BPH

benign prostatic hyperplasia lecture by dr. donald

BPH

a non-cancerous prostate problem

BPH characteristics

1. abnormal growth

2. urethral compression

3. hindered urine flow

4. urine retention and need for frequent urination

5. complete blockage may occur

symptomatic BPH is common in which age group and why

men 60 years and older

due to androgen driven growth in size of the prostate

what usually causes lower urinary tract symptoms of BPH

static and dynamic factors and/or detrusor factors

what is BPH directly correlated with

age

chief etiologic factors for BPH

1. advanced patient age

2. stimulatory effect of androgens

epithelial tissue

anatomical lining of the of prostate

glandular tissue with androgen dependent growth

stromal tissue

anatomical component of prostate

smooth muscle that contains alpha receptors

capsule

anatomical component of prostate

contains alpha receptors

what type of receptors are found in the stromal tissue and the capsule of the prostate

alpha

delete

delete

types of lower urinary tract symptoms of BPH

1. obstructive symptoms

2. irritative symptoms

obstructive lower urinary tract symptoms

hesitancy, weak stream, straining to urinate, dribbling, and incomplete emptying

irritative lower urinary tract symptoms

dysuria, urinary frequency, urgency, and nocturia

complications of untreated BPH

1. chronic renal failure

2. gross hematuria

3. overflow urinary incontinence or unstable bladder

4. recurrent urinary tract infection

5. bladder diverticula

6. bladder stones

drug classes that cause worsening of lower urinary tract symptoms with BPH

1. androgens

2. alpha-adrenergic agonists

3. anticholinergic agents

4. methylxanthines

5. diuretics

6. sedatives

example of an androgen drug

testosterone

how does testosterone (androgens) lead to lower urinary tract symptoms of BPH

stimulate prostate enlargement

how do alpha adrenergic agonists cause LUTS

stimulate contraction of prostatic and bladder neck smooth muscle

examples of alpha adrenergic agonists

phenylephrine

pseudoephedrine

how do anticholinergic agents cause LUTS

block detrusor muscle contraction and impair bladder emptying

examples of anticholinergics

Antihistamines, phenothiazines, tricyclic antidepressants, antiparkinsonian agents

how do methylxanthines cause LUTS

act as a diuretic

examples of methylxanthines

caffeine

how do diuretics cause LUTS

produce polyuria

examples of diuretics

thiazide and loops

how do sedatives cause LUTS

may cause functional incontinence

example of sedatives

benzodiazepines and ethanol

diagnostic and monitoring parameters (only give 4 categories)

anatomical

clinical

lab

physiological

anatomical diagnostic and monitoring for BPH

digital rectal exam

clinical diagnostic and monitoring for BPH

AUA symptom score index

lab diagnostic and monitoring for BPH

urinalysis

prostate specific antigen

prostate specific antigens for diagnostic and monitoring BPH

not very specific - approximately 25% of men with BPH have PSAs of >4 ng/mL

physiological diagnosis and monitoring for BPH

peak and avg. urine flow rates, post void residual volume, and voiding diaries

T/F: AUA is a diagnostic tool

F

AUA symptom score index stages

mild: 0-7

moderate: 8-10

severe: 20-35

smallest noticeable change of the AUA symptom score index

+/-3 points

AUA symptom score index can be assessed by who?

interviewer or self

which ppl are not indicated for a specific tx for BPH

patients with mild disease who are asymptomatic or have mildly bothersome symptoms and no complications of BPH disease

how to manage patients with mild disease who are asymptomatic or have mildly bothersome symptoms and no complications of BPH disease?

watchful waiting

what does watchful waiting for BPH consist of

behavior modification and return visits in 6-12 month intervals for assessment of worsening symptoms or signs of BPH

goals of BPH therapy

1. reduce or eliminate obstructive and irritative voiding symptoms

2. slowing disease progression (compare to baseline, symptoms, BUN, creatinine should improve)

3. preventing disease complications and reducing the need for surgical intervention

4. avoiding or minimizing adverse treatment effects

5. providing economical therapy

6. maintaining or improving quality of life

when is surgery indicated for BPH

severe symptoms and BPH complications

when is drug therapy for BPH indicated

moderate to severe symptoms but no BPH complications

meds used for treatment of BPH

1. alpha 1 adrenergic antagonists

2. 5 alpha reductase inhibitors

3. phosphodiesterase inhibitors

4. anticholinergic agents

alpha 1 adrenergic antagonists use for BPH

interim/temporary measure that relieves voiding symptoms

5 alpha reductase inhibitors use for BPH

delays symptom progression and reduce the incidence of BPH-related complications in men with enlarged prostates

phosphodiesterase inhibitors use for BPH

indicated for pts with BOTH mod-severe BPH and erectile dysfunction

anticholinergic agents use for BPH

indicated for moderate to severe lower urinary tract symptoms with a predominance of irritative voiding symptoms

what drug classes address dynamic symptoms of BPH

1. alpha adrenergic antagonists

2. phosphodiesterase 5 inhibitors

the drug classes that address dynamic conditions ____ decrease prostate size

do not

how do alpha adrenergic antagonists and PDE5i address dynamic symptoms of BPH

relax the intrinsic urethral sphincter and prostatic smooth muscle, enhancing urinary outflow from the bladder; PDEs also relax bladder base

first gen alpha blocker example

phenoxybenzamine

limitations of phenoxybenzamine

blocked alpha-1 and -2 with severe cardiovascular side effects

MOA of alpha blockers for BPH

relax muscle and improve lower urinary tract symptoms associated with BPH

alpha 1a receptors mediate…

smooth muscle contraction in prostate, bladder base, and proximal urethra

alpha 1b receptors mediate…

smooth muscle contraction in vasculature

2nd gen alpha blockers

1. doxazosin (cadura)

2. terazosin (hytrin)

3. alfuzosin (uroxatral)

brand name of doxazosin

Cadura

brand name of terazosin

Hytrin

brand name of alfuzosin

uroxatral

3rd gen alpha blockers

1. tamsulosin (flomax)

2. sildosin (rapaflo)

brand name of tamsulosin

flomax

brand name of silodosin

Rapalfo

indication to switch between classes for treatment of BPH

SEs

switching for efficacy is not an indication

generations of alpha antagonists that are considered equally effective for treatment of BPH

2nd and 3rd

2nd and 3rd gen alpha antagonists used to treat BPH lead to an improvement in the AUA score by ____

30-40%

2nd and 3rd gen alpha antagonists used to treat BPH leads to a reduction in…

PVR urine volume

2nd and 3rd gen alpha antagonists used to treat BPH leads to increased urinary flow rate by _____

2-3 mL/s

alpha blockers have no effect on…

prostate volume or PSA levels

mechanism of action of 2nd gen alpha blockers

antagonize peripheral vascular alpha 1 receptors in addition to those in the prostate

AEs of 2nd gen alpha blockers

1. first dose syncope

2. orthostatic hypotension

3. dizziness

doxazosin:

1. dosing options

2. max dose

3. titration?

1. 2, 4, or 8 mg qd hs

2. 8 mg

3. double dose every 2 weeks

Terazosin:

1. dosing options

2. max dose

3. titration?

1. 1, 2, 5, or 10 mg qd hs

2. 10 mg

3. double dose every 2 weeks

Alfuzosin:

1. dosing options

2. max dose

3. titration?

1. 10 mg qd hs

2. 10 mg

3. none!

relief onset of BPH when initiating 2nd gen alpha blockers

1-2 weeks

pain relief onset of BPH when initiating 2nd gen alpha blockers

2-4 weeks

alfuzosin is considered to be _____

uroselective

what does uroselective mean

it means that the drug has a preference for the receptors in the urinary tract rather than elsewhere in the body, this means they are less likely to cause ADE like hypotension and other CV issues

what may make alfuzosin clinically uroselective

1. higher concentrations of alfuzosin achieved in prostate vs serum

2. decreased BBB penetration

3. absence of high peak serum levels with extended release formulation

4. fixed dosing schedule of the extended release formulation

2nd gen formulation in addition to alfuzosin that may have the same benefits as alfuzosin (less CV AEs)

cardura XL (doxazosin)

alpha blocker not recommended for BPH bc of CV AEs

prazosin

what are the third generation alpha blockers

tamsulosin

silodosin

tamsulosin brand name

flomax

silodosin brand name

rapaflo

Tamsulosin:

1. dosing options

2. when to take

1. 0.4 or 0.8 mg

2. 30 mins after the same meal every day

Silodosin:

1. dosing options

2. when to take

1. 4-8 mg

2. any time of the day

silodosin must be adjusted for which pts

hepatic and renal impaired

silodosin is a substrate for…

CYP3A4 and P-glycoprotein

SEs of 2nd and 3rd gen alpha blockers are ____

dose related

AEs of 2nd gen alpha blockers

syncope, dizziness, hypotension, ED

AEs of 3rd gen alpha blocker

tiredness and asthenia

anejaculation

flu like symptoms

nasal congestion

ED

floppy iris syndrome

note: patients must tell their doctors if theyre on alpha blockers

result of alpha blockade during cataract surgery

pupillary constriction occurs and the iris billows out

___ should not be used as first line antihypertensive therapy or alone for the dual treatment of hypertension and BPH

doxazosin

T/F alpha blockers halt disease progression or delay surgical intervention

false

which alpha blockers are uroselective and have fewer CV AEs than immediate release formulations of terazosin or doxazosin

1. extended release formulation of alfuzosin

2. 3rd gen uroselective agents

what can both BPH and ED be associated with

increased vascular smooth muscle tone and pelvic atherosclerosis

PDE inhibitors are thought to... by increasing cGMP

relax smooth muscle in the prostate and bladder neck

AE of alpha adrenergic antagonists and 5 alpha reductase inhibitors that is likely to be response to PDE inhibitors

ED

what is the only PDE inhibitor approved for BPH

tadalafil