IC19 Benign Prostate Hyperplasia Flashcards
description of BPH
Progressive condition; worsens over time
* Lower urinary tract signs & symptoms (LUTS)
* Negative impact on QOL
Non-malignant growth of some components of prostate
physiology - types of tissues
- epithelial (static)
- stromal (dynamic)
physiology: epithelial tissues
Testosterone converted to dihydrotestosterone [DHT] by enzyme type II 5α-reductase, in the prostate
* DHT ⇒ stimulates growth of prostate
physiology: stromal tissues
Innervated by α1 adrenergic receptors
pathophysiology
based on static & dynamic components
static
High levels of DHT ⇒ enlargement of prostate tissue
dynamic
Increased smooth muscle tissue & agonism of α1 receptors
→ vasoconstriction of prostate
⇒ narrowing of urethra outlet (smaller)
overall outcome
Urethral obstruction + signs & symptoms
phases of bladder response to obstruction
- early phase
- middle phase
- late phase
phases of bladder response to obstruction
(1) early
Bladder muscle forces urine through narrowed urethra by contracting more forcefully
Urine able to pass out normally → lesser signs & symptoms
phases of bladder response to obstruction
(2) middle
- Bladder muscles gradually become thicker (hypertrophy) to overcome the obstruction
- Detrusor muscles achieving highest state of hypertrophy ⇒ muscle decompensates (cannot contract strongly)
phases of bladder response to obstruction
(3) late
Detrusor muscle become irritable &/ or overtly sensitive (overactivity/ instability) → contract abnormally in response to small amounts of urine in bladder ⇒ need to urinate frequently
signs & symptoms (general + 2 main types)
Start to occur in ⅓ men >65 years
Most usually remain asymptomatic
Lower urinary tract symptoms (LUTS)
main types
1. obstructive
2. irritative
obstructive symptoms
when + how it occurs & what are the symptoms
- More often in early disease
- Narrowed urethra → difficult to pass urine
- Detrusor muscle not irritable/ overactive YET
Hesitancy, weak stream, sensation of incomplete emptying, dribbling, straining, intermittent flow
irritative symptoms
when + how it occurs & what are the symptoms
- When detrusor muscle decompensates
- Occurs after several years of untreated BPH
Dysuria → pain on urination
Due to bladder continuously contracting
Frequency, nocturia, urgency, urinary incontinence
Assessing BPH
D, U, U, P, P
- Digital rectal exam (DRE)
- Ultrasonography
- Maximum urinary flow rate (Qmax)
-
Postvoid residual (PVR)→ amount of urine left in bladder after urinating
<100 mL = normal; >200 mL = inadequate emptying -
Prostate specific antigen (PSA)
Might be elevated in BPH & positively correlated with prostate volume
Helps predict progression of BPH (>1.5 ng/ mL)
Higher risk for prostate cancer
drug exacerbating BPH + reasons
Anticholinergic: decrease bladder muscle contractility
* Antihistamines, tricyclic antidepressants
α1 adrenergic agonists: contraction of prostate smooth muscles
* Decongestants
Opioid analgesics: increase urinary retention
Diuretics: increase urinary frequency
Testosterone: stimulate prostate growth
management of BPH
when to watch, when to initiate pharmacotherapy
watch
* Mild symptoms (IPSS <8)
* moderate/ severe symptoms (IPSS ≥ 8) who are not bothered by symptoms (IPSS QOL <3)
initiate
symptomatic patients who are bothered by it (IPSS QOL ≥ 3) & those with complications
non-pharmacological methods
- Limited fluid intake in evening
- Minimise caffeine & alcohol intake
- To take time to empty bladder completely & often
- Avoid medications that can exacerbate symptoms
pharmacological therapy
- a1 adrenergic antagonists
- 5a reductase inhibitors
- PDE5 inhibitors
- antimuscarinics
(1) a1 adrenergic antagonists
types
MOA, drugs, titration
non-selective
* Antagonises both peripheral vascular & urinary α1 adrenergic receptors
* Doxazosin, terazosin
* Need to titrate slowly to therapeutic dose (risk of hypotension & syncope)
selective
* Antagonises only urinary α1A adrenergic receptors (predominant in prostate & LUT)
* Alfuzosin, Tamsulosin, Silodosin
* No need for titration (lesser risk of titration)
(1) a1 adrenergic antagonists
indication
general; selective vs non-selective
general
reducing LUTS (moderate/ severe) with SMALL prostate (<40g)
Selective
For patients who don’t require added BP lowering effect
non-selective
* Beneficial in hypertensive patients requiring additional BP lowering effect
* To avoid in patients with hx of syncope
* Not to use as monotherapy with HTN & BPH concurrently
(1) a1 adrenergic antagonists
clinical effects
prostate size, PSA, onset, what happens if discontinue
- Do not reduce prostate size
No prevention for progression of BPH/ need for surgery - No effect on PSA
- Onset → fast; days to weeks
- Signs & symptoms will recur if discontinued
(1) a1 adrenergic antagonists
SE
General
muscle weakness, fatigue, ejaculatory disturbances, headache
To give bedtime administration ⇒ decreases orthostatic effects
(1) a1 adrenergic antagonists
SE (selective)
Low to none peripheral vascular dilation
Less hypotension/ syncope
Ejaculatory disturbances (delayed/ retrograde)
* Silodosin > Tamsulosin > Alfuzosin
* Lesser sexual dysfunction than 5ARIs
(1) a1 adrenergic antagonists
SE (non-selective)
Dizziness
First dose syncope → body not adjusted yet
Orthostatic hypotension
(1) a1 adrenergic antagonists
SE: intraoperative floppy iris syndrome
how it occurs, approach to prevention
- Occurs if patient takes α1 adrenergic antagonists before cataract surgery
Mostly tamsulosin - Due to blockage of α1 receptors in iris dilator muscle ⇒ pupil will constrict (smaller)
- Men should avoid initiation of α1 adrenergic antagonists until surgery completed OR hold at least 14 days before surgery
(2) 5ARIs
drugs
Finasteride, dutasteride
(2) 5ARIs
indications
- reducing LUTS (moderate/ severe) with LARGE prostate (>40g)
- Alternative for patients who want to avoid surgery OR cannot tolerate α1 antagonist
- Decreases PSA levels → use in patients with initial PSA > 1.5 ng/mL
Important to obtain PSA levels before initiating therapy ⇒ cannot be interpreted after initiation
(2) 5ARIs MOA
Inhibits 5α reductase (Type II) → decrease conversion from testosterone to DHT ⇒ reducing the size of prostate
(2) 5ARIs SE
- Ejaculatory disorders (reduced semen during ejaculation or delayed ejaculation)
higher risk than α1 antagonist - Decreased Libido (3 -8%)
- Erectile Dysfunction (ED) (3-16%)
- Gynecomastia and breast tenderness (1.0%)
(3) PDE5i
background
drug, effect on prostate size, onset
Tadalafil
Does not affect prostate size
Onset: days to weeks
(3) PDE5i indications
- Add on therapy for patients with concomitant ED
- Monotherapy for patients with BPH-LUTS with or without concurrent ED
Younger age, low BMI, higher baseline symptoms
(3) PDE5i MOA
(unknown) Likely smooth muscle relaxation
(3) PDE5i SE
Significant hypotension
(4) antimuscarinics indications
PVR requirement
- Add on therapy for patients with irritative voiding symptoms (mimic overactive bladder)
- PVR must be <250 mL
(4) antimuscarinics MOA
Block muscarinic receptors in detrusor muscles ⇒ decrease involuntary contraction of bladder
combination therapy
- a1 antagonists + 5ARIs
- 5ARIs + PDE5i
- a1 antagonists + PDE5i (rare)
combination therapy
purpose
Better effects than monotherapy; long term use is safe with mild AE
Beneficial for individuals with moderate symptoms & prostate size > 25g
* IPSS 8-19, IPSS QOL 5-6 (must be affected by the symptoms)
(1) a1 antagonists + 5ARIs
effect onset, indication, possible combi
- α1 blockers provide benefit within weeks + 5ARI require months for optimal effects
- For symptomatic patients with enlarged prostate
- Possible combinations
MTOPS: doxazosin + finasteride
CombAT: tamsulosin + dutasteride - After 6 months of combination therapy → can discontinue α1 blockers in moderate BPH
(2) 5ARIs + PDE5i
indication, note for cardiac patients
- To mitigate sexual AE: from 5ARI/ concomitant ED
- Take note in people with cardiac comorbidities (along BPH & ED → very common)
Unstable angina: should not initiate PDE5I → contraindicated with concomitant use of nitrates
(3) a1 antagonist + PDE5i
reasons for rarity, dosing requirements, prostate size
- Rarely used; can cause severe life threatening hypotension
Need to use uro-selective α1 instead - Important to optimise/ stabilise α1 antagonist dose FIRST before adding PDE5I
PDE5I to use lowest effective dose - Does not help with large prostate size
