BPH 1 Flashcards
What area of the prostate represents 70% of prostatic volume and is where a majority of prostate cancers form?
Peripheral Zone (posterior)
Which area of the prostate is where BPH occurs?
Transitional Zone
What are the 3 types of tissue in the prostate gland?
- Epithelial
- Stromal
- Capsule
Which prostate tissue?
- “glandular tissue”
- Produces prostatic secretions
- Androgens stimulate this tissue growth
Epithelial
Which prostate tissue?
- “smooth muscle”
- embedded with alpha 1 adrenergic receptors
- _____ causes smooth muscle contraction–> extrinsic compression of urethra, reduction of urethral lumen, & decreased urinary bladder emptying
Stromal
- norepinephrine
Which prostate tissue?
- “outer shell”
- “fibrous connective tissue & smooth muscle”
- embedded w/ alpha 1 adrenergic receptors
- when stimulated w/ _____, this tissue contracts around the urethra
Capsule
- norepinephrine
_____ is the principal testicular androgen
______ is the principal adrenal androgen
- These 2 hormones are responsible for what 3 things?
- testosterone
- androstenedione
- penile & scrotal enlargement
- increased muscle mass
- maintenance of normal male libido
Testosterone and Androsenedione are the principal testicular and adrenal androgens which are converted by ______ in the ___ cells to —-> _____ (an active metabolite)
- 5 alpha-reductase
- target
- dihydrotestosterone (DHT)
____ is considered a more potent androgen than testosterone in the prostate
DHT
In the prostate, ___ induces growth and enlargement of the gland
DHT
2 types of 5 alpha-reductase. Which one?
- localized to sebaceous glands in the frontal scalp, liver, and skin
- DHT produces at these target tissues causes _____ and _______
Type 1 enzyme
- acne & increased body/facial hair
2 types of 5 alpha-reductase. Which one?
- localized to prostate, genital tissue, & hair follicles of scalp
- In the prostate, DHT induces growth and enlargement of gland
Type 2 enzyme
- The normal prostate is composed of a higher amount of ___ tissue than _____ tissue (2:1)
- This ratio is exaggerated in BPH (__:1)
- stromal : epithelial
- 5
Epithelial TIssue (glandular tissue)
- DHT production involves _____
- DHT is responsible for ______
- ______ reduces an enlarged prostate gland, but only by __%
- 5 alpha reducatse
- growth & enlargement of prostate gland
- 5 alpha reductase inhibitors / 25%
- Epithelial tissue has a ____ process
- Stromal tissue has a _____ process
- static
- dynamic
Stromal Tissue (smooth muscle)
- _______ receptors, when stimulated cause smooth muscle contraction in the enlarged prostate and in the bladder base, obstructing urine flow.
- Therefore, ______ are quickly effective in symptomatic management of urinary flow
- alpha 1 adrenergic receptors
- alpha 1 adrenergic ANTagonists
Adrenaline levels are never _____!
static
What aggravates BPH?
Stress bc/ it increases norepinephrine –> alters urination
Pathogenesis of BPH
- ______ factors relate to anatomic enlargement of the prostate gland, which produces a physical block at the bladder neck and thereby obstructs urinary outflow.
- Enlargement of the gland depends on ____ stimulation of ____ tissue and ____stimulation of ____ tissue in the prostate
- Static
- androgen / epithelial
- estrogen / stromal
Pathogenesis of BPH
- ______ factors relate to excessive alpha adrenergic tone of the stromal component of the prostate gland, bladder neck, and posterior urethra
- Results in contraction of the prostate gland around the urethra and narrowing of the urethral lumen
Dynamic
Pathphys of BPH
- Chronic prostatic inflammation
- Advanced atherosclerosis of blood supply to pelvis
- Decreased release of _____ (vasodilator)
- Decreased production of _______ at the bladder neck and in the prostate
- nitric oxide
- cyclic guanosine monophosphate (cGMP)
2 types of sxs of BPH. Which one?
- urinary hesitancy
- urine dribbling
- bladder fullness post voiding
obstructive
2 types of sxs of BPH. Which one?
- result from long-standing obstruction at the bladder neck
- urinary frequency
- urinary urgency
- nocturia
irritative
PSA level of ____ has been used as a surrogate marker for an enlarged prostate gland and those at risk for developing complications of BPH disease
1.4 ng/mL
Sxs of BPH are collectively referred to as ____.
LUTS
(lower urinary tract symptoms)
3 goals of BPH tx
- control sxs
- prevent progression of complications
- delay need for surgical intervention
Tx for mild asymptomatic disease or mildly bothersome sxs and no complications of BPH disease
No specific tx indicated
- watchful waiting
- behavior modification
- return visits at 12 month intervals for assessment of worsening sxs or signs of BPH
Tx for moderate or severe level sxs (obstructive voiding sxs and irritative voiding sxs) = signs of detrusor instability
Drug therapy or surgery is indicated
3 types of BPH drugs
(what does each do?)
- Interfere w/ testosterone’s stimulatory effect on prostate gland enlargement (reducing static factor)
- Relax prostatic smooth muscle (reducing dynamic factor)
- Relax bladder detrusor muscle (improving the urine storage capacity of the bladder)
What 3 BPH drugs reduce the dynamic factor?
- Doxazosin (bloack alpha 1 adregnergic receptors in stromal tissue - nonselective) *initially used for HTN
- Tamsulosin (blocks alpha 1A receptors - selective) $$$ expensive
- Tadalafil - PDE5 (causes smooth muscle relaxation of prostate, bladder neck, & prostatic urethra)
Slow titration for immediate release terazosin & doxazosin
- Slow titration up to therapeutic maintenance dose is necessary to minimize _____ and ______
- orthostatic hypotension
- first dose syncope
Which BPH drug reduces the static factor and blocks 5 alpha reductase enzyme?
Finasteride
Which BPH drug relaxes detrusor muscle of bladder?
Oxybutynin
An alpha 1 adrenergic antagonist is an “___” measure
- relieves voiding sxs (not being able to void)
- Patients w/ prostates of at least __ g, ________ delay sxs progression and reduce the incidence of BPH related complications
“interim”
- 40
- 5-alpha reductase inhibitors
- All ______ are equally effective in relieving BPH sxs
- Older 2nd gen immediate release formulations ( ____ and ____) can cause adverse CV effect
- ____
- _____
- ______
- 3rd gen, pharmacologically uroselective agents (____ and ____) are good alternatives to the 2nd gen…
- alpha 1 adrenergic antagonists
- terazosin & doxazosin
- 1st dose syncope
- orthostatic hypotension
- dizziness
- tamsulosin & silodosin
What is the “gold standard” drug w/o CV effects?
Tamsulosin (3rd gen)
Which drug?
- alpha 1 adrengergic antagonist
- extended release 2nd gen
- functionally uroselective
- fewer CV effects than immediate release formulations of terazosin or doxazosin
- Uncertain if this drug has the same CV safety as tamsulosin
Alfuzosin
Which type of drug?
- Useful primarily for pts w/ large prostates greater than 40g who wish to avoid surgery and can tolerate the SE of alpha adrenergic antagonists
- SLOW onset of action
- taking up to 6 months to exert maximal clinical effects
5 alpha reductase inhibitors
3 ADEs of 5-ARI
- Decreased libido
- ED
- Ejaculation disorders
Which drug?
- Floppy Iris Syndrome
- Priapism
- Monitor: BP and HR
*
Alpha Adrenergic Antagonist
(Alfuzosin, Terazosin, Doxazosin 2nd gen)
(Tamsulosin, silodosin 3rd gen)
Which drug?
- Erectile dysfunction
- Decreased libido
- Ejaculatory dysfunction
- Gynecomastia
- Monitor: PSA
- Pt’s PSA level should decrease by 50% if adherent to therapy
5 ARI
(Finasteride, Dutasteride)
AAA or 5-ARI?
- Relaxes prostatic smooth muscle
- Peak onset 1-6 weeks
- 1-2 doses / day
- CV effects
AAA (alpha 1 adrenergic antagonist)
AAA or 5-ARI?
- Decreases prostate size
- Halts disease progression
- Peak onset 3-6 months
- Dosing once / day
- Decreases PSA
- No CV effects
5-ARI
PDE inhibitor or Anticholinergic Agent?
- Relaxes prostatic smooth muscle
- Peak onset 4 weeks
- No sexual dysfunction adverse effects
- ADE: mild hypotension
PDE Inhibitor
PDE Inhibitor or Anticholinergic Agent?
- Peak onset 1-2 weeks
- Relieves irritative sxs
- ADE: ED
- causes tachycardia
Anticholinergic Agent
PDE inhibitor or Anticholinergic?
- Dizziness
- Nasal congestion
- Dyspepsia
- Back pain
- Myalgia
- Hearing loss
PDE inhibitor
PDE inhibitor or Anticholinergic?
- Dry mouth
- Constipation
- Tachycardia
- Blurry vision
- Acute urinary retention
- Drowsiness
- Confusion
- Angioedema*
- Anaphylaxis*
- ED
Anticholinergic
3 things you should monitor when prescribing PDE inhibitor
- BP
- Pulse
- Hearing loss
3 things you should monitor when prescribing anticholingerics
- Mental status
- Bowel habits
- Ability to urinate
(BAM)
If the patient experiences hearing loss, discontinue _____.
Tadalafil (PDE-5 inhibitor)
Which drug?
- Peak onset 2 weeks (may take 8 w)
- Not effective in relieving bladder outlet obstruction
- Effective in relieving irritative sxs
- Causes HTN
Beta 3 Adrenergic Agonists
(Mirabegron)
Beta 3 Adrenergic Agonist (Mirabegron)
- When stimulated, ____ is produced which relaxes the detrusor muscle
- What other 3 things does this drug accomplish?
- cAMP
- reduces irritative voiding sxs
- increases bladder capacity
- increases intervals between voidings
2 things to monitor when prescribing Beta 3 Adrenergic Agonist (Mirabegron)
- BP
- Bowel habits
3 SE of Beta 3 Adrenergic Agonist (Mirabegron)
- HTN
- Constipation/Diarrhea
- Impaired cognition
- What are the 2 surgical options for BPH?
- Which allows for biopsy?
- TURP / Green Light
- TURP = biopsy
(Surgeries indicated for mod-severe sxs)
(Pts who do not respond to/do not tolerate drugs/complications of BPH)
