Tx of BPH

Question 1

Describe the localization of a1 receptors in the male urinary tract

Answer 1

Alpha 1a receptors predominate in the lower GU tract (trigone of the bladder, prostatic urethra and prostate gland), whereas alpha 1d receptors are more common in the destrussor muscle of the urinary bladder

Question 2

What are some a1-blockers?

Answer 2

Przocin, Alfuzosin, Terazocin, Doxazocin, Tamsulosin, Silodosin

Question 3

How are a1 blockers given? DOA?

Answer 3

Orally (CYP interactions). The DOA of most of these drugs is long except prazosin, which shows variability among pts. and most be titrated

Question 4

What are some common AEs of a1-blockers?

Answer 4

orthostatic hypotension and syncope

Xerostomia, dizziness, HA, nausea

Question 5

Which a1 blockers are selective against a1a receptors? AEs?

Answer 5

Tamsulosin and Silodosin (AEs include diminished effects on CV function, dopamine blockage, and increased sexual (reverse ejaculation) dysfunction)

Question 6

All a1 blockers have comparable efficacy. What are some advantages and disadvanatages of a1a blockers?

Answer 6

advantages- no need for dose titration

disad.- abnormal ejaculation (more with silodosin)

Question 7

What is the generally accepted best a1 blocker for BPH?

Answer 7

alfuzosin (has very little side effects)

Question 8

How does NO act at a molecular level?

Answer 8

cGMP mechanisms leading to influx of Ca2+ and smooth muscle relaxation, vasodilation of the penial arteries and erection

Question 9

How do PDE5 inhibitors work?

Answer 9

they prevent breakdown of cGMP by pDE5, rsulting in prolonged erection

Question 10

What are some PDE5 inhibitors?

Answer 10

Tadalafil (Cialis)- only one for BPH tx

Avanafil, Sildenafil, Vardenafil

Question 11

What are some AEs of Tadalafil?

Answer 11

HA, nausea, nasopharyngitis, URTIs

non-arteritic ischemic optic neuropathy, retinal artery occlusion, hearing loss

Question 12

What does the enzyme 5a-reductase do?

Answer 12

converts testosterone to DHT

Question 13

What are the types of 5a-reductase?

Answer 13

Type I: mostly found in non-genital skin, liver, and bone

Type II: mostly found in urogenital tissue and genital skin

Question 14

What are the 5a-reductase inhibitors?

Answer 14

Finasteride (type I) and Dutasteride (type I and II)

Question 15

Describe 5a-reductase inhibitors

Answer 15

They are competitive binders that bind for a long time and are metabolzied hepatically

Question 16

AEs of 5a-reductase inhibitors?

Answer 16

• category X preg
• low incidence of AEs but can get ejaculation and erectile dysfunction, decreased libido, and gynecomastia

Also decreases PSA levels (caution in a pt. with prostate cancer)

Question 17

What are Beta-sitosterols?

Answer 17

Natural products that have been shown to improve urinary symptom scores and flow measures but did not significantly reduce prostate size

Question 18

What is Saw palmetto?

Answer 18

Natural product for BPH- no evidence it’s effective- DONT recommend

Question 19

Drugs for erectile dysfunction

Question 20

What is Alprostadil?

Answer 20

A drug that mimics PGE1. It works by activating adenylate cyclase, which synthesizes cAMP from ATP to promote smooth muscle relaxation and erection

Very few AEs due to localized injection in the penis

Question 21

How is Alprostadil given?

Answer 21

Either intra-urethral suppository palced to dissolve in residual urine and then absorbed across the urethral wall or via direct injection into the corpus cavernosum

Question 22

What are the benefits of local placement of Alprostadil?

Answer 22

Minimal systemization, rapid onset (minutes), and a lasting effect for hrs.

Question 23

AEs of Alprostadil?

Answer 23

penile (36%), urethral (13%), and testicular (5%) pain

rare CV effects

Question 24

DD interactions with PDE5 inhibitors?

Answer 24

contraindicated with nitrates

caution with alpha blockers (increased hypotension), and other 3A4 drugs

Question 25

Other AEs of PDE5 inhibitors?

Answer 25

Well tolerated but naopharyngitis, URTIs, vision and hearing loss

vardenafil has a risk of QT prolongation

Question 26

Note that the hormonal supplementation of testosterone has been shown to improve erectile dysfunction in hypogonadal men and may improve the response to PDE5 inhibitors

Question 27

What is Yohimibine?

Answer 27

An alpha-2 receptor inhibitor that appears to involve blockade of post-synaptic adrenergic receptors and stimulating pre-synaptic hetero-receptors on NANC nerves to cause vasodilation

Question 28

AEs of Yohimibine?

Answer 28

• not all that effective
• crosses BBB potentially producting anxiety, antidiuresis, dizziness, HTN, etc.

MAOI action at high dose (tyramine and caffeine interactions possible)

-worsens renal function

Question 29

Note that many many drugs list ED as a potential AE so keep that in mind during evaluation

Question 30