BPH & ED Flashcards
How is dihydrotestosterone (DHT) formed and what does it do?
Testosterone converted to DHT by 5 alpha reductase in prostate
DHT: normal growth / enlargement of prostate
What is the prostate made up of?
- epithelial tissue (growth stimulated by androgens)
- stromal tissues innervated by alpha1 adrenergic receptors
Pathophysiology of BPH (short term)?
Static component
- testosterone converted to DHT -> prostate enlarges
Dynamic component
- increase smooth muscle tissue & agonism of alpha1 receptors -> narrowing of urethra outlet
=> urethral obstruction, s&sx
Pathophysiology of BPH (long term)?
- early phase: bladder muscle force urine thru narrowed urethra by contracting more forcefully
- over time, bladder (detrusor) muscle becomes thicker (hypertrophy)
- detrusor muscle becomes irritable +/ overly sensitive (detrusor overactivity / instability) -> contract abnormally in response to small amt of urine in bladder
What is LUTS and what does it consist of?
Lower urinary tract sx
- obstructive sx (early stage): hesitancy, weak stream, sensation of incomplete emptying, dribbling, straining, intermittent flow
- irritative sx (late stage If untreated): dysuria, frequency, nocturia, urgency, UI
Complications of BPH?
- recurent UTI
- bladder stones
- acute urinary retention
- UI
- hematuria
What score is used for BPH and what is the score & sx for:
- mild
- moderate
- severe
AUA-SI score
- mild ≤7: asymptomatic / mildly sx
- moderate 8-19: the above + obstructive & irritative voiding sx
- severe ≥20: the above + ≥1 complications of BPH
What is the prostate specific antigen (PSA) for BPH?
> 1.5ng/mL
What postvoid residual is considered inadequate emptying? What is normal?
> 200 mL
(normal <100mL)
What medications contribute to BPH? Why?
- anticholinergics (decrease bladder contractility)
- alpha1 adrenergic agonist (contract prostate smooth muscle)
- opioid (increase urinary retention)
- diuretics (increase urinary frequency)
- testosterone (stimulate prostate growth)
When should treatment be started for BPH? When can watchful waiting be considered?
Start: if sx bother pt / complications
Watchful waiting: mild, or moderate-severe with no bothering sx
Nonpharm for BPH? (5)
- limit fluid intake in the evening
- minimise caffeine & alcohol intake
- take time to empty bladder completely & often
- avoid meds that worsen sx
- transurethral resection of prostate (for complications)
What pharm options are used for BPH obstructive sx?
- alpha1 adrenergic antagonist
- 5 alpha reductase inhibitors
- PDE5 inhibitors (only tadalafil)
What are selective and nonselective alpha1 antagonists?
- selective: alfuzosin, tamsulosin, silodosin
- nonselective: terazosin, prazosin, doxazosin
Are selective or nonselective alpha1 antagonists preferred for BPH? When should the non-preferred one be used?
preferred: selective
nonselective preferred if pt has BPH + HTN (but cannot use as monotherapy)
What are the following indicated for BPH:
- alpha1 antagonist
- 5 alpha reductase inhibitor
- PDE5 inhibitor
- alpha1 antagonist: moderate-severe LUTS with small prostate (<40g)
- 5 alpha reductase inhibitor: moderate-severe LUTS with large prostate (>40g), if PSA >1.5ng/mL
- PDE5 inhibitor: add-on for pts with BPH-LUTS +- ED
Which meds for BPH can decrease prostate size?
5 alpha reductase inhibitor
Examples of 5 alpha reductase inhibitors?
Finasteride, dutasteride
SE of alpha1 antagonist?
- hypotension (nonselective > selective) & related SE
- HA (dilation of brain vessels)
- ejaculatory disturbance (delayed / retrograde)
- intraoperative floppy iris syndrome (for tamsulosin) -> complicates cataract & glaucoma surgery
What should pts with cataract & glaucoma surgery do if they plan to start tamsulosin? What are they trying to avoid?
Avoid intraoperative floppy iris syndrome
avoid initiation until surgery has been completed, or hold 2-3w before surgery
What do the selective alpha adrenergic receptors target?
urinary alpha1 adrenergic receptors in prostate, prostatic urethra, bladder neck
Do the following have fast or slow onset:
- alpha1 antagonist
- 5 alpha reductase inhibitor
- PDE5 inhibitor
- alpha1 antagonist: fast
- 5 alpha reductase inhibitor: slow (6-12m)
- PDE5 inhibitor: fast
SE of 5 alpha reductase inhibitor?
- ejaculatory disturbance, less libido, ED
- gynecomastia
Which pts will benefit from combi therapy of BPH meds? What combi should be used for what indication?
Benefits pts with moderate sx & prostate >25g
- alpha1 antagonist + 5ARI: sx pts with enlarged prostate (most common)
- 5ARI + PDE5i: pts with ED or experience ED from 5ARI use
- alpha1 antagonist + PDE5i: rarely used due to hypotension
What pharm option can be used for irritative BPH sx? When is it indicated?
- antimuscarinics (oxybutynin, tolterodine, solifenacin)
- indicated for pts with irritative sx & PVR <250mL
What is considered ED?
persistent (≥6m) inability to achieve or maintain erection of sufficient duration & firmness to complete satisfactory intercourse
How do PDE5 inhibitors work?
Inhibit PDE5 enzymes -> more cGMP -> smooth muscle relaxation & vasodilation -> erection
Only after sexual stimulation
Examples of PDE5 inhibitors?
sildenafil, vardenafil, tadalafil, avanafil
When and how (food) should the PDE5 inhibitors be taken?
- sildenafil: 1h before sex, empty stomach
- vardenafil: 1h before sex, empty stomach
- tadalafil: up to 36h before sex, regardless of food
- avanafil: 30min before sex, regardless of food
Major interactions with PDE5 inhibitors?
- CYP3A4 inhibitors -> increase serum conc of PDE5i
- nitrates -> life threatening hypotension
How long to space nitrates from PDE5i?
- avanafil: 12h after
- sildenafil, vardenafil: 24h after
- tadalafil: 48h after
SE of PDE5i?
- hypotension (dizzy)
- HA, flushing, rhinitis (vasodilation)
- muscle & back pain (tadalafil due to PDE 11 affinity)
- QTc prolongation (vardenafil)
- photosensitivity, colour discrimination (sildenafil & vardenafil due to PDE6 in retina)
- prolonged erections & priapisms (go A&E if >4h)
What can be used for ED?
- PDE5 inhibitors
- testosterone (for sx hypogonadism)
- alprostadil
When should testosterone be discontinued for ED?
if no improvement of ED sx after 3m
Do PDE5 inhibitors and alprostadil require sexual stimulation to work?
PDE5i yes, alprostadil no
