Benign Prostate Hyperplasia Therapeutics

BPH Assessment

• History

• Urinalysis

• DRE

• PSA

• Symptoms survey

• Others

  • SrCr, Cytology, Uroflow, Voiding diary, PVR, sexual function questionnaire

AUA symptom score index

If have a lot of almost always, you want to refer.

• Mild 0-7 points

• Moderate 8-19 points

• Severe 20-35 points

International Prostate Symptom Score (I-PSS)

Asks the same 7 questions as AUA plus a QoL question! Same scoring system.

What questions do AUA and I-PSS ask?

FUNWISE

• Frequency

• Urgency

• Nocturia

• Weak stream

• Intermittency

• Straining

• Emptying (sensation of incomplete emptying)

Boyarsky Index

Total on 9 questions, differentiating between obstructive and irritative symptoms. Can help guide on which type of drug therapy to recommend.

What are the obstructive symptoms?

• WISE + D

  • weak stream

  • intermittency

  • straining (hesitance)

  • emptying (incomplete voiding)

  • dribbling

What are the irritative symptoms?

• FUN + D

  • frequency

  • urgency

  • nocturia

  • dysuria

Typical signs and symptoms of mild BPH

• AUA < 7

• asymptomatic

• peak urinary flow <10mL/s

• PVR >25-50mL

Typical signs and symptoms of moderate BPH

• AUA 8-19

• obstructive and irritative symptoms

• peak urinary flow <10mL/s

• PVR >25-50mL

Typical signs and symptoms of moderate BPH

• AUA >=20

• obstructive and irritative symptoms

• peak urinary flow <10mL/s

• PVR >25-50mL

• 1+ complications of BPH

BPH Goals of Therapy

• Reduce LUTS associated with BPH

  • reduce AUA score ~3 points

  • increase urinary flow

  • normalize PVR < 50mL

• Improve QoL

• Reduce risk of surgical intervention

• prevent progression of disease

• decrease long-term sequalae of bladder outlet obstruction

Management plan for mild symptoms of BPH

Watchful waiting

Management plan for moderate symptoms of BPH

• With ED → alpha1 blocker, PDE inhibitor or both

• small prostate + low PSA → alpha1 blocker

• large prostate + increased PSA → alpha1 blocker + 5alpha-reductase inhibitor

• mostly irritative symptoms → alpha1 blocker + anticholinergic/mirabegron

Management plan for severe symptoms of BPH

• complication of BPH → surgery

What are the potential complications of BPH?

• urinary retention → acute renal failure

• persistent/intermittent gross hematuria

• overflow urinary incontinence

• urinary stasis → recurrent UTIs

• bladder diverticula (out-pouching, weakness)

• bladder stones

• bladder outlet obstruction → chronic renal failure

Where do muscarinic receptors work on the prostate/bladder?

In the detrusor muscle. Activation of the muscarinic receptors, blocks the contraction of the bladder. So inhibiting the muscarinic receptors would allow for contraction.

Where do alpha-adrenergic receptors work on the prostate/bladder?

Found in the bladder neck, urethra and prostate. Activation promotes contractions. So, inhibiting would allow for relaxation and better flow.

Where do Beta3 receptors work on the prostate/bladder?

Found in the smooth muscle of the bladder. Activation causes relaxation of the detrusor muscle.

What does watchful waiting look like for BPH patients?

• used in no symptoms or mildly bothersome without complications

• regular follow-up at 6-12 to reassess symptoms and signs of progression

  • questionnaire at each visit

  • flow rate and PVR

  • DRA ± PSA

Non-pharm behaviour modifications to minimize LUTS

• restrict fluids at bedtime

• minimize caffeine and alcohol

• frequent emptying of bladder (scheduled)

• avoid drugs that may exacerbate

  • move diuretics away from bedtime

What needs to be considered when choosing a pharmacological therapy?

• symptom severity

• risk of complications based on size/PSA level

• patient preference (medical vs surgical)

• cost

• concurrent medical treatments

  • ED

  • overactive bladder/irritative voiding

What are the 2 main classes of drugs that are used to treat BPH?

• alpha1 adrenergic blockers

• 5alpha reductase inhibitors

How do alpha1 adrenergic blockers work in terms of BPH?

Reduces dynamic factors

• causes smooth muscle relaxation in prostate, bladder neck and prostatic urethra

What are the alpha1 adrenergic blockers? And which are prostate specific?

• Silidosin

• Alfuzosin

• Tamsulosin

• Prazosin

• Terazosin

• Doxazosin

bolded = prostate specific (SAT)

Why might it be important to use a prostate specific alpha1 adrenergic blocker?

Reduces the risk of orthostatic hypotension. Useful in older adult patients.

How do 5alpha reductase inhibitors work in terms of BPH?

Reduce static factor

• inhibits the conversion of testosterone to DHT → reduces growth of prostate

What are the 5alpha reductase inhibitors?

• finasteride

• dutasteride

What other drugs can be used for BPH?

Improve storage capacity of bladder → relaxes detrusor muscle

• antimuscarinics

• PDE5 inhibitors

• mirabegron

What is the min difference in terms of symptom management for 5alpha reductase inhibitors and alpha1 adrenergic blockers?

• 5alpha reductase inhibitors

  • impact underlying disease and decrease prostate volume

• alpha1 adrenergic blockers

  • rapid symptoms relief but no change in disease progression

What are some cautions with the alpha1 adrenergic receptors?

• caution in liver impairment

• Prazosin and Silodosin - reduce dose for renal impairment

• Tamsulosin and Terazosin - caution in renal impairment

• Tamsulosin - rare ADE of intraoperative floppy iris syndrome

When would you choose a non-selective alpha1 adrenergic blocker over uroselective?

If a patient also have uncontrolled hypertension

What is “first-dose phenomenon” in terms of alpha1 adrenergic receptor blockers?

• fast and large drop in BP and sudden syncope after first dose

  • especially with non-selective

• may be accompanied by tachycardia - to try and overcome drop in BP

  • increases risk of MI or angina

• Prevent by starting low and slow

Onset of alpha 1 adrenergic blockers?

1-6 weeks for onset of effect. Similar onset between agents.

What are come cautions with 5alpha reductase inhibitors?

• use with caution in liver impairment

  • no dose adjustments needed

• Dutasteride has more drug interactions because metabolized by CYP3A4

• ADR = sexual dysfunction

• teratogenic

Onset of action for 5alpha reductase inhibitors?

3-6 months for onset of effect. Reduces the prostate volume by 20-30% and PSA levels by 50%. Similar efficacy between agents

What are antimuscarinic agents used for in BPH?

Reducing irritative voiding symptoms

What are the different antimuscarinic agents used in BPH?

• darifenacin

• fesoterodine

• oxybutynin (IR, ER, gel, patch)

  • IR can be used as PRN

• solifenacin

• tolterodine (IR, ER)

• trospium

What are the common ADEs with antimuscarinics?

• dry mouth

• constipation

• tachycardia

Onset of effect for antimuscarinics in BPH?

1-2 weeks for onset of effect

Use of PDE5 inhibitors in BPH?

• relaxes the smooth muscle around the prostate

• used if combo with ED

• Needs to be doses 5mg daily

• tadalafil is only one with official indication

Onset of PDE5 inhibitor for BPH?

4 weeks for onset of effect

Use of mirabegron in BPH?

• indicated for overactive bladder with symptoms of urgency, urgency incontinence and urgency frequency

• used is cannot use antimuscarinic

Onset for mirabegron in BPH?

2-8 weeks for onset of effect

Use of desmopressin in BPH?

• increases water reabsorption in distal tubules and collecting ducts

• considered if more advances symptoms or problematic nocturia

• need to monitor sodium due to potential for hyponatremia

Procedure options for BPH

• Prostatectomy = gold standard

  • TURP

  • Open surgical procedure

• TUIP

• minimally invasive surgeries

  • transurethral needle ablation

  • green light laser

  • microwave thermotherapy