1
Q
What area of the prostate represents 70% of prostatic volume and is where a majority of prostate cancers form?
A
Peripheral Zone (posterior)
2
Q
Which area of the prostate is where BPH occurs?
A
Transitional Zone
3
Q
What are the 3 types of tissue in the prostate gland?
A
- Epithelial
- Stromal
- Capsule
4
Q
Which prostate tissue?
- “glandular tissue”
- Produces prostatic secretions
- Androgens stimulate this tissue growth
A
Epithelial
5
Q
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
A
Stromal
- norepinephrine
6
Q
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
A
Capsule
- norepinephrine
7
Q
_____ is the principal testicular androgen
______ is the principal adrenal androgen
- These 2 hormones are responsible for what 3 things?
A
- testosterone
- androstenedione
- penile & scrotal enlargement
- increased muscle mass
- maintenance of normal male libido
8
Q
Testosterone and Androsenedione are the principal testicular and adrenal androgens which are converted by ______ in the ___ cells to —-> _____ (an active metabolite)
A
- 5 alpha-reductase
- target
- dihydrotestosterone (DHT)
9
Q
____ is considered a more potent androgen than testosterone in the prostate
A
DHT
10
Q
In the prostate, ___ induces growth and enlargement of the gland
A
DHT
11
Q
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 _______
A
Type 1 enzyme
- acne & increased body/facial hair
12
Q
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
A
Type 2 enzyme
13
Q
- The normal prostate is composed of a higher amount of ___ tissue than _____ tissue (2:1)
- This ratio is exaggerated in BPH (__:1)
A
- stromal : epithelial
- 5
14
Q
Epithelial TIssue (glandular tissue)
- DHT production involves _____
- DHT is responsible for ______
- ______ reduces an enlarged prostate gland, but only by __%
A
- 5 alpha reducatse
- growth & enlargement of prostate gland
- 5 alpha reductase inhibitors / 25%
15
Q
- Epithelial tissue has a ____ process
- Stromal tissue has a _____ process
A
- static
- dynamic
16
Q
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
A
- alpha 1 adrenergic receptors
- alpha 1 adrenergic ANTagonists
17
Q
Adrenaline levels are never _____!
A
static
18
Q
What aggravates BPH?
A
Stress bc/ it increases norepinephrine –> alters urination
19
Q
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
A
- Static
- androgen / epithelial
- estrogen / stromal
20
Q
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
A
Dynamic
21
Q
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
A
- nitric oxide
- cyclic guanosine monophosphate (cGMP)
22
Q
2 types of sxs of BPH. Which one?
- urinary hesitancy
- urine dribbling
- bladder fullness post voiding
A
obstructive
23
Q
2 types of sxs of BPH. Which one?
- result from long-standing obstruction at the bladder neck
- urinary frequency
- urinary urgency
- nocturia
A
irritative
24
Q
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
A
1.4 ng/mL
25
Sxs of BPH are collectively referred to as \_\_\_\_.
LUTS
| (lower urinary tract symptoms)
26
3 goals of BPH tx
* control sxs
* prevent progression of complications
* delay need for surgical intervention
27
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
28
Tx for moderate or severe level sxs (obstructive voiding sxs and irritative voiding sxs) = signs of detrusor instability
Drug therapy or surgery is indicated
29
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)
30
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)
31
**Slow titration for immediate release terazosin & doxazosin**
* Slow titration up to therapeutic maintenance dose is necessary to minimize _____ and \_\_\_\_\_\_
* orthostatic hypotension
* first dose syncope
32
Which BPH drug **reduces the static factor** and _blocks 5 alpha reductase enzyme?_
Finasteride
33
Which BPH drug relaxes detrusor muscle of bladder?
Oxybutynin
34
**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
35
* 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
36
What is the "gold standard" drug w/o CV effects?
Tamsulosin (3rd gen)
37
**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
38
**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
39
3 ADEs of 5-ARI
* Decreased libido
* ED
* Ejaculation disorders
40
**Which drug?**
* Floppy Iris Syndrome
* Priapism
* Monitor: BP and HR
*
Alpha Adrenergic Antagonist
(Alfuzosin, Terazosin, Doxazosin 2nd gen)
(Tamsulosin, silodosin 3rd gen)
41
**_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)
42
**AAA** or **5-ARI?**
* Relaxes prostatic smooth muscle
* Peak onset 1-6 weeks
* 1-2 doses / day
* CV effects
AAA (alpha 1 adrenergic antagonist)
43
**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
44
**PDE inhibitor** or **Anticholinergic Agent?**
* Relaxes prostatic smooth muscle
* Peak onset 4 weeks
* No sexual dysfunction adverse effects
* ADE: mild hypotension
PDE Inhibitor
45
**PDE Inhibitor** or **Anticholinergic Agent?**
* Peak onset 1-2 weeks
* Relieves irritative sxs
* **ADE:** ED
* causes tachycardia
Anticholinergic Agent
46
**PDE inhibitor or Anticholinergic?**
* Dizziness
* Nasal congestion
* Dyspepsia
* Back pain
* Myalgia
* Hearing loss
PDE inhibitor
47
**PDE inhibitor or Anticholinergic?**
* Dry mouth
* Constipation
* Tachycardia
* Blurry vision
* Acute urinary retention
* Drowsiness
* Confusion
* Angioedema\*
* Anaphylaxis\*
* ED
Anticholinergic
48
3 things you should monitor when prescribing PDE inhibitor
* BP
* Pulse
* Hearing loss
49
3 things you should monitor when prescribing anticholingerics
* Mental status
* Bowel habits
* Ability to urinate
## Footnote
**(BAM)**
50
If the patient experiences hearing loss, discontinue \_\_\_\_\_.
Tadalafil (PDE-5 inhibitor)
51
**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)
52
**Beta 3 Adrenergic Agonist (Mirabegron)**
* When stimulated, ____ is produced which relaxes the detrusor muscle
* What other 3 things does this drug accomplish?
* cAMP
1. reduces irritative voiding sxs
2. increases bladder capacity
3. increases intervals between voidings
53
2 things to monitor when prescribing Beta 3 Adrenergic Agonist (Mirabegron)
* BP
* Bowel habits
54
3 SE of Beta 3 Adrenergic Agonist (Mirabegron)
* HTN
* Constipation/Diarrhea
* Impaired cognition
55
* 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)
P2 E1 SG
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