BPH

pharmachieve

BPH

• non-cancerous enlargement of the prostate

• can cause urinary symptoms identical to prostate cancer

  • not cancer —> cant spread to other parts of body

• common in older men

• cause elevated PSA (prostate specific antigen)

• prostate enlargement depends on DHT

  • Type II 5 alpha reductase metabolizes circulating testosterone into DHT —> binds to androgen receptors = BPH

• 3 components:

  1. Mechanical obstruction by enlarged prostate

  2. Dynamic obstruction caused by tone of prostatic smooth muscle

  3. the reaction of the bladder to the obstruction

clinical presentation

1. urinary frequency - need to urinate frequently

2. urinary urgency - sudden, urgent need to urinate

3. hesitancy - difficulty initiating

4. incomplete bladder emptying - feeling of persistent residual urine

5. straining - need strain or push to initiate and maintain urination

6. decreased force of stream - loss of force of urinary stream

7. dribbling - loss of small amounts of urine

Storage related symptoms = FUN

• Frequency

• Urgency

• Nocturia

Voiding related symptoms

• Hesitancy

• incomplete bladder emptying

• straining

• decrease force of stream

• dribbling

risk factors

1. Aging —> not common <40

2. Family hx (close male relative)

3. Medications = mimic or exacerbate symptoms

   • antihistamines

   • diuretics

4. African descent males

5. Lifestyle

   • obesity increases risk

6. Comorbidities

   • diabetes and heart disease can increase risk

drug causes

• Antihistamines

  • prevent bladder muscle from contracting

• Decongestants

  • tighten muscles in prostate and bladder neck = more difficult for urine to leave bladder

• Diuretics

  • increased urine production

• Opiates

  • impaired bladder contractility

• TCAs

  • anticholinergic effects

goals of therapy

1. provide relief or resolution of lower urinary tract symptoms (LUTS)

2. decrease risk of progression of BPH

3. prevent complications from bladder outlet obstruction

4. early diagnosis of prostate cancer

5. reduce risk of surgical intervention

non pharm

Watchful waiting

• periodic visits to physician —> no treatment

Lifestyle changes

• fluid restriction

• avoid irritative beverages (caffeine or alcohol)

• avoidance and/or monitoring of some medications (diuretics, decongestants, antihistamines, antidepressants)

• elevate legs before resting if existing pedal edema

• timed voiding (bladder retraining)

• pelvic floor exercises

• treat constipation

Surgery

treatment options

• alpha blockers

• 5-alpha reductase inhibitors

• PDE5 inhibitors

• antimuscarinics

• Beta 3 Adrenergic agonists

• Desmopressin

algorithm

alpha blockers

Selective = SAT (when your on an airplane, the seat your selected, you SAT ahead of time)

• Silodosin

• Alfuzosin

• Tamsulosin

Nonselective = DT —> need dose titration bc it can cause decrease in BP

• Doxazosin

• Terazosin

tips:

• work FAST! but does NOT decrease risk of progression (little impact on prostate growth)

  • effects in 1 week but can take up to 6 weeks for full effect

• all equally effective

• interactions:

  • Antihypertensives (increased hypotension)

  • CYP3A4 inhibitors

• s/e:

  • Dizziness (esp with Doxazosin and Terazosin)

  • HA

  • Asthenia (abnormal weakness)

  • Nasal congestion

  • Hypotension

  • Tamsulosin = floppy iris syndrome (only issue if having cataract surgery), retrograde ejaculation

  • Silodosin = retrograde ejaculation

• use selective ones to reduce risk of hypotension

• minimize s/e of doxazosin and terazosin by taking at bedtime

• renal: Silodoson

  • CrCl 30-50 = reduce dose

  • CrCl <30 = AVOID

• Silodosin and Alfuzosin = take with food

• provide symptomatic relief

• used in patients awaiting surgery/ unwilling for surgery

• rare: allergic reaction to tamsulosin in patients with sulfa allergy

5 alpha reductase inhibitors

Finasteride, Dutasteride

• REDUCE PROSTATE SIZE! = decrease risk of progression = decrease risk of surgical intervention (most effective if prostate is large; prostate vol >30ml)

• SLOW!! takes 6-12 months for symptomatic relief

• decrease PSA by 50%

• lifelong therapy —> if stop, prostate will re-grow

• interactions:

  • CYP3A4 inhibitors (dutasteride only) = Clarithromycin, itraconazole, fluconazole, verapamil, amiodarone

• S/E: low risk

  • Impotence

  • sexual dysfunction

  • decreased libido

  • decreased semen quantity at ejaculation

  • gynecomastia (rare)

  • risk of suicidal ideation (rare; finasteride)

• use in patients awaiting surgery/ unwilling for surgery

• compliance is important for effective decrease

• hazardous drug handling consideration!

tadalafil

• PDE5 inhibitor —> used DAILY

• Quick onset!

• used for daily management of erectile dysfunction and BPH

• s/e:

  • dyspepsia

  • HA

  • nasal congestion

  • back pain

  • flushing

  • visual disturbances

  • permanent vision or hearing loss (rare)

• interactions:

  • Alpha blockers

  • nitrate based meds = fatal hypotension

• CrCl < 30 = avoid once daily dosing

• AVOID NITRATES!!!! decrease in BP!!

• can take w or w/o food

antimuscarinics

Fesoterodine, Oxybutynin, Solifenacin, Tolterodine

• QUICK onset!

• symptomatic relief of overactive bladder (helpful for storage sx) = FUN sx

• s/e:

  • Dry mouth

  • drowsiness

  • constipation

  • small risk of urinary retention —> use with caution if residual urine vol >250 cc

• interactions:

  • TCA’s

  • Anticholinergics

• used in combo with alpha blockers!

• oxybutynin = most anticholinergic

• Tolteridone = doesnt cross BBB = good in elderly

• DO NOT USE IN UNCONTROLLED NARROW ANGLE GLAUCOMA!

mirabegron ER

• Beta 3 adrenergic agonist

• symptomatic relief of overactive bladder

• s/e:

  • Hypertension —> AVOID IN UNCONTROLLED HTN

  • Nsopharyngitis

  • UTI

  • Tachycardia

• interactions:

  • moderate inhibitor of CYP2D6 (substrates = Fluoxetine, Paroxetine, Venlafaxine, Mirtazapine, Codeine)

  • weak inhibitor of PgP

• well tolerated

• can be used in combo with antimuscarinics

• should not be chewed or crushed

desmopressin

• used in nocturnal polyuria = decreases # nocturnal voids and increases hrs of undisturbed sleep

• QUICK ONSET —> 1 hr

• s/e:

  • Hyponatremia

  • Xerostomia (dry mouth)

  • HA

  • Dizziness

  • Abdominal pain

• interactions:

  • Loop diuretics

  • corticosteroids

  • any hyponatremia associated agents

• Na levels must be taken at baseline in all men, then 7 days and then 30 days after starting

• Sodium levels should be taken with dose increases and periodically during treatment

combination therapy

Alpha blockers (silodosin, alfuzosin, tamsulosin, doxazosin, terazosin) + 5-Alpha reductase inhibitors (dutasteride and finasteride)

• appropriate and effective in patients with LUTS associated with prostate enlargement (>30 ml)

• rapid relief by alpha blocker and sustained relief of symptoms from 5-alpha reductase inhibitors (by decreasing PSA, prostate volume, altering disease progression and preventing need for surgery)

• cons:

  • additive side effects

  • increased associated with new cardiac failure (high risk for non-selectiv alpha blockers)

• most improvement in LUTS = improves symptoms and flow rate vs either agent alone

• if successfully treated, can discontinue alpha blocker after 6-12 months

• if sx re-occur: can restart alpha blocker

monitoring