Benign Prostate Hyperplasia Flashcards
What is BPH?
- Describe the condition and its impacts
BPH - non-malignant growth of some components of the prostate (e.g., transitional zone)
It is a progressive condition that results in:
- Lower urinary tract signs and symptoms (LUTS)
- Negative impact on QoL
Describe the physiology of the Prostate
- Epithelial (glandular) tissue
- Androgen (DHT) stimulates its growth/enlargement
- Testosterone secreted by testicles and adrenal gland is converted by type II 5a-reductase to DHT in the prostate - Stromal (smooth muscle) tissue
- innervated by a1 adrenergic receptors
PATHOPHYSIOLOGY OF BPH
Describe the pathogenesis of BPH (static and dynamic component)
*Etiology is unknown, likely due to age + hormonal factors
- Static component
- Hormonal factors (T => DHT)
- Enlargement of prostate tissue - Dynamic component
- Incr smooth muscle tissue and agonism of a1 receptors (contraction of the prostate smooth muscles)
- Narrowing of urethra outlet
=> Both components contribute to urethral obstruction/signs and symptoms
PATHOPHYSIOLOGY OF BPH
What happens to the bladder response to obstruction in the short term?
Bladder/detrusor muscles able to forcefully contract to force urine through the narrowed urethra
PATHOPHYSIOLOGY OF BPH
What happens to the bladder response to obstruction in the long term?
Bladder muscle gradually thickens (hypertrophy) overtime
Once highest state of hypertrophy, muscle decompensates
Detrusor muscle becomes irritable and overly sensitive (detrusor overactivity or instability), contracts abnormally in response to small amounts of urine in the bladder
Results in increase urinary frequency
What are the signs and symptoms of BPH
- Organize the Lower urinary tract symptoms (LUTS) into obstructive/voiding symptoms and irritative/storage symptoms
Many pts remain asymptomatic initially, s/s start to occur in 1/3 men older than 65yo
Obstructive/Voiding symptoms (early in disease):
- Hesitancy
- Weak stream
- Sensation of incomplete emptying
- Dribbling
- Straining
- Intermittent flow
Irritative/Storage symptoms (occurs after several years untreated):
- Dysuria
- Frequency
- Nocturia
- Urgency
- Urinary incontinence
LUTS is not specific to BPH, what are some other causes of LUTS?
UTIs, prostate or bladder cancer, diabetes mellitus
What are some ways to conduct assessment of BPH? *5 ways
- Digital rectal exam
- Ultrasonography
- Maximum Urinary Flow Rate (Qmax)
- Prostate specific antigen (PSA)
- Postvoid residual (PVR)
What is the relevance of PSA?
Might be elevated in BPH, positively correlated with prostate size
Can predict progression of BPH (>1.5ng/mL)
Higher risk for prostate cancer
What are the PVR volumes after voiding in normal and inadequate emptying?
What is the relevance of PVR in BPH treatment?
PVR <100ml in normal circumstance (adequate emptying)
PVR >200ml in inadequate emptying
When use anticholinergics (for irritative/storage symptoms), PVR must be <250ml or <150ml if conservative
Recall the AUA-SI score for mild, moderate, and severe BPH, and describe the symptoms and signs for each severity.
Mild
- =<7
- Asymptomatic or mildly symptomatic
Moderate
- 8-19
- All of the above s/s + obstructive voiding symptoms + irritative voiding symptoms
Severe
- >=20
- All of the above + one or more complications of BPH
- Consider Transurethral Resection of Prostate (TURP)
What are some complications of BPH?
*1 or more complications = severe BPH, consider surgery
- Recurrent UTI
- Bladder stones
- Acute urinary retention
- Urinary incontinence (if bladder is overactive)
- Hematuria
For assessment of BPH, medication history must be taken to ensure medications don’t cause development/worsening of BPH.
What are some medications that may worsen BPH?
- Anticholinergics
- a1 adrenergic agonist
- Opioid analgesic
- Diuretics
- Testosterone
Explain how anticholinergics may worsen BPH
Anticholinergics - antihistamines (all gen), TCA
- Decrease bladder muscle contractability
Explain how alpha-1 adrenergic agonist may worsen BPH
Alpha-1 adrenergic agonist (e.g., decongestants - pseudoephedrine)
- Contraction of prostate smooth muscle
Explain how opioid analgesics may worsen BPH
Opioid analgesics (e.g., morphine, tramadol)
- Increase urinary retention
Explain how diuretics may worsen BPH
Diuretics
- Increase urinary frequency
Explain how testosterone may worsen BPH
Testosterone
- Stimulate prostate growth
Management of BPH
Watchful waiting is recommended for which group of patients?
Patients with mild symptoms (AUA SI score =<7)
or
Patients with moderate symptoms (AUA SI score 8-19) who are not bothered by symptoms
Management of BPH
How often should reassessment of symptoms using the AUA SI be done
Annually or more frequent
Management of BPH
What are some non-pharmacological methods?
- Limit fluid intake in the evening to reduce nocturia
- Minimize caffeine and alcohol intake as these can act as diuretics and increase urinary frequency
- Educate patients to take time to empty bladder completely and often (impt as residual urine can cause overactive bladder)
- Avoid medications that exacerbate symptoms
Management of BPH
When should pharmacologic treatment be started?
Symptoms become bothersome or complications occur
Management of BPH
What are the 5 key considerations in choosing BPH treatment?
- LUTS severity (AUA-SI score)
- Prostate size
- Concurrent comorbidities
- PSA value
- Presence of irritative/storage symptoms
Management of BPH
Explain the MOA of alpha-1 adrenergic antagonist for the treatment of BPH
Alpha-1 adrenergic antagonist
- MOA: decrease muscle tone, relax prostate smooth muscle, hence reduce bladder obstruction and improve urinary flow
Management of BPH
What are the 2 types of alpha-1 adrenergic antagonist, and list examples
- Non-selective a1 adrenergic antagonist
- Doxazosin
- Terazosin
- Prazosin (not recommended for use in BPH, use in HTN)
=> Antagonize both peripheral vascular and urinary a1 receptors, need to titrate slowly to therapeutic dose to reduce risk of hypotension and syncope (due to vasodilation)
- Selective a1 adrenergic antagonist
- Alfuzosin
- Silodosin
- Tamsulosin
=> Antagonize urinary a1 receptors in the prostate and LUT only, hence lesser risk of hypotension, no dose titration needed
Management of BPH
Which group of patient most likely to benefit from alpha-1 adrenergic antagonist?
a1 adrenergic antagonist effective in reducing LUTS, especially in those classified with moderate or severe LUTS, with small prostate <40g
*s/s likely recur if discontinued (therefore, require long-term therapy to maintain effect)
Management of BPH
alpha-1 adrenergic antagonist does not have effect on _______
No effect on prostate size, does not reduce PSA value
Hence, does not offer prevention for progression of BPH or need for surgery
Management of BPH
Describe the onset of alpha-1 adrenergic antagonist
Fast onset (days to weeks) - just dilates the prostate smooth muscle
Management of BPH
Describe the side effect profile of alpha-1 adrenergic antagonist
General SEs: *think dilation
- muscle weakness, fatigue, ejaculatory disturbance, headache, back pain etc.
- bedtime administration to decrease orthostatic effect
Non-selective:
- dizziness
- first dose syncope and orthostatic hypotension
Uroselective:
- Low to none peripheral vascular dilatation hence less hypotension or syncope
- Ejaculatory disturbance (delayed or retrograde ejaculation)
Management of BPH
Describe the syndrome related to cataract surgery that occurs due to the use alpha-1 adrenergic antagonist
Intraoperative Floppy Iris Syndrome (IFIS)
- Condition that complicates cataract surgery
- MOA linked to blockage of a1 receptor in iris dilator muscle, cause iris prolapse
- Most commonly linked to TAMSULOSIN*
*Avoid initiation of a1 adrenergic antagonist until the cataract surgery has been completed OR hold 2-3 weeks before surgery
Management of BPH
When might non-selective a1 adrenergic antagonists be useful?
When pt has concurrent BPH + HTN, and require additional BP lowering
BUT NOT used as monotherapy for pt with concurrent BPH + HTN as it will not be sufficient
Note that in BEERs list, a1 adrenergic antagonist is listed as a drug to avoid in patient with history of syncope
If pt does not require BP lowering effect, use selective instead
Management of BPH
Explain the MOA of 5 alpha reductase inhibitors (5ARI) for the treatment of BPH
MOA; inhibits type II 5a reductase, hence decrease conversion from testosterone to DHT, reduce prostate size, and cause less urine obstruction and improve urinary flow
Finasteride, Dutasteride
Management of BPH
Which group of patient most likely to benefit from 5ARI?
5ARI indicated for:
- Moderate or severe LUTS, with large prostate >40g
- Patients who want to avoid surgery
- Patients who cannot tolerate SE of a1 antagonist
- Initial PSA >1.5ng/ml
Management of BPH
What is 5ARI effect on PSA?
Because it reduces prostate size, 5ARI reduces PSA levels as well, thus consider adding if initial PSA >1.5ng/ml
Hence, slows progression of disease, decrease need for surgery
*Note that PSA should be obtained BEFORE initiating therapy, as PSA levels are not easily interpretable after initiation
Management of BPH
Describe the onset of 5ARI
Slow onset 6-12 months, as it takes time to reduce prostate size
Management of BPH
Describe the side effect profile of 5ARI
- Ejaculatory disorders (reduced semen during ejaculation, delayed ejaculation) (*higher risk than a1 antagonist)
- Decreased libido (dcr testosterone)
- Erectile dysfunction (dcr testosterone)
- Gynecomastia and breast tenderness (dcr testosterone)
- Less risk of hypotension
Management of BPH
What are some contraindications to the use of 5ARI?
5ARI is carcinogenic and teratogenic
Not to be handled by pregnant/child bearing age females
CI in pregnant women and children
Note that Finasteride (anti-androgenic) can be used for hirsutism in women
Management of BPH
Explain the MOA of phosphodiesterase 5 inhibitor (PDE5) for the treatment of BPH
Which PDE5 is approved for use in BPH?
PDE5i is used in ED
However, Tadalafil is approved for BPH, exact MOA is unknown, likely smooth muscle relaxation
Management of BPH
Which group of patient most likely to benefit from PDE5i?
Usually as add-on therapy, for patients with concomittant ED
- E.g., 5ARI + PDE5i (can cancel out effect on ED)
Management of BPH
What is PDE5i effect on PSA?
Does not affect prostate size, does not affect PSA
Management of BPH
Describe the onset of PDE5i
Fast onset (days to weeks) - dilates
Management of BPH
There has been increasing evidence to support the use of PDE5i as monotherapy in BPH with or w/o concomitant ED
Who might benefit from this monotherapy?
Postulated MOA: smooth muscle relaxation
Not yet approved as monotherapy for BPH with or w/o ED, but maybe in the future
Administration of Tadalafil 5mg daily for younger patients with low BMI and higher baseline symptoms
Management of BPH
Which group of patient is most likely to benefit from combination therapy?
Individuals with moderate symptoms (AUA-SI score 8-19) and prostate size >25g
Management of BPH
Discuss combination therapy (a1-antagonist + 5ARI) *most common combi
Benefits of this combi:
- Studies have shown that long-term use of this combi is safe with only mild adverse effects
- a-blocker fast onset within weeks, 5-ARI take months to shrink prostate
Combi is reserved for:
- Symptomatic patients with enlarged prostate
After 6 months of this combi,
- a1-blocker can be discontinued in moderate BPH, because prostate should be small enough and BPH management no longer require dilation of prostate smooth muscle by a1-blocker
Management of BPH
Discuss combination therapy (5ARI + PDE5i)
Benefits of this combi:
- PDE5i can mitigate sexual adverse effects that may arise from 5-ARI / concomitant erectile dysfunction
However, pt with BPH and ED often have cardiac comorbidities
- If unstable angina, do not initiate PDE5i as contraindicated with concomitant use of nitrates
Management of BPH
Discuss combination therapy (a1-antagonist + PDE5i)
*This combi is rarely used, if used choose uroselective a1 blocker
Downsides to this combi:
- Severe life threatening hypotension (both cause vasodilation)
- Does not shrink prostate
Dosing:
- Optimize/stabilize a1 antagonist dose first before adding PDE5i
- PDE5i should be added at lowest effective dose possible
Management of BPH
*The above drugs all dealt with obstructive/voiding symptoms (due to narrow urethral)
What drug can be used for irritative/storage symptoms (due to overactive bladder)?
Antimuscarinic
- ADD ON for pt with irritative voiding symptoms
- MOA: block muscarinic receptors in detrusor muscle, decrease involuntary contraction of the bladder
- Agents: Oxybutynin, Tolterodine, Solifenacin etc.
- PVR <250ml (<150ml) to prevent bladder from bursting due to too much urine not being voided
- Historically, anticholinergics CI in BPH due to concern for urinary retention, but studies have found minimal risk
