Lecture 9: Drugs for Benign Prostatic Hyperplasia and Incontinence

-Increased BMI

-Metabolic Syndrome

-Diet high in fat and red meat

Factors that increase BPH risk

AUA Symptom Index

severity of incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia

0-7

symptom score for mild BPH

8-19

symptom score for moderate BPH

20-35

symptoms score for severe BPH

-Opioids

-Anticholinergics

-Sympathomimetics

medications that may cause/worsen urinary retention in BPH

-Limit evening fluid intake

-Avoiding excess alcohol and irritative foods

-Increased physical activity

What are some lifestyle changes that may reduce LUTS in BPH?

-Alpha 1 blockers

-5-alpha reductase inhibitors

-Anticholinergics

Drugs for moderate to severe BPH symptoms

-Medical hx

-Physical exam

-International Prostate Symptom Score (IPSS)

-Urinalysis

-Counsel and follow up in 4-12 weeks

Describe the initial evaluation for a pt presenting with bothersome LUTS that is possibly due to BPH

Alpha-1 Blocker

First line initial therapy for BPH

Alpha-1 Blocker

-Alfuzusin

-Doxazosin

-Prazosin

-Silodosin

-Tamsulosin

-Terazosin

Alpha-1 Blocker

"-osin"

5α-Reductase Inhibitor

-Dutasteride

-Finasteride

5α-Reductase Inhibitor

"-asteride"

Alpha-1 Blocker

Indications:

-BPH

-HTN

-Ureteric Stone

Alpha-1 Blocker

blocks alpha receptors to decrease bladder/prostate smooth muscle tone and improve urine flow

-Bladder base

-Bladder neck

-Prostate

-Prostatic capsule

-Prostatic urethra

locations of alpha 1 receptors

Alfuzosin and Silodosin

Which Alpha 1 blocker:

CIs: potent 3A4 inhibitors and hepatic impairment

Silodosin

the only alpha blocker that is contraindicated in renal impairment

Alpha-1 Blocker

AEs:

-hypotension

-dizziness, syncope, tachycardia

-erectile or ejaculation dysfunction, decreased libido, gynecomastia

Start with low dose and titrate gradually

how can you minimze the AEs of alpha blockers?

PDE-5 Inhibitors

Alpha-1 blockers should not be used with what other drug?

5α-Reductase Inhibitor

-consider if enlarged prostate (>30 g/cc)

-allow >3 months for response

-can be used in combo with alpha blockers

-overall reduces prostate cancer incidence, but may increase risk of high grade prostate cancer

Finasteride

which 5α-Reductase Inhibitor can be used for male pattern alopecia?

5α-Reductase Inhibitor

-inhibits enzyme that converts testosterone to DHT

-reduces DHT levels

-Pregnancy

-Female of child bearing age

CIs for 5α-Reductase Inhibitor

5α-Reductase Inhibitor

AEs:

-erectile of ejaculation dysfunction

-decreased libido

-gynecomastia

PDE-5 Inhibitors

-Sildenafil

-Vardenafil

-Tadalafil

Tadalafil

Which PDE-5 Inhibitor has an FDA indication for BPH?

-PDE-5 inhibitors

-NSAIDs

-Cetrorelix

what other drugs have off label uses for BPH?

Cetrorelix

-GnRH receptor antagonist

-may improve LUTS in BPH

-Loop Diuretics (Furosemide) (~6 hrs before bedtime)

-Desmopressin (if furosemide does not work)

Medications for Nocturia in BPH

-Saw palmettoberry

-Stinging nettle

-African plum

-Purple cone flower

-South African star grass

-Rye pollen extract

-Pumpkin seeds

-Trembling aspen leaves

Natural Products for nocturia in BPH (not recommended by AUA)

Bladder Overactivity (UUI)

-strong and sudden urgency to void

-frequency with urgency

-large amount of urinary leakage with each episode of incontinence

-nocturnal incontinence

-nocturia

-struggle to reach the toiled in time

Urethral Underactivity (SUI)

-leaking during physical activity

-have the ability to reach toilet in time

-no nocturia or frequency

-Alpha blockers

-ACE-is

meds that may contribute to Stree UI

-Diuretics

-Alcohol

Drugs that may contribute to Urge UI

-Celecoxib

-Thiazolidinediones

-Sedatives/Hyponotics

drugs that may contribute to functional UI

-CCBs

-Opioids

-Skeletal muscle relaxants

-Antidepressants

-Anti-parkinson meds

-Antihistamines

-Sedatives/hypnotics

-Alcohol

drugs that may contribute to overflow UI

ACE inhibitors

"-prils"

ARBs

"-sartans"

Thiazolidinediones

-bind peroxisome proliferator-activated receptor (PPAR) gamma in adipocytes to promote adipogenesis and fatty acid uptake (in peripheral but not visceral fat).

- Pioglitazone (Actos)

- Rosiglitazone (Avandia)

-Bladder training

-Pelvic floor muscle training >3 months

-Containment devices

-Alter fluid intake

non-pharm first line managment for uncomplicated UI

Anticholinergics

first line for Urge UI (overactive bladder) if bladder training is ineffective

-Mirabegron

-OnabotulinumtoxinA

Second line medication options for urge UI (overactive bladder)

Duloxetine

first line for Stress UI if PFMT (kegels) is ineffective

-Duloxetine

-Alpha Receptor Agonist

-Topical Estrogens

pharmacological options for Stress UI

Topical Estrogen

treatment of choice for postmenopausal woman with stress UI and atrophic vaginitis

Anticholinergics

-Darifenacin

-Fesoterodine

-Oxybutynin

-Solifenancin

-Tolterodine

-Trospium

Anticholinergics

-block M3 receptors and relax bladder wall

Anticholinergics

Indications:

-bladder muscle dysfunction (overactive bladder)

-alternative treatment in BPH for LUTS without elevated postvoid residual

-Gastric or Urinary Retention

-Uncontrolled Glaucoma

CIs for Anticholinergics

Anticholinergics

AEs:

-acute urinary retention

-blurred vision, dry mouth, confusion, asthma, tachycardia, constipation, sedation

QT prolonging drugs

Anticholinergics should not be used with what other drugs?

Alpha-1 Blocker

Anticholinergics can be used in combination with an __________________________:

-reduces storage symptoms and urinary frequency

-may increase risk of acute urinary retention

Mirabegron

-beta 3 agonist

-relaxes detrusor muscle during storage phase

-alternative first line for overactive bladder

Mirabegron

AEs:

-HTN

-UTI

-headache

-dry mouth

-constipation

OnabotulinumtoxinA

-administered via intravesical (bladder wall) injections

-blocks release of ACh from local motor nerves

-long lasting muscle paralysis (3+ months)

-Infection at injection site

-Urinary retention or postvoid residual urine volume (>200 mL)

CIs for OnabotulinumtoxinA

OnabotulinumtoxinA

AEs:

-injection site pain

-increased risk fo UTI

-may spread and cause swallowing or breathing difficulties

OnabotulinumtoxinA

BBW: effects may spread from site of injection to produce symptoms hours to weeks after injection, including swallowing or breathing dificulties

Duloxetine

-serotonin and norepinephrine reuptake inhibitor (SNRI)

-involved in control of urethral smooth muscle and external urethral sphincter

-taper upon discontinuation to avoid withdrawal symptoms

Duloxetine

AEs:

-nausea and constipation

-dry mouth, insomnia

-increased suicidal thoughts/behavior

Duloxetine

BBW: increased suicidal thoughts/behaviors

Topical Estrogens

-enhances proliferation or urethral epithelium

-increases number/sensitivity of alpha receptors in bladder neck and proximal urethra

Alpha Receptor Agonists

-Pseudoephedrine

-Phenylephrine

Alpha Receptor Agonists

-consider for stress UI

-stimulates alpha 1 receptors to constrict the urethral smooth muscle

Alpha Receptor Agonists

AEs:

-htn

-HA

-dry mouth

-nausea

-insomnia/restlessness

-Uncontrolle dHTN

-Tachyarrhythmias

-CAD

CIs for Alpha Receptor Agonists

Bethanechol

-indicated for urinary retention

-stimulates ACh release to increase parasympathetic activation and detrusor muscle tone

Bethanechol

CIs:

-hyperthyroidism

-peptic ulcer

-bronchial asthma

-bradycardia

-hypotension

-vasomotor instability

-CAD

-epilepsy

-parkinsonism

-GI obstruction

-Bladder neck obstruction

-questionable strength/integrity of GI tract or bladder wall

-peritonitis

Bethanechol

AEs:

-flushing, abdominal cramps, diarrhea, urgent desire to urinate

-seizure, acute asthma exacerbation

-OMT

-Acupuncture

-Anti-incontinence devices

-Supportive care

Additional Non-pharmacologic Non-surgical Treatments for Urinary retention