Term
| receptor activity in the bladder, urethra, prostate |
|
Definition
ACETYLCHOLINE:
agonists - contract bladder smooth muscle
antagonists - relax bladder smooth muscle
ALPHA1 ADRENERGIC:
agonist - contracts urethra, bladder neck, prostate tissue
antagonist - relax urethra, bladder neck, prostate tissue
smooth muscle of the bladder responds to calcium; CCBs (nifedipine, amlodipine) can cause similar effects to anticholinergics |
|
|
Term
|
Definition
the definition of clinical BPH includes 3 considerations: symptoms, prostate size, and obstruction
men may have LUTS (lower urinary tract symptoms), with or without an enlarged prostate, and these men may or may not have bladder outflow obstruction
obstruction and/or irritative symptoms can occur both in the presence and in the absence of BPH
for example, the irritative symptoms commonly arising in women as they age are not attributed to an enlarged prostate
conversely, a man may have prostatic enlargement without experiencing obstructive or irritative symptoms
technically, BPH is diagnosed in the presence of histologic evidence of hyperplasia whereas the term lower urinary tract symptoms (LUTS) refers to a clinical syndrome characterized by irritative and/or obstructive symptoms
LUTS can occur regardless of whether or not BPH is present
few patients have histologic documentation of BPH, but they have presumptive BPH on the basis of findings of prostate enlargement during digital rectal exam or imaging studies. these patients are considered to have CLINICAL BPH (presumptive BPH that has not been histologically confirmed) |
|
|
Term
| prevalence of LUTS with age |
|
Definition
[image]
study results indicated that most symptoms gradually progress with age - particularly nocturia, which showed the most dramatic increase
other symptoms including hesitancy (data not shown), weak stream, urgency, and frequency, were more frequently seen in the older population
even in "normal" subjects, urinary symptoms and urodynamic variables may evolve with age; in elderly subjects they warrant careful interpretation |
|
|
Term
|
Definition
androgens are required for normal cell proliferation and differentiation in the prostate, and also actively inhibit cell death
in the prostate 5alpha reductase converts testosterone into 5alpha DHT
DHT induces androgenic effects by binding to androgen receptors; is a more potent androgen than testosterone |
|
|
Term
|
Definition
young adult male:
20-25 grams
enlarged:
greater than or equal to 30 grams
significantly enlarged:
greater than or equal to 40 grams
CombAT study: mean 55 grams |
|
|
Term
| Clinical LUTS/BPH OBSTRUCTIVE symptoms |
|
Definition
obstructive = voiding issue
hesitancy
straining
weak flow
terminal dribbling
prolonged voiding
incomplete emptying
retention |
|
|
Term
| Clinical LUTS/BPH IRRITATIVE symptoms |
|
Definition
irritative = storage issue (similar to overactive bladder disorder)
frequency
urgency
nocturia
urge incontinence
small voided volume
dysuria |
|
|
Term
|
Definition
URINARY RETENTION
RENAL IMPAIRMENT
URINARY TRACT INFECTION
gross hematuria
bladder stones
bladder damage
OVERFLOW INCONTINENCE
WORSENING SYMPTOMS (AUA-SI SCORE) |
|
|
Term
|
Definition
occurs when intravesicular pressures exceed intraurethral pressures - ONLY at HIGH volumes
bladder outlet obstruction - BPH, neoplasm
impaired afferent sensation
diabetic neuropathy, spinal cord lesions below T-11
MUSCLE RELAXANTS, CALCIUM CHANNEL BLOCKERS, ANTICHOLINERGICS (ALL RELAX THE BLADDER)
clinical features: palpable or percussable bladder, suprapubic tenderness, low urinary flow rates, INCREASED POST-VOID RESIDUAL URINE (PVR) |
|
|
Term
|
Definition
amount of urine remaining in the bladder following attempt by the patient to empty the bladder
normal: < 50 cc
increased: > 50 cc
assessed by straight catheter placement post void or estimated with bladder scanner |
|
|
Term
| acute urinary retention (AUR) |
|
Definition
painful
initial management by catheterization (often in ER setting)
refractory urinary retention may require surgical intervention |
|
|
Term
| American Urological Association - Symptom Index (AUA-SI) |
|
Definition
scored from 0-35 with 35 the worst
DON'T HAVE TO KNOW CUT OFFS...BUT:
mild = 0-7
moderate = 9-19
severe = 20-35 |
|
|
Term
| prostate specific antigen (PSA) |
|
Definition
normal PSA: < 4 ng/ml
elevated PSA: > 4 ng/ml
screening PSA for prostate cancer:
several factors can increase PSA - prostatitis, BPH, digital rectal exam, ejaculation in last 24 hours, catheterization
other parameters:
PSA velocity/density - how quickly the number rises
just a screening tool, not a great predictor of prostate cancer |
|
|
Term
| MEDICATIONS THAT MAY EXACERBATE LUTS |
|
Definition
drugs with ANTICHOLINERGIC ACTIVITY:
antihistamines
antidepressants
overactive bladder medications
mechanism - lessen detrusor muscle contractions
daily use associated with 2-3 point increase in AUA-SI
SYMPATHOMIMETIC AGONISTS
appetite suppressants
decongestants
mechanism - block relaxation of the internal urethral sphincter
DIHYDROPYRIDINE CALCIUM CHANNEL BLOCKERS
nifedipine
amlodipine
mechanism - relax smooth muscle
symptoms may also be increased with caffeine and alcohol |
|
|
Term
|
Definition
watchful waiting
MEDICAL THERAPY:
ALPHA BLOCKERS
5ALPHA REDUCTASE INHIBITORS
ANTICHOLINERGICS/ANTISPASMOTICS (for irritative symptoms only!)
PHYTOTHERAPY (herbs)
TADALAFIL (Cialis)
surgery:
transurethral resection of the prostate (TURP)
transurethral incision of the prostate (TUIP)
transurethral microwave thermotherapy |
|
|
Term
|
Definition
alpha1 blockers: terazosin (Hytrin), doxazosin (Cardura), tamsulosin (Flomax), alfuzosin (Uroxatral), silodosin (Rapaflo)
prazosin (Minipress) not FDA approved for BPH
phenoxybenzamine - old school, blocks alpha1 and alpha2; tachycardia and arrhythmias
inhibit alpha adrenergic mediated contraction of prostatic smooth muscle = relief of bladder outlet obstruction
FIRST LINE OF PRESCRIBED MEDICAL THERAPY
efficacy documented by multiple clinical randomized trials; long term efficacy is less well documented
low risk of morbidity
can be discontinued at any time
WORK QUICKLY - DAYS TO WEEKS
titration required with terazosin and doxazosin b/c of BP effects
all have a possible interaction with PDE-5 inhibitors
alfuzosin (Uroxatral) and silodosin (Rapaflo) should not be administered with potent CYP3A4 inhibitors (ketoconazole) |
|
|
Term
| alpha adrenergic blockers for BPH: adverse events profiles differ slightly |
|
Definition
dizziness, fatigue or somnolence, and nasal congestion reported for all alpha blockers
headache worse with alfuzosin (Uroxatral) and silodosin (Rapaflo)
hypotention, dizziness, and syncope worst with terazosin (Hytrin) and doxazosin (Cardura)
no BP effects with tamsulosin (Flomax)
sligh BP effects with alfuzosin (Uroxatral) and silodosin (Rapaflo)
abnormal ejaculation worst with silodosin (Rapaflo), followed by tamsulosin (Flomax)
if patient is complaining of this symptoms recommend alfuzosin (Uroxatral)
intraoperative floppy iris syndrome is possible with all
DO NOT recommend stopping the alpha blocker; the patient will be given eye drops before surgery to prevent this problem |
|
|
Term
| what to expect from medical therapy for BPH with alpha blockers: terazosin (Hytrin), doxazosin (Cardura), tamsulosin (Flomax), alfuzosin (Uroxatral), and silodosin (Rapaflo) |
|
Definition
averate 4-6 point improvement in AUA-SI
patients will perceive this level of symptom improvement as a meaningful change
symptoms improvement may be noticeable in DAYS TO WEEKS |
|
|
Term
| 5alpha reductase inhibitors |
|
Definition
type 2: finasteride (Proscar)
type 1 and type 2: dutasteride (Avodart)
reduce DHT levels in serum and prostate
reduces prostate size, increases peak urinary flow, and reduces BPH symptoms
most useful in men with enlarged prostates (> 35 grams)
not as effective for symptom relief as alpha blockers |
|
|
Term
| what to expect from medical therapy for BPH with 5alpha reductase inhibitors: finasteride (Proscar) and dutasteride (Avodart) |
|
Definition
average 3 point improvement in AUA-SI; perceived as a meaningful change
symptom improvement takes MUCH longer (UP TO 6 MONTHS OR LONGER)
combination therapies produce on average 5-7 point improvement in AUA-SI; symptom improvement may begin in days to weeks (due to alpha blocker initially) |
|
|
Term
| ADRs with 5alpha reductase inhibitors |
|
Definition
primarily sexually related including decreased libido, ejaculatory dysfunction, erectile dysfunction
breast changes (lumps, pain, or nipple discharge)
LOWERS PSA BY ABOUT 50%
if a patient's PSA stays constant while on a 5alpha reductase inhibitor, it should be interpreted as an increase
combination therapy:
ADRs reflect the combined AE profile of both alpha blockers and 5alpha reductase inhibitors |
|
|
Term
|
Definition
decrease fluid intake at bedtime
decrease caffeine and alcohol intake
avoid cold medications with alpha sympathomimetic/anticholinergic drugs
use a voiding diary to record symptoms
use of dietary supplements? usually not recommended |
|
|
Term
|
Definition
an adequate duration for treatment trial is at least 2-4 weeks after patient has achieved usual maintenance dose (alpha blockers)
medical therapy for BPH is intended to be continuous
if alpha blocker is discontinued it should be reinstituted using initial dosing regimen and titrated to effective dose
may take SIGNIFICANTLY longer to see benefits with 5alpha reductase - up to 6 months! |
|
|
Term
| contraindications and precautions |
|
Definition
alpha blockers and 5alpha reductase inhibitors are metabolized in the liver (CYP3A4)
caution advised in patients with impaired hepatic function
caution in patients with moderate to severe hepatic impairment, and in combination with potent CYP3A4 inhibitors (ritonavir, ketoconazole), for ALFUZOSIN IN PARTICULAR
5alpha reductase inhibitors - contraindicated for pregnant women
patients should be cautioned that pregnant women should not handle crushed or broken tablets
patients should be advised not to donate blood until at least 6 months since last dose to avoid transfer to pregnant females |
|
|
Term
| combination therapy of alpha blocker and 5 alpha reductase inhibitor |
|
Definition
appropriate for men with LUTS associated with demonstrable prostate enlargement
addition of a 5alpha reductase inhibitor to an alpha blocker has been shown to reduce risk of BPH related complications
those most likely to benefit from combination therapy are those with high risk of progression (larger prostates)
one combo product available commercially (Jalyn - dutasteride + tamsulosin) |
|
|
Term
| medical therapy of prostatic symptoms (MTOPS) trail |
|
Definition
primary research question: to determine if medical therapy prevents or delays the clinical progression of BPH as defined by 1 or more of the following:
AUR
renal insufficiency due to BPH
recurrent UTI
incontinence
> 4 point risk in baseline AUA-SI confirmed within 2-4 weeks
combination therapy (doxazosin + finasteride) was better than any therapy alone and better than placebo
MTOPS study demonstrated that long term medical therapy with an alpha blocker, 5alpha reductase inhibitor, or both, not only improves symptoms but also reduces the clinical progression of BPH, defined as:
worsening of symptoms (increased AUA-SI)
acute urinary retention
incontinence
urinary tract infection
renal insufficiency |
|
|
Term
|
Definition
similar to MTOPS
placebo, doxazosin, finasteride, or both
primary outcome = urinary flow rate and symptom control
doxazosin superior to placebo, finasteride, or both
finasteride not different from placebo |
|
|
Term
|
Definition
also similar to MTOPS, but more severe BPH (mean prostate size 55 cc)
tamsulosin, dutasteride, or both
2 years - combo therapy improved symptoms and flow rates
4 years - combo superior to tamsulosin, but no dutasteride alone; combo better than either monotherapy for clinical progression |
|
|
Term
| tamsulosin + tolterodine (Detrol) for LUTS and OAB |
|
Definition
men with symptoms of both BPH and overactive bladder (urgency, frequency, nocturia)
placebo, tolterodine, tamsulosin, or both
placebo and monotherapy showed no benefit in symptoms, but combo therapy did (urgency, incontinence, nocturia)
antimuscarinics not currently included in treatment guidelines
patient on anticholinergic with BPH. how do you measure if his obstructive symptoms are getting better? (relaxing the bladder too much)
PVR
if PVR goes from 30 to 150 then he is getting some urinary retention |
|
|
Term
|
Definition
mild sx:
watch and wait
OR
alpha antagonist
OR
5 alpha reductase inhibitor
if response, continue; no response, combo or surgery
moderate sx:
alpha antagonist
OR
5alpha reductase inhibitor
if response, continue; no response, combo or surgery
moderate to severe sx (with large prostate):
alpha antagonist
AND
5alpha reductase inhibitor
if response, continue; no response, surgery
severe sx and complications:
surgery |
|
|
Term
|
Definition
extract from the Saw Palmetto Berry
MOA:
thought to have 5alpha reductase properties
possibly anti inflammatory properties
efficacy - may reduce symptoms of BPH
ADRs - mild GI distress; generally safe
some concerns of masking prostate cancer due to potential to lower PSA
Saw Palmetto for BPH Study:
no significant change in AUA-SI or peak urinary flow rates at 1 year
found no significant lowering of PSA |
|
|
Term
| prostate cancer screening |
|
Definition
digital rectal exam:
useful tool; can detect cancer in some men with normal PSA
sensitivity of DRE is 59%
some limitations - only posterior and lateral parts can be palpated; early/small tumomrs may not be palpated
PSA testing (prostate specific antigen):
20-30% of tumors missed if PSA used alone
15% of men with intermed or high grade tumors had wnl SPA
some suggest - PSA density/velocity
biopsy:
consider if abnormalities noted with DRE or PSA
PSA in combination with a DRE is the BEST screening tool; if these are suspicious, you move on to the prostate biopsy
"PSA based screening results in small or no reduction in prostate cancer specific mortality and is associated with harms related to subsequent evaluation and treatments, some of which may be unnecessary" |
|
|
Term
| prostate cancer - chemoprevention |
|
Definition
| no benefit of vitamin E, selenium, dutasteride, or finasteride on prostate cancer risk |
|
|
