IC18 BPH + ED Flashcards
What is the definition of BPH? (3 points)
Benign Prostatic Hyperplasia
Definition:
- Lower urinary tract signs and symptoms (LUTS)
- Negatively impact on QOL
- Non-malignant growth of prostate components e.g. transitional zone
What is the physiology of the prostate?
Physiology of prostate:
- Epithelial (glandular) tissue –> androgens stimulate its growth
a. Testosterone is converted to dihydrotestosterone (DHT) by Type II 5α-reductase in prostate
b. DHT is needed in normal growth and enlargement of prostate - Stromal (smooth muscle) tissue –> innervate by α1 adrenergic receptors
What is the pathogenesis of BPH?
Pathogenesis
- Mainly age and hormonal factors
- Static component:
Hormonal factors
testosterone –> DHT
Enlargement of prostate tissue - Dynamic Component:
Increase smooth muscle tissue and agonism of α1-receptors (vasoconstriction)
Narrowing of urethra outlet
–> Urethral obstruction / Signs and symptoms
Long Term
- Bladder response to obstruction
o Early phase: bladder muscle force urine through narrowed urethra by contracting more forcefully
o Over time: bladder muscle gradually becomes thicker (hypertrophy) to overcome obstruction
o Once reach highest state of hypertrophy, muscle decompensates
o Detrusor muscle becomes irritable and/or overly sensitive (detrusor overactivity or instability), contracting abnormally in response to small amounts of urine –> increase frequency of urine
What are the S&S of BPH?
Signs and Symptoms
Commonly asymptomatic, symptoms only occur in 1/3 men who are >65y/o
LUTS:
- Weak stream
- Increase frequency
- Nocturia
- Intermittent stream (urinary stream is not continuous)
- Incomplete emptying
- Straining
- Increase urgency
*LUTS not specific to BPH, other things can cause LUTS
e.g. prostate/bladder cancer, UTIs, diabetes mellitus
Obstructive /Voiding Symptoms
(early BPH):
- Hesitancy
- Weak stream
- Sensation of incomplete emptying
- Dribbling
- Straining
- Intermittent flow
Irritative/Storage symptoms
(Late BPH)
[Occurs after several years of untreated BPH]:
- Dysuria
- Nocturia
- Increase frequency (overly sensitive so can’t control when you have a small amt of urine)
- Increase urgency
- Urinary Incontinence (loss of bladder control, involuntary peeing)
What are the classifications of symptoms (severity) for BPH?
Severity AUA – SI score Usual Signs and Symptoms:
- Mild <= 7 Asymptomatic or mildly symptomatic
- Moderate 8-19 All of the above s/s AND Have obstructive voiding and irritable voiding symptoms
- Severe >= 20 Signs and symptoms AND complications
Complications:
- Recurrent UTI
- Bladder stones
- Acute urinary retention
- Urinary incontinence
- Hematuria
(Consider transurethral resection of prostate (TURP) when have complications)
What are the test and cut offs when evaluating BPH?
Assessment of BPH:
- Digital Rectal exam – normal prostate should be smooth
- Ultrasonography
- Maximum urinary flow rate (Qmax) – if there is some sort of obstruction, will have weak stream
- Prostate Specific Antigen (PSA)
a. The bigger the prostate, the higher the PSA
b. Predict progression of BPH –> PSA > 1.5 ng/mL
c. Higher risk of prostate cancer - Postvoid Residual (PVR)
a. <100 mL normal
b. >200 mL – inadequate emptying
What are the medications that can worsen BPH? (5 meds)
- Anticholinergics
e.g. antihistamines, tricyclic antidepressants, anti-muscarinic
- Decrease bladder muscle contractability -> increase urinary retention
- Alpha1 adrenergic agonist e.g. decongestant
- Contraction of prostate smooth muscles
- Opioid analgesic –> Increase urinary retention
- Diuretics –> Increase urine frequency
- Testosterone –> Increase prostate growth
When to start therapy for BPH? What to do if mild symptoms?
Management + when to start pharmacological therapy:
- As long as BPH does NOT affect QOL/not bothered, just watch and assess annually + non-pharm (be it mild, moderate or severe)
- START medications when moderate to severe and are bothered by symptoms
- Assess using AUA-SI score annually
- Advise regarding non-pharmacological
What are the non-pharm management of BPH?
Non-pharmacologicals
- Drink less water in the evening –> reduce urine frequency
- Eat less caffeine and drink less alcohol –> reduce urine frequency
- Take time to completely empty bladder
- Avoid medications that worsens BPH (anticholinergics, alpha receptor agonist, opioids analgesics, diuretics, testosterones)
What is the MOA of alpha 1 Receptor antagonist?
MOA
Mod-severe with small prostate (<40g)
Reversibly inhibit alpha1 adrenergic receptors
–> reduce smooth muscle contraction and cause vasodilation (dynamic component)
Non-selective (blood vessels, heart, peripheral, LUT)
- E.g. Doxazosin, Terazosin, Prazosin (not reco in BPH)
- Titrate dose slowly –> due to hypotension and syncope
Uroselective (blood vessel, prostate, LUT)
- E.g. Alfuzosin, Tamsulosin, Silodosin
NO effect on prostate size, prevention of BPH progression, need for surgery and PSA
Fast onset (days to weeks)
What are the non-selective alpha blockers?
Doxazosin, terazosin, prazosin
What are the uro-selective alpha blockers?
Alfuzosin, tamsulosin, silodosin
What are the ADRs of the class, non-selective and selective alpha blockers?
ADR
- Muscle weakness
- Fatigue
- Ejaculatory disturbance
- Headache (thus give bedtime dose)
Non-selective:
- Orthostatic hypotension
- 1st dose Syncope
- Dizziness
Uroselective:
- Ejaculatory disturbances (delayed or retrograde ejaculation)
- Silodosin > Tamsulosin > Alfuzosin
- (Tamsulosin) Intraoperative floppy iris syndrome
- CI in cataract surgery
- Block a1 receptors in iris dilator muscle
- Avoid starting until surgery is complete
What are the special considerations for using non-selective alpha blockers and selective alpha blockers?
Special Considerations
- Non-selective ARA:
o Use if need additional blood pressure lowering effect
o Avoid in patients at risk of syncope
o Should NOT be given as monotherapy for patients with BPH and HTN, need give with other meds - Selective ARA
o Used if don’t need extra anti-hypertensive effects
When to consider adding 5aRI? What is the MOA of 5aRI?
MOA
Mod-severe with large prostate (>40g)
Consider adding if PSA > 1.5ng/mL
Competitively bind to 5alpha reductase
- prevent the conversion of testosterone to DHT by 5alpha reductase
- less DHT
- reduce size of prostate (static component) + slows BPH progression + need for surgery
- Reduces PSA (obtain PSA before starting therapy)
E.g. Finasteride, dutasteride
Slow onset (6 months to a year)
What is the ADR of 5aRI?
ADR (More sexual dysfunction that Alpha1 ARA)
- Ejaculatory disorders
- Loss of libido
- ED (due to less DHT)
- Gynecomastia and breast tenderness
What is the CI for 5aRI?
Special Considerations CI:
- Women, children, pregnancy
Which PDE5i is used for BPH? How is PDE5i often used in clincial practise for BPH?
ONLY Tadalafil allowed for BPH
Adjunct therapy for BPH
What is the counselling tips for use of PDE5i? (When to take in general)
Counselling tips
- Take without regard to timing of sexual activity (becos it will only cause an erection when have sexual stilmulation)
What is the MOA of anti-muscarinic?
MOA:
Used ONLY when have irritable or overly sensitive bladder (late BPH, urinary frequency and nocturia)
Given when PVR < 250mL(can’t be more than this if not burst)
Blocks the muscarinic receptors in detrusor muscles of bladder
- Reduce involuntary contraction of bladder
- Reduce urinary incontinence
An anti-cholinergic medication (counterintuitive since these meds cause BPH)
- But works since this medication can help to reduce urine frequency
When do we use combi therapy for BPH?
What are the diff combis?
Combination Therapy:
When to use:
- Moderate LUTS symptoms (8-19) AND prostate > 25g
1. Alpha1 ARA + 5aRI
2. 5aRI + PDE5i
3. Alpha1 ARA + PDE5i
What are examples of A blockers + 5aRI? What is the benefit?
Alpha1 ARA + 5aRI
- E.g. Doxazosin (NS) + Finasteride OR Tamsulosin (S) + Dutasteride
- One acts on dynamic (within weeks) while the other works on the static component (require months)
What is 5aRI + PDE5i best used for? Why?
5aRI + PDE5i
- Best combi for patients with BPH and ED
- Cancel each other out wrt ED (5alpha RI cause ED while PDE5i treats ED)
What to look out for when using A blocker + PDE5i?
Alpha1 ARA + PDE5i
- Rare
- High risk of severe life-threatening hypotension
- Use uroselective Alpha1 ARA
- Want to use lowest dose for both
- Start with Alpha1 ARA and stabilize on it before adding PDE5i
- Would NOT address prostate enlargement