BPH & ED

Question 1

How is dihydrotestosterone (DHT) formed and what does it do?

Answer 1

Testosterone converted to DHT by 5 alpha reductase in prostate

DHT: normal growth / enlargement of prostate

Question 2

What is the prostate made up of?

Answer 2

• epithelial tissue (growth stimulated by androgens)
• stromal tissues innervated by alpha1 adrenergic receptors

Question 3

Pathophysiology of BPH (short term)?

Answer 3

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

Question 4

Pathophysiology of BPH (long term)?

Answer 4

• 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

Question 5

What is LUTS and what does it consist of?

Answer 5

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

Question 6

Complications of BPH?

Answer 6

• recurent UTI
• bladder stones
• acute urinary retention
• UI
• hematuria

Question 7

What score is used for BPH and what is the score & sx for:
- mild
- moderate
- severe

Answer 7

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

Question 8

What is the prostate specific antigen (PSA) for BPH?

Answer 8

> 1.5ng/mL

Question 9

What postvoid residual is considered inadequate emptying? What is normal?

Answer 9

> 200 mL
(normal <100mL)

Question 10

What medications contribute to BPH? Why?

Answer 10

• anticholinergics (decrease bladder contractility)
• alpha1 adrenergic agonist (contract prostate smooth muscle)
• opioid (increase urinary retention)
• diuretics (increase urinary frequency)
• testosterone (stimulate prostate growth)

Question 11

When should treatment be started for BPH? When can watchful waiting be considered?

Answer 11

Start: if sx bother pt / complications

Watchful waiting: mild, or moderate-severe with no bothering sx

Question 12

Nonpharm for BPH? (5)

Answer 12

• 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)

Question 13

What pharm options are used for BPH obstructive sx?

Answer 13

• alpha1 adrenergic antagonist
• 5 alpha reductase inhibitors
• PDE5 inhibitors (only tadalafil)

Question 14

What are selective and nonselective alpha1 antagonists?

Answer 14

• selective: alfuzosin, tamsulosin, silodosin
• nonselective: terazosin, prazosin, doxazosin

Question 15

Are selective or nonselective alpha1 antagonists preferred for BPH? When should the non-preferred one be used?

Answer 15

preferred: selective

nonselective preferred if pt has BPH + HTN (but cannot use as monotherapy)

Question 16

What are the following indicated for BPH:
- alpha1 antagonist
- 5 alpha reductase inhibitor
- PDE5 inhibitor

Answer 16

• 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

Question 17

Which meds for BPH can decrease prostate size?

Answer 17

5 alpha reductase inhibitor

Question 18

Examples of 5 alpha reductase inhibitors?

Answer 18

Finasteride, dutasteride

Question 19

SE of alpha1 antagonist?

Answer 19

• hypotension (nonselective > selective) & related SE
• HA (dilation of brain vessels)
• ejaculatory disturbance (delayed / retrograde)
• intraoperative floppy iris syndrome (for tamsulosin) -> complicates cataract & glaucoma surgery

Question 20

What should pts with cataract & glaucoma surgery do if they plan to start tamsulosin? What are they trying to avoid?

Answer 20

Avoid intraoperative floppy iris syndrome

avoid initiation until surgery has been completed, or hold 2-3w before surgery

Question 21

What do the selective alpha adrenergic receptors target?

Answer 21

urinary alpha1 adrenergic receptors in prostate, prostatic urethra, bladder neck

Question 22

Do the following have fast or slow onset:
- alpha1 antagonist
- 5 alpha reductase inhibitor
- PDE5 inhibitor

Answer 22

• alpha1 antagonist: fast
• 5 alpha reductase inhibitor: slow (6-12m)
• PDE5 inhibitor: fast

Question 23

SE of 5 alpha reductase inhibitor?

Answer 23

• ejaculatory disturbance, less libido, ED
• gynecomastia

Question 24

Which pts will benefit from combi therapy of BPH meds? What combi should be used for what indication?

Answer 24

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

Question 25

What pharm option can be used for irritative BPH sx? When is it indicated?

Answer 25

- antimuscarinics (oxybutynin, tolterodine, solifenacin) - indicated for pts with irritative sx & PVR <250mL

Question 26

What is considered ED?

Answer 26

persistent (≥6m) inability to achieve or maintain erection of sufficient duration & firmness to complete satisfactory intercourse

Question 27

How do PDE5 inhibitors work?

Answer 27

Inhibit PDE5 enzymes -> more cGMP -> smooth muscle relaxation & vasodilation -> erection Only after sexual stimulation

Question 28

Examples of PDE5 inhibitors?

Answer 28

sildenafil, vardenafil, tadalafil, avanafil

Question 29

When and how (food) should the PDE5 inhibitors be taken?

Answer 29

- 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

Question 30

Major interactions with PDE5 inhibitors?

Answer 30

- CYP3A4 inhibitors -> increase serum conc of PDE5i - nitrates -> life threatening hypotension

Question 31

How long to space nitrates from PDE5i?

Answer 31

- avanafil: 12h after - sildenafil, vardenafil: 24h after - tadalafil: 48h after

Question 32

SE of PDE5i?

Answer 32

- 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)

Question 33

What can be used for ED?

Answer 33

- PDE5 inhibitors - testosterone (for sx hypogonadism) - alprostadil

Question 34

When should testosterone be discontinued for ED?

Answer 34

if no improvement of ED sx after 3m

Question 35

Do PDE5 inhibitors and alprostadil require sexual stimulation to work?

Answer 35

PDE5i yes, alprostadil no