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Flashcards in Tx of BPH Deck (30):
1

Describe the localization of a1 receptors in the male urinary tract

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

2

What are some a1-blockers?

Przocin, Alfuzosin, Terazocin, Doxazocin, Tamsulosin, Silodosin

3

How are a1 blockers given? DOA?

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

4

What are some common AEs of a1-blockers?

orthostatic hypotension and syncope

Xerostomia, dizziness, HA, nausea

5

Which a1 blockers are selective against a1a receptors? AEs?

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

 

6

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

advantages- no need for dose titration

disad.- abnormal ejaculation (more with silodosin)

7

What is the generally accepted best a1 blocker for BPH?

alfuzosin (has very little side effects)

8

How does NO act at a molecular level?

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

9

How do PDE5 inhibitors work?

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

10

What are some PDE5 inhibitors?

Tadalafil (Cialis)- only one for BPH tx

Avanafil, Sildenafil, Vardenafil

11

What are some AEs of Tadalafil?

HA, nausea, nasopharyngitis, URTIs

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

12

What does the enzyme 5a-reductase do?

converts testosterone to DHT

13

What are the types of 5a-reductase?

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

Type II: mostly found in urogenital tissue and genital skin

14

What are the 5a-reductase inhibitors?

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

15

Describe 5a-reductase inhibitors

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

16

AEs of 5a-reductase inhibitors?

-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)

17

What are Beta-sitosterols?

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

18

What is Saw palmetto?

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

19

Drugs for erectile dysfunction

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20

What is Alprostadil?

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

21

How is Alprostadil given?

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

22

What are the benefits of local placement of Alprostadil?

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

23

AEs of Alprostadil?

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

rare CV effects

24

DD interactions with PDE5 inhibitors?

contraindicated with nitrates

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

25

Other AEs of PDE5 inhibitors?

Well tolerated but naopharyngitis, URTIs, vision and hearing loss

vardenafil has a risk of QT prolongation

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

27

What is Yohimibine?

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

28

AEs of Yohimibine?

-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 

29

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

30

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