Bother

Moderate to Severe bother

Prostate SmallPSA Low

Prostate LargePSA Hight

Prostate SmallPSA Low

α adnenergicblocker

5α reductase InhibitorCombination Pα

Prostate LargePSA High

No Treatment

Prevertive Therapy ?5α Reductase Inhibitor

FISIOLOGI FISIOLOGI αα BLOCKERBLOCKER αα11- adreno receptors predominate in the - adreno receptors predominate in the

prostateprostate Prostatic smooth muscle is sympathhetically Prostatic smooth muscle is sympathhetically

innervatedinnervated Sympathetic nerve impluse result in release of Sympathetic nerve impluse result in release of

noradrenaline ( stored within nerve terminals )noradrenaline ( stored within nerve terminals ) Into the synaptic cleft Into the synaptic cleft bind by bind by αα11--

adrenoreceptorsadrenoreceptors αα11-adrenoreceptors simulation -adrenoreceptors simulation Influx Influx

intracellularintracellular CaCa++ ++ smooth muscle contraction smooth muscle contraction

Alpha BlockerAlpha Blocker Kontraksi otot polos prostat : alpha – receptor Kontraksi otot polos prostat : alpha – receptor

mediated sympathetic stimulationmediated sympathetic stimulation Kontraksi otot polos ( kapsul, adenoma, leher Kontraksi otot polos ( kapsul, adenoma, leher

buli-buli) : kontribusi 40 % obstruksibuli-buli) : kontribusi 40 % obstruksi Alpha blocker :Alpha blocker :

Relaksasi otot polos prostatRelaksasi otot polos prostat Mengurangi keluhanMengurangi keluhan Memperbaiki pancaran kencingMemperbaiki pancaran kencing

Distribution of Distribution of αα- Adrenoreceptors- Adrenoreceptorsin the Lower Urinary Tractin the Lower Urinary Tract

Steven A Kaplan, MD Department of Urology, College of Physicians & Surgeons, Columbia University, New York, NY

αα-Blockers-Blockers NonselectiveNonselective

- Phenoxybenzamine- Phenoxybenzamine Short-acting selective Short-acting selective αα1-blocker1-blocker

- Prazosin- Prazosin Long-acting selective Long-acting selective αα1-blocker1-blocker

- Alfuzosin- Alfuzosin- Doxazosin- Doxazosin- terazosin- terazosin

Long-acting selective Long-acting selective αα1-subtype1-subtype- Tamsulosin- Tamsulosin

Mc Vary K, Medication Management of Benign Prostatic Hyperplasia in the long term care Mc Vary K, Medication Management of Benign Prostatic Hyperplasia in the long term care setting, Princeton CME,setting, Princeton CME,

September 14 2007 WWW. Princetoncme.comSeptember 14 2007 WWW. Princetoncme.com

5- reduktase inhibitor - finasteride

- episteride- dutastride

mekanisme kerja menghambat perubahan hormon testosteron DHT

T DHT

Decrease in volume

IndicationIndication BPH No complicationBPH No complication IPSS : 8 – 18IPSS : 8 – 18 Q max : 10 – 15Q max : 10 – 15Contra Indication :Contra Indication :

HypotensionHypotensionHypersensitive reactionHypersensitive reactionAcute or chronic urinary retentionAcute or chronic urinary retention

- Renal insufisiensiRenal insufisiensi- Recurren hematuriaRecurren hematuria- Recurren urinary tract infectionRecurren urinary tract infection- Vesicolithiasis or Baladder diverrticulaVesicolithiasis or Baladder diverrticula

Adverse EventsAdverse Events

AdverseAdverseEffectEffect

TerazosinTerazosin(n = 636)(n = 636)

PlaceboPlacebo(n = 360)(n = 360)

Asthenia/fatigueAsthenia/fatigue 7.4%7.4% 3.3%3.3%PosturalPostural 3.9%3.9% 0.8%0.8%hypotensionhypotensionDizzinessDizziness 9.1%9.1% 4.2%4.2%

SomnolenceSomnolence 3.6%3.6% 1.9%1.9%Nasal congestion/Nasal congestion/ 1.9%1.9%** 00

Rhinitis ImpotenceRhinitis Impotence 1.6%1.6%** 0.6%0.6%

Terazosin Adverse Effects

Doxazosin Adverse EffectsDoxazosin Adverse Effects

AdverseAdverseEffectEffect

DoxazosinDoxazosin(n = 665)(n = 665)

PlaceboPlacebo(n = 300)(n = 300)

DizzinessDizziness(includes (includes

vertigo)vertigo)15.6%15.6%** 9.0%9.0%

FatigueFatigue 8.0%8.0%** 1.7%1.7%HypotensionHypotension 1.7%1.7%** 00EdemaEdema 2.7%2.7%** 0.7%0.7%DyspneaDyspnea 2.6%2.6%** 0.3%0.3%

Tamsulosin Adverse EffectsTamsulosin Adverse Effects

Adverse Adverse EffectEffect

Tamsulosin Tamsulosin 0.4 mg0.4 mg

(n = 502)(n = 502)

Tamsulosin Tamsulosin 0.8 mg0.8 mg

(n = 492)(n = 492)

PlacePlacebobo

(n = (n = 49493)3)

DizzinessDizziness 14.9%14.9% 17.1%17.1% 10.110.1%%

Abnormal Abnormal ejaculatioejaculationn

8.4%8.4% 18.1%18.1% 0.2%0.2%

AstheniaAsthenia 7.8%7.8% 8.5%8.5% 5.5%5.5%Libido Libido

decreaseddecreased 1.0%1.0% 2.0%2.0% 1.2%1.2%

AmblyopiaAmblyopia 0.2%0.2% 2.0%2.0% 0.4%0.4%

Alfuzosin Adverse EffectsAlfuzosin Adverse Effects

Adverse EffectAdverse Effect AlfuzosinAlfuzosin(n = 473)(n = 473)

PlaceboPlacebo(n = 678)(n = 678)

Upper Upper respiratoryrespiratory

tract infectiontract infection3.0%3.0% 0.6%0.6%

DizzinessDizziness 5.7%5.7% 2.8%2.8%HeadacheHeadache 3.0%3.0% 1.8%1.8%FatigueFatigue 2.7%2.7% 1.8%1.8%

5α Reductase inhibitor adverse effect

Common adverse drugs reactions include :Common adverse drugs reactions include : ImpotenceImpotenceDecreased libidoDecreased libidoDecreased ejaculate volumeDecreased ejaculate volume

Rare : breast tendernes and enlargment.Rare : breast tendernes and enlargment.

Thank youThank you